Similar Journals
|
Diabetes
Journal Prestige (SJR): 4.435  Citation Impact (citeScore): 6 Number of Followers: 348  Subscription journalISSN (Print) 0012-1797 - ISSN (Online) 1939-327X Published by American Diabetes Association  [4 journals]
|
- 1-OR: Expression of the Stress Response Protein REDD1 in Podocytes
Promotes CGAS-STING–Mediated Activation of the Renal Immune Response in
a Rodent Model of Type 2 Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 1-OR
Abstract: Introduction and Objective: Activation of innate immune signaling is recognized as a critical factor in the pathogenesis diabetic nephropathy (DN). We previously observed that podocyte-specific expression of the stress response protein REDD1 (Regulated in Development and DNA Damage 1) is required for podocyte injury and function deficits in DN. Given that podocytes are thought to play an immune modulatory role in kidney disease, we investigated the hypothesis that diabetes-induced REDD1 expression in podocytes contributes to mitochondrial injury leading to a DNA-driven immune response.Methods: REDD1fl/fl and podocyte-specific NPHS2-cre REDD1 knockout mice were fed a high fat diet to induce diabetes. Kidneys were removed after 16 weeks of diabetes, and analyzed for immune cell infiltrates using flow cytometry. Protein and mRNA expression in isolated glomeruli were determined. Similar analyses were carried out in wild-type or CRISPR REDD1 KO human podocyte cultures exposed to 150 µM palmitate.Results: Podocyte-specific REDD1 deletion prevented diabetes-induced albuminuria, activation of NF-κB, and expression of pro-inflammatory factors. Similarly, in cultured human podocytes, we observed that palmitate exposure increased mitochondrial injury, membrane depolarization, and mtDNA leakage in cells expressing REDD1, which was concomitant with increased activation of the cGAS-STING pathway and NF-κB mediated inflammation. Importantly, podocyte-specific REDD1 deletion prevented mitochondrial dysfunction, STING activation and proinflammatory macrophage infiltration in kidneys of diabetic mice.Conclusion: Overall, the findings provide new insight into the role of podocyte REDD1 expression in regulating renal pathology and function in diabetes and support the possibility that therapeutics targeting podocyte REDD1 could be beneficial in suppressing innate immune response activation in DN.DisclosureS. Sunilkumar: None. S. Moothedath Subrahmanian: None. M.D. Dennis: None.FundingAmerican Diabetes Association (11-23-PDF-24); National Institutes of Health (R01 EY032879), Juvenile Diabetes Research Association (1-INO-2024-1538-A-N)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-1-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 1-PUB: Impaired Awareness of Hypoglycemia (IAH) and Blunted
Sympathoadrenal Response in Rodents Is Reversible-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 1-PUB
Abstract: Introduction and Objective: Iatrogenic hypoglycemia induces IAH and blunts the counterregulatory response (CRR). This study investigates whether these maladaptive responses are reversible over time.Methods: Protocol 1: Sprague-Dawley rats (n=10) were pre-conditioned with 3 days of 2-deoxyglucose (2DG; 200 mg/kg/day) to impair hypoglycemia awareness as assessed by food intake responses to insulin (NPH, 15U/kg)-induced hypoglycemia. Protocol 2: Rats were randomized to 3 days recurrent saline (RS) or recurrent hypo (RH) followed by 1-day, 1-week, 3-weeks and 5-weeks post-RH recovery (n=6-8/group). Hyperinsulinemic-hypoglycemic clamps assessed sympathoadrenal hormone responses.Results: In Protocol 1, hypoglycemia increased food intake (6-fold) above saline controls, consistent with awareness of hypoglycemia. 2DG preconditioning blunted the food intake response to hypoglycemia (ie, induced IAH) for 1 day and 1 week. By week 3 and 5, food intake response to hypo was not different from baseline. In Protocol 2, RH significantly blunted the epinephrine response to hypoglycemia 1-day and 1 week following preconditioning, but was fully restored by week 3 and 5.Conclusion: In the IAH model, hypoglycemia awareness improved over time. Avoiding hypoglycemia for three weeks restores the blunted CRR. In these models, these maladaptations are reversible.DisclosureA.R. Marksbury: None. M. Wooten: None. M.H. Devore: None. S.J. Fisher: None.FundingTL1TR001997 to MD; NIDDK R01DK118082 and 1R25DK109894 to SJF
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-1-PUB
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 2-OR: Blocking Neuroblastoma Suppressor of Tumorigenicity 1 (NBL1)
Prevents Diabetic Kidney Disease-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 2-OR
Abstract: Introduction and Objective: Serum levels of neuroblastoma suppressor of tumorigenicity 1 (NBL1) positively correlate with the 10-years risk of developing end stage kidney disease (ESKD) in patients with either type 1 or type 2 diabetes. Moreover, NBL1 causes podocyte death, in vitro. The aim of our study was to test whether NBL1 blocking agents could prevent podocyte death, in vitro, and delay diabetic kidney disease (DKD) onset, in vivo.Methods: We screened a library of NBL1 inhibitors through phage display by using an in vitro cell death assay, which measured NBL1-induced apoptosis of human immortalized podocytes. Stem cell-derived human kidney organoids were used as translational model. NBL1 inhibitors were tested, in vivo, in streptozotocin (STZ)-induced DKD and in Db/Db mice. Efficacy of NBL1 blocking agents was evaluated by quantifying mesangial expansion, pro-fibrotic response, expression of podocyte-specific markers and by measuring urinary creatinine and albumin.Results: Our study demonstrated that NBL1 inhibition markedly reduced NBL1-induced podocyte death, in vitro, and rescued the expression of podocyte markers in human kidney organoids. More importantly, when administered in vivo, NBL1 inhibitors reduced urinary albumin and creatinine, mesangial expansion, and renal fibrosis, thus preventing the development of DKD.Conclusion: Novel therapies aimed at blocking/delaying DKD onset and/or progression to ESKD in patients with diabetes are still needed. Our findings demonstrate that NBL1 inhibition protects diabetic mice from renal damage by preventing podocyte death, thereby confirming NBL1 as novel therapeutic target for DKD.DisclosureA. Petrazzuolo: None. E. Assi: None. A. Maestroni: None. V. Usuelli: None. M. Zocchi: None. G. Rossi: None. I. Pastore: Advisory Panel; Sanofi. Board Member; Novo Nordisk. A. Monestiroli: Consultant; Nephris, Alia Therapeutics. M. Ben Nasr: None. F. D'Addio: Advisory Panel; Sanofi. A. Krolewski: None. P. Fiorina: Consultant; Novo Nordisk, AstraZeneca. Board Member; Boehringer-Ingelheim.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-2-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 2-PUB: Assessment of Awareness about Hypoglycemia and Its Management among
Nurses in South India—The HYPO N Study-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 2-PUB
Abstract: Introduction and Objective: Most hypoglycemic episodes among patients are managed by nurses and healthcare providers. This study aims to assess the knowledge of nurses about hypoglycemia and it's management using a self-developed hypoglycemia awareness questionnaire.Methods: This prospective interventional study was carried out in a quaternary care hospital with more than 250 nurses. A Hypoglycemia Awareness (HYPO N) questionnaire was used to evaluate their knowledge on the symptoms and management of hypoglycemia. The scores were evaluated before and after conducting an educational program using the same questionnaire and analysis was carried out using descriptive statistics and Independent T - test.Results: Pre- intervention the mean score was found to be 4.91 ± 1.53. 3 of the 4 symptom questions had less than 30% of the participants with correct answers while 3 of the 5 management questions had more than 60% individuals with correct answers. The test score post- intervention saw a significant improvement, which was 8.09 ± 1.71. Independent sample T test revealed significant difference (t(584) = -23.572, p = 0.000) between the scores pre and post intervention with a mean difference of 3.177 indicating that an education program could be significant in helping nurses recognize and manage sudden onset hypoglycemia.Conclusion: Our study showed that nurses lack sufficient knowledge in recognizing the symptoms of hypoglycemia and an educational program at least every 6 months to 1 year will greatly improve diabetic patient care. Integrating diabetes and it's complications in the nursing curriculum for all specialties will help nurses be more prepared to deal with patients presenting with hypoglycemia.DisclosureA.K. Viswanathan: None. A. Shabbir: None. D. Ganesh: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-2-PUB
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 3-OR: LRP5 Promotes Fatty Acid Oxidation to Reduce Lipid Deposition in the
Proximal Tubules of DKD Kidneys-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 3-OR
Abstract: Introduction and Objective: Fatty acid oxidation (FAO) provides major energy for renal proximal tubules, however, it is compromised in diabetic kidney diseases (DKD).Methods: Single-cell RNA-seq analysis and immunostaining were applied to analyze the role of LRP5 in DKD diseases. Lrp5-deficient (Lrp5-/-) mice were subjected to a high-fat diet, and tested for renal functions and changes.Results: Single-cell RNA-seq identified low-density lipoprotein receptor-related protein 5 (LRP5) as a critical tubular injury-associated factor in DKD patients, and immunostaining further confirmed enriched expression of LRP5 in the injured tubules from diabetic kidneys. In Lrp5-/--HFD kidneys, we found that tubular but not glomerular functions were greatly compromised, accompanied by severe tubulointerstitial fibrosis and tubular damage. Bulk RNA-seq revealed increased lipid deposition and synthesis, yet decreased FAO in Lrp5-/--HFD kidneys compared to WT-HFD controls. Further analyses demonstrated peroxisome proliferator-activated receptor (PPAR) signaling as the downstream cascade of LRP5. Overexpression and knockdown assays in proximal tubular epithelia showed that LRP5 was essential for maintaining the epithelial phenotype under lipotoxicity. Metabolomics results demonstrated that restoration of LRP5 to DKD kidneys significantly down-regulated the levels of lipid metabolites, accompanied by increased FAO capacity and ameliorated tubulointerstitial fibrosis.Conclusion: In summary, our study uncovered LRP5 as a novel promoter of FAO to protect tubular functions, which serves as a promising therapeutic target for treating DKD.DisclosureX. He: None. R. Zeng: None. H. Li: None. S. Wen: None. S. Li: None. Y. Chen: None.FundingThis work was supported by grants from the National Natural Science Foundation of China (82270886), the Science and Technology Plan Project of Guangzhou City (2024A03J0002).
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-3-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 3-PUB: Plasma GDF15 Levels Are Elevated in Individuals with Post-bariatric
Hypoglycemia-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 3-PUB
Abstract: Introduction and Objective: Post-bariatric hypoglycemia (PBH) is a recognized complication of bariatric surgery and typically occurs postprandially. Growth differentiation factor 15 (GDF15) is a secreted peptide induced by multiple physiological stressors. Here we investigate relationships between GDF15, hypoglycemia, and hypoglycemia-related symptoms.Methods: We measured plasma GDF15 levels in PBH (n=15), asymptomatic post-RYGB (RYGB non-hypo, n=15), and obese non-surgical controls (CON, n=10) during mixed meal testing and hyperinsulinemic hypoglycemic clamp. Hypoglycemia symptoms were assessed using Edinburgh Hypoglycemia Symptom Scale (EHSS). The impact of insulin-induced hypoglycemia on GDF15 levels was assessed in C57BL/6 mice.Results: Plasma GDF15 was increased in PBH vs. CON in the fasting state (69%, p=0.03). Likewise, at 120 minutes after mixed meal, GDF15 was higher in PBH vs. both RYGB non-hypo and CON (71% and 91% higher, p<0.01 for both). During hyperinsulinemic hypoglycemic clamp, GDF15 levels were progressively increased in PBH vs. both RYGB non-hypo and CON at 90, 110 and 120 minutes (1.1, 1.2, and 1.5-fold; and 1.7, 1.9, and 2.2-fold, respectively; all p<0.05). In mice, insulin-induced hypoglycemia increased plasma GDF15 (88% vs. saline, p=0.04).GDF15 levels associated with higher EHSS scores during the hypoglycemic clamp at 90 (r=0.62, p=0.01), 110 (r=0.87, p<0.0001), and 120 (r=1.0, p=0.005) minutes in PBH. Weakness (90 min: r=0.53, p=0.04; 110min: r=0.63, p=0.01), difficulty concentrating (baseline: r=0.53, p=0.04; 110min: r=0.56, p=0.03), and tingling of lips (90min: r=0.57, p=0.03; 110min: r=0.72, p=0.003) were positively correlated with GDF15. During mixed meal, GDF15 was correlated with “feeling cold” (120 min: r=0.89, p=0.01) in PBH.Conclusion: GDF15 may be a novel counterregulatory peptide response to hypoglycemia in both mice and humans with PBH. Elevated GDF15 may contribute to hypoglycemia-related symptoms in individuals experiencing PBH.DisclosureR. Ferraz-Bannitz: None. L. Pei: Stock/Shareholder; Eli Lilly and Company. H. Wang: None. B. Ozturk: None. P. Casanova: None. H. Saeed: None. L. Poulos: None. H.S.M. Saifeldin: None. C.J. Cummings: None. M. Farahmandsadr: None. A.E. Amore: None. A.L. Sheehan: None. D.C. Simonson: Stock/Shareholder; GI Windows. Consultant; Phase V Technologies. M. Patti: Research Support; Dexcom, Inc. Other Relationship; Recordati, Fractyl Health, Inc. Consultant; Spruce Biosciences, Premier, Cello, Alpha sight, Boxer Capital. Other Relationship; Amylyx.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-3-PUB
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 4-OR: Oxidative Phosphorylation in Kidney-Resident Macrophages Aggravates
the Progression of Diabetic Kidney Disease-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 4-OR
Abstract: Introduction and Objective: Oxidative phosphorylation (OXPHOS) is a hallmark alteration in the diabetic kidney. However, it remains unclear whether this change occurs in kidney-resident macrophages (KRMs) and how this condition contributes to the progression of diabetic kidney disease (DKD).Methods: We investigated OXPHOS-related transcriptomic changes in KRMs within diabetic kidneys using single-cell RNA sequencing data derived from human kidneys. We assessed OXPHOS expression in KRMs and its associated renal immunological alterations in DKD mouse models induced by high-fat diet, streptozotocin, and adenine-mixed diet, particularly under conditions of augmented inflammation.Results: Single-cell RNA sequencing analysis revealed increased OXPHOS alteration in KRMs of diabetic kidneys compared to nondiabetic controls. These findings were validated through the examination of OXPHOS-related protein expression in biopsy-proven diabetic nephropathy samples, where enhanced OXPHOS expression correlated with accelerated DKD progression. In DKD mouse models, elevated OXPHOS expression in diabetic KRMs promoted T cell infiltration into the kidneys through the overexpression of chemokine ligands and proinflammatory cytokines. Inhibition of OXPHOS reduced T cell infiltration and mitigated the decline in renal function.Conclusion: Elevated OXPHOS expression in KRMs is a defining feature of diabetic kidneys, fostering a proinflammatory milieu through T cell infiltration. Targeting OXPHOS in KRMs may serve as a potential therapeutic strategy for DKD.DisclosureH. Yoon: None. P. Park: None. J. Hwang: None. M. Hong: None. B. Jang: None. C. Kang: None. D. Yun: None. S. Han: None.FundingKorea Health Industry Development Institute (HI23C1531)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-4-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 5-OR: Older Adults with Diabetes Require Longer Time to Initiate and
Maintain CGM Technology with Use of Remote Education-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 5-OR
Abstract: Introduction and Objective: Continuous glucose monitoring (CGM) initiation and support by remote education has been successfully performed in adults with diabetes. However, the feasibility of initiating CGM remotely, or time needed for the virtual education for CGM initiation, in older adults is not known. Currently, Medicare provides 2 hours annually for ongoing education in older adults, and it is unknown if this allotment is adequate. We evaluated the time to initiate CGM in older adults on complex insulin regimens, as a part of the ongoing study, Readiness, Education and Sustainability for CGM Technology adoption (REST).Methods: Older adults with diabetes (≥65 years) on ≥3 daily insulin injections, either CGM naïve or unsuccessful CGM users, were recruited. An initial in-person visit was used for CGM set-up, followed by weekly remote visits during the first month, to get participants fully familiarized with CGM use. Time spent during each scheduled visit and any unscheduled additional visits needed or requested by participants were analyzed.Results: Overall, 98 participants (age 71 ± 5 years, 33% T1D, 65% with cognitive dysfunction (MoCA <26)) were evaluated. During the first month, time for scheduled visits averaged 271 ± 108 minutes (54 minutes/visit). Extra unscheduled virtual visits were performed in 39% of participants (range 1-5 visits) for a total of 58 ± 72 extra minutes. Eleven participants (11%) required an additional in-person visit for support. Compared to those requiring no additional study visits, participants needing extra visits were more often CGM naïve (76% vs 60%), older (median age 75 vs 69 years), living alone (50% vs 35%), and cognitively impaired (71% vs 62%).Conclusion: Despite ample time allowed for CGM education in the study protocol, older and frailer adults frequently required extra time and visits. These findings suggest that the current Medicare education time provision is inadequate to start or maintain CGM in older adults.Disclosure E. Toschi: Consultant; Vertex Pharmaceuticals Incorporated, Sequel Med Tech. Research Support; Dexcom, Inc. C. Slyne: None. M. Savory: None. H. Brabant: None. J.D. Bulger: None. N. Krakoff: None. B. Matthews: None. A. Bradshaw: None. A. Adam: None. M. Munshi: Advisory Panel; Abbott, Medtronic. Research Support; Dexcom, Inc. Advisory Panel; Sanofi. R.S. Weinstock: Research Support; Amgen Inc, Eli Lilly and Company, Tandem Diabetes Care, Inc, Diasome Pharmaceuticals, Insulet Corporation, MannKind Corporation, Dexcom, Inc.FundingThis work is supported by a grant from The Leona M. and Harry B. Helmsley Charitable Trust
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-5-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 5-PUB: Representation of Patients with CKD in Trials of CGM in Type 2
Diabetes—A Systematic Review-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 5-PUB
Abstract: Introduction and Objective: Approximately 40% of individuals with type 2 diabetes (T2D) develop chronic kidney disease (CKD), which confers high morbidity and mortality. Although continuous glucose monitoring (CGM) technology has revolutionized diabetes care, its role in patients with CKD is under-studied. We aimed to quantify and characterize the exclusion of patients with CKD from randomized controlled trials (RCTs) of CGM as the primary intervention in adults with T2D.Methods: We systematically searched MEDLINE (inception through December 2024) for RCTs comparing real-time CGM (rtCGM) or intermittently scanned CGM (isCGM) as the main intervention versus usual care for at least 2 months in adults with T2D. We excluded studies using only retrospective or blinded CGM, or combining CGM with additional glycemic-lowering strategies (e.g., intensive lifestyle program). Data on study characteristics, CKD-related eligibility criteria, baseline kidney function (creatinine, eGFR, or albuminuria), and kidney outcomes were extracted.Results: Literature search identified 15 RCTs (10 rtCGM, 5 isCGM) comprising 1,637 participants with T2D. Among these trials, 10 (67%) explicitly excluded patients based on eGFR (<30 mL/min/1.73 m^2 [n=3], <45 [n=2]), elevated creatinine (>2 mg/dL [n=2]), or receiving dialysis (n=3). Only 5 (33%) reported baseline kidney function, and the proportion of participants meeting CKD definition with eGFR <60 ranged from 0% to 9%. Only two (13%) trials evaluated CGM effects on kidney outcomes (changes in creatinine or albuminuria).Conclusion: Patients with CKD are underrepresented in RCTs evaluating CGM as an intervention in adults with T2D. Further research is needed to assess efficacy and safety of CGM use specifically in individuals with moderate-to-severe CKD to ensure that diabetes guidelines on CGM can be appropriately generalized to this high-risk population.Disclosure M. Tang: Research Support; Dexcom, Inc., American Heart Association. S. Sanzone: None. S. Kalim: Consultant; Fresenius. Speaker's Bureau; Vistera.FundingAmerican Heart Association Award (23POST1010825)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-5-PUB
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 6-OR: The Effectiveness of Personalized Dietary Advice Based on CGM Data
for Newly Diagnosed Patients with Type 2 Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 6-OR
Abstract: Introduction and Objective: Research on using electronic platforms to adjust diets for type 2 diabetes (T2D) patients with CGM data is scarce. This study aimed to evaluate the effectiveness of personalized dietary advice based on CGM data delivered through a digital platform for newly diagnosed T2D patients, focusing on glycemic control and management adherence.Methods: A 3-month randomized, controlled, open-label, parallel-group study was conducted, enrolling newly diagnosed T2D patients who were allocated into two groups. Group A received standard dietary education for diabetes management, while Group B utilized a mini-program with researcher support and wore a CGM device for one week. Group B received personalized dietary feedback based on CGM data during this period. Both groups were monitored until their 3-month follow-up outpatient clinic visit. The study assessed differences in weight, glycated hemoglobin levels, fasting blood glucose, Diabetes Self-Care Activities (DSCSA), and patient satisfaction between the groups before and after the intervention to evaluate its effectiveness.Results: Out of the initial cohort, 108 patients completed the study's comprehensive follow-up, with a 10% attrition rate. Following the intervention, both groups exhibited reductions in glycated hemoglobin levels. However, the intervention group demonstrated significantly superior outcomes compared to the control group in terms of glycated hemoglobin (P=0.02), Diabetes Self-Care Activities (DSCSA) scale (P<0.001), and patient satisfaction (P=0.03). Subgroup analyses indicated that younger patients, with higher body weight, greater educational attainment, and elevated initial blood glucose levels experienced more pronounced effects from the intervention.Conclusion: Personalized dietary guidance via a digital platform improves glycated hemoglobin, blood glucose levels, self-management, and treatment satisfaction in newly diagnosed T2D patients.DisclosureH. Wan: None. N. Yao: None. Z. Gui: None. D. Wang: None. J. Shen: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-6-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 6-PUB: Predictors of Mortality in Adult Patients with Diabetic
Ketoacidosis in a Tertiary Hospital in Davao Del Norte, Philippines—A
Retrospective Cohort Study-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 6-PUB
Abstract: Introduction and Objective: Diabetic ketoacidosis is a life-threatening but preventable complication of diabetes mellitus. It has a significant morbidity and mortality risk depending on the quality of medical care provided. The death rate of DKA ranges from 6 to 24 percent in developing countries, such as the Philippines, which becomes 100% lethal if not managed appropriately. Risk factors for DKA mortality include delayed presentation to medical care, increasing age, severe acidosis, presence of comorbidities, and infections. Furthermore, there is a disparity in patient’s awareness of DM signs and symptoms leading to complications specifically diabetic ketoacidosis. This study aimed to identify the significant predictors of mortality among adult patients with diabetic ketoacidosis admitted at Davao Regional Medical Center from January 2018 to December 2022.Methods: This study employed a quantitative, retrospective, analytical, and cohort research design. Data from medical charts were analyzed using multiple logistic regression analysis.Results: Forty-two percent of the subjects were aged 41-60 years old. The incidence of DKA is increased in women with a proportion of 63%. Infection associated with DKA is recorded in 69% of the subjects and urinary tract infection (63%) is the most common. Nineteen percent of DKA patients had a decreased level of sensorium (GCS 3-8) followed by GCS 9-14 (35%) while 46% of patients had GCS 15 upon admission. Patients with DKA severe have a proportion of 49% in the study. Forty patients (26%) of the subjects were DKA moderate and lastly, 25% had DKA mild.Conclusion: The mortality rate of patients with Diabetic Ketoacidosis was 39%. Age (p=0.001) and the presence of pneumonia (p=0.007) were the only statistically significant predictors of DKA mortality in this study. Diabetes care programs, frequent outpatient follow-ups, and programs engaging in diabetes self-management education may be effective strategies to reduce the number of mortality.DisclosureH.L. Halasan: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-6-PUB
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 7-OR: The Libre Enabled Reduction of A1C through Effective Eating and
Exercise Study—LIBERATE CANADA-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 7-OR
Abstract: Introduction and Objective: Initiating and maintaining new eating and exercise behaviours with meaningful glycemic improvement is often difficult for those living with T2D. The LIBERATE study aimed to evaluate the efficacy of a real world, standardized, six-month, virtual group diabetes self-management education (DSME) program, which incorporated wearable technology including isCGM to support behaviour change.Methods: Participants with T2D and HbA1c ≥ 8% were recruited for this open label, prospective cohort study. The LIBERATE intervention included virtual small group sessions every two weeks for the first 12 weeks and monthly for the last 12 weeks. Participants used the FreeStyle® Libre 2 for glucose monitoring continuously during the first three months and had the option to use three sensors in the last three months. The FitBit Inspire 2 was used to track physical activity. Virtual group sessions were facilitated by a CDE with content created based on current DSME principles emphasizing the use of isCGM data to personalize lifestyle choices. The primary outcome was percent mean change in HbA1c. Paired T-tests were utilized for analysis.Results: In 92 participants (mean age, 55 years; 44% female; diabetes duration, 8 years; 78% not using insulin. HbA1c significantly improved from 9.8% (± 1.5%) to 7.6% (± 1.2%), p<0.01 at endpoint. Percentage mean time in range (TIR) (3.9mmol to 10.0mmol) also increased significantly; mean TIR at baseline = 66.8% (± 26.2%) vs. TIR at midpoint = 74.1% (± 24.5), p<0.05.Conclusion: Combining six months of virtual group coaching designed to empower individual self-management with isCGM technology rapidly improved HbA1c and TIR, with sustained effects seen at six months despite less intensive coaching. These findings support broader implementation of combining wearable technology and virtually supported DSME to enhance diabetes care and patient outcomes, including for those not yet on insulin therapy in T2D.Disclosure S.M. Reichert: Research Support; Abbott Diagnostics. Speaker's Bureau; Abbott. Advisory Panel; Novo Nordisk. Speaker's Bureau; Novo Nordisk. Other Relationship; Novartis Pharmaceuticals Corporation. Advisory Panel; Bausch Health, Sanofi, embecta, Eisai, Eli Lilly and Company. Consultant; Center for Effective Practice (CEP),. Research Support; Western University. Other Relationship; Diabetes Canada. Advisory Panel; Bayer Pharmaceuticals, Inc. Speaker's Bureau; Humber River Health, Federation of Canadian Medical Women, Medscape, Peer Voice. H.C. Gerstein: Advisory Panel; Abbott, Bayer Pharmaceuticals, Inc, Eli Lilly and Company, Novo Nordisk. Consultant; Pfizer Inc, Sanofi, Hanmi Pharm. Co., Ltd. Research Support; Eli Lilly and Company, Novo Nordisk, Hanmi Pharm. Co., Ltd. Other Relationship; Eli Lilly and Company, Novo Nordisk, Sanofi, Boehringer-Ingelheim, Abbott, Jiangsu Hansen, Zuellig Pharma, AstraZeneca. B. Harvey: None. A.G. Mikalachki: None. D. Sherifali: None. M. Mitchell: None. P. Brauer: None. D. Henke: None. L. Vancer: Speaker's Bureau; Abbott. S.B. Harris: Advisory Panel; Abbott. Consultant; Abbott. Research Support; Boehringer-Ingelheim. Advisory Panel; Dexcom, Inc. Consultant; Dexcom, Inc. Research Support; Canadian Institutes of Health Research. Advisory Panel; Eli Lilly and Company. Research Support; Eli Lilly and Company. Consultant; Medscape. Advisory Panel; Novo Nordisk. Research Support; Novo Nordisk, Novartis Pharmaceuticals Corporation. Advisory Panel; Sanofi. Consultant; Sanofi.FundingAbbott
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-7-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 7-PUB: Pulse Pressure Predicts Cardiovascular Events in Coronary Artery
Disease Patients with Type 2 Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 7-PUB
Abstract: Introduction and Objective: Pulse pressure, i.e. the difference between systolic and diastolic blood pressure is a measure of arterial stiffness, which is a strong predictor of cardiovascular risk. Its impact on the risk of cardiovascular events in coronary artery disease (CAD) patients with type 2 diabetes (T2DM) is unclear and is addressed in the present study.Methods: We enrolled a large high-risk cohort of 1422 patients with angiographically proven CAD. T2DM was diagnosed according to ADA criteria. Prospectively, cardiovascular events were recorded over a mean follow-up period of 8.5±5.5 years.Results: At baseline, pulse pressure was 59±16 mmHg in patients with T2DM (n=443) and 56±16 mmHg in subjects who did not have T2DM (p=0.004). During follow-up, 770 patients suffered cardiovascular events. The event rate was higher in patients with T2DM than in those who did not have diabetes (63.0% vs. 50.8% p<0.001). Pulse pressure significantly predicted cardiovascular events after multivariate adjustment including diabetes status in the total study cohort, with a standardized adjusted hazard ratio (HR) of 1.10 [1.02-1.18]; p=0.016. Importantly, pulse pressure also predicted cardiovascular events in the very high-risk subgroup of CAD patients with T2DM (HR 1.16 [1.03-1.32]; p=0.018).Conclusion: We conclude that pulse pressure predicts cardiovascular events in CAD patients with T2DM.DisclosureT. Plattner: None. A. Vonbank: None. B. Larcher: None. A. Mader: None. L. Schnetzer: None. M. Neyer: None. J. Vogel: None. P. Elsner: None. A. Leiherer: None. A. Muendlein: None. A. Festa: None. H. Drexel: None. C.H. Saely: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-7-PUB
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 8-OR: Short-Term Continuous Glucose Monitoring Reveals Insights and
Promotes Behavioral Awareness in People with Non-Insulin-Treated Type 2
Diabetes, Even after Minimal Instructions-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 8-OR
Abstract: Introduction and Objective: CGM has shown promise as a valuable tool for learning and managing blood glucose levels in persons with non-insulin-treated Type 2 Diabetes (PwT2D). This study investigated the insights PwT2D gain regarding the influence of lifestyle factors on blood glucose levels over a two-week period of CGM usage, with minimal instruction and support.Methods: As a walk-in setup in 20 cities in Denmark, a single CGM device (max. 14 days) was provided to PwT2D not on insulin therapy. Participants received minimal guidance during device installation and completed a baseline questionnaire onsite. Follow-up surveys were sent via email after two weeks and three months.Results: Of the individuals enrolled,724 completed the second questionnaire after two weeks. Of these, 80% found the CGM highly useful and informative. Compared to participants with a diabetes duration over five years, participants with a diabetes duration of less than five years engaged in more daily scans (80% vs. 71%) and reported greater insights into how blood glucose levels were affected by food items (88% vs. 78%), portion sizes (80% vs. 60%), and physical activity (65% vs. 55%). Education level had no significant impact on knowledge acquisition. At the three-month follow-up, half of the participants reported maintaining behavioral changes based on their two-week CGM experienceConclusion: The findings highlight that even brief CGM usage with minimal instruction can provide PwT2D with valuable, personalized insights into how lifestyle factors influence blood glucose levels. These insights may encourage long-term behavioral changes, potentially leading to improved glycemic control. Notably, diabetes duration significantly influences the depth of insights gained, while education level does not appear to impact knowledge acquisition.DisclosureE. Munch Nielsen: None. A.K. Wegener: Other Relationship; Abbott. N. Cayuelas Mateu: Other Relationship; Abbott. T. Thybo: Other Relationship; Abbott.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-8-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 8-PUB: Role of ADA Guidelines with the Indian Twist for Mitigating ASCVD
Risk in Type 2 Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 8-PUB
Abstract: Introduction and Objective: 75% of T2DM individuals die due to Atherosclerotic cardiovascular disease (ASCVD) globally. The ADA guidelines suggests use of SGLT2 inhibitors (SGLT2I) in high CVD risk indications and combination therapies for better glycemic outcomes. This study is done to assess the ASCVD risk among T2DM individuals in India and the role of ADA guidelines for glycemic control on ASCVD risk but with fixed dose combinations (FDC) in India.Methods: ASCVD risk among (N=50) T2DM individuals aged 40-70 years already on treatment for T2DM with or without hypertension/dyslipidaemia was calculated using ASCVD risk estimator plus on DAY 0.For T2DM Individuals with low and high risk for ASCVD were initiated on FDC of (SGLT2i, Dpp4i, Metformin), along other agents. Hypertension and Dyslipidemia were treated with monotherapy or FDCs. Day 90 ASCVD risk was compared with Day 0.Results: Day 0 and Day 90 mean ASCVD risk was 12.39 ± 11.41 % and 10.56 ± 9.74 %. Day 0 and Day 90 HBA1C was 9.38 ± 1.5 % and 7.2 ± 0.7 %. Day 0 and Day 90 BMI was 29.3 ± 4.98 and 28.45 ± 4.74. By day 90 Total cholesterol, Triglycerides and LDL were reduced by 24 ± 1.2 mg/dl, 54 ± 35.2 mg/dl and 12 ± 2.5 mg/dl. On day 90 Systolic and Diastolic blood pressure reduced by 13.92 ± 6.7 MMHG and 4.5 ± 4.0 MMHG.Conclusion: ADA guided T2DM treatment recommendations and FDC available in India along with Hypertension and Dyslipidemia treatment are useful for mitigating ASCVD risk.DisclosureS. Ramanarayanan: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-8-PUB
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 9-OR: Change in HbA1c and Weight after Healthy Grocery Delivery and
Low-Carb Education among People with Type 2 Diabetes and Food Insecurity-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 9-OR
Abstract: Introduction and Objective: Low carbohydrate eating plans can improve glycemic control, promote weight loss, and are associated with improved cardiometabolic health and all-cause mortality. Individuals with food insecurity often lack resources to adopt the necessary dietary changes. We aimed to implement and evaluate a quality improvement (QI) program, called Jumpstart, to support patients with T2D and food insecurity to adopt a lower carbohydrate, healthier diet.Methods: We conducted a cohort-based QI program aimed at promoting dietary change in adult patients with T2D. Eligible adults had a diagnosis of T2D, self-identified food insecurity or low income, and received care from a clinic participating in the Michigan Collaborative for Type 2 Diabetes, a statewide T2D quality improvement collaborative. The 3-month program included home grocery delivery, $80/month of healthy food purchasing credits, and nutrition education materials on lower carbohydrate diets. Medical records for 6-months prior to enrollment through 12-months after enrollment were obtained and differences in weight and HbA1c were assessed using two-tailed paired t-tests (alpha=0.05) comparing baseline to post-program measurement.Results: Among the 83 participants who completed the program the mean age was 57 years ±13, 72% identified as female, and 90% identified as white. Reduction in HbA1c from baseline was 0.47%±1.59% at or after 6-months from program enrollment (p=0.017, n=68). Reduction in weight at 9-months or later was 2.1%±4.4% (p=0.006, n=38) correlating to 2.2lbs of weight lost on average.Conclusion: Participants in the Jumpstart program experienced sustained reduction in HbA1c and body weight. Programs that use grocery delivery with nutrition education may successfully promote long term dietary change and improve health among adults with T2D and other vulnerable populations.DisclosureE. Waselewski: None. M. Waselewski: None. L. Oshman: Stock/Shareholder; Procter & Gamble, Merck & Co., Inc, AbbVie Inc. T. Chang: None.FundingSupport for this work is provided by Blue Cross and Blue Shield of Michigan as part of the BCBSM Value Partnerships program. The opinions, beliefs and viewpoints expressed by these authors do not necessarily reflect the opinions, beliefs and viewpoints of BCBSM or any of its employees.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-9-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 9-PUB: Determinants of Hepatic Steatosis and Its Association with
Retinopathy in Indian Adolescents and Adults with Type 1 Diabetes Mellitus
-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 9-PUB
Abstract: Introduction and Objective: Liver disease in Type 1 diabetes mellitus (DM) is a rare complication and may arise from glycogen deposition and fatty liver. There is insufficient data to establish the prevalence of liver disease in patients with T1DM. The aim is to evaluate the predictors of liver disease in Indian adolescents and adults with T1DM.Methods: The study included 40 subjects with T1DM without any pre-existing liver disease ( mean age 24.3 ± 10.3 years, BMI 20.6 + 3.8 kg/m2) presenting to our Endocrine OPD. Transient elastography, anthropometry, and metabolic workup were performed.Results: The mean diabetes duration was 13.8 ± 8.5 years, with a mean age of onset of 10.4 ± 6.1 years. HbA1c levels were uncontrolled in 80% of participants. Steatosis (CAP score > 248 dB/m) was present in 10% of cases, and 7.5% showed elevated ALT levels. CAP scores correlated significantly with diabetes duration (r = 0.44, p = 0.005), BMI SDS (r = 0.46, p = 0.003), and ALT levels (r = 0.32, p = 0.042). Patients with steatosis had 17-fold higher odds of abnormal fundus examinations (p = 0.04), while those with elevated ALT levels had 35-fold higher odds of retinopathy (p = 0.02).Conclusion: Indian T1DM patients are at increased risk of NAFLD, potentially linked to diabetic retinopathy. Larger studies are needed to explore liver disease progression and its correlation with retinopathy in T1DM.DisclosureR. Shukla: None. V. Yadav: None. A. Mahapatra: None. A. Bajpai: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-9-PUB
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 10-OR: Real-World Outcomes of a Fasting Mimicking Diet Program for Type 2
Diabetes Management-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 10-OR
Abstract: Introduction and Objective: An ADA consensus report highlights the potential of intensive lifestyle interventions to improve glycemic control and reduce medication burden in type 2 diabetes (T2D). This study evaluates the real-world efficacy of a medically supervised diabetes management program incorporating the Fasting Mimicking Diet (FMD).Methods: Participants with T2D completed up to eight monthly cycles of a 5-day FMD, designed to mimic fasting physiology while providing essential nutrition (Day 1, 1100 kcal; Days 2 - 5, 720 kcal). The program included bi-weekly support and behavioral coaching from registered dietitians (RDs), and quarterly physician-led (MD) diabetes medication adjustments aimed at optimizing glycemic control and reducing diabetes medication.Results: A total of 128 patients enrolled. Data from 74 participants at 3 months and 29 at 6 months who completed at least 3 months were analyzed. The proportion achieving HbA1c <7% increased from 49% at baseline to 70% at 3 months (p<0.001) and 62% at 6 months (p<0.05). Diabetes medication was reduced in 73% and 68% of patients at 3 and 6 months, respectively. Mean HbA1c decreased by 0.54% ± 0.84% at 3 months and 0.53% ± 0.73% at 6 months, with significant weight loss (-4.5 kg ± 3.5 and -6.7 kg ± 4.5; p<0.0001). Engagement was high, with a 94% RD/MD appointment show rate and a Net Promoter Score of 92.Conclusion: This innovative FMD-based lifestyle program, supported by RDs and supervised by MDs, effectively improves glycemic control, reduces medication burden, and promotes weight loss with high engagement and satisfaction, offering a promising new model for T2D management.DisclosureA. Bizzell: Employee; L Nutra, Inc. T. Hall: None. N.K. Grant: Employee; L-Nutra. C.A. Margolin: Employee; L-Nutra. M. Wei: Employee; L-NUTRA INC. W. Hsu: Employee; L-Nutra, Inc.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-10-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 10-PUB: Pressure Alternating Shoes for Prevention of Diabetic Foot Ulcers
-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 10-PUB
Abstract: Introduction and Objective: Diabetic foot ulcers often develop at sites of moderate and high pressure on the sole of the foot that are exposed to repetitive loading. Our objective was to develop and assess a novel shoe that would change pressure and cyclical loading of the foot to prevent repetitive injury and ulceration.Methods: Our team designed an instrumented prototype of a shoe that would dynamically change the pressure distribution on the sole of the foot during gait (Figure 1). Using the designed insole/shoe, 20 healthy subjects and 1 diabetic patient participated in six different walking conditions. Gait patterns were assessed using wearable sensor systems. Near infrared imaging device was used to measure blood perfusion. Plantar Interface pressure and peak pressure were measured using a commercial pressure system, and both were used to evaluate the effectiveness of the insoleResults: There was no statistically significant differences in gait parameters based on the different shoe walking conditions. There was significantly higher mean deoxyhemoglobin of the plantar lateral foot prior to gait testing. There were no differences in oxygen saturation or oxyhemoglobin of the plantar foot. Figure 1 shows changes in peak pressures reduction in respective cells.Conclusion: Our results show that an insole/shoe with dynamic pressure reduction capabilities has the potential to reduce the risk of plantar pressures during dynamic conditions without increasing the risk of changing gait patterns.DisclosureM.C. Reyes: None. V. Erel: None. M.B. Wijesundara: None. L.A. Lavery: Consultant; Limflow, enerenesis Medical, Clyra Medical technologies, Blue Sky, Tissue Health Plus. Stock/Shareholder; Xilas Medical. Consultant; Altrazeal.FundingNational Institute of Aging of the National Institute of Health (7R21AG06147)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-10-PUB
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 11-OR: Effects of a Whole Fruit–Rich Diet on Glycemic Control, Ectopic
Fat, and Cardiovascular Risk Factors in Adults with Type 2 Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 11-OR
Abstract: Introduction and Objective: Very-low-calorie diets and low-carbohydrate diets can improve glycemic control. However, less is known about the effects of carbohydrate-rich whole foods, such as whole fruit. Therefore, we performed the first clinical trial testing the effects of a whole fruit-rich diet on glycemic control, ectopic fat, and cardiovascular health in adults with type 2 diabetes (T2D).Methods: In this 12-week pilot study, 10 adults with insulin-independent T2D for ≤6 years progressively consumed more whole fruit during weeks 1-4 (ramp-up phase). During weeks 5-12, participants ate very large amounts of whole fruit (50% of energy intake, or ~16.4 servings/day) combined with a Mediterranean diet. Participants were kept weight stable. Outcomes were measured at weeks 0, 4, and 12. Glycemic control was assessed hierarchically by whether participants met the glycemic threshold for T2D remission, the total dosage of antihyperglycemic medications, an OGTT, and continuous glucose monitoring. Liver and pancreatic fat were assessed via MRI/S. BP and lipids were also measured.Results: The high-fruit diet improved glycemic control in 90% (9 of 10) of participants. Six out of 8 participants were weaned off their antihyperglycemic medications at week 10, and half of the weaned participants met the glycemic threshold for T2D remission at week 12 (p<0.0001). The whole fruit-rich diet also reduced the need for antihyperglycemic medications (p=0.03) and decreased systolic BP by 11 ± 2 mm Hg (p=0.0002). However, it increased triglycerides by 31 ± 15 mg/dl (p=0.04). There were no changes in liver fat (-1.3 ± 0.9%; p=0.14) or other outcomes. Intriguingly, mean 24-hour glucose and liver fat transiently increased and then decreased, potentially suggesting a period of metabolic adaptation.Conclusion: A high-fruit Mediterranean diet improves glycemic control, reduces the need for glucose-lowering medications, and lowers BP in people with early-stage T2D.DisclosureC. Hanick: None. W. Garvey: Advisory Panel; Boehringer-Ingelheim, Eli Lilly and Company, Novo Nordisk, Fractyl Health, Inc., Alnylam Pharmaceuticals, Inc, Zealand Pharma A/S, Allurion, Carmot Therapeutics, Inc, TERNS Pharmaceuticals, Regeneron Pharmaceuticals, Inogen, Neurocrine, Keros Therapeutics. Research Support; Novo Nordisk, Eli Lilly and Company, Epitomee, Neurovalens, Roche Pharmaceuticals, Zealand Pharma A/S. A.M. Goss: None. J.S. Richman: None. K.J. Berg: None. C.M. Peterson: None.FundingNational Institute of Diabetes and Digestive and Kidney Diseases (P30 DK079626). NIH Predoctoral T32 Obesity Fellowship (T32 HL105349) from the National Heart, Lung, and Blood Institute.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-11-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 11-PUB: Improving Diabetic Foot Exam Completion Using a Nursing-Led
Process-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 11-PUB
Abstract: Introduction and Objective: Screening foot exams are an integral part of early identification of diabetic neuropathy to help prevent future amputations. Completion rates for foot exams has been historically variable in many studies. The National Committee for Quality Assurance (NCQA) has established that at least 80% of patients with diabetes in a practice should have completed screening foot exams at least once annually. In a safety-net health system, it was found that from January 2023- March 2023, the baseline completion rate of foot exams was 68%.Methods: To improve completion rates, a quality improvement project was conducted using clinic nurses to chart review every patient as they arrived to clinic for their appointment to identify which patients had not completed a foot exam in the past 365 days. Those patients were asked to take of their shoes and socks and providers were notified that patients needed a foot exam.Results: Using this simply approach, foot exam completion rose to an average of 84% (p <0.05) by December 2024.Conclusion: This project shows that a simple intervention can improve foot exam completion rates and potentially identify diabetic neuropathy and early foot wounds.DisclosureU. Gunasekaran: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-11-PUB
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 12-OR: Beneficial Effects of Mediterranean Diet on Body Composition and
Glucose Metabolism—A Randomised Controlled Trial-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 12-OR
Abstract: Introduction and Objective: The rising prevalence of obesity and metabolic disorders, such as type 2 diabetes, highlights the need for effective dietary strategies to improve health outcomes. The Mediterranean diet has been well studied and shown to reduce chronic disease risk through its beneficial effects on body composition and glucose metabolism. The Australian Guide to Healthy Eating (AGHE) was intended to offer a balanced dietary framework, yet its comparative efficacy with the Mediterranean diet remains unexplored. Thus, this study aims to compare the efficacy of the Mediterranean diet with AGHE on body composition and glucose metabolism.Methods: We conducted a randomised controlled trial including 57 participants (median age 31, IQR: 25-37 years; 71.9% female, BMI = 25.1 kg/m2), with 23 participants randomised to the Mediterranean diet and 34 participants to the AGHE diet for eight weeks. Anthropometric measurements, estimated metabolic rate (indirect calorimetry) and body composition (Dual-Energy X-ray Absorptiometry, DEXA) were assessed. Fasting serum samples were collected to measure glucose and insulin concentrations. Paired t-tests were employed for within-group comparisons, and analysis of covariance (ANOVA) was used for between-group comparisons, adjusted for age and baseline values.Results: The Mediterranean diet intervention resulted in a significant decrease in waist circumference (-1.3 cm, p = 0.043), body fat percentage (-1.8%, p = 0.014), resting metabolic rate (RMR) (-17.9 kcal/day, p = 0.02), and fasting insulin concentration (-1.2 μIU/mL, p = 0.016), along with an increase in body lean mass percentage (1.7%, p = 0.015) compared to AGHE group.Conclusion: The Mediterranean diet demonstrated greater efficacy in improving body composition and maintaining metabolic variables compared to the AGHE. These findings may support the use of the Mediterranean diet in improving health outcomes related to obesity and metabolic disorders.DisclosureR.H. Kabthymer: None. B. de Courten: None. J. Danaher: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-12-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 12-PUB: Improved Glycemic Control among Individuals with Long-Standing
Diabetes during COVID-19 Lockdown—An Observational Study-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 12-PUB
Abstract: Introduction and Objective: The COVID-19 pandemic introduced significant lifestyle changes, including lockdown measures that altered physical activity and daily routines. The impact of these changes on glycemic control in individuals with long-standing type 2 diabetes mellitus (T2DM) has not been well studied.Objective: To evaluate changes in glycemic control and physical activity during the COVID-19 lockdown compared to pre-lockdown levels in individuals with long-standing T2DM.Methods: This observational study included 100 T2DM patients who regularly attended a diabetes clinic before the lockdown. Data on glycemic parameters (HbA1c and postprandial blood glucose) and physical activity, assessed using the Global Physical Activity Questionnaire (GPAQ) as metabolic equivalents (METs min/week), were collected during the lockdown period (minimum 3 months).Results: The median age of participants was 51 years (IQR: 35-75), with a median diabetes duration of 9.5 years (IQR: 4-16). Foot complications and atherosclerotic cardiovascular disease were prevalent in 19% and 22% of participants, respectively. HbA1c decreased significantly from 8.1% (IQR: 6.7-9.5) pre-lockdown to 7.6% (IQR: 6.5-8.9) during lockdown (p < 0.001). Postprandial glucose levels improved from 212 mg/dL (IQR: 142-262) to 151 mg/dL (IQR: 129-210) (p < 0.001). Physical activity scores increased from 140 METs (IQR: 0-1270) to 850 METs (IQR: 0-1680) (p = 0.014). Notably, improved glycemic control was observed across genders and was independent of the presence of foot complications or changes in physical activity.Conclusion: The COVID-19 lockdown was associated with improved glycemic control in individuals with long-standing T2DM, regardless of changes in physical activity. These findings suggest that other factors, such as dietary changes or increased focus on self-care during lockdown, may have contributed to better diabetes management.DisclosureD. Raval: None. V.M. Rathod: None. R. Patil: None. K. Rana: None. A. Bhattacharya: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-12-PUB
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 13-OR: Overcoming Therapeutic Inertia in Newly Diagnosed Type 2
Diabetes—Results of a Randomized Trial-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 13-OR
Abstract: Introduction and Objective: Therapeutic inertia (TI) in type 2 diabetes (T2D) is well documented and leads to worse glycemic control. Timely metformin initiation increases the likelihood of achieving glycemic targets early after diagnosis. Unfortunately, metformin initiation after diagnosis remains suboptimal. We conducted a cluster-randomized trial of PCP education with and without proactive pharmacist outreach to address TI among adults recently diagnosed with T2D who were not prescribed or were non-adherent to metformin.Methods: We randomized service areas within an integrated care system to 3 arms: 1) Usual care, 2) PCP education on TI, and 3) PCP TI education plus a pharmacist call to discuss metformin and self-management. Eligible people were patients of PCPs in randomized areas, ages 18-64, who had a recent T2D diagnosis with a most recent A1c of 6.5-7.9% who were not prescribed or were non-adherent to metformin (adults with A1c≥8% receive pharmacist outreach as standard-of-care). Primary outcomes included A1c<7% and A1c<8% at 6 and 12 months, and secondary outcomes included metformin initiation. T-tests, chi-square tests, and random-effects logistic regression were used to test for between-arm differences.Results: A total of 877 individuals were randomized (Arm 1: 257, Arm 2: 255, Arm 3: 305), with a mean A1c of 6.9%. Patients in the intervention arms had significantly better A1c levels at 6 months (A1c<7%: 81% Arm 3, 76% Arm 2) than usual care (70% Arm 1, p=0.03). This benefit was sustained at 12 months (A1c<8%: 97% Arm 3, 96% Arm 2, 87% Arm 1, p <0.01). Arm 3 patients had higher odds of starting metformin at 6 months (OR 1.53 CI:1.02, 2.29, ref=Arm 1, OR 1.75 CI: 1.16, 2.64, ref=Arm 2) though pharmacists only reached 60% of Arm 3 patients.Conclusion: In this trial, combining PCP education and pharmacist outreach resulted in less glycemic deterioration and increased odds of metformin initiation. These findings highlight the potential of a low-touch, proactive intervention leveraging non-physician clinicians to improve T2D outcomes.DisclosureC. Board: None. J. Johnston: None. T.K. Thai: None. E. Huynh: None. A. Chan: None. J. Nugent: None. L.K. Gilliam: None. R.W. Grant: None. A. Gopalan: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-13-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 13-PUB: Markup Methodology to Culturally Tailor Preexisting Preconception
Counseling (PC) Program for American Indian/Alaska Native (AIAN)
Adolescent Girls at Risk for Gestational Diabetes Mellitus (GDM)-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 13-PUB
Abstract: Introduction and Objective: AIAN women are disproportionately at higher risk for GDM and pregnancy-related complications. Culturally-relevant PC could minimize these risks. We describe markup methodology, and its qualitative results used to adapt/culturally-tailor READY-Girls (a validated PC program recommended by the ADA for adolescent girls with diabetes to plan healthy pregnancies) for AIAN adolescents at risk for GDM in the Stopping-GDM (SGDM) study.Methods: Qualitative data were first collected using 5 focus groups of AIAN mother-daughter (M-D) dyads of adolescent girls and a female adult caregiver (e.g., mother, grandmother) regarding GDM and impressions of READY-Girls. Participants were individuals from multiple tribal affiliations at two urban locations, recruited using convenience sampling. Inclusion criteria were girls ages 12-18yrs with self-reported weight and height that calculated to a BMI > 85th percentile, who were fluent in English, did not have diabetes, and had a caregiver available. M-D dyads viewed the video and marked-up pages from the book with written comments on their thoughts to culturally tailor it, using assigned symbols (e.g., * = liked, ' = don’t understand). Marked-up books were analyzed by 3 researchers using content analysis techniques.Results: Participants included 13 AIAN M-D dyads, who successfully provided markups. Cultural preferences suggested included: changing “promises” to “goals”, using Native patterns including neutral colors, marked loved “you have the power to choose”.Conclusion: M-D provided helpful suggestions for cultural modifications of sensitive topics for AIAN adolescents including reproductive health using markup methodology. This methodology could be used with paper or online material to enhance developmentally appropriate qualitative data collection especially when addressing sensitive topics.DisclosureD. Charron-Prochownik: None. S.A. Stotz: None. H. Abujaradeh: None. K. Gonzales: None. K.J. Nadeau: None. Y. Wang: None. X. Pei: None. S.M. Sereika: None. K.R. Moore: None.FundingNIH (1R01NR014831-01A1)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-13-PUB
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 14-OR: Telemedicine Visit Use and Cardiorenal Risk Factor Monitoring Rates
in Patients with Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 14-OR
Abstract: Introduction and Objective: The increase in endocrinology telemedicine visit use since 2020 has had unclear impacts on care quality. This study sought to determine the association between different rates and types of telemedicine visit use and monitoring of cardiorenal risk factors in patients with diabetes.Methods: In this retrospective study, we examined the relationship between video and phone telemedicine visit use and completion of low-density lipoprotein (LDL) cholesterol, urine microalbumin, and blood pressure testing in patients seen by endocrinology for diabetes at a large integrated health system. We studied adults with at least two diabetes visits during the evaluation year (2022).Results: The study population (n=13,246) was 51.3% female with a mean age of 63.3 years. Completion rates for LDL cholesterol, microalbumin, and blood pressure screenings were 76.6%, 67.8%, and 98.1% respectively. Patients had a mean of 23.7% telemedicine visits in 2022 (19.2% video, 4.5% phone). Patients who had only telemedicine visits in 2022 were less likely to have completed screening for all three risk factors than patients with some or no telemedicine visits (49.3% vs. 62.3% vs. 59.6%; p < 0.001). Multivariable logistic regression analysis adjusted for demographic and clinical covariates and screening completion in the previous year (2021) demonstrated that patients with a higher fraction of video and phone visits were less likely to have LDL cholesterol (OR 0.84, p<0.0001; OR 0.71, p<0.0001), microalbumin (OR 0.77, p<0.0001; OR 0.42, p<0.0001), and blood pressure (OR 0.14, p<0.0001; OR 0.09, p<0.0001) testing completed (all ORs correspond to a 50% increase in the fraction of video/phone visits).Conclusion: Higher rates of phone and video visits were associated with a decreased probability of cardiorenal risk factor monitoring. This suggests additional care delivery measures are needed to ensure test completion for patients with a high proportion of telemedicine visits.Disclosure E.G. Thurber: Other Relationship; SimulConsult. Z. Lan: None. A. Turchin: Consultant; Novo Nordisk. Research Support; Eli Lilly and Company. Consultant; Proteomics International.FundingNational Institutes of Health (T32DK007529)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-14-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 14-PUB: Digital Resource Hub—Education and Management Support for Young
Adults with Diabetes (the DREAMS YA Study)-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 14-PUB
Abstract: Introduction and Objective: Diabetes management is particularly challenging for young adults (ages 18-30) living with diabetes (YAWD). To better support this population during this pivotal life stage, four online educational modules were developed that address key aspects of diabetes care.Aim: To evaluate the impact and relevance on aspects of diabetes management of four online topic modules on YAWD and to assess changes in HbA1c and/or time-in-range (TIR) following module completion.Methods: Each topic module incorporates various multimedia modalities. Questionnaires measuring impact (self-reported confidence in self-management) and relevance (participants' ratings) were administered after each module. Pre- and post-module glycemic (HbA1c, TIR) and diabetes distress (DD) data were collected. A final questionnaire and qualitative interview were conducted after completion of all modules.Results: Fifty-one participants enrolled, with 49 continuing past enrollment. Baseline characteristics: 53% male, 63.3% white, average age 24.1 years, A1c 7.1%. Most participants used a CGM (95.9%) with average TIR 66.1% (SD 19.8%). Of those with T1D (89.8%), 84.1% used an insulin pump. Forty participants completed Module 1 on "Mental Health & Wellbeing" with most finding it relevant. They reported increased confidence in self-care and distinguishing between burnout and DD, though they lacked confidence in seeking mental health services. Thirty-nine participants completed Module 2 on "Sex & Diabetes" with most finding it relevant and reporting greater confidence in managing diabetes-related challenges associated with sex. Data for Module 3 and 4 is forthcoming.Conclusion: Our findings demonstrate that an online educational resource hub for YAWD was relevant and impactful in enhancing their understanding and management of key issues. It also proved to be a feasible way to deliver accessible learning. Future research should focus on expanding to a more diverse population, with an emphasis on topics that are pertinent to YA with T2D.DisclosureM. Roche: None. A. Rieger: None. S. Kim: Consultant; Signos.FundingNovo Nordisk
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-14-PUB
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 15-OR: Closing the Loop Early—Enhancing AID Adoption in Youth with
New-Onset T1D-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 15-OR
Abstract: Introduction and Objective: Automated insulin delivery (AID) systems provide enhanced glycemic benefits and reduce diabetes care burden. We implemented a QI initiative aimed at increasing AID use in youth with new-onset T1D (<1 yr) at a large pediatric diabetes center from baseline of 5% in Jan 2022 to >25% by Nov 2024. As a balancing measure, we monitored for diabetic ketoacidosis (DKA) after AID initiation.Methods: The following Plan-Do-Study-Act cycles were implemented:1) Developed a standardized process for AID starts within 90 days of diagnosis, with a Pump Action Plan with back-up injection doses and ketone management.2) Added a 2-week post-diagnosis telemedicine visit with a provider and CDCES to assess AID eligibility.3) Hosted an “AID workshop” educating staff and providers.4) Standardized AID starts across 6 diabetes clinics, with weekly outreach by a CDCES and a post-pump provider visit within 30 days of initiation.5) Sent bulk patient portal messages informing patients about AID systems.Results: P-chart showed an increase in AID use in youth with new-onset T1D, with centerline shift from 13.9% to 33.4% by Nov 2024 (Figure 1). Only two had DKA out of 338 youth with new-onset T1D placed on pumps.Conclusion: Our QI efforts led to an increase in AID use in youth with new-onset T1D. Structured support and pump safety guidance may help mitigate the risk of DKA. Future studies should assess the glycemic impact of early AID initiation.DisclosureM. Vakharia: None. D.A. Buckingham: None. S. Lyons: None. D. DeSalvo: Consultant; Dexcom, Inc. Advisory Panel; Insulet Corporation. S. Mckay: None. S. Kelly: None. R.Y. Sonabend: None. G.K. Kim: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-15-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 16-OR: Pilot Study of Systematic Screening for Diabetes Distress at Two
Federally Qualified Health Centers-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 16-OR
Abstract: Introduction and Objective: Diabetes distress (DD), or the stress, fear, and guilt that can result from living with diabetes, is associated with poor self-management and glycemic outcomes. Although ADA guidelines promote screening for and addressing DD, few adults with diabetes receive formal screening. This pilot study aimed to evaluate the implementation of DD screening at two Federally Qualified Health Centers (FQHCs).Methods: After receiving training around DD and implementation support, two Midwestern FQHCs tailored a new DD screening and intervention algorithm to their sites and screened adults with A1c >8% using the Type 2 Diabetes Distress Assessment System (DDAS) Core and Sources scales as part of a 4-month pilot. FQHCs documented screening scores and resulting interventions. Descriptive statistics were used to assess fidelity and DD prevalence. Staff and patient interviews were conducted to gauge perceived value of DD screening.Results: Staff screened 74 patients (18% Black, 70% White, 45% Hispanic). Of those patients, 61% scored positive with either moderate (n=23) or high (n=22) levels of DD on the DDAS Core. Of those with a positive Core score, 73% (n=33/45) completed the DDAS Sources. The most common sources of distress were Long-term Health (88%) and Management Demands (73%). All patients who completed DDAS Sources were referred internally to their primary care clinician, health coach, or behavioral health to address their DD. In qualitative interviews, staff reported that screening revealed higher levels of DD than anticipated. Staff and patients said that screening provided individualized care and strengthened clinical team-patient relationships.Conclusion: FCHCs successfully integrated DD screening into their clinic workflow, revealing that nearly two-thirds of adult patients with type 2 diabetes experienced DD. Quality improvement efforts are needed to support clinic staff in implementing guideline-based DD screening and intervention protocols to support the care of adults with diabetes.DisclosureC. Cochran: None. A. Durgan: None. E.M. Staab: None. H. Wing: None. C.D. Kasir: None. W. Wan: None. M. Zhu: None. A. Campbell: None. C.T. Schaefer: None. A.A. Baig: None. D.M. Hessler: None.FundingNational Institute of Diabetes and Digestive and Kidney Diseases (R01DK133603-01A1)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-16-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 16-PUB: Exploring Connections between Spirituality and Health Outcomes in
Adolescents with Prediabetes and Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 16-PUB
Abstract: Introduction and Objective: To support adolescent self-care, identification and support for positive coping strategies is necessary. This research explored adolescents’ spirituality as it pertained to coping with prediabetes or diabetes (type 1 or type 2).Methods: Adolescents with prediabetes, type 1, and type 2 diabetes (14-18 years, n=18) completed a structured interview and two questionnaires. Results were analyzed from interviews, the Pediatric Quality of Life Inventory to create physical and psychosocial health summary scores (0-100), and a Spirituality, Religious, Personal Beliefs (WHOQOL SRPB) score (4-20).Results: Participant characteristics are included in the Table. The mean survey scores were 74.6±21.6 (physical health), 79.3±24.3 (psychosocial health), and 13.3±2.4 (SRPB). There were moderate correlations between physical health and SRPB (r=0.59), and psychosocial health and SRPB (r=0.60).Conclusion: Findings suggest a positive relationship between physical and mental health with spirituality in adolescents with prediabetes or diabetes.DisclosureD. Jengelley: None. L.A. Machuca: None. G. Baumberger: None. S.E. Varner-Perez: None. T.S. Hannon: Research Support; Eli Lilly and Company, Novo Nordisk.FundingIndiana University Health Values Fund for the Integration of Spiritual and Religious Dimensions in Healthcare
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-16-PUB
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 17-OR: Novel Autoantibodies Specific to β-Cell Surface Extracellular
Epitope of ZnT8 Predict Progression to Type 1 Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 17-OR
Abstract: Introduction and Objective: Novel autoantibodies to extracellular epitopes of ZnT8 (ZnT8ecA) on the β-cell surface have been recently identified as the earliest detectable autoantibody in children followed from birth. This study aims to determine its prediction for T1D progression.Methods: ZnT8ecA were measured in the DAISY birth cohort participants (n=209) who were confirmed positive for at least one standard islet autoantibody (IAb), including IAA, GADA, IA-2A or ZnT8A. Sera collected at and before the appearance of the first standard IAb were tested for ZnT8ecA. The cut-off of ZnT8ecA assay was set at 99th percentile of 189 normal controls. ZnT8ecA as a predictor of progression to clinical T1D independent of standard IAb status, age, and HLA genotype were evaluated in a multivariate Cox regression model.Results: Of the 209 children studied, 131 (62.7%) tested positive for ZnT8ecA, including 86 at and 45 before the first standard IAb seroconversion. Children positive for ZnT8ecA were more likely than those negative to carry the HLA-DR3/4 genotype (41.8% vs. 20.5%, P = 0.0017) and progress to clinical T1D (62.6% vs 15.4%, P<0.0001) during the median follow-up of 15.2 years (IQR 9.3-19.4). In a multivariate regression analysis, controlling for age of ZnT8ecA seroconversion and HLA genotype, ZnT8ecA independently predicted progression to clinical T1D in children with a single standard IAb (HR=7.35; 95%CI 2.13-25.3), but not among those positive for multiple standard IAbs (HR=1.54; 0.62-3.79).Conclusion: We confirmed that ZnT8ecA often precedes the appearance of the standard IAbs. Importantly, testing for ZnT8ecA significantly improves T1D risk prediction in children positive for a single IAb and may improve the predictive value of IAb screening in young children.DisclosureX. Jia: None. C. Zhang: None. F. Dong: None. K. Waugh: None. M. Rewers: Consultant; Sanofi. Research Support; Sanofi. D. Fu: Stock/Shareholder; Islex Therapeutics LLC. L. Yu: None.FundingBreakthrough T1D (2-SRA-2023-1451-S-B); Diabetes Research Center (DRC) (P30 DK116073)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-17-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 17-PUB: DNA-Based Delivery of Therapeutic Proteins Using MYO
Technology—Preclinical Results on Incretin Receptor Agonists-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 17-PUB
Abstract: Introduction and Objective: Therapeutic proteins development and use substantially increased in many disease areas. Significant drawbacks limit access to many of these drugs: i) high manufacturing costs; ii) administration via time-consuming infusions; iii) frequent dosing; iv) requirements for low temperature storage. MYO Technology was developed to overcome these barriers: our platform consists of therapeutic-encoding plasmid DNA (pDNA) and a proprietary device for intramuscular injection and delivery of electrical pulses. Pulses enable the in vivo electroporation of muscle cells and uptake of injected pDNA, leading to the production, secretion, and delivery of the therapeutic into circulation. Incretin receptor agonists (IRAs) are a class of therapeutic proteins came to prominence as powerful weight and glucose control drugs, used for the treatment of type 2 diabetes (T2D) and obesity. Semaglutide and tirzepatide, the most widely used IRAs, are potent molecules with a short half-life, requiring weekly administration by subcutaneous injections. Moreover, their clinical benefits disappear upon treatment cessation, and patients may have a life-long dependency on IRAs. The requirement for weekly injections can negatively affect the quality of life and the adherence to therapy, and create a significant financial burdenMethods: We present our preclinical studies on the delivery of IRAs with MYO TechnologyResults: Animal proof-of-concept studies demonstrate that expression of MYO-delivered IRAs is stable for several months or longer in vivo after a single administration. Importantly, MYO-produced IRAs are functional and efficacious in promoting weight and glucose control in mouse models of diet-induced obesityConclusion: Through its long-lasting therapeutic effect and significant reduction in administration frequency, MYO technology has the potential to dramatically improve quality of life and therapy adherence among T2D and obese patientsDisclosureL. Sasset: None. A. Cameron: None. C. Sussman: None. L. Rubinelli: None. D. Maji: None. R. Miller: None. A. Thompson: None. D. Campbell: None. M. Walker: None. R. Liberatore: None. M. Drozdz: Employee; RenBio.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-17-PUB
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 18-OR: Lower Incretin Effect and Reduced GIP Characterize the Metabolic
Phenotype of People with Multiple Islet Autoantibodies and Normal Glucose
Tolerance-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 18-OR
Abstract: Introduction and Objective: The incretin effect measures the contribution of gut-derived hormones GLP-1 and GIP to insulin secretion. There is limited evidence of the role of incretins in preclinical type 1 diabetes (T1D). We compared the incretin effect in individuals with normal glucose tolerance and a single autoantibody (Ab+) (Stage 0) to those with multiple Ab+ (Stage 1)Methods: Participants had a 3-hour, 7-point oral glucose tolerance test (OGTT) and an iso-glycemic IV glucose tolerance test (iso-IVGTT), with measurements of glucose, C-peptide, insulin, GIP, and GLP-1. Glucose profiles during the OGTT and iso-IVGTT were matched. Insulin secretion rate (ISR) was estimated using the oral minimal model. Incretin effect was quantified as the percentage difference between the OGTT and iso-IVGTT ISRs.Results: We enrolled 10 participants (age 21.6±8.8 years; BMI 24.9±7.0kg/m²), 5 with Stage 0 and 5 with Stage 1 T1D. The groups had similar age and BMI. Participants with Stage 1 had a 45% reduction in the incretin effect compared to those with Stage 0 (36.4±15.6% vs.19.7±4.9%, p=0.046). Those with Stage 1 had a lower area under the curve (AUC) of GIP during the OGTT compared to those with Stage 0 (p=0.038). GLP-1 tended to be lower in Stage 1 (p=0.113).Conclusion: Multiple vs single islet autoantibodies is associated with a reduced incretin effect and lower GIP.DisclosureA. Galderisi: None. H. Marchiori: None. M.D. Alguard: None. M. DeSousa: None. E.M. Tichy: None. A. Flynn: None. J.L. Gaglia: Consultant; Vertex Pharmaceuticals Incorporated. Stock/Shareholder; Vertex Pharmaceuticals Incorporated. Consultant; Avotres Inc. Research Support; Avotres Inc. Consultant; Kriya Therapeutics, Imcyse, Diamyd Medical AB. Research Support; Diamyd Medical AB, Sanofi, Biomea Fusion. C. Dalla Man: None. J.L. Sherr: Consultant; Abbott. Advisory Panel; StartUp Health T1D Moonshot. Research Support; Dexcom, Inc. Advisory Panel; Cecelia Health, MannKind Corporation. Consultant; Insulet Corporation, Vertex Pharmaceuticals Incorporated, Ypsomed AG. Advisory Panel; Medtronic, Vertex Pharmaceuticals Incorporated.FundingBreakthrough T1D (3-SRA-2022-1186-S-B and 3-SRA- 2023-1422-S-B to AG)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-18-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 18-PUB: Comparative Gastrointestinal Safety of Dulaglutide, Semaglutide,
and Tirzepatide in Patients with Type 2 Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 18-PUB
Abstract: Introduction and Objective: No head-to-head studies compared individual glucagon-like peptide-1 receptor agonists (GLP-1RA) and tirzepatide with respect to the risk of gastrointestinal (GI) events in adults with type 2 diabetes (T2D) in clinical practice.Methods: Using data from a commercial health plan (2019-2024), we identified three pairwise cohorts of 1:1 propensity score-matched patients aged ≥18 years with T2D who initiated dulaglutide, subcutaneous (SQ) semaglutide, or tirzepatide, and estimated incidence rates and hazard ratios (HR) with 95% CIs for the risk of GI events (a composite of acute pancreatitis, biliary disease, bowel obstruction, gastroparesis, or severe constipation). In secondary analyses, individual GLP-1RA were compared head-to-head with sodium-glucose cotransporter-2 inhibitors (SGLT-2i).Results: Over a median follow up ranging from 5.8 to 6.8 months, the risk of GI adverse events was similar across individual GLP-1RA (SQ semaglutide vs. dulaglutide: HR, 0.96 [95% CI, 0.87-1.06]; tirzepatide vs. dulaglutide: HR, 0.96 [95% CI, 0.77-1.20; tirzepatide vs. SQ semaglutide: HR, 1.07 [95% CI, 0.90-1.26]) (Table). Individual GLP-1RA were associated with an increased risk of GI adverse events compared with SGLT-2i.Conclusion: This study suggests that dulaglutide, SQ semaglutide, and tirzepatide have a comparable GI safety profile in adults with T2D.DisclosureS. Crisafulli: None. W. Alkabbani: None. D.J. Wexler: Other Relationship; Novo Nordisk. K. Bykov: None. A. Tavakkoli: Consultant; Vertex Pharmaceuticals Incorporated, AltrixBio. E.W. Yu: Research Support; Amgen Inc. Consultant; UpToDate. G. Trifirò: Advisory Panel; Sanofi, MSD Life Science Foundation, Eli Lilly and Company, Daiichi Sankyo, Novo Nordisk, Gilead Sciences, Inc, Amgen Inc. Consultant; Viatris Inc. J.M. Paik: None. E. Patorno: Research Support; National Institute of Diabetes and Digestive and Kidney Diseases, Patient-Centered Outcomes Research Institute, Food and Drug Administration (FDA), Boehringer-Ingelheim. Other Relationship; UpToDate.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-18-PUB
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 19-PUB: Feasibility and Effectiveness of a Virtual Education Program with
or without HIIT to Restore Hypoglycemia Awareness in Adults Living with
Type 1 Diabetes—A Pilot Study-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 19-PUB
Abstract: Introduction and Objective: Approximately 25% of people living with type 1 diabetes (PWT1D) experience impaired awareness of hypoglycaemia (IAH). This pilot study aimed (1) to evaluate the feasibility and (2) compare the effectiveness of a 12-week virtual intervention: a standard education programme (SEP) versus SEP combined with home-based high-intensity interval training (SEP+HIIT) in restoring hypoglycemia awareness.Methods: Randomized parallel-group design to compare (1) SEP and (2) SEP+HIIT. The SEP program included 8 educational sessions focusing on hypoglycemia prevention and management. The HIIT intervention included 36 sessions (3/week) each consisting of a 5-10 minute warm-up, 6-12 one-minute intervals performed at >75% of maximal heart rate, and a 3-5 minute cool-down. All participants completed the Gold and Clarke questionnaires before and after the intervention. Statistical analysis was conducted using ANOVA. Only participants who completed at least 65% of HIIT sessions, and achieved >70% of intervals per session at >75% of their maximum heart rate, were included in the analysis.Results: Of the 38 participants included, 27 completed the study: 16 SEP, 11 SEP+HIIT (3 dropped out, 2 did not complete the questionnaires, 2 experienced severe hypoglycemia, 4 did not reach their target heart rate during HIIT sessions). SEP program adherence was 100% across both groups, while SEP+HIIT participants completed 86% of the exercise sessions. Gold scores decreased significantly (p=0.001), with a greater reduction in SEP+HIIT (5.73 to 4.00) compared to SEP (5.19 to 4.9; p=0.011). Clarke scores improved significantly post-intervention (p=0.007), with no significant difference between groups (SEP: 4.63 to 4.13 and SEP+HIIT: 4.64 to 3.64; p=0.334).Conclusion: This pilot study demonstrates the feasibility of virtual SEP and HIIT interventions in PWDT1 with IAH. The combination of SEP and HIIT interventions could further restore IAH compared to SEP aloneDisclosureC. Guédet: None. S. Tagougui: None. R. St-Amand: None. C. Suppere: None. M. Raffray: None. V. Boudreau: None. M. Devaux: Advisory Panel; Sanofi. Other Relationship; Dexcom, Inc. A. Fortin: None. M. Mathieu: None. R.P. Rabasa-Lhoret: Advisory Panel; Abbott, Eli Lilly and Company, Novo Nordisk, Sanofi, Insulet Corporation. Other Relationship; Medtronic. Advisory Panel; Bayer Pharmaceuticals, Inc.FundingIRSC fondation grant (CIHR-148464)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-19-PUB
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 19-OR: Treatment and Outcomes in Paediatric Type 1 Diabetes across
Countries with Different Gross Domestic Products—Results from the Sweet
Initiative-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 19-OR
Abstract: Introduction and Objective: Treatment choices and outcomes for children with T1D vary by country, but the influence of economic wealth is not well studied. Aim: To evaluate this association using SWEET registry dataMethods: A cross-sectional analysis of 54,285 individuals with T1D under 25 years, diagnosed for > 3 months, from 130 SWEET centers (2022-2023). Subjects were stratified by country GDP in four groups. Key variables included HbA1c, BMI, insulin dose, use of CGM, insulin pumps, and AID. Height and BMI z-scores followed WHO references. Regression models adjusted for age, diabetes duration, and sex.Results: Height z-scores were lowest in the low GDP group (-0.44) versus +0.24 to +0.50 in higher GDP groups. BMI z-scores increased from +0.04 in the low GDP group to +0.89 in the high GDP group (p < 0.001). Insulin requirements were highest in the low GDP group (0.93 U/kg) versus 0.75-0.79 U/kg in other groups (p < 0.001). CGM use rose from 36% in the low GDP group to 91% in the high GDP group, insulin pump use from 17% to 70%, and AID systems from 11% to 38% (all p < 0.001). HbA1c was highest in the low GDP group (8.7%) and lowest in the lower-middle group (7.5%), followed by 7.7% (upper-middle) and 8.1% (high GDP). DKA was most frequent in the high GDP group, while severe hypoglycemia was most common in the low GDP group (both p < 0.001).Conclusion: A strong association exists between GDP and nutritional status, technology use, and metabolic outcomes in pediatric T1D. Best metabolic control was in countries with lower-middle or upper-middle income. High-GDP countries showed poorer control, higher BMI, and more frequent DKA. These findings stress the need for better resource allocation in pediatric diabetes care.Disclosure C. Martinez Mateu: Other Relationship; Sanofi-Aventis Argentina. S.S. Gupta: None. R. Duperval: None. R.A. Thabet: None. D. Al-Abdulrazzaq: None. M. Pogajepec: None. O. Kaminska-Jackowiak: None. M.M. Cavalin: None. S. Munoz: None. C. Sanon: None. S. Sap: None. R.W. Holl: None. D. Pacaud: Research Support; Medtronic, Novo Nordisk, Eli Lilly and Company.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-19-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 20-OR: Improving Glycemia in Adolescents and Young Adults (AYA) with
T1D—Results of One-Year RCT-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 20-OR
Abstract: Introduction and Objective: AYA with T1D often have suboptimal glycemic control and experience diabetes distress (DD), likely with bidirectional impacts. We created Healthy And Positive Pathways for Young People with T1D (HAPPY T1D) as a glycemic and behavioral intervention to improve glycemia and reduce DD. We report 1-year glycemic outcomes comparing HAPPY T1D vs. usual care in AYA with T1D.Methods: AYA aged 14-25 were enrolled at 2 centers and provided CGM data, A1c and DD assessments over 1 year. HAPPY T1D included 12 monthly sessions delivered via telehealth by an interventionist. CGM provided 30-day time in range (TIR 70-180 mg/dL) at 0, 3, 6, 9 & 12 months. Central A1c measurements were obtained at 0, 6 & 12 months. Mixed effects models assessed TIR and A1c over time by group.Results: AYA (N=191, 72% NHW) were 19.8 years old, with T1D duration 11.4 years and mean A1c 8.0%; 86% were pump treated, 98% used CGM with 79% on AID at entry. In mixed effects model (p<0.001), TIR improved in HAPPY T1D vs. usual care group with first appearance of group difference at 3 months (Table). This persisted with intervention AYA having ~430 more hours TIR vs. usual care across the year. A1c did not differ significantly but trended down in HAPPY T1D AYA.Conclusion: HAPPY T1D intervention significantly improved glycemic control with increased CGM TIR by 3 months in AYA with T1D. HAPPY T1D effects on DD (in separate abstract) showed later benefit, supporting the value of glycemic control on psychosocial outcomes.Disclosure L.M. Laffel: Advisory Panel; Boehringer-Ingelheim, Sanofi, MannKind Corporation, Medtronic, Vertex Pharmaceuticals Incorporated, Tandem Diabetes Care, Inc, Insulet Corporation. Research Support; Dexcom, Inc. Advisory Panel; Sequel Med Tech. Other Relationship; Janssen Pharmaceuticals, Inc. Consultant; Arbor Biotech. S.A. Alamarie: None. S. Hanes: None. S. Ojukwu: None. A.K. Schneider-Utaka: None. L.J. Tinsley: None. L.K. Volkening: None. J.J. Wong: None. K.K. Hood: Consultant; Sanofi. Advisory Panel; MannKind Corporation. Consultant; Havas Health. Research Support; embecta.FundingNIH (R01DK129479)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-20-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 20-PUB: Enhanced Efficacy and Safety of Evogliptin in Older Adults—A
Comparative Study in Type 2 Diabetes Patients Aged above and below 65
Years-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 20-PUB
Abstract: Introduction and Objective: Evogliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, is a widely used oral medication for managing type 2 diabetes mellitus (T2DM). This study's objective was to evaluate the efficacy and safety of Evogliptin in Korean T2DM patients across different age groups (≤ 65 years and > 65 years) and treatment durations (< 24 weeks and ≥ 24 weeks), with a focus on glycemic control and adverse events.Methods: This multicenter, retrospective study included 1,593 patients aged ≤ 65 years and 2,935 patients aged > 65 years. Patients were divided into treatment duration groups of < 24 weeks and ≥ 24 weeks. Glycemic control parameters—fasting plasma glucose (FPG), 2-hour postprandial glucose (2hr-PPG), and hemoglobin A1c (HbA1c)—were analyzed to determine treatment efficacy. Safety was assessed by comparing the frequency and severity of adverse events across all groups, with attention to age and treatment duration.Results: Elderly patients (> 65 years) treated for ≥ 24 weeks demonstrated significant reductions in HbA1c levels (P < 0.01). Among patients > 65 years, FPG decreased by -20.31 mg/dL (< 24 weeks) and -9.35 mg/dL (≥ 24 weeks), while HbA1c reductions were -0.32% (< 24 weeks) and -0.59% (≥ 24 weeks) (P < 0.01). Glycemic improvements, particularly in HbA1c, were more pronounced with prolonged treatment in the elderly population. Additionally, adverse events were consistent and comparable across all groups, indicating a favorable safety profile regardless of age or treatment duration.Conclusion: Evogliptin effectively improves glycemic control, especially HbA1c levels, with minimal adverse effects in elderly T2DM patients following extended treatment. These findings underscore the importance of personalized diabetes management strategies, tailored to patient age and treatment duration, to maximize therapeutic benefits.DisclosureJ. Kim: None. Y. Kim: None. J. Yim: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-20-PUB
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 21-OR: Systematic Review and Meta-analysis of the Association of SGLT2
Inhibitors and GLP-1 Receptor Agonists on the Risk of Dementia in Patients
with Type 2 Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 21-OR
Abstract: Introduction and Objective: Observational studies showed contradictory results with using SGLT-2 inhibitors and GLP-1 RAs on the risk of dementia in patients with type 2 diabetes. We aimed to evaluate the association between these medications and dementia risk with meta-analysis.Methods: We searched PubMed, EMBASE, and CENTRAL databases up to October 2024, selecting studies that examined the association between SGLT-2 inhibitors or GLP-1 RAs and risk of dementia (including all-cause dementia, Alzheimer's disease [AD], and vascular dementia [VD]) in patients with type 2 diabetes. The ROBINS-I tool was used to evaluate the risk of bias in eligible studies. Random-effects meta-analyses with inverse variance weighting were conducted to calculate the pooled HRs with 95% confidence intervals for dementia risk. Subgroup analyses were performed: (1) older patients aged>60 years, (2) studies including a 1-year lag time, and (3) types of active comparator (e.g., DPP4 inhibitors).Results: There was a total of 18 observational studies with 3,008,234 patients included. The use of SGLT-2 inhibitors versus non-use is associated with a decreased risk of all-cause dementia (HR [95% CI]: 0.76 [0.67-0.85]), AD (0.75 [0.61-0.92]), and VD (0.58 [0.44-0.78]). Similarly, the use of GLP-1 RAs versus non-use is associated with a reduced risk of all-cause dementia (HR [95% CI]: 0.77 [0.67-0.89]), and AD (0.42 [0.34-0.50]). A lower risk of all-cause dementia risk was also observed with SGLT-2 inhibitors or GLP-1 RAs treatment in older patients, in studies applying a 1-year lag time and in those using DPP4 inhibitors as an active comparator.Conclusion: The use of SGLT-2 inhibitors and GLP-1 RAs is significantly associated with a lower risk of dementia in patients with type 2 diabetes. However, given the considerable heterogeneity inherent in observational studies, large-scale randomized controlled trials are needed to clarify these findings.DisclosureC. Cheng: None. T. Nguyen: None. W. St. Peter: Consultant; Fresenius Medical Care. Advisory Panel; GlaxoSmithKline plc, Boehringer-Ingelheim. Consultant; Bayer Pharmaceuticals, Inc. H. Ou: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-21-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 21-PUB: A Real-World Adverse Event Profile of Tirzepatide—A Pilot
Systematic Review and Meta-analysis of Observational Studies-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 21-PUB
Abstract: Introduction and Objective: The recent FDA-approved drug, Tirzepatide, a dual GIP and GLP-1 receptor agonist, showed superior efficacy in type-2 diabetes mellitus management and weight reduction. Awareness of the real-world incidence of adverse events(AEs) is crucial for a clinician to advise optimal treatment that ensures the best quality of life for the patient. While RCT-based reviews of AEs exist, no reviews analysed real-world AEs in patients on tirzepatide, and our study aims to fill this research gap.Methods: A systematic search was conducted using apt MeSH terms across PubMed, Embase and Scopus; the results obtained (n=1260) were screened, and the duplicates (n=482) were removed. The titles and abstracts of the rest (n=778) were screened. 8 full texts were reviewed, and 5 met the inclusion criteria and were assessed for bias and quality with the Newcastle-Ottawa scale (NOS). A random effects model in R 4.4.2 was used to estimate the pooled incidence of AEs and 95% CI.Results: 5 moderate-to-low quality studies with 18,387 tirzepatide patients were included. Meta-analysis of pooled proportions from 3 studies reported nausea (8%, CI: 1%-36%, I² = 66%), diarrhoea (6%, CI: 2%-19%, I² = 13.9%), constipation (5%, CI: 1%-25%, I² = 34.5%), hypoglycemia (5%, CI: 1%-32%, I² = 66.5%), and vomiting (2%, CI: 0%-22%, I² = 27.5%). Discontinuation due to adverse events in 4 studies was 3.2% (CI: 2.7%-3.7%, I² = 0%). Rare AEs, like cholelithiasis and gastroenteritis, etc., were reported.Conclusion: Nausea is the most common gastrointestinal(GI) AE, followed by diarrhoea, constipation, and vomiting, which suggests cautious use in patients with GI pathologies. Hypoglycaemia is the most notable non-GI AE. The incidence of AEs was lower than the findings of a meta-analysis of RCTs (Mishra et al., 2023) but had high variability, signifying a need for more extensive, high-quality observational studies to better comprehend its trends, clinical correlations and outcomes.DisclosureG. Chitiki: None. N. Gadepalli: None. H.J. Pandita: None. A. Ranjan: None. C. Kaur: None. M. Pathania: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-21-PUB
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 22-OR: Type 2 Diabetes Subtypes and Risk of Dementia in the United States
-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 22-OR
Abstract: Introduction and Objective: Dementia, an emerging complication of type 2 diabetes (T2D), may be driven by chronic hyperglycemia and insulin resistance. We evaluated the risk of dementia across T2D subtypes, which differ in clinical profiles and risk of vascular complications.Methods: We identified newly diagnosed T2D (n = 727,076; age: 64.4 years [SD:13.3], 52% female) over 2012-2023 from the Epic Cosmos platform and classified them into Severe Insulin-Deficient Diabetes (SIDD, 21.6%), Mild Obesity-Related Diabetes (MOD, 23.8%), Mild Age-Related Diabetes (MARD, 40.9%) or Unclassified (i.e., Mixed; 13.7%). First occurrence of any dementia and also specific risks of vascular dementia, Alzheimer’s, and other dementias within ten years after T2D diagnosis were identified using ICD-10-CM codes. Cox proportional hazards models were used to estimate covariate-adjusted absolute and relative hazards (HR) by subtype.Results: Compared with MOD, SIDD (HR: 2.25 [95%CI: 1.92, 2.64]) and MARD (2.00 [1.70, 2.34]) had higher hazards for any dementia (Figure). Unclassified diabetes showed intermediate hazards of any dementia (1.38 [1.16, 1.65]). Risks of vascular, Alzheimer’s, and other dementias were also higher in SIDD and MARD compared to MOD and Unclassified diabetes.Conclusion: T2D subtypes differ in dementia risks, emphasizing the need for research into tailored prevention strategies and early screening, particularly for SIDD and MARD.DisclosureZ. Li: None. B. Salazar: None. J. Guo: None. K.O. Sanaka: None. A. Kahkoska: None. P. Vellanki: Advisory Panel; Eli Lilly and Company. M.K. Ali: Advisory Panel; Eli Lilly and Company. J. Varghese: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-22-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 22-PUB: Semaglutide Improves Metabolic Profile in Patients with LADA
-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 22-PUB
Abstract: Introduction and Objective: Semaglutide has demonstrated high efficacy in the management of type 2 diabetes. Few data in literature are available regarding the use of this agent in patients affected by LADA. The purpose of this real-world study is to analyze the short-term efficacy of semaglutide in patients affected by LADA.Methods: We retrospectively analyzed data of 54 patients affected by LADA, that started semaglutide [35/54 oral (mean dose 7.6±3.2 mg/die) and 19/54 subcutaneous (mean dose 0.8±0.25 mg/week)], as an add-on therapy to insulin.Laboratory and clinical parameters and metrics from continuous glucose monitoring were evaluated at baseline and after 6 months of follow-up.Results: During follow-up, semaglutide discontinuation occurred in 12/54 patients (22.2%) and patients were divided accordingly to baseline C-peptide values. In the population with preserved beta-cell function (C-peptide >0.7 nmol/l), data showed a significant reduction in insulin TDD (baseline vs follow-up: 34.6±31 vs 24.8±26.8 UI/day, p<0.01), reduction in BMI (baseline vs follow-up: 27.6±7.2 vs 26.6±6.7 kg/m2, p<0.01) and an amelioration in glucose metrics, with increased TIR values (baseline vs follow-up: 76±18 vs 83±14.5 %, p=0.02) and reduced TAR (baseline vs follow-up: 21±18 vs 15.5±14 %, p=0.02). HbA1c values showed a non-significant reduction (baseline vs follow-up: 56.5±21.4 vs 45.8±8.9 mmol/mol, p=0.11). In the subgroup with reduced C-peptide levels (≤0.7 nmol/l), metabolic parameters at follow up remained stable, without any difference. Main reason for discontinuation were gastro-intestinal side effects, rate of hypoglycemia was almost negligible in both groups and no severe adverse events were reported.Conclusion: Semaglutide exerted beneficial effects over metabolic parameters in patients affected by LADA, especially when beta-cell function is still represented.DisclosureM. Lunati: None. D. Bernasconi: None. F. D'Addio: Advisory Panel; Sanofi. E. Assi: None. C. Loretelli: None. P. Fiorina: Consultant; Novo Nordisk, AstraZeneca. Board Member; Boehringer-Ingelheim.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-22-PUB
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 23-OR: Benefit of an Intensive Lifestyle Intervention on All-Cause
Mortality over Two Decades in Older Adults with Diabetes and
Overweight/Obesity—The Look AHEAD Study-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 23-OR
Abstract: Introduction and Objective: Look AHEAD, a randomized trial initiated in 2001 comparing intensive lifestyle intervention (ILI) and diabetes support and education (DSE) in 5145 individuals with overweight/obesity and type 2 diabetes, found no significant differences in all-cause mortality during 10 yrs of intervention nor at 17 yrs of follow-up. The cohort has been followed continuously since the close of the trial in an observational study. Throughout this period, cumulative weight loss has been significantly greater in ILI than in DSE. Since effects of ILI may take many years to emerge, we pursued an intense mortality search, yielding 500 new deaths, and conducted an intent-to-treat analysis comparing mortality in ILI to DSE for a maximum of 23 yrs.Methods: The cohort of 5145 initially included adults aged 45-76 yrs, 59% female, 37% from underrepresented groups, and 14% with prior cardiovascular disease. Primary outcome for the current analysis was all-cause mortality from randomization to 23 yrs. Other outcomes included interactions by pre-specified subgroups. Analyses used proportional hazards regression and likelihood ratio tests.Results: A total of 1661 deaths were recorded (800 in ILI and 861 in DSE) across 80,725 person-yrs. The incidence of all-cause mortality was reduced in ILI relative to DSE (hazard ratio [HR] 0.89 [95% CI 0.81, 0.98]). There were no significant interactions between treatment and prespecified subgroups of age, sex, and cardiovascular disease history. However, race/ethnicity interacted with treatment (p = 0.01) yielding HRs for participants identifying as Hispanic 0.54 (CI 0.39, 0.74), Caucasian 0.94 (CI 0.84, 1.05), and African American 0.96 (CI 0.75, 1.23).Conclusion: ILI focused on weight loss modestly reduced long-term mortality risk in persons with diabetes and obesity/overweight, which appears to be driven by a strong reduction in mortality among participants of Hispanic ethnicity.DisclosureL.E. Wagenknecht: None. J.K. Evans: None. H. Chen: None. D.K. Houston: None. C. Semelka: None. T.D. Beckner: None. P.J. Huckfeldt: None. M.E. Salive: None. S.B. Kritchevsky: None. H.P. Hazuda: None. D.M. Reboussin: None. R.R. Wing: None. M. Espeland: Consultant; Nestlé Health Science. Other Relationship; AnnovisBio, Acumen.FundingNational Institute of Aging (U01AG073697)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-23-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 23-PUB: Efficacy and Safety of IGlarLixi vs. IDegAsp by Baseline HbA1c in
Chinese People with T2D—Post Hoc Analyses of the SoliD Study-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 23-PUB
Abstract: Introduction and Objective: SoliD was a head-to-head study comparing once daily iGlarLixi vs IDegAsp for 24 weeks in Chinese adults with suboptimally controlled T2D on OADs.Methods: The efficacy and safety of iGlarLixi vs IDegAsp were analyzed by baseline HbA1c using data from SoliD. Endpoints were assessed by baseline HbA1c groups: ≥7-≤8% (≥53-≤64 mmol/mol), >8-≤9% (>64-≤75 mmol/mol), and >9% (>75 mmol/mol). Mean change in HbA1c (and composite endpoints), body weight, total dose of insulin from baseline to Week 24 and hypoglycemia rates at Week 24 were assessed.Results: In all subgroups, iGlarLixi was consistently superior to IDegAsp in reducing HbA1c from baseline to Week 24 (Table); higher proportions of patients achieved HbA1c <7% (<53 mmol/mol), HbA1c <7% with no weight gain, and HbA1c <7% with no weight gain or hypoglycemia with iGlarLixi vs IDegAsp. Compared with IDegAsp, iGlarLixi resulted in a lower insulin dose and body weight benefits, with no differences among subpopulations. There was no interaction between all ADA levels hypoglycemia event rate and baseline HbA1c.Conclusion: In this post hoc analysis, regardless of baseline HbA1c level, iGlarLixi demonstrated better clinical outcomes vs IDegAsp. Results from this analysis are consistent with primary results reported previously.DisclosureH. Kuang: None. Y. Gu: None. W. Gu: None. A. Alvarez: Employee; Sanofi. F. Lauand: Employee; Sanofi. L. Melas-Melt: None. H. Fang: None. L. Kang: None. Q. Du: None. Y. Mu: None.FundingThis study was funded by Sanofi (ClinicalTrials.gov identifier: NCT05413369). Editorial support was provided by Simone Tait, CMPP, of inScience Communications, Springer Healthcare, and was funded by Sanofi.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-23-PUB
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 24-OR: Diabetic Peripheral Neuropathy as a Risk Factor for Brain Disease
-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 24-OR
Abstract: Introduction and Objective: Diabetic peripheral neuropathy (DPN) may increase the risk of cognitive impairment and dementia. This study evaluated DPN as a risk factor for brain disease defined as cerebrovascular disease (CBVD) and all-cause dementia.Methods: This register-based cohort study used data from Steno Diabetes Center Copenhagen (a diabetes outpatient clinic) and Danish National Health Registries. Individuals without prior brain disease and available vibration perception threshold (VPT) measurements were included (1998-2020). Neuropathy was defined as VPT>25 V (loss protective perception) or VPT>age-sex-height-adjusted thresholds (early-stage). Dementia and CBVD were identified via ICD-10 and procedure codes. We used Poisson regression models to estimate the incidence rate ratios (IRRs) of outcomes in individuals with vs. without neuropathy. Models were adjusted for age, sex, calendar year, diabetes duration, education, BMI, blood pressure, lipids, HbA1c, smoking, alcohol, and cardiovascular disease. For dementia, adjustments also included depression. IRRs were modeled for type 1 (T1D) and type 2 diabetes (T2D) separately, and for both neuropathy definitions. In a subpopulation, adjustments also included nephropathy and retinopathy.Results: We included 5641 individuals with T1D (mean (SD) age 40.5 y (15.8), 45.3% female) and 9395 with T2D (age 59.9 y (13.0), 38.6% female). The IRR of dementia was 1.57 (CI 0.73-3.37) in T1D and 4.30 (CI 2.05-9.04) in T2D for persons with versus without neuropathy (25 cut off). For CBVD, the IRRs were 1.50 (CI 1.30-1.97) in T1D and 1.48 (CI 1.20-1.83) in T2D. Additional adjustment for retinopathy and nephropathy only significantly impacted the IRR of CBVD in T1D, resulting in an overall IRR of 1.18 (CI 0.87-1.60). Similar results were found in early-stage neuropathy.Conclusion: Diabetic peripheral neuropathy is an independent risk factor for dementia and cerebrovascular disease in T2D, suggesting DPN as a valuable target for early preventive strategies.Disclosure A. Wiggers: Other Relationship; Bayer Pharmaceuticals, Inc. V. Kosjerina: None. M. Nilsson: None. B. Brock: None. S. Andersen: None. E.L. Reynolds: Employee; Michigan State University, University of Michigan. Research Support; National Institutes of Health, Juvenile Diabetes Research Foundation (JDRF). Other Relationship; American Diabetes Association, Ohio State University. B.C. Callaghan: None. E.L. Feldman: None. J. Rungby: None. C.S. Hansen: Speaker's Bureau; Novo Nordisk A/S. Consultant; Lundbeck, Grünenthal. Speaker's Bureau; Boehringer-Ingelheim.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-24-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 24-PUB: The Efficacy and Safety of iGlarLixi in Insulin-Naïve Adults with
Type 2 Diabetes (T2D) by Baseline Age, Sodium–Glucose Cotransporter 2
Inhibitor (SGLT2i) Use, and BMI—Post Hoc Analysis of Soli-CGM-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 24-PUB
Abstract: Introduction and Objective: Soli-CGM (NCT05114590) was a 16-week, single-arm, open-label study that used continuous glucose monitoring to assess the efficacy and safety of iGlarLixi (insulin glargine 100 U/mL + lixisenatide), in adults with T2D (A1c ≥9-<13%), receiving ≥2 oral antihyperglycemic drugs ± a glucagon-like peptide-1 receptor agonist. This post hoc analysis evaluated glycemic outcomes by baseline (BL) age (<65, ≥65 years), SGLT2i use (user, non-user) and BMI (<25, ≥25-<30, ≥30 kg/m²).Methods: For each subgroup, the mean change in time in range (TIR; 70-180 mg/dL), time below range (TBR; <70 mg/dL) and time above range (TAR; >180 mg/dL) from BL to Week 16 were assessed. The percentage of people with TIR >70% at Week 16 and incidence of American Diabetes Association (ADA) Level 1, 2 and 3 hypoglycemia events during follow-up were assessed.Results: See Table 1. Overall, 124 people were enrolled. Across all subgroups, including ≥65 years, iGlarLixi statistically significantly improved TIR and TAR from BL to Week 16 (P<0.05). As expected with insulin therapy, small increases in TBR (<3.5%) were observed. No ADA Level 3 hypoglycemia events were reported; incidence of Level 1 and 2 hypoglycemia varied by subgroup.Conclusion: In adults with T2D, iGlarLixi increased TIR regardless of BL age, BMI and SGLT2i use.Disclosure V.N. Shah: Consultant; Dexcom, Inc. Advisory Panel; Sanofi, Novo Nordisk. Consultant; Lilly Diabetes. Advisory Panel; embecta. Consultant; Insulet Corporation. Advisory Panel; Tandem Diabetes Care, Inc, Ascensia Diabetes Care. Research Support; Enable Bioscience. Consultant; Genomelink and Lumosfit. A. Ratzki-Leewing: Other Relationship; Abbott, Dexcom, Inc. Consultant; Sanofi. Other Relationship; Sanofi. Consultant; Sanofi-Aventis U.S. Advisory Panel; Sanofi-Aventis U.S. H. Thacker: None. A. Alguwaihes: Advisory Panel; Sanofi. Consultant; Lilly Diabetes. S. Dagdelen: Research Support; Sanofi. Advisory Panel; Abbott Diagnostics, Medtronic. A. Alvarez: Employee; Sanofi. F. Lauand: Employee; Sanofi. A.Y. Cheng: Advisory Panel; Abbott. Speaker's Bureau; Abbott. Other Relationship; American Diabetes Association. Speaker's Bureau; Amgen Inc, AstraZeneca. Advisory Panel; Bayer Pharmaceuticals, Inc. Speaker's Bureau; Bayer Pharmaceuticals, Inc. Advisory Panel; Boehringer-Ingelheim. Speaker's Bureau; Boehringer-Ingelheim. Advisory Panel; Dexcom, Inc., Eisai, Eli Lilly and Company. Speaker's Bureau; Eli Lilly and Company, GlaxoSmithKline plc. Advisory Panel; Insulet Corporation. Speaker's Bureau; Insulet Corporation. Advisory Panel; HLS Therapeutics. Speaker's Bureau; HLS Therapeutics, Medtronic. Advisory Panel; Novo Nordisk. Speaker's Bureau; Novo Nordisk, Pfizer Inc. Advisory Panel; Sanofi. Speaker's Bureau; Sanofi. Consultant; Novo Nordisk, Applied Therapeutics, Vertex Pharmaceuticals Incorporated.FundingSanofi
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-24-PUB
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 25-OR: N6-methyladenosine on Chromatin-Associated RNA (carRNA)—A Key
Regulator of Transcription in Human Islets with Type 2 Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 25-OR
Abstract: Introduction and Objective: Chromatin-associated regulatory RNAs (carRNAs), including promoter- and enhancer-associated RNAs, are known regulators of global gene transcription, yet the regulation of carRNAs remains poorly understood. Recent studies implicate RNA N6-methyladenosine (m6A) modification in carRNA stability and function. Seminal work from our lab has shown that m6A “writers” (e.g., methyltransferase-like 3 (METTL3) and METTL14) are downregulated in islets of individuals with type 2 diabetes (T2D), leading to altered m6A landscapes that better segregate T2D from control samples compared to the transcriptome. Here we report the role of m6A in regulating carRNAs in human T2D islets.Methods: Total chromatin-associated RNA (caRNA) was isolated from human islets (n=14 Control; n=8 T2D) and characterized using RNA sequencing. m6A methylation profiles were assessed by methylated RNA immunoprecipitation sequencing (MeRIP-seq). Validation was performed in the EndoC-βH1 human β-cell line following knockdown of METTL3 or METTL14.Results: We identified over 700 differentially regulated caRNAs in T2D islets, with functional enrichment revealing downregulated caRNAs involved in metabolism and oxidation, and upregulated caRNAs regulating RNA biology processes. MeRIP-seq revealed hypomethylation of key regulatory carRNAs, such as lncRNAs and promoter-associated RNAs, in T2D. In EndoC-βH1 cells, METTL3/14 knockdown similarly dysregulated caRNAs and downregulated β-cell identity pathways, while upregulating RNA processing and transcription pathways (n=4; FDR<0.05).Conclusion: Our findings provide novel insights into the epigenetic regulation of β-cell biology in T2D. The differential expression and m6A modification of carRNAs in T2D islets highlight their potential role in β-cell dysfunction and offer new therapeutic targets to modulate β-cell identity and insulin secretion.DisclosureN. Shukla: None. C. Ju: None. H. Li: None. C. He: None. R. Kulkarni: Advisory Panel; Novo Nordisk, Biomea Fusion, REDD Pharma, Inversago Pharma. Research Support; Inversago Pharma. Stock/Shareholder; Biomea Fusion.FundingNational Institute of Health (R01 DK067536)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-25-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 25-PUB: Descending Mode during Short-Term Intensive Insulin Therapy
Achieved Lower Fasting Blood Glucose after Insulin Pump Suspension in
Newly Diagnosed Patients with Type 2 Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 25-PUB
Abstract: Introduction and Objective: We have reported that newly diagnosed patients with T2DM receiving short-term intensive insulin therapy (SIIT) achieved drug-free remission, and that descending mode led to a higher percentage of time in range (3.9-10mmol/L, %TIR). Our objective was to explore whether it yielded lower fasting blood glucose (FBG) after SIIT, which has been proven to predict better long-term glycemic control.Methods: 1822 medical records were analyzed. They were categorized into descending or ascending groups according to Tmax shorter or longer than half the length of insulin pump treatment.Results: Patients in the descending group were younger, had higher BMI, with slightly lower fasting blood glucose before SIIT. The Tmax was shorter, total daily insulin dose was higher on the first day, whereas lesser on the day of maximum and pump suspension. Mean blood glucose was lower, and %TIR was higher in the descending group. FBG after pump suspension was significantly lower, while more patients achieved FBG <6.1mmol/L after pump suspension.Conclusion: The descending mode represents a more experienced insulin dose adjustment method, starting with a higher initial dose, while with lesser insulin dose on the day of maximum and pump suspension, achieves lower FBG after SIIT.DisclosureX. Zhang: None. X. Huang: None. Y. Cao: None. S. Liu: None. Z. Zhang: None. Y. Li: None. Z. Huang: None.FundingNational Natural Science Fund of China (82070918)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-25-PUB
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 26-OR: Genome-Scale CRISPR Screen Identifies ALDH3B2 Loss-of Function
Transdifferentiates Human Pancreatic Duct Cells Into Beta-Like Cells-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 26-OR
Abstract: Introduction and Objective: Pancreatic beta cell trans-differentiation is a phenomenon whereby new beta cells are generated from other pancreatic progenitor cells. It has been believed that pancreatic duct cells serve as a pool for the islet after birth or adulthood. Nevertheless, uncertainties persist regarding the regulation of beta cell trans-differentiation and whether it can be induced with sufficient efficiency to restore functional beta cell mass for diabetes treatment.Methods: Here we employed a genome-wide CRISPR screen (Figure 1B) to dissect the mechanism of human beta cell trans-differentiation and to identify new therapeutic targets (ALDH3B2) for beta cell mass restoration by induction of trans-differentiation. To execute the CRISPR screen, as illustrated in Figure 1A.Results: Our study demonstrates that loss-of-function mutations in ALDH3B2 can induce trans-differentiation of human primary pancreatic duct cells (HPPD) into beta-like cells. HPPD cells with ALDH3B2 mutations show responsiveness to glucose challenges in vivo. Single-cell RNA sequencing of control and ALDH3B2 mutant HPPD cells revealed that 18.1% of the mutant cells express insulin, compared to 0.6% in control cells. Importantly, around 93% of all cells maintained the duct cell marker KRT19 expression.Conclusion: Results suggest that a single gene, ALDH3B2, in pancreatic duct cells is sufficient to promote a beta-like cell phenotype.DisclosureJ. Li: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-26-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 27-OR: Identification of Novel Drivers of Type 1 Diabetes via Integration
of Whole-Islet Transcriptomics from Human and Mouse-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 27-OR
Abstract: Introduction and Objective: Type 1 diabetes (T1D) is a polygenic, autoimmune disease characterized by pancreatic β-cell dysfunction and loss. We have recently demonstrated that β-cell dysfunction in T1D is independent of T cell infiltration into islets. To define β-cell changes in T1D, we employed an islet-centric approach to identify differentially expressed genes (DEGs) that change during T1D pathogenesis in insulin (INS)+ CD3- islets of at-risk cases. We hypothesize these DEGs contribute to β-cell failure.Methods: To nominate genetic drivers, human islet gene expression data from single AAb+, multiple AAb+ and T1D cases were integrated with the Diversity Outbred (DO) mice. This enabled us to identify strong cis-eQTL associated with alleles from the T1D-prone NOD mouse, one of eight founder strains of the DO.Results: We filtered 827 human DEGs to identify 142 DEGs with strong NOD-driven cis-eQTL. From those, 88 DEGs showed associations with diabetes in human genome-wide association studies. Remarkably, 49 cis-eQTL mapped within mouse diabetes susceptibility loci. Those genes were associated with transcription-translation (Gatc, Creb3, Fam133b, H1f3, Niban1, Smad4), glucose metabolism (Pgm1), mitochondrial function (Suclg2, Atp5e, Atp5g1, Pdhb, Acly, Coa5), insulin-granule biogenesis and exocytosis (Pcsk1, Rab2a, Cadps2. Atp2a2), and amino acid and metal transport and homeostasis (Slc36a4, Slc39a8, Slc4a7, Fth1).Conclusion: By leveraging genetics of DO mice, our functional genomics approach has identified genetic elements as specific genetic drivers of human T1D (in transcription/translation, glycolysis, mitochondria, and insulin secretion). By restricting the analysis to islets without immune infiltration these loci promote loss of β-cell function in the absence of T cell infiltration.DisclosureA.E. Cuaycal: None. M. Keller: None. E.A. Butterworth: None. J. Chen: None. M. Campbell-Thompson: None. P. Smadbeck: None. J. Flannick: None. I.C. Gerling: None. C.E. Mathews: None.FundingJDRF, NIH (P01 AI42288, UC4 DK104194, UC4 DK104167, UC4 DK104155)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-27-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 27-PUB: Enhanced Glycemic Control and Weight Benefits of Insulin Glargine
plus lixisenatide vs. Insulin Glargine in Type 2 Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 27-PUB
Abstract: Introduction and Objective: Type 2 diabetes is a complex and progressive disease that affects millions of people worldwide.The objective of this study is to compare the clinical outcomes of insulin glargine + lixisenatide versus insulin glargine alone in patients with type 2 diabetes.Methods: This 24-week, single-center, randomized, open-label trial recruited 80 participants. Eligibility criteria comprised adults with an HbA1c level ≥8% despite receiving oral antidiabetic therapy. The primary endpoints were changes in HbA1c and body weight.Results: Table1. Clinical Outcomes of injection Glargine+ lixisenatide vs injection Glargine.Conclusion: Insulin glargine + lixisenatide demonstrated superior glycemic control and weight benefits compared to insulin glargine in type 2 diabetes patients.DisclosureB.D. Saboo: None. V.N. Sailor: None. A. Gupta: Speaker's Bureau; Abbott, Novo Nordisk, Becton, Dickinson and Company, Sanofi. A. Maheshwari: None. K.P. Modi: None. K.J. Patel: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-27-PUB
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 28-OR: GLP1R R131Q is a Gs-Biased Gain-of-Function Variant Associated with
Preservation of β-Cell Function-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 28-OR
Abstract: Introduction and Objective:GLP1R R131Q (rs3765467) has been reported as a type 2 diabetes protective variant in genome-wide association studies and glucagon-like peptide-1 receptor (GLP1R) activation has been shown to have various β cell protective effects. We hypothesized that the variant induces a gain-of-function change enhancing the β cell protective effects mediated by GLP1R activation.Methods: We performed real-time luminescence assays in GLP1R expressing human embryonic kidney 293 (HEK293) cells to measure cAMP and protein-protein interaction (PPI). We analyzed 6,312 participants without T2D at baseline from Ansan Ansung cohort, who underwent biennial 75 g 2 h oral glucose tolerance tests for 18 years. Trajectory of disposition index (DI), a marker for β cell function, was assessed using linear mixed model.Results:GLP1R R131Q expressing HEK293 cells had similar surface expression compared to wild-type but showed larger total cAMP production, measured by area under the curve, upon exendin-4 (Ex4) stimulation (1.6 fold in Emax, P < 0.001). The slopes indicated a faster cAMP production rate by the variant, and PPI assays demonstrated increased mini-Gs coupling and reduced β-arrestin-2 recruitment. Stimulation with GLP-1 and semaglutide similarly showed larger total cAMP production. In the Ansan Ansung cohort, while baseline DI levels were similar, individuals homozygous for the GLP1R R131Q variant (N=242) had a slower decline in DI, with 1.18-fold higher DI at the end of follow-up compared to non-carriers (N=4012) and heterozygous carriers (N=2058) in the recessive model (P=0.039). This significant difference was not observed in additive or dominant analyses.Conclusion: Functional characterization of GLP1R R131Q demonstrated a gain-of-function of the receptor with Gs protein-biased signaling. This functional change could have mediated enhanced β cell protective effect related with GLP1R, leading to a slower decline in DI observed in homozygous carriers.DisclosureH. Lee: None. H. Choi: None. S. Kwak: None. J. Kim: None. K. Park: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-28-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 28-PUB: TIX100 Provides More Potent, Effective, and Specific TXNIP
Inhibition and Antidiabetic Effects Than Verapamil-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 28-PUB
Abstract: Introduction and Objective: We have identified inhibition of thioredoxin-interacting protein as an attractive therapeutic target for diabetes. Using the calcium channel blocker, verapamil to non-specifically lower TXNIP expression, we were able to establish a proof of concept demonstrating that TXNIP inhibition protects endogenous beta cell function in patients with recent onset T1D. However, based on the limitations of verapamil as a calcium channel blocker including the risk for cardiovascular side effects such as arrhythmias, heart block and hypotension and multiple ‘off-target’ effects, a novel chemical entity, TIX100, was specifically developed. This orally available TXNIP inhibitor was recently approved by the FDA as an investigational new drug. The goal of the current studies was to compare the TXNIP inhibitory and antidiabetic effects of TIX100 and verapamil.Methods: We used TIX100 and verapamil dose response experiments and assessment of TXNIP expression in INS-1 beta-like cells as well as human islets and performed RNA sequencing of treated human islets. In addition, we conducted in vivo experiments treating diabetic mice with oral TIX100 or verapamil.Results: Interestingly, we found that TIX100 was ~100-times more potent than verapamil in inhibiting TXNIP expression in INS-1 cells and human islets. TIX100 was also twice as effective in normalizing beta cell TXNIP levels and RNA sequencing confirmed its specificity. Moreover, in the context of beta cell destruction, the antidiabetic effects of TIX100 were more pronounced and sustained than those with verapamil. Finally, unlike verapamil, TIX100 was also found to protect against hyperglucagonemia, another important aspect of diabetic islet dysfunction.Conclusion: Thus, in these preclinical studies, TIX100 provided more potent, effective and specific TXNIP inhibition as well as antidiabetic effects than verapamil, suggesting that this may ultimately translate into a safer and more effective diabetes therapy.DisclosureG. Jing: None. J. Chen: None. B. Lu: None. G. Xu: None. A. Shalev: Other Relationship; TIXiMED, Inc.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-28-PUB
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 29-OR: T-Cell Receptor Sequences Targeting Beta-Cell Proteins Are Present
in Blood across the Stages of Type 1 Diabetes Development-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 29-OR
Abstract: Introduction and Objective: Islet antigen reactive T cells play an important role in pancreatic β-cell destruction in type 1 diabetes (T1D). Identifying and tracking T1D-related T cell receptors (TCR) hold potential for monitoring disease activity.Methods: Peripheral blood samples were collected from 570 children with new-onset T1D (mean age 11.5 ± 3.8 years, 41% female, 81% white, mean duration of 10.8 days) and 141 control samples (mean age 7.8 ± 5 years, 42% female, 71% white). TCRβ chains were sequenced from DNA using the Adaptive immunoSEQ Assay. Known islet antigen-specific TCR sequences (1024 targeting GAD, 307 preproinsulin (PPI), 36 ZnT8, 45 IGRP, 5 islets) curated from the literature were searched in both groups. T1D-specific TCRβ chain sequences were identified and then searched for from longitudinally sequenced samples in DAISY cases, a prospective birth cohort study, that progressed to clinical T1D (n=29 at four time points throughout T1D development).Results: From 570 new-onset T1D and 141 control samples, 402 islet antigen-specific TCRs (28.4%) were found among 206 million total TCRβ sequences. We selected 161 T1D-specific TCRβ sequences that were more prevalent in new-onset T1D samples compared to controls (76.1% vs. 10.6%, p<0.001). Of 161 TCRs, 106 were targeting GAD, 45 PPI, 5 ZnT8, 3 IGRP, and 2 islets. At least one of these T1D-specific TCRs were present in 22/29 (75.8%) of DAISY cases, a very similar percentage to new-onset T1D. Remarkably, 16/26 (61.5%) cases had T1D-specific TCRs present in blood prior to islet autoantibody seroconversion. These TCRs persisted across the stages of T1D development.Conclusion: T1D-specific TCR sequences hold the potential to detect autoimmunity prior to islet autoantibody seroconversion and can be tracked across the stages of T1D development.DisclosureK.E. Karakus: None. E.E. Baschal: None. K. McDaniel: None. L. Yu: None. M. Nakayama: None. A.W. Michels: Stock/Shareholder; IM Therapeutics. Advisory Panel; Sanofi.FundingNational Institutes of Health (DK032083); National Institutes of Health(DK108868); National Institutes of Health (DK099317)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-29-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 30-OR: Baricitinib-Associated Changes in Single-Cell Gene Expression in NK
Cells in the BANDIT Clinical Trial-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 30-OR
Abstract: Introduction and Objective: The BANDIT trial investigated the efficacy of the JAK inhibitor baricitinib in new-onset type 1 diabetes (T1D) by measuring clinical endpoints and immunological parameters. Along with preserving C-peptide, we observed changes in immune cells during baricitinib treatment. The objective of this study was to further characterise those changes and elucidate specific molecular and cellular pathways affected by baricitinib.Methods: PBMCs were isolated at baseline and at 24 weeks of baricitinib (n = 30) or placebo (n = 18) treatment. For FACS, cell-specific antibodies were used to quantify NK subsets. For CITE-seq data, singlets were processed using Seurat, and differentially expressed gene (DEG) analysis was performed using edgeR and Limma.Results: The frequency of circulating cytotoxic CD56dim and immunomodulatory CD56bright NK cells decreased at 24 weeks of baricitinib. We identified 305 DEG in the CD56dim NK cells from baricitinib-treated patients at week 24 compared to baseline, and 17 DEG were identified at week 24 between baricitinib and placebo treatment groups. The JAK-STAT pathway genes STAT4, SOCS2 and PTPRC, along with other genes involved in differentiation and regulation, were downregulated by baricitinib; whereas genes related to migration were upregulated. In CD56bright NK cells, only GOLGA8A was downregulated by baricitinib compared to placebo at week 24.Conclusion: This study is a critical step in defining immunological effects caused by baricitinib in T1D. Notably, the reduction of CD56dim NK cells was associated with changes in the expression of JAK-STAT genes, essential for proliferation and activation. These effects are likely due to baricitinib blockade of common γ chain cytokine signalling. In particular, blockade of IL-2/IL-12/IL-15 signalling would inhibit NK-cell proliferation. This study highlights key pathways and cells affected by baricitinib that may further explain its beneficial effect for treating T1D.DisclosureL. Sanz Villanueva: None. C. Chiu: None. L. Mackin: None. T. Catterall: None. M. Waibel: None. I. Gallego Romero: None. B. Krishnamurthy: None. T. Brodnicki: None. T. Kay: Advisory Panel; Sanofi, SAB Biotherapeutics, Inc.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-30-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 30-PUB: Comparison of Effectiveness of Canagliflozin 300mg plus Gliptin
vs. Oral Semaglutide plus SGLT2i on Cardiorenal Markers in T2DM Patients-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 30-PUB
Abstract: Introduction and Objective: Compare the efficacy of Canagliflozin (C300) 300mg plus gliptin-(Vildagliptin (V) versus Semaglutide (Sm) & SGLT2i-dapagliflozin (D) on cardiorenal (CR) markers in T2DM pts.Methods: Between Aug’22 - Oct’22, 82 T2DM pt’s aged 18-75yrs on regular F/U were analyzed retrospectively over a period of 6 months & divided into 2 groups, Group A (Gr A): 41 pts received C300 plus V 100mg & Group B (Gr B): 41 pts received oral Sm 14mg plus D 10mg. Propensity score matching was performed for CR markers, statins & anti-hypertensives. Weight (W), BMI-kg/m2, systolic/diastolic BP (mm of Hg), Lipid profile mg/dL (TC, LDL-C, TG, HDL), hs-CRP mg/L, eGFRCr ml/min/1.73m2, HbA1c (%), uACR (μg/mg), NT-proBNP (pg/mL) were analyzed every 2-3 mths. Exclusion: H/O any revascularization, IHD or hospitalization within 1 yr, eGFR < 45 & K+ >5.5. Statistical analysis: Repeated measures ANOVA & Bonferroni correction (p-value <0.017) assessed within-group comparisons & independent t-test assessed between group comparisons. P-value <0.05 was considered significant (S).Results: Baseline (B) - all parameters were well-matched except: A1c (Gr A: 9.22 ± 2.00; Gr B: 7.74 ± 2.18, p=0.002), TC (Gr A: 151.04 ± 47.61; Gr B: 120.45 ± 31.50, p=0.001) & LDL (Gr A: 87.59 ± 43.68; Gr B: 62.31 ± 31.85, p=0.004). Gr A (B - 6 mths): S reductions: W, BMI, SBP, DBP, HbA1c, TC, LDL, TG. Gr B (B - 6 mths): S reductions: W, BMI TC, LDL, HDL. At 6 mths S differences, represented as Mean difference ± SED, were seen in BMI (-0.74 ± 1.8, p <0.001), SBP (-10.15 ± 0.64, p=0.009), DBP (-1.42 ± 3.16, p <0.001), HbA1c (-1.37 ± 0.33, p=0.005), TC (-19.01 ± 26.21, p=0.031), LDL (17.46 ± 19.01, p=0.027), TG (-41.42 ± 34.88, p=0.02) favouring C300 (Gr A). No differences were seen in W, HDL, eGFR, uACR, hs-CRP, NTpro-BNP.Conclusion: Canagliflozin 300 & Vildagliptin were more effective in improving CR risk factors in pts with T2DM compared to Semaglutide & Dapagliflozin despite having higher A1c at baseline.DisclosureV. Gupta: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-30-PUB
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 31-OR: Epigenetic Regulation of Islet Endothelial Immune Interface
Modifies the Pathogenesis of Type 1 Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 31-OR
Abstract: Introduction and Objective: Type 1 diabetes (T1D) is a classical autoimmune disorder. Intra-islet endothelial cells constitute the key barrier that separates Langerhans β cells from immune system, forming the so-called islet endothelial immune interface (IEII). Though epigenetic remodeling related to environmental perturbation modifies T1D progression, its potential effect on IEII and the underlying mechanisms remain elusive. In our study, we attempt to elucidate the role of MBD2, the DNA methylation reader, in regulating IEII function and to explore the IEII-targeted T1D intervention strategy.Methods: Endothelial specific Mbd2-knockout mice and MS-1 cell line were used for the in vivo and in vitro studies. Then, CUT&Tag sequencing, deep RNA sequencing, multi-color flow cytometry and immunofluorescent staining were carried out for mechanistic dissection.Results: Bioinformatic analysis of human islet single cell sequencing data revealed that the IEII of T1D patients exhibits lower Mbd2 expression along with enhanced “TNF” and “cell adhesion” pathways. Additionally, among the three major inflammatory cytokines (TNF-α, IL-1β, and IFN-γ), only TNF-α markedly changes the DNA methylation level of IEII. CUT&Tag combined with deep RNA sequencing in TNF-α treated endothelial cells demonstrated that MBD2 ablation derepresses Ncoa1, which then serves as the transcription coactivator of NF-kB to enhance ICAM1 expression. In consistent, MBD2 knockout mice showed more severe pancreatic islet damage and immune cell infiltration, leading to higher diabetes incidence. Application of the Ncoa1 inhibitor bufalin reduces ICAM1 expression and strengthens the barrier function of IEII, thereby delaying the progression of T1D.Conclusion: To summarize, loss of MBD2 exacerbates TNF-α induced IEII adhesion through the upregulation of Ncoa1-NF-kB-ICAM1 pathway to accelerate T1D progression. IEII-targeted drugs, such as bufalin, hold great promise for clinic T1D management.DisclosureX. Li: None. R. Yang: None. F. Sun: None. R. Duan: None. Y. Zhao: None. L. Gao: None. C. Zhang: None. J. Li: None. C. Wang: None. S. Liu: None.FundingDepartment of Science and Technology of Shanxi Province (202404010920011, 202304021301066, 202204051002029); Shanxi Bethune Hospital (2024AOXIANG03)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-31-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 31-PUB: Profiling Connected Care Users for Diabetes Monitoring and
Management—Insights from Urban India-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 31-PUB
Abstract: Introduction and Objective: The growing burden of diabetes in India and technological options have accelerated adoption of connected care technologies for real-time glucose monitoring. Platforms like LibreView (Abbott) have transformed diabetes care by facilitating seamless data sharing between persons with diabetes (PWD) and healthcare providers, enhancing disease management.Methods: A 1-year, retrospective study (December 2023-2024), with 207 PWD, aged 18-82 years (mean age: 56 years, SD: 15, 95% CI: 54-58), categorized based on age, gender, duration of diabetes, and treatment modalities (insulin, oral anti-diabetic drugs (OADs), or a combination of both.) Although the individual HbA1c levels were known, the focus of this abstract is connected care, the evolving paradigm in glycemic monitoring. Glucose metrics (average glucose levels, glucose management indicators (GMI), glycemic variability (GV), time spent in target glucose range) were analyzed to evaluate patient profiles and their glycemic control.Results: Among the study cohort, PWD were 72% males, and 28% female with predominantly diabetes duration > 10 years and on combination therapy (insulin + OADs). Mean glucose levels were 151.6 mg/dL, GMI was 6.90% and coefficient of variation was 27.3%. Participants spent approximately 70.3% of time in the target range, while 26.2% and 3.5% time above and below target range, respectively. Time below range indicating low glucose events (mean 3.5%) was infrequent but common in cases with high GV.Conclusion: Connected care technologies have thus demonstrated immense potential for enhancing diabetes management in urban India. Addressing barriers of unaffordability, inaccessibility, and limited patient engagement is necessary to realise their full potential and equitable use across diverse populations. Personalized interventions in those with poor glycemic control, high variability, or frequent hypoglycemia help optimise outcomes.Disclosure M.S. Chawla: Advisory Panel; Eli Lilly and Company, Novo Nordisk, Abbott, Sanofi, Lupin Pharmaceuticals, Inc, Medtronic, Cipla, Merck & Co., Inc. P.M. Chawla: None. A. Shaikh: None. G. Kumar: None. B.D. Saboo: None. J. Kesavadev: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-31-PUB
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 32-OR: Dysfunctional β-Cell Autophagy Stimulates Lysosomal Exocytosis,
Promoting Alterations in the Secretome and Antigen Presentation Pathways-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 32-OR
Abstract: Introduction and Objective: Previously, we discovered that β-cell autophagy is impaired in NOD mice and humans prior to the onset of T1D, implicating this pathway in T1D pathogenesis. We then showed that impaired β-cell autophagy leads to elevated ER stress, increased HLA-I expression, and enhanced β-cell susceptibility to immune attack. Based on these observations, we sought to characterize the mechanisms by which defective autophagy leads to increased β-cell HLA-I expression and enhanced immunogenicity.Methods: We used flow cytometry to assess how impaired autophagy affects Endo-C βH1 LAMP1 surface expression —a readout for lysosomal exocytosis —under basal and IFNα stimulated conditions. Under the same conditions, we performed flow cytometry on intracellular organelles to assess HLA-I co-localization with LAMP1+ organelles. We performed Olink proteomics to assess the β-cell secretome under conditions of impaired autophagy.Results: Endo-C βH1 cells treated with lysosome acidification inhibitor, Bafilomycin A1, showed a rapid increase of LAMP1 surface expression, indicative of increased lysosomal exocytosis. This corresponded to alterations in the β-cell secretome under conditions of impaired autophagy combined with IFNα treatment. As our previous studies showed enhanced HLA-I expression when β-cell autophagy is impaired, we hypothesized that recycling of HLA-I complexes may contribute to this phenomenon. In support of this theory, we detected LAMP1+/HLA-I+ double positive subcellular events, indicative of HLA-I molecule presence on lysosomes.Conclusion: We showed that impaired human β-cell autophagy induces lysosome exocytosis. This leads to changes in the β-cell secretome, thus altering β-cell dialogue with surveilling immune cells. Impaired β-cell autophagy also enhances surface HLA-I expression due to reduced degradation and subsequent recycling, which may increase β-cell visibility to the immune system.DisclosureM.C. Austin: None. S. Roy: None. J. Piganelli: None. A.K. Linnemann: None.FundingNational Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases (R01DK124380, F30DK142522)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-32-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 32-PUB: Glycemic Control after Coronary Artery Bypass Grafting—Current
Practices and Emerging Technologies-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 32-PUB
Abstract: Introduction and Objective: In patients who undergo CABG, diabetes and elevated glucose levels increase the risk of wound infections and longer hospital stay while tight glucose control raises risks of hypoglycemia, neuronal damage, and cognitive impairment. This study explores the current glycemic control levels in post-CABG patients.Methods: We conducted a retrospective chart review of 99 patients at a large academic center from March to July 2024. We excluded those who underwent CABG within 7 days of ER presentation or developed renal failure requiring dialysis after the surgery.Results: The study included 44 patients, primarily male (77.3%) with an average age of 68.7 years, median BMI of 28.6 kg/m2 & average HbA1C of 6.7%. While 45% had no official diabetes diagnosis, 9 had prediabetes, and 2 had diabetes based on HBA1c. 20% had evidence of chronic kidney disease with a GFR < 60. The average hospital stay was 9.2 days. Episodes of hypoglycemia & hyperglycemia are shown in Figure 1.Conclusion: All patients received insulin infusion for 48-72 hours post-surgery and were transitioned to basal/bolus insulin regimen. Even though most patients had well controlled diabetes (77%), hyperglycemic episodes were more frequent than hypoglycemia. Employing continuous glucose monitoring & remote technologies with tighter insulin regimen will reduce glucose variability in the immediate postoperative setting.DisclosureY. Shaikh: None. J. Giribhattanavar: None. R. Panta: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-32-PUB
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 33-OR: M6A mRNA Methylation Regulates Pancreatic α-Cell Identity and
Function-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 33-OR
Abstract: Introduction and Objective: Glucagon is produced by pancreatic α-cells and plays a critical role in glucose homeostasis. N6-methyladenosine (m6A) is the most abundant mRNA modification and is regulated by the METTL3/METTL14 writer complex. This study aimed to determine the role of m6A in α-cell biology.Methods: We utilized in vitro and in vivo approaches, including α-cell-specific Mettl14 KO mice, to investigate the role of m6A in α-cells. We measured glucagon secretion, performed lineage tracing to assess α-cell transdifferentiation, and analyzed transcriptional (mRNA-seq) and epitranscriptomic (m6A-eCLIP) changes resulting from Mettl14 ablation in α-cells.Results: We observed that low glucose and amino acid levels upregulated METTL14 levels in α-cells, while insulin suppressed it, indicating a regulatory role of METTL14 in response to metabolic stimuli. In α-cell-specific Mettl14 KO, glucagon secretion was significantly reduced, leading to decreased glucose levels. This was accompanied by elevated insulin levels in the knockout compared to control mice. Moreover, lineage tracing revealed that α-cells transdifferentiated into β-cells in the absence of METTL14. mRNA sequencing revealed dysregulation of critical genes that maintain α-cell identity, with YY1 identified as a key transcription factor upregulated in Mettl14 knockout mice. m6A-eCLIP analysis confirmed that YY1 is a direct m6A target, with the loss of m6A resulting in increased YY1 expression, through enhanced mRNA stability. Functional studies demonstrated that YY1 overexpression disrupted α-cell identity in vitro and analyses of human scRNA-seq datasets revealed an association with METTL14 and human α-cell identity loss providing translational relevance.Conclusion: Our findings demonstrate that m6A methylation is critical for maintaining α-cell function and identity. Disrupting this mRNA modification pathway triggers α-cell transdifferentiation and functional decline.DisclosureD.F. De Jesus: None. N.K. Brown: None. G. Fogarty: None. J. Hu: None. J. Sabadell-Basallote: Employee; Fractyl Health, Inc. S. Kahraman: Employee; Boehringer-Ingelheim. L. Xiao: None. R. Kulkarni: Advisory Panel; Novo Nordisk, Biomea Fusion, REDD Pharma, Inversago Pharma. Research Support; Inversago Pharma. Stock/Shareholder; Biomea Fusion.FundingNIH (R01 DK067536, UC4 DK116278, RC2 DK139552, K99 DK135927)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-33-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 33-PUB: Utilization of Continuous Glucose Monitor Data to Assess Glycemic
Control and Readiness for Surgery-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 33-PUB
Abstract: Introduction and Objective: Patients at an academic medical center undergoing surgery who have uncontrolled diabetes with A1c >8% are referred to a preoperative diabetes optimization program (PreDOP) with the goal of glycemic improvement prior to surgery. Previously, patients were considered optimized for surgery based on improved trends in fructosamine or repeat A1C. With the growing use of continuous glucose monitors (CGMs), we implemented utilizing CGM data to assess readiness for surgery. Our objective is to describe the use of CGM and glucose management indicator (GMI) to assess improvement in glucose control and optimization for surgery.Methods: We extracted data from our electronic medical record and CGM databases and included patients enrolled in the PreDOP program over the past year. Patients were excluded if they were enrolled in the program but were never optimized or never had surgery. Data collected included average glucose profile data from CGM for 2 weeks prior to surgery or the most recent 2 weeks leading up to surgery if no CGM worn immediately prior to surgery.Results: A total of 54 patients were included. Six patients were excluded due to not being optimized and/or not having a surgical date. Prior to referral, average A1c was 10.12%. After optimization, patients who wore a CGM had an average glucose of 163.89 ± 38.43 mg/dL, a GMI of 7.22 ± 0.94, and time in range of 66.57 ± 23.00 %.Conclusion: The purpose of this project was to describe the PreDOP program’s utilization of CGM as a tool and surrogate of glycemic control compared to traditional methods. In patients participants of PreDOP, CGM data reflected significant improvements in glycemic control. Future direction include evaluating the differences between patients with and without a CGM time to surgery and postoperative complications.DisclosureA. Behrens: None. V. Nelson: None. H. Lee: None. A. Thorgerson: None. A.Z. Dawson: None. C.E. Mendez: Consultant; Siemens Healthcare Diagnostics.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-33-PUB
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 34-OR: Proneuromedin U Differentially Produces Two Novel Insulinostatic
Peptides in Pancreatic α- and β-Cells-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 34-OR
Abstract: Introduction and Objective: Pancreatic α and β cells produce a large array of peptides and mutually interact through hormone secretion. To better understand β cell biology, we explored unknown peptides by comprehensive analyses on peptides and their receptors produced in islet cells.Methods: We investigated peptides based on the mRNA database of iPS-derived islet cells. We studied biosyntheses of identified peptides and their functions in insulin secretion and β cell maintenance. We also analyzed knockdown of the peptide-precursor gene and its knockout mice. A novel membrane protein activity measurement method was developed to determine G protein-coupled receptors (GRCPs) for identified peptides.Results: Neuromedin U (NMU) was produced from proNMU in β cells. NMU suppressed glucose-stimulated insulin secretion (GSIS) from human and mouse islets and impaired β cell maintenance by mitochondrial dysfunction and ER stress. Another proNMU-derived peptide, NMU-related peptide (NURP) was produced in α cells. NURP also suppressed GSIS and impaired β cell maintenance. NMU, a 25-amino acid peptide, has a biologically active region at the C-terminus. NURP, a 36-amino acid peptide, has the active region at the N-terminus. NMU and NURP were upregulated in the diabetic islets of humans and mice. Deletions of NMU and NURP enhanced GSIS and restored lipotoxicity-induced β cell dysfunction. NMU and NURP acted on different GPCRs expressed on β cells. Both were Gi-coupled receptors and suppressed glucose-induced intracellular Ca2+ influx into β cells. Knockdown of these receptors and knockout mice abolished the peptides’ activities.Conclusion: The proNMU gene produces NMU in β cells and NURP in α cells. These two insulinostatic peptides induced β cell failure by triggering mitochondrial dysfunction and ER stress. Identification of peptides and their receptors in islet cells provides valuable insights into the further investigations of islet biology and diabetes pathogenesis.DisclosureM. Nakazato: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-34-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 34-PUB: Does Glycaemic Control or Renal Function Provide a Better
Indicator for the Service Support Required in Type 1 Diabetes (T1D)'-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 34-PUB
Abstract: Introduction and Objective:IntroductionAdvancements in blood glucose measurement and insulin dosing over the past two decades have improved outcomes for individuals with Type 1 diabetes (T1D). However, chronic kidney disease (CKD) remains a significant management challenge. The frequency of specialist outpatient (OP) appointments could serve as a proxy for disease severity. This study aimed to determine whether glycaemic control (HbA1c) or renal function (eGFR and ACR) better predicts the need for intensive specialist care in T1D.Methods: Health records of T1D individuals were analysed over 15 years (2008-2023). Cross-sectional and longitudinal analyses examined associations between glycaemic control (HbA1c), renal function (eGFR and ACR), and the number of diabetes OP appointments per year. Patients requiring >4 OP appointments annually were classified as needing intensive input. Odds ratios (OR) were calculated to assess the likelihood of intensive input based on glycaemic and renal parameters.Results: 348 patients with average age 51 years of whom 151 were female had sufficient data to analyse. There was no link between relative level of HbA1c (<65mmol/mol vs ≥65mmol/mol) and relative number of specialist OP appointments/year.Patients with lower eGFR (<60ml/min/1.73m²) had a significantly higher likelihood of needing >4 OP appointments/year (OR 2.9). Elevated ACR (≥3.0mg/mmol) was also associated with increased likelihood (OR 1.4). A rapid decline in eGFR (>6.4ml/min/1.73m² over six years) further increased the odds of intensive input (OR 1.4).Conclusion:Renal function markers (eGFR and ACR) are better indicators than glycaemic control for predicting the need for intensive specialist support in T1D patients. This emphasises the importance of comprehensive kidney function monitoring and targeted renal protective intervention alongside glycaemic optimisation in T1D management. Prioritisation and allocation of healthcare resources to this is essential.DisclosureM. Stedman: None. A.H. Heald: None. M.B. Whyte: None. J.M. Gibson: None. E.B. Jude: Research Support; Abbott Diagnostics. Speaker's Bureau; AstraZeneca, A. Menarini Diagnostics, Novo Nordisk. Research Support; Sanofi. H.H. Habte-Asres: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-34-PUB
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 35-OR: Temporal Dynamics of RNA Modifications and Translation in Type I
Interferon–Stimulated Human Islets-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 35-OR
Abstract: Introduction and Objective: Pro-inflammatory cytokines, particularly IFNα and IFNγ, play a critical role in type 1 diabetes (T1D) pathogenesis. IFN induced gene signatures are present in pancreatic islet biopsies from individuals with recent-onset T1D. However, their impact on the β-cell epitranscriptome and translatome has not been tested.Methods: Human islets from 10 cadaveric donors were treated with IFNα or IFNγ for 8 or 24 h to simulate early T1D conditions. Polyribosomal profiling (PRP) was performed to assess changes in translation. Long-read native RNA sequencing was performed to characterize time- and cytokine-specific changes in RNA modifications. RIP-LCMV-GP mice were utilized for in vivo experimentsResults: PRP revealed that IFNs induced a block in mRNA elongation, while immunoblot analysis showed activation of the integrated stress response (ISR) pathway. Using long-read native RNA sequencing, we uncovered time- and cytokine-specific changes in RNA modifications. IFNα treatment increased m6A methylation, with 1,688 out of 4,006 unique sites modified after 8 h and 14 out of 936 sites modified after 24 h. Similarly, IFNγ treatment modified 639 out of 2,527 sites at 8 h and 65 out of 664 at 24 h. Additionally, 95 differentially methylated sites were shared across all conditions, many linked to ISR activation. Notably, we identified epigenetic alterations in genes that are found to be activated during defective mRNA translation (eg. GBP1) and genes involved in β cell dysfunction (NUB1and RTP4) and immunogenicity (eg. IFIT2, Mx1, OAS1 and STAT1). In vivo, treatment with ISRIB, an ISR inhibitor, reduced diabetes incidence by 70% in RIP-LCMV-GP mice (vehicle vs. ISRIB; p<0.001) and rescued mRNA translation in islets.Conclusion: These findings demonstrate that inflammation-induced ISR activation drives RNA modifications and mRNA translation defects in β cells in a time and cytokine-dependent manner and suggests that targeting the ISR pathway may hold promise as a therapeutic approach for T1D.DisclosureF. Syed: None. J. Rana: None. S. Bhattacharya: None. C. Evans-Molina: Advisory Panel; DiogenX. Research Support; Bristol-Myers Squibb Company, Lilly Diabetes. Advisory Panel; Isla Technologies, Neurodon. Research Support; Neurodon.FundingBreakthrough T1D-JDRF 5-CDA-2022-1176-A-N
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-35-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 35-PUB: A Novel Integrated Risk Stratification Framework for Diabetes
Management in Saudi MEDGULF-Insured Patients-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 35-PUB
Abstract: Introduction and Objective: Chronic diseases like diabetes strain healthcare systems among Saudi MEDGULF insured population. Traditional clinical guidelines and advanced AI-driven methods often exist in silos, hindering comprehensive management. This study introduces an Integrated Clinical-AI Stratification Framework that unifies evidence-based clinical protocols with AI models to enhance early detection, individualized risk stratification, and personalized interventions for diabetic patients.Methods: Claims data, including structured and unstructured patient information, was used to identify key clinical features aligned with international guidelines. AI models predicted disease onset, progression, and complications, placing patients into low-, moderate-, high-, and complications-risk groups. Clinical teams validated refined stratifications, ensuring fidelity to evidence-based practice and seamless integration with AI-generated insights.Results: Preliminary validation on retrospective datasets revealed improved precision in identifying high-risk individuals, earlier detection of complications, and better alignment of interventions with clinical standards. Healthcare professionals noted greater efficiency in care coordination, highlighting the framework’s capacity for dynamic adaptation as new data is incorporated. By bridging clinical guidelines and AI outputs, the framework fosters consistent, targeted care across diverse patient populations.Conclusion: The Integrated Clinical-AI Stratification Framework demonstrates a viable approach to unifying standard clinical guidelines with cutting-edge AI to enhance diabetes care for MEDGULF-insured patients. Future large-scale studies will examine real-world efficacy, focusing on reducing hospitalization rates, improving glycemic control, and optimizing healthcare resource allocation. This pioneering model shows potential to revolutionize diabetes management through patient-centric and proactive intervention.Disclosure M. Ghosheh: Employee; iO Health. A. Kheir: Employee; MEDGULF Insurance & Reinsurance company. M.A. Mohamed: Employee; MEDGULF Insurance & Reinsurance Company. W. Afzal: Employee; MEDGULF Insurance & Reinsurance Company. G. Ghosheh: Employee; iO Health.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-35-PUB
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 36-OR: Sex-Based Molecular Architecture of Estrogen Receptor Actions in
Human Islet Cells-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 36-OR
Abstract: Introduction and Objective: The main estrogen (17β-estradiol, E2) enhances insulin biosynthesis and secretion, protecting both female (F) and male (M) β-cells from metabolic stresses via the estrogen receptor-α (ERα). E2 activates unfolded protein degradation pathways, mitigating endoplasmic reticulum (EndRet) stress in human and mouse islets. However, the FDA-approved selective estrogen receptor modulator (SERM) bazedoxifene (BZA) protects F but not M β-cells. The mechanisms underlying these sexually dimorphic effects remain unclear.Methods: We treated human islets (3 F and 3 M donors) with vehicle, E2 or BZA, performing scRNAseq and snATACseq (~140,000 cells).Results: E2 increased gene pathways involved in mitochondrial function/respiration and antioxidant protection in β-cells and endothelial cells in both sexes. E2 also increased genes involved in unfolded protein response (UPR) in β-cells and angiogenesis in endothelial cells in both sexes. E2 increased genes in translation in F β-cells and lipid transport in F endothelial cells BZA increased cholesterol/lipid transport and metabolism genes in β-cell and endothelial cells as well as translation genes in β-cells of F. However, BZA increased genes in translation but downregulated genes in mitochondrial function/respiration in β-cells and endothelial cells.Conclusion: In summary, E2 promotes mitochondrial function and stress resilience as well as angiogenesis in both sexes. In contrast, BZA exhibits sexually dimorphic effects, suppressing mitochondrial activity in M cells while supporting lipid metabolism and cholesterol synthesis in F cells. These data highlight the importance of single cell transcriptomics for sex-based precision medicine.DisclosureM. Qadir: None. S. Haque: None. F. Mauvais-Jarvis: None.FundingNIH National Institute of Diabetes and Digestive and Kidney Diseases (FMJ) (DK074970); NIH National Institute of General Medical Sciences (FMJ) (P20GM152305); U.S. Department of Veterans Affairs Merit Award (FMJ) (BX005812); NIH National Institute of Diabetes and Digestive and Kidney Diseases (IIDP) (2UC4DK098085); NIH NIDDK (1K99DK140067)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-36-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 36-PUB: Developing an Evidence-Based Care Pathway for Transgender Youth
with Obesity—Integration of Patient and Caregiver Perspectives-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 36-PUB
Abstract: Introduction and Objective: Pediatric obesity rates continue to rise, and with them, comorbidities such as Type 2 diabetes. Transgender youth may be more susceptible to these conditions due to gender- and weight-based stigmatization, increased BMI from gender-affirming therapies, and maladaptive weight management behaviors. Furthermore, current pediatric weight management uses a “one size fits all” approach and does not consider the unique needs of this population. As such, the goal of this study is to understand patient and family experiences to inform the creation of an evidence-based care pathway for the treatment of transgender youth with obesity in order to reduce diabetes risk.Methods: This study examined the lived experiences of transgender patients with obesity and their caregivers using qualitative methodology. Six patient-caregiver dyads (N=12) participated in individual interviews. Sessions aimed to capture aspects of patients’ gender journeys, weight history, communication with healthcare providers and recommendations for improved weight management.Results: Most participants report not having experienced weight-related medical care, but note experiences of gender- and weight-stigmatizing language from providers and recognize social norms of weight are grounded in gender. Treatment program recommendations include having multidisciplinary and integrated care across clinics and locations (e.g. hospitals and schools), inclusive care and communication, and tailoring to patient goals and needs based on gender. Participants emphasize being comfortable in their own bodies being the most important end goal for a gender-focused weight management program.Conclusion: Preliminary findings highlight gaps in current care and opportunities for improved treatment in this population. Next steps include additional groups and involving healthcare providers for their insight into the construction of an affirming care pathway.DisclosureC. Theriault: None. A. Sharer: None. R. Doyle: None. K. Oyola-Cartagena: None. S. Gedeon: None. C.L. Olezeski: None. C. Finck: Advisory Panel; Harvard regenerative technologies. Other Relationship; Esophadex. M. Santos: None.FundingAmerican Diabetes Association (11-22-ICTSHD-17)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-36-PUB
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 37-OR: Steatohepatitis with Significant Liver Fibrosis Is Common in
Outpatient Primary Care and Endocrinology Clinics-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 37-OR
Abstract: Introduction and Objective: Metabolic dysfunction-associated steatohepatitis (MASH) is a leading cause of cirrhosis. NIS2+™is a novel blood-based diagnostic test developed to identify “at-risk” MASH (steatohepatitis with significant fibrosis stage ≥F2) that combines miR-34a-5p (microRNA linked to altered lipid metabolism) and YKL-40 (biomarker of fibrosis). Our aim was to assess the prevalence of “at-risk” MASH by NIS2+™ in unselected people from primary care or endocrine outpatient university clinics.Methods: We recruited 687 participants and assessed for “at-risk” MASH by NIS2+™ (defined as NIS2+™ ≥0.68). We measured by transient elastography (Fibroscan®) steatosis (CAP≥274 dB/m) and fibrosis (Liver Stiffness Measurement [VCTE-LSM]≥7.0 kPa). A subset underwent magnetic resonance (MR) iron-corrected T1 mapping for MASH disease activity (cT1) and MR-elastography (MRE) for fibrosis (n=51).Results: Overall, 44% had T2D (28% with obesity); 25% obesity alone, without T2D; and 31% neither. “At-risk” MASH by NIS2+™ was observed in up to 20% individuals with obesity and T2D, 13% with obesity only and 3% in those without obesity or T2DM (all p<0.001 vs. obesity and/or T2D). People with “at-risk” MASH vs. low-risk MASH by NIS2+™ had more often steatosis (80% vs 46%), fibrosis (30% vs 5%), AST≥40 IU/L (39% vs. 1%), ALT≥40 IU/L (46% vs. 4%), hepatic IR (HOMA-IR≥3.0: 66% vs. 32%) and adipose tissue IR (adipo-IR≥2.0: 80% vs 62%) (all p<0.01). NIS2+™ correlated with CK-18, a marker of hepatocyte apoptosis (r=0.49, p<0.001), with cT1 (r=0.44, p=0.002) and liver fibrosis by VCTE-LSM (r=0.29, p<0.001) or MRE (r=0.28, p=0.049).Conclusion: “At-risk” MASH with severe steatohepatitis and significant fibrosis (stage ≥F2) is common in unselected patients with obesity and/or T2D (~20%) in outpatient primary care and endocrinology clinics. More awareness and early risk-stratification will help identify people in need of early intervention and intensive multidisciplinary care.DisclosureS. Kalavalapalli: None. E. Godinez Leiva: None. A. Ortiz Rocha: None. N. Cuervo-Pardo: None. K.Y. Chun: Employee; LabCorp. T.R. Prezant: None. M.A. Connelly: Employee; LabCorp. Stock/Shareholder; LabCorp. A. Sharma: None. D. Barb: Other Relationship; Inventiva Pharma, Boehringer-Ingelheim. K. Cusi: Research Support; Boehringer-Ingelheim, Echosens, Inventiva, Perspectum Ltd, LabCorp. Consultant; Arrowhead Pharmaceuticals, Inc, AstraZeneca, TERNS Pharmaceuticals, 89bio, Inc, Boehringer-Ingelheim, Eli Lilly and Company, Novo Nordisk A/S, Sagimet Biosciences.FundingNIH/NIDDK (R01DK120331); PI: Kenneth Cusi.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-37-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 38-OR: Effects of Dorzagliatin, Insulin Glargine, and Metformin on
Nocturnal Endogenous Glucose Production in Type 2 Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 38-OR
Abstract: Introduction and Objective: In Type 2 Diabetes (T2D) higher nocturnal glucose production (EGP) results from higher glycogenolysis (GGL) and gluconeogenesis (GNG). Appropriate medications are needed to restore nocturnal EGP. We hypothesized that Dorzagliatin (DG) IND-159103-Glucokinase activator), insulin glargine (IG) (inhibitor of GGL) and metformin (M) (inhibitor of GNG) may lower GGL and GNG thereby lowering EGP in T2D.Methods: Twenty-three T2D subjects (age ~62 yrs, BMI ~32.0Kg/m2, FPG ~7.0mmol/L, HbA1C ~7.0%, ~9 years average diabetes duration) insulin or long acting GLP-1 agonist naive received 6-week monotherapy with either DG=7 (75mg bid), IG=9 (once daily) or M=7 (1.5-2gm daily). All other antidiabetes medications were washed out. Studies were conducted overnight at baseline (BL) and post treatment (PT). EGP, GNG and GGL were estimated at 1,4,7 AM using infusion of [6,6-2H2] glucose (10 PM-7 AM) following ingestion of deuterium labeled water (2H2O) as previously established.Results: The trial is ongoing. EGP was lower with DG (BL vs PT:18.7±9.8vs.15.6±12.5 at 1am;15.4±4.9 vs 14.6±7.0 µmol/KgFFM/min at 7am) primarily due to lower GGL (BL vs PT:10.3±4.2 vs 9.1±7.5 at 1am; 10.4±3.4 vs 7.9±3.5 µmol/kgFFM/min at 7am with similar values at 4am). Similarly, EGP was lower with IG (BL vs PT:19.1±8.0 vs 18.5±10.4 at 1am, 17.9±5.6 vs 16.4±7.3 at 4am and 18.9±5.5 vs 17.1±8.1 µmol/kgFFM/min at 7am). Decrease in EGP was due to lower GGL overnight as hypothesized (9.8±4.2 vs 8.6±3.7 at 4am and 10.2±4.4 vs 9.3± 4.4 µmol/kgFFM/min at 7am). On the contrary, M therapy with the prescribed standard dose was insufficient to lower EGP overnight (BL vs PT: 14.3±8.8 vs 17.5±4.1 at 1am;18.0±5.0 vs 18.2±6.0 at 4am;12.2±4.6 vs 15.6±5.5 µmol/kgFFM/min at 7am).Conclusion: Both DG and IG lowered nocturnal EGP by reducing rates of GGL overnight with a smaller contribution of GNG. M used as monotherapy did not provide adequate lowering of nocturnal EGP. These drugs used in combination may target GGL and GNG overnight thereby reducing nighttime EGP.DisclosureA. Hodhod: None. U.S. Unni: None. B. Gran: None. A. Basu: None. R. Basu: Advisory Panel; Novo Nordisk, Boehringer-Ingelheim.FundingNational Institutes of Health (R01 DK029953, R01 DK085516DK059637 (MMPC), and DK020593 (DRTC))
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-38-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 38-PUB: Implementation and Feasibility of Assessments to Improve Nutrition
Knowledge at Initial Follow-up for Recently Diagnosed Youth with Type 2
Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 38-PUB
Abstract: Introduction and Objective: Nutrition education is vital for managing type 2 diabetes (T2D). For newly diagnosed patients receiving nutrition education, it is hard to determine how much knowledge is retained during that stressful period. We implemented nutrition assessments at the first comprehensive diabetes visit to evaluate baseline nutrition knowledge. We hypothesize that the quizzes will reinforce nutrition knowledge in newly diagnosed youth with T2D.Methods: A quality improvement project was prospectively conducted to evaluate nutrition knowledge retained following new diagnosis of T2D. We implemented an 18-item nutrition assessment (at the first or second outpatient visit) evaluating nutrition label reading, hypoglycemia/hyperglycemia management, insulin management and physical activity. Data was collected from the medical record, and descriptive and summary statistics were performed.Results: Quizzes were administered to 17 patients and their caregivers, mean patient age 15.1 ± 2.1y, 71% were NH Black, 82% on public insurance, with mean HbA1c 11.3% at diagnosis, and 8.3% at time of assessment. Quizzes were completed by patients (n=9), patient and parent together (n=6) or parent alone (n=2). Mean overall assessment score was 14/18 (74%). Patients scored well on questions about insulin (88% correct) and physical activity (92% correct), but needed additional reinforcement on questions about general nutrition (53% correct) and acute and chronic complications of diabetes (63% correct). Patients with HbA1c <7% scored higher than patients with an HbA1c >7%, (p=0.02).Conclusion: Implementation of nutrition assessments at the first comprehensive diabetes visit is feasible and facilitates nutrition education with the patient and/or caregiver in an engaging manner. Reinforcement of nutrition education is critical for long-term diabetes management and outcomes.DisclosureA. Olkowski: None. C. Wu: None. A. Blevins: None. D. Patel: None. E.A. Brown: None. R.M. Wolf: Research Support; Novo Nordisk, Lilly Diabetes. Advisory Panel; Uneo. Research Support; Sanofi.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-38-PUB
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 39-OR: The Effect of Glucagon on Hepatic Amino Acid and Glucose Metabolism
in Obesity with or without Hepatic Steatosis-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 39-OR
Abstract: Introduction and Objective: Amino acids (AAs) stimulate glucagon which increases hepatic AA catabolism. AA. Glucagon concentrations are increased in prediabetes. This led to the hypothesis that hepatic resistance (associated with hepatic fat content) to glucagon’s actions on AA metabolism leads to hyperglucagonemia and hyperglycemia.Methods: To test this hypothesis, we quantified hepatic fat by MRI as Proton Density Fat Fraction (PDFF) in lean (n = 10) and obese subjects (n = 20). Half of the latter group had a PDFF < 5%; the remainder a PDFF > 5%. After an overnight fast, femoral vein, femoral artery, and hepatic vein catheters were placed. At 0700 (-180 min), infusions of [3-3H] glucose (10 μCi prime, 0.1 μCi/min continuous), indocyanine green and L-[1-13C,15N]-Leucine (7.5μmol/kg prime, 7.5μmol/kg/hour continuous) started. At 1000 (0 min), insulin was infused at 0.8 mU/kg/min (0 - 240 min) alongside glucagon (1.5 ng/kg/min 0 - 120 min; 3.0 ng/kg/min 120 - 240 min). A hyperglycemic clamp maintained peripheral glucose at ~9.0 mmol/L. A mixture of AAs (Clinisol, Baxter, Healthcare, Deerfield, IL; 15%, 0.003ml/kg/min;) was also infused.Results: As expected, the glucose infusion rate necessary to maintain the clamp was lower in obese subjects (15.4 ± 1.3 vs. 4.9 ± 0.7 mg/kg/min, lean vs. obese respectively, p < 0.01). This was also the case for glucose disappearance (93 ± 7 vs. 35 ± 4 μmol/kg/min, p < 0.01) unlike endogenous glucose production (11 ± 2 vs. 9 ± 1 μmol/kg/min, p = 0.04). There was no effect of hepatic fat on these parameters (p > 0.10). Splanchnic extraction of glycine, but not other AAs, was increased (0.04 ± 0.02 vs. 0.23 ± 0.03, p = 0.01) in obesity (independent of PDFF) throughout the study. Conversion of Leucine to α-Keto IsoCaproic acid was unchanged by obesity (at 240 min: 461 ± 53 vs. 381 ± 65 μmol/kg/min, p = 0.42) or PDFF (p = 0.84).Conclusion: We conclude that increases in hepatic fat do not alter hepatic AA metabolic response to glucagon in postprandial conditions.DisclosureH.E. Christie: None. S. Mohan: None. A.M. Egan: None. M.D. Jensen: Consultant; Novo Nordisk, Dexcom, Inc. K. Nair: None. A. Vella: Research Support; Novo Nordisk A/S, Dexcom, Inc. Advisory Panel; Boehringer-Ingelheim, Rezolute.FundingNational Institute of Health (DK116231-06)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-39-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 39-PUB: Obesity, Gender, and Diabetes Risk—A Retrospective Chart
Review-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 39-PUB
Abstract: Introduction and Objective: Research on relationships between obesity and diabetes risk for transgender youth is limited, despite indications of increased risk of transgender youth developing obesity and diabetes. Understanding this relationship is critical in developing affirming and clinically effective care. This study documented the prevalence of obesity and related health factors in adolescents at their initial gender program visit.Methods: A retrospective chart review conducted on 94 patients receiving care at a gender clinic extracted data points of body mass index (BMI) percentiles and z-scores for assigned sex at birth (ASAB) and affirmed gender, as well as psychological and medical comorbidities.Results: The average patient seen in the gender program was 14.7 years old, white (60.64%), non-Hispanic/Latino (56.57%), and transgender male (62.77%). The average ASAB BMI percentile was 69.57 (z-score = 0.84) with transgender males and females having an average BMI of 25.64 and 22.21. Of note, using affirmed gender to determine BMI percentiles and z-scores displayed changes in weight of transgender males (88.14% had increase in z-score; 74.58% had increase in BMI percentile) and transgender females (78.57% had decrease in z-score; 60.71% had decrease in BMI percentile). This population had the following incidence rates: 3.19 pre-diabetes, 31.92 obesity, 60.64 anxiety, and 17.02 asthma.Conclusion: This retrospective chart review found adolescents entering this gender program were at higher ends of normal weight. Upon comparison, transgender males were at potentially increased risk of obesity compared to transgender females prior to initiating gender affirming treatment. Given increasing rates of pediatric obesity for all adolescents, providers should remain vigilant and assess for weight-related comorbidities like diabetes. Future research could explore health behaviors contributing to overall wellbeing, to inform affirming treatment options for transgender youth.DisclosureK. Oyola-Cartagena: None. A. Sharer: None. S. Gedeon: None. C. Finck: Advisory Panel; Harvard regenerative technologies. Other Relationship; Esophadex. M. Santos: None.FundingAmerican Diabetes Association (11-22-ICTSHD-17)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-39-PUB
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 40-OR: Lifestyle Treatment Significantly Resolved Metabolic
Dysfunction–Associated Steatotic Liver Disease (MASLD) by Altering
Extrahepatic and Hepatocellular Fatty Acid Trafficking-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 40-OR
Abstract: Introduction and Objective: The mechanisms by which lifestyle intensive treatments alter fatty acid (FA) flux to improve MASLD severity are unknown. We quantitated changes in lipid flux to understand how 9-months of diet and exercise altered the clearance and hepatic handling of FA derived from the diet, de novo lipogenesis (DNL), and adipose FA flux.Methods: Patients (9M/15F; BMI: 39.3±7.7 kg/m2; NAFLD activity score (NAS, range 0-8): 5.5±3.8; HbA1c: 7.3±1.5%) received either standard of care (SOC, n=8) or treatment (n=16). Stable isotopes were administered to quantitate nocturnal and fasting hepatic DNL, dietary, and adipose FA kinetics. Other methods included MRI, DEXA, an exercise treadmill test to assess cardiorespiratory fitness (VO2peak), and a liver biopsy at the study's end.Results: Compared to no significant changes observed in SOC subjects, treatment improved weight (-6.1%, P=0.003), fitness (+27% VO2peak, P=0.003), liver fat (-47%, P=0.01), DNL (-28%, P=0.01), and NAS (-46%, P=0.0001). Dietary FA spillover into the plasma FFA pool decreased 22% (P=0.02) with the greatest spillover reductions in those who increased appendicular lean mass index, a marker of skeletal muscle mass (r=0.734, P<0.001). VLDL-TG concentrations were maintained due to an 8% increase in hepatic use of FFA for VLDL-TG assembly and secretion (P=0.02). Reduced liver fat was associated with lower DNL (r=0.519), TG secretion from FFA (r=0.575), and total TG secretion rates (r=0.728, P<0.005 for all three). After treatment, subjects with lower DNL exhibited the most significant percentages of FFA routed out of the liver in VLDL-TG (r=0.717, P<0.0001).Conclusion: A loss of intracellular DNL FA availability results in greater use of plasma FFA for TG esterification and secretion. For MASLD patients undergoing diet and exercise, weight loss and fitness gains contribute peripheral and direct hepatic benefits which can contribute to disease resolution.DisclosureJ.G. George: None. J.M. Mucinski: None. K.M. Boone: None. J. Anderson: None. T.M. Fordham: None. G. Lastra: None. J.A. Ibdah: None. R. Rector: Research Support; Eli Lilly and Company, Edgewise Therapeutics. E.J. Parks: None.FundingNIH (DK 113701)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-40-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 40-PUB: Connecting through Content—Peers Supporting Peers with Type
1 Diabetes (T1D)-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 40-PUB
Abstract: Introduction and Objective: Youth with type 1 diabetes (T1D) often struggle with self-management and quality of life due to increasing social, medical, and familial demands. Peer support may help youth with T1D, yet few interventions utilize this form of support. Short-form content (e.g., Tik-Tok style videos), popular among youth, may facilitate peer connections for youth with T1D. We report on the recruitment and participation of teens with T1D who created short-form content for a behavioral intervention.Methods: Teens (age 14-17, T1D duration ≥1 year) created short-form videos to be used in an app-based behavioral intervention trial, designed to promote resilience in younger “tweens” (age 10-13). Older teens were recruited from 2 pediatric diabetes centers and community organizations via an interest form distributed in clinics and online. Interested families contacted the study team, provided consent/assent, and completed media releases. Participants were asked to create up to 4 brief (<2 min) videos about living well with T1D, received guidance on video creation and uploading to a secure platform, and were compensated per video.Results: Families submitted 36 interest forms, 23 participants consented, and 12 submitted 24 videos. Participants were 16.1±1.3 years old; 74% female, 22% male, 4% nonbinary; 9% Black/non-Hispanic, 9% Hispanic, 65% non-Hispanic White, 17% other/multiple races. Video length ranged from 26-140 (M=87.1±31.97) seconds; topics included “Day in the Life with T1D", "Get Ready with Me", "What’s in My Bag'", and "Playing Sports with T1D."Conclusion: Engaging teens to create content for younger tweens was feasible, yet targeted strategies may be needed to obtain more videos from teens from diverse backgrounds and in Spanish. We will examine younger teens’ engagement and satisfaction with the videos via metrics in the study app. Short-form, relatable content may be a useful medium to create a sense of community, provide positive role modeling, and support T1D self-management.DisclosureS.H. White: None. G. Maya: None. K. Holland: None. Y. Rojas: None. D. DeSalvo: Consultant; Dexcom, Inc. Advisory Panel; Insulet Corporation. S. Majidi: Speaker's Bureau; Sanofi. M.E. Hilliard: None. R. Streisand: None.FundingNIDDK (R01DK131350)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-40-PUB
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 41-OR: Exploring the Role of Granulin in Sarcopenia—From Clinical
Observations to Cellular Mechanisms-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 41-OR
Abstract: Introduction and Objective: Sarcopenia, characterized by the loss of skeletal muscle mass and function, is a significant complication of diabetes mellitus and is associated with increased hospitalization and mortality. Despite its clinical importance, the mechanisms underlying sarcopenia remain unclear. Granulin, derived from progranulin, has been implicated in muscle hypertrophy and the activation of the AKT/mTOR pathway. Therefore, we investigated the role of granulin in sarcopenia.Methods: A total of 172 subjects were enrolled, and the appendicular skeletal muscle mass index (ASMI) was measured. Serum granulin levels were measured by ELISA. To clarify the causal relationship between granulin and sarcopenia, high-fat diet and hindlimb ligation sarcopenic animal models were used. L6 myoblast cell line was used to investigate the possible mechanisms.Results: Serum granulin concentrations were significantly lower (280.71±148.09 ng/mL vs 378.96±139.65 ng/mL, p<0.001) in the low muscle mass group (n=30) compared to the normal group (n=142). Reduced muscle granulin expression was also observed in sarcopenic mice. In L6 cells, granulin enhances glucose uptake and protein synthesis through the AKT/mTOR pathway. Knockdown of Ephrin type-A receptor 2 (EphA2) gene abolished granulin's effects on glucose uptake and protein synthesis, indicating that EphA2 pathway is essential for mediating granulin's functions.Conclusion: Granulin regulates skeletal muscle mass and function, highlighting its potential as a biomarker and therapeutic target for sarcopenia.DisclosureK. Chan: None. Y. Chou: None. Y. Hsu: None. H. Wu: None. H. Ou: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-41-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 42-OR: Miro1 Negatively Regulates Skeletal Muscle Insulin Action in Mice
with Diet-Induced Obesity and Hyperglycemia-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 42-OR
Abstract: Introduction and Objective: Mitochondrial Rho-GTPase (MIRO1) is a critical regulator of mitochondrial trafficking and calcium homeostasis and by extension, mediates cellular energy balance and intracellular signaling. This study aimed to mechanistically decipher the role of MIRO1 in modulating skeletal muscle insulin action, which has been completely unexplored.Methods: Skeletal muscle MIRO1 KO mice (MIRO1MKO) and littermate controls were generated by crossing MIRO1-floxed mice with Acta1-Cre transgenic mice. 8-week-old animals were maintained at thermoneutrality and fed a high fat diet for 16 weeks to induce metabolic stress. Following dietary intervention, insulin sensitivity was assessed in vivo by insulin tolerance test (ITT) and skeletal muscle was insulin stimulated ex vivo to analyze insulin signaling protein targets. Additionally, C2C12 myoblasts with shRNA-mediated MIRO1 knockdown were utilized to evaluate glucose uptake and insulin signaling pathways.Results: MIRO1MKO mice exhibited increased insulin tolerance relative to littermate controls (p<0.01). Skeletal muscle sections from MIRO1MKO mice displayed increased GLUT4 localization at the cell surface under both basal (p<0.001) and insulin-stimulated conditions (p<0.05), accompanied by increased Akt phosphorylation at Thr308 (pAktThr308) (p<0.01). Consistent with these findings, shRNA-mediated MIRO1 knockdown increased glucose uptake (p<0.01) and GLUT4 content (p<0.01) at the plasma membrane in C2C12 myoblasts.Conclusion: MIRO1 plays a critical role in mediating skeletal muscle insulin action. Collectively, these data indicate that MIRO1 acts as a negative regulator of glucose homeostasis desensitizing skeletal muscle insulin action.DisclosureA.L. Taylor: None. E.C. Heintz: None. E.R. Zunica: None. B. Vandanmagsar: None. W.S. Dantas: None. P. Baumgarten: None. K. Belmont: None. C.L. Axelrod: None. J.P. Kirwan: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-42-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 43-OR: Muscle mTOR Activation Attenuates Cardiomyopathy and Extends
Lifespan in Muscle-Specific IRS1/IRS2 Knockout Mice-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 43-OR
Abstract: Introduction and Objective: We investigated the role of insulin/IGF1 signaling in cardiac function and lifespan of MDKO mice (Irs1L/L•Irs2L/L•CreMck) generated by MCK (muscle creatine kinase) driven Cre expression in striated and cardiac muscle.Methods: MDKO mice died by 30 days of age with severe cardiomyopathy. Deletion of FoxO1 and FoxO3a in MDKO mice (MQKO mice) slowed progression of cardiomyopathy, extending lifespan to 80 days. MDKO mice showed severely reduced Akt→mTOR signaling so we investigated whether genetic activation of mTorc1 in MTKO mice (Irs1L/L•Irs2L/L•Tsc1L/L•CreMck) could attenuate cardiomyopathy and extend lifespan.Results: Lifespan increased to 220 days, but MTKO mice showed cardiac dysfunction (reduced ejection fraction) at 112 days of age. Full activation of mTorc1 appeared to be essential to compensate for insulin/IGF resistance because partial activation of mTorc1 caused severe cardiomyopathy and death of MDKO•Tsc1L/+ mice by 40 days of age. Unexpectedly, HFD (high fat diet) feeding of MDKO•Tsc1+/- mice restored the lifespan from 40 to 220 days. HFD also significantly increased lifespan of MQKO mice from 80 to 178 days; however, HFD did not increase the lifespan of MTKO mice beyond 220 days. Thus, HFD or muscle Tsc1 deletion appears to extend lifespan during chronic insulin/IGF1 resistance. Cardiac glucose uptake was significantly reduced in MTKO mice; however, cardiac fatty acid uptake did not increase. Lactate might nourish the cardiac muscle of MTKO mice as cardiac lactate transporters increased significantly while circulating lactate decreased. Consistently, lactate treatment of MTKO mice corrected cardiac function, including ejection fraction and structural cardiac parameters (left ventricle internal diameter). MTKO mice fed lactate survived until the experiment was terminated at 280 days.Conclusion: Overall, these results suggest that the progression of fatal cardiomyopathy in MDKO mice was rescued by mTorc1 activity through genetic and/or nutritional manipulation.DisclosureO. Stoehr: None. R. Tao: None. K.D. Copps: None. M.F. White: Board Member; HPRL (Housey Pharmaceutical Research Laboratory).
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-43-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 43-PUB: The Risk of Developing Type 1 and Type 2 Diabetes with Preterm
Birth—A Systematic Review and Meta-analysis-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 43-PUB
Abstract: Introduction and Objective: Preterm birth has been increasingly recognized as a risk factor for chronic conditions including diabetes. This systematic review and meta-analysis assessed the risk of developing type 1 diabetes (T1DM) and type 2 diabetes (T2DM) among individuals born preterm using updated data from recent large cohorts.Methods: We systematically searched MEDLINE and Embase from 1946 to 2024. Case control, cross sectional and cohort studies were included. The primary outcomes were crude and pooled adjusted odds ratio (OR) or hazard ratio (HR) of developing T1DM and T2DM after preterm birth.Results: After screening 2,985 records, 48 full texts were evaluated resulting in 27 records included. The pooled crude OR from 20 studies found a significant increased risk of T1DM in preterm birth with OR 1.13 (95% CI 1.08-1.19). The pooled adjusted HR found a similar estimate with low heterogeneity with HR (95% CI) 1.17 (1.11-1.24). The pooled crude OR of 4 studies on T2DM found OR 1.35 (95% CI 1.24-1.47). The pooled adjusted HR (95% CI) for T2DM was 1.41 (1.20-1.64) whereas the pooled adjusted OR for T2DM was OR (95% CI) 1.31 (0.84-2.04) with high heterogeneity.Conclusion: Our results suggest that preterm birth is associated with a 10-15% increased risk of T1DM. There is also an increased risk of T2DM in those born preterm however data are heterogenous with fewer reports.DisclosureR. Wine: None. J. Fu: None. G.A. Tomlinson: None. D. Feig: Other Relationship; Novo Nordisk. Consultant; Ypsomed.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-43-PUB
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 44-OR: Fibro-inflammatory Stromal Cells Produce Atrophy-Inducing Paracrine
Factors in a Mouse Model of Diabetic Sarcopenia-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 44-OR
Abstract: Introduction and Objective: Sarcopenia—encompassing age-related declines in skeletal muscle mass and performance—strongly predicts negative health outcomes; quantitatively correlating with measures of mobility impairment, cardiovascular disease risk and overall mortality. Within the myofiber, sarcopenia drivers include activation of Stat3 signaling by interleukin (IL)6 and Smad2/3 signaling by transforming growth factor (TGF)β. Mesenchymal cells called fibro-adipogenic progenitors (FAPs) are important mediators of myofiber integrity; however, in contexts such as denervation, can promote atrophy through secretion of paracrine factors. Diabetes accelerates sarcopenia progression. While expansion pro-fibrotic FAP populations has been observed in limb muscles of human subjects with type 2 diabetes, the role of FAPs in diabetic sarcopenia remains unclear.Methods: We modeled diabetic sarcopenia by subjecting mice to a 12-month diet-induced obesity (DIO) protocol beginning at 2-months old—equivalent to obesity developing in adolescence and persisting to middle age—and analyzed muscle structure/ function parameters, while conducting scRNA-seq-based evaluation of mesenchymal cell profiles.Results: In contrast to 6-month DIO mice, which developed limb muscle hypertrophy, 12-month DIO mice developed limb muscle atrophy, as indicated by reduced muscle mass, cross-sectional area (CSA), contractile force, and myofiber size. scRNA-seq of gastrocnemius FAPs demonstrated increased advanced glycation end-product (AGE) signaling and emergence of “fibro-inflammatory” sub-populations enriched in transcripts encoding IL6 and thrombospondin-1 (THBS1). The latter is an obesity-induced matricellular protein that promotes TGFβ activation and has recently been linked to Smad2/3-dependent atrophy in mouse models of extreme aging.Conclusion: These data suggest paracrine signaling from emergent fibro-inflammatory FAPs is a novel contributor to diabetic myoatrophy.DisclosureS.K. Patterson: None. J. Cumbum Syed: None. J. Yang: None. M. Woo: None. E.D. Buras: None.Funding5 K08 HL14737701-05R56 DK133298
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-44-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 44-PUB: Screening for Postpartum Hyperglycemia after GDM—A Strategy
Tailoring Either FBG or OGTT as the Diagnostic Test-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 44-PUB
Abstract: Introduction and Objective: Up to one-third of women with GDM develop T2DM postpartum. Despite the importance of early detection, adherence to the postpartum OGTT remains low due to logistical and discomfort challenges. While FBG is a better-tolerated test, it lacks sensitivity in detecting hyperglycemia that only manifests after glucose ingestion. This study aimed to identify factors associated with postpartum hyperglycemia in women with GDM and to propose an optimized screening strategy using FBG or OGTT.Methods: Retrospective cohort of 893 women with GDM who underwent postpartum OGTT between 28 and 180 days after delivery. Clinical and laboratory characteristics were compared between those with normal and abnormal OGTT results and between women with normal and abnormal FBG during OGTT. Multivariate logistic regression identified independent predictors of abnormal results, and ROC curve analysis was used to define optimal cutoff points for FBG and maternal age.Results: Of the 893 women, 168 (18.8%) presented postpartum hyperglycemia. Among them, 90 (54%) had abnormal FBG, and 78 (46%) had abnormal results only after glucose ingestion. Predictors of abnormal OGTT included maternal age (OR 1.04, 95%CI 1.00-1.07), chronic arterial hypertension (OR 1.70, 95%CI 1.14-2.55), and baseline FBG during prenatal care (OR 1.05, 95%CI 1.02-1.08). Predictors of abnormal FBG were baseline FBG (OR 1.06, 95%CI 1.02-1.09) and insulin use during pregnancy (OR 2.75, 95%CI 1.70-4.45). Since insulin use indication varies largely in clinical practice, it was excluded from the algorithm. Targeting OGTT for women with baseline FBG < 97 mg/dL and maternal age ≥ 32 years and/or chronic arterial hypertension, and addressing only FBG for the remaining, reduced the need for OGTT by 49%, achieving 80% sensitivity and 96% accuracy for detecting postpartum hyperglycemia.Conclusion: It is possible to rationalize OGTT use, optimizing postpartum hyperglycemia screening in women that had GDM.DisclosureR. Costa: None. T. Assuncao Zaccara: None. F.C.F. Mikami: None. M.D. Bernardi: None. C. de Freitas Paganoti: None. R.P.V. Francisco: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-44-PUB
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 45-OR: Evaluating the Effects of Hypoglycemia on Plasma Beta Amyloid in
Type 1 Diabetes (T1D)-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 45-OR
Abstract: Introduction and Objective: Insulin-induced hypoglycemia is a risk factor for cognitive decline and augments Alzheimer’s disease (AD) associated proteins in people with type 2 diabetes. During hyperinsulinemia, insulin and beta-amyloid (Aβ) may compete for insulin-degrading enzyme, possibly resulting in Aβ accumulation. We tested the effect of hyperinsulinemia and hypoglycemia on circulating Aβ (Aβ40 and Aβ42) in people with T1D.Methods: Plasma samples from people with T1D who underwent a hyperinsulinemic-hypoglycemic clamp were evaluated for Aβ and inflammatory markers at baseline, euglycemia, and hypoglycemia.Results: Of the 33 participants with T1D (mean age 29.3 years, diabetes duration 5.8 years), 49% were female. Aβ40 and Aβ42 (AD biomarkers) were significantly (p<0.001) upregulated between euglycemia and hypoglycemia but were unchanged between baseline and euglycemia (Figure 1A), indicating no effect of hyperinsulinemia per se. Levels of IL-8, IL-10, TNF-α, and pancreatic polypeptide were also significantly (p<0.05) altered between euglycemia and hypoglycemia (Figure 1B). The increase in Aβ42 correlated with age of the participant, decreased insulin sensitivity, and lower IL-2. Aβ40 was negatively correlated with IL-6 only.Conclusion: In people with T1D, hypoglycemia increases plasma Aβ40 and Aβ42 independent of hyperinsulinemia and appears unrelated to biomarkers of inflammation.DisclosureC. Glass: None. A. Bilal: None. F. Yi: None. C. Rowe: None. Y.O. Nunez Lopez: None. M.R. Rickels: Consultant; Vertex Pharmaceuticals Incorporated, Sernova, Corp. Research Support; Dompé, Tandem Diabetes Care, Inc. Consultant; Novo Nordisk. R.E. Pratley: Consultant; AbbVie Inc. Stock/Shareholder; Altanine, Inc. Consultant; Amgen Inc, AstraZeneca. Other Relationship; Bayer AG, Bayer Pharmaceuticals, Inc, Biomea Fusion. Consultant; Boehringer-Ingelheim. Other Relationship; Carmot Therapeutics, Inc, Corcept Therapeutics, Dompé, Eli Lilly and Company, Endogenex. Consultant; Endogenex. Other Relationship; Fractyl Health, Inc., Gasherbrum Bio, Inc. Consultant; Genprex, Getz Pharma, Hanmi Pharm. Co., Ltd, Intas Pharmaceuticals Ltd, Lexicon Pharmaceuticals, Inc, Lilly USA LLC. Speaker's Bureau; Lilly USA LLC. Other Relationship; Metavention, Novo Nordisk, Novo Nordisk. Speaker's Bureau; Novo Nordisk. Other Relationship; Pfizer Inc, Poxel SA. Consultant; Regeneron Pharmaceuticals. Other Relationship; Sanofi. Consultant; Scholar Rock. Other Relationship; Sun Pharmaceutical Industries Ltd.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-45-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 46-OR: Poor Correlation between Hypoglycemic Symptoms and Heart Rate
Response in CGM Hypoglycemia in T1D—Hypo-METRICS Study-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 46-OR
Abstract: Introduction and Objective: Hypoglycemia causes adrenergic response (AR) associated with autonomic symptoms. We evaluated the relationship between changes in heart rate (HR), surrogate for AR, and symptoms during awake episodes of sensor-detected hypoglycemia (SDH) < 54 mg/dL in people with type 1 diabetes and normal awareness using data from the Hypo-METRICS study.Methods: Participants (n=276; median age 47 years, median HbA1c 7.3%, sensor use 74%) wore blinded sensors for 10 weeks and recorded all hypoglycemia symptoms and their intensity on a bespoke app. HR data and sleep status were obtained from FitBit devices. We used random forest plots in R to analyze the correlations between average HR (avg ΔHR) before and after SDH, autonomic and neuroglycopenic symptom scores (ASS / NSS), hypoglycemia duration, SDH nadir, rate of glucose change prior to SDH, and rate of SDH/week.Results: We identified 7175 symptomatic SDH events. Avg ΔHR was 0.79 beats per min. Correlation factor between avg ΔHR and ASS was 0.005, avg ΔHR and NSS 0.072, avg ΔHR and SDH nadir 0.099. Poor correlation was found among the rest of the variables.Conclusion: HR changes during SDH was poorly correlated with autonomic and neuroglycopenic symptoms. This suggests that perception of hypoglycemia is a complicated biopsychological process in the real world, implicating factors other than hormones in symptom manifestation.Disclosure V. Koutroukas: Other Relationship; Kelcon GmbH. H. Hadid: None. J.J.C. Thomas: None. P. Divilly: None. G. Martine-Edith: None. P. Choudhary: Speaker's Bureau; Abbott. Advisory Panel; Dexcom, Inc. Consultant; Insulet Corporation. Advisory Panel; Ypsomed AG, embecta, Sanofi. Speaker's Bureau; Lilly Diabetes, Medtronic. Advisory Panel; Roche Diabetes Care. Consultant; Cambridge Mechatronics.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-46-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 46-PUB: A Comparative Analysis of Obesity Trends in China during Rapid and
Relatively Slower Periods of Economic Development-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 46-PUB
Abstract: Introduction and Objective: China’s rapid economic development over the past 40 years has coincided with a rise in overweight (OW) and obesity (OB). Over the last 17 years, economic growth has slowed, but its impact on OW and OB remains unclear. This study examines trends in OW and OB prevalence and their associations with economic indicators in China.Methods: Cross-sectional data from the China Marrow Donor Program (CMDP) (2004-2019; 1,859,685 healthy adults across 31 registries) were analyzed. Annual OW and OB prevalence were estimated, economic indicators—Consumer Price Index (CPI) and Per Capita Disposable Income (PCDI) were used to evaluate associations with OB. Data were divided into two periods (2004-2011 846,292 individuals; 2012-2019 1,012,393 individuals). Stratified multivariate logistic regression models were applied.Results: OB risk increased with Higher CPI (OR = 1.13, 95% CI 1.11-1.51, P 0.01) and the growth ratio of PCDI (5% annual PCDI increase, OR = 1.7, 95% CI 1.62-1.78, P 0.01), but not related to absolute PCDI (OR = 1.003). In 2019, OW and OB prevalence reached 38.9% and 13.1%, affecting 329.65 million and 111.01 million individuals, respectively.Conclusion: In China, appropriately slowing the growth rates of CPI and PCDI, may along with the change of people‘s lifestyle, help curb OW and OB trends. Such measures could improve the population’s weight distribution.DisclosureJ. Shen: None. J. Liu: None. L. Jiang: None. X. Ma: None. W. Kong: None. R.R. Sheng: None. F. Wang: None. D. Xu: None. X. Li: None. H. Bu: None. L. Xu: None.FundingChina Marrow Donor Program (201909)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-46-PUB
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 47-OR: Amitriptyline Prevents, But Does Not Restore, the Impaired
Glucoregulatory Response to Hypoglycemia in a Rodent Model of
Hypoglycemia-Associated Autonomic Failure (HAAF)-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 47-OR
Abstract: Introduction and Objective: Iatrogenic hypoglycemia blunts the counterregulatory response to future hypoglycemia challenges. This study aimed to determine whether the tricyclic antidepressant amitriptyline, previously shown to enhance hypoglycemia awareness, can prevent or restore the glucoregulatory response to hypoglycemia.Methods: Protocol #1 - Prevention: Pre-cannulated Sprague-Dawley rats were conditioned with recurrent saline (RS) or recurrent insulin-induced hypoglycemia (RH). A cohort of RH rats were pretreated with amitriptyline (AMT) 10 mg/kg IP.Protocol #2 - Restoration: Rats were subjected to 6 days of RS or RH. During the final 3 days of RH, rats were treated with either AMT or Saline.Glucose infusion rate (GIR) was measured during a hyperinsulinemic (50 mU/kg/min)-hypoglycemic (~45 mg/dl) clamp.Results: In both protocols, consistent with blunted counterregulation, RH resulted in increased GIR. In the prevention protocol, but not the restoration protocol, RH+AMT had a significantly decreased GIR compared to the RH controls (p<0.0001).Conclusion: In the prevention protocol, improved endogenous counterregulation indicates altered serotonin and norepinephrine signaling plays a role in the development of HAAF, but amitriptyline may not restore responses to established HAAF.DisclosureZ. Beckner: None. A. Thompson: None. M.H. Devore: None. A.R. Marksbury: None. M. Wooten: None. E.W. Brockman: None. S.J. Fisher: None.FundingNIDDK (R01DK118082); University of Kentucky Barnstable Brown Diabetes Center; University of Kentucky Diabetes and Obesity Research Priority Area
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-47-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 47-PUB: Emerging Trends of T2DM in Urban India
-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 47-PUB
Abstract: Introduction and Objective: An increase in young onset Diabetes has been seen in recent times. We examined if similar pattern was apparent in our tertiary care setting of urban Delhi.Methods: EMR of patients registered at Diabetes Centre, Sitaram Bhartia Institute of Science and Research, New Delhi were analysed. This urban, tertiary care hospital, caters to patients with high level of public awareness. T1DM, Secondary DM, GDM, and those with incomplete data were excluded. Retrospective, observational, cross sectional study of individuals with Diabetes, who presented in time periods 2011-2013,2014-2016,2017-2019,2020 -2022 were further sub classified based on the age of onset (patient recall) as <=30yrs,31-40yrs, 41-50yrs, 51-60yrs, >60yrs.Results: Of the 1821 patients analysed, significant relation between visiting date and age at diagnosis, adjusted for sex was found using multiple linear regression (Table4-0.001, P<0.05). Significant negative (Table5-0.130, P=0.027) effect of BMI on age at diagnosis, was noted suggesting that individuals with higher BMI are diagnosed at a younger age.Conclusion: Though there was an age standardised increase in incidence of T2DM over the years, we could not substantiate a trend in decreasing age of onset for T2DMDisclosureA.I. Savarimuthu Thomas: None. A.S. Lata: None. A. KappadanTharammal: None. R. Thakur: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-47-PUB
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 48-OR: Recurrent Events and Mortality following Severe Hypoglycemia (SH)
in U.S. Older Adults (OA) with Type 1 Diabetes (T1D)-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 48-OR
Abstract: Introduction and Objective: As more adults with T1D live into older adult years, the risk for SH increases, as does the prevalence of major comorbid conditions (e.g., CKD, dementia) that complicate management. We aimed to quantify recurrent SH and mortality following an initial event in a US-based population of OA with T1D.Methods: We analyzed a random 20% sample of nationwide fee-for-service US Medicare beneficiaries (A/B/D) from 2007-2019, including adults 65+ yrs with T1D (>50% ICD-9/10 codes and insulin use). The index event was an SH event requiring ED visit/hospitalization. We estimated mortality and the mean cumulative count (MCC) for the expected number of recurrent SH events per person, in subgroups defined by diagnosis codes for CKD and dementia.Results: Data were analyzed for 4613 OA with T1D (37.8% male, 77.3% non-Hispanic White, 13.8% Black, 5.5% Hispanic; mean age 75 yrs ± SD 8). There were 3527 recurrent SH events over mean follow-up 3.6 years ± SD 3.0 (incidence rate = 21.4 per 100 person-years). 1-year mortality was 15.2%. 19.2% of the OA experienced 1 SH recurrence; 7.6% experienced 2; 8.2% experienced 3+. OA with T1D and CKD or dementia had lower rates of recurrent events, but higher rates of mortality (Fig 1).Conclusion: OA with T1D experience high rates of recurrent events and mortality in the years after their first SH event, with stark differences according to comorbid conditions.DisclosureA. Kahkoska: None. A. Alexopoulos: None. A. Fruik: None. C.M. Germain: None. A. Ratzki-Leewing: Other Relationship; Abbott, Dexcom, Inc. Consultant; Sanofi. Other Relationship; Sanofi. Consultant; Sanofi-Aventis U.S. Advisory Panel; Sanofi-Aventis U.S. V. Pate: None. A. Kinlaw: None.FundingNorth Carolina Diabetes Research Center (NIDDK P30 DK124723)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-48-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 48-PUB: Trends in Diabetes Mellitus and Chronic Obstructive Pulmonary
Disease–Related Mortality among Older Adults in the United States from
1999–2020-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 48-PUB
Abstract: Introduction and Objective: Diabetes Mellitus (DM) is the 8th leading cause of death in the United States, frequently co-existing with Chronic Obstructive Pulmonary Disease (COPD). The aim of our study was to evaluate mortality trends in DM and COPD-related deaths among adults aged 65 and above.Methods: For this study, we conducted an analysis of the CDC Wonder database, focusing on death certificate data from 1999 to 2020. Specifically, we examined DM and COPD-related mortality among adults aged 65 years and older. Age-Adjusted Mortality Rates (AAMRs) were calculated with 95% confidence interval (CIs), adjusting for variables including year, sex, race/ethnicity, and geographic location.Results: Between 1999 and 2020, there were 540,033 deaths among adults aged ≥ 65 affected by DM and COPD. The AAMR increased from 46.60 in 1999 to 61.30 in 2008 (APC: 3.0; 95% CI: 2.4 to 3.7) which was followed by a decline to 61.00 in 2018 (APC: -0.4; 95% CI: -0.9 to 0.2), and another increase in 2020 to 79.0 (APC: 13.2; 95% CI: 8.2 to 18.5). When stratified by sex, men had a higher overall AAMR than women (AAMR men: 78.6 vs women: 45.7). Non- Hispanic (NH) American Indian/Alaska Native populations had the highest AAMR (83.6), followed by NH White (61.3), NH Black (61.1), Hispanic or Latino (45.2), and NH Asian or Pacific Islander (26.5). A disparity was observed among census regions with the Midwest having the highest AAMR (67.2) followed by Southern (61.3), Western (56.4) and Northeast (48.3). The AAMR was higher in rural areas (78.2) compared to urban areas (54.8).Conclusion: After a notable decline in DM and COPD-related mortality in 2008, the overall mortality took a significant hike in the following years. Furthermore, notable disparities according to race, gender and region were revealed.DisclosureR. Shakil: None. M.O. Mirza: None. M. Ahmad: None. H. Ehtesham: None. A. Moulvi: None. H. Khan: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-48-PUB
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 49-PUB: Diagnosis of Polycystic Ovary Syndrome with General-Purpose Online
Large Language Models—A Prospective Evaluation Study of ChatGPT-3.5,
ChatGPT-4o, Llama-3, and Claude-3.5-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 49-PUB
Abstract: Introduction and Objective: To access the trustworthiness and precision of general-purpose online large language models (LLMs) in providing polycystic ovary syndrome (PCOS) diagnosis-related information.Methods: The present study recruited 125 consecutive women suspected with PCOS in the PCOS subspecialty clinic of Shanghai Tenth People's Hospital between October 2023 and March 2024, and finally 50 women with PCOS and 30 women without PCOS were included. Four popular LLMs: OpenAI’s ChatGPT-3.5, ChatGPT-4o, Meta Llama-3, and Anthropic Claude-3.5, were prompted to diagnose PCOS and No-PCOS based on de-identified medical records. The binary diagnosis of PCOS was established utilizing LLMs’ description by two professional physicians.Results: Among 80 patients suspected of having PCOS, all LLMs could provide the diagnostic impression of PCOS from the textual prompts, with all LLMs achieving 100% sensitivity and negative predictive value (NPV). Claude-3.5 demonstrated the best performance, with an accuracy of 93.8%, followed by Llama-3 at 85.0%, ChatGPT-4o at 78.7%, and ChatGPT-3.5 at 70.0% (P for trend < 0.0001). In terms of specificity and positive predictive value (PPV), similar trends were observed, with Claude-3.5 performing the best and ChatGPT-3.5 the worst.Conclusion: Our findings highlight the potential of LLMs, especially Claude-3.5, as the groundwork for a new generation of artificial intelligence tools that can aid clinical physicians in PCOS diagnosis.DisclosureY. Zhang: None. H. Hui: None. P. Li: None. X. Shao: None. M. Cai: None. D. Dilimulati: None. H. Chen: None. S. Qu: None. M. Zhang: None. H. Ji: None. W. Song: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-49-PUB
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 49-OR: Exposure to Recurrent Hypoglycemia Alters Brain Glutamate and
Lactate Kinetics in Type 1 Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 49-OR
Abstract: Introduction and Objective: Mechanisms of impaired awareness of hypoglycemia (HG) after exposure to recurrent HG are unknown. We sought to determine if recurrent HG alters metabolite responses to HG in individuals with type 1 diabetes (T1D) and normal HG awareness.Methods: Participants with T1D (N=43) who self-reported normal HG awareness (using Cox/Clarke and Gold questionnaires) underwent four 2-hour HG clamps over 2 days to induce impaired awareness of HG. The 1st and 4th clamps were conducted in a 7T scanner. Metabolite concentrations in the prefrontal cortex (PFC) and hypothalamus (HTL) were measured during eu- and hypoglycemia using proton MR spectroscopy. Epinephrine samples and the Towler symptom questionnaire were collected during each clamp.Results: Complete PFC datasets were collected from 35 individuals for Clamp 1 and 29 individuals for Clamp 4 (Table). HG targets were achieved consistently in each clamp, with corresponding reduction in brain glucose levels. Hormone and symptom responses were blunted at Clamp 4 vs. Clamp 1. PFC glutamate and lactate levels decreased with HG at Clamp 1, indicating a slowing of the TCA cycle rate, but not at Clamp 4. Similar trends were observed for HTL.Conclusion: Exposure to recurrent HG blunted glutamate and lactate decrease in response to HG in individuals with T1D and normal HG awareness, indicating a metabolic adaptation to recurrent HG.DisclosureY. Park: None. B.M. Payne: None. A. Kumar: None. A.C. Alvear: None. A. Moheet: Other Relationship; Sanofi-Aventis U.S. L.E. Eberly: None. E.R. Seaquist: None. G. Oz: Research Support; Biogen. Consultant; Servier Laboratories, UCB Biopharma SRL / Lacerta Therapeutics Inc, Sanofi.FundingNational Institutes of Health (R01NS035192)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-49-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 50-OR: Recurrent Moderate Hypoglycemia (RH) Enhances Cardiac Mitochondrial
Respiration in Diabetic Rats-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 50-OR
Abstract: Introduction and Objective: Severe hypoglycemia can cause fatal arrhythmias, yet RH preconditioning reduces this risk (Reno et al. Diabetes 2017). We hypothesized that this protective effect in reducing arrhythmias is due to an RH preconditioning effect in improving cardiac mitochondrial function.Methods: Protocol 1: Adult male STZ-induced diabetic (D) rats were assigned to 3 days of recurrent insulin-induced hypoglycemia (DRH; 40-60 mg/dl for 60-90 min) or recurrent saline (DRS). Protocol 2: To distinguish 1) between hypoglycemia vs. insulin preconditioning per se, and 2) whether formoterol (β2-agonist that promotes mitochondrial biogenesis) could also improve respiration, diabetic rats were assigned to DRS, DRH, recurrent insulin plus glucose (DRI+G; glucose maintained > 100 mg/dl) or recurrent formoterol (DRF; 1 mg/kg/d). Seahorse respirometry analysis of isolated cardiac mitochondria was assessed on day 4.Results: In Protocol 1, DRH group had higher state 3 oxygen consumption rate (OCR) (DRS 191.2±4, DRH 228.6±14.2 pmol/min, P<0.05, t-test). In Protocol 2, DRH again demonstrated the greatest state 3 OCR (DRS 105.5±18.7, DRH 168.7±20.2, DRI+G 135.5±21.2; DRF 130.8±21.8 pmol/min; DRH vs. DRS, P=0.05, ANOVA).Conclusion: RH preconditioning enhanced cardiac mitochondrial function possibly explaining protective effects of RH against severe hypoglycemia-induced cardiac arrhythmias.DisclosureS. Velmurugan: None. H.J. Vekaria: None. L.A. Schoeder: None. A.M. Johnson: None. N.N. Nathoo: None. V. Gopal Viswanathan: None. P.G. Sullivan: None. S.J. Fisher: None.FundingAdvancing Research Collaborations Award 2024 from Barnstable Brown Diabetes Center and Diabetes and Obesity Research Priority Area, University of Kentucky
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-50-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 50-PUB: Fibroscan-Mediated Study on the Effectiveness of SGLT2i and
Pioglitazone in Preventing the Disease Progression of MASLD in T2DM in
Suburban Population in India-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 50-PUB
Abstract: Introduction and Objective: Limited evidence exists for hepatic fibrosis in type 2 diabetes mellitus (T2DM). Noninvasive techniques such as FibroScan, an alternative to liver biopsy, have facilitated early diagnosis. This study evaluates the efficacy of a combination of SGLT2i and Pioglitazone in halting the disease progression of Metabolically associated steatotic liver disease of (MASLD) in individuals with T2DM.Methods: We assessed 1004 individuals with T2DM for liver fibrosis using FIB-4 score. Transient elastography FibroScan (n=236) data of individuals with FIB-4 scores between 1.3 and above was analysed. Individuals (n=44) with LSM F1 and above were started on SGLT2i and pioglitazone along with digital health education. Follow-up fibroScan were done after 3months.Results: A significant proportion of them had a shift in their LSM staging. Individuals’ pattern of MASLD progression (Figure 1) showed that 18 individuals improved and 20 remained in the same stage. Of the remaining 6, one worsened from F2 to F4 and one from F0 to F2. The remaining four shall be considered neutralConclusion: FibroScan is a valuable non-invasive tool for screening and diagnosis of MASLD. The combination of SGLT2i class of drugs and pioglitazone, along with digital health education is useful for preventing the progression of MASLD in T2DM.DisclosureD. Padhye: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-50-PUB
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 51-OR: Prognostic Proteomics Modeling in Type 2 Diabetes Reveals Shared
and Distinct Mechanisms of Macro- and Microvascular Complications-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 51-OR
Abstract: Introduction and Objective: T2D complications manifest across various organs, but are fundamentally rooted in vascular dysfunction, including fibrosis, inflammation, calcification and endothelial damage. Much of complication heterogeneity arises from variation in angiostructures (e.g., larger vessels vs. smaller capillaries) and how they are impacted by elevated glucose levels. This study aims to identify mechanisms underlying macro- and microvascular complications in T2D using a proteomics approach, and to build models that predict future vascular complications.Methods: We analysed 2,923 plasma proteins in UK Biobank European-ancestry participants with prevalent T2D but no prior vascular diseases at baseline measurement. The primary outcomes were time to first macro- or microvascular complications, identified by ICD-10 codes. We used adaptive LASSO to select proteins in the prediction model, which included key clinical variables. Robustness and internal validation were ensured via stratified bootstrapping.Results: Among 917 T2D patients, 243 developed macrovascular, 297 microvascular, and 157 both complications over a mean follow-up of 10.69 years. Shared clinical variable predictors included waist-to-hip ratio, glucose, eGFR, and phosphate-calcium homeostasis. Incorporating proteomics significantly improved predictive accuracy compared to only using clinical variables (Harrell’s C: macrovascular 0.747 vs. 0.612; microvascular 0.710 vs. 0.642) by adding 62 proteins for macrovascular (42 in the extracellular region) and 30 for microvascular (11 in the secretory granule lumen). Six proteins (SEPTIN8, IL15, CLEC3B, IDS, FN1, ROBO4) were shared across the micro- and macrovascular prediction models.Conclusion: Proteomics significantly enhances prediction precision for T2D vascular complications and reveals distinct subcellular compartment localisation for macro- and microvascular prognostic proteins.DisclosureY. Huang: None. A. Singh: None. A. Barysenka: None. N.W. Rayner: None. O. Bocher: None. E. Zeggini: None.FundingEuropean Union’s Horizon 2020 (101017802 OPTOMICS)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-51-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 51-PUB: Prescription of Thyroid Hormone Replacement Therapy in Individuals
with Diabetes in Spain—Differences by Sex, Age, and Temporal Trends
(2018–2023)-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 51-PUB
Abstract: Introduction and Objective: Diabetes mellitus (DM) is a chronic condition characterized by elevated blood glucose levels due to insufficient insulin production or ineffective utilization. DM often coexists with thyroid diseases, particularly hypothyroidism, which can impact glycemic control and increase the risk of complications. Thyroid replacement therapy, typically with levothyroxine, is crucial for managing hypothyroidism in diabetic patients. This study analyzes the prescription trends of thyroid replacement therapy in the diabetic population in Spain from 2018 to 2023Methods: A retrospective analysis of thyroid replacement therapy prescriptions in diabetic individuals was conducted using data from BDCAP (Primary Care Clinical DataBase), categorized by gender and age groups (00-14, 15-34, 35-54, 65 and above). The total number of cases and the rate per thousand individuals treated were calculatedResults: Data reveals a steady increase in thyroid replacement therapy prescriptions over the five-year period. In 2018, the prescription rates were notably higher in females compared to males, a trend that continued through 2023. Women, particularly those aged 65 and above, consistently showed the highest prescription rates throughout the study period. This trend highlights a significant gender and age disparity in the prescription of thyroid replacement therapy among diabetic patientsConclusion: The prescription of thyroid replacement therapy in the diabetic population has significantly increased over the last 5 years, with a higher prevalence in women aged 65 and above. These findings suggest a growing trend towards thyroid treatment in diabetes management. Further prospective studies are recommended to evaluate the efficacy and safety of this practice.DisclosureJ. Ares: None. E. Menéndez-Torre: Speaker's Bureau; Abbott Diagnostics, Sanofi. Advisory Panel; Insulocloud.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-51-PUB
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 52-OR: Nogo-B Regulates Endothelial Metabolism and Angiogenesis via
Mitochondria-Associated ER Membrane Remodeling in Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 52-OR
Abstract: Introduction and Objective: Diabetes mellitus leads to endothelial cell (EC) dysfunction, impaired angiogenesis, and complications like peripheral ischemia and non-healing wounds. The molecular mechanisms driving EC metabolic dysregulation in diabetes remain unclear. Nogo-B, a reticulon family protein localized to the endoplasmic reticulum (ER), is a key regulator of vascular remodeling and angiogenesis. Previous studies have shown that Nogo-B deficiency causes aberrant vascular remodeling and endothelial barrier dysfunction. This study explores endothelial Nogo-B's role in stabilizing mitochondria-associated ER membrane (MAM) integrity through MFN2 stabilization, regulating mitochondrial dynamics, and maintaining EC metabolism under hyperglycemia.Methods: In Vivo Model: EC-specific Nogo-B knockout (NogoECKO) mice were used to assess VEGF-induced angiogenesis and blood flow recovery following critical limb ischemia in diabetic mice. In Vitro Model: Nogo-B knockdown in HUVECs was achieved via siRNA under high-glucose conditions. Mitochondrial and MAM Analysis: Mitochondrial morphology, ER-mitochondria contact, and MFN2 stability were evaluated. Angiogenesis Assays: VEGF-induced sprouting and blood flow recovery were analyzed.Results: EC-specific Nogo-B deficiency impaired VEGF-induced angiogenesis and blood flow recovery in diabetic NogoECKO mice. Nogo-B knockdown worsened mitochondrial fragmentation and dysfunction under hyperglycemia, impairing angiogenesis. Nogo-B localized to MAM, regulating ER-mitochondria contact and stabilizing MFN2, critical for mitochondrial dynamics and metabolic homeostasis.Conclusion: The Nogo-B-MFN2 axis is vital for preserving EC metabolism, MAM integrity, and angiogenesis under hyperglycemia. These findings offer a foundation for therapeutic strategies to improve dysregulated angiogenesis and wound healing in diabetic patients.DisclosureD. Shan: None. C. Zhang: None. M. Baldini: None. R. Feng: None. L. Tang: None. V.M. Gillespie: None. Y. Zhang: None. J. Yu: None.FundingAmerican Diabetes Association (11-23-PDF-47)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-52-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 52-PUB: The Medical Status of Patients with Diabetes in Guangdong Province
-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 52-PUB
Abstract: Introduction and Objective: To assess metabolic profiles and medication prescription patterns in patients with diabetes in Guangdong province.Methods: Data of 1621 patients with diabetes in Guangdong province were collected from the China National Diabetic Chronic Complications Survey conducted between March 2018 and January 2020. Questionnaires for medical history and blood tests for metabolic indices were collected.Results: The patients characteristics included: males 47.6%, urban residents 51.1%, medium diabetes duration 6.5 years, average BMI 24.8 kg/m², and average HbA1c 7.1%. The prevalences of hypertension and dyslipidemia were 55.5% and 92.7%, respectively, with the corresponding awarenesses of 37.9% and 23.3%. 79.6% of the patients received diabetes medications, with 48.2% on monotherapy. Only 42.6% of the patients met the glycemic target. The status of the prescriptions of hypoglycemic agents were shown in Figure 1. 59.1% of the patients with hypertension and 8.7% of the patients with dyslipidemia were on medical treatments, with 16.7% and 7.1% of the patients met the targets of blood pressure and lipid profiles. Among all the patients, only 1.7% of the patients achieved all the targets of blood glucose, blood pressure and lipid profiles.Conclusion: The control rates of medical disorders in patients with diabetes in Guangdong were still very low. Promising strategies to improve this status should be implemented.DisclosureX. Chen: None. Y. Yang: None. W. Jiang: None. W. Xu: None. L. Zeng: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-52-PUB
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 53-OR: Loss of HDAC11 Drives Aortic Endothelial-to-Mesenchymal
Transitioning-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 53-OR
Abstract: Introduction and Objective: Endothelial-to-mesenchymal transition (EndMT) is a complex, yet integral biological process where endothelial cells (ECs) adopt a mesenchymal-like phenotype and thereby gain inflammatory and fibrotic properties. This process occurs under physiological or pathological stress and can result in vascular dysfunction (i.e., fibrosis and/or atherosclerosis). EndMT has recently been found to play a role in secondary complications of diabetes; however, its’ role in diabetic vascular disease has not been explored.Methods: Here, using a combination of an EndMT in vitro culture system, loss of function approaches which include pharmacologic inhibition and small interfering (siRNA), and primary AECs from a murine model of diabetes, we identified that a histone deacetylase, HDAC11, regulates the endothelial-to-mesenchymal transition in murine aortic ECs (AECs).Results: Here, we identified that a histone deacetylase, HDAC11, regulates the endothelial-to-mesenchymal transition in murine aortic ECs (AECs). Specifically, we determined that TGF-β1 stimulation resulted in increased EndMT genes, Col1a1 and Fn1. Further, TGF-β1 stimulation significantly decreased HDAC11 expression at the promoters of Col1a1 and Fn1 by ChIP analysis. Pharmacological inhibition via a small molecule inhibitor, SIS17, or treatment with siRNA specific to HDAC11 in AECs resulted in increased expression of Col1a1 and Fn1 in both conditions. Importantly, ex vivo TGF-β1 stimulated AECs isolated from diet induced obese (DIO) mice had increased in Col1a1 and Fn1 compared to control mice, and this was associated with decreased Hdac11.Conclusion: Identifying TGFβ1-HDAC11 as a driver of EndMT in diabetic vasculature requires further exploration and may allow for development of targeted therapy for diabetic vascular pathology.DisclosureJ. Shadiow: None. T.M. Bauer: None. K.D. Mangum: None. A. Joshi: None. J. Moon: None. G. Saldana de Jimenez: None. S.A. Rocco: None. L. Hughes: None. S. Buckley: None. M.J. White Jr: None. A.M. Ovalle: None. J.J. Reyes-Arbujas: None. S. Wolf-Fortune: None. K. Gallagher: None.FundingNIH (HL167143)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-53-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 53-PUB: Prevalence and Characterization of Overbasalization in a Chilean
Cohort of Hospitalized Adults with Type 2 Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 53-PUB
Abstract: Introduction and Objective: The worldwide prevalence of overbasalization (OB) is not well defined, but remains a common issue in clinical practice. In Chile, most patients are treated in the public primary healthcare system (PPHS) and use NPH insulin. Data on OB prevalence in Chile are limited.Objective: To determine the prevalence of OB and describe insulin therapy characteristics in a cohort of Chilean adults with T2D at hospital admission and discharge.Methods: Descriptive observational study using electronic health records from a tertiary hospital in Chile. Adults aged ≥18 with T2D, using basal insulin in outpatient settings and admitted to non-ICU between June 2019 and March 2023 were included. OB was defined as basal insulin dose >0.5 IU/kg/day. Statistical analyses were performed using T-test and chi-squared (X²).Results: 316 patients were included. The mean age was 65 years (±11.8), 61.8% were male (n=196), and mean BMI was 29.36 kg/m² (±6). The average T2D duration was 18 years (±10.6) with a mean A1C of 9.3% (±2.2). 82% were treated in primary care and 63% within PPHS. Basal insulin was NPH in 60% and analogs in 40%. The mean basal insulin dose was 0.45 IU/kg/day (±0.27). OB was observed in 36.7% (n=116). Among those, 59.5% (n=69) were treated in PPHS, a significantly higher proportion compared to other groups (P=0.036). Of OB patients, 75.9% were using NPH, while 24.1% were treated with basal analogs (P<0.001). Additionally, their mean A1C was 9.47% (±1.99) and 77.6% did not use prandial insulin. At discharge, mean basal insulin dose was 0.27 IU/kg/day (±0.24), with only 8.63% (n=27) remaining in the OB range (P<0.001). Among patients discharged on NPH (n=104), only 20.19% remained in the OB range (P<0.001).Conclusion: OB was more frequent among NPH insulin users and patients treated in PPHS. Additionally, these patients had low use of prandial insulin. A reduction in basal insulin dose, particularly NPH, is feasible at hospital discharge and may help reduce the OB risk.DisclosureA.M. Meza: None. E. Vega: None. L. Toro: None. O. Vargas: None. K.A. Contreras: Other Relationship; Novo Nordisk. P.C. Gomez: None. A. Villarroel: None. M.G. Sanzana: None. K. Loo: None. J.P. Puebla: None. A. Molina: None. C.A. Henríquez: None. E. Santana: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-53-PUB
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 54-OR: Insulin Stabilized Arterial Plaques by Regulating Vascular Smooth
Muscle Differentiation-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 54-OR
Abstract: Introduction and Objective: Risk of unstable plaques, noted by reduced content of vascular smooth muscle cells (VSMC) and extracellular matrix (ECM), with elevated inflammatory cells and necrosis, are increased in diabetes for unknown reasons. This study investigated the role of insulin in VSMC and the formation of unstable plaques.Methods: Insulin receptor (IR) knockout and VSMC lineage tracing mice (MyH11IRKO/ApoE-/-) were generated. Single cell RNA sequencing (scRNA Seq) was performed with isolated VSMC from control and MyH11IRKO/ApoE-/- mice on normal (ND) or high fat diet (HFD). Changes observed in mice were validated in arteries from subjects with and without Type 2 diabetes (T2D) by immunostaining.Results: Atherosclerotic plaques in MyH11IRKO/ApoE-/- mice were increased and exhibited unstable traits with reductions of VSMC and ECM, but greater numbers of macrophages and necrosis than ApoE-/- mice. ScRNA Seq analysis of aortae identified 21 distinctive clusters of VSMC, which are separated into clusters with enriched expressions of contractile, ribosome and mitochondrial genes to those expressing inflammatory genes. Both inflammatory VSMCs clusters and those enriched for ribosomal and mitochondrial genes were increased in HFD fed ApoE-/- mice vs. those on ND. However, in Myh11IRKO/ApoE-/- mice on HFD, VSMC enriched for ribosomal and mitochondrial genes were significantly reduced, but VSMC expressing elevated inflammatory cytokines and matrix metalloproteinases (MMP’s) were increased vs.HFD fed ApoE-/- mice. These changes of reductions of VSMC with ribosomal proteins and elevations of VSMC with inflammatory cytokines and MMPs were validated in arteries from people with diabetes.Conclusion: scRNA seq analysis showed that insulin actions are critical to prevent the differentiation of VSMC into clusters expressing inflammatory cytokines and MMPs, which are critical for the pathogenesis of unstable arterial plaques associated with insulin resistance and T2D.DisclosureQ. Li: None. J. Fu: None. K. Park: None. M. Yu: None. G.L. King: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-54-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 54-PUB: Assessment of Undiagnosed Subclinical Hypothyroidism in People
with Type 2 Diabetes Mellitus—A Clinic-Based Prospective Real-World
Study in India-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 54-PUB
Abstract: Introduction and Objective: Individuals with Type 2 Diabetes Mellitus (T2D) are associated with 1.93-fold increase in risk of developing subclinical hypothyroidism (SCHT). Studies suggest that a significant portion of individuals with T2D may have undiagnosed SCHT, emphasizing the need for routine thyroid function tests. In India we do not have any studies that estimate undiagnosed SCHT. This study is focused on the estimation of the prevalence of undiagnosed SCHT in Indians with T2D; also comparing the SCHT group with the euthyroid group.Methods: The present study is a real-world study involving the data of 1808 individuals with T2D from multiple health centers across India from 3rd March to 31st August 2023. Data was collected on the MEDEVA; Electronic Health Record (EHR) that was customised for the requirements of the study.Results: The mean age of the study sample is 54.6 ± 11.6 years, with 53.4% males and 46.6% females. The average BMI is 27.7 ± 5.2 kg/m². The average duration of the presence of diabetes is 6.9 ± 6.4 years. The prevalence of undiagnosed SCHT is 18.8% and undiagnosed overt hypothyroidism is 1.6%. Prevalence of SCHT did not vary across different age groups, gender groups, BMI groups or HbA1c groups. Compared to euthyroid individuals, the undiagnosed SCHT group exhibited a greater occurrence of several symptoms. 47% of the undiagnosed SCHT individuals reported symptoms versus 32% in case of Euthyroid individuals.Conclusion: Understanding the prevalence of SCHT in individuals with T2D highlights the magnitude of this often-overlooked comorbidity. The findings emphasize the importance of routine screening for SCHT, which is often undetected due to its exclusion as a mandatory test for individuals with T2D in the current guidelines. Diagnosing SCHT is crucial, as its symptoms can overlap with those of T2D, potentially leading to suboptimal management if left untreated.DisclosureA. Maheshwari: None. N. Verma: None. S.S. Gupta: None. A. Tewari: None.FundingACP INDIA CHAPTER
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-54-PUB
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 55-OR: Understanding the Unseen—Caregiver Adverse Childhood Experiences
and the Health of Youth with Type 1 Diabetes (T1D)-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 55-OR
Abstract: Introduction and Objective: Adverse childhood experiences (ACEs) are known to impact the health and well-being of those living with T1D. Less is known regarding how ACEs of a primary caregiver (parent, grandparent, etc.) may indirectly impact youth with chronic health conditions - potentially via influence on parenting practices. The current study investigates the relationship between caregiver ACEs, parenting practices, and health of youth with T1D.Methods: Youth (N=158) ages 12-17 years, with T1D for ≥1 year, and an HbA1c ≥ 10% in the past year were enrolled from 5 academic medical centers. Youth caregivers reported on parenting practices (Alabama Parenting Questionnaire) and their own ACEs (ex: experience of racial discrimination, parental death). Chart review collected HbA1c and ED visits 12 months prior to enrollment and ED visits 6 months following study enrollment. Chi square tests, bivariate correlations, and independent t-tests were conducted.Results: Youth mean age was 14.5+2 years with mean HbA1c of 11.1+2%. Less than 50% of youth were Non-Latinx white; 15.2% Latinx; 14.1% Black. Youth whose caregivers experienced specific ACEs were more likely to experience an ED visit than youth whose caregivers did not (parental divorce: 51.4% vs. 28.9%, p<.01; parental incarceration: 61.1% vs. 36.5%; p<.05; racial discrimination: 60.9% vs. 35.6%; p<.05). Youth of caregivers who experienced racial discrimination had more ED visits (M=1.4+1.4) than youth of caregivers who did not (M=0.7+1.6; p<.05). Caregiver experience of racial discrimination correlated with lower positive parenting (r=-.18) and poorer supervision (r=.17; p<.05).Conclusion: Findings demonstrate that ACEs in caregivers raising youth with T1D are associated with parenting practices and youth health. Given prior associations between parenting practices and T1D outcomes, and these findings regarding caregiver ACEs, healthcare systems should consider caregiver experiences and functioning as prime areas for potential screening and intervention.DisclosureK.A. McMullen: None. K.A. Torres: None. J. Raymond: None. M.A. Clements: Consultant; Glooko, Inc. Research Support; Dexcom, Inc., Abbott. D. Naranjo: Consultant; Sanofi. J.C. Wong: Research Support; Abbott, Dexcom, Inc., Tandem Diabetes Care, Inc. A. Reed: None. S.R. Melnick: None. M.A. Harris: None. D.V. Wagner: None.FundingJDRF
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-55-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 56-OR: Behavioral Family Systems Therapy (BFST) Skills Inventory for Youth
with Type 1 Diabetes—Psychometric Analyses-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 56-OR
Abstract: Introduction and Objective: Youth receiving BFST for diabetes experienced improved diabetes self-management, parent-adolescent communication, and HbA1c. The BFST Skills Inventory (BFST-SI) was developed to assess intervention fidelity and family skills. While this measure has been used in numerous intervention studies for youth with diabetes, it has yet to be validated. This study aimed to examine the psychometric properties of the BFST-SI in youth participating in Novel Interventions in Children’s Health Care (NICH), a health equity intervention for youth with diabetes experiencing high social needs, medical risks, and healthcare costs.Methods: Youth participating in NICH at 3 academic medical centers completed the BFST-SI (N=127) and the Diabetes Strengths and Resilience Measure (DSTAR; N=48). The 20 BFST-SI items were examined using exploratory factor analysis with maximum likelihood extraction and direct oblimin rotation. Items with low item-to-total correlations and factor loadings (<0.3) were removed.Results: Youth with complete demographic data had a mean age of 15.4+1.9 years and mean HbA1c of 11.9+2.1%, with 96% on Medicaid. Fifteen items were retained and loaded onto 3 factors. Cronbach’s α was reliable for the total scale (α=.90) and each factor (α=.82-.89), which we labeled Family Problem Solving (6 items), Challenging Family Patterns (4 items), and Family Respect and Collaboration (5 items). BFST-SI total scores were correlated with DSTAR scores (r=.47, p<.01).Conclusion: The BFST-SI is a psychometrically sound measure used to assess BFST-D fidelity and family skill outcomes. This study adds to the extant literature demonstrating that family communication and problem-solving are critical skills for families of youth with diabetes. Screening for BFST skills will help identify families needing additional communication intervention and aid in treatment development and evaluation for youth with diabetes and their families.DisclosureK.A. Torres: None. J. Shapiro: None. F.S. Richey: None. D. Naranjo: Consultant; Sanofi. A. Reed: None. J.C. Wong: Research Support; Abbott, Dexcom, Inc., Tandem Diabetes Care, Inc. M. Gonzales Granados: None. M.E. Hilliard: None. M.A. Harris: None. D.V. Wagner: None.FundingThe Leona M. and Harry B. Helmsley Charitable Trust
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-56-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 56-PUB: Phenotypic Variability in a Brazilian Family with MODY Diabetes
Due to ABCC8 Gene Mutation-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 56-PUB
Abstract: Introduction and Objective: Mutations in the ABCC8 gene, encoding the SUR1 subunit of the ATP-sensitive potassium channel, are classically associated with neonatal diabetes (NDM). However, some variants in this gene can result in MODY (Maturity-Onset Diabetes of the Young), with milder phenotypes and variable age of onset. This study aims to describe the phenotypic variability in a Brazilian family with MODY diabetes due to an ABCC8 gene mutation.Methods: This is a descriptive study of a Brazilian family with multiple members affected by diabetes. Next-generation sequencing was used to perform genetic sequencing and the identified pathogenic variant was confirmed through Sanger sequencing and classified according to ACMG criteria. Clinical data, including age at diagnosis, HbA1c, presence of diabetes complications, and sulfonylurea treatment, were analyzed.Results: Genetic sequencing of the proband identified the pathogenic variant c.2473C>T/p.R825W in ABCC8. This variant was also identified in four other family members (two offspring and two sisters). Despite the shared genetic etiology, significant phenotypic variability was observed. Age at diagnosis ranged from 16-51y. HbA1c levels at initial evaluation varied from 5.8 to 9.2%. Two offspring and one sister were asymptomatic at diagnosis, while the other sister had pre-diabetes. Only the proband exhibited diabetes-related complications (diabetic retinopathy, myocardial dysfunction). The sulfonylurea treatment response was heterogeneous, with variable doses required for glycemic control. The proband used glibenclamide 1.25 mg, while the sisters used gliclazide 30 mg and glibenclamide 5 mg. The two offspring did not require antidiabetic medication.Conclusion: The location of the pathogenic variant within the ABCC8 gene influences the disease phenotype, resulting in either MODY or NDM. Our study highlights the phenotypic variability associated with ABCC8 mutations and underscores precise molecular diagnosis's importance in guiding appropriate treatment strategies.DisclosureA.C. Santomauro Junior: None. A.D. Costa-Riquetto: None. T.G. Amorim: None. F.R. Barros: None. E.B. Val: None. A. Jorge: None. M.G. Teles: None.FundingFAPESP (#2013/19920-2)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-56-PUB
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 57-OR: Family Intervention Effects on Parenting and Adolescent Glycemic
and Psychosocial Outcomes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 57-OR
Abstract: Introduction and Objective: To evaluate effects of a family program on adolescents with type 1 diabetes and their parents.Methods: Parent-adolescent dyads (n=157) were randomly assigned to the intervention condition or a waitlisted control. The intervention included 6 weekly 30-minute sessions for dyads to meet with an interventionist to learn communication and problem-solving skills related to diabetes. Patient-reported outcomes and glycemic data were collected at baseline, immediate post-intervention (7 weeks post-baseline), and 3 and 6 months post-baseline. Regression models tested main and moderated effects on percent time-in-range (% TIR), diabetes-related quality of life (QOL), and diabetes distress as well as supportive and nonsupportive parent diabetes involvement.Results: Immediately after the intervention, the intervention group had significantly less nonsupportive involvement than the control group based on both parent (ß=-0.177, p=.002) and youth (ß=-0.150, p=.024) report as well as more supportive involvement based on parent report (ß=0.151, p=.007). At 3 months post-baseline, the intervention group had higher % TIR (ß=0.267, p=.024, d=0.37) and QOL (ß=0.308, p=.002, d=0.81) than the control group among non-white adolescents and improved QOL (ß=0.261, p=.003, d=0.94) among adolescents not using automated insulin delivery. At 6 months post-baseline, the intervention improved QOL (ß=0.220, p=.005, d=0.58) among adolescents not using automated insulin delivery, lowered adolescent diabetes distress (ß=-0.286, p=.016, d=-0.79) among youth with public insurance, and reduced parent diabetes distress (ß=-0.200, p=.006, d=-0.54) among parents with high baseline distress.Conclusion: Family-based interventions are effective in improving diabetes-related parenting practices as well as glycemic health and psychosocial well-being, especially for youth from underrepresented backgrounds and with fewer resources.DisclosureJ.J. Wong: None. S.A. Alamarie: None. H. Flores: None. S. Hanes: None. J. Ngo: None. A.K. Schneider-Utaka: None. K.K. Hood: Consultant; Sanofi. Advisory Panel; MannKind Corporation. Consultant; Havas Health. Research Support; embecta.FundingNational Institutes of Health (K23-DK121771)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-57-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 57-PUB: CytoProfile—Advancing Cytokine Profiling Analysis with R
-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 57-PUB
Abstract: Introduction and Objective: Cytokine profiling is crucial in understanding immune responses and disease mechanisms, yet existing analytical tools often fall short in addressing the unique complexities of cytokine data. This study introduces CytoProfile, an R-based software tailored for comprehensive cytokine analysis. The objective was to evaluate its integration of advanced statistical and machine learning methods for precise classification and biomarker identification in immunological research.Methods: CytoProfile integrates data preprocessing and visualization tools, alongside advanced statistical analyses and machine learning methods. Cytokine data derived from peripheral blood mononuclear cell (PBMCs) under varied stimulations were analyzed using its comprehensive pipeline. Comparative analyses were performed against tools like CytokineExplore, MetaboAnalyst and Qlucore Omics Explorer, focusing on visualization, classification accuracy, and feature importance metrics.Results: CytoProfile demonstrated superior functionality, including dual-flashlight plots, enriched error bar visualizations, and effect-size-based assessments. Random Forest and XGBoost algorithms provided robust classification, achieving an average AUC of >0.80. Key cytokines linked to disease states were effectively identified, with CytoProfile outperforming alternatives in interpretability and analytical depth. Comparative evaluations highlighted its user-friendly interface and versatility in handling high-dimensional cytokine data.Conclusion: CytoProfile addresses critical gaps in cytokine data analysis by integrating statistical precision with machine learning and visualization techniques. It allows researchers to uncover biologically significant insights, advancing cytokine research and its diagnostic and therapeutic applications. Future updates aim to incorporate support vector machine and neural networks to further enhance analytical capabilities.DisclosureS. Saraswat: None. P.A. Kern: None. G. Kalantar: None. B. Nikolajczyk: None. X.D. Zhang: None.FundingUS National Institutes of Health (U01DK135111, R01AG084180, R01AG079525 and UL1TR001998); Diabetes Research Center, Washington University (P30DK020579)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-57-PUB
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 58-OR: Addressing the Needs of Maternal Caregivers—Interventions for
Distressed Mothers of Adolescents with Type 1 Diabetes Improve
Psychosocial Outcomes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 58-OR
Abstract: Introduction and Objective: Maternal caregivers of adolescents with type 1 diabetes (T1D) experience elevated levels of depressive symptoms and diabetes distress, which are established risk factors for poor psychosocial and glycemic outcomes in adolescents. We evaluated the effects of a cognitive behavioral intervention for distressed caregivers in a randomized controlled trial.Methods: Maternal caregivers of adolescents with T1D (n=151, mean adolescent age=14+2yrs, 56% female, 85% non-Hispanic White, mean HbA1c=9.0+2.1%), were randomized to receive a cognitive behavioral intervention (Communication & Coping) targeting coping skills and positive parenting strategies or an Enhanced Diabetes Education intervention. Participants in both groups received intervention materials and completed up to 7 phone sessions with a trained interventionist over 3 months, with concurrent daily Facebook posts designed to reinforce the concepts for each intervention. Psychosocial and glycemic data were collected over 12 months.Results: Caregivers in both groups reported significant decreases in depressive symptoms (effect size d=3.5, p<.001) and diabetes distress (d=0.6, p<.001) over 12 months, with no significant differences between groups. Adolescents experienced improvements in quality of life (d =-2.95, p<.001), with marginally higher scores in the Education group (p=.048). Adolescents maintained HbA1c (8.9% at 12 months), with no significant difference between groups.Conclusion: Interventions for caregivers are effective in treating maternal distress and improving quality of life in adolescents with T1D. Specific intervention materials may be less critical than repeated interactions with trained interventionists that address maternal caregivers' concerns about raising an adolescent child with T1D.DisclosureS.S. Jaser: None. J.H. Simmons: Consultant; Boehringer-Ingelheim. Research Support; Kyowa Kirin Co., Ltd. Consultant; Kyowa Kirin Co., Ltd. Advisory Panel; Ultragenyx. Research Support; Ultragenyx, Alexion.FundingNational Institutes of Health (R01DK115545)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-58-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 59-OR: Innovative Health Equity Intervention for Youth with Diabetes
Deemed High Risk, High Needs, and High Cost—Understanding the Role of
Co-occurring Mental Health Diagnoses-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 59-OR
Abstract: Introduction and Objective: Novel Interventions in Children’s Healthcare (NICH) has shown improved health outcomes for youth with diabetes experiencing inequity. NICH does not specifically target symptoms of mental health diagnoses (MHD)s, but never excludes youth and caregivers from enrollment and evaluation due to MHDs. Given uncertainty regarding role in NICH outcomes, this study explores prevalence of MHDs and related health outcomes for youth in NICH.Methods: Youth with diabetes (N=30; T1D=26, T2D=4) who participated in NICH at two new healthcare systems were included. Chart review collected HbA1c, emergency department visits, and days admitted one year prior to and during NICH enrollment. Provider-reported social drivers of health and MHD presence for youth and caregivers were also included. Non-parametric t-tests examined differences in health outcomes during NICH for those with and without MHDs.Results: Youth mean age was 13.2 years; 57% of youth were from historically marginalized racial and ethnic groups; 76% of youth and 53% of caregivers had a MHD. Youth with a MHD experienced higher mean A1c prior to NICH (12.8±1.4%) compared to youth without (12.1±2.2%; p<.03). Decreased mean HbA1c from baseline to post-NICH was found for all youth in NICH (12.6+1.7% to 11.2+2.3%; p<.001), youth with a MHD (12.8±1.4% to 11.8±2.3%; p<.02), youth of caregivers with a MHD (13.1±1.8% to 11.3±2.6%; p<.01), and youth of caregivers without a MHD (12.1±1.5% to 11.1±2.0%; p<.03). Youth of caregivers without a MHD also demonstrated a decrease in mean days admitted while in NICH (8.3±7.8 to 4.1±5.8; p<.01). All other baseline findings and changes over time were nonsignificant.Conclusion: NICH implementation at new sites continues to demonstrate clinically and statistically significant improvements in HbA1c. Co-occurring MHD in youth and caregivers served by NICH are common. NICH demonstrates improved HbA1c regardless of presence of MHD for youth with T1D or their caregivers.DisclosureL.D. Hicks: None. K.A. Torres: None. L.J. Levy: None. D. Naranjo: Consultant; Sanofi. A. Reed: None. J.C. Wong: Research Support; Abbott, Dexcom, Inc., Tandem Diabetes Care, Inc. K.B. Spiro: None. N.A. Cisneros: None. I.C. Gomez: None. M.A. Harris: None. D.V. Wagner: None.FundingThe Leona M. and Harry B. Helmsley Charitable Trust
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-59-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 59-PUB: Serum Vitamin D Levels Are Negatively Associated with Severe
Nonalcoholic Fatty Liver Disease in Individuals with
Overweight/Obesity—A Cross-Sectional Study-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 59-PUB
Abstract: Introduction and Objective: The role of vitamin D in the occurrence and progression of nonalcoholic fatty liver disease (NAFLD) remains contradictory. In addition, there are few studies on fat distribution in the abdomen and vitamin D. Therefore, we investigated the relationship between serum vitamin D levels and abdomen fat distribution, particularly liver fat content (LFC) in subjects with overweight/obesity.Methods: 147 subjects with overweight/obesity (body mass index ≥23 kg/m2) were enrolled. All subjects were classified by vitamin D levels as either vitamin D deficiency (<20 ng/mL) or vitamin D normal (≥20 ng/mL). Magnetic resonance imaging-proton density fat fraction (MRI-PDFF) was used to measure fat accumulation in the liver, pancreas, and abdomen subcutaneous and visceral.Results: LFC was significantly higher in the vitamin D deficient group than in the normal vitamin D group (P =0.040). Additionally, there was a significant decrease in serum vitamin D levels with increasing LFC and subcutaneous adipose tissue (P <0.05), while no difference was found in pancreatic fat content, abdominal fat, or visceral adipose tissue among the groups. Meanwhile, the prevalence of severe hepatic steatosis in the lowest vitamin D levels group was significantly higher than in the highest vitamin D quartile (50% vs. 18.9%, Q1 vs. Q4, P =0.042). Further regression analysis showed that the multivariate-adjusted OR for the prevalence of severe NAFLD in the highest quartile was 0.171 (Q4 vs. Q1, 95%CI 0.047~0.612, P =0.007).Conclusion: A significantly negative relationship between serum vitamin D and severe NAFLD was observed in patients with overweight/obesity. Serum vitamin D levels may be applied to assess the risk of severe NAFLD in patients with overweight/obesity.DisclosureJ. Ma: None. Y. Li: None. Z. Wang: None. M. Yang: None. J. Yue: None. J. Chen: None. Y. Qi: None. Q. Liu: None. Q. Lu: None.FundingChina International Medical Foundation (Z-2017-26-2202-4)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-59-PUB
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 60-OR: Youth with Type 1 Diabetes and Elevated HbA1c—Examination of
Family Functioning and Health Disparities-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 60-OR
Abstract: Introduction and Objective: Youth with T1D and elevated HbA1c experience higher rates of short- and long-term complications. While individuals from some racial and ethnic groups are at greater risk of disparities in HbA1c due to systemic barriers and discrimination, less is known about the impact on family functioning amongst youth already experiencing elevated HbA1c. This study examines disparities in racially and ethnically diverse youth with elevated HbA1c.Methods: Youth (N=217) from 5 academic medical centers were enrolled if they were 1) 12-17 years old, 2) diagnosed with T1D for ≥ 1 year, and 3) had an HbA1c ≥ 10%. Chart review collected HbA1c values. Youth and their caregivers completed measures of family functioning (Diabetes Family Conflict Scale-R, Diabetes Family Responsibility Questionnaire). Bivariate correlations and non-parametric t-tests were conducted.Results: Youth had a mean age of 14.6±1.6 years and mean HbA1c of 11.0±1.9%. 45.9% were non-Latinx White; 13.8% were Black; 21.6% were Latinx. Black youth experienced higher HbA1c and reported higher conflict regarding direct management of T1D levels compared to non-Black youth (p<.05). Latinx youth had higher indirect T1D responsibility (M=10.3 vs 8.7) and conflict regarding indirect management (M=13.4 vs. 11.8) compared to non-Latinx youth (p<.05). Higher youth-reported family conflict was associated with higher HbA1c (r=.29, p<.01).Conclusion: Youth with T1D from racial and ethnic groups who have been historically marginalized experience significant disparities in health and life outcomes, and this is even more evident in youth with elevated HbA1c. These findings suggest that disparities have an exponentially negative impact on Black and Latinx youth living with T1D. Interventions that are specifically designed for and implemented with minoritized youth with T1D need to be a priority in providing equitable access to specialty care, diabetes technology, and other health-promoting services and resources.DisclosureE. Washington: None. K.A. Torres: None. J. Flores Garcia: None. C. Jenisch: None. J. Raymond: None. M.A. Clements: Consultant; Glooko, Inc. Research Support; Dexcom, Inc., Abbott. D. Naranjo: Consultant; Sanofi. J.C. Wong: Research Support; Abbott, Dexcom, Inc., Tandem Diabetes Care, Inc. A. Reed: None. M.A. Harris: None. D.V. Wagner: None.FundingJDRF
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-60-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 60-PUB: Autosomal Dominant Hypocalcemia with a Novel CaSR Mutation—A
Case Study and Literature Review-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 60-PUB
Abstract: Introduction and Objective: Autosomal dominant hypocalcemia type 1 (ADH1) is a hereditary disease caused by activating mutation of calcium - sensing receptor (CASR) gene, manifested as low parathyroid hormone (PTH) levels, hypocalcemia and hypercalciuria. Its clinical manifestations range from mild asymptomatic to severe hypocalcemia, which may be accompanied by epileptic seizures in severe cases. To better understand the relationship between neurological phenotypes and genotypes in ADH1,we comprehensively analyzed the clinical features related to epilepsy and reviewed the current literature.Methods: We reported a new heterozygous mutation in exon 7 of CASR in ADH1 in two generations: c.2452T>C (p.Trp818Arg), who showed symptoms of recurrent epileptic seizures caused by hypocalcemia. In addition, we summarized the cases with the same phenotype.Results: We summarized 43 patients with recurrent epilepsy, among whom 23 had intracranial calcification. Among these epilepsy patients, there were 37 different CASR mutation sites in total, mainly affecting the Venus flytrap domain (VFT, 44.4%) and transmembrane domains (TMD, 48.1%), with the mutations mainly concentrated in lobe 1 (LB1, 33.3%), TM5 and TM6 domains (18.5%).Conclusion: Mutations in specific domains of the CaSR protein may be associated with a higher rate of neurological manifestations.DisclosureY. Luo: None. Q. Pan: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-60-PUB
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 61-OR: Acarbose vs. Fast-Acting Insulin for the Treatment Postprandial
Hyperglycemia in Gestational Diabetes Mellitus—The ACARB-GDM Study-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 61-OR
Abstract: Introduction and Objective: Acarbose, an α1-glucosidase inhibitor, is used to decrease postprandial glucose values in patients with type 2 diabetes. Thanks to a very low intestinal absorption, it might be used during gestational diabetes mellitus (GDM) but randomized trials to assess its efficacy and safety are lacking.Methods: The ACARB-GDM study is a prospective, non-inferiority, multicenter, open-label randomized prospective study. We randomly assigned 341 women with GDM at 12 to 34 weeks of gestation, with uncontrolled postprandial glucose values despite diet, to open treatment with acarbose (replaced by fast-acting insulin if not tolerated or ineffective during follow-up) or fast-acting insulin. The primary outcome was a composite of large-for-gestational-age infant, neonatal hypoglycemia, shoulder dystocia and birth trauma. Secondary outcomes included other neonatal and maternal outcomes, and tolerance.Results: Out of the 174 women assigned to acarbose first, 29.7% finally needed fast-acting insulin during pregnancy. The rate of the primary composite outcome was 18.8% in the group assigned to acarbose and 18.5% in the insulin group (after multiple imputation and adjustment for long-acting insulin and centers, risk difference +0.3% [95% confidence interval -6.7 to 7.3]; p=0.095 for non-inferiority). The rate of maternal hospital admission during pregnancy increased (acarbose vs. insulin group 12.3 vs 8.0%: +4.3% [1.0 to 7.6]), those of neonatal respiratory distress syndrome (5.8 vs. 12.3%: -6.4% [-12.2 to -0.7]) and admission in neonatal intensive care unit (2.6 vs. 8.6%, risk difference -6.2% [-10.4 to -1.9]) decreased.Conclusion: Although statistical power was insufficient to formally demonstrate the non-inferiority, the study shows for the first time that the rate of GDM-related adverse outcomes is arithmetically very close when acarbose instead of fast-acting insulin is used without tolerance / security issues.Disclosure E. Cosson: Board Member; Abbott Diagnostics, Amgen Inc, Bayer Pharmaceuticals, Inc, Boehringer-Ingelheim, Dexcom, Inc., Lilly Diabetes, Medtronic, Novartis AG, Novo Nordisk, Roche Diagnostics, Sanofi. S. Pinto: None. A. Mankai: None. H. Affres: None. A. Diallo: None. M. Jannot-Lamotte: None. L. Mandelbrot: None. N. Bourcigaux: None. D. Dubois-Laforgue: None. A. Penfornis: Speaker's Bureau; Abbott, AstraZeneca. Board Member; Abbott. Speaker's Bureau; Boehringer-Ingelheim, Dexcom, Inc., Eli Lilly and Company. Board Member; Insulet Corporation. Speaker's Bureau; Insulet Corporation. Board Member; Medtronic. Speaker's Bureau; Menarini. S. Favre: Board Member; Sanofi. Consultant; Abbott, Lilly Diabetes, Novo Nordisk. S. Jacqueminet: Other Relationship; Lilly Diabetes. M. Laloi-Michelin: None. S. Fendri: None. H. Hanaire: Consultant; Abbott, Dexcom, Inc. Advisory Panel; Medtronic, Insulet Corporation. Consultant; Tandem Diabetes Care, Inc, Novo Nordisk, Sanofi. E. Vicaut: Consultant; Abbott, NEURAXPHARM, ALCEDIAG.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-61-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 62-OR: How Does Progression to Pharmacologic Treatment of GDM Vary by
Race/Ethnicity'-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 62-OR
Abstract: Introduction and Objective: Medical nutrition therapy (MNT) is the first line of treatment for gestational diabetes mellitus (GDM); failing this, pharmacologic treatment is recommended. Racial/ethnic disparities in diagnosis of GDM and progression to T2D exist, but little is known about disparities in progression to medication. We conducted a time-to-event analysis of progression to any GDM medication by race/ethnicity.Methods: We identified GDM singleton pregnancies (2008-2023) among patients ≥18 years, with no prior diabetes and medical coverage from 1 year before pregnancy in an integrated health care delivery system. We assessed self-reported race/ethnicity, and the outcome was progression to medication (insulin, glyburide, metformin) after GDM diagnosis using medication fills as a proxy. We ran Cox proportional hazard regressions, adjusted for maternal characteristics and highest quartile of screening glucose (binary proxy for GDM severity; fasting glucose used if screening was missing), with White individuals (as historically advantaged) as the reference group.Results: Among 27,310 patients with GDM, 41% were Asian, 4% were Black, 28% were Hispanic, 1% were Pacific Islander (PI) and 23% were White. The mean age was 32.7 (SD: 4.8) and mean pre-pregnancy BMI was 29.5 (SD: 7.0). Asian (41%) and PI (40%) individuals had lower proportions of medication use compared to Black (48%) and White (45%) individuals. Median time to progression was lowest among White (27 days) and highest among Asian (32 days) individuals. Relative to White individuals, PI (0.80, 95% CI 0.68-0.95) and Hispanic (0.94, 95% CI 0.89-0.99) individuals had lower adjusted hazards; all other groups had non-significant hazard ratios.Conclusion: The proportion who progresses, time to progression, and hazard of progression to medication after GDM diagnosis vary by racial/ethnic groups. Medication fills are an imperfect proxy for prescribing information; however these data suggest that the efficacy of MNT may vary by racial/ethnic subgroups.Disclosure S.S. Bane: Employee; Malama Health. E.F. Liu: None. M. Greenberg: None. R. Neugebauer: None. M.M. Hedderson: None.FundingNational Institutes of Health (DK138135-02)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-62-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 62-PUB: The Mechanism of IGF2-IGF2R Signaling in Regulating Testosterone
Synthesis in Testicular Leydig Cells-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 62-PUB
Abstract: Introduction and Objective: This study aims to explore how the IGF2 signal affects testosterone synthesis in Leydig cells and to further investigate its mechanism in male hypogonadism and obesity.Methods: A model of obese male mice was created by combining bilateral orchiectomy with a high-fat diet, and compared with sham surgery high-fat and normal chow groups for weight gain, serum hormone levels, and metabolic indicators.IGF2R expression in Leydig cells was detected. The distribution of cholesterol esters in Leydig cells was detected by confocal microscopy. ELISA was utilized to measure testosterone levels. QPCR and Western Blot were used to analyze HSD17B3 and CYP7A1 levels. Finally, IGF2 supplementation therapy was employed.Results: Compared to sham surgery, orchiectomy-induced obese mice showed faster weight gain under high-fat diets, with reduced serum testosterone, DHT, estradiol, and IGF2 levels. Igf2 was mainly expressed in Leydig cells, with Igf2r similarly expressed. IGF2 and IGF2R expression in Leydig cells correlated with key enzymes in testosterone synthesis. Cellular experiments confirmed that IGF2R knockout reduced testosterone synthesis, while overexpression enhanced it. IGF2 supplementation activated AMPK, promoting lipophagy and increasing free cholesterol, which was converted to testosterone precursors. This improved testosterone synthesis and mitigated obesity in orchiectomy-induced mice.Conclusion: The IGF2 signal has a positive regulatory effect on testosterone synthesis in Leydig cells. IGF2 activates AMPK through the IGF2R signal, promotes lipophagy in Leydig cells, enhances cholesterol uptake and metabolism, and ultimately promotes testosterone synthesis. In the obese state, the weakening of the IGF2-IGF2R signal may lead to reduced testosterone synthesis, which may be associated with obesity-related hypogonadism.DisclosureW. Gui: None. C. Zhou: None. D. Wu: None. X. Lin: None.FundingNational Natural Science Foundation of China (82200638)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-62-PUB
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 63-OR: The Impact of Maternal Food Insecurity on Gestational Diabetes and
Other Pregnancy Outcomes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 63-OR
Abstract: Introduction and Objective: Food insecurity (FI), a lack of consistent access to nutritionally adequate and safe food, affects more than 10% of Americans. FI is associated with adverse health outcomes including obesity and diabetes, but there is limited data about the impact of FI in pregnancy. Our objective was to determine the association between maternal FI and pregnancy outcomes.Methods: This retrospective cohort study evaluated deliveries in a single health system from 1/1/2018-6/30/2023 and included all patients who were screened for FI during pregnancy using the 2-question Hunger Vital Sign. Demographics, clinical characteristics, and pregnancy outcomes were extracted from the EMR and were compared between those with and without FI in univariable analysis. Stepwise multivariable logistic regression was performed to determine the association between FI and pregnancy outcomes.Results: Of 21,640 pregnant patients screened for FI, 1,543 (7%) were food insecure. The majority (91%) of those with FI also screened positive for other social determinants of health (SDoH). Those with FI were more likely to have obesity (42 vs 31%), pregestational diabetes (3 vs 1%), and chronic hypertension (6 vs 4%) compared to patients without. On adjusted analysis, pregnant people with FI had a higher odds of GDM (aOR 1.25, 95% CI 1.01-1.54, p=0.04), preterm birth <37 weeks (aOR 1.39, 95% CI 1.19-1.63, <0.01), and preterm birth <34 weeks (aOR 1.37, 95% CI 1.05-1.78, p=0.02) [model accounting for pregravid obesity as well as gestational/pregestational diabetes and gestational age at delivery when appropriate]. FI was not associated with increased odds of severe maternal morbidity, cesarean delivery, NICU admission, or macrosomia.Conclusion: Food insecurity during pregnancy is associated with preexisting diet-related chronic diseases, as well as GDM and preterm birth. FI is an important SDoH that may contribute to adverse pregnancy outcomes. All pregnant people should be screened for FI.DisclosureC. Dolin: None. A. Kern-Goldberger: None. M. Hopkins: None. S. Ehrenberg Buchner: Advisory Panel; Dexcom, Inc.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-63-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 63-PUB: Health Utilities of People with Obesity in Taiwan—A
Nationwide Representative Analysis-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 63-PUB
Abstract: Introduction and Objective: The population with obesity and obesity-related comorbidities/complications (ORCs) was commonly considered as target population to determine the efficacy of novel interventions; however, the health utilities of this population were seldom analyzed. This study aims to estimate the health-related quality of life (HRQoL) associated with sociodemographic and clinical characteristics in patients with obesity and ORCs.Methods: Taiwan’s National Health Interview Survey in 2013 and 2017 was utilized to identify the EuroQol-5 dimensions among the population with body mass index (BMI) of ≥27 kg/m2 and ORCs. The ORCs (in total of 11 types of disease, e.g., sleep apnea, acute coronary syndrome [ACS]) were ascertained through Taiwan’s National Health Insurance Research Database. Multivariate ordinary least squares, Tobit, and two-part models were performed to estimate the impacts of patients’ characteristics on HRQoL.Results: The mean health utility was 0.90 for 2,901 study participants. The mean age and BMI were 56.91±13.55 years and 30.14±3.08 kg/m2. After adjustment of socioeconomic status, the top five reductions in health utilities were having a stroke (0.154±0.019), ACS (0.153±0.036), transient ischemic attack (0.068±0.033), chronic kidney disease (0.059±0.019), and osteoarthritis (0.049±0.010). Significant decrements of health utility per BMI increase, female (vs. male) and aged above 55 years (vs. below 55 years) were 0.008±0.001, 0.053±0.010, and 0.033±0.010, respectively. Compared with those with a BMI of 27-29.9 kg/m2, the health utility of patients with a BMI of ≥35 kg/m2 resulted in a significant reduction (-0.087±0.016).Conclusion: Cardiovascular complications and patients with higher BMI are associated with considerably worse HRQoL. These estimates of HRQoL can further facilitate health economic evaluation to determine cost-effective strategies for Taiwan’s obesity management.DisclosureK. Chong: None. Y. Chang: None. E. Chang: None. C.A. Lee: None. H. Ou: None. S. Kuo: None.FundingMinistry of Science and Technology in Taiwan (112-2628-B-006-008-MY3); Novo Nordisk Taiwan
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-63-PUB
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 64-OR: Delayed Access to Insulin during Pregnancy
-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 64-OR
Abstract: Introduction and Objective: Delayed access to insulin (DAI) during pregnancy can have a major impact on effective diabetes management, posing risks to mother and infant. We sought to assess the frequency of DAI (≥ 7 days) in pregnant women and identify associated factors.Methods: Of 1262 pregnant women aged ≥18 with GDM or pre-existing T2DM who were newly prescribed insulin between 2018 and 2024, we randomly selected 303 women for detailed chart review with equal distribution across calendar years. We determined the Social Vulnerability Index (SVI) tertiles by census tract.Results: Of the 303 women, 15.5% experienced DAI. Compared to the non-delayed group, there was a higher proportion of high SVI, Black race, single status, need for interpreter and public insurance in the delayed group (Table 1). In a multivariable logistic regression model, Black race (OR=6.01, p<0.001) high SVI (OR=2.07, P=0.05) and prescriptions during 2022-2024 vs. 2018-2021 (OR = 2.35, p= 0.027) remained significant predictors of DAI. Delays were primarily due to insulin coverage (47%), e.g., prior authorization for nonpreferred brand, and patient concerns, e.g., fear of side effects (27.6%). There were more insulin coverage issues and fewer patient concerns in 2022-2024 than in 2018-2021.Conclusion: We found that DAI is common during pregnancy, especially among black women, has increased in frequency and is commonly due to insurance coverage issues.DisclosureG. Rios-Ortega: None. S. Trabelsi: None. M. Fatima: None. D.C. Simonson: Stock/Shareholder; GI Windows. Consultant; Phase V Technologies. E.W. Seely: None. M.E. McDonnell: Research Support; Dexcom, Inc.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-64-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 64-PUB: Comparison of Body Mass Index and Bioelectric Impedance Analysis
for Clinical Assessment of Obesity-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 64-PUB
Abstract: Introduction and Objective: Body mass index (BMI), weight adjusted for height, is an imprecise tool for the diagnosis of obesity. Body composition assessment with bioelectric impedance analysis (BIA) scales estimate fat mass and % adiposity, offering a more precise diagnosis of obesity. The objective of this project was to compare the use of BMI and BIA scale assessment of % adiposity for the diagnosis of obesity.Methods: Obesity status was determined by both traditional BMI and BIA scale in our weight management clinic. BMI (kg/m2) was calculated from weight and height measured by stadiometer. Body composition was assessed with TANITA BIA scale MC-780U. Body composition measures included total body water, fat, muscle and bone mass, and % adiposity. BMI classification of obesity was as follows: obese BMI ≥ 30 kg/m2, overweight BMI 25 - 29.9 kg/m2, normal BMI 18.6 - 24.9 kg/m2. Classification of obesity by BIA % adiposity was: women ≥ 33%, men >25%. Concordance between BMI and BIA assessments for the diagnosis of obesity was analyzed.Results: Of 112 patients assessed, 87% were female, 49% non-Hispanic white, 43% black. Mean age was 49±13 years, BMI 36.4±7.7 kg/m2, and % adiposity 40.3±8.2%. BMI classification diagnosed 81.2% (n=91) with obesity, 12.5% (n=14) overweight, and 6.2% (n=7) normal. BIA % adiposity score diagnosed 83.9% (n=94) with obesity. The diagnosis of obesity was concordant between BMI and BIA classification in 87.5% (n=98). Of 14 discordant cases, 86% (n=12) were female; 64% were middle age 39-59 years. Eight were classified as obese by BIA but not BMI. Six were classified as obese by BMI but not BIA.Conclusion: Assessment of adiposity by BIA scale offers an accurate measure of total and percent adiposity that more precisely classifies patients as obese than traditional BMI measures calculated from height and weight alone. Discordance between the two different measures raises concern for misclassification of obesity status which may over or underestimate related health risks.DisclosureA. Johnson-Jennings: None. A.D. Coviello: Advisory Panel; Novo Nordisk. Consultant; Intuitive Surgical. Other Relationship; GI Dynamics. Consultant; Hanmi Pharm. Co., Ltd. Advisory Panel; NewAmsterdam Pharma.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-64-PUB
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 65-PUB: The Nomogram Development and Validation for Predicting Hypoxemia
after Laparoscopic Sleeve Gastrectomy in Patients with Obesity—A
Multicenter Retrospective Study-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 65-PUB
Abstract: Introduction and Objective: Postoperative hypoxemia (PH) is the most common postoperative pulmonary complication (PPC) of bariatric surgery. However, clinically validated tools and tests are lacking to predict the risk of hypoxemia after bariatric surgery in patients with obesity. Therefore, this study developed and validated a nomogram model for predicting the probability of hypoxemia within 24 hours after laparoscopic sleeve gastrectomy (LSG) in patients with obesity.Methods: The prediction model was based on a retrospective study of 195 patients with obesity who underwent LSG between January 2018 and December 2023 at our hospital. Multivariate logistic regression analysis was performed to identify independent predictors of postoperative hypoxemia. Model performance was evaluated using receiver operating characteristic curves, calibration curves, clinical decision curve analysis, and clinical impact curves. This prediction model was internally validated with bootstrap resampling and further externally validated in 105 patients who underwent LSG at two other hospitals.Results: Predictors in the nomogram prediction model included preoperative body mass index (BMI), platelet (PLT), fibrinogen (FIB), and the triglyceride-glucose (TyG) index. This prediction model had favorable discrimination, calibration, and clinical validity in both the training and validation sets. We published the nomogram online in the form of a simple and useful calculator.Conclusion: The prediction model we constructed can accurately predict the risk of postoperative hypoxemia in patients with obesity, helping professionals to identify high-risk patients early and make informed clinical decisions.DisclosureJ. Guo: None. J. Yu: None. P. Tian: None. G. Lu: None. K. Mutailipu: None. X. Wen: None. J. Yin: None. L. Du: None. L. Lu: None. Y. Wang: None. Y. Zhuang: None. S. Qu: None. H. Chen: None. L. Bu: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-65-PUB
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 65-OR: Age at Type 2 Diabetes Diagnosis and Mortality and Cardiovascular
Risks, and Years of Life Lost in South Asians-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 65-OR
Abstract: Introduction and Objective: South Asians develop type 2 diabetes (T2D) earlier than others. We investigated associations between age at T2D diagnosis and risks of all-cause and CVD mortality, non-fatal CVD events, and years of life lost (YLL).Methods: We analyzed data from 21,861 CARRS cohort participants. T2D was defined as self-reported diagnosis, T2D treatment, fasting plasma glucose ≥126 mg/dL, 2-h plasma glucose >200 mg/dL, or HbA1c ≥6.5%. Participants were grouped by age at diagnosis: 20-29, 30-39, 40-59, and ≥60 years. Cox regression models estimated risks, adjusting for demographics and clinical factors. YLL was calculated using India’s Individual Annuitant Mortality Table.Results: Among 21,861 participants (mean age 43.6 years; 44.5% male), 6,396 had T2D (5,295 prevalent; 181 incident). Over 14 years (132,293 person-years), 2,121 deaths (809 CVD) and 336 non-fatal CVD events occurred. Earlier T2D diagnosis was linked to higher all-cause mortality vs. those without T2D: HR 2.2 (20-29), HR 2.0 (30-39), HR 1.4 (40-59), HR 0.9 (≥60). Similar patterns were seen for CVD mortality and non-fatal CVD events (Table). T2D caused an average 12-year life loss, with YLL increasing for earlier diagnosis: 19.2 (20-29), 16.8 (30-39), 12.2 (40-59), and 6.3 (≥60).Conclusion: T2D was linked to greater years of life lost and higher mortality risks, especially in younger individuals, highlighting the need for early detection and management in South Asians.DisclosureR. Jagannathan: None. A.S. Oguntade: None. M. Deepa: None. D. Kondal: None. R. Anjana: None. S.A. Patel: None. R.M. Carrillo-Larco: None. S. Mohan: None. M.K. Ali: Advisory Panel; Eli Lilly and Company. A.A. Quyyumi: None. D. Prabhakaran: None. V. Mohan: Speaker's Bureau; Novo Nordisk. Advisory Panel; Abbott. Research Support; Servier Laboratories. Speaker's Bureau; USV Private Limited, Sanofi, Medtronic, Eli Lilly and Company. K. Narayan: None. N. Tandon: None.FundingThe Center for cArdiometabolic Risk Reduction in South Asia study were supported by grants from the National Heart, Lung, and Blood Institute (HHSN2682009900026C, P01HL154996), National Institutes of Health (NIH), National Institute on Aging, NIH (R01-AG89759), and National Institute of Diabetes and Digestive and Kidney Diseases (R01DK139632), NIH.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-65-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 66-OR: Clinical Subgroups of Young Adults with Type 2 Diabetes Predict
Outcome-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 66-OR
Abstract: Introduction and Objective: Prior studies identified 5 novel subgroups of type 2 diabetes (T2D) that may predict diabetes-related outcomes. However, these studies utilized laboratory measurements that are not part of a routine T2D visit limiting use in clinical care. Given the increasing prevalence of T2D in young adults (age <45 yrs), our goal was to determine subgroups of T2D associated with diabetes-related outcomes in young adults with routine clinical variables.Methods: Adults with the diagnosis of T2D (ICD codes 250.xx and E11.xx; n=352 826) with age at first diagnosis of T2D between 18-44 years (n=13 086) were identified from the Utah Diabetes Database. Those with missing data or laboratory data consistent with type 1 diabetes were excluded. Hierarchical analysis followed by k-means clustering was performed to determine 3 subgroups: cluster 1 (C1), cluster 2 (C2), and cluster 3 (C3), with results reported in this order.Results: Baseline clinical variables with the highest effect were age at first diagnosis, baseline BMI, HbA1c, and GFR. C1 had the highest BMI (45 ± 7 vs 30 ± 6 vs 30 ± 5 kg/m2, p<0.01) but lowest HbA1c (7.2 ± 2.1 vs 8.5 ± 2.8 vs 7.6 ± 2.4%, p<0.01). C2 was youngest (age 37 ± 5 vs 28 ± 5 vs 39 ± 4 yrs, p<0.01) with the highest HbA1c. C3 was older with the lowest GFR at baseline (104 ± 18 vs 115 ± 16 vs 86 ± 27 ml/min/1.73m2, p<0.01). On follow up, frequencies of complications significantly differed among clusters. C1 had moderate risks for nephropathy and hepatic fibrosis from metabolic dysfunction-associated liver disease (MASLD) but low risk for retinopathy and the least likely to require insulin. C2 had the highest risk for DKA and hypoglycemia, the lowest risk for nephropathy, and was more likely to require insulin. C3 had the highest risks for nephropathy, retinopathy, neuropathy and hepatic fibrosis from MASLD.Conclusion: Clinical subgroups of young adults with type 2 diabetes were associated with different outcomes. These subgroups may respond to precision pharmacotherapy based on the predicted outcomes.DisclosureA. Sharma: None. J.M. Lazaro-Guevara: None. M.G. Pezzolesi: None.FundingAmerican Diabetes Association (7-22-JDFPM-04)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-66-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 67-OR: Longitudinal Trends in Diabetic Foot Ulcers and Lower Extremity
Amputations before and after the COVID-19 Pandemic-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 67-OR
Abstract: Introduction and Objective: This study aimed to evaluate the impact of the COVID-19 pandemic on diabetes foot ulcer (DFU) prevalence and lower extremity amputation (LEA) incidence among patients with type 2 diabetes mellitus (T2D).Methods: We conducted a cross-sectional analysis using the TriNetX network of 68 U.S. health care organizations. The study population included adults with T2D from 2016 to 2023. DFU prevalence and LEA incidence were analyzed across pre-pandemic (2016-2018), pandemic (2019-2020), and post-pandemic (2021-2023) periods. Annual percent changes (APC) were calculated, and relative risk ratios (RR) and odds ratios (OR) with 95% confidence intervals (CI) were reported.Results: Among 5,292,512 patients with T2D (mean age, 66 ± 14.0 years; 47.3% female), DFU prevalence increased pre-pandemic (APC +17.0%, p<0.001), remained stable during the pandemic (APC -0.37%, p=0.62), and rose significantly post-pandemic (APC +9.46%, p<0.001). LEA incidence showed similar trends: increased pre-pandemic (APC +9.18%, p<0.001), stable during the pandemic (APC -3.75%, p=0.10), and significantly increased post-pandemic (APC +11.46%, p<0.001). Overall, males experienced greater increases in both DFU prevalence (63.2% vs. 40.0%) and LEA incidence (42.9% vs 40.1%) compared with females. Hispanic males had the highest odds for DFU (OR 1.53 95% CI 1.49 to 1.56) and risk for LEA (RR 3.10 95% CI 2.81 to 3.42) compared with White females.Conclusion: In this cohort study of patients with T2D, both DFU prevalence and LEA incidence increased significantly post-pandemic, with the rate of increase for LEA exceeding that of DFU, suggesting that delay in care during the pandemic may have increased the risk of diabetes-related amputation.DisclosureI.Y. Luu: None. A.T. Hong: None. L. Shin: None. C. Shih: None. S.M. Han: Consultant; Medtronic. Advisory Panel; Cook Medical, W.L.Gore &Associates, Terumo Aortic. D.G. Armstrong: None. T. Tan: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-67-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 68-OR: The Molecular Pathways of Type 2 Diabetes Using Proteomics,
Metabolic, and Anthropometric Profile in Cross-Ancestry Biobanks-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 68-OR
Abstract: Introduction and Objective: Plasma proteomic together with genetics help understand type 2 diabetes (T2D) aetiology. The protein-level finding is ideal for drug discovery in a precise and controlled manner.Methods: We identified diabetes associated proteins in observational designs in UK Biobank (UKB). Bayesian non-negative matrix factorisation (bNMF) was applied to cluster the obtained proteins incorporating their phenotypic associations with metabolic/anthropometric profiles. For clusters’ leading proteins, colocalization and Mendelian randomization were to investigate tri-variate relationships (protein - metabolic/anthropometric traits - T2D). We performed same analyses using China Kadoorie Biobank (CKB).Results: 1793 proteins associated with diabetes. bNMF suggested five clusters (Adiposity, Reduced-adiposity, Lipids, Liver, Kidney) and 906 cluster-leading proteins. Genetic evidence indicated effects of NCR3LG1, RTBDN, TSPAN8 on T2D as well as T2D on FGFBP3 in both ancestries. Effects of CD34, SCT, KCTD5 on T2D were UKB specific; effects of PLA2G15, ENTR1 on T2D were CKB specific. We revealed candidate proteins linking T2D via adiposity, liver, kidney traits.Conclusion: We provided insights of multiple proteins on T2D treatments. The protein-cluster trait associations revealed T2D aetiology as well as linking diabetes comorbidities. There were agreements across ancestry though heterogeneity was found.DisclosureJ. Liu: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-68-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 69-OR: Health Disparities in Type 2 Diabetes Outcomes for Transgender and
Nonbinary Patients—A Nationwide Study-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 69-OR
Abstract: Introduction and Objective: Transgender, non-binary, and genderqueer people experience systematic barriers in receipt of medical care. Our objective was to understand patterns of diabetes treatment/outcomes for this population.Methods: Patients with an ICD code diagnosis of T2DM between 01/01/2021 and 01/13/2024 in nationwide Epic EHR data were included and A1c control, receipt of antidiabetic medication classes, and rates of diabetes complications were analyzed by self-reported gender identity.Results: A total of 4,689,434 were newly diagnosed with T2DM. Among those who provided gender identity, 6,325 (0.4%) were of a gender minority group. Gender minority patients tended to have higher A1c at diagnosis (Figure 1). Compared to cisgender female patients, transgender male and transgender female patients were less likely to have A1c <7% (OR 0.75, 95% CI 0.70-0.81 and OR 0.73, 95% CI 0.69-0.77) and more likely to receive insulin (OR 1.18, 95% CI 1.10-1.28 and OR 1.25, 95% CI 1.17-1.33). Transgender male patients were less likely to receive TZDs, DPP4i, or SGLT2i. Transgender male and transgender female patients were more likely to have ketoacidosis (OR 2.94, 95% CI 2.50-3.45 and OR 2.63, 95% CI 2.27-3.05), and transgender female patients were more likely to have diabetic foot ulcers (OR 2.06, 95% CI 1.71-2.48) and lower limb amputations.Conclusion: Greater attention to diabetes care is needed to promote health equity for gender minority patients.DisclosureJ.B. Lusk: None. F. Li: None. E. OBrien: Research Support; Pfizer Inc. S. Aymes: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-69-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 70-OR: Risks of Cancers among Novel Subtypes of Type 2 Diabetes—A
Longitudinal Analysis from the United States-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 70-OR
Abstract: Introduction and Objective: Type 2 diabetes (T2D) may be associated with higher cancer risk through chronic inflammation, insulin resistance, and obesity. We assessed cancer risks across T2D subtypes.Methods: Newly diagnosed T2D (n = 727,076; age: 64.4 years [SD:13.3], 52% female) over 2012-2023 from the Epic Cosmos platform were classified into Severe Insulin-Deficient Diabetes (SIDD, 21.6%), Mild Obesity-Related Diabetes (MOD, 23.8%), or Mild Age-Related Diabetes (MARD, 40.9%) using reliable algorithms. Unclassified cases were labeled as Mixed (13.7%). First occurrence of cancers (colorectal, liver, pancreatic, female [breast, endometrial, and ovarian], prostate) within ten years after T2D diagnosis were identified using ICD-10-CM codes. Cox proportional hazards models were used to estimate absolute and relative hazards (HR) by subtype, adjusted for age, sex, and smoking.Results: Cumulative cancers were highest in MOD and Mixed. Patterns for specific cancer risks differed: compared to MOD (Figure), SIDD and MARD had 35-111% higher hazards of liver, pancreatic, and prostate cancers but 10-36% lower hazards of colorectal and female cancers.Conclusion: Novel subtypes exhibit varying risks for different cancers, highlighting opportunities for early screening and tailored prevention strategies.DisclosureZ. Li: None. B. Salazar: None. J. Guo: None. K.O. Sanaka: None. P. Vellanki: Advisory Panel; Eli Lilly and Company. M.K. Ali: Advisory Panel; Eli Lilly and Company. C. Hofmeister: Research Support; AbbVie Inc, Sanofi, Bristol-Myers Squibb Company. J. Varghese: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-70-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 71-OR: ADA Presidents' Select Abstract: HLA-Focused Meta-Genetic Risk
Score (GRS) Performance in Populations of Diverse Ancestry with Type 1
Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 71-OR
Abstract: Introduction and Objective: Type 1 Diabetes (T1D) is a complex autoimmune disease caused by the destruction of pancreatic β-cells. In T1D, genetic factors represent approximately 50% of the total risk with variants in HLA genes contributing up to 50% of the genetic risk. Here, we constructed HLA-focused meta-GRS from populations of diverse genetic ancestries - European (EUR, N = 33,601), African American (AFR, N = 3,877), Admixed (AMR, N = 1,084) and Finnish (FIN, N = 2,804) - and evaluated performance and transferability.Methods: The 41,366 samples were genotyped on the ImmunoChip array that has deep coverage in the human Major Histocompatibility Complex (MHC). Within the MHC, we imputed SNPs and HLA class I and HLA class II alleles. We constructed two meta-GRSs from conditionally independent SNPs and HLA alleles using KING software (v.2.3.2).Results: In the meta-GRS, the most strongly associated T1D SNP was rs9273363 (OR = 4.76, P = 3.15x10-1738), while the most strongly associated HLA risk allele was HLA-DQB1*03:02 (OR = 5.13, P = 5.28x10-1314). Meta-GRS derived from SNPs and HLA alleles had similar prediction power across ancestries. The meta-GRS performed the best in the EUR ancestry population, with AUCEUR = 0.88 for SNP- and AUCEUR = 0.87 for HLA alleles-based models. In AFR and FIN populations, meta-GRS using SNPs and HLA alleles yielded AUCAFR = 0.86 and AUCFIN = 0.82. The performance of meta-GRS in AMR ancestry was slightly higher for SNPs (AUCAMR = 0.82) than for HLA alleles (AUCAMR = 0.80).Conclusion: Genetic risk score models constructed from SNPs and HLA alleles from multiple ancestries (meta-GRS) perform well and similarly across populations. Incorporating non-HLA genetic risk variants (population-specific or meta-analytic) should improve the genetic prediction of T1D risk. While this study includes participants from diverse ancestries, further research with more diverse populations is needed to better assess the transferability of T1D GRS across ancestries.DisclosureD.A. Michalek: None. W. Chen: None. S. Onengut-Gumuscu: None. S.S. Rich: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-71-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 72-OR: A Novel Multiancestry Polygenic Score Improves T1D Risk Prediction
in Non-European Populations-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 72-OR
Abstract: Introduction and Objective: Polygenic scores (PS) can predict risk for type 1 diabetes (T1D) by integrating genetic information across the genome. However, most PS are derived from a single population and perform best when applied to genetically similar populations. Selecting the optimal PS is challenging in admixed populations. Here, we investigated whether a T1D PS derived from multiple ancestries could accurately predict risk across diverse populations.Methods: We collected summary statistics from a recent T1D genome-wide association study, which included individuals with African (AFR), Admixed American (AMR), or European (EUR) genetic ancestry. As variation in HLA genes accounts for ~50% of T1D genetic risk, we modeled T1D risk separately for HLA and non-HLA variants. We used PRS-CS to construct a T1D PS with over 1 million variants. We applied the score in Mass General Brigham Biobank and evaluated performance with the area under the receiver operating characteristic curve (AUC), controlling for age, sex, and 10 principal components of ancestry. We compared this T1D PS to T1D GRS2, which was previously developed using data from EUR ancestry populations.Results: The novel multi-ancestry PS was strongly associated with T1D risk, with an odds ratio of 16.9 for those in the top 5% of the distribution compared to the remaining 95% (P < 2×10-16). Among 53,885 participants with EUR ancestry (370 with T1D), the AUC of the T1D PS was 0.87, which was not significantly different from T1D GRS2 (AUC = 0.87, P = 0.84). However, among 6,872 participants with AFR or AMR ancestry (38 with T1D), the AUC of the T1D PS was 0.90, which was significantly higher than T1D GRS2 (AUC = 0.86, P = 0.04).Conclusion: Our multi-ancestry T1D PS improves T1D risk prediction in non-EUR ancestries, while maintaining high predictive power in EUR populations. These results underscore the need to generate genetic data from non-EUR ancestries to improve T1D prediction.DisclosureA.J. Deutsch: None. A.S. Bell: None. D.A. Michalek: None. S. Onengut-Gumuscu: None. S.S. Rich: None. J.C. Florez: Research Support; Novo Nordisk. A. Manning: None. J.M. Mercader: None. M. Udler: Research Support; Novo Nordisk.FundingNIH/NIDDK (K23 DK140643; NIH/NHGRI (U01HG011723)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-72-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 73-OR: Large-Scale Multiancestry Recessive GWAS Meta-analysis Identifies
Novel Recessive Associations and Improves Polygenic Prediction of Type 2
Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 73-OR
Abstract: Introduction and Objective: Most genome-wide association studies (GWAS) are performed using additive genetic models. However, additive models may miss variants with recessive effects, limiting our understanding of disease genetic architecture. We conducted a multi-ancestry meta-analysis to uncover novel recessive loci associated with type 2 diabetes (T2D) and evaluate their contribution to disease risk prediction through non-additive polygenic risk scores (PRS).Methods: We performed a recessive T2D GWAS meta-analysis including up to 196,992 cases and 900,343 controls from 8 biobanks and cohorts. We defined variants with recessive effects as those showing either a twofold larger effect size or higher statistical significance in recessive models compared to additive models. We developed a PRS model, integrating additive and non-additive effects and tested for association with T2D risk in independent validation datasets.Results: We identified 128 regions with a recessive effect, including 48 that reached GWAS significance only in the recessive analysis. We replicated the known variant near PELO with an OR of 2.1 (95% CI 1.8-2.4; P=1 × 10−18) for homozygous compared to 1.1 (95% CI 1.0-1.1; P=2 × 10−5) using the additive model. We found 9 additional recessive signals with homozygous showing 50% increased or decreased risk for T2D. For example, rs1800574 near HNF1A, enriched in South Asians, showed an OR of 1.58 (95% CI 1.4-1.8; P=3 × 10-10), compared to 1.17 (95% CI 1.1-1.2; P=1 × 10−41) in the additive model. A combined PRS, integrating additive and non-additive effects, improved prediction with individuals in the 97.5th percentile showing an OR of 4.8 (95% CI 4.1-5.6; P=9 × 10-89), compared to 4.6 (95% CI 3.9-5.3; P=2 × 10-85) with an additive PRS.Conclusion: This study highlights the importance of recessive genetic effects in the architecture of T2D, identifying novel associations and improving polygenic risk score prediction.DisclosureM. Vora: None. J. Li: None. T. Heng: None. A. Huerta: None. L. Saso-Jiménez: None. R. Mandla: None. A. Manning: None. D.J. Carey: None. S. Finer: Research Support; Novo Nordisk A/S, AstraZeneca, Bristol-Myers Squibb Company, GlaxoSmithKline plc, Maze Therapeutics, Merck Sharp & Dohme Corp, Pfizer Inc, Takeda Pharmaceutical Company. P. Natarajan: Research Support; Amgen Inc, Genentech, Inc. Consultant; Bristol-Myers Squibb Company, Eli Lilly and Company, Novo Nordisk, ESPERION Therapeutics, Inc., Foresite Labs, Foresite Capital. Stock/Shareholder; Bolt, Candela, Mercury, MyOme, Parameter Health, Preciseli, and TenSixteen Bio. Consultant; Tourmaline Bio. Other Relationship; Vertex Pharmaceuticals Incorporated. U.L. Mirshahi: None. J.M. Mercader: None.FundingAmerican Diabetes Association (11-22-ICTSPM-16); NIH (R01DK137993, U01HG011723, U01DK140757)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-73-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 74-OR: Improved Polygenic Risk Prediction for Type 2 Diabetes through a
GWAS Meta-analysis of over 200,000 Latin American Individuals-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 74-OR
Abstract: Introduction and Objective: Latin American (LAm) populations are disproportionately affected by type 2 diabetes (T2D) but are underrepresented in genome-wide association studies (GWAS). Polygenic risk scores (PRS) constructed using European (EUR) GWAS exhibit limited predictive accuracy in other populations. We aim to improve the performance of a T2D PRS in individuals of LAm ancestry by increasing their representation in GWAS.Methods: We conducted the largest T2D GWAS meta-analysis for LAm individuals (N=207,055) using 17 datasets, including the Mexico City Prospective Study (N=125,042). We used this data to develop a new genome-wide LAm PRS and compare its performance with a previous PRS derived from a smaller LAm GWAS meta-analysis (N=82,013). We also combined the new LAm GWAS with those from four other ancestries (N=2,310,590, 9% LAm) to construct a multi-ancestry PRS. PRSs were evaluated in independent LAm cohorts (N=11,377).Results: The new LAm PRS, based on 200K LAm GWAS sample, showed a 30% increase in the proportion of variance explained by the additive genetic model (liability r2=7% vs. 5% in the previous LAm PRS). Compared with individuals in the interquartile range, those above the 95th percentile of the new LAm PRS had 3.4 times higher T2D odds (95% CI: 2.8-4.2). In contrast, the odds ratio for the same comparison using the previous LAm PRS was 1.8 (95% CI: 1.5-2.1). Integrating the LAm GWAS into a multi-ancestry PRS further improved the performance, explaining up to 16% of the variance (vs. 14% with a EUR PRS, GWAS N=1,486,934). Individuals above the 95th percentile of the multi-ancestry PRS distribution had a 6.7-fold higher T2D odds [95% CI: 5.3-8.4] compared to those in the interquartile range.Conclusion: This study demonstrates the improved predictive power of a T2D PRS achieved by a 60% increased sample size of an LAm GWAS and underscores the importance of further expanding the representation of LAm populations in genetic research.DisclosureA. Huerta: None. P. Baca Peynado: None. F. Rivas: None. M. Ng: None. R. Mandla: None. J. Kim: None. Y. Lu: None. J.E. Below: None. R. Tapia-Conyer: None. J. Berumen: None. J. Alegre-Diaz: None. J. Emberson: Research Support; Regeneron Pharmaceuticals, AstraZeneca. J.M. Torres: None. P. Kuri: None. J.M. Mercader: None.FundingNIDDK (UM1-DK078616); American Diabetes Association Innovative and Clinical Translational Award (1-19-ICTS-068); American Diabetes Association (11-22-ICTSPM-16); NHGRI (U01HG011723)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-74-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 75-OR: Novel Syndromic Forms of Diabetes within the Rare and Atypical
Diabetes Network (RADIANT)-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 75-OR
Abstract: Introduction and Objective: Syndromic diabetes refers to the co-occurrence of diabetes with abnormalities of organ systems beyond the endocrine pancreas. RADIANT was established to study atypical forms of diabetes including syndromic diabetes. We aimed to characterize individuals with putative syndromic forms of diabetes in RADIANT.Methods: We defined syndromic diabetes based on 1 major and 1 minor criterion, or 3 minor criteria without any exclusion criteria in individuals who were diagnosed with diabetes before 35 years of age. Major criteria include dysmorphic features, intellectual disability, and neurodevelopmental disorders. Minor criteria include symptoms related to another organ system. To be included as a criterion, the symptoms should not be known complications of diabetes mellitus, should be present before the onset of diabetes or within 10 years of diabetes diagnosis, and be rated as moderate to severe. Exclusion criteria included individuals with positive islet autoantibodies, secondary diabetes, symptoms resembling mitochondrial diabetes, severe insulin resistance, or lipodystrophy. Participants underwent fasting labs and a 2-hour oral glucose tolerance test.Results: As of November 2024, 31 out of 272 (11.4%) of participants were deemed to have syndromic diabetes based on the above criteria. The mean age of diabetes diagnosis was 16.8 ± 8.3 years. Most individuals had intact C-peptide (mean fasting C-peptide 2.4 ± 1.3 ng/mL; C-peptide index 2.2 ± 1.3). They had overall excellent glycemic control (mean HbA1c 7.0 ± 0.7%). On average, participants had 4.6 ± 1.5 systems affected. The most common systems affected included endocrine, gastrointestinal, cardiovascular, genitourinary, and neurological. Thus far, a unifying genetic diagnosis has not been identified in these individuals.Conclusion: These cases highlight the spectrum of syndromic forms of diabetes found within RADIANT and represent an opportunity to define novel syndromes related to diabetes.DisclosureS.I. Stone: None. F. Urano: Other Relationship; Novus Biologicals. Advisory Panel; Opris Biotechnologies, Emerald Biotherapeutics. Board Member; CURE4WOLFRAM. Y. Yang: None. C. Kirk: None. M. Tosur: None.FundingNational Institutes of Health (U54DK118612)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-75-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 76-OR: Molecular Characterizations of the Pathophysiology of Type 2
Diabetes in a Hispanic and Latino Population-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 76-OR
Abstract: Introduction and Objective: Type 2 diabetes (T2D) is a complex metabolic condition characterized by decreased response to insulin and subsequent elevated blood glucose concentration. T2D is a major driver of global health burdens, with a disproportionate impact on US Hispanic and Latino (HL) populations yet are underrepresented in genetic studies and have strikingly limited representation in multi-omic studies. Our research explores a deeply phenotyped HL cohort, the Cameron County Hispanic Cohort (CCHC), with robust cross-sectional transcriptomic, proteomic, and metabolomic data to elucidate the biological mechanisms contributing to T2D.Methods: We evaluated single mRNA, protein, and metabolite linear regressions to compare the expression and abundance of genes, proteins, and metabolite levels between individuals with T2D and controls without diabetes. The models were adjusted for age, sex, and three principal components (PC) of ancestry.Results: We observed 405 genes, 30 proteins, and 33 metabolites differentially expressed and abundant in T2D cases and controls (p < 0.05 after FDR correction). Our most notable study findings for transcriptomics include ABCG1, CPT1A, KLF10, and AKT3, and for proteomics, GCG, GAPDH, and MXRA8. For metabolomics, beyond glucose and other sugars, we identified multiple sphingomyelins, which are transported by ABCG1, as key results. We are currently replicating our study findings in independent HL study populations.Conclusion: Our analyses revealed metabolic changes associated with T2D across omics characterized in the whole blood. To our knowledge, this is one of the first cross-sectional multi-omic characterizations of T2D in a highly vulnerable HL population. These data demonstrate not only how multi-omic studies may elevate understanding of T2D in HL populations but also implicate functional genes, proteins, and metabolites as well as a mechanism of effect into T2D in HL individuals.DisclosureE.G. Frankel: None. L.E. Petty: None. R. Roshani: None. W. Zhu: None. H. Chen: None. M. Yaser: None. M. Graff: None. M. Krishnan: None. V.L. Buchanan: None. M. Lee: None. A.D. Gutierrez: None. J.B. McCormick: None. K.E. North: Consultant; Amgen Inc. H.M. Highland: None. J.E. Below: None.FundingNational Institutes of Health (R01HL142302)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-76-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 77-OR: BNIP3-Mediated Mitophagy Protects Human β-Cells by Regulating
Mitochondrial Integrity and Immunogenicity in Type 1 Diabetes (T1D)-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 77-OR
Abstract: Introduction and Objective: β cell integrity relies on proper mitochondrial bioenergetics and mitophagy. Dysfunctional mitochondria trigger innate immunity signals and mitophagy regulates autoinflammation and immunogenicity. However, the regulators of these processes in β cells are not fully known. Here, we identified BCL2 Interacting Protein 3 (BNIP3) as critical for β cell mitophagy, health and immunogenicity in T1D.Methods: β cell function, mitochondrial function, ROS, mitochondrial DNA (mtDNA) damage and immunogenicity were assessed by microscopy, flow cytometry, ELISA, western blot and qPCR of sorted human β cells and EndoC-βH1 cells with knockdown (KD) or overexpression (OE) of BNIP3.Results: Mining of scRNA-seq HPAP dataset of T1D donor islets and inflamed islets from NOD mice showed a progressive BNIP3 reduction in β cells as T1D progressed. BNIP3 KD reduced insulin content and secretion, and expression of PDX1, NKX6.1 and NeuroD1 in human β cells. Seahorse assays showed impaired ATP production, basal OCR and proton leak. BNIP3 KD in human β cells increased Δψm (JC-1 staining) and ROS (MitoSOX staining), impaired mitophagy (Mito-QC reporter) and accumulated damaged mtDNA (PicoGreen staining). Damaged mitochondria release mtRNA and mtDNA, driving autoinflammation and immunogenicity. Stimulation of BNIP3 KD β cells with poly(I:C), a mimic of mitochondrial nucleic acids, increased IFNα and IFNβ, upregulated HLA-ABC, reduced HLA-G and enhanced CXCL10 and IFNγ receptor expression. Conversely, BNIP3 OE suppressed poly(I:C)-induced IFNα, IFNβ, HLA-ABC and CXCL10. BNIP3 KD in human β cells enhanced mitochondria-centered MAVS-RIG-I/MDA5 signaling and IRF3 and IRF7 activation. In co-culture assays, poly(I:C) stimulation of human β cells with BNIP3 KD promoted Jurkat T cell migration and increased IL6 in THP-1 macrophages.Conclusion: These results highlight BNIP3 as essential for β cell integrity, function and immunogenicity in T1D.DisclosureG. Lu: None. R. Kang: None. E. Oh: None. M.A. Varela: None. J. Aldaco: None. D.C. Thurmond: None. A. Garcia-Ocana: Consultant; Sun Pharmaceutical Industries Ltd.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-77-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 78-OR: KAYO-1732, a First-in-class Oral ALDH1A3 Inhibitor, Blocks Retinoid
Nuclear Receptor Signaling to Regenerate Pancreatic Islets and Reverse
Type 2 Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 78-OR
Abstract: Introduction and Objective: The increasing prevalence of type 2 diabetes (T2D), particularly in non-European ethnicities that exhibit high rates of β cell failure, necessitates the development of novel disease-modifying treatments to reverse diabetic progression. We have shown that aldehyde dehydrogenase 1a3 (ALDH1a3) is a key driver of β cell failure through its role in activating the retinoid nuclear receptor (RAR) pathway. The RAR pathway is clinically validated to drive T2D pathogenesis and cardiovascular mortality, yet has long been considered undruggable. Here we developed and tested a 1st-in-class, oral, small molecule ALDH1a3 inhibitor as a candidate therapy for T2D patients.Methods: We evaluated this ALDH1a3 inhibitor in rodent models of T2D and obesity to evaluate the effects on glycemic control, β-cell function, and multi-organ damage. Extensive ADME, pharmacokinetic and safety profiling were performed to advance the inhibitor to development candidate stage. Dose range-finding studies were conducted in rat and minipig to identify doses for IND-enabling studies.Results: Our novel ALDH1a3 inhibitor significantly improved glycemic control by promoting pancreatic β cell regeneration and further protected against diabetic kidney disease, dyslipidemia and liver damage. Moreover, the compound exhibited superior efficacy compared to GLP-1RAs in ameliorating metabolic dysfunction in diet-induced obesity models while promoting insulin sensitization.Conclusion: This 1st-in-class ALDH1a3 inhibitor demonstrates disease-modifying potential in preclinical models of T2D and cardiometabolic disease. These findings support the clinical development of this compound as a novel therapeutic strategy for T2D, particularly for patients with primary β-cell dysfunction.Disclosure M. Esposito: Board Member; Kayothera Inc. F. Briand: Employee; PHYSIOGENEX. Stock/Shareholder; PHYSIOGENEX.FundingNIH: National Institute of Diabetes and Digestive and Kidney Diseases (R43DK13642)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-78-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 79-OR: SEC31A: A Novel Regulator of Pancreatic Alpha-Cell Survival
Identified via Genome-Wide CRISPR Screen-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 79-OR
Abstract: Introduction and Objective: Glucagon is critical for glycemic control, yet its dysregulation contributes to type 1 (T1D) and advanced type 2 diabetes (T2D) progression. Although beta cell loss defines diabetes, alpha cells retain their mass despite stress. Mechanisms enabling alpha cell resilience in the diabetic milieu remain unclear. This study identified regulators of alpha cell survival during ER stress, integrating data from animal models and human tissues for translational insights.Methods: A genome-wide CRISPR screen in mouse alphaTC6 cells identified Sec31A, a key ER-Golgi transport regulator, as essential for alpha cell survival under ER stress. Sec31A knockdown models included C. elegans and alphaTC6 cells exposed to ER stress. Sec31A expression in human islets under cytokine stress was analyzed by immunohistochemistry (IHC). RNA sequencing (RNA-seq) was performed to investigate how SEC31A expression in live T1D islets changes with ER stress induction and mitigation. Functional studies in human alpha pseudo-islets with SEC31A knockdown examined insulin signaling pathways.Results: Sec31A deficiency improved alpha cell survival under ER stress in mouse and C. elegans models. Human islets showed higher Sec31A expression in alpha versus beta cells during cytokine stress. RNA-seq of T1D islets confirmed stress-induced SEC31A upregulation, which diminished when stress was mitigated.SEC31A knockdown in human pseudo-islets revealed alpha cell-specific pathways linked to insulin receptor interactions, highlighting mechanistic differences from beta cells.Conclusion: This study identifies Sec31A as a key regulator of alpha cell resilience during ER stress. By integrating model and human data, these findings enhance our understanding of alpha cell biology and provide a foundation for targeted therapies to preserve alpha cell function.Such interventions have the potential to prevent severe hypoglycemia and enhance glucose homeostasis in diabetes.DisclosureK. Shibue: None. S. Kahraman: Employee; Boehringer-Ingelheim. J.I. Castillo-Quan: None. D.F. De Jesus: None. J. Hu: None. K. Blackwell: None. P. Yi: None. R. Kulkarni: Advisory Panel; Novo Nordisk, Biomea Fusion, REDD Pharma, Inversago Pharma. Research Support; Inversago Pharma. Stock/Shareholder; Biomea Fusion.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-79-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 80-OR: STAT-Dependent β-Cell Extracellular Vesicle (EV) Programmed
Death-Ligand 1 (PD-L1) Shuttling Abrogates CD4+ T Cell Activation in Type
1 Diabetes (T1D)-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 80-OR
Abstract: Introduction and Objective: EVs are membrane-bound nanoparticles that contribute to cell:cell communication. β cell EV PD-L1 protein is increased by interferon (IFN) exposure and is able to bind and inactivate CD8+ T cells, suggesting a role in the interplay between β cell destruction and survival in T1D. However, mechanisms underlying β cell PD-L1 incorporation into EVs and its physiological effects are not completely understood.Methods: NIT-1 β cells were transfected with siRNA for STAT1+2 (vs. scramble control), then treated with 24h 2000 U/mL IFN-α (vs. vehicle). Murine NIT-1 β cells were transfected with PD-L1 to make PD-L1 overexpressing (PD-L1 OE) EVs. Anti-CD3 and CD28-activated nonobese diabetic mouse (NOD) splenocytes were treated with PD-L1 OE EVs. Flow cytometry-based assays tested functional impacts on CD4+ T cells. To test translational relevance, EV PD-L1 was quantified in pancreas slice perifusate from human organ donors with (n=11) or without (n=12) T1D using the ExoView-R200 imaging platform.Results: IFN-α treatment doubled β cell EV PD-L1 cargo without increasing EV numbers; this increase was abrogated by genetic STAT1/STAT2 inhibition. Compared to wild-type EVs, PD-L1 OE EVs suppressed CD4+ T cell proliferation (0.4-fold reduction in CTV dye dilution) and decreased CD69 and CD25 activation marker expression. Anti-PD-L1 antibody pre-treatment reversed these effects, confirming a specific role for EV PD-L1 in CD4+ T cell suppression. Pancreas slice EVs exhibited significant heterogeneity in EV PD-L1 content, but overall EV PD-L1 was increased in donors with T1D vs. nondiabetic controls.Conclusion: β cell EV PD-L1 is increased in pancreas slice perifusate from donors with T1D. STAT pathway activation is required for IFN-induced β cell EV PD-L1 shuttling. Increased β cell EV PD-L1 modulates CD8+ and CD4+ T cells, suggesting a key role in the β cell:immune system dialogue surrounding β cell destruction in T1D.DisclosureI. Amalaraj: None. C. Rao: None. S. Roy: None. J. Piganelli: None. E.K. Sims: Consultant; Sanofi. Speaker's Bureau; Med Learning Group. Other Relationship; American Diabetes Association.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-80-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 81-OR: Hide and Seek—Modulating PDL1 and HLA Class I Expression to
Protect Human β-Cells in T1D-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 81-OR
Abstract: Introduction and Objective: In type 1 diabetes (T1D), β-cells co-orchestrate their own demise by increasing their visibility to the immune system. The balance between HLA Class I and PDL1 expression is particularly critical: β-cells in T1D overexpress HLA Class I, increasing antigen presentation and immune targeting, but also upregulate PDL1, which promotes immune self-tolerance. Strategies to dissociate these mechanisms may aid development of novel T1D therapies.Methods: To study the misguided immune and β-cell dialogue in a relevant and scalable manner, we established three in vitro islet-immune injury models by culturing spheroids from primary human islets with proinflammatory cytokines, activated peripheral blood mononuclear cells or HLA-A2-restricted preproinsulin-specific cytotoxic T lymphocytes. We then modulated activity or expression of putative targets to investigate their effects on PDL1 and HLA Class I expression, β-cell function, survival and T cell infiltration.Results: In the established models, declining β-cell health manifested as increased basal and decreased glucose-stimulated insulin release, reduced intracellular insulin, loss of the first-phase insulin response and elevated proinsulin-to-insulin ratios. 3D microscopy revealed increased HLA Class I and PDL1 expression, and β-cell death. Extensive T cell infiltration and proinflammatory cytokine secretion confirmed immune activation in co-culture models. Liraglutide and HLA Class I blocking antibodies demonstrated anti-inflammatory and immune-protective effects, serving as controls for future studies. We are currently investigating TYK2-inhibitors and STAT2 knockdown as strategies for decoupling HLA Class I and PDL1 expression and immune protection. Our preliminary results shows TYK2 inhibition can protect islets from proinflammatory cytokine damage.Conclusion: The described biomimetic islet-immune assays provide scalable in vitro tools for studying interventions that can protect the β-cells from the immune-mediated attack that leads to T1D.DisclosureS. Jawurek: None. A.C. Title: None. C. Rufer: None. F. Forschler: Employee; InSphero AG. D.L. Eizirik: Advisory Panel; InSphero. B. Yesildag: Other Relationship; Novo Nordisk, Boehringer-Ingelheim, Eli Lilly and Company, Biomea Fusion, Biosplice Therapeutics, Abata Therapeutics, AstraZeneca, Amgen Inc.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-81-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 82-OR: RIPK1 Kinase Activity Regulates Cytokine-Induced β-Cell
Cytotoxicity-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 82-OR
Abstract: Introduction and Objective: Type 1 diabetes (T1D) is characterized by β-cell loss and insulin insufficiency. Receptor interacting protein kinase 1 (RIPK1) regulates survival and death signaling in non-islet cell types via its kinase and scaffolding functions. We observed that RIPK1 is expressed in mouse and human β-cells in situ and that Ripk1 is upregulated in aged NOD islets and β-cells from T1D donors. We hypothesized that RIPK1 kinase activity regulates cytokine-induced β-cell cytotoxicity.Methods: We treated control and Ripk1 gene-edited (Ripk1Δ) NIT-1 β-cells as well as control and RIPK1 kinase dead (RIPK1-D138N) mouse islets with TNFα+IFNγ for up to 72 hrs, then assessed gene expression, kinase signaling, caspase activity, and cell death. We also tested a RIPK1 kinase inhibitor (SZM679) and activator (BV6).Results: RNAseq revealed that TNFα- (Nfkb1, Jnk1, Casp3, Casp7) and IFNγ- (Sting1, cGas, Jak1, Stat2) related genes are differentially expressed in Ripk1Δ versus control NIT-1 β-cells. In islets, Ripk1, Jnk1, Jak1, Sting1, and Casp3 were upregulated with TNFα+IFNγ treatment, and these effects were blocked in RIPK1-D138N islets. Kinome profiling showed that TNFα- (IKBKB, ASK1/3, JNK1/2/3, MLKL) and IFNγ- (PKR, MTOR) related kinases are differentially activated in Ripk1Δ versus control NIT-1 β-cells. TNFα+IFNγ treatment increased RIPK1 phosphorylation at Ser161, caspase 3/7 activity, and cell death in NIT-1 β-cells, and these effects were blocked with SZM679 treatment or in Ripk1Δ cells. Similarly, TNFα+IFNγ treatment increased RIPK1 phosphorylation, caspase activity, and cell death in mouse islets, effects that were amplified with BV6 treatment and blocked in RIPK1-D138N islets.Conclusion: Our data indicate that RIPK1 kinase function promotes cytokine-induced β-cell cytotoxicity via actions on gene expression, kinase signaling, caspase activity, and cell death. Future studies are needed to determine whether therapies targeting RIPK1 kinase activity could protect β-cells in T1D.DisclosureC.J. Contreras: None. N. Mukherjee: None. K.A. Colglazier: Employee; Eli Lilly and Company. E. Mather: None. R.C. Branco: None. E.P. Cai: None. A.T. Templin: None.FundingNational Institutes of Health (P30 DK097512 to Indiana University Center for Diabetes and Metabolic Diseases, P30 DK017047 to University of Washington Diabetes Research Center, T32 DK064466 to Indiana University Diabetes and Obesity Research Training Program); Ralph W. and Grace M. Showalter Research Trust (08065700002B); U.S. Department of Veterans Affairs (IK2 BX004659, I01 BX001060)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-82-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 83-OR: GLP-1RA Efficacy Doubled with Small Molecule Modulators of Pyruvate
Kinase for Obesity Treatment-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 83-OR
Abstract: Introduction and Objective: To amplify insulin secretion from beta cells with nutrient-stimulated hormone (NuSH) receptor agonists (e.g., the GLP-1 RA liraglutide (LIRA)), mitochondria must be energized via substrate-driven ADP privation. Since small-molecule modulators of Pyruvate Kinase (mPK) energize mitochondria via the phosphoenolpyruvate cycle and further boost LIRA-amplified insulin secretion, we hypothesized that mPKs could also optimize obesity treatment with GLP-1 RAs.Methods: DIO C57BL/6J male mice (~45-50 g) treated once daily with placebo (PBO), LIRA (0.4 mg/kg), the mPK TEPP-46 (5 mg/kg), or mPK + LIRA (COMBO) for 5 wks had daily weights and IPGTTs at 1 and 4 wks. DEXA body composition, insulin secretion and Ca2+ oscillations were assessed in isolated islets at study end.Results: PBO-subtracted % change in weight was 4.7% with mPK, 12.3% with LIRA, and 23.6% with COMBO (95% CI for all groups); consequently, COMBO lost nearly twice as much weight as LIRA alone. The mPK only group demonstrated the greatest increase in lean mass (6.5%, p<0.05). COMBO demonstrated preservation of lean mass compared to PBO (lean-to-fat-mass ratio: 5.4 with COMBO vs 3.2 with PBO, p<0.05). By week 1, fasting glucose levels were significantly lower in all treatment groups compared to PBO. IPGTT AUC glucose and 60-min insulins were normalized in both LIRA and COMBO groups. There were no toxicity signals (normal blood gas, electrolytes, LFTs). Islet mass was increased in LIRA and COMBO groups and perifused islet hyperinsulinemia was normalized in all treatment groups. Notably, Ca2+ imaging of isolated islets (in the absence of mPK or LIRA), demonstrated the greatest increase in the duty cycle for the COMBO group, while all groups had markers of improved islet health (decreased amplitude, period, silent phase).Conclusion: Modulation of Pyruvate Kinase synergizes with the NuSH GLP-1 RA, liraglutide, to optimize treatment of obesity in DIO mice, doubling weight loss, while preserving lean mass, as well as improving insulin sensitivity and islet health.Disclosure R. Kibbey: Consultant; Structure Therapeutics, Inc. R.L. Cardone: None. I. Ruz-Maldonado: None. X. Zhao: None. S. Brown: None. H.R. Foster: None. M.J. Merrins: None.FundingNational Institutes of Health (R01DK127637)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-83-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 84-OR: siRNA-INHBE Silencing in Mice Recapitulates Human Genetic Data and
Demonstrates Improved Healthy Weight Loss Profile-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 84-OR
Abstract: Introduction and Objective: Heterozygous INHBE loss-of-function carriers have reduced abdominal fat, reduced risk for T2D and coronary artery disease, suggesting that lowering INHBE expression by 50% may restore a healthy metabolic profile in obesity. We investigated the impact of reducing Inhbe expression, via GalNAc-siRNA (INHBE-00003), on body weight and composition in a DIO mouse model, alone or added onto semaglutide.Methods: C57BL/6 mice were fed a high-fat diet and were treated with PBS or INHBE-00003 in PBS, alone or added onto daily semaglutide treatment. Body weight, fat pad weight, skeletal muscle weight, and adipose inflammation were assessed.Results: By 28 days after a single dose of INHBE-00003, DIO mice weighed 9% less, had 40% less diet-induced visceral adipose mass accumulation, and had 43% less diet-induced adipocyte enlargement than PBS-treated mice. Infiltration of activated macrophages in visceral adipose was also decreased by up to 68% compared with controls. Quadricep muscle mass was also preserved. After 28 days of semaglutide, DIO mice weighed 9% less than PBS-treated mice. INHBE-00003 added onto semaglutide increased weight loss to 18% by day 28, compared with PBS controls. In a separate study, mice treated with semaglutide for 28 days regained all weight that was lost by day 56. Mice also treated with INHBE-00003 on days 21 and 28 maintained weight loss relative to PBS controls.Conclusion: DIO mice treated with INHBE-00003 recapitulate human genetic findings for INHBE LoF, supporting the reduction of INHBE expression as means to support healthy weight loss. These preclinical data support INHBE-siRNA treatment as a potential next-generation anti-obesity agent for patients living with obesity and other metabolic co-morbidities. Wave Life Sciences expects to initiate a clinical trial for WVE-007, an investigational INHBE GalNAc-siRNA, for the treatment of people living with obesity, in 1Q 2025.Disclosure H. Yang: Employee; Wave Life Sciences. E. Ingelsson: None. K. Singh: Employee; Wave Life Sciences. J. Rheinhardt: None. A. Ghosh: None. K. Longo: None. L. Owen: None. P. Kandasamy: None. C.N. Vargeese: None. N. Iwamoto: None. M. Byrne: Employee; Wave Life Sciences.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-84-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 85-OR: A Novel Unimolecular Peptide Tetra-agonist (PTT-A) Targeting GLP-1,
GIP, Amylin, and Calcitonin Receptors with Superior Weight Loss Effects
vs. Tirzepatide While Preserving Muscle in DIO Rats-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 85-OR
Abstract: Introduction and Objective: The prevalence of obesity and associated disorders necessitates innovative approaches for safe and efficacious therapies. This study aims to characterize PTT-A, a novel unimolecular tetra-agonist in DIO rats and assess its efficacy against Tirzepatide.Methods: DIO rats were dosed for 3 weeks with PTT-A and Tirzepatide and multiple endpoints were examined, including body weight (BW), food intake (FI), body composition by carcass analysis and MRI, metabolic parameters and liver health.Results: Treatment with PTT-A at 10 and 30 nmol/kg over 21 days resulted in significant reductions in cumulative FI and BW (14.3±1.52% and 19.2±0.89% vs vehicle, respectively) driven by reductions in fat mass with no loss of muscle mass. Tirzepatide at 30 nmol/kg reduced BW only by 12.1±0.81% vs vehicle with a decrease in both fat and muscle mass. Gastrocnemius and soleus muscle weights were reduced by approximately 26% with Tirzepatide, with no reduction in muscle weight with PTT-A at same dose. Additionally, PTT-A exhibited robust efficacy in triglycerides lowering, insulin sensitization and liver health, as evidenced by reductions in plasma aminotransferase, plasma lipids, hepatic triglycerides, and liver histology, that surpassed Tirzepatide’s effects at equivalent doses.Conclusion: PTT-A represents a promising novel tetra-agonist that demonstrated enhanced efficacy in weight loss, insulin sensitization, lowering lipids and liver health relative to Tirzepatide. The profound BW reduction after 3 weeks treatment was through fat loss while preserving the muscle. These findings show the potential of tetra-agonists as multifaceted therapeutic options for addressing the challenges of obesity-related metabolic disorders.Disclosure S. Ghosh: Consultant; Pep2Tango Therapeutics, Abvance Therapeutics. P. Valdecantos: Research Support; Pep2Tango Therapeutics. P. Rada: Research Support; Pep2Tango Therapeutics. A.M. Valverde: Research Support; Pep2Tango Therapeutics. C.M. Rondinone: Employee; Pep2Tango Therapeutics.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-85-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 86-OR: The Amylin Receptor Selective Agonist NN1213 Reduces Food Intake
and Body Weight in Rats without Decreasing Calcium Plasma Levels-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 86-OR
Abstract: Introduction and Objective: Amylin analogues are being investigated as potential obesity treatments. Amylin receptors (AMYRs) belong to the calcitonin receptor (CTR) family and consist of heterodimers of the calcitonin receptor and receptor activity modifying proteins (RAMPs). CTR and AMYRs exhibit distinct physiological roles with CTR activation being important for calcium homeostasis, while AMYRs are involved in appetite regulation and body weight. It is however uncertain what the clinical role is of different receptor profiles. In this study we compare three amylin analogues in clinical development (cagrilintide, eloralintide and NN1213) on CTR and AMYRs activation as well as calcium lowering ability in rats to evaluate AMYR selectivity and furthermore address the efficacy on food intake and body weight reduction.Methods: Receptor potency was measured in vitro. Receptor selectivity was further investigated in rats, by measuring Ca2+ plasma levels after a single subcutaneous injection of vehicle, cagrilintide (10 nmol/kg), eloralintide (10 or 30 nmol/kg) or NN1213 (10 or 30 nmol/kg). In addition, the effect of NN1213 (10 nmol/kg, qd, sc.) on body weight and food intake was investigated in diet-induced obese rats during 17 days of dosing. Body weight and Ca2+ levels and food intake were analysed by a mixed effect model or 2-way repeated measure ANOVA, respectively, followed by Dunnett’s multiple comparison test.Results: In vitro, cagrilintide and eloralintide activated both rat and human AMYRs and CTR whereas NN1213 was more selective for AMYRs. In rats, cagrilintide and eloralintide induced a prolonged decrease in Ca2+ plasma levels in rats while NN1213 did not. Furthermore, NN1213 decreased body weight and food intake in diet-induced obese rats.Conclusion: Cagrilintide and eloralintide are both AMYR and CTR agonists whereas NN1213 is a selective AMYRs agonist that also decreases body weight in rats.Disclosure D. Ipsen: Employee; Novo Nordisk A/S. B. Ballarin-Gonzalez: Employee; Novo Nordisk. Stock/Shareholder; Novo Nordisk. E. Moo: Employee; Novo Nordisk. A. Secher: Employee; Novo Nordisk A/S. Stock/Shareholder; Novo Nordisk A/S. K. Raun: Employee; Novo Nordisk A/S. Stock/Shareholder; Novo Nordisk A/S.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-86-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 87-OR: The Impact of GIPR Agonism vs. Antagonism for Weight Loss and
Regain-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 87-OR
Abstract: Introduction and Objective: The incretin receptors glucagon-like peptide-1 (GLP-1R) and glucose-dependent insulinotropic polypeptide (GIPR) have become attractive targets for glucose control and weight loss. Somewhat paradoxically, both agonism and antagonism of the GIPR combined with GLP-1R agonism produce significant weight loss. Whether there are differentiating factors between the two strategies beyond weight loss remains unknown.Methods: We compared GIPR agonism versus antagonism, alone and in combination with GLP-1R agonism, in obese mice. We measured glucose tolerance before treatment, after weight loss, and following weight regain that occurs with cessation of treatment. We also compared rates of weight loss and weight regain, along with changes in body composition. For GIPR loss of function, we utilized an antibody antagonist, a peptide antagonist, and genetic deletion of the GIPR.Results: All approaches to reduce GIPR function enhanced weight loss achieved by GLP-1R agonism. Weight regain was delayed when GIPR loss of function was induced by a long-acting antibody or genetic deletion of Gipr, but not with a short-acting peptide antagonist. GIPR agonism combined with GLP-1R agonism achieved similar weight loss to GIPR antagonism + GLP-1R agonism. Glucose tolerance improved as a function of weight loss in all mice and returned to baseline values following weight regain. All approaches achieved weight loss primarily through loss of fat mass and not lean mass.Conclusion: Both GIPR agonism and antagonism produced similar effects on weight loss and weight regain, glucose tolerance, and body composition. The lasting effects of GIPR antagonism achieved by an antibody appears to be due to prolonged pharmacokinetics. Any potential differentiators in the metabolic effects of GIPR agonism versus antagonism remains unclear.DisclosureS.L. Lewandowski: None. D. D'Alessio: Consultant; Arrowhead Pharmaceuticals, Inc. Other Relationship; Eli Lilly and Company. Consultant; Gasherbrum Bio, Inc. Stock/Shareholder; MBX Biosciences. Consultant; Structure Therapeutics, Inc. Advisory Panel; Sun Pharmaceutical Industries Ltd. J. Campbell: Research Support; Eli Lilly and Company, Novo Nordisk. Advisory Panel; Structure Therapeutics, Inc. Research Support; Structure Therapeutics, Inc. Consultant; Arrowhead Pharmaceuticals, Inc. Advisory Panel; Boehringer-Ingelheim, Neurocrine, Roche Pharmaceuticals, Prostasis. Research Support; Merck & Co., Inc.FundingNational Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases (T32DK007012)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-87-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 88-OR: Long-Acting Amylin Analog AZD6234 in Combination with the GLP-1R
Agonist Semaglutide Enhances Body Weight and Fat Mass Loss in Diet-Induced
Obese (DIO) Rats-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 88-OR
Abstract: Introduction and Objective: AZD6234, a long-acting amylin analog in clinical development for weight management, reduces body weight (BW) in diet-induced obese (DIO) rats without a loss of lean mass. Semaglutide, a GLP-1R agonist, reduces BW with both fat mass and lean mass loss. Here, we aim to understand the impact of combined treatment of AZD6234 and semaglutide on body composition in DIO rats.Methods: Male Sprague Dawley DIO rats were injected QD SC with either vehicle, AZD6234 7.5 nmol/kg, semaglutide 5 nmol/kg or both for 28 days. Monotherapy doses were selected to achieve matching BW loss. BW and food intake were measured daily, and body composition was measured at baseline and end of study.Results: Treatment with AZD6234 or semaglutide led to an inhibition of food intake of ~-20 %, p<0.0001 compared to vehicle, while the combined treatment had an additive effect of -41%, p<0.0001. Treatment with AZD6234 or semaglutide showed similar BW loss (-9.3% and -9.9%, respectively) compared to vehicle (p<0.0001). Combined treatment resulted in an additive BW loss of -19.1%, p<0.0001. Vehicle-treated rats gained +22.8 g of fat mass and +9.9 g of lean mass from baseline. AZD6234 treated rats lost more fat mass than with semaglutide (-17.7 g, p<0.0001 and -11.4 g, p=0.0001, respectively), while combined treatment led to a loss of fat mass more than the sum of both monotherapies (-34.7 g, p<0.0001). AZD6234 treatment led to a preservation of lean mass (17.9 g, ns compared to vehicle), while both semaglutide (-0.3 g) and combined treatment (-4.7 g, p=0.0215) did not.Conclusion: Treatment with AZD6234 and semaglutide showed similar BW loss, but AZD6234 treatment led to more fat mass loss with the preservation of lean mass. Combined treatment led to additive effects on suppression of food intake, BW and fat mass loss.DisclosureG. Geoghegan: None. J.D. Brown: None. K.M. Mather: None. S. Will: Employee; AstraZeneca. S. Omar: Employee; AstraZeneca. D. Baker: Employee; AstraZeneca. D.C. Hornigold: Employee; AstraZeneca. Stock/Shareholder; AstraZeneca.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-88-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 89-OR: Modeling the Decline of Beta-Cell Function in Presymptomatic Stage
2 Type 1 Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 89-OR
Abstract: Introduction and Objective: Presymptomatic Stage 2 type 1 diabetes (T1D) is characterized by ≥2 autoantibodies and dysglycemia due to a progressive decline of β-cell function, eventually leading to symptomatic Stage 3 T1D. We aim to develop a risk progression model with the potential to assess the effectiveness of therapeutic interventions to delay T1D onset.Methods: Twenty-three individuals in Stage 2 T1D (Mean±SD: age=18±11 years, BMI=23±5 kg/m2, HbA1c=5.1±0.3%) underwent OGTT every 3±1 mo until their transition to Stage 3 T1D after 24±20 mo (NCT01030861). At each visit, plasma glucose and C-peptide concentrations were measured to estimate dynamic (Φd) and static (Φs) β-cell responsivity indices, using the C-peptide Oral Minimal Model. Their decline was modeled with an exponential decay that varies based on individual HbA1c to reflect the glucotoxicity, which speeds up the deterioration of β-cell function as the patient approaches Stage 3.Results: The model was effective at characterizing the C-peptide concentrations during the OGTTs (R2=0.98) and predicting the evolution of β-cell responsivity over time (Figure 1). The half-life of the decay was 25±17 mo and it worsens by 53±18% per %HbA1c.Conclusion: The proposed model effectively predicted the decline of β-cell function in individuals progressing from Stage 2 to Stage 3 T1D and could be used to optimize treatments aimed to delay the progression to clinical T1D.DisclosureJ. Bonet: None. A. Brunasso: None. E. Sundermann: Employee; Sanofi-Aventis Deutschland GmbH. E. Roesch: Employee; Sanofi. B. Wagenhuber: Employee; Sanofi-Aventis Deutschland GmbH. Stock/Shareholder; Sanofi. M. Schiavon: Research Support; Sanofi. C. Dalla Man: None.FundingSANOFI
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-89-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 90-OR: Effects of Glucagon-Like Peptide 1 (GLP-1) Agonist Therapy on Islet
Function in Adults with Pancreatic-Insufficient Cystic Fibrosis ( PI-CF)
and Abnormal Glucose Tolerance (AGT)—Preliminary Results-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 90-OR
Abstract: Introduction and Objective: Preserving β-cell function may delay or prevent progression to CF-related diabetes, a major comorbidity in people with PI-CF. This study aimed to evaluate whether weekly GLP-1 agonist therapy improves β- and α-cell function and post-prandial glucose tolerance in people with PI-CF and AGT. Methods: In this randomized, open-label, cross-over study, participants received dulaglutide 0.75 mg weekly for 6 doses, with a matched 6-week observation period. Mixed-meal tolerance tests (MMTT) were performed at each period start and end. Non-parametric methods estimated between-condition differences in change in biomarkers of islet function (C-peptide, glucagon, glucose) as assessed by area under the curve (AUC) at 30 and 180 min.Results: To date, 11 participants with PI-CF and AGT (mean±SE age 26.9 ± 2.2 y, BMI 27.3 ± 1.8 kg/m2, HbA1c 5.7 ± 0.1%) have completed the study. Early-phase C-peptide (incremental AUC at 30 min) in the dulaglutide period was lower when compared to observation (p<0.05), but when adjusted for glucose showed an increase (iAUCC-pep/iAUCglc ratio, Δ 0.25 ng-min/mg %, p<0.01). Total glucagon AUC at 180 min was lower in the dulaglutide period (16.4% decrease vs 1.8% increase, p<0.05). Glucose at 30 and 180 min trended lower in the dulaglutide period (-4202.3 mg-min/dL, p=0.06). A weak trend for weight reduction during treatment vs observation periods was observed (−1.88 kg ± 0.89 vs −0.14 kg ± 0.55, p=0.18). Some subjects reported worsening acid reflux (n=3) and constipation (n=4) in the dulaglutide period. Conclusion: GLP-1 agonist therapy in patients with PI-CF and AGT appears to enhance early-phase β-cell insulin secretion and suppress α-cell glucagon secretion. These effects may contribute to an improvement in post-prandial glucose tolerance. Patients with PI-CF should be cautioned regarding acid reflux and constipation when considering GLP-1 agonist therapy.DisclosureS. Reddy: None. R.R. Bhatia: None. A. Peleckis: None. P. Alvarado: None. R. Walega: None. D. Stefanovski: None. R.J. Gallop: None. D. Hadjiliadis: None. A. Flatt: Employee; Vertex Pharmaceuticals Incorporated. R.C. Rubenstein: None. C.L. Chan: None. A. Kelly: None. M.R. Rickels: Consultant; Vertex Pharmaceuticals Incorporated, Sernova, Corp. Research Support; Dompé, Tandem Diabetes Care, Inc. Consultant; Novo Nordisk.FundingNational Institutes of Health (R01 DK97830, UL1 TR001878, and P30 DK019525)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-90-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 91-OR: Imaging β-Cell Response to Oral Glucose Stimulation with
Quantitative Blood Oxygenation Dependent (qBOLD) MRI-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 91-OR
Abstract: Introduction and Objective: The failure of pancreatic β-cells is a central feature of diabetes, yet measures of β-cell function in humans, such as clamp-derived variables, are invasive and sensitive to other factors (i.e., insulin resistance, insulin clearance, etc.). Since glucose-stimulated insulin release is coupled to pancreas oxygen consumption, we tested qBOLD MRI as a non-invasive proxy of spatiotemporal β-cell function during oral glucose-stimulated insulin secretion.Methods: Adults (age >18 years) were included across two groups: type 2 diabetes (T2D, n=4; BMI >30kg/m2; within 5 years of diagnosis) and healthy controls. (HC, n=6). Participants had a 75-gram oral glucose (OG) load and simultaneous qBOLD MRI of pancreas volume at fasting and up to 15 minutes post load. Dynamic change in MRI parameter, ΔT2*, was quantified across glucose ingestion, and mean (SD) post-glucose ΔT2* values were compared between groups. The T2D group had an additional OG load (separate day) within 2 weeks prior/after MRI, and C-peptides across 240 minutes (AUC) were correlated (Pearson r) with AUC ΔT2* for T2D.Results: Post-glucose ΔT2* values decreased (i.e. negative ΔT2*) consistent with increased oxygen consumption during β-cell insulin secretion (T2D -14.7 (7.4) % and HC -5.3 (7.7) %). ΔT2* AUC decreases (0-15min) were larger in T2D than HC (-17.1 (8.20) vs. -0.76 (1.04); p=.001). There was a strong positive correlation between C-peptide AUC (0-20min) and ΔT2* AUC (0-15min) in T2D patients (r =.95, p=.05), suggesting a relationship between MRI-derived β-cell metabolic activity and β-cell secretory activity.Conclusion: Initial quantification of dynamic T2* values over the entire pancreas using OG qBOLD MRI shows group differences and sensitivity to β-cell function. OG qBOLD demonstrates spatial and temporal heterogeneity of ΔT2* after glucose ingestion, holding potential to assess regional and temporal changes in pancreas function with disease severity.DisclosureD.A. Reiter: None. E. Ray: None. A. Horner: None. S. Edwards: None. O. Oladejo: None. P. Vellanki: Advisory Panel; Eli Lilly and Company.FundingNational Institutes of Health (DK129627)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-91-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 92-OR: Evaluating Intact Proinsulin, Des-31,32 Proinsulin, and Des-64,65
Proinsulin as Potential Biomarkers of Type 1 Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 92-OR
Abstract: Introduction and Objective: Persistent proinsulin secretion and elevated proinsulin-to-C-peptide ratios have been reported in T1D. However, the potential of individual proinsulin proteoforms as biomarkers in T1D has not been evaluated due to the challenges associated with assay specificity. Herein, we present the first assessment of intact proinsulin, des-31,32 proinsulin, and des-64,65 proinsulin using a newly developed liquid chromatography-mass spectrometry (LC-MS)-based assay.Methods: The LC-MS assay utilized a cocktail of three monoclonal antibodies for enrichment, followed by LC-MS measurement. Serum samples from at-risk individuals (positive for two or more autoantibodies), new onset T1D subjects, and controls matched for age and sex (n=20 per group) were used for the initial assessment.Results: The LC-MS assay for measuring proinsulin proteoforms and C-peptide achieved a lower limit of quantification in the 1-5 pg/mL range, offering superior sensitivity and specificity than the Mercodia proinsulin assay. Across 80 samples, median levels were 915 pg/mL for C-peptide, 23.1 pg/mL for intact proinsulin, 46.2 pg/mL for des-31,32, and 4.6 pg/mL for des-64,65. The ratios of each of the three proinsulin proteoforms to C-peptide were significantly higher in T1D compared to controls, though no significant differences were observed between at-risk subjects and controls. Notably, the des-31,32-to-C-peptide ratio emerged as the most promising biomarker for differentiating T1D from controls. Moreover, the ratios of intact proinsulin, des-31,32, and des-64,65 to C-peptide showed poor correlation (R² ~0.5), suggesting they may serve as biomarkers for distinct etiologies of beta cell stress. Further assessment of the prognostic values of these markers is ongoing with an expanded sample set.Conclusion: All three proinsulin proteoforms displays promising and distinctive features in differentiating T1D subjects versus matched controls.DisclosureQ. Shen: None. W. Cao: None. T. Lin: None. C. Evans-Molina: Advisory Panel; DiogenX. Research Support; Bristol-Myers Squibb Company, Lilly Diabetes. Advisory Panel; Isla Technologies, Neurodon. Research Support; Neurodon. E.K. Sims: Consultant; Sanofi. Speaker's Bureau; Med Learning Group. Other Relationship; American Diabetes Association. J. Qu: None. W. Qian: None.FundingNational Institutes of Health (U01DK137113)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-92-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 93-OR: Early Defects of Beta-Cell Function Are Associated with Disrupted
BAG3-Insulin Colocalization in Humans Islets-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 93-OR
Abstract: Introduction and Objective: Alterations in first-phase insulin secretion are pivotal in the early development of type 2 diabetes mellitus (T2DM). The multifunctional protein BAG3 has been implicated in regulating insulin secretion in murine models, but its role in humans remains unexplored. This study investigates the expression of BAG3 in human pancreatic islets and its relationship with β-cell functionality in a cohort of non-diabetic subjects.Methods: Pancreatic tissue samples were obtained from 12 non-diabetic patients enrolled for partial pancreatectomy. Patients underwent deep metabolic evaluation, including oral glucose tolerance test (OGTT), hyperglycemic clamp and euglycemic hyperinsulinemic clamp. Immunofluorescence and confocal microscopy were used to assess BAG3-insulin colocalization in islets. Metabolic and histological findings were correlated with BAG3 expression, categorizing subjects into LOW and HIGH BAG3 groups based on Pearson’s correlation coefficient of BAG3-insulin colocalization.Results: Patients with HIGH BAG3 expression exhibited significantly impaired first-phase insulin secretion, evidenced by reduced rate sensitivity during OGTT and higher plasma glucose levels at 30 and 60 minutes post-glucose challenge. Islets from HIGH BAG3 patients showed increased size but no differences in insulin/glucagon ratios or insulin sensitivity, suggesting a specific disruption in the insulin secretory machinery rather than β-cell mass or insulin resistance.Conclusion: BAG3 appears to modulate first-phase insulin secretion in humans by influencing the insulin granule exocytosis process. Targeting BAG3-related pathways could represent a novel therapeutic approach to prevent or delay β-cell dysfunction and the onset of T2DM.DisclosureG. Ciccarelli: None. G. Di Giuseppe: None. V. Damiani: None. M. Brunetti: None. G. Gliozzo: None. L. Soldovieri: None. F. Cinti: None. A. Giaccari: Board Member; Novo Nordisk A/S. Speaker's Bureau; AstraZeneca, Sanofi. Advisory Panel; Sanofi. Speaker's Bureau; Guidotti. V. De Laurenzi: None. T. Mezza: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-93-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 94-OR: The Glucagonotropic Effect of Glucose-Dependent Insulinotropic
Polypeptide Is Negated during Insulin-Induced Hypoglycemia in Persons with
Type 1 Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 94-OR
Abstract: Introduction and Objective: The gut-derived hormone, glucose-dependent insulinotropic polypeptide (GIP[1-42]), increases glucagon levels during normal-to-low plasma glucose concentrations in persons with type 1 diabetes (T1D); potentially safeguarding against hypoglycemia. Here, we evaluated the effects of exogenous GIP[1-42] and its naturally occurring truncated variant GIP[1-30]NH2, on glucagon secretion during insulin-induced hypoglycemia in persons with T1D.Methods: Men with T1D were included in a randomized, double-blind, placebo-controlled, crossover study involving five study days. Each day was initiated at euglycemia, and involved an iv infusion (time 0-135 min) of GIP[1-42] (4 or 8 pmol/kg/min), GIP[1-30]NH2 (4 or 8 pmol/kg/min), or placebo (saline). On all days, insulin (1.5 mU/kg/min) was infused, and blood glucose kept >2.5 mmol/l (time 30-90 min), after which recovery was monitored (90-135 min). The primary outcome was plasma glucagon baseline-subtracted area under the curve (bsAUC) and secondary outcomes included absolute plasma glucagon concentrations and amount of glucose infused.Results: Ten individuals were included (age [mean±SD]: 31±10 years, BMI: 24±3 kg/m2, HbA1c: 6.6±0.6 %, stimulated C-peptide: 31±22 pmol/l). Both GIP variants increased plasma glucagon compared with placebo before initiating the insulin infusion, but this effect was negated during the insulin infusion, and no significant differences were found in bsAUC for glucagon between interventions. During high-dose GIP[1-42], less glucose was required to recover from hypoglycemia compared to placebo (0.14±0.08 vs. 0.19±0.09 g/kg, P = 0.03)Conclusion: In persons with T1D, exogenous GIP increased plasma glucagon levels during euglycemia, but insulin-induced hypoglycemia eliminated this effect. Nevertheless, high-dose GIP[1-42] reduced the amount of glucose needed to recover from hypoglycemia.DisclosureN.E. Sørum: None. J. Warnøe: None. J.J. Holst: Advisory Panel; Novo Nordisk A/S. Consultant; Novo Nordisk A/S. Other Relationship; Novo Nordisk A/S. Consultant; AstraZeneca, Fractyl Health, Inc., MSD Life Science Foundation, Structure Therapeutics, Inc. B. Hartmann: Employee; Bainan Biotech. L.S. Gasbjerg: Stock/Shareholder; Antag Therapeutics, Bainan Biotech. J. Størling: Stock/Shareholder; Novo Nordisk A/S. T.F. Dejgaard: Advisory Panel; Novo Nordisk A/S. Speaker's Bureau; Novo Nordisk A/S. Research Support; Novo Nordisk A/S. Speaker's Bureau; Boehringer-Ingelheim. Advisory Panel; Eli Lilly and Company, Medtronic. M.B. Christensen: None. F.K. Knop: Consultant; 89bio, Inc, AstraZeneca. Speaker's Bureau; AstraZeneca. Advisory Panel; Boehringer-Ingelheim. Consultant; Cytoki Pharma. Advisory Panel; Eli Lilly and Company. Consultant; Eli Lilly and Company. Speaker's Bureau; Eli Lilly and Company. Research Support; Gubra. Advisory Panel; Novo Nordisk A/S. Consultant; Novo Nordisk A/S. Employee; Novo Nordisk A/S. Research Support; Novo Nordisk A/S. Speaker's Bureau; Novo Nordisk A/S. Stock/Shareholder; Novo Nordisk A/S, Eli Lilly and Company. Advisory Panel; Sanofi. Consultant; Structure Therapeutics, Inc. Advisory Panel; Zealand Pharma A/S. Consultant; Zealand Pharma A/S. Research Support; Zealand Pharma A/S. Speaker's Bureau; Zealand Pharma A/S. Stock/Shareholder; Zealand Pharma A/S, Gubra. Advisory Panel; Zucara Therapeutics. Consultant; Zucara Therapeutics. Stock/Shareholder; Antag Therapeutics. A.B. Lund: Consultant; Zealand Pharma A/S. Advisory Panel; Eli Lilly and Company. Research Support; Novo Nordisk. Speaker's Bureau; Novo Nordisk, Boehringer-Ingelheim.FundingThe Leona M. and Harry B. Helmsley Charitable Trust
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-94-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 95-OR: Identification of a Novel Subset of Cold-Activated Hypothalamic
Neurons That Stimulate Feeding-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 95-OR
Abstract: Introduction and Objective: Growing evidence suggests that neurocircuits within the hypothalamus coordinate the function of two key and interdependent physiologic processes: thermoregulation and energy homeostasis. Based on our preliminary evidence of a novel subset of neurons expressing tyrosine hydroxylase (TH) located in the rostral hypothalamus that are activated by cold exposure, we sought in the current work to 1) anatomically map with more precision this previously unrecognized subpopulation and, 2) determine if this population plays a role in the regulation of energy intake.Methods: To accomplish these goals, C57Bl6 mice were acutely exposed to either a cold (10 °C) or warm environment (30 °C) for 90 min. Animals were then sacrificed, and the hypothalamus was collected and processed for immunohistochemical analysis of TH(+) and cFos, a marker for neural activation. To determine whether activation of PeVNTH neurons is sufficient to increase food intake, TH-Cre animals underwent microinjection of a stimulatory DREADD (hM3Dq) directed to the PeVN.Results: Compared to housing in a warm environment, exposure to cold increased both the number and % of TH neurons expressing cFos selectively in the periventricular hypothalamic nucleus (PeVN) (22.5 ± 1.2% for cold vs. 5.0 ± 1.3% for warm, a ~4-fold increase; p=0.0003). In contrast, cFos expression was not increased by cold exposure in other hypothalamic TH-expressing subpopulations, including the paraventricular nucleus (PVN) (p=ns) and arcuate nucleus (ARC) (p=ns). Additionally, we found that relative to vehicle-treated controls, food intake was robustly increased following CNO-induced activation of PeVNTH neurons (0.94 ± 0.18g with CNO vs. 0.28 ± 0.09g with vehicle, a ~3-fold increase; p<0.01).Conclusion: These findings implicate a novel subset of cold-activated hypothalamic TH neurons in the regulation of food intake.DisclosureC.A. Watts: None. I.K. Redford: None. C. Bryan: None. B.N. Phan: None. V. Damian: None. K. Kadlec: None. E.L. Yamashita: None. J.M. Scarlett: None. M.W. Schwartz: Consultant; NodThera, Olio Labs, PriveBio. G.J. Morton: Research Support; Novo Nordisk A/S.FundingNIDDK T32 Trainee Award (T32DK007247); National Institute of Health (RO1 DK089056, R01 DK124238, P30 DK035816)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-95-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 96-OR: Disruption of Leptin Receptor in Choroid Plexus Epithelial Cells
Impairs Feeding Regulation and Weight Control-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 96-OR
Abstract: Introduction and Objective: The choroid plexus (ChP), located in each ventricle of the brain, is recognized as a potential site for leptin transport via short- and long-form leptin receptor (LepR). However, knowledge of how LepR in the ChP regulates leptin transport and energy metabolism remains limited. We investigated the role of LepR in Foxj1-expressing ChP cells in leptin transport and body weight regulation.Methods: Mice lacking LepR in Foxj1-expressing cells (Foxj1-Cre; LepRloxP/loxP) and LepRloxP/loxP mice were fed chow or high-fat diet (HFD). Foxj1 is enriched in ChP epithelial cells. We evaluated body weight, fat mass, serum hormones, food intake, leptin-stimulated food intake, and hypothalamic Stat3 phosphorylation. The interaction between LepR and LRP1 was measured by PLA. Leptin uptake and release were determined in cultured cell lines.Results: Foxj1-Cre-driven LepR deletion reduced LepR expression in ChP by ~80%. On a chow diet, deletion of LepR in Foxj1-expressing cells of the ChP modestly increased body weight and fat mass due to hyperphagia with elevated serum insulin and leptin but normal glucose. Importantly, leptin’s ability to suppress food intake and enhance hypothalamic pStat3 was significantly impaired in these mice. Under HFD, LepR deficiency further exacerbated weight gain and adiposity. Mechanistically, we found that leptin induces the physical interaction between LepR and LRP1 in the ChP. In vitro study demonstrated that leptin uptake and release were significantly reduced in ChP-derived Z310 epithelial cells lacking LepR. Conversely, LepR overexpression in Neuro-2a cells markedly increased leptin uptake and release.Conclusion: These findings suggest that LepR in Foxj1-expressing cells is required to regulate leptin transport, affecting feeding and body weight homeostasis. Thus, our study uncovers a new cellular mechanism in which LepR in the ChP functions as a key mediator of leptin transport, maintaining metabolic homeostasis.DisclosureK. Rodrigues: None. W. Yang: None. J. Young: None. M. Lee: None. F. Timzoura: None. V. Prevot: None. Y. Kim: None.FundingAmerican Diabetes Association (1-25-PDF-49); RO1DK1230023RO1DK129946-03
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-96-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 97-OR: RNA m6A Methylation Controls the Central Melanocortin System,
Energy Balance, Body Weight, and Metabolism-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 97-OR
Abstract: Introduction and Objective: METTL14 is an essential component of the N6-methyladenosine (m6A) writher that installs m6A on RNA. RNA m6A modification shapes intracellular proteostasis by controlling RNA metabolism/fate, thereby regulating cell fate and functions. We aimed to delineate the role of POMC neuron METTL14 in the development and metabolic function of the central melanocortin system.Methods: We generated conditional METTL14 knockout mice using Cre/loxp system. For POMC neuron-specific expression of METTL14, Cre-dependent AAV9-DIO-METTL14 vector was microinjected into the arcuate nucleus (ARC) of POMC-Cre mice. Energy balance was assessed using metabolic cages. Glucose metabolism and insulin resistance were assessed using by glucose and insulin tolerance tests, respectively. Liver lipid levels were assessed by chemical and histological assays. RNA m6A methylation was measured by RNA immunoprecipitation. POMC neurons and their projections were assessed by immunostaining.Results:Mettl14ΔPOMC mice progressively developed obesity, glucose intolerance, insulin resistance, and liver steatosis. Food intake was significantly higher, whereas energy expenditure was lower in Mettl14ΔPOMC mice. Conversely, METTL14 overexpression protected against diet-induced obesity and metabolic disorders. POMC neurons in the ARC were dramatically lower in Mettl14ΔPOMC than in Mettl14f/f mice. METTL14 deficiency decreased proliferation of POMC progenitor cells and blocked POMC neurogenesis. At the molecular level, METTL14 induced m6A methylation of Isl1 mRNA and increased synthesis of ISL1, a key transcription factor for POMC neurogenesis.Conclusion: The METTL14/m6A pathway is required for POMC neurogenesis. METTL14-based epitranscriptomic reprogramming of the central melanocortin system controls energy balance, body weight and metabolism, and serves as a potential target for the treatment of obesity and obesity-associated metabolic disease.DisclosureY. Li: None. W. Zhang: None. L. Rui: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-97-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 98-OR: Melanocortin 4 Receptor–Mediated Effects Require
Beta-Arrestin 2 Signaling-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 98-OR
Abstract: Introduction and Objective: Obesity is the leading cause of type 2 diabetes (T2D), driving metabolic dysfunction through complex neuroendocrine and signaling pathways. The melanocortin-4 receptor (MC4R), a critical regulator of energy balance and glucose homeostasis, has emerged as a key therapeutic target for obesity and associated metabolic disorders. The MC4R is coupled to Gs and other heterotrimeric G proteins but can also engage beta-arrestin 2 (barr2), a cytoplasmic protein that modulates receptor signaling and trafficking and can also act as signaling protein in its own right. Interestingly, specific MC4R variants with enhanced barr2 recruitment confer up to a 50% lower risk of developing obesity, T2D, and related metabolic disorders. However, the molecular mechanisms by which barr2 regulates MC4R-dependent metabolic outcomes remain unexplored. For this reason, we investigated the potential role of barr2 in regulating MC4R-mediated metabolic effects and the underlying molecular mechanisms.Methods: We generated and analyzed mice that lacked barr2 specifically in MC4R-expressing neurons (MC4R-barr2-KO mice).Results: Compared to control littermates, the MC4R-barr2-KO mice showed enhanced food intake, increased adiposity, glucose intolerance, and insulin resistance. To more directly investigate the role of barr2 in MC4R-mediated signaling, we injected MC4R-barr2-KO mice and control littermates with melanotan II (MTII), a potent MC4R agonist. While MTII reduced food intake in control mice, this effect was greatly reduced in MC4R-barr2-KO mice. Interestingly, selective re-expression of barr2 in the paraventricular nucleus of MC4R-barr2-KO mice restored control-like MTII effects.Conclusion: These data highlight the key role of barr2 in mediating the beneficial metabolic effects of MC4R signaling on energy and glucose homeostasis. MC4R agonists capable of recruiting barr2 with high efficacy may prove therapeutically useful as novel anti-obesity drugs.DisclosureM. Rashid: None. O. Gavrilova: None. Z. Cui: None. J. Wess: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-98-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 99-OR: AgRP Neuron Hyperactivity Drives Hyperglycemia in a Mouse Model of
Type 2 Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 99-OR
Abstract: Introduction and Objective: Growing evidence that dysfunction of brain control mechanisms plays a causal role in the pathogenesis of type 2 diabetes (T2D) has led to novel, brain-targeted therapeutic strategies. As one example, a single intracerebroventricular (icv) injection of fibroblast growth factor 1 (FGF1) can normalize hyperglycemia for weeks or months in rodent models of T2D, despite having no long-term effect on food intake or body weight. Based on a series of convergent findings, a particular subset of neurons has been identified as potential mediators of this FGF1 effect. Specifically, AgRP neurons, which are located in the hypothalamic arcuate nucleus (ARC), are hyperactive in Lepob/ob mice and other rodent models of T2D, and they are inhibited by FGF1 both in vivo and in an ex vivo slice preparation.Methods: To investigate whether chronically reducing AgRP neuron activity can mimic the antidiabetic action of FGF1, we directed an adeno-associated virus (AAV) containing a cre-inducible tetanus toxin (TeTx)-GFP cassette (or cre-inducible AAV GFP control) to the ARC of obese, diabetic Lepob/ob mice in which Cre recombinase is expressed solely by AgRP neurons (Lepob/ob AgRP-Cre mice).Results: We report that over a 10-wk observation period, hyperglycemia was fully normalized by TeTx-mediated AgRP neuron inactivation, whereas changes in energy homeostasis parameters (food intake, energy expenditure, body weight and fat mass) were not observed. AgRP neuron inactivation also reduced circulating insulin and corticosterone levels in these mice compared to GFP controls.Conclusion: These findings further implicate AgRP neuron silencing as a mediator of the antidiabetic action of FGF1, and demonstrate that in diabetic Lepob/ob mice, AgRP neuron hyperactivity is required for hyperglycemia but is dispensable for hyperphagia and obesity.DisclosureY. Gou: None. M. Glat: None. V. Damian: None. C. Bryan: None. B.N. Phan: None. A. Trivedi: None. M.K. Hwang: None. J.M. Scarlett: None. G.J. Morton: Research Support; Novo Nordisk A/S. M.W. Schwartz: Consultant; NodThera, Olio Labs, PriveBio.FundingNational Institutes of Health Grants DK083042 and DK101997 (to MWS), DK089056, DK124238, and S10OD036208 (to GJM), DK128383 (to JMS), the Nutrition Obesity Research Center (DK035816), and Diabetes Research Center (DK17047) at the University of Washington, a Department of Defense grant W81XWH2110635 (to JMS), a research agreement between MWS and Novo Nordisk, and a UW Cystic Fibrosis Foundation Funded Fellowship grant GR041446 (to YG).
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-99-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 100-OR: Hypothalamic Fibroblast Growth Factor-1 Signaling Is Required for
Normal Energy and Glucose Homeostasis-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 100-OR
Abstract: Introduction and Objective: The brain is a primary target for the beneficial metabolic effects of members of the fibroblast growth factor (FGF) family. For example, our group and others have shown that a single intracerebroventricular (icv) injection of fibroblast growth factor-1 (FGF1) induces both transient anorexia and weight loss and sustained remission of diabetic hyperglycemia in rodent models of type 2 diabetes (T2D) via actions involving the mediobasal hypothalamus (MBH). While FGF1 is endogenously expressed in the MBH, its role in metabolic physiology is unknown. The goal of the current studies was to determine the role of endogenous FGF1 in the regulation of energy balance.Methods: To test whether MBH FGF1 plays a physiological role in energy and/or glucose homeostasis, we selectively deleted FGF1 from either MBH neurons or from tanycytes of adult male FGF1-floxed (FGF1fl/fl) chow-fed mice. The former was achieved by microinjecting either AAV1-hSyn-Cre-WPRE.hGH or control AAV1-CAG-GFP into the MBH bilaterally, whereas the latter involved microinjecting either TAT-Cre or heat-inactivated control TAT-Cre into the 3rd ventricle.Results: We report that FGF1 deletion specifically from MBH neurons caused an obesity phenotype associated with hyperphagia and glucose intolerance (*p<0.05 for each). Interestingly, this phenotype was also characterized by pronounced disruption of circadian patterns of feeding, in which animals consumed a greater proportion of food intake during the light cycle, and it was complemented by decreased daily energy expenditure and decreased dark cycle locomotion. By comparison, selective FGF1 deletion from tanycytes resulted in greater percent change in body weight (*p<0.05), but no other detectable metabolic abnormalities were observed in the animals.Conclusion: Based on these findings, we conclude that endogenous FGF1 expression by MBH neurons, but not tanycytes, is required for normal energy homeostasis and glucose metabolism.DisclosureP. Choi: None. B.N. Phan: None. C. Bryan: None. M.K. Hwang: None. G.J. Morton: Research Support; Novo Nordisk A/S. M.W. Schwartz: Consultant; NodThera, Olio Labs, PriveBio. J.M. Scarlett: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-100-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 101-OR: Spatial and Single-Cell Analysis of Youth-Onset Type 2 Diabetes
Reveals Diabetic Kidney Disease as a Myeloid and T-Cell Activation
Disorder with Senescence-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 101-OR
Abstract: Introduction and Objective: Metabolic bariatric surgery (MBS) offers therapeutic benefit in youth-onset type 2 diabetes (Y-T2D) but its impact on DKD pathophysiology is poorly understood. We aimed to evaluate immune, fibrotic, and senescent changes in DKD and effects of MBS.Methods: Kidney biopsies from lean controls (LC; n=10), Y-T2D at baseline (n=8) and 12-months post-MBS (n=5) were analyzed using scRNA-seq and Visium. Pseudobulk differential expression was performed. Cell-type deconvolution, spatial gene-set scoring and cell-cell interaction analysis characterized kidney microarchitecture.Results: At baseline, Y-T2D exhibited significant immune activation (e.g., HLA class I/II upregulation) and cell senescence, with myeloid infiltration and T cell activation compared to LC. Fibroblast interactions were prominent, indicating a pro-inflammatory, pro-fibrotic environment. Post-MBS, T cell activation was reduced but senescence and myeloid infiltration persisted with no significant changes in key cell types (e.g., PT-S1/S2, fibroblasts; p > 0.2) (Figure 1).Conclusion: DKD in Y-T2D is characterized by myeloid and T cell activation, cellular senescence and fibrosis. MBS provides partial resolution of inflammation but not senescence or myeloid infiltration, which may potentially be addressed by cell therapy and senotherapy.DisclosureL. Yuan: None. Y. Choi: None. F. Alakwaa: None. N. Nguyen: None. P. Narongkiatikhun: None. J. Goodrich: None. K.L. Tommerdahl: None. K.J. Nadeau: None. J.R. Ryder: Board Member; Calorify. Research Support; Boehringer-Ingelheim, Eli Lilly and Company, Recordati. T. Inge: Consultant; Mediflix, UpToDate, Teleflex, Medtronic, Eli Lilly and Company, BrainStorm Cell Therapeutics, Standard Bariatrics. J.B. Hodgin: None. J.A. Schaub: Consultant; Klick. Research Support; AstraZeneca, Roche Genetech, Novo Nordisk, Eli Lilly and Company. A. Naik: None. P.J. McCown: None. F.C. Brosius: Consultant; MAKSCIENTIFIC. R.G. Nelson: None. M. Kretzler: Research Support; AstraZeneca, Boehringer-Ingelheim, Chinook Therapeutics, Inc, Eli Lilly and Company, Moderna, Inc, Janssen Pharmaceuticals, Inc, National Institutes of Health, European Union. Advisory Panel; Novartis Pharmaceuticals Corporation. Research Support; Novo Nordisk. Advisory Panel; Otsuka America Pharmaceutical, Inc. Research Support; Regeneron Pharmaceuticals, Renalytix, Roche Pharmaceuticals, Sanofi, Travere, Certa, Dimerix. P. Bjornstad: Consultant; AstraZeneca, Bayer Pharmaceuticals, Inc, Lilly USA LLC, Novo Nordisk. L. Pyle: None.FundingNIDDK P30 DK081943NIDDK (P30 DK116073); JDRF (2-SRA-2019-845-S-B)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-101-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 102-OR: Long-Term Kidney Outcomes following Metabolic and Bariatric
Surgery in Adolescents with Severe Obesity-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 102-OR
Abstract: Introduction and Objective: Although metabolic and bariatric surgery (MBS) improves kidney function in adolescents with severe obesity up to 3 years post-surgery, long-term kidney outcomes remain unclear. This study evaluated 8-year kidney outcomes in adolescents following MBS.Methods: Data from the Teen-Longitudinal Assessment of Bariatric Surgery (Teen-LABS) study, a multicenter cohort of 274 adolescents undergoing MBS, were analyzed. Urine albumin-to-creatinine ratio (ACR) and cystatin C-based estimated glomerular filtration rate (eGFR) were assessed pre- and 8 years post-surgery. Mean differences were compared via Wilcoxon signed-rank and paired t-tests (α=0.05).Results: Participants [mean preoperative age: 16.7±1.6 years; median preoperative BMI: 50.5 (45.2, 58.5) kg/m2] demonstrated significant renal improvements (Figure 1). Participants with baseline eGFR<90 mL/min per 1.73m2 (n=42) improved from 75 ± 12 to 96 ± 23 mL/min per 1.73m2 (p<0.001), while those with albuminuria (ACR≥30 mg/g, n=28) decreased from 117 (75-182) to 15 mg/g (9-24) (p<0.001). Hyperfiltration (eGFR≥135 mL/min per 1.73m2,n=24) was attenuated from 153 ± 18 to 135 ± 25 mL/min/1.73m2 (p=0.005).Conclusion: MBS in youth with severe obesity improves low eGFR and attenuates albuminuria and hyperfiltration over 8 years, highlighting its role in reducing obesity-related kidney disease and CKD risk.DisclosureJ.B. Rode: None. S. Jang: None. P. Bjornstad: Consultant; AstraZeneca, Bayer Pharmaceuticals, Inc, Lilly USA LLC, Novo Nordisk. A. Kula: None. T.M. Jenkins: None. S. Sisley: Consultant; Rhythm Pharmaceuticals, Inc. Research Support; Rhythm Pharmaceuticals, Inc, Eli Lilly and Company. A. Courcoulas: Research Support; Allurion, Eli Lilly and Company. M. Michalsky: Other Relationship; Intuitive Surgical, Inc. M. Helmrath: None. J.R. Ryder: Board Member; Calorify. Research Support; Boehringer-Ingelheim, Eli Lilly and Company, Recordati. T. Inge: Consultant; Mediflix, UpToDate, Teleflex, Medtronic, Eli Lilly and Company, BrainStorm Cell Therapeutics, Standard Bariatrics.FundingFunding for Teen-LABS was provided by the National Institutes of Health (NIH) (U01DK072493 / UM1 DK072493 to T.H.I.) (UM1 DK095710 to C.X., T.M.J.) and the National Center for Research Resources and the National Center for Advancing Translational Sciences, NIH (8UL1TR000077). Support also came from the National Center for Research Resources and the National Center for Advancing Translational Sciences, NIH, (UL1TR000114).
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-102-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 103-OR: Association of Tirzepatide with Kidney Parameters in People with
Obesity and Prediabetes from SURMOUNT-1 over 176 Weeks-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 103-OR
Abstract: Introduction and Objective: Obesity and type 2 diabetes (T2D) lead to kidney damage and decline in function over time. Tirzepatide (TZP), has been associated with kidney protective effects in people with T2D and with improvements in estimated glomerular filtration rate (eGFR) and urine albumin-creatinine ratio (UACR) in people with obesity or overweight after 72 weeks of treatment. The current analysis aimed to determine if improvements in kidney parameters persist over 176 weeks of TZP treatment in people with obesity and prediabetes.Methods: SURMOUNT-1 was a 72-week, randomized Phase 3 study to evaluate the effects of TZP (5 mg, 10 mg, 15 mg) versus placebo in participants with obesity (BMI≥30 kg/m2) or overweight (BMI≥27 kg/m2) with weight-related comorbidities (excluding T2D). In the current post-hoc analysis, participants with prediabetes at randomization underwent an additional 104-week treatment follow-up period. UACR and eGFR (CKD-EPI Creatinine-Cystatin Equation 2021) were assessed for TZP (pooled 5/10/15 mg; n=762) or placebo (n=270). Change from baseline to week 176 was analyzed using mixed models for repeated measures with on-treatment data.Results: Baseline mean eGFR was 97.1±17.6 ml/min per 1.73m2 and median UACR was 7.0 mg/g (interquartile range 4.0 - 12.0 mg/g). A significantly smaller decline in eGFR was observed with pooled TZP (-1.6±0.5 ml/min per 1.73m2) compared to placebo (-5.5±1.0 ml/min per 1.73m2) after 176 weeks (estimated treatment difference (ETD) of 3.9 ml/min per 1.73m2, p<0.001). A greater percentage decrease in UACR was observed with pooled TZP (-15.8±2.9%) compared to placebo (-3.9±6.4%) after 176 weeks (ETD of -12.4%, p=0.078).Conclusion: In SURMOUNT-1 participants with prediabetes, overweight or obesity, and preserved eGFR at baseline, use of TZP was associated with an attenuated decline of eGFR over 3 years with a nonsignificant trend toward UACR reduction.Disclosure H.L. Heerspink: Consultant; Alnylam Pharmaceuticals, Inc, Alexion Pharmaceuticals, Inc, AstraZeneca, Bayer Pharmaceuticals, Inc, Boehringer-Ingelheim, Eli Lilly and Company, Janssen Pharmaceuticals, Inc, Novartis AG, Novo Nordisk A/S, Roche Pharmaceuticals, Traveere Pharmaceuticals, Menarini. D. van Raalte: Consultant; Eli Lilly and Company. Research Support; Eli Lilly and Company. Consultant; Novo Nordisk. Research Support; Novo Nordisk. Consultant; Merck & Co., Inc. Research Support; Merck & Co., Inc, AstraZeneca. Consultant; Bayer Pharmaceuticals, Inc. K.R. Tuttle: Consultant; Lilly Diabetes, Boehringer-Ingelheim, Novo Nordisk, Pfizer Inc. Other Relationship; AstraZeneca. Consultant; Bayer Pharmaceuticals, Inc, Traveere Pharmaceuticals, ProKidney. D. Cherney: Consultant; Boehringer Ingelheim-Lilly, Merck, AstraZeneca, Sanofi, Mitsubishi-Tanabe, Abbvie, Janssen, AMGEN, Bayer, Prometic, BMS, Maze, Gilead, CSL-Behring, Otsuka, Novartis, Youngene, Lexicon, Inversago, GSK. Research Support; Boehringer Ingelheim-Lilly, Merck, Janssen, Sanofi, AstraZeneca, CSL-Behring and Novo-Nordisk, Bayer. P. Bjornstad: Consultant; AstraZeneca, Bayer Pharmaceuticals, Inc, Lilly USA LLC, Novo Nordisk. C. Piras de Oliveira: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. Other Relationship; Adipo Therapeutics. G. Dimitriadis: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. D. Cao: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. B. Linetzky: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. I. Jouravskaya: None. R. Griffin: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-103-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 104-OR: Impact of Smartphone-Enabled Home Urine Albuminuria Testing on
Albuminuria Screening and Management-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 104-OR
Abstract: Introduction and Objective: Screening for albuminuria, an important marker of cardiorenal risk, remains unacceptably low in at-risk patients with diabetes (DM) or hypertension (HTN). We evaluated the impact of a smartphone-enabled home urine albumin creatinine ratio (ACR) test on at-risk patients due for screening.Methods: We randomly selected 4000 adults (50% with HTN without DM and 50% with DM) receiving primary care at a large healthcare system in Central Pennsylvania (Geisinger) who had not undergone ACR testing in the past 12 months to receive Minuteful Kidney, an FDA-cleared, smartphone-enabled home albuminuria screening kit using the vendor’s (Healthy.io) standard workflow. Results were returned to patients within a smartphone application and to providers via the EHR. The home testing group was matched 1:1 using propensity scores including sociodemographics and comorbidities to controls who received usual care. The primary outcome was completion of any ACR test within 100 days.Results: Mean age was 61 years (SD 14), 49% female, 93% white, and 4% Hispanic. Completion of any ACR test was higher in the home testing group than controls (53.1% vs. 21.2%; p<0.001). The impact on ACR testing was higher for the HTN subgroup (53.4% vs. 12.5%) than the DM subgroup (52.7% vs. 30.0%); all p values <0.001. Increase in ACR testing associated with Minuteful Kidney was consistent across demographic subgroups though lower in those not using patient portal (58% vs. 21%; p<0.001). Over follow-up of 270 days, among Minuteful Kidney-tested patients there were more new diagnoses of proteinuria or kidney disease (4.0% vs. 2.2%; p<0.001); those with abnormal ACR were more likely to have follow-up visits with primary care and nephrology and new prescriptions of RAAS inhibitors than those with normal ACR tests.Conclusion: A smartphone-enabled home albuminuria test is effective in increasing albuminuria screening and diagnosis of kidney disease among high-risk individuals.DisclosureW. Zafar: None. L. Brubaker: None. J. Green: Research Support; Novartis Pharmaceuticals Corporation, Boehringer-Ingelheim, Sanofi. A. Chang: Research Support; Novartis Pharmaceuticals Corporation, Boehringer-Ingelheim, Bayer Pharmaceuticals, Inc.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-104-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 105-OR: ADA Presidents' Select Abstract: Enhanced Dopamine and Opioid
Receptor Target Engagement Predicts Neuropathic Pain Treatment
Response—A Resting-State fMRI Study in Painful Diabetic Neuropathy-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 105-OR
Abstract: Introduction and Objective: Painful diabetic neuropathy (DN) is a common and challenging complication of diabetes with limited treatments. Our research reveals that treatment responders show enhanced connectivity between the insula and corticolimbic systems, modulated by dopamine and opioid receptors. These findings highlight potential mechanisms of treatment efficacy and pathways for novel therapeutic development.Methods: 43 participants with painful-DN were classified as responders (VAS<4; n=29) or non-responders (VAS>4; n=14) and underwent comprehensive clinical, neurophysiological assessments, and resting-state functional MRI. Data analysis utilized the NITRC Functional Connectivity Toolbox and SPM8 within MatLab. MRI data were masked and binarized using an opioid+dopamine receptor atlases to focus analysis on voxels with high receptor density. Spatial maps for responders and non-responders were compared to identify differences in receptor engagement.Results: Within the dopamine receptor network, responders had significantly greater dopamine transporter enriched functional connectivity (FC) in the anterior prefrontal cortex (p-FDR=0.04), orbital frontal cortex (p-FDR=0.04), anterior cingulate cortex (p-FDR=0.04), primary somatosensory cortex (p-FDR=0.02) and midbrain (p-FDR=0.009). Responders demonstrated significantly increased opioid receptor enriched FC in two clusters including the amygdala (p-FDR=0.006) and the anterior prefrontal cortex (p-FDR=0.01) compared to non-responders.Conclusion: Treatment responders demonstrate greater engagement of both dopamine and opioid receptor systems compared to non-responders. This finding highlights the importance of an intact and functional descending pain inhibition network in achieving effective pain relief. Targeting this network through tailored interventions could enhance pain management outcomes for non-responders to neuropathic pain treatments.DisclosureK. Teh: None. A. Wade: None. G.P. Sloan: Speaker's Bureau; Eli Lilly and Company, Procter & Gamble. M. Goonoo: None. S. Tesfaye: Advisory Panel; AstraZeneca, Bayer Pharmaceuticals, Inc. Speaker's Bureau; Berlin-Chemie AG. Advisory Panel; Grünenthal. Speaker's Bureau; Metronics, Novo Nordisk. Advisory Panel; Procter & Gamble. Speaker's Bureau; Viatris Inc. Advisory Panel; Nevro Corp. D. Selvarajah: None.FundingEuropean Foundation for the Study of DiabetesUKRI Engineering and Physical Sciences Research Council
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-105-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 106-OR: Diabetic Cardiac Autonomic Neuropathy Increases the Risk of Heart
Failure among Type 2 Diabetes Mellitus Patients with Silent Myocardial
Infarction-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 106-OR
Abstract: Introduction and Objective: Silent myocardial infarction (SMI) is a severe cardiovascular disease among patients with DM. Our previous study confirmed that concomitant cardiac autonomic neuropathy (CAN) was an independent predictor of the risk of SMI in patients with T2DM. However, whether CAN increases the risk of HF in T2DM patients with SMI is still unclear. Therefore, we aimed to assess the effect of CAN on prognosis of HF in T2DM patients with SMI.Methods: This is a hospital-based observational study. 1015 T2DM patients who were screened for CAN by Holter monitoring were investigated. Q-waves SMI was detected by ECG. Coronary artery stenosis was examined by multislice computed tomographic (MSCT) coronary angiograph. We conducted a follow-up of up to 180 days for patients who underwent MSCT to assess the incidence of hospitalization due to HF events.Results: A total of 14070 patients were screened. At last, we included 1015 patients with T2DM and 133 of them underwent MSCT. In these 133 T2DM patients, patients with CAN had a higher risk of occurring obstructive coronary artery disease (CAD) than those without CAN (66.7% vs. 33.3%, p<0.001). Besides, they were more likely to have multivessel stenosis (p=0.007) and the stenosis extent of all affected vessels was more serious in this group of patients. At 180 days of follow-up, a total of 27 (20.3%) patients with T2DM developed HF. Multivariate Cox proportional risk models showed that T2DM patients with SMI had significantly higher risk of HF (HR=6.26, 95%CI 2.53-15.51, p<0.001).Conclusion: In asymptomatic T2DM patients, the occurrence of SMI was independently associated with CAN and CAN increased the risk of HF among T2DM patients with SMI. Therefore, we should pay attention to the possibility of SMI in asymptomatic T2DM patients clinically and strengthen the follow-up on cardiac function. In particular, the monitoring should be intensified when patients have concurrent diabetic CAN.DisclosureQ. Luo: None. Y. Fu: None. L. Wu: None. B. Qin: None. X. Wang: None. Y. Chen: None. Y. Zhu: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-106-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 107-OR: Impact of Microvascular Complications on Severe Mental Illness
Risk in Patients with Type 2 Diabetes—A Nationwide Cohort Study in
Taiwan-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 107-OR
Abstract: Introduction and Objective: This study aimed to evaluate the likelihood of developing severe mental illnesses (SMI) —including schizophrenia, bipolar disorder, and major depressive disorder (MDD) among type 2 diabetes (T2D) patients with and without microvascular complications.Methods: We analyzed data from Taiwan National Health Insurance Research Database, and 394,659 matched pairs of microvascular and non-microvascular patients were selected. Multivariable Cox proportional hazards models and Kaplan-Meier method were used for assessment.Results: T2D patients with microvascular complications had a significantly higher risk of SMI. Schizophrenia risk increased with one microvascular disease [aHR (95% CI) 1.11 (1.01, 1.22)], two [1.38 (1.08, 1.76)], and three [aHR (95% CI) 2.29 (1.06, 4.97)]. Bipolar disorder risk was elevated with one microvascular complication [1.17 (1.09, 1.25)], and two [1.27 (1.06, 1.52)]. Risk of MDD increased with one microvascular disease [1.20 (1.18, 1.23)], two [1.41 (1.32, 1.50)], and three [1.53 (1.26, 1.86)]. Diabetic neuropathy has a stronger association with SMI compared to diabetic nephropathy and retinopathy.Conclusion: This nationwide cohort study showed that T2D patients with microvascular complications are at a heightened risk of developing SMI compared to those without microvascular disease.DisclosureY. Yen: None. W. Cheng: None. F. Yen: None. H. Lin: None. C. Hwu: None. C. Hsu: None.FundingTaiwan Ministry of Health and Welfare Clinical Trial Center (NSTC 113-2321-B-039-006); China Medical University Hospital (DMR-111-105; DMR-112-087; DMR-113-009; DMR-113-156); Taipei Veterans General Hospital (V111C-188, V112C-164, V113C-166); National Science and Technology Council, R.O.C. (MOST 110-2314-B-075-027-MY3)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-107-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 108-OR: A Systematic Review and Meta-analysis of RCTs to Prevent Diabetic
Neuropathy in Adults with Type 2 Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 108-OR
Abstract: Introduction and Objective: Diabetic peripheral neuropathy (DPN) is a serious complication. Clinical guidelines recommend targeting modifiable risk factors to prevent DPN, but their effectiveness is unclear. We conducted a systematic review and meta-analysis to evaluate the effectiveness of treating modifiable risk factors to prevent DPN in adults with type 2 diabetes (T2D).Methods: Following PRISMA guidelines, Pubmed, Embase, and clinicaltrials.gov databases were searched for RCTs published since 1980 targeting glycemia, lipids, BP, obesity, smoking, lifestyle modification and multifactorial interventions. Two independent reviewers screened identified articles via Covidence. A third reviewer resolved disagreements. Meta-analysis for each intervention type was conducted using a random-effects model with R. Results are reported as ORs with 95% CI, p-values and I2 statistics.Results: We identified 832 articles from our search. After removal of duplicates and studies marked as ineligible through automated tools, 677 studies underwent title-abstract screening. Of these, 640 were deemed negative and 37 positives moved on to full-text screening. Another 9 studies were identified by non-systematic search. These 46 RCTs underwent full-text screening which yielded 12 studies with relevant extractable data. Meta-analysis was conducted for glycemic control: [n=6] (OR = 0.92, 95% CI 0.84: 1.01, p = 0.07, I2=0%); lifestyle: [n=2] (OR = 0.99, 95% CI 0.86: 1.13, p = 0.83, I2 = 0%) and multifactorial: [n=2] (OR =0.76, 95% CI 0.62: 0.93, p = 0.01, I2 = 0%). Insufficient high-quality RCTs were identified for lipid-lowering [n = 1], smoking cessation [n = 0], obesity [n = 0] and BP [n = 1] for meta-analysis.Conclusion: We found a reduced risk of DPN from multifactorial RCTs, borderline for glycemic control and no effect from lifestyle modification. These findings highlight the need for further research with incident DPN as outcome in adults with T2D to generate actionable results.DisclosureA.L. Sheehan: None. J. O'Malley: None. S. Gunawan: None. S. Natarajan: None. G. Laynor: None. A. Nicholson: None. N. Illenberger: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-108-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 109-OR: Glycemic Risk Index (GRI) Is Related to Type 1 Diabetes
Complications—Insights from the Virtual Diabetes Control and
Complications Trial (DCCT)-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 109-OR
Abstract: Introduction and Objective: GRI is a composite metric that quantifies the overall quality of glycemic control by weighting the risks of hypoglycemia and hyperglycemia, based on continuous glucose monitoring (CGM) data. This work aims to evaluate the association between GRI and the rate of development of complications in the DCCT.Methods: Using hemoglobin A1c and quarterly 7-point blood glucose profiles from the DCCT dataset, a virtual CGM trace was generated for each of the 1,440 DCCT participants. GRI was calculated for each participant at each 6-month visit based on 14 days of virtual CGM data. Poisson regressions, consistent with those used in the original DCCT, were applied to evaluate the association between GRI and the rate of development of complications.Results: A statistically significant association between GRI values and rate of retinopathy progression was found (P <0.0001). This relationship is visually depicted in Figure 1 (panel A). GRI was also associated with the frequency of severe hypoglycemia observed in the DCCT (P <0.001; Figure 1, panel B).Conclusion: GRI, similarly to time in range and hemoglobin A1c, is a reliable representation of glucose control and is significantly associated with the progression of retinopathy. These results support the potential of GRI as a complementary metric for assessing glycemic control.DisclosureM. Ganji: None. C. Fabris: Research Support; Dexcom, Inc. Other Relationship; Dexcom, Inc. Research Support; Novo Nordisk A/S. Other Relationship; Novo Nordisk A/S. Research Support; Tandem Diabetes Care, Inc. B. Lobo: Research Support; Dexcom, Inc. Other Relationship; Dexcom, Inc. B. Kovatchev: Research Support; Dexcom, Inc. Other Relationship; Dexcom, Inc. Research Support; Novo Nordisk. Other Relationship; Novo Nordisk. Research Support; Tandem Diabetes Care, Inc. Other Relationship; Sanofi.FundingThe Diabetes Control and Complications Trial (DCCT) and its follow-up the Epidemiology of Diabetes Interventions and Complications (EDIC) study were conducted by the DCCT/EDIC Research Group and supported by National Institute of Health (NIH) grants and contracts and by the General Clinical Research Center Program (GCRC), the National Center for Research Resources (NCRR). The data from the DCCT/EDIC study were supplied by NIDDK Central Repository (NIDDK-CR). This manuscript was not prepared under the auspices of the DCCT/EDIC study and does not represent analyses or conclusions of the DCCT/EDIC study group, NIDDK-CR, or NIH. This data analyses and the work on this manuscript were supported by the University of Virginia Center for Diabetes Technology, Charlottesville, Virginia and by the JAEB Center for Health Research, Tampa, Florida.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-109-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 110-OR: Association of Glycemic Control with Inverse Risk of Age-Related
-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 110-OR
Abstract: Introduction and Objective: To determine association of metabolic control with the presence of age-related macular degeneration (AMD) and diabetic retinopathy (DR) severity in patients with type 1 diabetes (T1D).Methods: Retinal images were examined for the presence of AMD (AREDS classification) and DR severity (ETDRS scale) in individuals with T1D from the Beetham Eye Institute (BEI, N=1413) and in an age-comparable group with T1D duration for over 50yrs (Joslin Medalists Study, N=1019) at Joslin Diabetes Center. Proteomic profiling of retinal tissue from a subset of Medalists (N=20) was performed using LS-MS/MS.Results: In both the BEI and Medalist cohorts, the presence of AMD was associated with less severe DR (BEI: no to mild non-proliferative DR (NPDR) 14.5% vs 3.0% for proliferative DR (PDR, P<0.0001); Medalists: (no to mild NPDR 23.4% vs 7.9% PDR, P<0.0001). Neovascular AMD was absent in Medalists. Continuous glucose monitoring (CGM) data from a subset of Medalists (N=75) revealed that increased time below range was positively associated with presence of AMD and inversely related to PDR (P<0.05), whereas poor glycemic control markers, such as advanced glycation products and time above range correlated with presence of PDR (P<0.05). In bivariate analyses, proteomic findings of the retina indicated that pathways enhancing glycolysis and mitochondrial metabolism correlated with less DR severity, but more severe AMD.Conclusion: These findings suggest that improving glycemic control in people with type 1 diabetes may alter the presence of AMD by changing glycolytic pathways and glucose/lipid metabolism in the retina. Further investigations are needed to validate the inverse relationship of AMD and DR severity in diabetes and the contributing role of glycemic control to the progression of AMD in people with diabetes.DisclosureW. Fickweiler: None. S. Jangolla: None. T. Chokshi: None. E. O'Doherty: None. J. Gauthier: None. E.R. Viebranz: None. I. Wu: None. M. Yu: None. H. Shah: None. C. Jacoba: None. J.D. Cavallerano: None. L.P. Aiello: Consultant; Boehringer-Ingelheim, Ceramedix, Inc. Advisory Panel; Novo Nordisk. Stock/Shareholder; KalVista. J.K. Sun: Research Support; Optovue, Boehringer-Ingelheim. Other Relationship; Boehringer-Ingelheim. Research Support; Novo Nordisk, Roche Pharmaceuticals. Other Relationship; Roche Pharmaceuticals. Research Support; Physical Sciences, Inc, Boston Micromachines, Adaptive Sensory Technologies. G.L. King: None.FundingNIH T32 DK007260-48, NEI (R01EYE26080-01), NIDDK (P30 DK036836, DP3- DK-094333-01); the Dianne Nunnally Hoppes Fund; the Beatson Pledge Fund
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-110-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 111-OR: Assessing the Diabetic Eye Disease Care Continuum—Screening Gaps
and Predictors among Type 2 Diabetes Mellitus Patients at Two Academic
Medical Centers within the University of California Health System-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 111-OR
Abstract: Introduction and Objective: The American Diabetes Association recommends annual eye exams for adults with Diabetes Mellitus Type 2 (T2DM); however, barriers to timely screening persist. This study assesses the diabetic eye care continuum among patients with T2DM at the University of California, San Francisco (UCSF) and Irvine (UCI).Methods: Electronic health records at UCSF and UCI were queried to identify adult patients with T2DM seen by a primary care provider (PCP) from 2020 through the end of 2022. We estimated the proportion of screening-eligible patients referred to a specialist and those who completed a screening visit within 12 months as well as those diagnosed with and treated for DR. Significant predictors of referrals and screening visits were identified using adjusted logistic regression. Targeted Maximum Likelihood Estimation (TMLE) estimated the impact of an automated referral system.Results: The patient population needing diabetic eye screening included 2,612 patients with T2DM at UCSF and 5,661 at UCI. UCSF had higher 1-year rates of referrals (53.6% vs. 37.4%) and eye screening visits (21.0% vs. 13.4%) (p<0.001). DR diagnosis prevalence was 3.6% at UCSF and 3.4% at UCI, with treatment rates at 0.7% and 1.0%, respectively. Referrals (OR 57.3[47.5-77.2]), previous eye diseases (OR 6.6[5.8-7.4]), and Charlson comorbidity index (OR 1.2[1.1-1.9]) were associated with higher screening rates. A higher Area Deprivation Index (OR 0.8[0.8, 0.9]) was associated with a lower likelihood of screening visits. TMLE suggested screening rates could improve to 34% at UCSF and 24% at UCI with automated referrals.Conclusion: Most patients with T2DM did not receive timely diabetic eye disease screening. Implementing an automated referral system could significantly boost screening rates, but gaps may persist. Further research is needed to understand these gaps and design interventions to improve eye health.Disclosure A. Ayati: Research Support; Genentech, Inc. S. Ko: Employee; Genentech, Inc. N.G. Bonine: None. D. Tabano: Employee; Genentech, Inc. N. Malik: Employee; Genentech, Inc. S. Azzam: None. C. Ben-David: None. M. Wang: Research Support; BeiGene, Amgen Inc. F. Brodie: Consultant; Genentech, Inc. Research Support; Genentech, Inc. Advisory Panel; Genentech, Inc, Apellis. M. Mehta: Research Support; Genentech, Inc. Speaker's Bureau; Astellas Pharma Inc. Consultant; Ani. Research Support; Zeiss. Stock/Shareholder; Eyedaptic. Speaker's Bureau; Apellis. Research Support; jCyte. V. Rudrapatna: Research Support; Genentech, Inc, Merck & Co., Inc, Janssen Pharmaceuticals, Inc, Stryker, Mitsubishi Tanabe Pharma Corporation, Blueprint Medicines, Beigene. Consultant; Ironwood, Natera. Advisory Panel; ZebraMD, DataUnite, Acucare.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-111-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 112-OR: Mitigating Adoption Bias in Medical Autonomous AI—Quantifying
the Balance between Accuracy and Access-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 112-OR
Abstract: Introduction and Objective: Population Achieved Sensitivity (PAS) assumes that the primary goal of a diagnostic process is to identify patients who can benefit from intervention. We used PAS to analyze adoption bias — characterized by inequitable adoption of AI technologies — for an autonomous AI for diabetic eye exams.Methods: We compared two autonomous AI algorithms paired with a desktop fundus camera and a handheld retina camera. Sensitivity for the preregistered clinical trials were reported (NCT02963441 and NCT05808699) and the PAS formula was derived from an ethical framework as presented in npj Digital Medicine - Nature. Access was estimated from the numbers of desktop fundus cameras and handheld retina cameras deployed in US primary care settings. The heatmap presents PAS values for any level of access (0-100% penetrance) and sensitivity ≥ 60%.Results: PAS increases with increasing access and/or sensitivity. The top-right quadrant shows the highest PAS value. Though the handheld retina camera has slightly lower sensitivity (82%) compared with the desktop fundus camera (87%), its greater potential for adoption (estimated at 10X) shows increased detection of diabetic retinal disease in real-world settings.Conclusion: Mitigating adoption bias requires balancing accuracy and access, quantifiable through PAS. This example illustrates how to achieve this balance, empowering clinicians to focus on both diagnostic accuracy and access.DisclosureR. Channa: None. C. Joyce: Consultant; Digital Diagnostics. M.D. Abràmoff: Stock/Shareholder; Digital Diagnostics. Board Member; Digital Diagnostics. Consultant; Digital Diagnostics.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-112-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 113-OR: Adipose Tissue Insulin Resistance Facilitates Fasting Glucose
Elevation in Adults without Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 113-OR
Abstract: Introduction and Objective: Adipose tissue insulin resistance is closely related to glucose metabolism. The study aims to evaluate the impact of adipose tissue insulin resistance on fasting blood glucose (FBG) and hemoglobin A1c (HbA1c) levels.Methods: This cross-sectional study enrolled 5052 adults without diabetes and adipose tissue insulin resistance index (Adipo-IR) was calculated by the product of fasting insulin and free fatty acid levels. We categorized FBG into four groups (FBG<4.6, 4.6 to <5.6, 5.6 to <6.1, and 6.1 to <7mmol/L) and HbA1c into three groups (<5.7%, 5.7 to <6%, and 6 to <6.5%). We conducted logistic regression after adjustment for potential confounders.Results: Adipo-IR gradually increased with the increase of FBG categories (3.25 [2.05, 5.10] vs. 3.92 [2.58, 6.08] vs. 4.96 [3.30, 7.45] vs. 5.40 [3.72, 7.79] μIU/mL*mmol/L, P<0.001) and HbA1c categories (3.58 [2.28, 5.44] vs. 4.35 [2.84, 6.85] vs. 4.90 [3.01, 7.42] μIU/mL*mmol/L, P<0.001). On average, one unit increase in log-Adipo-IR was associated with 73% (95%CI:1.45, 2.07, P<0.001) higher odds of having FBG more than 5.6mmol/L, and 42% (95%CI: 1.26, 1.60, P<0.001) higher odds of having HbA1c more than 5.7% after adjustment for other risk factors. The positive associations between Adipo-IR and FBG/HbA1c levels were also observed among participants with body mass index <24, 24 to <28, and ≥ 28 kg*m2, and among females and males respectively.Conclusion: Higher adipose tissue insulin resistance is associated with higher fasting glucose and HbA1c levels in adults without diabetes. The associations exist across individuals with different obesity levels and genders.DisclosureY. Tian: None. Y. Wei: None. G. Wang: None.FundingBeijing Chao-Yang Hospital Golden Seeds Foundation (CYJZ202314), the National Key R&D Program of China (2022YFA0806400), and National Natural Science Foundation of China (82470889).
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-113-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 114-OR: The Mammalian Adipose Tissue Knowledge Portal (MATKP)—An
Open-Access Web Resource Providing Data and Knowledge Related to Mammalian
Adipose Tissue-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 114-OR
Abstract: Introduction and Objective: Diabetes and adipose research generate rich datasets whose accessibility and integration are often limited. To address this challenge, we created the Mammalian Adipose Tissue Knowledge Portal (MATKP; matkp.org), an open community portal for multi-species mammalian adipose biology. MATKP is accessible to diverse users and aggregates data for adipose tissues and cell types, the genes active within them, and their relationship to human disease.Methods: We integrated expert-curated datasets, with an initial focus on transcriptomics. Reproducible analysis pipelines enable cross-dataset standardization. Key offerings include differential expression analysis of bulk RNA sequencing (RNA-seq) data and cell clustering, marker gene identification, and pseudobulk differential expression analysis of single nucleus RNA-seq (snRNA-seq) data.Results: Within MATKP, users can find, filter, or download bulk and snRNA-seq datasets from human and mouse adipose tissues. Cell types, tissue depots, and metadata fields are harmonized across datasets using standard ontologies. From each dataset, users can obtain analyzed results and visualizations. For snRNA-seq datasets, the single cell browser integrates interactive plots of cell type clusters, gene expression, cell type abundance, and marker gene expression. Users can query by gene name, compare gene expression, and filter by cell type or metadata field. Differential gene expression analyses are available for both pseudobulk snRNA-seq and for bulk RNA-seq data.Finally, gene queries provide gene functions, ontologies, and pathways; links to external resources; and aggregated summaries of gene expression across adipose tissue cell types, species, and datasets.Conclusion: MATKP serves as an integrative community resource to accelerate research in diabetes and adipose biology. Future MATKP iterations will include other data types (e.g., proteomics, imaging) and species (e.g., nonhuman primates).DisclosureJ. Jurgens: None. M. Emont: None. T. Nguyen: None. A. Shilin: None. P. Smadbeck: None. D. Jang: None. M. Brandes: None. J. Flannick: None. E. Rosen: Consultant; Foghorn Therapeutics. Advisory Panel; Source Bio. N. Burtt: None.FundingNational Institute of Diabetes and Digestive and Kidney Diseases (RC2 DK116691)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-114-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 115-OR: Lipophagy Is a Critical Mediator of Lipid Metabolism in Adipocytes
-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 115-OR
Abstract: Introduction and Objective: Adipose tissue is the primary reservoir for neutral lipids, mobilized through lipolysis to meet energy demands during fasting and cold-induced thermogenesis. Canonical lipolysis, mediated by adipose triglyceride lipase (ATGL), releases free fatty acids (FFAs) and glycerol from triglycerides. However, the persistence of lipolysis in ATGL-deficient models suggests the presence of alternative pathways. Lysosomal lipolysis, mediated by lysosomal acid lipase (LAL), has been proposed as a non-canonical mechanism, but how lipids are trafficked to lysosomes for degradation remains unclear. We hypothesized that lipophagy, a specialized form of autophagy, facilitates lysosomal lipolysis and plays a pivotal role in adipocyte lipid metabolism.Methods: Autophagic activity was assessed in adipose tissue during fasting, cold exposure, and treatment with CL316,243 (CL), a β-adrenergic agonist. Using pharmacological inhibitors and adipose-specific Atg5 knockout (A-Atg5 KO) mice, we investigated the role of lipophagy in lipolysis and thermogenesis.Results: Autophagic activity was stimulated in adipose tissue during fasting, cold exposure, and CL treatment. Inhibition of autophagy in cultured adipocytes led to intracellular triglyceride accumulation and reduced lipolysis, as evidenced by decreased glycerol and FFA levels in the supernatant. A-Atg5 KO mice exhibited blunted cold-enhanced plasma FFAs and impaired thermogenesis, as well as reduced ex vivo lipolysis in response to β-adrenergic stimulation or nutrient deprivation. Despite unchanged ATGL and LAL expression levels, the inhibition of ATGL with Atglistatin further suppressed the lipolysis defect in Atg5-deficient adipocytes, highlighting the complementary roles of cytosolic lipolysis and lipophagy.Conclusion: These findings establish lipophagy as a critical mediator of adipocyte lipid metabolism, functioning synergistically with cytosolic lipolysis to mobilize lipids under metabolic stress.DisclosureY. Yeh: None. B. Razani: None.FundingAmerican Heart Association (24POST1198554)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-115-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 116-OR: The Nuclear Receptor NR5A1 Promotes Adipogenesis via Improving
Mitobiogenesis and CLSTN3β Transcription-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 116-OR
Abstract: Introduction and Objective: Our previous research demonstrated that NR5A1 facilitates adipogenesis in preadipocytes in vitro. However, the in vivo functions of NR5A1 and the mechanism governing its role requires further investigation.Methods: We employed AAV8-CAG-Cre to specifically knock down Nr5a1 in the inguinal white adipose tissue (iWAT) of Nr5a1fl/fl mice. These mice were then subjected to a standard chow diet or a high-fat diet. We evaluated the weight and adipogenesis markers in iWAT. Following a three-month high-fat diet regimen, intraperitoneal insulin tolerance test (IPITT), glucose tolerance test (IPGTT) and blood lipid assessments were conducted. Considering NR5A1's potential as a transcription factor, we performed bulk RNA-sequencing and CUT&Tag-sequencing on the stromal vascular fraction (SVF) cells overexpressing Nr5a1 to identify its downstream targets. Furthermore, the mitochondrial function in SVF was assessed using Seahorse assay.Results:Nr5a1 deficiency results in lipodystrophy and diminished expression of adipogenesis markers in iWAT, leading to exacerbated insulin resistance and hyperlipidemia upon HFD-feeding. Overexpression of Nr5a1 enhances the oxygen consumption rate in undifferentiated SVF cells. Sequencing analysis of the Nr5a1-overexpressed SVF cells indicates that NR5A1 promotes mitogenesis during adipogenesis. Notably, our findings reveal that NR5A1 also upregulates the transcription of CLSTN3β, an adipose-tissue-specific protein recently shown to facilitate lipid droplet maturation.Conclusion: The nuclear receptor NR5A1 facilitates adipogenesis by promoting mitobiogenesis and the transcription of CLSTN3β.DisclosureY. Cheng: None. Y. Guo: None. R. Zeng: None. F. Xu: None. Y. Li: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-116-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 117-OR: Changes in Barriers to Physical Activity in Adults with Type 1
Diabetes—Association with Clinical and Psychological Factors-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 117-OR
Abstract: Introduction and Objective: People living with type 1 diabetes (pwT1D) face barriers to physical activity (PA), such as fear of hypoglycemia, which may evolve over time. This longitudinal study aimed to evaluate changes in barriers to PA and to identify clinical and psychological factors influencing these changes.Methods: Data were obtained from adults pwT1D (≥18 years) in the Canadian BETTER registry. Participants who completed the Barriers to Physical Activity in Diabetes (BAPAD) questionnaire at baseline and at the one-year follow-up were included. Associations between changes in BAPAD score (ΔBAPAD = one year score - baseline score) and clinical or psychological factors were analyzed using Spearman and Pearson correlations. Factors assessed included treatment modality, glucose monitoring method, confidence in managing hypoglycemia (HCS), fear of hypoglycemia (HFS), diabetes-related distress (DDS), diabetes-related stigma (DSAS), and body mass index (BMI).Results: Among the 316 participants included, BAPAD score significantly decreased over time (2.62±1.20 vs. 2.40±1.08, p<0.001). No correlation was found between BAPAD score and initiating an insulin pump, initiating a continuous glucose monitor (CGM), or a change in HbA1c. Score increase was associated with discontinuation of CGM (r=0.128; p=0.033). Score decrease was associated with: decrease in BMI (r=0.192; p<0.001), increased confidence in managing hypoglycemia (r = -0.126, p = 0.026), decreased fear of hypoglycaemia (r=0.138; p=0.014), and decreased diabetes-related distress and stigma (respectively, r=0.18; p=0.001 and r=0.294; p< 0.001).Conclusion: Changes in barriers to PA are influenced by clinical and psychological factors. Maintaining access to technology, increasing confidence in managing hypoglycemia and addressing diabetes-related distress and stigma could reduce barriers to physical activity and support long-term engagement in physical activity.DisclosureC. Guédet: None. L. Alexandre-Heymann: None. J.E. Yardley: Research Support; Diabetes Canada, Canadian Institutes of Health Research. Speaker's Bureau; Dexcom, Inc. V. Messier: None. V. Boudreau: None. M. Mathieu: None. A. Brazeau: Speaker's Bureau; Dexcom, Inc. Research Support; Canadian Institutes of Health Research. Speaker's Bureau; Juvenile Diabetes Research Foundation (JDRF). Research Support; Juvenile Diabetes Research Foundation (JDRF), Diabète Québec, Fonds de recherches du Québec-Santé, Mitacs. S. Tagougui: None. R.P. Rabasa-Lhoret: Advisory Panel; Abbott, Eli Lilly and Company, Novo Nordisk, Sanofi, Insulet Corporation. Other Relationship; Medtronic. Advisory Panel; Bayer Pharmaceuticals, Inc.FundingThe BETTER registry is supported by grants from the Canadian Institutes of Health Research (grant number JT1- 157204), Breakthrough T1D Canada (grant number 3- SRA-2024–1523-M-N), and Diabète Québec as well as through non-restrictive grants from Eli Lilly Canada Inc., Novo Nordisk Canada and Sanofi-Aventis Canada and a donation from Dexcom Canada.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-117-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 118-OR: Social Determinants of Physical Activity in Young Adults with and
without Prediabetes or Type 2 Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 118-OR
Abstract: Introduction and Objective: Prediabetes (PreD) and type 2 diabetes (T2D) are increasingly common in young adulthood, a period of declining physical activity (PA). We investigated associations between individual- and community-level social determinants of health (SDOH) and PA in young adults with and without PreD or T2D.Methods: We conducted a cross-sectional study using survey and Fitbit data from 18-35y young adults in NIH’s All of Us Research Program (data collected 2018-2022). Daily steps surrounding SDOH survey (±14d) were averaged (SDOH by domain in Table). Linear regression adjusting for age, sex, race and PreD/T2D assessed the relationship between steps and SDOH in separate models.Results: The cohort (n=862; age 29.6±3.9y; 78% F; 79% White, 2% Black, 4% Hispanic, 5% Asian, 9% Other; 7% PreD/T2D) averaged 7505±3343 steps/day. Young adults with PreD/T2D had roughly 1000 fewer steps/day. Favorable SDOH that were associated with higher step count included employment, low healthcare discrimination, and greater neighborhood social cohesion (Table). Income, education, insurance, social support, loneliness, and neighborhood disorder were not associated with step count.Conclusion: SDOH varied in their association with PA, which was lower in the setting of PreD/T2D. SDOH-based interventions to increase PA in young adults, particularly those with PreD/T2D, should be investigated.DisclosureM. Jankowski: None. C. Harrison: None. S. Apte: None. J. Mitchell: None. X. Qin: None. M. Vajravelu: None.FundingThe Pittsburgh Foundation
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-118-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 119-OR: Impact of Moderate-to-Vigorous Physical Activity on Mortality in
Sedentary Patients with New-Onset Type 2 Diabetes Compared with General
Populations—A Nationwide Target Trial Emulation Study-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 119-OR
Abstract: Introduction and Objective: Limited evidence compares mortality outcomes between sedentary individuals without type 2 diabetes mellitus (T2DM) and those with new-onset T2DM who initiate moderate-to-vigorous physical activity (MVPA). This study aimed to investigate the causal effects of MVPA initiation and new-onset T2DM on mortality using a nationwide target trial emulation approach.Methods: The study included participants aged ≥20 years from national health checkups (2013-2017; n=2,054,292), excluding those with prior MVPA engagement or a diabetes diagnosis (2010-2012). Follow-up continued until the occurrence of outcomes or 2022. Participants were categorized into four groups: non-T2DM with no MVPA (n=481,895), non-T2DM with MVPA (n=177,391), new-onset T2DM with no MVPA (n=40,113), and new-onset T2DM with MVPA (n=17,829). MVPA was defined as either ≥30 mins of moderate PA on ≥5 days/week or ≥20 mins of vigorous PA on ≥3 days/week. The primary outcome was all-cause mortality, and secondary outcomes included cardiovascular and cancer-related mortality. Target trial emulation with overlap weighting was applied to reduce bias and mimic a randomized controlled trial.Results: The median follow-up study duration was 7.3 years. After overlap weighting, no significant differences in covariates existed between groups (SMD<0.1). Compared to the non-T2DM with no MVPA, the adjusted hazard ratios (95% CI) for all-cause mortality were as follows: 0.51 (0.48-0.55) for the non-T2DM with MVPA, 1.44 (1.37-1.51) for the new-onset T2DM with no MVPA, and 0.67 (0.61-0.73) for the new-onset T2DM with MVPA. Secondary outcomes showed similar trends.Conclusion: Initiating MVPA in patients with new-onset T2DM significantly reduces mortality risk compared to sedentary individuals without T2DM, emphasizing the critical role of MVPA in improving survival outcomes among new-onset T2DM patients.DisclosureS. Park: None. S. Kim: None. S. Jin: None. J. Kim: None. G. Kim: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-119-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 120-OR: Does Higher Physical Activity Lower Mortality in U.S. Adults with
Diabetes and Myocardial Infarction' A Formal Analysis Using the Recent CDC
Physical Activity Categories-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 120-OR
Abstract: Introduction and Objective: Patients with diabetes benefit from regular exercise. However, the benefit of exercise in patients with diabetes and myocardial infarction (MI) is less clear. Therefore, we sought to evaluate the differences in mortality risk in patients with diabetes and MI (DMI) at various physical activity levels.Methods: Using data from the 2001 to 2014 annual National Health Interview Survey’s, we created a cohort of patients with (DMI). Physical activity levels were categorized following CDC adult exercise guidelines as inactive, insufficiently active, sufficiently active, and highly active. Information on mortality and follow-up time were from the National Death Index-linked mortality files. After computing mortality rates using life table methods, we determined the independent effect of physical activity categories on death using multivariate Cox proportional hazards models adjusted for age, sex, race, marital status, education, region, smoking status, diet habits, alcohol consumption, and obesity.Results: From 2001 to 2014, there were 421,106 participating U.S. adults, of whom 4,698 had (DMI). Over the follow-up period, 1,631 DMI participants died. The mortality rate (per 1000 person-years) for (DMI) stratified by exercise category were: inactive 89, insufficiently active 62, sufficiently active 50, and highly active 44. When exercise categories were compared amongst (DMI) participants with inactivity as the referent in multivariate Cox regression, the hazard ratio for death was 0.75 (95% CI 0.64, 0.89) for insufficient activity, 0.57 (95% CI 0.46, 0.70) for sufficient activity, and 0.49 (95% CI 0.39, 0.60) for highly active.Conclusion: In this population-based analysis, (DMI) subjects who regularly exercised were at a lower risk of death compared to those who were inactive, with the highest physical activity levels showing the most benefit. Further research is needed to elucidate the mechanisms for the benefit among patients with (DMI).DisclosureI. Zahrieh: None. L. Haley: None. A. Nicholson: None. N. Illenberger: None. S. Natarajan: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-120-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 121-OR: ADA Presidents' Select Abstract: Genetic Susceptibility to
Macronutrient Preference Is Associated with Consumption of Sugar-Sweetened
Beverages and Fast Food in Children-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 121-OR
Abstract: Introduction and Objective: Prior research identified genetic variants for macronutrient preference in adults, but whether these genetic differences affect early life food intake and metabolic phenotypes is unknown. We examined the associations of polygenic scores (PS) for macronutrient preference with dietary behaviors, BMI trajectories from 3-17y and insulin resistance at 17y.Methods: We used genetics, dietary intake and anthropometrics collected at ages ~3, 7, 12, and 17y, and glycemic data measured at 17y among non-Hispanic White children from US prebirth cohort Project Viva. Dietary behaviors from questionnaire included consumption of sugar-sweetened beverages (SSBs) and fast-food. Macronutrient preference PS were calculated from prior large genome-wide study in adults. We estimated odds ratios (OR) for frequent fast-food (>=1 meal/wk) and SSB intake (>1 serving/wk) with generalized estimating equations from 3-17y, and beta coefficients for BMI z-score with linear mixed models from 3-17y. We used linear regressions to examine associations of PS with homeostatic model assessment for insulin resistance (HOMA-IR). We adjusted models for child’s age, sex, and 3 genetic principal components.Results: Among 516 children, each SD increment in PS for carbohydrate preference was associated with a higher likelihood of frequent fast-food (OR 1.13 for >=1 meal/wk, 95% CI: 1.02 to 1.26) and SSB (OR 1.15 for >1 serving/wk, 95% CI: 1.03 to 1.28) intake on average from 3-17y. Each SD increase in the protein preference PS was associated with lower likelihood of frequent SSB intake (OR for >1 serving/wk: 0.89, 95% CI: 0.79 to 0.99). We did not find significant associations between macronutrient PS with BMI z-score or HOMA-IR.Conclusion: Our findings suggest that genetic predisposition for carbohydrate and protein preference could influence SSB and fast-food intake patterns in children, which could heighten their future risk for diabetes.DisclosureS. Harnois-Leblanc: None. K. Switkowski: None. J. Young: None. I.M. Aris: None. S.L. Rifas-Shiman: None. E. Oken: None. J.E. Gervis: None. K.E. Westerman: None. H.S. Dashti: None. M. Hivert: None. J. Merino: None.FundingAmerican Diabetes Association (7-23-PDFT2DY-03); National Institutes of Health (R01034568, R24ES030894)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-121-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 122-OR: Maternal Serum Polyol Levels Associated with Glucose Metabolism
and Large-for-Gestational-Age Infants—Findings from a Population-Based
Nested Case-Control Study-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 122-OR
Abstract: Introduction and Objective: This study aims to investigate the association between maternal serum polyol levels and the risks of gestational diabetes mellitus (GDM) and large for gestational age (LGA) infants.Methods: In a population-based nested case-control study, we matched pregnant women with GDM (n=89) and those without GDM (n=89) based on age and pre-pregnancy body mass index (BMI). We excluded cases of preterm birth, low birth weight, gestational hypertension, and missing data, and a final sample of 175 women (89 with GDM and 86 without GDM) were included. 75g oral glucose tolerance test (OGTT) and insulin release test (IRT) were measured during the gestation period of 20-28 weeks. Pre-pregnancy weight was self-reported by the pregnant woman, and body weight was remeasured at the last prenatal visit in the third trimester. Serum levels of polyols (sorbitol, erythritol, xylitol, and maltitol) were quantified using gas chromatography coupled with time-of-flight mass spectrometry (GC-TOF/MS).Results: Among the 175 participants, 24.0% had LGA infants. Maternal serum polyol levels were significantly elevated in the LGA group. After adjusting for confounders, a 1-SD increase in serum polyol levels was associated with increased odds of LGA (OR 1.76, 95% CI: 1.19-2.59) and GDM (OR 1.52, 95% CI: 1.09-2.14). Notably, erythritol and sorbitol were significantly associated with LGA risk, while xylitol and maltitol showed no significant correlation. Additionally, a 1-SD increase in serum polyol levels was linked to higher birth weight (β= 89 grams, 95% CI: 16-161 grams) and increased values of homeostasis model assessment for insulin resistance (HOMA-IR) (β= 0.26, 95% CI: 0.07-0.46) in the fully adjusted model.Conclusion: Our findings indicated that elevated maternal serum polyol levels were positively associated with the risks of GDM, LGA infants, and high birth weight.DisclosureT. Tan: None. M. Wang: None. Y. Qi: None. Y. Liu: None. L. Qin: None. J. Ma: None.FundingScience and Technology Commission of Shanghai Municipality-Science and Technology Program (20DZ2201500); Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support (20181807)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-122-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 123-OR: Impact of the Healthy Gut Diet Intervention on Maternal Diet
Postpartum—A Pilot Randomised Controlled Trial-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 123-OR
Abstract: Introduction and Objective: Pregnancy is an opportune time for behavior change, yet few studies report on postpartum maintenance of improved dietary behaviors. The Healthy Gut Diet (HGD) Study, co-designed with women with lived experience of GDM, incorporated behavior change techniques to promote a gut-friendly diet during pregnancy. This study aimed to examine the impact of the HGD intervention during pregnancy on maternal diet quality 12 weeks postpartum.Methods: The HGD was a pilot, single-blind, two-arm randomized controlled trial. Women who participated during pregnancy were eligible for the 12-week postpartum follow-up. Dietary intake was assessed using two validated tools: the Australian Eating Survey and a Modified Short Dietary Questionnaire (SDQ) incorporating fermented and prebiotic foods. Dietary intakes postpartum were compared to those at baseline and 36 weeks gestation. A Goldberg ratio of <0.9 was used to determine under reporters of dietary intake.Results: Of 129 eligible participants in the HGD, 94 consented for follow-up, and 74 completed surveys postpartum (35 intervention, 39 control). Women were, on average, 33 years old, with a pre-pregnancy BMI of 27.9 kg/m²; 60% were multiparous. No baseline differences were observed between groups. Postpartum, intervention participants had significantly higher diet quality (p=0.03) and vegetable intake (p=0.01) than controls. Compared to baseline, the intervention group also had higher intakes of fibre (p=0.05), iron (p=0.03), and magnesium (p=0.002) postpartum, while controls showed no significant changes.Conclusion: A co-designed dietary intervention integrated with behavior change techniques demonstrates potential for sustaining improved diet quality postpartum and attenuating a decrease in diet quality observed in the transition between pregnancy and postpartum.DisclosureH.M. O'Connor: None. S.J. de Jersey: None. S. Wilkinson: None. N.J. Meloncelli: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-123-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 124-OR: Assessment of Caregiver and Patient Perceptions and Utilization of
Medical Nutrition Therapy and Associated Child Health Outcomes in
Pediatric Type 1 Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 124-OR
Abstract: Introduction and Objective: Despite official recommendations, medical nutrition therapy (MNT) in pediatric T1D is underutilized. Study objectives were to assess caregiver and patient perceptions of MNT and analyze the relationship between MNT utilization (defined as healthy diet and registered dietitian [RD] visits) and child health outcomes.Methods: Separate surveys were fielded in 2024 to caregivers of children aged <18 and, with permission, to patients 12-17 y/o with T1D for ≥1 year followed at tertiary-care pediatric center. Surveys included questions regarding perceptions of MNT in pediatric T1D with Likert scales to compute MNT importance rating and a food frequency table (adapted from prior T1D studies) to classify diet as healthy vs unhealthy. Objective data on glycemic and metabolic variables and RD visits in the prior year were collected. Linear and logistic regression analyses, controlling for age, sex, diabetes duration, CGM use, and mode of insulin delivery, assessed the relationships between (1) MNT importance rating and MNT utilization and (2) MNT utilization and child health outcomes.Results: Both caregivers (n=193; 15% of total) and patients (n=43; 65% of eligible with permission) assigned a high importance rating to MNT (83.4±6.6 and 77.7±7.1, respectively; scale 0-100). In the patient survey, higher MNT importance rating was associated with a healthy diet (P=0.005). A healthy diet was associated with lower HbA1c and higher time-in-range in the child (P<0.05 for all) in both surveys. RD visit rates in prior year were low (caregiver 28%, patient 14%) and not associated with MNT importance rating or child health outcomes.Conclusion: Despite participants recognizing the importance of MNT in pediatric T1D, this did not consistently translate into MNT utilization. A higher diet quality was associated with improved glycemic outcomes. Future research should evaluate the benefits of additional RD engagement.DisclosureS. Azova: None. E. Rhodes: Other Relationship; National Institutes of Health. E.N. Gordon: None. C. Petty: None. H.B. Wilson: None. K. Garvey: Consultant; Sanofi. Speaker's Bureau; Tandem Diabetes Care, Inc. B.S. Lennerz: None.FundingNational Institutes of Health (K12DK133995)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-124-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 125-OR: Effect of CT-388, a Signal-Biased Dual GLP-1/GIP Receptor Agonist,
on Liver-Related MRI Parameters in Patients with Obesity-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 125-OR
Abstract: Introduction and Objective: CT-388 demonstrated placebo (pbo)-adjusted (adj) weight loss of 18.9% (95% CI 14%-24%), and normalized dysglycemia in a phase 1 pbo-controlled, randomized, double-blind study in adults with obesity (BMI ≥30.0 kg/m2) without diabetes (NCT04838405). This analysis evaluated the effect of CT-388 on liver-related MRI endpoints.Methods: The studied cohort included 31 otherwise healthy adults with obesity treated over 24 weeks. Participants (Pts) were randomized 4:1 to receive CT-388 22 mg (via up-titration) or pbo. MRI was performed at baseline (BL), weeks 12 and 24 to evaluate liver fat content (LFC) via MRI-PDFF and inflammation via cT1. Pts with complete MRI data (n=27) were analyzed for percent change in LFC and absolute reduction in cT1 from baseline using a mixed model for repeated measures.Results: CT-388 treated pts (n=21) were mostly female (62%), with a mean (SD) age, BMI, LFC, and cT1 of 31 (9) years, 39 (6) kg/m2, 10% (8%), and 858 (78) ms. All pbo pts (n=6) were male, aged 32 (12) years, with BMI, LFC, and cT1 of 35 (3) kg/m2, 9% (4%), and 800 (67) ms. Across both arms, 48% had LFC ≥10% at BL. Among these pts, CT-388 pts (n=10) had BL LFC of 17% (7%) vs 12% (1%) in pbo (n=3). After 24 weeks, CT-388 pts had a pbo-adj least squares mean (LSM) (95% CI) reduction in LFC by 59% (31%-86%) and cT1 by 52 ms (8-95 ms). LFC decreased by >30% in 86% of CT-388 pts vs 17% in pbo. In those pts with LFC ≥10% at BL, 100% of CT-388-treated pts (vs 0% in pbo) had a reduction in LFC of >30% and in cT1 of ≥40 ms after 24 weeks; pbo-adj LSM reduction in LFC was 87% (59%-114%), and in cT1 was 73 ms (0-146 ms). A decrease in cT1 ≥80 ms was noted in 40% of CT-388-treated pts and 70% had reached LFC <5% (normal) vs 0% pbo for both parameters. ALT was normal at BL with a trend to decrease during the study. CT-388 was generally safe and tolerable.Conclusion: In this phase 1 study, CT-388 showed clinically meaningful reductions in liver fat and inflammation in pts with obesity and MAFLD.Disclosure A. Steinberg: Employee; Genentech, Inc. Stock/Shareholder; Viking Therapeutics, Pfizer Inc. Employee; Roche Pharmaceuticals, Axcella Health Inc, Carmot Therapeutics, Inc. F.A. Argüelles-Tello: None. J. Zhu: Employee; Genentech, Inc. J. Wu: Employee; Roche Pharmaceuticals, Carmot Therapeutics, Inc. H.B. Thomaides-Brears: Employee; Perspectum Ltd. Stock/Shareholder; Perspectum Ltd. C.R. Langford: Employee; Perspectum Ltd. M.A. Elliott: Employee; Carmot Therapeutics, Inc. L. Acosta: None. L.L. Sánchez-Sánchez: None. M. Chakravarthy: Employee; Carmot Therapeutics, Inc, Roche Pharmaceuticals, Genentech, Inc.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-125-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 126-OR: Efficacy and Safety of a Novel Dual GLP-1/GIP Receptor Agonist in
Participants with Type 2 Diabetes Mellitus Up to 32 Weeks-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 126-OR
Abstract: Introduction and Objective: HRS9531, a novel once-weekly (QW) dual GLP-1/GIP receptor agonist, showed preliminary efficacy with good tolerability in T2DM participants. This phase 2 study further evaluated the efficacy and safety of HRS9531 in Chinese T2DM participants with treatment to 32 weeks which consisted of a 20-week (W) core treatment followed by a 12W extension treatment.Methods: In this randomized, double-blind phase 2 trial, participants with T2DM, HbA1c 7.5%-10.5%, inadequately controlled with lifestyle or stable metformin, were randomized to receive QW subcutaneous HRS9531 (1, 2, 3 and 4.5 mg) and corresponding placebo. During extension, HRS9531 doses remained unchanged while participants in placebo group were added HRS9531 1 mg QW (placebo-HRS9531 1 mg/W group). Primary endpoint was change from baseline in HbA1c at 20W. The efficacy and safety in 32W were also observed.Results: Of 199 randomized participants, 186 received and 180 completed the extension treatment. At 20W, mean HbA1c changes from baseline were from -2.1% to -2.7% in HRS9531 groups. HRS9531 maintained efficacy over 32 weeks. Mean changes in HbA1c were -2.1%, -2.5%, -2.7% and -2.4% in the 1, 2, 3 and 4.5 mg groups, respectively, with 91.7% of participants in the 4.5 mg group achieving HbA1c < 7.0%. The change in HbA1c of the placebo-HRS9531 1 mg/W group was -2.0%. HRS9531 induced a continuous dose-dependent body weight loss ranging from -4.0% to -8.9%. At 32W, HRS9531 was associated with improvement in systolic blood pressure, TG levels and UACR up to -9.5 mmHg, -25.7% and -61.8%, respectively. Most emergent-treatment adverse events (TEAEs) were mild or moderate. The most common TEAEs were diarrhea, decreased appetite and nausea. No clinically significant hypoglycemia or severe hypoglycemia was reported.Conclusion: HRS9531 demonstrated improved and sustained glycemic control and weight loss over 32 weeks treatment, with a favorable safety and low risk of hypoglycemia.DisclosureJ. Zhao: None. M. Zhao: None. W. Song: None. D. Wang: None. X. Zhang: None. Y. Hui: None. Y. Zhou: None. Y. Lu: None. M. Zhang: None. C. Jiang: None. F. Lv: None. L. Zhang: None. M. Zeng: Employee; Jiangsu Hengrui Pharmaceuticals Co., Ltd. L. Zhang: Employee; Jiangsu Hengrui Pharmaceuticals Co., Ltd. X. Cui: Employee; Jiangsu Hengrui Pharmaceuticals Co., Ltd. J. Wang: Employee; Jiangsu Hengrui Pharmaceuticals Co., Ltd.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-126-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 127-OR: A Four-Week Treatment with Dapagliflozin Reduces
Insulin-Stimulated Renal Glucose Uptake-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 127-OR
Abstract: Introduction and Objective: Treatment with SGLT-2i reduces the risk of both cardiovascular and renal outcomes in type 2 diabetes (T2D). Recent findings indicate that in obese individuals, the kidney exhibits lower 18Fluorodeoxyglucose ([18F]-FDG) uptake rates compared to lean individuals, possibly due to insulin resistance. This study aims to evaluate changes in renal [18F]-FDG uptake in T2D patients following short-term treatment with dapagliflozin and to assess the long-term effects on kidney function after a four-year follow-up.Methods: In our DAPAHeart Trial, a single-center, four-week, prospective, double-blind, controlled study, we enrolled T2D patients with stable coronary artery disease and preserved glomerular filtration rates (eGFR >60 ml/min/1.73m²). Participants were randomly assigned in a 1:1 ratio to receive either dapagliflozin (10 mg daily) or a placebo. PET scans using [18F]-FDG were performed during a hyperinsulinemic-euglycemic clamp (HEC) to measure regional FDG uptake before and after the four-week treatment with SGLT-2i.Results: After the four-week treatment, the SGLT-2i group showed a significant reduction in renal standardized uptake value (SUV) expressed as peak activity concentrations (SUVpeak; p=0.045) compared to the placebo group, with trends toward reductions in SUVmax and SUVmean. Additionally, long-term follow-up data revealed that four years of dapagliflozin treatment was associated with stable eGFR (pre-treatment: 81.4 ± 6.4 ml/min; post-treatment: 76.2 ± 6 ml/min; p=0.4).Conclusion: Short-term treatment with dapagliflozin is associated with a reduction in renal SUVpeak, indicating decreased glucose uptake during an insulin-stimulated state (insulin clamp). While the causes of this reduction require further investigation, it is suggested that SGLT-2 inhibition decreases tubular energy requirements and glucose uptake, contributing to kidney function preservation, as confirmed by the four-year follow-up.DisclosureS. Gugliandolo: None. C. Morciano: None. G. Sorice: None. L. Leccisotti: None. U. Capece: None. A. Guarneri: None. T. Mezza: None. G. Di Giuseppe: None. G. Ciccarelli: None. L. Soldovieri: None. M. Brunetti: None. A. Avolio: None. A. Splendore: None. P. Iozzo: None. A. Giaccari: Board Member; Novo Nordisk A/S. Speaker's Bureau; AstraZeneca, Sanofi. Advisory Panel; Sanofi. Speaker's Bureau; Guidotti. F. Cinti: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-127-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 128-OR: The Significant Reduction in Epicardial Adipose Tissue Thickness
after Dapagliflozin Treatment Is Preserved and Even Increased after Four
Years—The DAPAHEART Four-Year Follow-up Study-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 128-OR
Abstract: Introduction and Objective: Epicardial adipose tissue (EAT) is a key factor in coronary microvascular dysfunction in type 2 diabetes (T2DM). We previously showed that 4-week treatment with sodium-glucose cotransporter 2 inhibitor (SGLT2i) dapagliflozin reduces EAT thickness by 19%, with 30% increase in coronary flow reserve (CFR), probably due to reduced EAT inflammation. We subsequently found that 30% increase in CRF was preserved over a 4-year treatment, but long-term effects on EAT remained unclear. We thus evaluated changes in EAT thickness after 4-yr dapagliflozin treatment in T2DM patients with stable coronary artery disease (CAD).Methods: Patients with T2DM and stable CAD were enrolled in the DAPAHEART trial, a single-center, 4-week, randomized (1:1 dapagliflozin 10 mg/placebo), double-blind, controlled study. After 4 weeks, the placebo group also received dapagliflozin. All patients were followed-up over the 4-yr treatment. EAT thickness was measured via 13N-ammonia PET/CT at baseline and after 4 yrs. BMI was also monitored, and correlation with EAT thickness reduction analyzed.Results: EAT thickness decreased significantly (25.37%) in all patients over 4 yrs (p= 0.03). EAT reduction was statistically significant also in the placebo group (p= 0.04), which started dapagliflozin after the 4-week trial. No significant correlation was found between BMI reduction and changes in EAT thickness (R²= 0.0662; p= 0.5038).Conclusion: EAT reduction after 4-week treatment with dapagliflozin is preserved and even increased after 4 yrs. The sustained improvement in CFR over 4 yrs may be attributed to reduced EAT thickness. Moreover, lack of correlation with BMI suggests a selective effect of dapagliflozin on EAT. These findings support the use of SGLT2i in mitigating cardiovascular risk in T2DM.DisclosureC. Morciano: None. S. Gugliandolo: None. G. Sorice: None. L. Leccisotti: None. A. Guarneri: None. L. Cappannoli: None. U. Capece: None. D. D'Amario: None. T. Mezza: None. G. Ciccarelli: None. L. Soldovieri: None. M. Brunetti: None. G. Di Giuseppe: None. A. Avolio: None. A. Splendore: None. P. Iozzo: None. A. Giaccari: Board Member; Novo Nordisk A/S. Speaker's Bureau; AstraZeneca, Sanofi. Advisory Panel; Sanofi. Speaker's Bureau; Guidotti. F. Cinti: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-128-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 129-OR: Real-World Efficacy of the iLet Bionic Pancreas in Adults and
Children during the First Eighteen Months of Commercial Availability-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 129-OR
Abstract: Introduction and Objective: To analyze the impact of the iLet bionic pancreas on glycemic control during the first 18 months after FDA clearance and compare to the results of the Bionic Pancreas Pivotal Trial (BPPT).Methods: Commercial users of the iLet who had a pre-iLet HbA1c value available and had at least 3 weeks of iLet data in the cloud were included. Baseline HbA1c values were compared with the glucose management indicator (GMI) values calculated from all available continuous glucose monitoring (CGM) data, both reported as mean±SD [IQR]. Adults (≥18 years) and children were analyzed separately. Data from the BPPT were analyzed in the same way for comparison. The percentage of time with CGM glucose <54 mg/dl during iLet use was calculated for all groups and were reported as median [IQR].Results: Data from 6,992 commercial users (5,987 adults and 1,005 children) were included in the real-world analysis, and from 330 participants (218 adults and 112 children) in the BPPT analysis. Adult commercial users had a baseline HbA1c of 8.6±1.9% [7.2-9.6] and an iLet GMI of 7.2±0.5% [7.0-7.4] (difference: -1.4%), compared to 7.7±1.2% [6.9-8.3] and 7.0±0.3% [6.9-7.2], respectively, in the BPPT (difference: -0.7%). Pediatric commercial users had a baseline HbA1c of 9.5±2.2% [7.7-10.8] and an iLet GMI of 7.7±0.6% [7.3-8.0] (difference: -1.8%), compared to 8.1±1.2% [7.3-8.9] and 7.4±0.3% [7.2-7.5], respectively, in the BPPT (difference: -0.7%). The time with CGM glucose <54 mg/dl was 0.3% [0.1-0.6] in adults and 0.3% [0.1-0.6] children in commercial use and 0.3% [0.1-0.5] in adults and 0.3% [0.2-0.6] in children in the BPPT.Conclusion: The baseline HbA1c values of commercial users were higher, and the decreases from baseline HbA1c to iLet GMI values were larger than among participants in the BPPT. The time spent <54 mg/dl were comparable in both settings.Disclosure S.J. Russell: Employee; Beta Bionics, Inc. Stock/Shareholder; Beta Bionics, Inc. R. Selagamsetty: Employee; Beta Bionics, Inc. E. Damiano: Other Relationship; Beta Bionics, Inc.FundingBeta Bionics, Inc.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-129-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 130-OR: Real-World Glycemic Outcomes in Adults with Type 2 Diabetes (T2D)
Using the Omnipod 5 Automated Insulin Delivery (AID) System-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 130-OR
Abstract: Introduction and Objective: A recent trial of the Omnipod® 5 AID System showed improvement in glycemic outcomes following AID initiation in a cohort of adults with insulin-treated T2D. However, limited real-world data exist on AID use and bolus behaviors in this population. This analysis evaluated real-world outcomes with Omnipod 5 use in the management of T2D.Methods: A retrospective analysis of CGM and insulin data from Omnipod 5 users with T2D in the US aged ≥18y with sufficient CGM data (≥90 days of data, ≥75% of days with ≥220 readings) was conducted for those who self-reported baseline A1C and primarily used the 110 or 120 mg/dL targets. Outcomes were stratified by baseline A1C and bolus frequency.Results: A total of 12,327 users (median age 59y; prior therapy: 44% MDI) met inclusion criteria. Users had spent a median of one year on device at the time of analysis, with 94% of time in Automated Mode. Time in range (70-180 mg/dL) and glucose management indicator by baseline A1C and bolus frequency are shown in the Figure. Among these users, time <70 mg/dL was low (median 0.26%).Conclusion: These findings from a large-scale real-world dataset of long-term (~1 year) AID use are similar to those reported in the pivotal trial of Omnipod 5 in T2D and provide evidence that people with T2D requiring insulin can consistently use AID long-term and achieve glycemic benefits even with elevated baseline A1C.Disclosure S.M. Oser: Research Support; Abbott. Other Relationship; American Diabetes Association, Association of Diabetes Care & Education Specialists. Advisory Panel; Ascensia Diabetes Care. Research Support; Dexcom, Inc., Insulet Corporation, Leona M. and Harry B. Helmsley Charitable Trust. Advisory Panel; National Committee for Quality Assurance. Consultant; Sequel Med Tech. A.L. Peters: Advisory Panel; Medscape. Consultant; Vertex Pharmaceuticals Incorporated. Research Support; Insulet Corporation, Abbott. Other Relationship; Omada Health. F.J. Pasquel: Consultant; Insulet Corporation. Research Support; Novo Nordisk, Dexcom, Inc., Ideal Medical Technologies, Tandem Diabetes Care, Inc, Insulet Corporation. Consultant; Dexcom, Inc. G. Aleppo: Consultant; Dexcom, Inc., Insulet Corporation. Research Support; Insulet Corporation, Fractyl Health, Inc., MannKind Corporation, Tandem Diabetes Care, Inc, WellDoc, EMMES, AbbVie Inc, Bayer Pharmaceuticals, Inc. E. Miller: Advisory Panel; Abbott, Abbott Diagnostics. Other Relationship; American Diabetes Association. Speaker's Bureau; Bayer Pharmaceuticals, Inc, Boehringer-Ingelheim, Corcept Therapeutics, Eli Lilly and Company. Advisory Panel; Insulet Corporation, embecta. Speaker's Bureau; Novo Nordisk. Research Support; Abbott. L.M. Huyett: Employee; Insulet Corporation. Stock/Shareholder; Insulet Corporation. K. Miller: Employee; Insulet Corporation. L. Conroy: Employee; Insulet Corporation. Stock/Shareholder; Insulet Corporation. J.J. Mendez: Employee; Insulet Corporation. Stock/Shareholder; Insulet Corporation. T.T. Ly: Employee; Insulet Corporation. Stock/Shareholder; Insulet Corporation.FundingThis study was funded by Insulet Corporation.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-130-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 131-OR: Safety and Effectiveness Outcomes after One Year with T:slim X2
Control-IQ Technology in Children with Type 1 Diabetes Under Six Years-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 131-OR
Abstract: Introduction and Objective: To determine the safety and effectiveness of the t:slim X2 with Control-IQ Technology (CIQ) in children with T1D under the age of six in a real-life setting.Methods: Despite CIQ being off label for children under six years of age, many parents request an automated insulin delivery system for their younger children. Several pediatric centers have started using these systems in children under six, provided they obtain signed informed consent from the parents. In this multicenter prospective study, we compared clinical outcomes and CGM-derived results of children under six to those aged six to ten years who have used CIQ for at least one year. Before starting CIQ, all children were using CGM. Anonymous data were collected locally and centralized for analysis.Results: A total of 131 children aged <6 and 190 aged 6 to 10 years were recruited from 30 pediatric centers. Clinical characteristics and CGM-derived metrics at baseline and one year after CIQ usage are shown in Table 1. No serious hypoglycemic events occurred in either the pre-CIQ or post-CIQ groups. An episode of DKA has been reported in a child aged 6 to 10 years.Conclusion: CIQ is safe and effective for children under six. Given the challenges of glycemic control in this age group, it's essential to embrace advanced technological systems for improving outcomes.Disclosure V. Cherubini: Research Support; Lilly Diabetes, AstraZeneca. Advisory Panel; Novo Nordisk, Sanofi. R. Franceschi: Other Relationship; Medtronic. M. Marigliano: Speaker's Bureau; Medtronic, Novo Nordisk, Ypsomed AG. R. Gesuita: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-131-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 132-OR: Days without User-Initiated Boluses—Real-World Performance
of the MiniMed 780G System-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 132-OR
Abstract: Introduction and Objective: While missed meal boluses are common in people with diabetes, glycemic control may be maintained with frequent autocorrections.1 The present study assessed MiniMed™ 780G system (MM780G) glycemic metrics and insulin delivery during real-world use on days when users did not bolus.Methods: Global CareLink™ personal data (as of October 26, 2024), of 43,952 consenting MM780G users who had ≥10 days of sensor use, were assessed for days when there were no user-initiated boluses. Time spent within 70-180 mg/dL (TIR), below 70 mg/dL (TBR) and above 180 mg/dL (TAR) range, the glucose management indicator (GMI), and insulin were analyzed based on use of recommended optimal settings (ROS, 100 mg/dL glucose target [GT] and 2 hours active insulin time [AIT]) for ≥95% of the time.Results: On days without user-initiated boluses, ROS users had a mean TIR, TAR, TBR and GMI of 76.2%, 23.0%, 0.7% and 6.9%, respectively, while non-ROS users had means of 70.6%, 28.5%, 0.7% and 7.1%, respectively (Figure). ROS users had a higher total daily insulin dose than non-users and ROS use was associated with more people achieving consensus TIR, TBR and GMI goals (Figure).Conclusion: These data demonstrate safe and effective glycemic control with the MiniMed™ 780G system on days without user-initiated boluses and a greater proportion of real-world users achieving glycemic goals when recommended optimal settings are used.Disclosure J.J.F. McVean: Employee; Medtronic. Z. Dai: Employee; Metronics. F. Niu: None. J. Shin: Employee; Medtronic. R.A. Vigersky: Employee; Medtronic.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-132-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 133-OR: Cellular miRNAs Form a Network of Epigenetic Regulation of Protein
Expression in Muscle in Type 2 Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 133-OR
Abstract: Introduction and Objective: miRNAs are emerging as significant regulators of metabolism in health and disease. Indeed, alterations in miRNAs can impact key metabolic pathways and processes such as adipocyte differentiation, insulin signaling, beta cell function, and inflammation. While substantial progress has been made in understanding miRNA involvement in T2D pathogenesis, how they might contribute to epigenetic regulation remains unclear.Methods: In the present study, we aimed to determine how T2D can modify the expression of cellular miRNAs in muscle using a disease-in-a-dish model in which iPS cells from T2D patients and controls were differentiated into myoblasts (iMyos) and cellular miRNAs assessed using a nuclease protection assay.Results: We find that compared to controls, iMyos from T2D patients, in vitro and in the absence of circulating factors, exhibit alterations in cellular miRNA expression with 22 significantly up-regulated and 49 down-regulated miRNAs. miRNAs were distributed across the whole genome. Importantly, overlapping of the miRNA-predicted targets with RNA seq and MS-based proteomics data revealed that for the up-regulated miRNAs, 120 of their predicted targets were downregulated at the protein level, with only 11 of these due to changes at mRNA levels. Likewise, for the down-regulated miRNAs, all 91 of their predicted targets were upregulated at protein level, while none were changed at mRNA level. Overexpression of miRNA mimics in iMyos further confirmed regulation of changes at protein levels, with minimal changes at mRNA levels. Thus, human iPSC-derived myoblasts exhibit dysregulated miRNA expression in vitro, and these altered miRNAs regulate protein expression with little change in mRNA, contributing to the pathogenesis of T2D.Conclusion: We conclude that miRNAs serve as an important epigenetic regulator of protein expression in muscle in insulin resistance of T2D and that cell T2D-induced cell intrinsic alterations in miRNA expression can drive important changes in their target proteins.DisclosureA. Nawaz: None. M. Lino: None. N. Haider: None. A. Gattu: None. C. Kahn: Consultant; Novo Nordisk, Cellarity. Advisory Panel; TIXiMED. Board Member; 1825.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-133-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 134-OR: NOD1 Deletion in Skeletal Muscle Protects against
Palmitate-Induced Insulin Resistance-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 134-OR
Abstract: Introduction and Objective: Nucleotide-binding oligomerization domain 1 (Nod1), an immune receptor, drives fat-induced insulin resistance. Recent studies show that whole-body and hematopoietic Nod1 knockout (KO) protect against insulin resistance. However, it remains uncertain whether the effect in whole-body KO is due to Nod1 deficiency in macrophages or in extra-macrophage cell(s). Nod1 is expressed in insulin-sensitive tissues, with evidence showing fatty acids activate Nod1 in adipocytes and Nod1 activators induce insulin resistance in hepatocytes, suggesting a potential role for extra-macrophage Nod1. To investigate the tissue-specific effects of Nod1, fat infusions were conducted in muscle-specific KO mice, as skeletal muscle is a primary site for insulin regulated glucose metabolism and whole-body Nod1KO mice are protected against peripheral insulin resistance.Methods: We have generated skeletal muscle specific Nod1KO mice by crossing Nod1 floxed mice with Myf6Cre+ mice. Both wild-type (WT, i.e. Nod1f/f and Myf6Cre+) and KO mice underwent a 48-hour infusion with ethylpalmitate, which is hydrolyzed in plasma into palmitate and ethanol to elevate circulating free fatty acids (FFA) in a non-toxic manner. After the infusion, we performed a hyperinsulinemic-euglycemic clamp to evaluate insulin sensitivity. A radioactive tracer (3-H3) was also used to differentiate hepatic from peripheral insulin resistance.Results: Nod1 deficiency in skeletal muscle alleviated palmitate-induced insulin resistance observed in WT mice. Tracer analysis showed that muscle Nod1KO significantly increased insulin-stimulated glucose utilization, however had no effect on hepatic glucose production.Conclusion: Our findings suggest that skeletal muscle-specific Nod1 deletion protects against palmitate-induced insulin resistance by enhancing peripheral insulin sensitivity. This highlights the critical role of muscle Nod1 in regulating insulin action and glucose metabolism.DisclosureS. Rahman: None. K. Sun: None. J. Park: None. M.A. Garcia: None. A. Giacca: None.FundingCanadian Institutes of Health Research (CIHR 507485)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-134-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 135-OR: Skeletal Muscle Insulin Sensitivity Shows Time-Dependent
Regulation by the Clock Output Gene DBP-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 135-OR
Abstract: Introduction and Objective: Circadian rhythm disruption is associated with metabolic disorders, yet the role of clock-controlled output genes in glucose metabolism remains unclear. We are studying how the D-box binding protein (DBP) influences insulin sensitivity and glucose homeostasis in a time-dependent manner.Methods: DBP knockout (KO) mice were established by restoring frozen embryo and using CRISPR-Cas9 system. Oral glucose tolerance tests (OGTT) and insulin tolerance tests (ITT) were performed at 12 and 13 weeks of age, respectively. Insulin secretion was also assessed by static incubation assay. Insulin sensitivity in the liver and gastrocnemius muscle (GM) was analyzed by measuring AKT phosphorylation and the content of 2-deoxy-D-glucose. Serum free fatty acid (FFA) levels were monitored every 4 hours. Transcriptome analysis was conducted on GM.Results: KO mice exhibited decreased insulin secretion, yet maintained normal glucose tolerance. Enhanced insulin sensitivity was observed in ITT at ZT1 but not at ZT13, as insulin sensitivity in wild-type (WT) mice varied with circadian rhythm. At ZT1, blood glucose levels 120 min after insulin loading were lower in KO mice (WT vs KO = 215 vs 123 mg/dL, p < 0.01). Akt phosphorylation at ZT1 showed no difference in the liver, but in the GM phosphorylation was about 3-fold higher in KO mice than in WT mice. 2DG content showed no difference in liver, but an approximately 4.5-fold increase in KO mice in GM. Plasma FFA levels decreased during the light cycle in KO mice. RNA sequencing identified 941 DBP-regulated genes in GM, with gene ontology analysis revealing enrichment in leukocyte-activation related pathways.Conclusion: DBP deficiency enhances muscle insulin sensitivity in a time-specific manner, potentially through the regulation of serum FFA levels and immune system, which may be mediated by serum FFA levels and immune system regulation. Our study suggests that DBP is a potential therapeutic target for insulin resistance.DisclosureA. Taguchi: None. Y. Kajimura: None. C. Yodokawa: None. Y. Fujioka: None. Y. Nagao: None. R. Hatanaka: None. S. Hiroshige: None. H. Mikami: None. Y. Tanizawa: Advisory Panel; Novo Nordisk A/S. Speaker's Bureau; Teijin Pharma Limited, Chiesi Pharma. Y. Ohta: None.Fundingthe Japan Society for the Promotion of Science, 23K06401 (to A.T), 19K09006 (to Y.O.), and 19H03710 (to Y.T.)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-135-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 136-OR: Placental-Derived MicroRNAs Modulate the Insulin Response in Human
Skeletal Myocytes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 136-OR
Abstract: Introduction and Objective: Maternal insulin resistance (IR) increases throughout pregnancy to support fetal growth, but excessive IR can lead to Gestational Diabetes Mellitus (GDM). Placental microRNAs (miRNAs) may regulate insulin during pregnancy. Higher plasma levels of miRNAs from the placenta-specific chromosome 19 miRNA cluster are linked to GDM development. However, the mechanisms by which miRNAs may regulate insulin responsiveness are unclear. We hypothesize that placental miRNAs act as endocrine molecules affecting the insulin response pathway, contributing to increased insulin resistance.Methods: Primary human skeletal myocytes were differentiated to myotubes to assess the impact of selected placental miRNA on the insulin response pathway. Insulin-sensitive glucose uptake was measured by incubating myotubes with tritium-labeled glucose following miRNA transfection and 100 nM insulin treatment for 1 hour. Proteins central to insulin signaling (insulin receptor (IRβ), insulin receptor substrate (IRS-1)) were extracted, and their total and phosphorylated levels were quantified following 100 nM insulin for 20 minutes, after transfection with either miR-scramble, hsa-miR-516b-5p, hsa-miR-517a-3p, hsa-miR-524-3p, or hsa-miR-1283 using automatic western blotting (WES).Results: We show that placental miRNAs, miR-516b-5p, miR-517a-3p, miR-524-3p, and miR-1283 repress the insulin response. Transfection with hsa-miR-1283 and insulin treatment led to a 50% reduction in glucose uptake (P<0.05, t-test), with similar results for the other miRNAs. We also observed a 40% decrease in IRβ levels and phosphorylation, and a 30% decrease in IRS-1 levels and phosphorylation (P<0.05, t-test). These reductions in IRβ and IRS-1 were consistent across all tested placental miRNAs.Conclusion: Placenta-derived miRNAs regulate glucose uptake and the insulin response in skeletal myocytes, supporting our hypothesis that placental miRNA act as endocrine factors modulating insulin resistance.DisclosureI. Soukar: None. T. Kaneko-Tarui: None. M. Hivert: None. P.F. O'Tierney-Ginn: Consultant; MEDIPOST Inc.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-136-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 137-OR: Towards Retrievable, Immune-Priviledged, 3D-Printed Hydrogels to
Deliver Functional Islets-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 137-OR
Abstract: Introduction and Objective: Transplantation of free islets is limited by the need for systemic immune suppression. To protect transplanted cells from the autoimmune response and avoid the negative effects of systemic immune suppression, which can include damage to remaining and transplanted beta cells, we are developing physical immune-protective hydrogels. We demonstrated good survival and function in our proprietary synthetic hydrogels in vitro and in vivo and are moving towards a single, retrievable device with a high surface area (LifeRaftsTM).Methods: Fluorescently labelled proteins were used for size exclusions experiments. Blood glucose, C-peptide, and HbA1c of encapsulated donor islets were measured following implantation into streptozotocin (STZ)-induced diabetic immunocompetent rodents. LifeRaftsTM were printed using a commercially available bioprinter and either assessed for viability and protein secretion in vitro or implanted into healthy animals to assess graft survival and host-implant interactions.Results: Protein exclusion could be fine-tuned to excluded IgG, while maintaining good cell viability after encapsulation or printing. Encapsulated rat islets demonstrated rapid and sustained blood glucose control for 110+ days in immunocompetent mice and rats while the functionality of human islet could be extended in mice and large animals, as indicated by reduced blood glucose and increased C-peptide and HbA1c levels. Explanted LifeRaftsTM showed visible blood vessels early post-implant.Conclusion: Our proprietary, retrievable hydrogels showed strong immune protection for both allogenic and xenogeneic transplantation, without any immunosuppression. Early LifeRaftsTM demonstrated promising tissue integration. We are currently preparing for functional studies using LifeRaftsTM, in pursuit of a single retrievable device for functional cell therapy.Disclosure H. Stover: Employee; Allarta Life Science Inc.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-137-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 138-OR: Cellular and Gene Therapy Development for Severe Hypoglycemia via
Direct Innovative Cell Conversion-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 138-OR
Abstract: Introduction and Objective: Direct cell fate conversion (DIVER), which bypasses pluripotent stem cells, enables somatic cells to directly transform into functional target cells. This next-generation regenerative medicine technology holds promise for severe diabetes mellitus. However, efficiency, quality, and safety improvements remain essential for clinical translation.Methods: We developed a novel DIVER protocol incorporating Ngn3, MafA, Pdx1, and a newly identified "K-factor." This protocol induces pancreatic islet-like cells (DiBic) from somatic cells in a single step. The efficacy of these cells was assessed through transplantation into streptozotocin (STZ)-induced type 1 diabetic mice. Additionally, in vivo gene therapy was tested using transgenic K-factor expression.Results: Our technology achieved over 80% conversion efficiency to insulin-producing cells. Transplanted DiBic reduced blood glucose and HbA1c in diabetic mice. The in vivo gene therapy normalized hyperglycemia within days. Immunohistochemistry confirmed robust insulin production in converted cells, demonstrating K-factor's ability to induce direct somatic cell reprogramming with high efficiency.Conclusion: Our findings establish a highly efficient and reproducible DIVER technology for cellular and gene therapy applications. This platform has transformative potential for the treatment of diabetes, either as a standalone regenerative therapy or in combination with existing treatments such as insulin injections or stem cell technologies. This study represents a critical step toward the practical application of regenerative medicine for severe diabetes mellitus.DisclosureM. Matsumoto: None.FundingJapan Agency for Medical Research and development, AMED (24bm1223024h0001, 24ym0126110h0002), JSPS KAKENHI (JP24936409), JST START Project Promotion Type (JPMJSF2307), Juntendo President Special Research Program Seeds A (GP22A-004, 2022-24), Kawano Masanori Memorial Public Interest Incorporated Foundation for Promotion of Pediatrics, KOSE Cosmetology Research Foundation
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-138-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 139-OR: AdoShell®, a Nonfibrotic Encapsulation System, Enables Stem
Cell-Derived Islets In Vivo Maturation for T1DM Treatment-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 139-OR
Abstract: Introduction and Objective: AdoShell® is an easily implantable and fully retrievable scaffold for islet transplantation aiming to cure diabetes by cell therapy without requiring immunosuppression. It is based on a permselective hydrogel film allowing insulin diffusion while preventing immune cells invasion. Having demonstrated in vivo immunoprotection and functionality with human islets enabling a First In Human study, the compatibility with stem cell-derived islets (SCDI) was demonstrated to alleviate the rarity of donor pancreas.Methods: SCDI were prepared as described in Barsby et al, 2022. They were then encapsulated in AdoShell® and evaluated in vitro by glucose and exenatide stimulated secretion assay (GSIS).AdoShell® SCDI were implanted in 3 NXG mice for 4 months, and explants were analyzed by GSIS, total insulin content, histology and immunohistochemistry.Results: Encapsulation of SCDI maintained in vitro functionality, insulin secretion level and intracellular content compared to naked SCDI.In vivo, encapsulated SCDI showed a steady increase in human C-peptide secretion over 2 to 3 months and reached a plateau, a kinetic comparable to published maturation phenotypes.After 132 days in vivo, explanted encapsulated SCDI showed increase of insulin secretion (3-fold), secretion indexes (1.5-fold), and total insulin content (2.4-fold) compared to pre-implantation levels. They maintained viability (well defined nuclei) with signs of maturation (clusters of endocrine cells with glucagon- or insulin- cells but no co-expressing cells). No signs of transdifferentiation was observed (no visible canalar or acinar cells).Conclusion: The ability of SCDI to mature in AdoShell® was demonstrated in vivo, a step towards treatment of type 1 diabetes with SCDI without requiring immunosuppression.Disclosure O. Jouannot: Employee; ADOCIA. Stock/Shareholder; ADOCIA. A. Martin: Employee; ADOCIA. Stock/Shareholder; ADOCIA. J. Brun: Employee; ADOCIA. Stock/Shareholder; ADOCIA. C. Gautier: Employee; ADOCIA. Stock/Shareholder; ADOCIA. C. Cocita: Other Relationship; ADOCIA. J. Saarimäki-Vire: None. T. Otonkoski: None. D. Balboa: None. N. Laurent: Employee; ADOCIA. Stock/Shareholder; ADOCIA. A. Gaffuri: Employee; ADOCIA. Stock/Shareholder; ADOCIA. R. Eloy: None. O. Soula: Board Member; ADOCIA. Stock/Shareholder; ADOCIA. Other Relationship; ADOCIA.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-139-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 140-OR: Durable Glycemic Control and Elimination of Exogenous Insulin Use
-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 140-OR
Abstract: Introduction and Objective: VX-880 is an allogeneic stem cell-derived, fully differentiated islet cell therapy in clinical development for T1D.Methods: This single-arm, open-label, phase 1/2/3 trial is evaluating VX-880 in T1D adults with impaired hypoglycemia awareness and ≥2 severe hypoglycemic episodes (SHEs) the year before enrollment. Participants receive a standard immunosuppression regimen. Enrollment and dosing in the phase 1/2 portion has completed and phase 3 is ongoing.Results: These results reflect 12 participants who received a full VX-880 dose as a single infusion and were followed for at least one year, as of October 2024. At baseline, all participants had multiple SHEs and undetectable fasting C-peptide. All 12 participants demonstrated engraftment with glucose responsive C-peptide production at Day (D)90 MMTT which was durable through Month (M)12. All 12 participants achieved ADA HbA1c target of <7% (mean: baseline=7.8%; M12=6.0%) and time in range target of >70% (mean: baseline=49.5%; M12=93%); and all were free of SHEs from D90 onwards. All 12 participants had reduction in exogenous insulin use (mean reduction: 92%) and 10/12 (83%) no longer required exogenous insulin at M12. Median duration free of exogenous insulin was 232 (69 to 441) days. All 12 participants were evaluable for and achieved the phase 1/2 primary endpoint of elimination of SHEs and HbA1c <7%. Most adverse events (AEs) were mild or moderate in severity. There were no VX-880-related serious AEs. Two deaths occurred; both were reported previously and unrelated to VX-880. Overall, the safety profile was consistent with the immunosuppressive regimen and islet infusion procedure.Conclusion: These durable clinical benefits of VX-880 with elimination of SHEs, improved glycemic control, and freedom from exogenous insulin support the curative potential of VX-880, the first and only allogeneic, stem-cell derived, islet cell therapy in pivotal development.Disclosure M.R. Rickels: Consultant; Vertex Pharmaceuticals Incorporated, Sernova, Corp. Research Support; Dompé, Tandem Diabetes Care, Inc. Consultant; Novo Nordisk. P. Witkowski: Advisory Panel; Vertex Pharmaceuticals Incorporated. Research Support; Sernova, Corp. Stock/Shareholder; Eledon. T.W. Reichman: Research Support; Vertex Pharmaceuticals Incorporated. Advisory Panel; Novo Nordisk. E.J. de Koning: None. J.F. Markmann: Consultant; iTolerance, Inc, Vertex Pharmaceuticals Incorporated. J.S. Odorico: Other Relationship; Regenerative Medical Solutions, Inc. Research Support; Juvenile Diabetes Research Foundation (JDRF). Other Relationship; Vertex Pharmaceuticals Incorporated, Veloxis. Research Support; National Institute of Diabetes and Digestive and Kidney Diseases. Consultant; UpToDate, Sernova, Corp. M. Wijkstrom: Consultant; Vertex Pharmaceuticals Incorporated. L.S. Kean: Consultant; Vertex Pharmaceuticals Incorporated. Research Support; Bristol-Myers Squibb Company, Tessera, Gilead Sciences, Inc, Novartis Pharmaceuticals Corporation. Advisory Panel; HiFi Bio. Research Support; Tonix, Merck & Co., Inc. C. Mathieu: Advisory Panel; Novo Nordisk, Sanofi, Eli Lilly and Company, Abbott, Medtronic, SAB Biotherapeutics, Inc, Roche Diabetes Care, Vertex Pharmaceuticals Incorporated, Biomea Fusion, Bayer Pharmaceuticals, Inc. A.L. Peters: Advisory Panel; Medscape. Consultant; Vertex Pharmaceuticals Incorporated. Research Support; Insulet Corporation, Abbott. Other Relationship; Omada Health. Y. Tan: None. K. Vanijcharoenkarn: None. D. Melton: Employee; Vertex Pharmaceuticals Incorporated. Stock/Shareholder; Sana Biotechnology. F. Pagliuca: Employee; Vertex Pharmaceuticals Incorporated. B. Bruinsma: Employee; Vertex Pharmaceuticals Incorporated. G. Marigowda: Employee; Vertex Pharmaceuticals Incorporated. C. Ricordi: Advisory Panel; Vertex Pharmaceuticals Incorporated, Novo Nordisk.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-140-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 141-OR: Safety, Tolerability, and Clinical Effects of Dapiglutide, a
Once-Weekly GLP-1R/GLP-2R Agonist-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 141-OR
Abstract: Introduction and Objective: Dapiglutide is a first-in-class GLP-1R/GLP-2R agonist in development for weight management designed to address low-grade inflammation and obesity-associated co-morbidities. Safety, tolerability, pharmacokinetics and pharmacodynamics of once-weekly s.c. dapiglutide were investigated in a phase 1b trial.Methods: In a double-blind, placebo-controlled trial, 54 healthy participants with BMI 27-39.9 kg/m2 (85% male, median age: 46 yrs, BMI: 30.0 kg/m2, body weight: 95.1 kg) were randomized (14:4) within 3 dose cohorts. Dose escalation every 2nd week was used to reach target doses of 7.5 mg, 10 mg and 13 mg during a 13-week treatment period. No lifestyle interventions were included in the trial.Results: Dapiglutide appeared safe with no related serious or severe adverse events (AEs). The most frequent AEs reported were gastrointestinal (GI) disorders and metabolism and nutrition disorders (mainly decreased appetite). Most AEs were mild. Two dapiglutide treated participants discontinued due to AEs (GI AEs). The pharmacokinetics showed dose proportionality and a mean half-life of 112-119 hours across the 3 dose cohorts. Low titers of ADA were detected at follow-up in 14.3% of the participants dosed with dapiglutide with no apparent impact on pharmacokinetics, efficacy or safety. After 13 weeks (of which 9, 7 and 5 weeks were on target doses), the placebo-corrected estimated mean decrease in body weight (efficacy estimand) was 6.7%, 8.3% and 7.1% for the dose cohorts of 7.5 mg, 10 mg and 13 mg, respectively. The mean body weight gain on placebo was 2.1%.Conclusion: Dapiglutide treatment of up to 13 mg appeared safe and well-tolerated with an AE profile similar to other incretin-based therapies. The placebo-adjusted reductions in body weight were up to a mean of 8.3% with dapiglutide after 13 weekly doses. The half-life of dapiglutide is suitable for once-weekly dosing. Doses up to 26 mg are currently being evaluated.Disclosure S. Maarbjerg: Employee; Zealand Pharma A/S. Stock/Shareholder; Zealand Pharma A/S. R. Zachariae: Employee; Zealand Pharma A/S. U. Hövelmann: None. N.J. Johansen: Employee; Zealand Pharma A/S. J.U.E. Lundahl: Employee; Zealand Pharma A/S. L.F. Larsen: Employee; Zealand Pharma A/S. N.S. Sørensen: Employee; Zealand Pharma A/S. E. Frary: Employee; Zealand Pharma A/S. T. Heise: Research Support; ADOCIA, Afon Technology, AstraZeneca, Altimmune Inc, Biocon, BIOTON, Civica Foundation, Eli Lilly and Company, Zealand Pharma A/S, Betagenon, Cass Pharmaceuticals, Novo Nordisk A/S, Corteria, Zealand Pharma A/S, Cytoki, Enyo Pharma, Gan & Lee Pharmaceuticals, Genova, Nanexa, Neodyne, SamChunDang Pharma. Co., Spiden, Sun Pharmaceutical Industries Ltd. Speaker's Bureau; Eli Lilly and Company, Novo Nordisk A/S. Consultant; Gan & Lee Pharmaceuticals.FundingZealand Pharma A/S
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-141-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 142-OR: Safety, Tolerability, Pharmacokinetics (PK), and Pharmacodynamics
(PD) of a Dual GLP-1/GIP Receptor Agonist (HDM1005)—A Phase I,
Randomized, Double-Blind, Placebo-Controlled, Single and Multiple
Dose-Escalation Study-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 142-OR
Abstract: Introduction and Objective: HDM1005 is a long-acting GLP-1R/GIPR peptide dual agonist that exhibits potent activity on both GLP-1 and GIP receptors. Here we report the results of a phase I study of HDM1005 in healthy participants (NCT06640647) and overweight/obese participants (NCT06637020).Methods: In this phase I study, we enrolled 64 participants in a SAD (doses 0.1-7 mg) study and 40 in a 4-week MAD (doses 0.5-4 mg) study. Participants were randomized (4:1) to receive subcutaneous injection of HDM1005 or placebo. Safety and tolerability, PK, and PD of HDM1005 were assessed.Results: The most common AEs with HDM1005 were decreased appetite and gastrointestinal AEs (nausea, vomiting, and abdominal distension), which were generally dose-dependent and mild in severity. No grade 3 hypoglycemia reported, no severe or serious events occurred and no early termination due to AE. Drug exposure were dose proportional across 0.1-7.0 mg. The mean t1/2 was approximately 3.5 days. After single and multiple doses, we observed significant and dose-dependent mean reduction in 0 to 2 h glucose AUC relative to placebo. In SAD, body weight loss was dose-dependent and the maximal mean loss on D8 was 3.92 kg (5.36%) in 5 mg group. In MAD, the mean reductions in body weight on D29 ranged from 4.79-7.76 kg (6.12%-10.29%) across 0.5-4.0 mg groups versus 3.13kg (3.71%) in placebo, and the weight loss maintained at 4 weeks after treatment discontinuation (difference relative to placebo from 3.29% - 6.05%). A weight reduction of > 5% by week 4 occurred in 87.5% in HDM1005 groups versus 25% in placebo. HDM1005 also reduced TC, TG and LDL-C levels by week 4.Conclusion: HDM1005 was well tolerated, had favorable PK, and led to promising body weight reduction and improvements in OGTT AUC0-2h and lipid profiles. Phase II studies of HDM1005 in obesity and T2DM are currently ongoing.DisclosureY. Du: None. W. Hu: None. Q. Zhang: None. Y. Fan: None. F. He: Employee; Hangzhou Zhongmei Huadong Pharmaceutical Co., Ltd. H. Lu: Employee; Huadong Medicine Co., Ltd, QILU Pharmaceutical. L. Shen: Employee; HuaDong Pharmaceutical Co., Ltd. X. Cong: Employee; Huadong Medicine Co., Ltd. L. Zhong: Employee; HuaDong Pharmaceutical Co.,Ltd. J. Li: Employee; Huadong Medicine Co., Ltd. J. Xu: Stock/Shareholder; Huadong Medicine Co. Ltd. Employee; Huadong Medicine Co. Ltd.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-142-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 143-OR: NA-931, a Novel Quadruple IGF-1-1, GLP-1, GIP, and Glucagon
Receptor Agonist Reduces Body Weight without Muscle Loss-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 143-OR
Abstract: Introduction and Objective: NA-931 is a quadruple agonist of the insulin-like growth hormone- (IGF-1), glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP) and glucagon receptor agonist for the potential treatment of metabolic disorders such as obesity.Methods: This is a randomized, double-blind, placebo-controlled, dose escalation, study to assess the safety and tolerability, pharmacokinetics, and pharmacodynamics of NA-931 when administered as single and multiple-ascending doses in overweight/obese participants. ClinicalTrials.gov ID NCT06615700Results: Body Weight Reductions: In the 28-day study, subjects receiving NA-931 (n=74) demonstrated dose-dependent reductions in mean body weight from baseline, ranging up to 6.4%. For doses ≥60 mg, placebo-adjusted reductions in mean body weight were maintained or improved at Day 35, seven days after the last dose of NA-931 was administered, ranging up to 5.3% relative to placebo. An exploratory assessment of the proportion of subjects achieving at least 5% weight loss after 28 days demonstrated that up to 63% of NA-931-treated subjects achieved ≥5% weight loss, compared with 0% for placebo.Safety and Tolerability: Among subjects receiving NA-931, emergent adverse events (TEAEs) were reported to date have been insignificant or mild. All observed gastrointestinal (GI) adverse events have been reported as insignificant or mild, with the majority (84%) reported as insignificant. Mild nausea and vomiting were not reported among any NA-931-treated subjects. Diarrhea was reported in one subject (2.3%) receiving NA-931 compared with two subjects (10%) receiving placebo. No muscle loss was observed. No clinically meaningful differences were reported for GI-related adverse events among subjects treated with NA-931 compared with placebo.Conclusion: We are conducting a Phase 2 trial with the oral formulation of NA-931 for the possible treatment of obesity.DisclosureL.L. Tran: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-143-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 144-OR: Sustained Weight Reduction by Thresholds in Adults with Obesity
and Prediabetes Treated with Tirzepatide over 176 Weeks (SURMOUNT-1)-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 144-OR
Abstract: Introduction and Objective: Sustained weight reduction long-term is associated with continued reduction in cardiovascular risk and mortality. Treatment with tirzepatide (TZP), a dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist, once weekly in participants with obesity or overweight without type 2 diabetes resulted in substantial body weight reductions in the SURMOUNT-1 (SM-1) trial. This SM-1 post-hoc analysis assessed the sustainability of weight reductions in participants with prediabetes over 176 weeks of treatment.Methods: On-treatment data from participants with prediabetes at randomization and with weight measurement available at Week 176 (5 mg, N=143; 10 mg, N=164; 15mg, N=151) vs placebo (N=114) were used for this analysis. Sustained weight reduction was defined as meeting the given threshold (≥5%, ≥10%, ≥15%, ≥20%) at a postbaseline weight measurement and then at all subsequent postbaseline weight measurements up to Week 176.Results: Participants who met the defined weight reduction thresholds of ≥5%, ≥10%, ≥15% and ≥20% at any time during the 176-week long trial with TZP across the 3 doses vs placebo were 99% vs 68%, 92-98% vs 40%, 70-93% vs 22%, and 48-80% vs 7%, respectively. Body weight reduction was sustained for longer in TZP-treated participants than those randomized to placebo (median: 167-168 vs 164 weeks, 160-161 vs 128 weeks, 141-153 vs 65 weeks, and 129-140 vs 65 weeks for weight reduction targets of ≥5%, ≥10%, ≥15% and ≥20% vs placebo, respectively).Conclusion: In SM-1 participants with obesity or overweight and prediabetes, treatment with TZP was associated with a longer continuous time spent with weight reduction ≥5%, ≥10%, ≥15% and ≥20% vs placebo over 176 weeks. The long-term cardiovascular impact of weight reduction with TZP treatment is under evaluation in an ongoing outcomes study (SURMOUNT-MMO, NCT05556512).Disclosure J.D. Ard: Research Support; Nestlé Health Science. Consultant; Eli Lilly and Company, Novo Nordisk, Weight Watchers International. Research Support; Weight Watchers International. Consultant; Boehringer-Ingelheim. Research Support; Boehringer-Ingelheim, Eli Lilly and Company, Epitomee. Consultant; Amgen Inc. Research Support; Regeneron Pharmaceuticals. Consultant; Regeneron Pharmaceuticals, Amplifier Therapeutics. C. Lee: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. D. Cao: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. L. Garcia-Perez: Employee; Eli Lilly and Company. A. Stefanski: Employee; Eli Lilly and Company. R. Griffin: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-144-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 145-OR: ADA Presidents' Select Abstract: Association of Age at Type 1
Diabetes Diagnosis with Fatal Cardiovascular and Kidney Events-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 145-OR
Abstract: Introduction and Objective: Individuals with type 1 diabetes (T1D) have a greater risk of complications and reduced life expectancy compared with those without diabetes. It is hypothesized that age at T1D diagnosis impacts clinical complications and mortality.Methods: A nationwide retrospective cohort study was conducted. Individuals ≥18 years of age with T1D with ≥1 entry in the Swedish National Diabetes Register (NDR) from 1998 through 2019 and matched controls were included. T1D status was based on insulin use and diagnosis at ≤30 years of age. Individuals with T1D with coexisting congenital, metabolic, or neurological disorders were excluded. Relationships between age at T1D diagnosis and fatal and nonfatal outcomes (eg, cardiovascular (CV) mortality, acute myocardial infarction (MI), peripheral arterial disease (PAD), end-stage renal disease) were analyzed using Cox proportional hazards models.Results: Individuals with T1D (n=34,155) had a mean age of 30.7 years and median follow-up of 12.9 years. Younger age at T1D diagnosis was associated with a higher risk of mortality and nonfatal outcomes. T1D diagnosis at < 10 years of age was associated with 16.3 life-years lost. The hazard ratio (HR) per 1-year older age at T1D diagnosis was 0.97 (95% CI: 0.97, 0.98) for CV mortality, indicating a 2.6% lower risk for every 1-year increase in age at diagnosis. The HRs per 1-year older age at T1D diagnosis were 0.99 (95% CI: 0.98, 0.99) for non-CV mortality, 0.96 for end-stage kidney disease (95% CI: 0.96, 0.97), 0.97 (95% CI: 0.96, 0.98) for PAD, 0.97 (95% CI: 0.96, 0.98) for acute MI, 0.97 (95% CI: 0.97, 0.98) for heart failure, and 0.97 (95% CI: 0.97, 0.98) for coronary heart disease. T1D diagnosis before age 10 was associated with the greatest risk of CV mortality (HR 5.7; 95% CI: 4.3, 7.6).Conclusion: Early onset of T1D carries increased risk of serious complications and death. These findings support the premise that delaying T1D onset in young individuals may reduce the risk of future complications.Disclosure A. Rawshani: Consultant; Sanofi. B. Eliasson: Other Relationship; Sanofi, Eli Lilly and Company, Novo Nordisk. Speaker's Bureau; Boehringer-Ingelheim. Other Relationship; Amgen Inc. Advisory Panel; Abbott, Bayer Pharmaceuticals, Inc. D.K. McGuire: Consultant; Novo Nordisk. Advisory Panel; Novo Nordisk. Consultant; Lilly USA LLC. Advisory Panel; Lilly USA LLC. Consultant; Boehringer-Ingelheim. Advisory Panel; Boehringer-Ingelheim, AstraZeneca, ESPERION Therapeutics, Inc., NewAmsterdam Pharma, Pfizer Inc. Consultant; Applied Therapeutics, Lexicon Pharmaceuticals, Inc, Bayer Pharmaceuticals, Inc, Amgen Inc, Kailera, Idorsia, Alveus, Metsera. N. Sattar: Other Relationship; Abbott, AbbVie Inc, Amgen Inc, AstraZeneca, Boehringer-Ingelheim, Eli Lilly and Company. Advisory Panel; Hanmi Pharm. Co., Ltd. Consultant; Carmot Therapeutics, Inc, Menarini. Other Relationship; Novartis AG, Novo Nordisk, Pfizer Inc, Roche Diagnostics. Consultant; GlaxoSmithKline plc, Metsera. Other Relationship; American Diabetes Association, Medscape. H.C. Gerstein: Advisory Panel; Abbott, Bayer Pharmaceuticals, Inc, Eli Lilly and Company, Novo Nordisk. Consultant; Pfizer Inc, Sanofi, Hanmi Pharm. Co., Ltd. Research Support; Eli Lilly and Company, Novo Nordisk, Hanmi Pharm. Co., Ltd. Other Relationship; Eli Lilly and Company, Novo Nordisk, Sanofi, Boehringer-Ingelheim, Abbott, Jiangsu Hansen, Zuellig Pharma, AstraZeneca. J. Isufi: None. N. Cui: None. O. Guenther: Employee; Sanofi. J.H. Zaccai: Employee; Sanofi. A. Mahieu: Employee; Sanofi. A. Rawshani: Consultant; Sanofi.FundingThis study was funded by Sanofi. Acknowledgments: Medical writing support was provided by Lauren Poppi, PhD, of IMPRINT Science, New York, NY, and was funded by Sanofi.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-145-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 146-OR: Understanding Early Disease Trajectories and Their Relationship to
Microvascular Complications-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 146-OR
Abstract: Introduction and Objective: Understanding early disease trajectories and their relationship to microvascular complications remains crucial in type 2 diabetes mellitus (T2DM). We employed machine learning to identify critical intervention windows and predictive patterns of microvascular complications.Methods: Machine learning analysis of 591 T2DM patients, focusing on disease discovery patterns, peripheral vascular status, and complication rates. Neural network modeling was used to identify temporal relationships between early disease markers and complication development. Primary outcomes included peripheral pulse status, retinopathy, and foot abnormalities across age groups.Results: AI analysis revealed three critical findings: 1) A significant "vascular preservation window" in early disease (peripheral pulses well felt: 95.5% in <40 years vs 83.5% in >50 years, p<0.001), 2) Early diagnosis patterns showed distinct clustering (26.1% diagnosed "today," with age-specific variations: 30.8% in <40, 19.5% in 41-50, 26.3% in >50 years), and 3) Novel "complication vulnerability phases" identified through machine learning, with the first phase occurring at 2.3±0.4 years post-diagnosis. Notably, liver function abnormalities showed age-specific patterns (ALT elevation: 25.0% overall, with significant age-group variations, p=0.013), emerging as an early marker for complication risk (OR: 1.9, 95% CI: 1.4-2.5).Conclusion: Our AI-driven analysis identifies a critical "vascular preservation window" and specific "complication vulnerability phases" in T2DM progression. These findings suggest optimal timing for aggressive intervention, particularly in patients diagnosed before age 40, and highlight liver function as a novel early marker for complication risk. This temporal framework provides new opportunities for precision-timed interventions in T2DM management.DisclosureS.K. Singla: None. S.M. Patil: None. A. Maheshwari: None. A.A. Shaikh: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-146-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 147-OR: Association of Body Mass Index and Time in Target Range with
All-Cause and Cardiovascular Mortality in Adults with Type 2 Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 147-OR
Abstract: Introduction and Objective: We aimed to characterize the long-term changes using body mass index (BMI) time in target range (TTR) and test its independent association with all-cause and cardiovascular mortality.Methods: This study included 3524 patients (58% men) aged 40-80 years with at least 3 BMI measurements within 4 years since their first inpatient diagnosis of type 2 diabetes. TTR was defined as the percentage of time during which BMI was within 18.5-27.9 kg/m2. The associations of BMI TTR with all-cause and cardiovascular mortality were analyzed using multivariable Cox models and restricted cubic spline.Results: The mean BMI was 24.9 ± 3.8 kg/m2 and the mean BMI during the follow-up was 24.6 ± 3.3 kg/m2. During a mean follow-up of 4.9 years, 787 patients died, of whom 158 were died due to cardiovascular events. Each 1 SD (14.4%) increase in BMI TTR was significantly associated with a decreased risk of all-cause mortality (hazard ratio [HR] 0.86, 95% confidence interval [CI] 0.82-0.90) and cardiovascular mortality (HR 0.87, 95%CI 0.78-0.98) after adjusting for variability of BMI and traditional cardiovascular risk factors. Similar associations remained consistent among patients with lower baseline or mean BMI, and independent of age. Furthermore, restricted cubic spline showed a nonlinear association and indicated that patients with TTR ≥71.4% was associated with a lower risk of all-cause and cardiovascular mortality.Conclusion: Higher BMI TTR was independently associated with lower risks of all-cause and cardiovascular mortality. Thus, appropriate approaches to elevate BMI TTR may help minimize the burden of all-cause and cardiovascular mortality for middle aged and older adults with type 2 diabetes.DisclosureY. Bao: None. T. Hu: None. Y. Xu: None. X. Li: None. X. Ma: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-147-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 148-OR: People with Type 2 Diabetes Are at Greater Risk for Liver Fibrosis
after Recent Myocardial Infarction-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 148-OR
Abstract: Introduction and Objective: Type 2 diabetes (T2D) is linked to increased risk of cardiovascular diseases and metabolic dysfunction-associated steatotic liver disease (MASLD, previously known as non-alcoholic fatty liver disease), both resulting in worse long-term outcomes. Non-invasive tests (e.g. non-alcoholic fatty liver disease fibrosis score (NFS), fibrosis-4 test (FIB-4)), are increasingly used for risk stratification of liver fibrosis. However, the link between myocardial infarction (MI) and risk of liver fibrosis is not yet well understood. We hypothesized that people with recent MI bear a higher risk of liver fibrosis within the first year post-MI.Methods: Participants of the DIabetes and ST-segment Elevation MI (DISTEMI) study underwent comprehensive phenotyping at 6-12 weeks after MI (0Y, n=103, age 61±9 years, 76% male, BMI 28±4 kg/m2) and were followed for one year (1Y, currently n=84). Based on a 75-g oral glucose tolerance test, participants were assigned to either normoglycemia (25%), prediabetes (46%) or T2D (29%). The ejection fraction (EF) was quantified bymagneticresonance imaging, while NFS and FIB-4 were calculated using laboratory and anthropometric parameters.Results: The EF declined by about 5% from 0Y to 1Y (53±10% vs 51±10%, p<0.01), which was mainly driven by the T2D group (52±12% vs. 48±11%, p<0.05). FIB-4 rose by about 12% (1.28±0.85 a.u. vs. 1.43±0.90 a.u., p<0.001), which was independent of age and glucose tolerance, while the NFS increased by 56% (-1.10±1.47 a.u. vs. -0.61±1.28 a.u., p<0.0001). At 1Y, EF was inversely associated with NFS (r=-0.27, p<0.05), but not with FIB-4 (r=-0.22, p=0.10).Conclusion: One year after myocardial infarction, people with type 2 diabetes show a reduction in the left ventricular ejection fraction along with a rise in indices of liver fibrosis. The intricate interaction between the liver and the heart in acute and chronic phase after recent MI deserves further studies to dissect the impact of organ specific and systemic metabolic alterations on organ function.DisclosureC. Möser: None. O.P. Zaharia: None. F.C. Michelotti: None. V. Schrauwen-Hinderling: None. S. Trenkamp: None. G. Heilmann: None. P. Bobrov: None. V. Burkart: None. R. Wagner: Speaker's Bureau; Boehringer-Ingelheim, Novo Nordisk. Advisory Panel; Sanofi. Speaker's Bureau; Sanofi. Advisory Panel; Lilly Diabetes. J. Szendroedi: Advisory Panel; Novo Nordisk, Lilly Diabetes, Novartis AG, Boehringer-Ingelheim. M. Cramer: None. C. Jung: None. M. Kelm: None. M. Roden: Research Support; Boehringer-Ingelheim. Advisory Panel; Echosens. Speaker's Bureau; Madrigal Pharmaceuticals, Inc. Advisory Panel; MSD Life Science Foundation. Board Member; Novo Nordisk. Advisory Panel; TARGET PharmaSolutions, Inc.FundingSpecial Research Area (Sonderforschungsbereich, SFB) 1116 B12
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-148-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 149-OR: Integrative AI-Based Risk Score for Cardiometabolic
Diseases—Comparing Cardiovascular Risk Prediction to the Framingham
Score-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 149-OR
Abstract: Introduction and Objective: Cardiovascular disease (CVD) is a major complication in diabetes, requiring effective risk prediction tools. This study developed an AI-driven scoring system for CVD prediction, comparing machine learning models with the Framingham risk score (FRS).Methods: We analyzed two health datasets, the China Health and Retirement Longitudinal Study (CHARLS) and Shanghai Diabetes Studies (SDS), each with a 5-year follow-up. CVD was defined based on clinical histories and self-reported diagnoses of heart disease or stroke. Predictors included anthropometric measures, baseline labs, and disease status. Non-collinear datasets were created using LASSO-based feature selection. Models predicted CVD and were evaluated using stratified cross-validation and external validation, employing AUC, F1, and ROC curve metrics.Results: Logistic regression outperformed other models with the highest AUC (0.66). Compared to FRS (AUC: 0.61), the AI model demonstrated superior predictive performance. External validation (SDS) confirmed these findings, with consistent metrics across datasets, supporting the robustness and generalizability of the AI-driven scoring system.Conclusion: An AI-driven scoring system outperformed the Framingham risk score, providing a robust and generalizable tool for CVD prediction in diabetes.DisclosureT. Julaiti: None. J. Pan: None.FundingHainan Provincial Natural Science Foundation of China (821MS159)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-149-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 150-OR: Elevated Anti-NFKBIB Autoantibodies as a Novel Biomarker for
Cardiovascular Disease in HLA-Positive Patients and Autoimmune Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 150-OR
Abstract: Introduction and Objective: Cardiovascular disease (CVD) poses a major risk for individuals with type 1 diabetes (T1D), who experience 2-3 times higher rates of CVD events compared to the general population. While traditional CVD risk factors have been extensively studied, the contribution of autoimmunity to CVD in T1D remains poorly understood.Methods: We screened a broad range of proteins targeted by autoantibody (AAbs) array in plasma samples from Joslin “Medalists” (T1D≥50 years) who are either HLA T1D risk allele (-) or (+), people with type 2 diabetes, and controls, and identified three novel target antigens positively correlated with coronary artery calcification scores. Among these, NFKB Inhibitor β (NFKBIB) was selected for further validation using a custom developed anti-NFKBIB AAb immunoassay.Results: From Anti-NFKBIB AAb immunoassays, elevated levels of anti-NFKBIB AAb (log2-transformed) were observed in HLA(+) Medalists (n=394) compared to HLA(-) Medalists (n=61) (β=0.57; p=0.0001). Within the HLA(+) group, higher anti-NFKBIB AAb levels were associated with 40.5% significantly more odds for a positive history of CVD (OR 1.405; 95% CI: 1.221-1.616). Immunoblot analysis confirmed that IgG isolated from plasma of HLA(+) individuals detected recombinant NFKBIB protein in a concentration-dependent manner, in contrast to IgG from HLA(-) individuals and controls (P=0.024). To validate these findings, we analyzed plasma anti-NFKBIB AAb levels from ApoE-/-/NOD mice with autoimmunity and control non-diabetic ApoE-/-/CongNOD mice using the same immunoassay. Significantly higher levels of anti-NFKBIB AAb were observed in ApoE-/-/NOD mice compared to controls (P=0.0024).Conclusion: These findings provide evidence to the hypothesis that AAb to an antigen in the inflammatory pathway is associated with CVD in people with T1D, suggesting that autoimmunity may contribute to atherosclerosis in T1D.DisclosureK. Park: None. L. Pham: None. M. Yu: None. S. Jangolla: None. M. Ma: None. Q. Li: None. E.R. Viebranz: None. J. Fu: None. I. Wu: None. H. Shah: None. A. Doria: Research Support; Abbott, Lexicon Pharmaceuticals, Inc, Dexcom, Inc. G.L. King: None.FundingBeatson Foundation (2023-018R01HL161864, P30DK036836-37)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-150-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 151-OR: Comparison of WBC SPECT/CT and MRI in Diagnosis and Treatment
Response of Diabetic Foot Osteomyelitis Using Paired Biopsies as Reference
Standard-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 151-OR
Abstract: Introduction and Objective: The objective of this study was to compare the performance of Tc-99m WBC SPECT/CT and MRI in subjects with suspected diabetic foot osteomyelitis (DFO) using bone biopsy as a reference standard.Methods: In total, 47 subjects with suspected DFO underwent MRI and Tc-99m WBC SPECT/CT imaging prior to bone biopsy. Subjects with soft tissue infection or DFO received a 6-8 week course of antibiotics. Post-therapy MRI, SPECT/CT, and bone biopsy were repeated in 20 subjects. Imaging studies and histopathology were blindly interpreted as either DFO positive or negative. Biopsies were considered positive if either bone culture or histopathology indicated bone infection. Imaging results were assessed against the reference biopsy to determine the sensitivity and specificity of each in both the initial diagnosis of DFO and monitoring response to antibiotic therapy.Results: Sensitivity, specificity, positive and negative predictive values on initial DFO diagnosis were 85%, 79%, 90% and 69% for SPECT/CT and 73%, 43%, 85% and 40% for MRI, respectively. The kappa coefficient of agreement between the two imaging modalities was only 0.47. Post-antibiotic imaging revealed identical sensitivity, specificity, positive and negative predictive values for SPECT/CT and MRI, with 75%, 75%, 40% and 92%, respectively.Conclusion: SPECT/CT demonstrated better sensitivity and specificity than MRI at initial diagnosis. However, MRI and SPECT/CT performed statistically equally in evaluation of DFO following antibiotic therapy. Our results indicate that compared to MRI, SPECT/CT is a viable, if not superior, method for primary non-invasive assessment of DFO.DisclosureO.K. Oz: None. A. Sherwood: None. P.A. Crisologo: None. A.L. Killeen: Advisory Panel; GMS Holding, Caleres, Inc. K.L. Rubitschung: None. H. Hwang: None. A. Chhabra: Consultant; Icon medical, treace med concepts. Advisory Panel; Ibl, inc. Research Support; Qure-ai, ibl, inc. Speaker's Bureau; Telemed clinics. R.W. Haley: None. L.A. Lavery: Consultant; Limflow, enerenesis Medical, Clyra Medical technologies, Blue Sky, Tissue Health Plus. Stock/Shareholder; Xilas Medical. Consultant; Altrazeal.FundingAmerican Diabetes Association (I-17-ICTS-056)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-151-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 152-OR: Public Transit Access and Limb Loss in Atlanta, GA
-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 152-OR
Abstract: Introduction and Objective: Low-income populations often use public transit to access healthcare. We hypothesized transit access impacts diabetic foot ulcer (DFU) outcomes as limb salvage requires frequent outpatient visits. We investigated the association between public transit availability and amputation-free survival after DFU hospitalizations.Methods: All patients residing in metropolitan Atlanta and admitted with a DFU to four Atlanta hospitals between 2016-21 were included. We calculated post-hospitalization amputation-free survival to estimate amputation hazard ratio (HR) with death as a competing risk. Census tract per square mile and per capita public transit frequency were the independent variables, and we calculated adjusted HRs (aHR) for age, sex, race, PAD, and ESRD.Results: Among 2864 patients, 949 (33%) died or had an amputation post-hospital discharge (table). For every 0.1 additional transit opportunities per capita, the amputation aHR was 0.969 (95%CI 0.939-0.999, p=.03). For every 100 additional transit opportunities per square mile, the amputation aHR was 1.008 (95%CI 1.006-1.177, p=0.4).Conclusion: Public transit frequency per capita protected against limb loss, but the frequency per square mile had an adverse impact on limb loss. Patient-centric data on transit barriers and use of transit for healthcare access is needed to explain these apparently contradictory census tract level findings.DisclosureM. Schechter: None. J.W. Wei: None. R.R. DSouza: None. H. Zhang: None. M.K. Ali: Advisory Panel; Eli Lilly and Company. L.A. Waller: None. H.H. Chang: None.FundingThis study was supported by the National Institute on Minority Health and Health Disparities (R21MD017943) and the Emory University Woodruff Health Sciences Center Synergy Award
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-152-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 153-OR: Impact of Three-Month Continuous Glucose Monitoring Program on
Glycemic Control and Diabetic Foot Wound Healing within a Safety-Net
Health System-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 153-OR
Abstract: Introduction and Objective: Diabetic foot wound is the leading cause of non-traumatic lower extremity amputations (NLEA) and is more prevalent among ethnic minorities and those of lower socioeconomic status. Good glycemic control (HgbA1c <8%) has been shown to lower the risk of NLEA and may improve wound healing. Since continuous glucose monitoring (CGM) has been associated with better glycemic control in patients with diabetes, the use of CGM in patients with diabetic foot wound has the potential to improve both glycemic and wound healing outcomes.Methods: In this study, we evaluated the efficacy of a short-term (3 months) CGM program, which included 2 clinic visits and remote glucose monitoring every 1 to 2 weeks, on glycemic and diabetic foot wound healing outcomes, using a historical cohort as a comparison group.Results: The study cohort (25 patients, age 48 ± 9 years, 72% male, 80% Hispanic, 12% Black, 80% on charity care) had similar demographics to the pre-intervention cohort (78 patients, age 51 ± 9 years, 81% male, 68% Hispanic, 21% Black, 67% on charity care). The HgbA1c at foot diagnosis was similar for the 2 groups (CGM 10.4% ± 2% vs. pre-intervention 11.1 ± 2%, p = 0.17), but the HgbA1c at 3 to 6 months follow-up was significantly lower in the CGM cohort (7.5 ± 0.9% vs. 8.5 ± 2.0%, p = <0.05). Moreover, 72% of the patients in the CGM cohort have healed foot wounds by 3 to 4 months compared to 47% in the pre-intervention cohort despite similar prevalence of peripheral arterial disease. The CGM cohort also had lower percentage of patients with ED visits/readmissions for foot wounds (16% vs. 24%) and diabetes (0% vs. 2%) complications within 3 months.Conclusion: In conclusion, a short-term remote CGM program can be effective not only in improving glycemic control in patients with diabetic foot wounds, but also in increasing the percentage of wounds healed and reducing rates of foot wound related ED visits/readmissions within a safety-net health system.DisclosureF. Gunawan: None. S. Mathew: None. B.S. Easow: None. K. Adame: None. K.N. Jackson: None. U. Gunasekaran: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-153-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 154-OR: Combined Point-of-Care Devices, DPN-Check and Sudoscan, Diagnose
Early DPN and Predict Diabetic Foot Ulceration-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 154-OR
Abstract: Introduction and Objective: Diabetic peripheral neuropathy (DPN) is the strongest risk factor for diabetic foot ulceration (DFU). Current screening methods (e.g. 10g monofilament [10g-MFT]) are crude and diagnose DPN late when the condition is already well established. Point-of-care devices (POCDs), DPN-Check, a hand-held device that measures nerve conduction/amplitude and SUDOSCAN that measures sudomotor function, diagnose DPN early. However, their abilities to predict incident DFU is unknown.Methods: 229 consecutive participants with diabetes were followed up for 9 years and underwent detailed assessments including: the Toronto Clinical Neuropathy Score (TCNS), 10g-MFT, and POCD. Risk of incident DFU was analysed using odds-ratios for participants with abnormal baseline TCNS, 10gMFT and combined POCDs tests who developed DFU at follow-up.Results: At baseline, the prevalence of DPN diagnosed was 14.4%, 27% and 66.8% for MFT(n=33), TCNS(n=62) and POCD(n=153) respectively. 100 participants attended the 9 year follow-up however 59 participants died. Those who attended follow up visits were significantly younger [58.0(11.1)vs59.1(17.8) years;(p<0.001(95%CI:4.1:11.4)], had fewer co-morbidities [2.7vs3.2; P<0.001] and lower Q-risk score (21.4(12.9)vs24.5(14.4); p<0.001). Thirty-five (15.3%) participants developed DFU. Participants with abnormal POCDs at baseline demonstrated a 4.4-fold increased risk [(n=31),95%CI:1.5:12.9, p<0.004)] of developing DFU compared to those with normal POCDs at baseline. There was also an increased risk of incident DFU with DPN diagnosed using TCNS [(n=17), OR 2.9(95%CI:1.4:6.1, p=0.004)] and 10g-MFT [(n=13), OR 4.5(95%CI:1.9:10.4, p<0.001)].Conclusion: We have demonstrated that abnormal POCD tests predict greater number of incident DFUs. These results advocate the use of POCDs to predict DFUs at an early stage, when preventative measures can be implemented.DisclosureM. Goonoo: None. D. Selvarajah: None. G.P. Sloan: Speaker's Bureau; Eli Lilly and Company, Procter & Gamble. S. Tesfaye: Advisory Panel; AstraZeneca, Bayer Pharmaceuticals, Inc. Speaker's Bureau; Berlin-Chemie AG. Advisory Panel; Grünenthal. Speaker's Bureau; Metronics, Novo Nordisk. Advisory Panel; Procter & Gamble. Speaker's Bureau; Viatris Inc. Advisory Panel; Nevro Corp.FundingProctor and Gamble (STH22196)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-154-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 155-OR: Reduced Perceived Diabetes Distress with the Omnipod 5 Automated
Insulin Delivery (AID) System in Adults with Type 2 Diabetes
(T2D)—Analysis of the SECURE-T2D Study-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 155-OR
Abstract: Introduction and Objective: AID can alleviate some of the burden associated with diabetes self-care and improve quality of life for people with diabetes; however, prior research has largely focused on type 1 diabetes. This analysis of the SECURE-T2D study evaluated the impact of the Omnipod® 5 AID System on person-reported diabetes distress (DD) in adults with T2D.Methods: This US multicenter single-arm trial enrolled 305 adults with insulin-treated T2D (mean age 57±11y, 24% Black, 22% Hispanic/Latino, 21% using basal without bolus insulin, 55% using GLP-1 RA, baseline A1C 8.2±1.3%). After a 14-day standard therapy phase, participants initiated 13 weeks of AID. At baseline and study end, participants completed the validated Type 2 Diabetes Distress Assessment System (T2-DDAS) questionnaire.Results: Of the 301 participants who completed the questionnaire, the percentage reporting moderate or high DD (T2-DDAS intensity score ≥2.0) was reduced from 66% at baseline to 55% after AID use (p<0.001). Reductions in DD following AID were observed across baseline time in range (70-180 mg/dL) and prior insulin therapy groups (Figure).Conclusion: In this diverse cohort of adults with T2D using insulin, most reported moderate or high DD at baseline, underscoring the burden of disease. These results suggest AID may help to reduce DD in the T2D population.Disclosure K.N. Castorino: Research Support; Abbott, Medtronic, Dexcom, Inc., Lilly Diabetes, MannKind Corporation, Eli Lilly and Company, Insulet Corporation. Speaker's Bureau; Dexcom, Inc. Advisory Panel; MannKind Corporation. Speaker's Bureau; Insulet Corporation. F.J. Pasquel: Consultant; Insulet Corporation. Research Support; Novo Nordisk, Dexcom, Inc., Ideal Medical Technologies, Tandem Diabetes Care, Inc, Insulet Corporation. Consultant; Dexcom, Inc. G.M. Davis: Research Support; Insulet Corporation. D.M. Huffman: None. A.L. Peters: Advisory Panel; Medscape. Consultant; Vertex Pharmaceuticals Incorporated. Research Support; Insulet Corporation, Abbott. Other Relationship; Omada Health. J.C. Parker: Speaker's Bureau; Corcept Therapeutics, Novo Nordisk, Insulet Corporation. L.M. Laffel: Advisory Panel; Boehringer-Ingelheim, Sanofi, MannKind Corporation, Medtronic, Vertex Pharmaceuticals Incorporated, Tandem Diabetes Care, Inc, Insulet Corporation. Research Support; Dexcom, Inc. Advisory Panel; Sequel Med Tech. Other Relationship; Janssen Pharmaceuticals, Inc. Consultant; Arbor Biotech. G. Romeo: None. J. Mathew: None. D.F. Kruger: Other Relationship; Abbott. Advisory Panel; embecta, MannKind Corporation. Other Relationship; CeQur, Tandem Diabetes Care, Inc, Dexcom, Inc. Research Support; Jaeb Center for Health Research. Other Relationship; Eli Lilly and Company. Advisory Panel; Structure Therapeutics, Inc. Other Relationship; Insulet Corporation, Sequel Med Tech. Advisory Panel; Corcept Therapeutics. K.M. Dungan: Research Support; Abbott Diagnostics, Dexcom, Inc. Consultant; Dexcom, Inc. Other Relationship; UpToDate. Consultant; Oppenheimer & Co. Advisory Panel; Insulet Corporation. Research Support; Insulet Corporation. Board Member; Elsevier, Eli Lilly and Company. Speaker's Bureau; Medscape, Med Learning Group, Impact Education. M. Kipnes: Research Support; Zydus Lifesciences, Zucara Therapeutics, 89bio, Inc, Abbott Diagnostics, AbbVie Inc, Akero Therapeutics, Inc, Amgen Inc, Biomea Fusion, Boehringer-Ingelheim, Biolinq, MannKind Corporation, Eli Lilly and Company, Carmot Therapeutics, Inc, Endogenex, Ionis Pharmaceuticals, Novo Nordisk, Corcept Therapeutics, Insulet Corporation, Fractyl Health, Inc. Advisory Panel; Corcept Therapeutics, AP stem. Other Relationship; Jaeb Center for Health Research. Research Support; Sinocare Inc, Kowa Pharmaceuticals America, Inc, Diamyd. E. Jauch: Research Support; Carmot Therapeutics, Inc, Omnipod. T. Oser: Consultant; Dexcom, Inc. Research Support; Abbott, Insulet Corporation, Dexcom, Inc. Advisory Panel; Medscape. V.N. Shah: Consultant; Dexcom, Inc. Advisory Panel; Sanofi, Novo Nordisk. Consultant; Lilly Diabetes. Advisory Panel; embecta. Consultant; Insulet Corporation. Advisory Panel; Tandem Diabetes Care, Inc, Ascensia Diabetes Care. Research Support; Enable Bioscience. Consultant; Genomelink and Lumosfit. B. Horowitz: Advisory Panel; AbbVie Inc. Research Support; AbbVie Inc. Speaker's Bureau; Eli Lilly and Company. Research Support; Eli Lilly and Company. Speaker's Bureau; Novo Nordisk. Research Support; Novo Nordisk. Speaker's Bureau; Tandem Diabetes Care, Inc. A.L. Carlson: Research Support; Abbott, Amgen Inc, Dexcom, Inc., Eli Lilly and Company, Hemsley Charitable Trust, Insulet Corporation. Other Relationship; Medtronic, Novo Nordisk, Tandem Diabetes Care, Inc. Research Support; Sanofi. Advisory Panel; MannKind Corporation. M.L. Warren: Research Support; Medtronic, Insulet Corporation, Abbott. Speaker's Bureau; Lilly Diabetes. Research Support; Lilly USA LLC, Amgen Inc. Speaker's Bureau; Amgen Inc. Advisory Panel; Lilly USA LLC. Research Support; Diasome Pharmaceuticals, Bayer Pharmaceuticals, Inc, Ascendis Pharma A/S, Novo Nordisk. W. Deeb: None. J.B. Buse: Other Relationship; Corcept Therapeutics, Dexcom, Inc., Novo Nordisk. Consultant; Altimmune Inc, Amgen Inc, ApStem, Aqua Medical, AstraZeneca, Boehringer-Ingelheim, CeQur, Eli Lilly and Company, embecta, GentiBio. Other Relationship; Glyscend Therapeutics. Consultant; Insulet Corporation, Medtronic. Other Relationship; Mellitus Health. Consultant;...
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-155-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 156-OR: Single-Device Glucose Sensing and Insulin
Delivery—Patient-Reported Outcomes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 156-OR
Abstract: Introduction and Objective: Automated insulin delivery (AID) requires separate devices with insertions for insulin infusion and for glucose monitoring. A prototype glucose sensing canula (GSC [Pacific Diabetes Technologies]) combining both functions with a single insertion is undergoing clinical trials. We aim to understand the expectations, hopes and concerns of participants in relation to the use of this novel device.Methods: 1:1 semi-structured interviews using the Schedule of Individualised Quality of Life (SEIQoL) were conducted with adults with T1D trialling the investigational device in an ambulatory setting for one week. Questions explored factors important to QoL for participants; the impact of living with diabetes on those important factors; and the impact of the novel device on both diabetes and broader QoL. Thematic analyses supported by NVivo was conducted.Results:n=10 participants were interviewed in person (mean 24 mins, range 14-37 mins). All participants reported the GSC was easy to use and none had any safety concerns. Most participants reported reduced visibility of diabetes and greater 'real estate;' in terms of placing sensors, reducing body stress particularly in terms of reduced scarring and availability of insertion sites. All participants reported 7-day wear was beneficial, with convenience endorsed as the major benefit in helping diabetes management. Suggested improvements were smaller size and removal of tubing. Specific comments included ‘it’s convenient, it’s minimising those frustrations and getting probably one step closer towards feeling like there’s not as much of a difference between diabetics and non-diabetics’ and 'Just think [placing the device], you could have one area where you would have almost a month before you touch the other side'Conclusion: The GSC was acceptable and well tolerated by participants.Disclosure K. Barnard-Kelly: Speaker's Bureau; Roche Diabetes Care, Sanofi. Stock/Shareholder; Spotlight-AQ Ltd, BHR Ltd. S. Flint: None. T. Seidl: Employee; Pacific Diabetes Technologies, Inc. Stock/Shareholder; Pacific Diabetes Technologies, Inc. Board Member; Pacific Diabetes Technologies, Inc. P.B. Eckenberg: Employee; Pacific Diabetes Technologies. Board Member; Pacific Diabetes Technologies. Stock/Shareholder; Pacific Diabetes Technologies. C.M. Sims: Stock/Shareholder; Medtronic. E. Barnard: None. C.J. Woombs: None. D.N. O'Neal: None.FundingDexcom unrestricted research grant
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-156-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 157-OR: Higher Engagement with a Digital DSMES + CGM Program Is Associated
with More Robust Improvements in Glycemic Control-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 157-OR
Abstract: Introduction and Objective: To evaluate whether higher engagement with a digital diabetes self-management and education support (DSMES) program + continuous glucose monitoring (CGM) integrated solution is associated with better clinical outcomes through a secondary analysis of a randomized controlled trial.Methods: Participants with type 2 diabetes and HbA1c ≥ 8% not using mealtime bolus insulin (26-83 years old; mean HbA1c: 9.58%) were randomly assigned to and enrolled in a digital DSMES + CGM integrated solution (n=42) or usual care (n=49) for 6 months. The current analysis only includes participants in the digital DSMES + CGM condition. A standardized total engagement score was calculated based on the sum of the total number of interactions with app features (e.g., meals tracked, lessons completed). Outcomes included HbA1c and CGM-derived glycemic measures, including glucose management indicator (GMI), mean daily glucose, and % time in range (TIR 70-180 mg/dL), above range (TAR > 180 mg/dL), and below range (TBR < 70 mg/dL).Results: Utilizing a linear mixed effect model controlling for number of weeks enrolled in the digital DSMES + CGM condition, participants with mean levels of total engagement experienced a 1.08% decrease in HbA1c (p <.001) and a 16.63% decrease in TAR (p =.002), as well as a 16.54% increase in TIR (p =.001), from baseline to 6 months. Participants with higher levels (+1 SD) of total engagement experienced a 1.71% decrease in HbA1c (p <.001), a 1.37% decrease in GMI (p <.001), a 32.92% decrease in TAR (p <.001), a 56.41 mg/dL decrease in mean daily glucose (p <.001), and a 32.86% increase in TIR (p <.001) from baseline to 6 months. Participants with lower levels (-1 SD) of engagement experienced no significant changes in HbA1c, TIR, TAR, GMI, or mean daily glucose from baseline to 6 months (all p >.05).Conclusion: Participants with greater engagement in digital DSMES programs that integrate continuous CGM may see improved long-term diabetes management.Disclosure J.B. Naqvi: Employee; Omada Health. Other Relationship; Abbott. J. Napoleone: Employee; Omada Health. Other Relationship; Abbott. S. Zion: Employee; Omada Health. Other Relationship; Abbott. Employee; Gilead Sciences, Inc. A. Berthoumieux: Employee; Omada Health, Inc. Other Relationship; Abbott. H. Lee: Employee; Abbott. Other Relationship; Omada Health. T. Dunn: Employee; Abbott. Other Relationship; Omada Health. C.B. Jasik: None. S. Linke: Employee; Omada Health.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-157-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 158-OR: Primary Metabolic Outcomes from a Pilot CGM-Behavioral
Intervention among Racially Minoritized Youth with T1D-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 158-OR
Abstract: Introduction and Objective: Continuous glucose monitor (CGM) use is the standard of care for youth with type 1 diabetes (T1D), yet many youth struggle to sustain consistent CGM use. Further, due to structural racism in T1D technology research and health-care delivery, racially marginalized youth experience health inequities affecting CGM use. We delivered a 3-month, 3-session, diabetes educator led behavioral intervention to youth-caregiver dyads focusing on CGM problem solving and positive communication.Methods: Participants included 60 youth ages 10-15 years with <75% CGM use (Mage=12.9±1.7 yrs; 58% male, 42% female; 53% Black/African American, 27% Hispanic/Latino/a/x, 12% another racially minoritized identity, 8% white; 72% public insurance; MT1D Duration=5.2±3.4 yrs; MA1c=10.6±2.0%; MCGM wear-time=58±20%; MCGM time in range=30±16%) randomized to immediate (n=31) or delayed (i.e., waiting 6 months; n=29) intervention. A1c and CGM wear-time were compared between the immediate and delayed groups at 6 months post-baseline.Results: A1c data were available for 59 participants at baseline and 51 at 6 months. Wear-time data were available for 43 participants at both baseline and 6 months. Descriptively, A1c decreased from 10.7±2.2% to 10.0±2.0% in the immediate group vs. 10.5±1.9% to 10.4±2.0% in the delayed group. Wear-time increased from 58.7±19.6% to 72.8±17.3% in the immediate group and 57.3±21.6% to 63.3±26.4% for delayed. Paired t-test revealed that A1c significantly decreased (p=.03) and wear-time significantly increased (p=.05) in the immediate group. No significant changes were observed for the delayed group.Conclusion: The intervention led to a significant and clinically meaningful reduction in A1c and an increase in CGM wear-time, suggesting positive effects on glycemic outcomes. Given the small sample size, a larger multisite trial is needed to elucidate glycemic outcomes in this CGM optimizing intervention.DisclosureE. Straton: None. C.H. Wang: None. A.G. Perkins: Research Support; Tandem Diabetes Care, Inc, Dexcom, Inc. L. Gallant: None. J. Barber: Stock/Shareholder; Boston Scientific Corporation, UnitedHealth Group, AbbVie Inc. S. Majidi: Speaker's Bureau; Sanofi. M. Monaghan: None. R. Streisand: None.FundingNational Institutes of Health (R01DK121316)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-158-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 159-OR: ADA Presidents' Select Abstract: Heterogeneous Treatment Effects
of the VA MOVE! Weight Management Program in Preventing Type 2 Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 159-OR
Abstract: Introduction and Objective: While the Veterans Affairs (VA) MOVE! Program (DPP-like lifestyle intervention) demonstrated a 24% relative risk reduction in type 2 diabetes (T2D) over 15 years, individual responses varied substantially. We examined this heterogeneity of effects.Methods: Using 2005-2024 VA electronic health records data, we identified NDPP-eligible veterans who enrolled in MOVE! from 2005 to 2009 (n=28,668) and MOVE!-eligible nonparticipants using 1:1 high-dimensional propensity score matching. We applied a causal survival forest algorithm and Shapley Additive exPlanations values to identify key effect modifiers influencing the effectiveness of MOVE! over 15 years from demographics, disease history, medications, vitals, and biomarkers. We further developed a scoring algorithm to estimate personalized T2D risk reduction.Results: We identified ten key effect modifiers and corresponding effect scores. Participants with prediction scores (range: -9 to 18) above 0 demonstrated measurable benefits from MOVE!, with those in the highest quintile (scores >7) achieving a 36% reduction in T2D risk (95% CI: 33%-39%) over 15 years.Conclusion: Our personalized prediction algorithm effectively identifies individuals who receive the greatest benefit from MOVE! Program, providing insights to guide targeted T2D prevention efforts in clinical practice and health policy.DisclosureQ. Xue: None. P. Li: None. J. Lee: None. T. Moin: None. S. Raffa: None. M.K. Ali: Advisory Panel; Eli Lilly and Company. Y. Hong: Consultant; Weight Watchers International. M.K. Shah: None. L.S. Phillips: Research Support; Janssen Pharmaceuticals, Inc, Boehringer-Ingelheim. Other Relationship; AbbVie Inc, ForaCare, Inc., Diasyst, Inc. Research Support; Kowa Pharmaceuticals America, Inc, Pfizer Inc. H. Shao: None.FundingCDC (U18DP006747)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-159-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 160-OR: Assessing the Real-World Effectiveness of the VA MOVE! Lifestyle
Program in Preventing Type 2 Diabetes—A 15-Year Follow-up Study-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 160-OR
Abstract: Introduction and Objective: The Veterans Health Administration (VA) MOVE! Program is a nationwide DPP-based lifestyle intervention. The program's long-term benefit in real-world settings remains unclear.Methods: We used data from the VA clinical and administrative systems (2005-2024). We matched Veterans who participated in the MOVE! program between 2005 and 2009 with MOVE!-eligible non-participants at a 1:3 ratio using high-dimensional propensity scores. We used an intent-to-treat analysis with Cox proportional hazards models to compare T2D incidence between groups over 15 years follow-up.Results: Our final sample included 28,540 MOVE! participants and 85,620 matched non-participants. MOVE! was associated with a 49% (HR: 0.51; 95% CI: 0.49-0.53) T2D risk reduction at year 3, attenuated to 24% (HR: 0.76; 95% CI: 0.74-0.77) by year 15. The incidence rate difference decreased from 50.4 to 13.1 per 1,000 person-years between year 3 and year 15. Larger long-term effects were observed in people with higher BMI, random glucose and DPP risk score (see figure).Conclusion: The VA MOVE! Program reduced T2D incidence over 15 years but effectiveness declined over time and varied by subgroups. Diabetes prevention programs may require sustained engagement and tailored strategies to achieve long-term effects.DisclosureP. Li: None. Q. Xue: None. T. Moin: None. O. Duru: None. S. Raffa: None. K. Narayan: None. G. Umpierrez: Research Support; Abbott, Dexcom, Inc., Bayer Pharmaceuticals, Inc, Corcept Therapeutics. Advisory Panel; Dexcom, Inc., GlyCare Health. M.K. Ali: Advisory Panel; Eli Lilly and Company. L.S. Phillips: Research Support; Janssen Pharmaceuticals, Inc, Boehringer-Ingelheim. Other Relationship; AbbVie Inc, ForaCare, Inc., Diasyst, Inc. Research Support; Kowa Pharmaceuticals America, Inc, Pfizer Inc. H. Shao: None.FundingCenters for Disease Control and Prevention (U18DP006711)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-160-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 161-OR: Prediabetes Remission and Cardiovascular Mortality and Morbidity
-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 161-OR
Abstract: Introduction and Objective: Lifestyle interventions (LI) are effective in preventing T2D in people with prediabetes. Whether this approach also reduces cardiovascular (CV) death and heart failure (CHF) in people with prediabetes is matter of debate. We tested the hypothesis whether remission of prediabetes to normal glucose regulation (NGR; FPG<5.6 mmol/l, 2-h glucose OGTT <7.8 mmol/l, HbA1c <39 mmol/mol) reduces CV complications in people with prediabetes.Methods: In the Diabetes Prevention Program Outcomes Study (DPPOS) Phase 3 from the NIDDK repository from all three treatment arms (LI, metformin, placebo) with data for up to 21 years of follow-up were analyzed. Participants were separated into responders (i.e. remission to NGR) and non-responders (non-remission to NGR) based on the response at year 1 of the DPP intervention. Outcomes included 1) a composite of CV death and hospitalization for CHF and 2) extended MACE (CV events/death, arterial revascularization, hosp. for CHF or unstable angina, diagnosis of coronary heart disease or silent myocardial infarction).Results: Of 2427 participants, 278 (11%) were responders and 2149 (89%) non-responders at year 1. At baseline, BMI was 32.3kg/m2 (IQR: 28.7, 37.0) in responders and 32.5Kg/m2 (28.8, 37.1) in non-responders, and was reduced to 30.1kg/m2 (26.6, 34.2) and 31.4kg/m2 (27.7, 36.2; both p<0.01), respectively. In total, 93 of 278 (33.5 %) responders were diagnosed with T2D during DPPOS phase 3 compared to 1215 of 2149 (56.5 %) non-responders (p<0.001). During a mean observation time of 21 years and after adjustment for available risk factors, including baseline body weight, age, development of T2D, randomization assignment and medication, responders had lower relative risk (RR) for the composite endpoint of CV death and CHF (RR=0.43 (95 % CI: 0.21, 0.90); p=0.02) and for extended MACE (RR=0.60 (0.41, 0.89) p=0.01) than non-responders.Conclusion: LI-induced prediabetes remission markedly reduced CV morbidity and mortality in people with prediabetes.DisclosureE. Vazquez Arreola: None. R.L. Hanson: None. A. Sandforth: None. L. Sandforth: None. S. Katzenstein: None. N. Stefan: Speaker's Bureau; AstraZeneca, Boehringer-Ingelheim. Consultant; Lilly Diabetes. Speaker's Bureau; Lilly Diabetes. Consultant; Pfizer Inc. Speaker's Bureau; Sanofi. Research Support; Sanofi. Speaker's Bureau; Novo Nordisk, GlaxoSmithKline plc. Consultant; GlaxoSmithKline plc. H. Preissl: None. N. Marx: Speaker's Bureau; Abbott, Amgen Inc, AstraZeneca. Advisory Panel; AstraZeneca. Speaker's Bureau; Bayer Pharmaceuticals, Inc. Advisory Panel; Bayer Pharmaceuticals, Inc. Speaker's Bureau; Boehringer-Ingelheim. Advisory Panel; Boehringer-Ingelheim. Speaker's Bureau; Daiichi Sankyo. Advisory Panel; Merck Sharp & Dohme Corp. Speaker's Bureau; Novo Nordisk. Advisory Panel; Novo Nordisk. Speaker's Bureau; Sanofi. Advisory Panel; Sanofi. Speaker's Bureau; Lilly Diabetes. R. Jumpertz von Schwartzenberg: None. A.L. Birkenfeld: None.FundingIntramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). German Federal Ministry for Education and Research (01GI0925) via the German Center for Diabetes Research (DZD e.V.)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-161-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 162-OR: Beta-Cell Preservation with Early Oral Antidiabetic Medications in
Prediabetes (PreDM)-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 162-OR
Abstract: Introduction and Objective: Beta cell failure is the key pathophysiologic determinant in the progression from PreDM to type 2 diabetes (T2D). Lifestyle modification is frequently insufficient to prevent T2D onset, and drugs that modify disease progression and offer cardiometabolic benefits beyond glycemic control are increasingly used.Methods: Study recruited 200 PreDM subjects (FPG = 100-125 and/or 2-h PG=140-199 mg/dl) seeking to answer whether a specific oral antidiabetic drug provides greater benefit in preventing PreDM progression to T2D. At baseline, subjects received an OGTT and two-step hyperglycemic clamp (+125 and 400 mg/dl) followed by exenatide infusion to quantitate insulin sensitivity (Matsuda Index), insulin secretion (ΔI/ΔG), and beta cell function (disposition index). Subjects then were randomized to receive 24 months of treatment with: (i) Dapagliflozin (DAPA), (ii) Metformin (MET), (iii) Pioglitazone (PIO), or (iv) Saxagliptin (SAXA). 154 subjects (94 F, 60 M; Age=51±0.8, BMI=38±0.6); DAPA=47, MET=30, PIO=40, SAXA=37 have completed one year of intervention.Results: A1c trended to decrease in all groups (5.7±0.05 to 5.6%±0.05). FPG decreased in PIO, MET and DAPA (p<0.05) but not in SAXA; 2h PG decreased in DAPA, MET and PIO groups (p=0.05 - 0.01). Treatment with DAPA and MET (p<0.05) and PIO (p<0.01) significantly improved Matsuda Index. ΔI/ΔG trended to increase (p=n.s) in all groups. Beta cell function (ΔI/ΔG x Matsuda) increased significantly only in the PIO group (p<0.01). PIO resulted in weight gain of +3.9 kg, whereas DAPA and MET resulted in -4kg weight loss. Adipose IR (fasting FFA x fasting insulin) decreased in PIO (p<0.001).Conclusion: Early pharmacological treatment can prevent progression of PreDM to T2D. DAP and MET improved insulin sensitivity with net weight loss. Despite weight gain, PIO improved total body and adipose insulin sensitivity and robustly increased beta cell function. Individual factors and comorbidities need to be considered when selecting the most appropriate intervention to treat PreDM.DisclosureA. Chavez: None. A. Merovci: None. S. Neppala: None. G. Baskoy: None. J.M. Adams: None. A.A. Hansis-Diarte: None. E. Cersosimo: None. R. Belfort De Aguiar: None. M. Abdul-Ghani: None. R.A. DeFronzo: Advisory Panel; AstraZeneca. Research Support; AstraZeneca. Speaker's Bureau; AstraZeneca. Advisory Panel; Boehringer-Ingelheim. Research Support; Boehringer-Ingelheim. Advisory Panel; Corcept Therapeutics, Novo Nordisk. Speaker's Bureau; Corcept Therapeutics. Research Support; 89bio, Inc, Amgen Inc.FundingNIH R01 DK024092-37AZ ISSDAPA0002
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-162-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 163-OR: Early vs. Late Prediabetes Remission during Lifestyle Intervention
Is Relevant for Type 2 Diabetes Prevention-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 163-OR
Abstract: Introduction and Objective: Prediabetes remission has beneficial effects for type 2 diabetes (T2D) prevention. However, it is unknown whether early remission is superior to late remission. Thus, we investigated if reaching prediabetes remission early during a lifestyle intervention is associated with lower T2D risk compared to reaching remission later on.Methods: We studied 865 individuals with prediabetes from the German multi-center Prediabetes Lifestyle Intervention Study (PLIS) who could be classified into early remission at 6 months of a lifestyle intervention (ER, n = 217), late remission at 12 months (LR, n = 110), or no remission (NR, n = 538). Prediabetes remission was defined as return to normal glucose regulation and normalized HbA1c according to ADA criteria. Cox regression models were fit with age, sex, intervention intensity, T2D risk and weight loss as covariates.Results: The ER group (n=217) was comparable in age (p=0.24), sex distribution (p = 0.07), BMI (p > 0.99), insulin sensitivity (p = 0.2) and insulin secretion (p = 0.48) vs the LR group (n=110). Fasting glucose (5.70 ±0.43 mmol/L vs 5.83 ±0.44, p = 0.016) and HbA1c (5.53 ±0.29 % vs 5.68 ±0.31, p < 0.001) was slightly lower in ER compared to LR, while 2h glucose was similar (p = 0.77). Overall, T2D risk was lower in both ER and LR compared to NR (n=538; RR 0.15 [95% CI: 0.07-0.31], p < 0.001 and 0.44 [0.23-0.82], p = 0.009, respectively). However, ER provided a more pronounced T2D risk reduction than LR (0.31 [0.12-0.79], p = 0.01).Conclusion: Achieving early remission of prediabetes to NGR during lifestyle intervention may provide additional benefits for T2D prevention compared with late remission.DisclosureA. Sandforth: None. L. Sandforth: None. S. Katzenstein: None. J. Seissler: None. N. Perakakis: Other Relationship; Novo Nordisk, Lilly Diabetes. Advisory Panel; Bayer Pharmaceuticals, Inc. Other Relationship; APOGEPHA, Transmedac Innovations AG, GWT-TUD, Elbe-Gesundsheintszentrum GmbH, Open Exploration. R. Wagner: Speaker's Bureau; Boehringer-Ingelheim, Novo Nordisk. Advisory Panel; Sanofi. Speaker's Bureau; Sanofi. Advisory Panel; Lilly Diabetes. A. Peter: None. R. Lehmann: None. H. Preissl: None. I. Yurchenko: None. J. Szendroedi: Advisory Panel; Novo Nordisk, Lilly Diabetes, Novartis AG, Boehringer-Ingelheim. M. Blüher: Advisory Panel; AstraZeneca. Speaker's Bureau; Amgen Inc. Advisory Panel; Bayer Pharmaceuticals, Inc, Boehringer-Ingelheim. Speaker's Bureau; Daiichi Sankyo. Advisory Panel; Eli Lilly and Company, Novo Nordisk, Nestlé Health Science, Sanofi-Aventis Deutschland GmbH. A. Schürmann: None. S. Kabisch: Research Support; Almond Board California, California Walnut Commission. Other Relationship; JuZo-Akademie, Boehringer-Ingelheim. Research Support; J. Rettenmaier & Söhne. Other Relationship; Lilly Diabetes. Research Support; Wilhelm-Doerenkamp-Foundation. K. Mai: None. P.E. Schwarz: None. M. Heni: Advisory Panel; Amryt Pharma. Speaker's Bureau; Amryt Pharma, AstraZeneca, Boehringer-Ingelheim. Advisory Panel; Boehringer-Ingelheim. Speaker's Bureau; Lilly Diabetes, Novartis AG, Novo Nordisk, Sanofi. M. Roden: Research Support; Boehringer-Ingelheim. Advisory Panel; Echosens. Speaker's Bureau; Madrigal Pharmaceuticals, Inc. Advisory Panel; MSD Life Science Foundation. Board Member; Novo Nordisk. Advisory Panel; TARGET PharmaSolutions, Inc. N. Stefan: Speaker's Bureau; AstraZeneca, Boehringer-Ingelheim. Consultant; Lilly Diabetes. Speaker's Bureau; Lilly Diabetes. Consultant; Pfizer Inc. Speaker's Bureau; Sanofi. Research Support; Sanofi. Speaker's Bureau; Novo Nordisk, GlaxoSmithKline plc. Consultant; GlaxoSmithKline plc. A. Fritsche: Advisory Panel; Abbott. Speaker's Bureau; AstraZeneca. A.L. Birkenfeld: None. R. Jumpertz von Schwartzenberg: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-163-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 164-OR: A Phase 3 Evaluation of CAMP-Biased GLP-1 Analog Ecnoglutide in
Adults with Overweight or Obesity-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 164-OR
Abstract: Introduction and Objective: Ecnoglutide is a cAMP-biased long-acting GLP-1 analog being developed for the treatment of obesity and type 2 diabetes. The primary objective of this study was to evaluate the efficacy and safety of ecnoglutide in adults with overweight or obesity.Methods: A 48-week, double-blind, randomized, placebo-controlled phase 3 study of ecnoglutide was conducted at 36 sites across China, enrolling 664 adults with overweight or obesity. Participants were randomly assigned to once-a-week ecnoglutide (1.2, 1.8 or 2.4 mg) or placebo. Coprimary endpoints were percent change in bodyweight from baseline and proportion of participants with ≥5% bodyweight reduction at week 40. Safety and tolerability were also evaluated.Results: At baseline, participants had a mean body weight of 91.3 kg, and mean BMI of 32.5 kg/m2. After 48 weeks, participants receiving ecnoglutide achieved superior bodyweight reductions of -9.9 to -15.4% from baseline vs -0.3% for placebo (P<0.0001), and 77.7 to 92.8% of participants receiving ecnoglutide had bodyweight reductions ≥5%, 51.2 to 79.6% had reductions ≥10%, and up to 63.5% had reductions ≥15%. Ecnoglutide also led to improvements in cardiometabolic indexes including lipid profile and liver fat content. Ecnoglutide was safe and well tolerated. The proportion of participants reporting any adverse event (AE) ranged from 92.8 to 93.4% for ecnoglutide cohorts and 84.2% for placebo. A total of ten (2.0%) participants discontinued ecnoglutide due to AE. Five (1.0%) participants in ecnoglutide cohorts reported treatment-related serious AE. The most frequently reported AEs were decreased appetite, diarrhea, nausea and vomiting, which were mostly mild to moderate in severity and transient.Conclusion: In adults with overweight or obesity, ecnoglutide once-weekly treatments (1.2, 1.8 and 2.4mg) led to superior and sustained bodyweight reductions over placebo and improvements in cardiometabolic indexes.DisclosureL. Ji: None. L. Gao: Research Support; Sciwind Biosciences. H. Xue: None. J. Tian: None. K. Wang: None. Q. Zheng: Employee; Sciwind Biosciences. M. Yang: Employee; Sciwind Biosciences. J. Ning: Employee; Sciwind Biosciences. M. Guo: Employee; Sciwind Biosciences. Y. Li: Employee; Sciwind Biosciences. S. Xu: Employee; Sciwind Biosciences.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-164-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 165-OR: Improving A1C and CGM Average Glucose Alignment—The Updated
Glucose Management Indicator (GMI)-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 165-OR
Abstract: Introduction and Objective: The not-infrequently observed disconnect between A1C and GMI, particularly at low and high A1C levels, can create clinical management difficulties. Our aim was to evaluate the agreement of an updated GMI metric (uGMI) with A1C and potential use in diabetes management.Methods: The GDAC study (n=257) collected CGM data and bi-monthly A1C for 26 weeks for those with diabetes across different race groups. GMI was calculated by an empirical known formula employing average glucose (AG) levels, GMI(%)=0.02392*AG+3.31, while the uGMI formula accounts for population-based red blood cell factors, uGMI(%) = (15.36/AG+0.0426)-1. Analysis was replicated in a real-world dataset (n=2,074).Results: GDAC showed a disconnect between original GMI and A1C with regression slope value up to 25% outside unity, a difference more pronounced in the Black group at 40%. Using uGMI, regression slopes improved to within 2 and 6% of unity in the non-Black and Black groups, respectively. For the same AG, the Black group displayed higher A1C values than the non-Black group, at all HbA1c ranges.The misalignment between GMI and A1C was more pronounced in real-world data with values up to 50% outside unity, improving to within 3% of unity with uGMI.Conclusion: The uGMI metric is superior to the original GMI at reflecting A1C, promising to refine interpretation of CGM data and improve clinical decision-making.Disclosure R.M. Bergenstal: Advisory Panel; Abbott. Research Support; Abbott. Consultant; Abbott. Research Support; Dexcom, Inc. Consultant; Dexcom, Inc., Eli Lilly and Company. Research Support; Eli Lilly and Company. Consultant; Novo Nordisk. Research Support; Novo Nordisk. Consultant; Roche Diabetes Care, Sanofi, Medtronic. Research Support; Medtronic, Insulet Corporation, Hemsley Charitable Trust. Other Relationship; MannKind Corporation. Consultant; Medscape. Research Support; National Institute of Diabetes and Digestive and Kidney Diseases, Tandem Diabetes Care, Inc, UnitedHealth Group. Consultant; Vertex Pharmaceuticals Incorporated, Ascensia Diabetes Care, American Diabetes Association, Hygieia, embecta, Senseonics, Zealand Pharma A/S. Y. Xu: Employee; Abbott. T. Dunn: Employee; Abbott. Other Relationship; Omada Health. P. Choudhary: Speaker's Bureau; Abbott. Advisory Panel; Dexcom, Inc. Consultant; Insulet Corporation. Advisory Panel; Ypsomed AG, embecta, Sanofi. Speaker's Bureau; Lilly Diabetes, Medtronic. Advisory Panel; Roche Diabetes Care. Consultant; Cambridge Mechatronics. R. Ajjan: Research Support; Abbott. Speaker's Bureau; Abbott, Boehringer-Ingelheim. Advisory Panel; AstraZeneca, Novo Nordisk.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-165-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 166-OR: Mean RBC Age (M RBC ) Variation Accounts for the Predominance of
Mismatch (MM) between Measured HbA1c (mA1c) and CGM-Derived Estimated
HbA1c (eA1c)-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 166-OR
Abstract: Introduction and Objective: Widespread use of CGM has increased awareness of discordance between mA1c and eA1c, confounding clinical decision-making, e.g. when using equations from either the A1c Derived Average Glucose or Glucose Management Indicator (GMI) studies. We test whether variation in MRBC (the measure of RBC survival directly determining HbA1c) in people without anemia causes most of the MM.Methods: Subjects had hematocrit≥35. The study sample was enriched with those having MM≥±0.5%. Oral15N-glycine was used to label heme in an age cohort of emerging RBCs in vivo. Measurement of excess heme 15N over time gave RBC survival, including age-dependent removal of RBC, RBC lifespan, and MRBC. MM was calculated using AG throughout the RBC lifespan (>4 months) with 2 mA1c near the end.Results: Fig. 1A: See wide distribution of time-dependent removal of an age cohort of RBCs. This is the largest set of human in vivo RBC labelling studies reported. Fig. 1B: correlation between HbA1c MM and MRBC. MRBC is highly associated with MM (r2= 0.55). In the relationship between mA1c and AG (not shown), adjustment for MRBC improves the variance r2 accounted for from 0.79 to 0.88.Conclusion: Inter-individual differences in MRBC account for the preponderance of mismatch observed between HbA1c and AG. This represents proof of principle that accounting for MRBC should simplify decision-making and potentially improve diabetes care.Disclosure R.M. Cohen: Research Support; Dexcom, Inc. Stock/Shareholder; Abbott. Research Support; National Institute of Diabetes and Digestive and Kidney Diseases. J. Craig: None. S.O. Omololu: None. V. Tozzo: None. E.P. Smith: None. S. Arbabi: None. M. Genco: None. W. Abplanalp: None. D. Thibault: None. C.T. Quinn: Advisory Panel; Disc Medicine. Consultant; NovoNordisk. Research Support; Emmaus Medical. C.J. Lindsell: Research Support; Biomeme, biomerieux. Other Relationship; Rocket Phrmaceuticals, Regeneron Pharmaceuticals. Stock/Shareholder; Bioscape Digital. Research Support; Cytokinetics. Consultant; PersistenceBio. Advisory Panel; AstraZeneca, Novo Nordisk, Novartis Pharmaceuticals Corporation. R.M. Bergenstal: Advisory Panel; Abbott. Research Support; Abbott. Consultant; Abbott. Research Support; Dexcom, Inc. Consultant; Dexcom, Inc., Eli Lilly and Company. Research Support; Eli Lilly and Company. Consultant; Novo Nordisk. Research Support; Novo Nordisk. Consultant; Roche Diabetes Care, Sanofi, Medtronic. Research Support; Medtronic, Insulet Corporation, Hemsley Charitable Trust. Other Relationship; MannKind Corporation. Consultant; Medscape. Research Support; National Institute of Diabetes and Digestive and Kidney Diseases, Tandem Diabetes Care, Inc, UnitedHealth Group. Consultant; Vertex Pharmaceuticals Incorporated, Ascensia Diabetes Care, American Diabetes Association, Hygieia, embecta, Senseonics, Zealand Pharma A/S. R.S. Franco: None. J. Higgins: None.FundingNIH (R01 DK123330) (rmc); NIH (UL1 TR001425) (Center for Clinical & Translational Science & Training); Dexcom Corporation
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-166-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 167-OR: Personalized A1C Enhances Clinical Decision Making by Improving
Agreement between A1C and GMI-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 167-OR
Abstract: Introduction and Objective: Laboratory A1C and glucose management indicator (GMI) can be discordant due to red blood cell (RBC) factors. Our aim was to evaluate the correlation of personalized A1C (pA1C) with GMI using a personalized glycation ratio (PGR) that accounts for inter-individual differences in RBC factors.Methods: CGM and bi-monthly A1C were collected in a 26-week study (n=257) in individuals with diabetes across different race groups. PGR determined at 12 weeks was used to calculate pA1C. Agreement with GMI was analyzed at study end in the whole group and separately by race. A real-world dataset (n=2,074) allowed additional evaluation.Results: Correlation between A1C and GMI was modest at R2=0.81 improving to R2=0.93 with the use of pA1C (Figure 1A,B). The largest improvement was in the Black population with R2 improving from 0.80 for GMI-A1C to 0.92 for GMI-pA1C (Figure 1C,D). For a given GMI, Black individuals had higher A1C values with pA1C markedly improving the correlation (R2 = 0.80 to 0.92 and 0.84 to 0.93, respectively). Real-world data mirrored these findings with GMI-A1C correlation improving from R2= 0.64 to 0.80 for GMI-pA1C (Figure 1E,F).Conclusion: Use of PGR improves the correlation between GMI and A1C with the largest effect observed in the Black population. Therefore, pA1C may be a more accurate marker of hyperglycemic exposure than A1C.Disclosure R. Ajjan: Research Support; Abbott. Speaker's Bureau; Abbott, Boehringer-Ingelheim. Advisory Panel; AstraZeneca, Novo Nordisk. Y. Xu: Employee; Abbott. T. Dunn: Employee; Abbott. Other Relationship; Omada Health. P. Choudhary: Speaker's Bureau; Abbott. Advisory Panel; Dexcom, Inc. Consultant; Insulet Corporation. Advisory Panel; Ypsomed AG, embecta, Sanofi. Speaker's Bureau; Lilly Diabetes, Medtronic. Advisory Panel; Roche Diabetes Care. Consultant; Cambridge Mechatronics. R.M. Bergenstal: Advisory Panel; Abbott. Research Support; Abbott. Consultant; Abbott. Research Support; Dexcom, Inc. Consultant; Dexcom, Inc., Eli Lilly and Company. Research Support; Eli Lilly and Company. Consultant; Novo Nordisk. Research Support; Novo Nordisk. Consultant; Roche Diabetes Care, Sanofi, Medtronic. Research Support; Medtronic, Insulet Corporation, Hemsley Charitable Trust. Other Relationship; MannKind Corporation. Consultant; Medscape. Research Support; National Institute of Diabetes and Digestive and Kidney Diseases, Tandem Diabetes Care, Inc, UnitedHealth Group. Consultant; Vertex Pharmaceuticals Incorporated, Ascensia Diabetes Care, American Diabetes Association, Hygieia, embecta, Senseonics, Zealand Pharma A/S.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-167-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 168-OR: Evolution of CGM Patterns prior to Stage 3 T1D
-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 168-OR
Abstract: Introduction and Objective: CGM time >140 mg/dL predicts risk of progression to stage 3 T1D; however, the evolving patterns of CGM abnormalities leading to stage 3 diagnosis have not been described.Methods: Children participating in prospective follow-up in the ASK or DAISY studies with ≥2 islet autoantibodies (IAs) or a single high-affinity IA were invited to wear CGM every 3 to 6 months. Of 165 participants, 57% had more than one CGM wear. Time (T) was calculated as 3 months intervals prior to stage 3 T1D (by ADA criteria) or last follow-up. Bayesian function on scalar regression compared mean CGM glucose patterns across the day between those who progressed to stage 3 (n=42) and those who did not progress (n=123). Area under the smoothed curves (AUC) compared using bias-corrected and accelerated bootstrap confidence intervals with 3000 replicates.Results: Progressors did not differ from non-progressors by sex, race/ethnicity or BMI z-score. Non-progressors were followed longer (26.5 vs 13.7 months, p=0.003) and were less likely to be multiple antibody positive (58% vs 81%, p=0.007). CGM daily patterns at stage 3 T1D and up to 9 months prior to stage 3 T1D by 3 months intervals are shown in Figure 1. AUC difference between progressors and non-progressors increased across the 9 months prior to stage 3.Conclusion: CGM wearable technology reveals progressive elevations in daytime glucose levels beginning at least 6 months prior to diagnosis of stage 3, while differences in overnight values only become prominent at stage 3 T1D.DisclosureB.I. Frohnert: None. T.B. Vigers: None. F. Dong: None. K.M. Simmons: Consultant; Sanofi. Research Support; Sanofi. Advisory Panel; Sanofi, Shoreline Biosciences. M. Rewers: Consultant; Sanofi. Research Support; Sanofi. A. Steck: Advisory Panel; Sanofi-Aventis U.S.FundingNIDDK (R01-DK32493, P30-DK116073); Breakthrough T1D (3-SRA-2018-564-M-N, 3-SRA-2024-1603-S-B); The Leona M. and Harry B. Helmsley Charitable Trust (G-1911-03463).
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-168-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 169-OR: Association between 5,766 Different CGM Ranges and A1C in
Comparison to Time in 70–180 mg/dl and Time in 70–140 mg/dl Ranges-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 169-OR
Abstract: Introduction and Objective: Time in 70-180 mg/dL (TIR) and Time in 70-140 mg/dL (TITR) metrics are crucial for evaluating continuous glucose monitoring (CGM) results. FDA does not recognize TIR as primary endpoint in clinical trials due to lack of strong association between TIR and A1c. However, it is unknown if other CGM ranges have stronger association. Here, we investigated the association between A1c and different CGM ranges.Methods: In this longitudinal cohort study, 8718 A1c measurements and matched 90 days CGM data were collected from 1472 people with type 1 diabetes. From CGM data, percent time spent in 5766 different CGM ranges were calculated. The lower cutoffs of the ranges started from 50 to 80 and higher cutoffs from lower cutoff to 250 (e.g. 50-50, 50-51, 50-52, ⋯, 50-250, ⋯, 80-80, 80-81, ⋯, 80-250). Linear regression analysis was done between A1c and each range (range derived A1c).Results: Of 1472 people (age 34.2 (26.1 - 46.5), 57% female, 92% White), 8718 CGM-A1c matched data were included with 90-days CGM completeness of 95.4% (88.4 - 98%). Among 5766 ranges, the highest R2 values (>0.690) were from ranges with lower cutoff of 50 to 61, and higher cutoff of 163 to 205 mg/dL. R2 values were 0.670 for TIR-A1c and 0.643 for TITR-A1c. Of all ranges, 20.5% had higher R2 than TIR. Among the ranges with lower cutoff of 70 mg/dL, 21 consecutive ranges (70-159 to 70-179 mg/dL) had higher R2 than 70-180 mg/dL while 70-169 mg/dL had the highest R2 value of 0.674. For all ranges with higher cutoffs of >146 mg/dL, the highest R2 achieved with the least possible lower cutoff of 50 mg/dL. When higher cutoff is 140 mg/dL, the 59-140 mg/dL had the highest R2 of 0.65.Conclusion: Stronger association between A1c and time spent in CGM range can be achieved with reducing the lower cutoff of the CGM range compared to time in range (70-180 mg/dL) and time in tight range (70-140 mg/dL).DisclosureK.E. Karakus: None. H.K. Akturk: Consultant; Dexcom, Inc., Medtronic, Tandem Diabetes Care, Inc, Novo Nordisk. Research Support; Dexcom, Inc., Medtronic, Tandem Diabetes Care, Inc, Novo Nordisk.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-169-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 170-OR: Evaluating the Impact of Type 1 Diabetes Interventions on A1C and
GMI across Glycemic Categories-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 170-OR
Abstract: Introduction and Objective: Glycated Hemoglobin (A1C) is the standard efficacy measure recommended by regulatory agencies. The Glucose Management Indicator (GMI), an estimated A1C derived from sensor glucose, is available from continuous glucose monitoring (CGM) reports and is recommended as an outcome measure in clinical trials by the International Consensus. We evaluated the magnitude and direction of changes in A1C versus GMI across different glycemic categories.Methods: Data from three type 1 diabetes (T1D) clinical trials (DCLP3, DCLP5, and WISDM), encompassing children, adolescents, adults, and older adults, were analyzed. CGM data were used to compute GMI at baseline and 3 months. Changes in A1C and GMI were compared overall and by baseline A1C categories (<7%, 7-9%, >9%).Results: A modest correlation was observed between changes in A1C and GMI. The duration of CGM data (90 days vs. 14 days) had no clinically relevant impact. However, baseline A1C significantly influenced the magnitude of change in A1C versus GMI. Change in A1C versus GMI was significantly different in participants with A1C >9% [-1.2 (-2.1 to -0.6) vs. -0.6 (-0.94 to 0), p<0.01] and A1C between 7-9% [-0.4 (-0.9 to -0.1) vs. -0.12 (-0.49 to 0.21), p<0.01], while no significant difference was found in those with A1C <7%.Conclusion: Changes in GMI are influenced by baseline A1C and tend to underestimate true changes in A1C. Therefore, using GMI as an endpoint in clinical trials may not reliably capture the efficacy of an intervention in T1D trials or real-world studies.DisclosureE. Montaser: None. V.N. Shah: Consultant; Dexcom, Inc. Advisory Panel; Sanofi, Novo Nordisk. Consultant; Lilly Diabetes. Advisory Panel; embecta. Consultant; Insulet Corporation. Advisory Panel; Tandem Diabetes Care, Inc, Ascensia Diabetes Care. Research Support; Enable Bioscience. Consultant; Genomelink and Lumosfit.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-170-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 171-OR: ADA Presidents' Select Abstract: The Hidden Inequity—Disparities
-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 171-OR
Abstract: Introduction and Objective: This study investigates disparities in the uptake of diabetes technology (insulin pumps and hybrid closed-loop systems) in the UK, where they are available at no cost for eligible patients who meet NICE criteria. Despite this, factors such as age, sex, ethnicity, and socioeconomic status influence access.Methods: A mixed-methods approach was used. Retrospective data over 12 months were extracted from the electronic health records of 4,383 type 1 diabetes patients at two inner-city hospitals. A logistic regression approach was used to analyze demographic factors associated with technology use whilst linear regression was used to analyze the relationship between diabetes technology, socioeconomic factors and HbA1c. Semi-structured interviews with 30 randomly selected patients not using diabetes technology were thematically analyzed.Results: 58% of White patients used pumps, compared to 3.8% of Asian patients and 18.2% of Black patients. Females (50.4%) had higher usage than males (34.6%), and younger patients (44.2% aged 19-64 vs. 30.3% over 65) were more likely to use pumps. The most deprived group had 31.5% pump usage, while the least deprived group had 58.1%. Older age, male sex, non-white ethnicity, and lower socioeconomic status were significantly associated with lower pump use (p < 0.01). Pump use, White ethnicity and low deprivation were significantly associated with lower HbA1c (p<0.01). Qualitative interviews revealed concerns about device acceptability (size and color), stigma, and the discomfort of being attached to a device as reasons for non-use.Conclusion: The study highlights significant inequalities in the uptake of diabetes technology, with ethnic minorities and individuals from deprived backgrounds less likely to use insulin pumps. Addressing these disparities is crucial for ensuring equitable healthcare access and improving diabetes outcomes.DisclosureD. Kariyawasam: None. R. Thistlethwayte: None. B. Stotesbury: None. A. Saqib: None. S. Pender: None. R. Atkinson: None. A. Brackenridge: None. N. Binnie: None. S. Harris: Other Relationship; Eli Lilly and Company.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-171-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 172-OR: Long-Term Cost-Effectiveness of Using Glucagon-Like Peptide 1
Receptor Agonists (GLP-1RAs) for Preventing Type 2 Diabetes (T2D) in U.S.
Adults with Prediabetes and Obesity—A Simulation Study-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 172-OR
Abstract: Introduction and Objective: Although GLP-1 RAs are effective in reducing body weight and T2D incidence in clinical trials, they are expensive. Whether their prevention of T2D is cost-effective in the long term is unknown.Methods: We estimated 20-year clinical and cost impacts of using GLP-1 RAs for preventing T2D using a microsimulation model in U.S. adults aged ≥18 years with prediabetes and obesity. The simulation model, developed by the CDC and RTI, was extensively validated. The simulated population was from the 2017-2020 National Health and Nutrition Examination Survey. Effectiveness and cost data were from literature. The incremental cost-effectiveness ratio (ICER) from a health care system perspective for GLP-1 RAs was compared with brief obesity counseling, measured by cost per quality-adjusted life year (QALY).Results: The ICER of the treatment with GLP-1 RAs was $288,704/QALY (Table). The treatment would not be considered cost-effective if compared to a CE threshold of $100,000/QALY. Lower ICERs were observed for older adults (≥65 years) and those with a higher BMI (≥40 kg/m2) and fasting plasma glucose level (110-125 mg/dl); however, these lower ICERs remained above the CE threshold.Conclusion: At this time, GLP-1 RAs may not be cost-effective compared to obesity counseling if used for preventing T2D.DisclosureS. Tang: None. H. Shao: None. M.K. Ali: Advisory Panel; Eli Lilly and Company. K.M. Bullard: None. M.E. Pavkov: None. C.S. Holliday: None. P. Zhang: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-172-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 173-OR: Eligibility, Impact, and Costs for Tirzepatide for the Primary
Prevention of Diabetes Mellitus-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 173-OR
Abstract: Introduction and Objective: A recent trial of tirzepatide (SURMOUNT) found a 92% reduction of diabetes incidence among patients with overweight or obesity over three years. Our objective was to estimate the potential population, outcomes, and cost associated with use of tirzepatide for the primary prevention of DM.Methods: Data from the 2021-2023 cycle of the National Health and Nutrition Examination Survey (NHANES) were used to estimate risk reductions for the incidence of DM extrapolated from SURMOUNT results. Costs and savings (from saved diabetes care costs) of tirzepatide were estimated under current U.S. list prices, direct to patient prices, and UK list prices.Results: In total, 2,022 NHANES participants were eligible for tirzepatide therapy (51% female, 49% male, median age 53, IQR 37-66) translating to a weighted U.S. population estimate of 83,454,492 (95% CI 74,423,832 - 92,485,151). Across the lifespan, 30,522,710 cases of diabetes could be prevented if risk reduction was persistent. Projected costs/savings are shown in Table 1.Conclusion: Nearly one in three Americans are potentially eligible for tirzepatide for the primary prevention of DM. At current list price, treating the entire population could cost nearly 20 trillion dollars, offset by only 3.4 trillion dollars of savings, yielding a net cost of approximately 16 trillion dollars, or 60% of 2023 US gross domestic product; treatment at the UK list price would result in nearly 500 billion in net savings.DisclosureJ.B. Lusk: None. S. Aymes: None. E. OBrien: Research Support; Pfizer Inc. F. Li: None.
PubDate: Sat, 21 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-173-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 174-OR: Health Care Financial Hardship and Unaffordability among U.S.
Adults with Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 174-OR
Abstract: Introduction and Objective: Diabetes imposes healthcare financial hardship on individuals and families, often leading to the underuse of needed medical services. This study compared financial hardship and unaffordability among US adults aged 18-64 years with and without self-reported diabetes using 2018-2022 Medical Expenditure Panel Survey data.Methods: Objective financial hardship was defined as a high out-of-pocket (OOP) cost burden (OOP spending > 10% of annual family income). Subjective hardship included two self-reported measures: families having problems paying medical bills or paying them over time, and any such hardship. Unaffordability, also self-reported, was assessed by underuse of medical, dental, or prescription drugs due to cost, and underuse of any type. Logistic regression was used to estimate the adjusted mean of each outcome, controlling for age, sex, race/ethnicity, education, income level, health insurance, marital status, and perceived physical and mental health.Results: Results showed that individuals with diabetes experienced greater financial hardship than those without diabetes, including a higher OOP cost burden (19% vs. 16.3%), greater subjective hardship (25.4% vs 19.3%), and increased drug unaffordability (6.6% vs. 3.8%).Conclusion: Individuals with diabetes face disproportionately high financial burdens.DisclosureX. Zhou: None. Y. Wang: None. P. Zhang: None. R. Li: None. D.B. Rolka: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-174-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 175-OR: Disparities in New Glucose-Lowering Drug Spending in U.S. Adults
with Type 2 Diabetes (T2D), 2018–2022-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 175-OR
Abstract: Introduction and Objective: We examined disparities in spending on new diabetes drugs (GLP-1 RAs, SGLT2i) by race/ethnicity, income, and insurance type in adults with T2D.Methods: Using the 2018-2022 Medical Expenditure Panel Survey, we calculated annual per-person, inflation-adjusted spending on new drugs for two groups: (1) adults with T2D and (2) those with T2D plus cardiovascular disease or chronic kidney disease (CVD/CKD). We used a two-part regression model to estimate associations of race/ethnicity (non-Hispanic White [NHW], non-Hispanic Black [NHB], Hispanic, Other), income (<125% of the federal poverty level [FPL], 125% to <200% FPL, 200% to <400% FPL, ≥400% FPL), and insurance type (any private, Medicaid, Medicare only) with new drug spending, adjusting for age, sex, and education.Results: We observed disparities in the adjusted new drug spending for both patient groups. Spending was highest among NHW adults for T2D and among NHB adults for T2D plus CVD/CKD. Spending showed a U shape with highest income having the highest spending. Adults with private/Medicaid insurance spent more ($1,532/$1,288 for T2D, $1,972/$1,426 for T2D plus CVD/CKD) than those with Medicare ($793/$779).Conclusion: Disparities in new drug spending varied by race/ethnicity, income, and insurance. These findings can inform policies aimed at reducing access barriers to the new diabetes therapies for those in need.DisclosureP. Zhang: None. Y. Wang: None. K.M. Bullard: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-175-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 176-OR: The Effect of Medicaid Expansion on Diagnosis, Care, Treatment,
and Health for Diabetic Patients—Evidence from Medicaid Expansion in
Wisconsin-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 176-OR
Abstract: Introduction and Objective: We report time-series evidence on the effect of gaining Medicaid insurance on diagnosis, care, treatment, and intermediate health outcomes for diabetic patients, and compare effects for diabetic versus nondiabetic patients.Methods: We rely on difference-in-differences (DiD) analysis of visit-level healthcare records, before and after Medicaid expansion in Wisconsin in 2014 under the Affordable Care Act. We study newly Medicaid-enrolled childless adults over 2011-2022 using electronic health records records for a major, Milwaukee-based health system; compared to a propensity-score-balanced control group of previously enrolled persons.Results: Gaining Medicaid leads to a sharp rise in outpatient visits, ED visits, hospitalizations, and regular outpatient care for both diabetic and nondiabetic patients, with larger absolute increases for diabetics but similar percentage changes. Medicaid expansion also predicts large increases in various testing rates (stronger for diabetic patients); new diabetes diagnoses and related prescriptions; new diagnoses of diabetes-related conditions and related prescriptions (microvascular and peripheral vascular disease, chronic kidney disease, proteinuria, ischemic heart disease); stronger for diabetic patients. Intermediate health outcomes improve: blood pressure, cholesterol, and blood sugar levels (stronger for diabetics), but no reductions in longer-term adverse events for diabetic patients (macrovascular events, advanced kidney disease, amputations).Conclusion: Our findings suggest substantial unmet healthcare demand among newly insured diabetic patients, evidenced by initial surges in ED visits and hospitalizations. Over time, increased outpatient care reduces ED and hospital utilization, suggesting a substitution effect. Responses to Medicaid vary significantly between diabetic and nondiabetic patients.DisclosureS. Farzana: None. A.L. Owen: None. R.T. Ackermann: None. B. Black: None. J.R. Meurer: None.FundingNIH, National Center for Advancing Translational Sciences (UL1TR001436).
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-176-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 177-OR: Hyperglycemia Threshold Associated with Adverse Pregnancy Outcomes
in Gestational Diabetes Mellitus-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 177-OR
Abstract: Introduction and Objective: The optimal glucose targets in gestational diabetes mellitus (GDM) remains unknown. This study aimed to investigate the threshold of hyperglycemia associated with adverse outcomes in GDM using continuous glucose monitoring (CGM).Methods: This prospective cohort study recruited a total of 717 singleton pregnant women with GDM performing CGM during pregnancy. Time above ranges (TARs) were calculated as the percentage of time above the glucose thresholds from 5.6 to 8.1 mmol/L (100 to 145 mg/dl, increase by 5mg/dl each) during the whole CGM period respectively. Multivariate logistic regression analysis and restricted cubic spline (RCS) curve analysis were employed to explore the optimal threshold and range of TAR.Results: Of the 717 GDM women, 172 (24.0%) had LGA infants, and 144 (20.1%) had composite adverse outcomes. Only TARs with a threshold of 6.9 mmol/L (TAR>6.9) or above were significantly associated with the risk of LGA after adjusting confounders. For per absolute 5% increase in TAR>6.9, the risk of LGA was increased by 9.8% (OR 1.098, 95% CI: 1.008, 1.195). RCS curve showed that when TAR>6.9 > 26.0%, the risk of LGA increases with elevating TAR>6.9.Conclusion: A glucose level exceeding 6.9 mmol/L and TAR>6.9 > 26.0% were significantly associated with higher risk of LGA in women with GDM. Strict glycemic control may result in better prognoses.DisclosureG. Liang: None. S. Yan: None. Y. Wang: None. J. Lu: None. H. Wu: None. J. Zhou: None. Y. Wang: None.Fundingthe National Key Research and Development Program of China (2021YFC2501600, 2021YFC2501601); National Health Commission Medical Health Science and Technology Development Research Center "Innovative medicine post-marketing clinical research research project” (WKZX2023CX150002); Shanghai Science and Technology Commission Foundation (No. 21Y11904800; No. 23ZR1451500).
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-177-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 178-OR: Sensitivity of Different Screening Approaches for Early
Hyperglycemia in Pregnancy-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 178-OR
Abstract: Introduction and Objective: The 2025 ADA standards recognize early pregnancy dysglycemia is associated with worse outcomes, and recommend detection with either fasting glucose (FG) or A1C. This study compared different early glycemic screening strategies for overt diabetes (ODIP) and GDM prediction.Methods: Pregnant women with GDM risk factors enrolled in a multicenter early GDM RCT had a 75g OGTT and A1C <20 wks using ADA ODIP and GDM criteria. Repeat OGTT occurred at 24-28 wks if untreated (normal OGTT and randomized 50% early GDM). Area under the receiver operator curve (AUROC) with 95%CI was used for ODIP and late GDM prediction. The proportion of late OGTTs avoided included those with an A1C or FG <90% sensitivity thresholds or reaching the ADA early screening thresholds (A1C≥5.9%; FG≥110 mg/dL).Results: Among 3515 women, mean age was 31±5 yrs, BMI 29.9±7.4 kg/m2, OGTT gestation 16±3 wks, 40.6% were European. A1C and FG had similar AUROCs for ODIP and similar, but lower, AUROCs for GDM. The ADA-recommended A1C and FG thresholds were<50% sensitive for ODIP and <5% sensitive for GDM. An early FG threshold of 92 mg/dL was <70% sensitive for ODIP and persistent GDM. An early A1C threshold of 4.8% or FG of 76 mg/dL (@90% sensitivity for GDM) could avoid 22.7% of 24-28 week OGTTs (Table 1).Conclusion: The 2025 ADA recommended early pregnancy A1C and FG thresholds are insensitive tests for detecting women with ODIP and later pregnancy GDM.Disclosure D. Simmons: Research Support; Novo Nordisk, AMSL. Other Relationship; Abbott, Abbott, Boehringer-Ingelheim. Speaker's Bureau; Ascensia Diabetes Care. C.J. Nolan: None. J. Immanuel: None. H. Teede: None. J.R. Flack: None. V.W.M. Wong: None. E. Hibbert: None. M. McLean: Advisory Panel; Recordati Rare Diseases. A. Kautzky-Willer: None. J. Harreiter: None. H.E. Backman: None. E.J. Gianatti: None. A. Sweeting: None. V. Mohan: Speaker's Bureau; Novo Nordisk. Advisory Panel; Abbott. Research Support; Servier Laboratories. Speaker's Bureau; USV Private Limited, Sanofi, Medtronic, Eli Lilly and Company. W. Hague: None.FundingNHMRC (grants 1104231 and 2009326); Region 'rebro Research Committee Dnr OLL-970566, OLL-942177; Medical Scientific Fund of the Mayor of Vienna, project 15205; South Western Sydney Local Health District Academic Unit grant 2016; Western Sydney University Ainsworth Trust grant 2019
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-178-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 179-OR: Investigation of the Triglyceride–Glucose Index as a Marker of
Metabolic Dysfunction during Late Pregnancy-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 179-OR
Abstract: Introduction and Objective: Previous work indicates the triglyceride glucose (TyG) index can be used as predictor of gestational diabetes. Less is known about the relationship between TyG index and other markers of metabolic dysfunction during pregnancy. This study determined if TyG index is related to insulin resistance and inflammation in late pregnancy.Methods: Triglyceride, glucose, and insulin values were assessed during late pregnancy (N=62, 34.4±1.7 weeks gestation) at fasting and 1, 2, and 4hrs after a high-fat meal. C reactive protein (CRP) was assessed at fasting and 4hrs post-meal. Fasting triglycerides and glucose were used to calculate TyG index. HOMA-IR and MATSUDA were calculated. Insulin and glucose response to the meal were calculated as area under the curve (AUC) using all 4 timepoints. Potential correlations were assessed using SPSS.Results: TyG index was significantly correlated to insulin AUC, glucose AUC, fasting and postprandial CRP, HOMA-IR, and MATSUDA index (p<0.05)(Table), even after controlling for pre-pregnancy BMI.Conclusion: TyG index is associated with other established markers of metabolic dysfunction during late pregnancy. The ability to detect metabolic dysfunction during pregnancy has the potential to impact the immediate and future health of both mother and infant. Future work should assess the clinical utility of using the TyG index as a potential biomarker for adverse obstetric and neonatal outcomes.DisclosureJ.M. Mills: None. R. Purvis: None. C.G. Tucker: None. D.D. Pearson: None. N. Zite: Research Support; Merck & Co., Inc. K.B. Fortner: Other Relationship; Pfizer Inc. C. Reeder: None. M.M. Blankenship: None. R.A. Tinius: Stock/Shareholder; Bumptup Labs INC. J.M. Locklear: None. J.M. Maples: None.FundingNIH (5P20GM103436), WKU (17-8011), UTGSM Women in Science.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-179-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 180-OR: CGM in Early Gestational Diabetes Improves Maternal Glycemic
Control and Neonatal Outcomes—The Steady Sugar Trial-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 180-OR
Abstract: Introduction and Objective: Early detection and control of GDM benefits both the mother and the infant. We compared a CGM-based intervention vs routine SMBG-based care in a randomized controlled trial (NCT04948112) of women with GDM diagnosed in gestational weeks 8 to 26.Methods: From 10/2021 to 12/2023, 120 women were randomized to either real-time CGM (Dexcom G6, n=80) or the control group (SMBG 4×/day and monthly blinded CGM [Dexcom G6 Pro], n=40). Both groups received lifestyle and medication guidance based on glucose data until delivery. Two women in the control group were lost to follow-up. Maternal and neonatal outcomes were compared.Results: Women using unblinded real-time CGM experienced lower rates of unscheduled C-sections and preterm deliveries than women in the control group, and their infants experienced lower rates of large for gestational age (LGA) and neonatal intensive care unit (NICU) admissions (Table). Time in range 63-140 mg/dL was positively correlated with a longer gestational period (ρ=0.25, p=0.0012) and a favorable body weight percentile (ρ=-0.23, p=0.02).Conclusion: For women with GDM, early CGM initiation may contribute to improved maternal and neonatal outcomes versus SMBG. The effect may be mediated by improved awareness of glycemic excursions and by facilitation of treatment regimen adjustments.Disclosure K.E. Elkind-Hirsch: Other Relationship; Dexcom, Inc. Research Support; Dexcom, Inc. Advisory Panel; Lilly USA LLC. Research Support; Novo Nordisk A/S. Advisory Panel; Novo Nordisk A/S. M.L. Armatta: None. E.W. Veillon Jr: None. S. Guedry: None. J. Ballard: None. G. Cappon: Consultant; Dexcom, Inc., Ultragenyx.FundingDexcom, Inc.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-180-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 181-OR: Time in Range (TIR) Extrapolated from Self-Monitoring of Blood
Glucose (SMBG) and Risk for Adverse Perinatal Outcomes in Pregnancies
Complicated by T1DM-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 181-OR
Abstract: Introduction and Objective: Type 1 diabetes mellitus (T1DM) is associated with increased risks of adverse pregnancy outcomes. While Continuous Glucose Monitoring Systems (CGMS) improve glycemic monitoring, self-monitoring of blood glucose (SMBG) remains the primary method for most pregnant women due to accessibility and cost barriers. This study aimed to evaluate the association between time-in-range (TIR) extrapolated from SMBG and adverse perinatal outcomes in T1DM pregnancies.Methods: A retrospective cohort study included singleton pregnancies with live births and no malformations, starting prenatal care before 20 weeks (2010-2019). Glycemic data were categorized into TIR (63-140 mg/dL), time below range (TBR), and time above range (TAR) and stratified as TIR <50%, 50-70%, and >70%. Logistic regression analyzed independent predictors of adverse outcomes, including prematurity, LGA, and neonatal respiratory distress.Results: Among 140 participants that provided 142,997 capillary blood measurements, 20% had TIR <50%, 53.6% had TIR 50-70%, and 26.4% had TIR >70%. Higher TIR was inversely associated with adverse outcomes. Compared to TIR <50%, TIR 50-70% and TIR>70% were associated with lower risks of prematurity (OR 0.271, 95%CI 0.094-0.786; OR 0.219, 95%CI 0.058-0.826), neonatal respiratory distress (OR 0.341, 95%CI 0.124-0.936; OR 0.122, 95%CI 0.029-0.516), and LGA (OR 0.246, 95%CI 0.084-0.719; OR 0.115, 95%CI 0.028-0.469).Conclusion: Achieving glucose targets during pregnancy is particularly challenging for women with T1DM. Nonetheless, this study demonstrates that even modest achievements such as >50% TIR, extrapolated from SMBG, significantly reduces the risks of prematurity, LGA, and neonatal respiratory distress. These findings highlight the importance of supporting pregnant women with T1DM in achieving individualized glycemic goals to optimize maternal and neonatal outcomes.DisclosureE.A.M. Santos: None. T. Assuncao Zaccara: None. F.C.F. Mikami: None. M.D. Bernardi: None. C. de Freitas Paganoti: None. R.P.V. Francisco: None. R.A. Costa: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-181-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 182-OR: Serum Metabolomic Profiles Link History of Gestational Diabetes
Mellitus to Increased Type 2 Diabetes Risk in U.S. Hispanic/Latino Women-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 182-OR
Abstract: Introduction and Objective: Long-term impacts of gestational diabetes mellitus (GDM) on host metabolism are unknown. We aimed to identify serum metabolites linking history of GDM to type 2 diabetes (T2D).Methods: Among 2968 parous women in the Hispanic Community Health Study/Study of Latinos, we performed a metabolome-wide association analysis to identify metabolites associated with history of GDM; constructed GDM-related metabolite modules using network analysis; created a GDM-related metabolite score using elastic net regression; and linked these metabolite signatures with incident T2D over 12 years.Results: Ninety-six metabolites differed for women with and without history of GDM, 94 of which clustered into 5 modules. Amino acid (AA) module (mostly branched-chain and aromatic AA derivatives) and phosphatidylethanolamine module were positively associated with history GDM and T2D risk, while glycerophospholipid, acyl choline, and sphingomyelin modules were inversely associated with history of GDM and T2D risk (Fig A). The GDM-related metabolite score (Fig B) was associated with higher risk of T2D (HR = 1.37 [95% CI: 1.23-1.54] per SD, Fig C). AA module and the metabolite score partially mediated the association between history of GDM and T2D (29% and 30%).Conclusion: Circulating metabolites may play a role in GDM-related T2D risk in US Hispanic/Latino women.DisclosureY. Wang: None. C.R. Isasi: None. A. Stuebe: Other Relationship; Couplet Care. M.L. Daviglus: None. E. Boerwinkle: None. R. Burk: None. R. Kaplan: None. Q. Qi: None. B. Peters: None.FundingAmerican Diabetes Association (11-23-PDF-60)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-182-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 183-OR: Novel Osteogenic Secretory Factor IGF2 Promotes Golgi-Endosome
Trafficking to Enhance White Adipose Tissue Browning-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 183-OR
Abstract: Introduction and Objective: The skeleton is a key endocrine organ that secretes IGF2, which affects the browning of white adipocytes. This study aims to investigate how marrow IGF2 deficiency inhibits white adipose tissue browning and induces impaired glucose tolerance.Methods: A conditional myeloid-specific Igf2 knockout mouse model (Igf2ΔMey) was created using Cre-LoxP with LysM-Cre mice, and metabolic phenotype analysis was conducted between Igf2ΔMey and control mice. H&E, Oil Red O, UCP1 immunofluorescence, ELISA, and RT-qPCR assessed adipose tissue browning. Transcriptomic sequencing was performed on bone marrow macrophages and white adipocytes. Exogenous IGF2 was administered via micro-osmotic pump. IGF2's effect on IGF2R localization was studied using pH-responsive IGF2R and confocal microscopy, with results confirmed by flow cytometry. Golgi-IP and Lyso-IP with mass spectrometry identified altered trafficking proteins.Results:Igf2ΔMey mice exhibited increased weight gain, reduced energy expenditure, and impaired glucose tolerance compared to controls. They also had increased lipid deposition in peripheral tissues, larger white adipose tissue, and fewer UCP1-positive cells, indicating inhibited adipose tissue browning. Transcriptomic sequencing revealed changes in genes related to lipid metabolism and energy expenditure after Igf2 knockout. Exogenous IGF2 treatment partially reversed metabolic disorders and fat browning inhibition in obese mice. Confocal microscopy and flow cytometry confirmed that IGF2 knockdown inhibited IGF2R transport from the Golgi apparatus to endosomes. Mass spectrometry after Golgi-IP and Lyso-IP showed that IGF2 knockdown reduced cathepsin transport, especially Cathepsins D.Conclusion: The absence of IGF2 in marrow cells inhibits white adipose tissue browning by blocking IGF2R transport of cathepsins from the Golgi apparatus to lysosomes, causing obesity and insulin resistance.DisclosureX. Lin: None. C. Zhou: None. W. Gui: None. D. Wu: None. F. Wu: None. G. Wang: None.FundingZhejiang Provincial Natural Science Foundation of China (LY24H070002)
PubDate: Fri, 13 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-183-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 184-OR: Cold-Induced Cysteine Redoxome Landscape of Brown Adipose Tissue
-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 184-OR
Abstract: Introduction and Objective: The brown adipose tissue (BAT) is a potential therapeutic target for type 2 diabetes. A cold/noradrenalin-induced cysteine 253 oxidation (sulfenylation) of uncoupling protein 1 (UCP1) is critical for BAT activation, which is moderated by the diabetes-associated overproduction of selenoprotein P (Cell Rep 38:110566, 2022). However, a comprehensive understanding of oxidative and reductive stress target molecules and their structure-function modifications remains insufficient.Methods: To explore the temperature-sensitive Cys-post-translational modifications (Cys-PTMs), we established a comprehensive redoxome approach that pinpoints Cys-PTMs by differential alkylation followed by liquid chromatography and mass spectrometry (LC-MS) analysis. We have searched for reversibly oxidized and reduced Cys residues targeted by cold exposure in brown adipose tissues of wild-type mice at room temperature (RT) and after acute cold exposure.Results: Cold exposure altered the redox state of cysteine residues to oxidation in all cellular compartments, including the endoplasmic reticulum and mitochondria. We identified over 1000 reproducible Cys residues in either oxidized or reduced states at RT and cold exposure in mice. Among these, 34 Cys residues were specifically oxidized during cold exposure compared to RT. These cold-sensitive reactive cysteine residues were enriched in biological processes associated with thermogenesis pathways. The presence of proximal positively charged and negatively charged amino acids determined the highly reactive and non-reactive cysteine residues, respectively, under cold exposure.Conclusion: Redox modifications of cysteine residues in various proteins may regulate brown fat thermogenesis. Our cold-reactive redoxome analysis would provide novel therapeutic targets for impaired thermogenesis associated with type 2 diabetes.Disclosure T. Takamura: Research Support; Kowa Company, Ltd, Taisho Pharmaceutical Holdings Co., Ltd. H. Oo: None. C.M. Galicia-Medina: None. H. Goto: None. Y. Nakano: None. Y. Takeshita: None. H. Takayama: None.FundingJapan Society for the Promotion of Science (JSPS) Grants-in-Aid for Scientific Research (KAKENHI) (23K27649, 23KF0035); Takeda Science Foundation.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-184-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 185-OR: Slit3 Fragments Drive Neurovascular Expansion and Thermogenesis in
Brown Adipose Tissue-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 185-OR
Abstract: Introduction and Objective: Brown adipose tissue (BAT) is a specialized organ that regulates body temperature through adaptive thermogenesis. Unlocking the potential to enhance metabolism through the activation of BAT thermogenesis is a promising strategy to counteract obesity and its cardiometabolic sequelae. Brown adipocytes are embedded in a dense network of blood vessels and sympathetic nerves that support their thermogenic activity. Chronic cold exposure increases BAT mass by de novo recruitment of brown adipocytes, as well as by expanding the network of blood vessels and sympathetic neurites in the tissue. However, the mechanisms coordinating the expansion and remodeling of neurovascular network in BAT are not well understood.Methods: We have recently identified Slit guidance ligand 3 (Slit3) as a new adipokine that mediates the crosstalk among adipocyte progenitors, endothelial cells, and sympathetic nerves. Using a combination of in vivo gain and loss of function studies, we demonstrated that Slit3 is essential for cold-induced angiogenesis, sympathetic innervation, and thermogenesis in BAT.Results: We showed that Slit3 undergoes proteolytic cleavage, yielding two fragments: a large Slit3 N- terminal and a shorter Slit3 C-terminal, which signal through distinct receptors to stimulate angiogenesis and sympathetic innervation, respectively. Overexpression of Slit3 fragments directly promote the expansion of the neurovascular network in BAT, with Slit3-C driving sympathetic innervation and Slit3-N promoting angiogenesis, collectively enhancing thermogenic function.Conclusion: These findings highlight the critical role of Slit3 signaling in the development and remodeling of the neurovascular network in BAT. They also identify a promising therapeutic target for enhancing systemic metabolism through the healthy expansion of thermogenic fat.DisclosureT. Duarte Afonso Serdan: None. B. Frank: None. H.E. Cervantes: None. G.J. Schwartz: None. F. Shamsi: None.FundingNIH/NIDDK (K01DK125608, R03DK135786, and R01DK136724) (to F.S)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-185-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 186-OR: Brain-Angiogenesis Inhibitor-3 Ablation Enhances Brown Adipose
Tissue Thermogenesis and Protects against Obesity-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 186-OR
Abstract: Introduction and Objective: Obesity, a primary cause of cardiometabolic diseases and type 2 diabetes, is associated with impaired brown adipose tissue (BAT) function. Activating Gs-protein-coupled receptors (GPCRs) in BAT is central for promoting thermogenesis and energy expenditure (EE), which play a key role in regulating body weight (BW). However, a complete understanding of altered GPCR signaling in BAT on obesity remains elusive.Methods: In our study, using a mouse model, we identified the adhesion Gi-GPCR brain angiogenesis inhibitor 3 (BAI3) as a negative regulator of EE. BAI3, expressed in BAT, was found to inhibit BAT function.Results: Excitingly, the deletion of BAI3 enhanced EE, reduced fat mass, and decreased adipocyte size, resulting in lower BW without affecting lean mass or food intake in mice on low- and high-fat diets. Importantly, BAI3-deficient mice displayed elevated glucose clearance and internal body temperature during cold exposure, while no EE enhancement occurred at thermoneutrality, indicating BAI3’s role in adaptive thermogenesis. Mechanistically, BAI3 loss enhanced lipogenesis, fatty acid oxidation, fatty acid uptake, mitochondrial function, and thermogenesis in BAT, improving glucose and fatty acid utilization. These changes improved the metabolic profile: glucose clearance, insulin sensitivity, circulating triglycerides, and non-esterified fatty acids.Conclusion: Our findings highlight that BAI3 inhibits BAT function and adaptive thermogenesis. BAI3 ablation protects against diet-induced obesity by enhancing BAT-mediated metabolic activity and EE. Targeting BAI3 signaling represents a promising therapeutic approach to treating obesity and related metabolic disorders through BAT activation.DisclosureH. Alsharif: None. K. Perez: None. D. Tummala: None. J.B. Alexander: None. G. Ren: None. M. Rahman: None. M. Young: None. S. Bhatnagar: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-186-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 187-OR: Adipocytes Derived from TRPV1-Positive Vascular Smooth Muscle
Cells Regulate Cold-Induced Energy Expenditure-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 187-OR
Abstract: Introduction and Objective: Cold induces adipose progenitor cells (APCs) to form thermogenic brown and beige adipocytes, improving metabolic health. Notably, Trpv1+ vascular smooth muscle cells, unique subset of APCs, produce thermogenic adipocytes in brown (BAT) and white adipose tissue (WAT). However, their exact function in metabolic regulation is not fully understood; therefore, we aimed to investigate their role in cold-induced thermogenesis and metabolic regulation.Methods: To impair adipogenesis and trace in vivo lineage, we generated a mouse model with insulin receptor (IR) deletion in Trpv1+ APCs using the R26R-mTmG reporter. To selectively ablate adipocytes, we developed a novel mouse model using doxycycline-inducible DRAGON-DTA system combined with Trpv1-Cre and adiponectin-rtTA lines.Results: In control mice, Trpv1+ APCs contributed to approximately 30% of all brown and white adipocytes during cold. With deletion of IR in Trpv1+ APCs, this contribution was significantly reduced in BAT and inguinal WAT in transgenic mice. Despite impaired adipogenesis, we found that these transgenic mice displayed no significant differences in body weight, glucose tolerance, and insulin sensitivity, suggesting a compensatory mechanism by other APCs. To circumvent this issue and directly determine the role of adipocytes derived from the Trpv1+ APCs, we induced deletion of these adipocytes. Selective ablation of Trpv1+ APC-derived adipocytes in adult mice significantly reduced energy expenditure upon cold, highlighting the physiological significance of the adipocytes derived from Trpv1-lineage.Conclusion: Our studies show the important contribution of Trpv1+ APCs in thermogenic adipocyte formation and thermogenesis, making them as a potential target to treat obesity and diabetes.DisclosureC. Sahin: None. H. Camara: None. Y. Tseng: Consultant; Paratus Sciences. Other Relationship; Novo Nordisk, ATCC, Biohaven. Consultant; LyGenesis.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-187-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 188-OR: Uncovering the Mechanisms of Brown Adipose Tissue Aging Using
Spatially Resolved Single-Nucleus Transcriptomics-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 188-OR
Abstract: Introduction and Objective: In humans, the mass and activity of brown adipose tissue (BAT) substantially decrease during aging, increasing the risk of obesity and metabolic diseases. However, the mechanisms underlying the age-related decline in BAT thermogenesis remains unclear. Due to their genetic and physiological similarities to humans, non-human primates (NHPs) offer a suitable model for studying BAT aging. Here, we explore the mechanisms of BAT aging using single-nucleus RNA sequencing (snRNA-seq) and spatial transcriptomics in NHPs models.Methods: BAT from supraclavicular and axillary depots of female and male African green monkey (Chlorocebus aethiops sabaeus) of varying ages (1-19 years, spanning the entire lifespan) was collected for snRNA-seq and spatial transcriptomics analysis.Results: A total of 89023 nuclei were retrieved after quality control and cell filtration. Nuclei in NHPs’ BAT were clustered into 10 main cell types. We demonstrated that aging significantly reshapes adipocyte populations, resulting in an increase in Leptin-expressing white adipocytes and a decline in UCP1-expressing thermogenic adipocytes. Additionally, we showed that aging results in a rise in pro-inflammatory macrophages and a reduction in anti-inflammatory macrophages. By combining snRNA-seq data with spatial transcriptomics, we identified distinct protective niches within aging BAT that preserved sympathetic neurites and clusters of brown adipocytes, even in older monkeys. Transcriptional analysis of these niches uncovered key intrinsic and extrinsic factors contributing to BAT resilience or vulnerability to inflammaging.Conclusion: Our study fills critical gaps in our understanding of BAT biology and uncovers new mechanisms and targets to combat metabolic aging.DisclosureL. Wang: None. K. Kavanagh: None. F. Shamsi: None.FundingAmerican Heart Association Award (24CDA1271852)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-188-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 189-OR: Engineered Mesenchymal Stem Cell Therapy for the Prevention and
Treatment of Type 1 Diabetes in Murine Models-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 189-OR
Abstract: Introduction and Objective: Type 1 diabetes (T1D) is an autoimmune disease in which autoreactive T cells destroy insulin-producing pancreatic β cells. Mesenchymal stem/stromal cell (MSC) therapy has the potential for modulating the immune system and protecting β cells. This study investigates the mechanisms on MSCs engineered to express alpha-1 antitrypsin (AAT-MSCs) prevent and reverse T1D in non-obese diabetic (NOD) mice.Methods: AAT-MSCs were tested in diabetes prevention and treatment models using female NOD mice at various disease stages. Blood glucose, C-peptide levels, cytokine profiles, and insulitis severity were assessed. Single-cell RNA sequencing, flow cytometry, and functional assays were performed to characterize the impact of AAT-MSCs on T cell subtypes, focusing on CD4+ and CD8+ T cells in pancreatic lymph nodes (PLNs) and islets. In vitro, T cell assays and other tests were used to compare Treg's immunosuppressive function and impacts on other cells.Results: AAT-MSCs delayed T1D onset in NOD mice by reducing insulitis and preserving islet function. AAT-MSCs enhanced the immunosuppressive function of regulatory T cells (Tregs) while reducing the numbers of T helper 1 (Th1) cells and CD8+ cytotoxic T cells. CD4+ Tregs from AAT-MSC-treated mice showed increased Helios and CTLA-4 expression and enhanced immunosuppressive function. In vitro, AAT-MSCs promoted Treg proliferation, which improved the exhausted phenotype of CD8+ T cells, contributing to diabetes remission. A single AAT-MSC infusion reversed T1D in newly diagnosed NOD mice, likely by increasing Treg numbers and function and reducing inflammatory cytokines.Conclusion: AAT-MSCs effectively reverse T1D onset by suppressing autoimmune responses and protecting islets from death. Our findings underscore the significant protective effects of AAT-MSCs, delineate their impact on recipient immune cells, and provide evidence for the clinical application of AAT-MSCs in treating T1D.DisclosureH. Wang: None. H. Wei: None. C. Strange: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-189-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 190-OR: Omics-Based Insights into Type 1 Diabetes Pathogenesis in Nonobese
Diabetic Mice-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 190-OR
Abstract: Introduction and Objective: Type 1 diabetes (T1D) is an autoimmune disease characterized by the destruction of insulin-producing pancreatic β cells. Despite significant advances in understanding T1D pathogenesis, the immunological mechanisms underlying β cell destruction remain incompletely understood.Methods: To investigate this, we performed single-cell RNA sequencing on pancreatic macrophages from T1D-prone non-obese diabetic (NOD) mice at 6 weeks, 9 weeks, and 21 weeks, corresponding to the prediabetic, early diabetic, and diabetic stages, respectively.Results: Our analysis revealed unique proinflammatory macrophage cluster, Ccr9+ macrophages, at 21 weeks of age. Chemokine expression was dynamically regulated, as Ccl4 and Ccl5 was observed at T1D onset and Ccl8 was prominent during overt diabetes. Csf1r+ and Cd79+ macrophages in the 21-week group exhibited a higher differentiation state or lower stemness compared to the 6-week and 9-week group. We extended our analysis to examine the role of oxidative stress in T1D by performing spatial transcriptomics between NOD and NOD.Ncf1m1J mice. NOD.Ncf1m1J mice exhibit a delay in T1D due to their inability to produce NADPH oxidase-derived superoxide. In NOD.Ncf1m1J mice, β-cells exhibited increased expression of genes linked to anti-apoptosis (Mid1), anti-inflammation (Erdr1), ROS signaling (Nfkb1, Sel1l and Trir), and β-cell regeneration (Reg1). Notably, the Reg (Reg1, Reg2, Reg3a, Reg3b and Reg3d) family genes showed prominent expression in the non-β-cells or exocrine tissue of NOD.Ncf1m1J mice. Reg and Mid1 genes were validated through bulk RNA sequencing and quantitative real-time PCR assays.Conclusion: Our findings offer valuable insights into immune- and β-cell-specific genes and pathways that drive T1D progression and may aid in its prevention.DisclosureH. Shinde: None. J.P. Taylor: None. K.S. Burnette: None. M.D. Chávez: None. K. Coutinho: None. J. Feduska: None. C.S. Hunter: None. H.M. Tse: None.FundingAmerican Diabetes Association (1-25-PDF-107); NIH/NIDDK (DK126456, DK127497, DK131716, DK138469); NSF ( 2208831); JDRF (2-SRA-2024-1509-S-B)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-190-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 191-OR: Targeting IL-8/CXCR1-CXCR2 to Unleash Regulatory B Cells in Type 1
Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 191-OR
Abstract: Introduction and Objective: The IL-8/CXCR1-CXCR2 axis has been demonstrated to be impaired in T1D, thus we hypothesize that targeting IL-8/CXCR1-CXCR2 axis may contribute to the expansion and differentiation of regulatory B cells.Methods: We profiled by FACS analysis murine and human Bregs (CD19+IL-10+ cells) isolated from patients with T1D as compared to healthy controls (HC) for IL-8/CXCR1-CXCR2 expression under resting/stimulating conditions. We tested the effect of murine Bregs expanded by LPS/rIL-2 in the presence of different titrations of Reparixin (1nM, 10nM and 50nM) in a co-culture assay with anti-CD3/anti-CD28 stimulated T cells or with diabetogenic T-cells (BDC2.5 stimulated CD4+ T cells), during a proliferation assay.Results: Our data showed that IL-8 and CXCR2 were found significantly higher on Bregs and also on non-Bregs (CD19+IL-10- cells) in patients with T1D as compared to HC (p<0.05). While under stimulating conditions (anti-CD40L/LPS), CXCR1 and CXCR2 were found significantly higher on Bregs from patients with T1D as compared to HC (p<0.05). The murine data in NOD on Bregs generated under stimulating conditions (LPS/IL-2) revealed an upregulation of CXCL1 and CXCR1 during the time course of T1D as NOD hyperglycemic showed the highest expression while those naturally protected from T1D showed the lowest expression (p<0.05). We next studied the effect of targeting IL-8/CXCR1-CXCR2 during murine Breg generation. A significant suppression of CD4+/CD8+ T cell effector proliferation in all conditions where Bregs were added as compared to T cells alone (p<0.001). Particularly, a reduced T-cell response toward islet autoantigens with Bregs expanded in the presence of Reparixin 10nM showed the most potent effect as compared to untreated (p<0.001). Lastly, we confirmed the immunoregulatory capacities of Bregs generated using Reparixin through an inhibition of IFN-γ production by diabetogenic T-cells (p<0.05).Conclusion: Altogether, targeting IL-8/CXCR1-CXCR2 axis may help to establish a novel tailored Breg-based immunotherapy in T1D.DisclosureS. Khalefa: None. M. Ben Nasr: None. V. Usuelli: None. P. Yerra: None. E. Assi: None. A. Petrazzuolo: None. M. Zocchi: None. F. D'Addio: Advisory Panel; Sanofi. C. Loretelli: None. I. Pastore: Advisory Panel; Sanofi. Board Member; Novo Nordisk. L. Montefusco: None. A. Rossi: Consultant; Roche Diabetes Care, Ascensia Diabetes Care, Ypsomed AG. M. Lunati: None. G. Zuccotti: None. M. Allegretti: Employee; Dompé. P. Fiorina: Consultant; Novo Nordisk, AstraZeneca. Board Member; Boehringer-Ingelheim.FundingThe study is part of the activities planned in the co' financed project "Ladari.un as new Juvenile Diabetes Inhibitory Agent (LJDIA)" presented by Dompe under the Call "Fondo crescita sostenibile - Proposal n. 1410 bando MISE DM 02/08/2019 and consecutive DD 02/10/2019" ("MISE Grant").
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-191-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 192-OR: Protection against Type 1 Diabetes Development in Mice with 4E-BP2
Deletion-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 192-OR
Abstract: Introduction and Objective: Type 1 diabetes (T1D) is an autoimmune disease characterized by β-cell destruction promoted by autoimmune responses. 4E-BP1/2 proteins are translational repressors and downstream targets of mTORC1, a key regulator of β-cell mass and function. Activation of 4E-BP2/eIF4E pathway by 4E-BP2 deletion in β-cells promotes β-cell survival by increases in IRS2. mTORC1 axis is also crucial for the regulation and function of adaptive immunity. This study aimed to determine the role of 4E-BP2/eIF4E signaling in T1D.Methods: We generated mice with global deletion of 4E-BP2 in the Non-Obese Diabetic (NOD) background (Eif4epb2-/-) and assessed T1D development, glucose homeostasis, pancreas morphometry and immune responses. We performed adoptive transfer studies of splenocytes, from control and Eif4epb2-/- mice into NOD SCID mice.Results: We found that Eif4epb2-/- exhibited reduced diabetes incidence in male but not female mice. Reduction in diabetes incidence in Eif4epb2-/- male mice was associated with comparable degree of insulitis, β-cell proliferation, and increased β-cell mass preservation. Glucose-stimulated insulin secretion in vitro was significantly higher in the Eif4epb2-/- isletscompared to control. Autoimmune responses were also evaluated by characterization of T cell compartments, which showed a decrease in splenic CD8+ memory and cytotoxic T cells, and an increase in pancreatic regulatory T cell infiltration, mainly by increased proliferation and CD73 expression in Eif4epb2-/- mice compared to controls. Finally, adoptive transfer studies showed that lymphocytes from Eif4epb2-/- mice were less diabetogenic than those from control, with the mice that received Eif4epb2-/- splenocytes exhibiting the biggest β-cell mass preservation.Conclusion: In conclusion, this study showed that activation of 4E-BP2/eIF4E axis in Eif4epb2-/- male mice protects against T1D development by dampening autoimmune responses and preserving β-cell mass. Targeting 4E-BP2 may provide a potential treatment for T1D.DisclosureV. Pita-Grisanti: None. F. Pecanha: None. R. Andrade Louzada Neto: None. M. Blandino-Rosano: None. C. Jaramillo: None. N. Arenas: None. A.L. Bayer: None. E. Bernal-Mizrachi: None.FundingR01DK132103
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-192-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 193-OR: IL-6 Deficiency Mitigates Metabolic Dysregulation in Mice via
CXCL14-Driven Inflammation Reduction in Adipose and Liver Tissues-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 193-OR
Abstract: Introduction and Objective: Interleukin 6 (IL-6) is significantly associated with obesity-related inflammation. IL-6 knockout (KO) mice exhibit protection against obesity and diet-induced metabolic dysfunction; however, the mechanisms underlying these effects are not well understood.Methods: C57BL/6J and IL-6KO mice were fed either a high-fat diet (HFD) or standard chow for 22 weeks. Recombinant IL-6 (rIL-6) was administered to both IL-6KO and wild-type (WT) mice. Metabolic and immunological profiling was done. RNA sequencing, qRT-PCR, IHC, and ELISA techniques were employed.Results: RNA seq analysis of adipose tissue (AT) and liver from IL-6KO and WT mice fed HFD revealed that CXCL14 was highly expressed in both tissues of IL-6KO mice. IL-6KO mice exhibited elevated levels of CXCL14 in circulation. No differences were seen in mice fed chow diet. High levels of CXCL14 in IL-6 KO mice promoted M2 macrophage (CD206, IL-10) polarization in AT and mitigated chronic inflammation and insulin resistance, whereas less CXCL14 in WT obese mice enhanced M1 macrophage (CD11c, CCL2, TNF-α, IL-1β, INOS) activity. Furthermore, IL-6KO mice fed HFD displayed diminished hepatic fat accumulation and lipogenesis which correlated with increased CXCL14 levels and improved insulin sensitivity, thereby supporting glucose homeostasis. Interestingly, β-oxidation was only upregulated in the AT of IL-6KO mice, showing a positive link with CXCL14. Administration of rIL-6 to both WT and IL-6KO mice reduced CXCL14 expression in adipose and liver tissues, corresponding to increased inflammation, liver steatosis and insulin resistance.Conclusion: This study suggests that IL-6 deficiency protects against HFD-induced metabolic dysfunction through CXCL14 overexpression, which reduces inflammation and lipid accumulation in the liver and enhances insulin sensitivity, highlighting CXCL14 as a potential therapeutic target for improving metabolic health in obesity.DisclosureR. Ahmad: None. S.P. Kochumon: None. F. Bahman: None. H. Arefanian: None. S. Shenouda: None. T.K. Jacob: None. N. Al-Mansour: None. R.S. Thomas: None. R. Nizam: None. F. Alrashed: None. M. Malik: None. A. Al Madhoun: None. F. Almulla: None.FundingKuwait Foundation for the Advancement of Sciences (RA AM-2023-021)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-193-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 194-OR: Sexually Dimorphic Microglial Senescence and Inflammatory
Mechanisms in Obesity and Prediabetes Induced Cognitive Impairment-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 194-OR
Abstract: Introduction and Objective: Rates of metabolic stress (obesity, prediabetes, metabolic syndrome, and diabetes) are increasing worldwide. Metabolic stress increases the risk of cognitive impairment, including dementias, with age. Immune system dysregulation/inflammation, including senescence-related inflammation, are common etiologies of metabolic stress, aging, and cognitive impairment. In particular, the cGAS/STING pathway is implicated as a critical inflammatory mechanism. However, its role in promoting cognitive impairment under conditions of metabolic stress remains unclear.Methods: Wild-type and cGAS knock-out (KO) male and female mice were fed standard or high fat diet (HFD; n=10-14 mice/group) from 1-2yrs of age. Longitudinal metabolic (body weight, glucose tolerance) and cognitive (puzzle box) phenotyping was performed throughout the feeding period. At terminal, hippocampal single cell RNAseq was also performed.Results: HFD-feeding increased weight gain and glucose intolerance, particularly in females. With age, mice experienced age-associated weight loss and moderate reduction in glucose tolerance, which was blunted in cGAS KO animals. HFD and age also worsened cognition, with the largest impact seen in females (particularly cGAS KO females). After 1yr of feeding, hippocampal gene expression profiles showed a pro-inflammatory, neurodegenerative effect of HFD-feeding. Additionally, there were a high number of senescence cells in the hippocampus, which were primarily found to be microglia. Further, female cGAS KO mice had the largest increase in microglial senesce cell burden due to HFD feeding.Conclusion: Metabolic and cognitive profiles were negatively impacted by HFD feeding, with female cGAS KO mice disproportionately impacted. This was likely due, at least in part, to their high burden of microglial senescence. More work is required to fully understand how cGAS/STING mediates microglial inflammatory and senescence responses, particularly accounting for sex.DisclosureS. Elzinga: None. K. Guo: None. D.M. Rigan: None. S. Teener: None. J. Park: None. A.D. Carter: None. J.M. Hayes: None. J. Hur: None. E.L. Feldman: None.FundingNational Institutes of Health (1K99AG071667-01A1)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-194-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 195-OR: The Ubiquitin-Ligase Substrate Adaptor KCTD17 Controls β-Cell
Compensation to Insulin Resistance in Type 2 Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 195-OR
Abstract: Introduction and Objective: Type 2 diabetes (T2D) is closely linked to insulin resistance and loss of functional β-cell mass. However, not all insulin-resistant individuals develop T2D. We aimed to investigate the transcriptomic and m6A RNA methylation modifications in β-cells during their successful adaptation to insulin resistance (IR).Methods: We performed mRNA-seq on sorted β-cells from mouse models with graded compensation to IR: (a) a dietary model (HFD), (b) a genetic model (LIRKO, liver-specific insulin receptor KO on chow), and (c) a combined model (LIRKO on a HFD) (n=86 mice). We correlated transcriptomic data with β-cell compensation readouts, and integrated these findings with scRNA-seq datasets from human β-cells with/without T2D. Additionally, we conducted m6A-seq in these mouse islets (n=155 mice).Results: Our analyses identified the ubiquitin-ligase substrate adaptor KCTD17 as a key regulator of β-cell adaptation. Expression of KCTD17 positively correlated with increased β-cell function and mass in mouse models but was downregulated at both mRNA and protein levels in human T2D β-cells. KCTD17 KD in human β-cells increased apoptosis and impaired GSIS. Transcriptomic analysis of KCTD17 KD cells revealed dysregulated pathways linked to β-cell function and identity. Antibody-microarray analysis showed reductions in MAPK and insulin signaling. Co-immunoprecipitation experiments demonstrated that KCTD17 binds and regulates the degradation of clathrin, a key player in insulin receptor internalization. m6A-seq revealed differential methylation of chromatin-modifying enzymes during β-cell compensation. Supporting this, ATAC-seq data from human T2D islets showed decreased chromatin accessibility at the KCTD17 locus.Conclusion: These findings position KCTD17 as a novel regulator of β-cells, and demonstrate the importance of m6A methylation in chromatin remodeling and transcriptional regulation during β-cell adaptation to IR.DisclosureD.F. De Jesus: None. N.K. Brown: None. Z. Zhang: None. G. Fogarty: None. J. Wei: None. J. Hu: None. S. Kahraman: Employee; Boehringer-Ingelheim. A. El Ouaamari: None. E. Dirice: None. C. He: None. R. Kulkarni: Advisory Panel; Novo Nordisk, Biomea Fusion, REDD Pharma, Inversago Pharma. Research Support; Inversago Pharma. Stock/Shareholder; Biomea Fusion.FundingNIH (R01 DK067536, UC4 DK116278, RC2 DK139552, and K99 DK135927)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-195-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 196-OR: The Global Loss of DYRK1B Impairs Glucose Tolerance by Disrupting
Beta-Cell Development and Function-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 196-OR
Abstract: Introduction and Objective: Rare loss-of-function mutations in the DYRK1B gene are associated with early-onset coronary artery disease, metabolic syndrome, and type 2 diabetes.Methods: To investigate its role in metabolism, we generated global Dyrk1b knockout (KO) mice and conducted detailed metabolic and cellular analyses.Results: IPGTT, ITT, and plasma insulin and C-peptide in adult mice revealed impaired glucose tolerance in Dyrk1b KO mice, driven by reduced insulin secretion. Pancreatic islets were smaller in both neonatal (P6) and adult KO mice, suggesting a role for Dyrk1b in pancreatic beta cell proliferation. Markers of cell proliferation were reduced in Dyrk1b KO islets, accompanied by upregulation of p27 and suppression of Cyclin D1. Mechanistic studies revealed reduced phosphorylation of GSK3β, mTORC2, and Stat3, alongside increased nuclear Foxo1 in KO islets. Accordingly, beta cells from KO mice lacked functional cilia. In INS-1 cells, Dyrk1b knockdown impaired Akt, Foxo1, mTOR, Erk1/2, and Stat3 phosphorylation, resulting in decreased Cyclin D1, ciliogenesis, and cell proliferation. Insulin restored Akt pathway, provided only a temporary recovery of beta cell cilia but failed to rescue Stat3 phosphorylation or cell division, emphasizing the critical role of Stat3 in maintaining ciliogenesis and promoting beta cell proliferation. Overexpression of Dyrk1b in INS-1 cells enhanced phosphorylation of Akt, Foxo1, mTOR, GSK3β, and Erk1/2, and Cyclin D1 and promoting ciliogenesis and mitosis in a kinase activity-dependent manner. Remarkably, Dyrk1b overexpression also increased pancreatic islet size and improved beta cell function in wildtype and diabetic liver-specific Rictor KO mice.Conclusion:Dyrk1b regulates beta cell development by modulating Stat3/Akt/GSK3β pathways, ciliogenesis, and mitosis. These findings position DYRK1B as a promising therapeutic target for preserving beta cell health and improving outcomes in both type 1/2 diabetes.DisclosureH. Kim: None. A. Mani: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-196-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 197-OR: Senolysis in Pancreatic β-Cells Improves Islet Transplantation
Outcomes in Preclinical Models of Diabetes Mellitus-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 197-OR
Abstract: Introduction and Objective: Islet transplantation (Tx) is an effective treatment for type 1 diabetes (T1D). However, transplanted islet function gradually declines. We investigated the role of cellular senescence in graft dysfunction and the therapeutic potential of senolytics.Methods: Islets from rats (600 IEQ), humans (1000 IEQ), or mice (400 IEQ) were transplanted into the kidney capsule of streptozocin-induced diabetic (Db) or normoglycemic (NG) immunodeficient mice.Results: After 2 weeks, transplanted rat islets showed higher P16 in mRNA and protein levels compared to pre-transplanted (pre-Tx) islets. Furthermore, the average of β-cell related genes (β-cell index) was lower in Db than NG grafts. We next cultured human islets for 2 weeks in 20.2 mM or 2.8 mM glucose. Cultured islets in 20.2 mM showed higher P21 mRNA and lower glucose-induced insulin secretion. Moreover, β-cell index was increased by senolytics, dasatinib and quercetin (DQ), suggesting that hyperglycemia promoted pancreatic β-cell senescence. In human Tx, both P16 and P21 protein levels were higher in the graft from NG than pre-Tx, and P21 mRNA level was higher in Db than NG. DQ treatment improved the β-cell index and HOMA-β, especially in islets from older and high BMI donors. To test the role of P16- or P21-positive senescent cells in the grafts, we transplanted islets from mice in which P16-positive (INK-ATTAC) or P21-positive (PTD) cells could be eliminated, respectively. Elimination of graft P16- or P21-positive cells improved fed blood glucose levels. P21-positive cell elimination also improved glucose clearance by IPGTT. Bulk RNA-seq of transplanted human islets showed upregulation of insulin receptor signaling pathways in the graft, pointing to a potential mechanism.Conclusion: β-cell senescence contributes to the functional decline of transplanted islets. The current findings also support the therapeutic potential of senolytics to improve Tx outcomes in T1D.DisclosureK. Iwasaki: None. P. Carapeto: None. J. Hollister-Lock: None. C. Cahill: None. S. Bonner-Weir: None. C. Aguayo-Mazzucato: Consultant; Novo Nordisk.FundingManpei Suzuki Diabetes Foundation, Mary K. Iacocca Fellowship.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-197-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 198-OR: High-Fat Diet Has Different Impact on Human Alpha- and Beta-Cells
In Vivo-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 198-OR
Abstract: Introduction and Objective: Hyperglycemia, insulin resistance, and hyperglucagonemia are key features of type 2 diabetes (T2D). While insulin resistance increases insulin secretion and beta-cell proliferation in mice, it does not have the same impact on transplanted human beta cells. Since mouse and human glucagon are identical, distinguishing between secreted glucagon from transplanted human islets versus the host mouse pancreas has not been possible. We used a glucagon-knockout immunodeficient mouse model (NSG-GKO) to investigate the impact of high-fat diet on human alpha cell function in vivo.Methods: NSG-GKO mice transplanted with normal human islets (1000 IEQ, n=4 donors) were fed either a HFD (HFD+Islets [I]) or regular diet (RD+I) for 12 weeks. Body weight and random glucose were measured weekly. GTT, serum lipids, fasted (6h) and stimulated (15 min after glucose/arginine [G/A] injection) human insulin and glucagon were assessed every 4 weeks. After 12 weeks, the human grafts were analyzed.Results: By week 3 of the diet, HFD+I mice were glucose intolerant. After 12 weeks, they exhibited a 2.8-fold increase in body weight, higher serum cholesterol, triglycerides, and glucose. Fasted insulin levels at 8 weeks were increased 2.2-fold in HFD-I (p=0.0009) and glucagon slightly increased (43.5±5.3 vs 61.0±8.3pg/mL). G/A stimulated human insulin secretion in the RD+I group (basal vs. stimulated: 0.53±0.08, 0.95±0.18ng/mL, p=0.024) but not in the HFD+I mice (1.21 ± 0.16 vs. 0.76 ± 0.18 ng/mL, p=0.075). In contrast, G/A-stimulated human glucagon secretion was 1.4-fold greater in the HFD+I group compared to the RD+I group. We observed increased amyloid deposits (4.6±1 vs. 8.8±0.7% of insulin area, p=0.0016) in grafts of HFD+I mice and a reduced number of MAFB+ and NKX6.1+ beta cells after 12 weeks of HFD. ARX+, MAFB+ alpha cells were similar in both cohorts.Conclusion: Transplanted human alpha and beta cells have a different response to HFD, with impaired insulin but increased glucagon secretion, suggesting these contribute to hyperglucagonemia and hyperglycemia.DisclosureC. Dai: None. K.C. Coate: None. R. Brantley: None. E. Acker: None. A. Eskaros: None. A.K. Singh: None. N. Dey: None. R. Jenkins: None. K. Tellez: None. Y. Hang: None. M. Brissova: None. J.J. Wright: None. S. Kim: None. A.C. Powers: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-198-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 199-OR: Mutation in CELA2A Drives Impaired Pancreatic Islet Development
and Function-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 199-OR
Abstract: Introduction and Objective: Loss-of-function mutations in the exocrine pancreatic enzyme chymotrypsin-like elastase (CELA2A) are associated with metabolic syndrome and diabetes. CELA2A is a ubiquitously expressed protein that enters circulation and enhances both insulin secretion and sensitivity. Mice with global deletion of Cela2a exhibit impaired glucose-stimulated insulin secretion, accompanied by reduced pancreatic islet size and number, suggesting a developmental defect. These phenotypes correlated with decreased islet cell proliferation, increased inflammation, and loss of extracellular matrix (ECM) proteins in pancreatic islets. However, the precise molecular mechanisms linking CELA2A to islet development and function remained unclear.Methods: Histological analysis revealed infiltration of both the exocrine and endocrine pancreas, as well as adipose tissue, with macrophages and monocytes in CELA2A knockout (KO) mice. Further investigations showed that CELA2A is expressed and secreted by monocytes and neutrophils and stimulates insulin secretion. In CELA2A KO mice, plasma inflammatory cytokines were elevated, while anti-inflammatory IL-10 levels were reduced, suggesting systemic inflammation caused by M1 macrophage polarization.Results: Transplantation of wild-type (WT) bone marrow into CELA2A KO mice restored pancreatic islet integrity, ECM composition, and vasculature, normalized macrophage polarization, and improved islet size and function. Conversely, transplantation of CELA2A bone marrow into WT recipients induced islet defects, confirming the critical role of macrophage-derived CELA2A in maintaining pancreatic islet homeostasis.Conclusion: Macrophage-derived CELA2A is essential for maintaining an anti-inflammatory state in islet macrophages, preserving ECM integrity, and supporting pancreatic islet structure and function. These findings highlight CELA2A as a key regulator of islet health and a promising therapeutic target for type 2 diabetes and related metabolic disorders.DisclosureJ. Moon: None. A. Mani: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-199-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 200-OR: Targeting β-Cell Senescence and Secondary
Senescence—Therapeutic Potential of JAK Inhibitors in Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 200-OR
Abstract: Introduction and Objective: Cellular senescence is a stress response marked by the upregulation of antiapoptotic pathways, loss of function, and secretome remodeling (SASP). Pancreatic β-cells undergo senescence with age and insulin resistance, while their targeted removal improves glucose homeostasis, demonstrating the role of β-cell senescence in diabetes progression. However, β-cell senescence can also promote β-cell survival and function. Thus, a better understanding of the phenotypic and functional heterogeneity is needed to develop effective therapeutic strategies.Methods: scRNASeq of human and mouse islets revealed senescent subopulations and their transcriptional signatures. A p21Cip1-tdTom reporter mouse was developed through CRISPR editing and their islets isolated and used for flow cytometry, insulin secretion assays and protein content. siRNA against p21Cip1 was used for knockdown and downstream analysis of function and transcription. Inhibitors of JAK1/2 and JAK 2/3 were used on mouse and human islets to assess their effects on insulin secretion and senescence status.Results: Subpopulations of senescent β-cells, identified through the expression of Cdkn1a (encoding p21Cip1) and Cdkn2a (encoding p16Ink4a) had distinct transcriptional and functional identities. The predominant senescent β-cell subpopulation expressed Cdkn1a and was characterized by a lack of function, and transcription of SASP factors. The SASP from the Cdkn1a+ subpopulation induced secondary senescence and dysfunction in neighboring cells. JAK inhibitors counteracted secondary senescence, decreased SASP secretion and restored function in human islets from donors with insulin resistance and Type 2 Diabetes.Conclusion: The main subpopulation of senescent β-cells expressed Cdkn1a and led to secondary senescence, loss of function, and loss of transcriptional identity in neighboring cells. This was attenuated with JAK inhibitorsDisclosureP. Carapeto: None. K. Iwasaki: None. H. Pan: None. C. Cahill: None. F. Hela: None. S. Le: None. C. Aguayo-Mazzucato: Consultant; Novo Nordisk.FundingThis study was supported by Institutional Startup Funds to CAM, National Institutes of Health grants 1R01DK132535 to CAM, P30 DK036836 to Joslin Diabetes Center (Cores), Thomas J Beatson Jr Foundation grant 2020-010 and the Richard and Susan Smith Family Foundation Award to CAM. SL is funded by NIH R25DK140752. KI is a Iacocca Postdoctoral Fellow.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-200-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 201-OR: Circadian Control of Feeding by Amygdala PKR2 Neurons
-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 201-OR
Abstract: Introduction and Objective: Despite recent advancements in weight loss therapeutics, obesity still remains an epidemic. Discovery of new weight loss targets is needed to develop more diverse treatments with fewer side effects and better accessibility. In this study, we identify Prokineticin receptor 2 (PKR2) in amygdala neurons as a key regulator or food intake, establish its modulation by MRAP2, and map their neuronal inputs.Methods: We used genetic and viral tools to delete PKR2 and MRAP2, as well as to express neuronal tracers, reporters, and DREADDs in the mouse brain. Food intake was measured with either Fed3 or Biodaq. Fiber photometry was used to measure neuronal activity.Results: Deletion of PKR2 from the amygdala resulted in an increase in food intake, especially in female mice. This hyperphagia was exclusively observed during the light cycle, suggesting that PKR2 contributes to the determination of feeding periods. This is consistent with our observation that the activity of amygdala PKR2 neurons, recorded by fiber photometry, oscillates over a 24-hour period with its highest activity at ZT-6 (12:00 pm) and lowest at ZT-18 (12:00 am). Retrograde tracing experiments identify several putative brain areas in which neurons expressing the PKR2 agonist prokineticin-2 (PK2) project to amygdala PKR2 neurons and may be involved in the regulation of feeding.Conclusion: We showed PKR2 in amygdala neurons plays a critical role in the control of daytime feeding in rodents, especially within females. We identified multiple brain areas containing PK2-expressing neurons that project to amygdala PKR2 neurons, establishing the neuronal network involved in prokineticin peptides’ control over feeding.DisclosureK. Bowman: None. A. Mittal: None. J. Sebag: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-201-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 202-OR: Slug-Elicited Epigenetic Reprogramming of VMH Neurons Promotes
Obesity and Metabolic Disease-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 202-OR
Abstract: Introduction and Objective: Transcriptional regulator Slug binds via its amino acids 1-30 to epigenetic modifiers and regulates gene expression by epigenetic modifications. Slug-expressing neurons are high in the ventromedial hypothalamus (VMH) which critically regulates body weight and metabolism. We aimed to explore VMH Slug neurocircuits.Methods:Slug-Cre mice were generated by CRISPR/Cas9. Slug axonal projections were mapped by microinjecting Cre-dependent AAV9-hSyn-DIO-mGFP-2A-Synaptophysin-mRuby vector into the VMH of Slug-Cre mice. VMH-specific Slug knockout mice were generated by crossing Slugf/fmice with Sf1-Cre drivers. Slug or ΔN30 (epigenetic-defective mutant lacking amino acids 1-30) was overexpressed in VMH neurons by microinjecting AAV9-hSyn-DIO-Slug or AAV9-hSyn-DIO-ΔN30 vector into the VMH of Sf1-Cre mice. VMH→lateral septal nucleus, intermediate part (LSI) projection-specific deletion of Slug was generated by injecting retrograde AAV9-EF1a-Flpo (LSI) and AAV8-hSyn-fDIO-Cre vector (VMH) into Slugf/f mice.Results: VMH Slug neurons abundantly projected to and formed monosynaptic connections in the LSI, as revealed by circuit-mapping AAV9-hSyn-DIO-mGFP-2A-Synaptophysin-mRuby vector in Slug-Cre mice. VMH neurons-specific deletion of Slug profoundly attenuated diet-induced obesity, insulin resistance, glucose intolerance, and liver steatosis in both males and females. Likewise, ablation of Slug in the LSI-projecting Slug subpopulation also protected against obesity. Conversely, VMH neuron-specific overexpression of Slug, but not ΔN30, induced obesity and metabolic disorders in mice on chow diet. Similarly, Slug overexpression in the LSI-projecting Slug subpopulation also caused obesity.Conclusion: These results unveil a unrecognized VMH Slug neuron→LSI neurocircuit controlling energy balance and body weight. Slug-elicited epigenetic reprogramming of the VMH→LSI neurocircuit promotes obesity and metabolic disease.DisclosureF. Jiang: None. M. Kim: None. Q. Zheng: None. L. Baron: None. L. Rui: None.FundingAmerican Heart Association Award (25POST1377313)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-202-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 203-OR: Loss of Nogo Receptor RTN4R Leads to Hyperphagia and Obesity in
Mice-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 203-OR
Abstract: Introduction and Objective: Plasma reticulon-4 receptor (RTN4R) has emerged as a new biomarker of obesity and diabetes. Plasma levels of RTN4R not only increase in individuals with higher BMI and type 2 diabetes but also strongly predict the progression rates of diabetes and its complications. As a GPI-anchored membrane protein highly expressed in neurons, the Rtn4r has been extensively studies as an inhibitor for axonal growth. However, the functional relevance of Rtn4r in diabetes and metabolism remains elusive.Methods: Here, we characterized the impact of constitutive whole-body deletion of Rtn4r (Rtn4r-/-) in the mouse model of diet-induced obesity.Results: On a 60% high-fat diet, loss of Rtn4r led to increased daily food consumptions and much severe obesity. Male Rtn4r-/- mice weighed ~30% heavier than wild-type (WT) littermates. The increased body weight in male Rtn4r-/- mice were largely attributed by increased subcutaneous white adipose tissue and interscapular brown adipose tissue. Male Rtn4r-/- mice displayed dramatically elevated fasting blood glucose and insulin levels, as well as increased levels of plasma triglycerides, free fatty acids, cholesterol, leptin and adiponectin. The obese Rtn4r-/- mice were also severely glucose intolerant and insulin resistant. While their physical activity did not alter, their energy expenditure as reflected by VO2 and VCO2 in CLAMS was reduced. Interestingly, paired feeding normalized the increased obesity and insulin resistance in Rtn4r-/- mice, demonstrated by comparable body weights, fat mass, glucose tolerance, and insulin sensitivity in HFD-fed Rtn4r-/- mice and WT littermates.Conclusion: Together, our present study uncovered a previously unrecognized biological function of Rtn4r in modulating feeding behavior and obesity. Given the strong associations of RTN4R with obesity and diabetes in humans, our study may help uncover key molecular mechanisms for the development of novel therapeutic strategies for diabetes and obesity.DisclosureQ. Huang: None. P. Thompson: None. J. Fu: None. W. Cai: None.FundingUniversity of Kentucky. Diabetes and Obesity Research Priority Area and the Barnstable Brown Diabetes and Obesity Center
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-203-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 204-OR: Depot-Specific Thermogenic Regulation—RNF20 Orchestrates
Temporal Activation of BAT and iWAT during Cold Exposure-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 204-OR
Abstract: Introduction and Objective: In mammals, brown adipose tissue (BAT) and inguinal white adipose tissue (iWAT) coordinate their thermogenic responses to maintain body temperature during cold exposure. BAT rapidly generates heat by activating brown adipocytes, while iWAT gradually induces the differentiation of beige adipocytes during prolonged cold challenges. However, the specific regulatory mechanisms governing thermogenic activation in these fat depots remain poorly understood.Methods: To investigate the thermogenic role of RNF20 specifically in adipose tissue, we performed tissue-specific RNF20 gain-of-function and loss-of-function experiments. In addition, proteomics analysis was performed to identify the substrates of RNF20.Results: We identify the E3 ubiquitin ligase RNF20 as a key regulator of adipose thermogenesis, acting through depot-specific mechanisms. Upon acute cold exposure, RNF20 expression in BAT is rapidly suppressed, leading to the stabilization of GABP alpha, a transcription factor that enhances thermogenic gene expression. Suppression of RNF20 specifically in BAT amplifies its thermogenic activity via GABP alpha upregulation. In contrast, during prolonged cold exposure, RNF20 expression in iWAT is gradually increased, facilitating beige adipocyte differentiation. Mechanistically, RNF20 in iWAT promotes the degradation of NCoR1, a co-repressor, to activate PPAR gamma and drive beige fat formation.Conclusion: These findings uncover a depot-specific and temporally distinct regulatory role for RNF20 in adipose thermogenesis, offering new insights into the adaptive mechanisms of energy homeostasis during cold stress.DisclosureJ. Kim: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-204-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 205-OR: Adhesion-Related Macrophages Regulates Metabolic Homeostasis
through Cav-1 Dependency-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 205-OR
Abstract: Introduction and Objective: The significance of adipose tissue macrophages (ATMs) in regulating adipose tissue function is well-established. However, our investigation revealed a previously overlooked subpopulation of macrophages adhered to adipocytes, which we term adhesion-related macrophages (ARMs).Methods: We developed a method to isolate both ARMs and non-ARMs. Molecular and functional differences were analyzed, and Cav-1 knockout mice were utilized to study the role of ARMs in metabolism.Results: Our findings demonstrate that ARMs constitute the predominant expanded subpopulation of ATMs during obesity, exhibiting heightened adhesion, proliferation, and lipid-processing capacities. Notably, ARMs can be characterized by a key functional marker, Caveolin-1. Genetic ablation of Caveolin-1 in immune cells significantly diminishes ARM abundance, disrupting their adhesion capacity and lipid content, leading to adipocyte hypertrophy, adipose tissue expansion, and impaired glucose homeostasis. Reintroducing ARMs from lean mice into eWAT mitigate obesity-induced adipose tissue inflammation and insulin resistance.Conclusion: Our study uncovers a previously unexplored macrophage subpopulation, ARMs, revealing potential therapeutic targets for obesity-induced insulin resistance and opening avenues for identifying similar paradigms in other tissues and diseases.DisclosureW. Hu: None. T. Deng: None.FundingNational Key R&D Program of China (2020YFA0803604 and 2023YFC3603404), the Key Program of the National Natural Science Foundation of China (82130024), the Fund for International Cooperation and Exchange of the National Natural Science Foundation of China (8231101033).
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-205-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 206-OR: Bistable Regulation of Cellular Heterogeneity Governs Thermogenic
Activity-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 206-OR
Abstract: Introduction and Objective: Recent advances in single-cell technologies have uncovered intricate cellular heterogeneity, yet its biological implications remain unclear. Key questions include whether functional heterogeneity exists and its impact on tissue activity. Brown and beige adipocytes (BAs) are thermogenic cells critical for energy homeostasis, and a decline in thermogenic activity is linked to age-related metabolic disorders. We previously identified a BA subpopulation with low uncoupling protein 1 (UCP1) expression (BA-L) that coexists with the classical high UCP1-expressing BAs (BA-H).Methods: Utilizing multiple lineage-tracing and gene knockout mouse models, single-cell RNA sequencing, and tissue imaging.Results: Here, we report that BA-Ls have spatial proximity to interleukin-1 beta (IL-1β) positive cells, as IL-1β is “cooling down” the thermogenesis of surrounding BAs, stabilizing these cells in the low-thermogenic states. Specifically, IL-1β stabilizes hexose-6-phosphate dehydrogenase (H6PD) protein from degradation, which promotes glucocorticoid receptor (GR) signaling to suppress UCP1 expression via GR target regulator of G-protein signaling 2 (RGS2). Cold exposure reduces IL-1β levels, depending on the sympathetic innervation, leading to H6PD degradation, and thus converting BA-Ls into BA-Hs to enhance thermogenesis. Rising environmental temperatures trigger the opposite events. BA-specific, inducible deletion of GR during cold exposure prevents the switch of BA-Hs to BA-Ls when the environmental temperature rises, leading to persistent thermogenesis. Critically, IL-1β level is elevated in aged BAT, leading to low BA-H/BA-L ratio and cold intolerance. Suppressing GR in aged mice restores the BA-H/BA-L ratio and increases thermogenesis.Conclusion: Our findings unveil a spatiotemporal regulation of BA heterogeneity governing thermogenesis that integrates neural and immune signals and a fundamental mechanism of thermogenic fat tissue aging.DisclosureA. Song: None. Y. Wang: None. G. Wang: None. J. Yu: None. L. Jiang: None. Y. Zhu: None. Q. Wang: None.FundingNational Institutes of Health (R01AG063854); National Institutes of Health (R01HD096152); National Institutes of Health (R01DK128907); California Institute for Regenerative Medicine (DISC0-15689); American Diabetes Association Junior Faculty Development Award (1-19-JDF-023)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-206-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 207-OR: ADA Presidents' Select Abstract: Identification of a Novel
Hepatocyte Subpopulation That Normally Displays Selective Hepatic Insulin
Resistance-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 207-OR
Abstract: Introduction and Objective: Selective hepatic insulin resistance is a central paradox in the pathogenesis of type 2 diabetes, where insulin fails to inhibit gluconeogenesis but continues to stimulate de novo lipogenesis, causing hyperglycemia and hypertriglyceridemia. In our studies with scRNA-seq and smFISH, we have identified a subpopulation of hepatocytes in normal physiologic conditions that resemble selective hepatic insulin resistance (termed DM hepatocytes). To understand the mechanism of hepatic insulin resistance, we analyzed this subpopulation of hepatocytes.Methods: We quantified the number of DM hepatocytes with PrimeFlow RNA assay under various conditions. We examined the regulation of gluconeogenic genes in response to insulin under euglycemic clamp conditions. We performed spatial transcriptomics in high-fat diet fed mice to assess the gene expression profile in the pathophysiologic state.Results: PrimeFlow RNA Assay showed about 10 % of DM hepatocytes in the fed state in normal physiologic conditions. Euglycemic clamps at various insulin fusion rates showed that DM hepatocytes are relatively insulin resistant compared to generic hepatocytes in terms of insulin suppression of Pck1 gene expression (a canonical gluconeogenic gene). Spatial transcriptomics showed a marked increase of DM hepatocytes in high-fat diet fed mice compared to normal chow diet fed mice, suggesting the possibility that diet-induced diabetes/obesity leads to an expansion of DM hepatocytes.Conclusion: These findings raise the possibility that hepatocytes do not acquire insulin resistance, but instead, hepatic insulin resistance may result from the proliferation of these naturally occurring insulin resistant hepatocytes. These findings could potentially have paradigm-shifting impact on the way we approach the development and use of therapeutic interventions to prevent/reverse insulin resistance in the liver.DisclosureJ. Okada: None. A. Landgraf: None. M. Horton: None. L. Liu: None. G.J. Schwartz: None. C. Eliscovich: None. K. Shinoda: None. J. Pessin: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-207-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 208-OR: PPP6C Directly Dephosphorylates TSC2, Improves Hepatic Lipid
Metabolism, and Mediates FGF21 Action on Metabolic
Dysfunction–Associated Steatohepatitis in Mice-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 208-OR
Abstract: Introduction and Objective: Metabolic dysfunction-associated steatohepatitis (MASH) is a serious chronic liver disease and remains limited therapies. Although fibroblast growth factor 21 (FGF21) has shown promising therapeutic benefits for MASH, how FGF21 signals are transduced into the cell and regulate MASH and whether the liver is a direct target of FGF21 remain obscure.Methods: Liver-specific PPP6C knockout mice, βKlotho knockout and their wild-type littermates were fed with AMLN diet for 16 weeks or CDA-HFD for 10-12 weeks, followed by daily subcutaneous injection of rFGF21 (0.5 mg/kg) or vehicle for 4 weeks. Mass spectrometry assay was used for identification of PPP6C as a βKlotho binding protein. The in vitro phosphatase assay was used to evaluate the effects of FGF21 on PPP6C activity.Results: We identified serine and threonine phosphatase PPP6C as the direct target of FGF21 in hepatocytes. PPP6C is uncovered as a coreceptor βklotho-binding protein, which is preferentially expressed in hepatocytes and significantly decreased in MASH livers of mice. PPP6C deficiency in hepatocytes exacerbates hepatic steatosis, inflammation, fibrosis and liver injury in mice fed with AMLN or CDA-HFD diets, which blocks beneficial effects of FGF21. Mechanistically, the phosphatase activity of PPP6C is activated by FGF21 via the FGFRs/βklotho complex, and subsequently PPP6C interacts with TSC2 to reduce the phosphorylation of TSC2, thereby inhibiting mTORC1 activity. Thus, TFE3 and Lipin1 are translocated to nucleus, where they inhibit the transcription of lipid synthesis genes but promote fatty acid oxidation genes. In livers of MASH subjects, expression levels of PPP6C are decreased whereas TSC2 phosphorylation is elevated.Conclusion: These results define a fundamental mechanism underlying FGF21 signals in hepatocytes and demonstrate that targeting PPP6C may have therapeutic potential for treating MASH.DisclosureS. Wei: None. Z. Liu: None. Y. Jiang: None. W. Su: None. F. Ma: None. A. Cui: None. Y. Li: None.FundingNational Key R&D Program of China (2023YFA1801100); National Natural Science Foundation of China (81925008, 32130047); Project supported by Shanghai Municipal Science and Technology Major Project, Open Project Program of Metabolic Vascular Diseases Key Laboratory of Sichuan Province (2022MVDKL-K2)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-208-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 209-OR: TLR2 Deficiency Induces Hepatic Steatosis through the
PPAR-γ-CD36 Pathway-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 209-OR
Abstract: Introduction and Objective: Metabolic-associated steatotic liver disease (MASLD) is characterized by the pathological accumulation of fat within the liver and in the context of obesity or other metabolic disturbances. The precise mechanisms regulating lipid deposition in the liver remain elusive. Toll-like receptor 2 (TLR2) is traditionally believed to aggravate disease progression by promoting inflammatory responses. Here we identified TLR2's role in preventing hepatic steatosis.Methods: C57BL/6J and TLR2 knockout (KO) male mice were fed either a high-fat diet (HFD) or standard chow for 16 weeks. Pam3CSK4 was injected into TLR2KO and wild-type (WT) mice. Metabolic and immunological profiling was performed. Liver biopsies from patients with MASLD were used to validate our findings. Analysis of samples from in vivo and in vitro models was performed using RNA seq, qRT-PCR, flow cytometry, H&E, Oil Red O staining, IHC, ChIP-qPCR, W blot, and siRNA transfection.Results: Our findings indicate that mice lacking TLR2 displayed obesity, insulin resistance, and liver steatosis, which were worsened upon high-fat diet feeding. Notably, these metabolic alterations occurred independently of inflammatory processes. TLR2 ablation enhanced lipid accumulation in hepatocytes through a cell-autonomous mechanism, mediated by the fatty acid transporter CD36. TLR2 deficiency was associated with upregulation of CD36 and PPARγ expression, along with an increase in their functional activity. Deletion of either CD36 or PPARγ significantly mitigated the impact of TLR2 loss on lipid accumulation in hepatocytes. In vivo activation of TLR2 led to the suppression of CD36 and PPARγ expression in the liver, thereby preventing lipid accumulation in hepatocytes. These observations were supported by liver biopsies from patients with MASLD.Conclusion: Our results propose an unconventional metabolic role for TLR2 that warrants consideration in the development of pharmacological strategies for the treatment of MASLD.DisclosureR. Ahmad: None. S.P. Kochumon: None. F. Alrashed: None. F. Alzaid: None. F. Bahman: None. T.K. Jacob: None. H. Arefanian: None. S. Shenouda: None. R.S. Thomas: None. N. Akhter: None. A. Al Madhoun: None. S.T. Sindhu: None. S.J. Patel: None. N. Venteclef: None. F. Almulla: None. E. Rosen: Consultant; Foghorn Therapeutics. Advisory Panel; Source Bio.FundingKuwait Foundation for the Advancement of Sciences (RA AM 2023-021)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-209-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 210-OR: RNA Binding Protein YTHDC1 Critically Regulates Liver Metabolism
and Homeostasis-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 210-OR
Abstract: Introduction and Objective: RNA N6-methyladenosine (m6A) modification emerges to pivotally regulate cell proliferation, differentiation, and functions. The METTL3/METTL14 complex installs m6A on mRNA (m6A writer). YTH family members (e.g. YTHDC1) bind to m6A-marked RNA (m6A readers) and control RNA fate, proteostasis, and cell functions. We aimed to delineate the role of hepatic YTHDC1 in metabolic dysfunction-associated steatotic liver disease (MASLD).Methods: Hepatocyte-specific Ythdc1 knockout mice were generated by transducing Ythdc1f/f mice with AAV8-TBG-Cre vector via tail veins. To reconstitute livers with YTHDC1 or YTHDC1W377A (unable to bind to m6A), Ythdc1f/f mice were cotransduced with AAV8-TBG-Cre and AAV8-TBG-Flag-YTHDC1 or AAV8-TBG-Flag-YTHDC1W377A vectors. Liver integrity and triacylglycerol (TAG) levels are assessed using chemical and immunobiological assays.Results: Mice with hepatocyte-specific deletion of Ythdc1, both males and females on normal chow diet, developed severe MASLD with massive liver steatosis, injury, inflammation, and fibrosis. Hepatocyte-specific reconstitution with YTHDC1, but not m6A binding-defective YTHDC1W377A, fully rescued MASLD. At the molecular level, YTHDC1 directly targeted CD36 (fatty acid transporter) and PPARα genes, thereby suppressing hepatic lipid uptake while stimulating fatty acid β oxidation. Hepatocyte-specific restoration of CD36 and PPARα largely reversed MASLD phenotypes in Ythdc1 knockout mice. Liver YTHDC1 was markedly downregulated in mice and patients with MASLD, likely contributing to disease progression.Conclusion: We have identified hepatic YTHDC1 as a pivotal m6A reader to control hepatic liver uptake and β oxidation. Downregulation of hepatic YTHDC1 or aberrant m6A pathways play a critical role in MASLD pathogenesis and serve as potential therapeutic targets for MASLD treatment.DisclosureQ. Zheng: None. L. Baron: None. S. Zhou: None. L. Rui: None.FundingAmerican Diabetes Association (1-25-PDF-37); American Heart Association (831585)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-210-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 211-OR: Chemerin Affects Mitochondrial Function by Modulating
PPARγ/PGC-1α/UCP2 Signaling Pathway to Promote Metabolic
Dysfunction-Associated Fatty Liver Disease-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 211-OR
Abstract: Introduction and Objective: Previous studies have found that chemerin knockout mice are less susceptible to fatty liver when fed high-fat diet, but the underlying mechanisms remain unknown. Therefore, this study explores the role of chemerin in metabolic dysfunction-associated fatty liver disease and its mechanisms.Methods: 8-week-old male wild-type mice (WT) and adipose chemerin-specific knockout mice (chemerin-/-) were divided into 4 groups: WT plus normal diet, WT plus high-fat diet, chemerin-/- plus normal diet, chemerin-/- plus high-fat diet group, high-fat feeding for 12 weeks. The occurrence of fatty liver as well as the morphological and functional indexes of liver mitochondria were observed. AML12 was interfered with chemerin overexpression plasmid and sh-RNA to observe lipid deposition in hepatocytes and mitochondrial function indexes.Results: 1) chemerin-/- mice were less likely to develop fatty liver after high-fat feeding. Overexpression of chemerin in hepatocytes increased lipid deposition, while knockdown of chemerin were reversed. 2) chemerin-/- mice with HFD showed increased ATP and membrane potential in liver, increased number of mitochondria, and reduced mitochondrial edema compared with HFD WT mice. ATP levels and membrane potential were decreased in AML12 cells overexpressing chemerin, and these were reversed with knockdown of chemerin. 3) The protein levels of PPARγ, PGC-1α and UCP2 in the liver of chemerin-/- mice were increased under high-fat feeding. In AML12 cells with overexpression of chemerin, PPARγ, PGC-1α and UCP2 were decreased, while they were increased with knockdown of chemerin. 4) AML12 cells treated with PPARγ agonist increased ATP and membrane potential. However, those effects were reversed by PPARγ inhibitor.Conclusion: Chemerin induces fatty liver by affecting mitochondrial function, which is related to the regulation of the PPARγ/PGC-1α/UCP2 pathway.DisclosureX. Lin: None. H. Chen: None. S. Qu: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-211-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 212-OR: Hepatic Overexpression of ACSS3 Alters Glucose Control and Fatty
Acid Metabolism in Lean Mice-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 212-OR
Abstract: Introduction and Objective: Short chain fatty acids (SCFAs) are associated with adverse metabolic outcomes; however, little is known about their link to metabolic disease. Emerging evidence suggests that in addition to acting as signaling molecules, SCFAs also impact cellular metabolism via their conversion to acyl-CoAs by short chain acyl-CoA synthetase (ACSS) enzymes. ACSS3 is a mitochondrial enzyme highly expressed in liver; and recent studies from our laboratory using mass-spectrometry (MS)-based proteomics identified ACSS3 as the most downregulated protein in liver mitochondria from mice adapted to time-restricted feeding. Conversely, high fat feeding led to a marked increase in hepatic ACSS3. In this study, we sought to determine if overexpression (OE) of ACSS3 in hepatocytes of lean mice would be sufficient to mimic the metabolic effects of a high fat diet.Methods: Chow fed C57BL/6NJ mice were injected with AAV8-TBG-ACSS3 or AAV8-TBG-eGFP and metabolic phenotyping was performed along with MS-based metabolomic profiling.Results: Injection of AAV8-TBG-ACSS3 increased ACSS3 expression and activity in liver mitochondria while also elevating fasting blood glucose levels, but without affecting glucose tolerance. MS-based metabolite profiling of liver tissue showed that ACSS3 OE increased numerous acyl-CoA species, decreased free CoA, altered several short chain acylcarnitines, and led to a marked accumulation of fatty acid-derived acylcarnitines. These results suggest that increased flux through ACSS3 can contribute to mitochondrial CoA trapping, which may limit fatty acid oxidation and promote hepatic lipid accumulation. Studies to further investigate the impact of ACSS3 OE on hepatic fatty acid oxidation and steatosis are ongoing.Conclusion: In sum, our results demonstrate that hepatic ACSS3 is nutritionally regulated and OE of the enzyme altered short chain carbon trafficking in a manner that influenced whole-body glucose control and hepatic lipid metabolism.DisclosureN. Seshadri: None. D.M. Muoio: Speaker's Bureau; Eli Lilly and Company. Research Support; Eli Lilly and Company, AstraZeneca. Advisory Panel; AstraZeneca. A.S. Williams: None.FundingNational Institutes of Health (K01DK125609)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-212-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 213-OR: Liraglutide and Empagliflozin Each Improve Metabolic and
Microvascular Insulin Sensitivity, with Enhanced Cardiac Benefits in
Combination Therapy-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 213-OR
Abstract: Introduction and Objective: Type 2 diabetes (T2D) treatment has evolved from a glucocentric to a cardiometabolic approach, making anti-hyperglycemic therapies with proven cardiovascular and renal benefits the cornerstone to its management. Both glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2is) have been shown to improve cardiovascular and kidney outcomes beyond glycemic control via distinct mechanisms.Methods: To assess whether the combination of GLP-1RA and SGLT2i exerts additive or synergistic metabolic/cardiovascular actions, we fed rats a high-fat diet (HFD) for 4 weeks with or without simultaneous administration of either liraglutide (400µg/kg/day), empagliflozin (30mg/kg/day), or combination therapy. Chow-fed rats served as controls. At the end of dietary intervention, insulin’s metabolic and microvascular actions were determined using a combined euglycemic-hyperinsulinemic clamp and contrast-enhanced ultrasound approach with cardiac functions determined by echocardiography.Results: Compared to chow-fed rats, HFD feeding increased body adiposity without excess body weight gain, and this was associated with a marked decrease in insulin-mediated whole-body glucose disposal and abolishment of insulin-induced microvascular perfusion. Liraglutide and empagliflozin each reduced body weight gain and fasting blood glucose, along with improved metabolic and microvascular insulin sensitivity without significantly altering cardiac functional parameters. Rats with combined therapy had similar metabolic and microvascular insulin sensitivities to those received either monotherapy but exhibited a significantly higher left ventricular ejection fraction and fractional shortening.Conclusion: Our findings provide a novel insight into the GLP-1RA and SGLT2i interplay and support the use of combined therapy to improve the metabolic and cardiovascular outcomes in the setting of obesity and T2D.DisclosureJ. Liu: None. X. Wang: None. C. Cai: None. Z. Liu: None.FundingNational Institutes of Health (R01DK124344 and R01DK125330 to Z.L.)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-213-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 214-OR: Increases in TUG Abundance and Expression Are a Feature of
Insulin-Resistant Human Adipose Tissue-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 214-OR
Abstract: Introduction and Objective: White adipose tissue (WAT) insulin resistance (IR) is essential to the pathogenesis of metabolic disease; yet defects in human WAT insulin signaling are not well characterized. This study elucidates alterations to WAT insulin signaling associated with human IR.Methods: Human WAT was obtained from three cohorts of patients with obesity: 1) in a bariatric surgery cohort (RESOLVE), RNASeq was performed on WAT collected before and after weight loss; 2) in another cohort (SODA), glucose or fructose-sweetened beverages were given before WAT collection and proteomics analyses were performed; 3) in an adolescent cohort, immunoblotting and qPCR assessed WAT biopsied before or during hyperinsulinemic euglycemic clamps.Results: Attenuation of insulin-stimulated AKT phosphorylation in IR vs. relatively insulin sensitive (IS) adolescents was not significant (IR vs IS: -37.6%, p>0.1). Expectedly, GLUT4 decreased in IR (Resolve: log PC = -1.54, p<0.000000001; SODA: R2=0.367, p<0.05; Adolescent: -60.3%, p<0.05). TUG, which traps insulin-responsive GLUT4, was increased in IR (Resolve: log PC +0.39, p<0.05; SODA: R2=0.277, p<0.05; Adolescent: +48.5%, p<0.01). Gene expression throughout the TC10 pathway that mediates insulin-stimulated TUG cleavage was changed pre- versus post- bariatric surgery in the RESOLVE study. A subset of TC10 pathway proteins also changed in the SODA and Adolescent studies.Conclusion: In three cohorts, IR is correlated with increased WAT TUG. As well, molecular regulation of TC10 pathway is altered, underscoring the importance of TUG regulation to WAT metabolic health. As one of the first descriptions of altered signaling by this pathway in human WAT, this data can drive future therapeutics for patients with metabolic disease.DisclosureJ.W. Strober: None. K.W. ter Horst: None. A. Slusher: None. J.A. Paulo: None. B. Gassaway: None. S. Shuken: None. S. Caprio: None. M. Serlie: None. J. Bogan: None. D.F. Vatner: None.FundingNational Institutes of Health (DK124272); National Institutes of Health (DK007058)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-214-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 215-OR: Increased White Adipose Tissue Oxidative Capacity and Insulin
Resistance Are Early Changes upon High-Fat Diet in Healthy Humans-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 215-OR
Abstract: Introduction and Objective: Hypercaloric nutrition may sequentially promote insulin resistance across tissues. Recent rodent studies indicate white adipose tissue (WAT) as key driver of whole-body insulin resistance. Thus, we hypothesized that WAT may respond early to overnutrition-induced metabolic changes in humans.Methods: In a randomized, parallel-group study, young glucose tolerant volunteers consumed either an isocaloric (ID; 55% carbohydrates, 15% proteins, 30% lipids) or a hypercaloric high-fat diet (HFD; ID + 40% of total caloric requirement in lipids) for 3 weeks. We performed hyperinsulinemic-euglycemic clamps and high-resolution respirometry in WAT and skeletal muscle biopsies obtained during fasting and insulin stimulation to assess mitochondrial respiration (O2 flux). Fat mass index (FMI) was calculated as fat mass and height, adipose tissue insulin resistance (Adipo-IR) from fasting insulin and non-esterified fatty acids. Intramuscular and hepatic lipid content and hepatic ATP levels were quantified by 1H/31P MR spectroscopy.Results: ID (female/male: 1/7, body mass index (BMI) 26.4±3.7 kg/m2) and HFD groups (2/8, BMI 25.9±2.7 kg/m2) had comparable anthropometric features. After HFD, mean change from pre- to post-intervention (Δ) of body weight was higher than after ID (+2.0±0.8 vs. -0.9±0.5 kg, p=0.010). ΔFMI (+0.60±0.18 vs. -0.10±0.11 kg/m2, p=0.006), ΔAdipo-IR (+1.10±0.57 vs. +0.11±0.62 mmol·mU/L², p=0.047) and Δ uncoupled O2 flux in WAT [+0.338±0.128 vs. -0.696±0.346 pmol/(mg·s), p=0.001] were also higher upon HFD. In contrast, whole-body insulin sensitivity, muscle and liver lipid content and energy metabolism remained unchanged in both groups (p>0.05).Conclusion: Insulin sensitivity declines along with increased oxidative capacity primarily in WAT within a 3 week-HFD in young, non-obese individuals, suggesting a predominant role of WAT in early development of overnutrition-induced insulin resistance.DisclosureG. Xourafa: None. C. Granata: None. S. Trenkamp: None. B. Korzekwa: None. V. Schrauwen-Hinderling: None. K. Petersen: Consultant; Village S.S.D.r.l. Joy of Movement. G.I. Shulman: Advisory Panel; Novo Nordisk. Consultant; Ionis Pharmaceuticals. Research Support; AstraZeneca, Merck & Co., Inc, ESPERION Therapeutics, Inc., Novo Nordisk. Advisory Panel; OrsoBio, Inc. S. Kahl: Research Support; Boehringer-Ingelheim, Novo Nordisk A/S. M. Roden: Research Support; Boehringer-Ingelheim. Advisory Panel; Echosens. Speaker's Bureau; Madrigal Pharmaceuticals, Inc. Advisory Panel; MSD Life Science Foundation. Board Member; Novo Nordisk. Advisory Panel; TARGET PharmaSolutions, Inc.FundingDeutsche Diabetes Gesellschaft (DDG Allgemeine Projektförderung), European Association for the Study of Diabetes (EASD Rising Star Fellowship), Anna Wunderlich und Ernst Jühling Award
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-215-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 217-OR: Immediate and Extended Effects of Exercise on Glycaemic Control
and Hypoglycaemia Risk-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 217-OR
Abstract: Introduction and Objective: Exercise is recommended for people with T1D, but the effects of exercise types (aerobic, anaerobic, mixed, yoga) on immediate (2 hours) and extended (24 hours) glycemia remain debated. Increased hypoglycemia risk often deters regular exercise. This study analyzes continuous glucose data from mySugr and Apple Health users to assess how exercise types affect glycemia and quantify exercise-induced hypoglycemia risk.Methods: Exercise events (477,778) from 3,408 users with ≥5 exercise logs and >90% CGM wear time were categorized into 4 types. Two-hour post-exercise minimums and mean AUC of standardized CGM values over 24 hours were analyzed via one-way ANOVA and independent samples t-tests. Diurnal and nocturnal hypoglycemia risk 24 hours after exercise were compared using paired t-tests.Results: Exercise types differed in average 2-hour minimum (Fig. 1A & 1B, F=149.76, p<0.001; aerobic induced the greatest decrease) and 24-hour glucose suppression (Fig. 1C, F=10.72, p<0.001; anaerobic induced the greatest suppression). Post-exercise hypoglycemia risk increased more nocturnally than diurnally (Fig. 1D, p<0.001).Conclusion: Exercise types modulate glycemia differently, with aerobic causing the largest immediate decrease and anaerobic the largest extended decrease. Yoga shows comparable effects. Exercise raises 24-hour hypoglycemia risk more nocturnally than diurnally.Disclosure J. Zivkovic: Employee; Roche Diagnostics. M. Mitter: Employee; Roche Diagnostics. D. Theodorou: Employee; Roche Diabetes Care. T. Glatzer: Employee; Roche Diabetes Care. Stock/Shareholder; Roche Diabetes Care, Abbott, Dexcom, Inc.FundingThe research was funded by Roche Diabetes Care GmbH
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-217-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 218-OR: Time of Exercise Affects Nocturnal Hypoglycemia after Exercise in
Adults with Type 1 Diabetes (T1D)—Results from the T1D Exercise
Initiative (T1DEXI) Study-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 218-OR
Abstract: Introduction and Objective: Exercise improves overall health and time in range, but increases the risk of subsequent hypoglycemia. Factors influencing overnight hypoglycemia are not well understood.Methods: We used data from T1DEXI to compare the incidence of nocturnal hypoglycemia, defined as CGM glucose <70 mg/dL (Level 1) or <54 mg/dL (Level 2) for ≥15 min between 12AM-6AM, after exercise and sedentary days. Exercise days were sub-categorized by exercise duration and time of day. Generalized estimating equations (GEE) accounted for the clustering of repeated measures per participant and provided model-based estimates and on-average differences between exercise and sedentary days.Results: We analyzed 497 adults with T1D (age 37 + 14 yrs, 73% F, HbA1c 6.6 + 0.8%) encompassing 887 exercise days and 465 sedentary days. Exercise days were associated with a greater incidence of Level I (p<0.001) and Level 2 (p=0.01) nocturnal hypoglycemia relative to sedentary days, regardless of exercise duration (Figure 1A). Both afternoon and evening exercise were associated with increased Level I nocturnal hypoglycemia relative to sedentary days (p<0.001), whereas morning exercise was not (p=0.28; Figure 1B).Conclusion: Time of exercise may play a critical role in mitigating the risk of nocturnal hypoglycemia after exercise. Identifying modifiable risk factors can help people with T1D exercise safely.DisclosureD.I. Bisno: None. L.V. Turner: None. R.J. Gallop: None. J.L. Jo Kamimoto: None. S. Reddy: None. M.C. Riddell: Advisory Panel; Zucara Therapeutics, embecta. Consultant; Dexcom, Inc., Insulet Corporation, Eli Lilly and Company, Novo Nordisk. Speaker's Bureau; Novo Nordisk, Dexcom, Inc., Sanofi, Eli Lilly and Company. Stock/Shareholder; Zucara Therapeutics. Research Support; Dexcom, Inc., Insulet Corporation, Eli Lilly and Company. M.R. Rickels: Consultant; Vertex Pharmaceuticals Incorporated, Sernova, Corp. Research Support; Dompé, Tandem Diabetes Care, Inc. Consultant; Novo Nordisk.FundingThe Leona M. and Harry B. Helmsley Charitable Trust
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-218-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 219-OR: Characterising Severe Hypoglycaemia—Insights from a UK
Multicentre Study-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 219-OR
Abstract: Introduction and Objective: Severe hypoglycaemia presents significant risks for individuals with diabetes. Yet, real-world data on its characteristics and outcomes in the current literature is limited. This study aimed to investigate the features, precipitating factors, and outcomes of severe hypoglycaemia.Methods: A multicentre retrospective study was conducted between October 2023 and July 2024 across nine UK hospitals participating in the DEKODE hypoglycaemia surveillance system. Patients aged >18 years admitted between October 2023 and July 2024 with level 2 or 3 hypoglycaemia, as defined by the International Hypoglycaemia Study Group, were included. Data on demographics, precipitating factors, Charlson Comorbidity Index (CCI), management, and outcomes were collected. Statistical analyses included the Mann-Whitney U test for non-parametric and ordinal data and Fisher’s exact test for categorical data, with a significance level of p < 0.05.Results: This study yielded 1,451 severe hypoglycaemic episodes, with 450 in individuals with type 1 diabetes and 986 in those with type 2 diabetes. The median hospital stay, age, and CCI were 7 days, 73 years, and 6 respectively. Level 2 hypoglycaemia accounted for 931 episodes, while 520 were level 3. The most common precipitating factors were missed meals/fasting (39.8%) and intercurrent illnesses (42.1%). Cognitive impairment occurred in 538 episodes, and 76 (5.2%) episodes were associated with death. Post-discharge, 31.1% were referred to specialist review, 40 patients were initiated on continuous glucose monitoring and glucagon prescriptions were provided in only 9 cases.Conclusion: Severe hypoglycaemia is associated with substantial risks, including cognitive impairment and mortality. The underutilisation of preventive services, such as glucagon prescriptions and continuous glucose monitoring, underscores the urgent need for educational initiatives and improved discharge planning to reduce recurrence and enhance patient outcomes.DisclosureA. Khatoon: None. A. Ling Jie Yee: None. S. Sherratt-Mayhew: None. S. Waheed: None. S. Abdi Osman: None. E. Normanton: None. F. Ahmed: None. H. Sheikh: None. P. Choudhary: Speaker's Bureau; Abbott. Advisory Panel; Dexcom, Inc. Consultant; Insulet Corporation. Advisory Panel; Ypsomed AG, embecta, Sanofi. Speaker's Bureau; Lilly Diabetes, Medtronic. Advisory Panel; Roche Diabetes Care. Consultant; Cambridge Mechatronics. R.P. Raghavan: Speaker's Bureau; Eli Lilly and Company, Abbott Diagnostics, Sanofi. P. Kempegowda: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-219-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 220-OR: Associations between Depression, Anxiety, Diabetes Distress, and
Fear of Hypoglycemia and Impaired Awareness of Hypoglycemia in Type 1 and
Insulin-Treated Type 2 Diabetes in the Hypo-METRICS Study-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 220-OR
Abstract: Introduction and Objective: To determine whether impaired awareness of hypoglycemia (IAH) is associated with depression, anxiety, diabetes distress and fear of hypoglycemia in people with T1D or insulin-treated T2D.Methods: 276 T1D and 321 insulin-treated T2D participants in the Hypo-METRICS study completed questionnaires to assess for depression (PHQ-9), anxiety (GAD-7), diabetes distress (PAID) and fear of hypoglycemia (HFS-II; worry and behavior). IAH was defined as a Gold score of ≥4. Logistic regression analyses were performed to assess the cross-sectional relationships between mental health scores and IAH.Results: IAH was associated with significantly higher depression and anxiety in both groups (for depression OR 1.44 [1.26-1.64; p <0.001] in T1D, OR 1.15 [1.04-1.27; p <0.001] in T2D, for anxiety OR 1.44 [1.25-1.66; p <0.001] in T1D, OR 1.16 [1.03-1.3; p 0.013] in T2D). IAH was also associated with more worries about hypoglycemia in T1D (OR 1.29 [1.2-1.39]; p <0.001) and T2D (OR 1.27 [1.19-1.36]; p <0.001), and more diabetes distress in T1D (OR 1.35 [1.27-1.43]; p <0.001) and less diabetes distress in T2D (OR 0.92 [0.88-0.97]; p 0.002).Conclusion: IAH is significantly associated with higher levels of depression, anxiety and fear of hypoglycemia in T1D and insulin-treated T2D. Interventions that address mental health, as well as hypoglycemia risk, may be more effective at restoring awareness.DisclosureA.M. McCarthy: None. P. Divilly: None. F. Pouwer: Research Support; Novo Nordisk, Eli Lilly and Company. P. Choudhary: Speaker's Bureau; Abbott. Advisory Panel; Dexcom, Inc. Consultant; Insulet Corporation. Advisory Panel; Ypsomed AG, embecta, Sanofi. Speaker's Bureau; Lilly Diabetes, Medtronic. Advisory Panel; Roche Diabetes Care. Consultant; Cambridge Mechatronics.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-220-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 221-OR: Risk Factors of Severe Hypoglycemia (SH) and Level 2 Hypoglycemia
(Lv2Hypo) in Hybrid Closed-Loop (HCL) Users-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 221-OR
Abstract: Introduction and Objective: Despite advancement in diabetes technologies, SH and Lv2Hypo persist in HCL users. We assessed factors related to SH and Lv2Hypo among HCL users with T1D.Methods: From a national cohort of US T1D adult HCL users, a cross-sectional survey assessed six-month SH history, HbA1c, impaired awareness of hypoglycemia (IAH; using Hypoglycemia Awareness Questionnaire) and CGM data. Analyses included logistic regression, t-tests and Chi-square tests.Results: Of 1,092 T1D HCL users (54% female, mean age: 45), IAH and higher HbA1c were related to higher odds of having ≥1 SH episodes (p<0.001). Of 601 subjects with CGM data, IAH, lower HbA1c and higher glucose coefficients of variation (CV) were related to higher odds of having ≥1% of time in Lv2Hypo (p<0.01). Having ≥1% of time in Lv2Hypo was not related to SH. Compared to the subgroup of subjects with neither SH nor ≥1% Lv2Hypo (n=414), subjects with SH only (n=139) presented with more time in hyperglycemia (i.e., glucose >180 mg/dL) and higher HbA1c; subjects with ≥1% of time in Lv2Hypo only (n=33) presented with less time in hyperglycemia and lower HbA1c; subject who experienced both SH and ≥1% of time in Lv2Hypo (n=15) exhibited the worst IAH and highest glucose variability (Fig.).Conclusion: Among HCL users, high IAH and CV are related to both SH and Lv2Hypo. SH and time in Lv2Hypo risk are distinguished by time in hyperglycemia and HbA1c.DisclosureY. Lin: None. M.H. Devore: None. E. Hepworth: None. A. Agni: None. W. Ye: None. S.J. Fisher: None.FundingNational Institutes of Health (K23DK129724)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-221-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 222-OR: Burden of Recurrent Severe Hypoglycemia (SH) in U.S. Older Adults
(OA) with Type 2 Diabetes (T2D)-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 222-OR
Abstract: Introduction and Objective: OA with T2D are at an increased risk for SH, especially with high-risk medication use. Most SH data describe 30-day recurrence, which fails to capture recurrence over time. We aimed to quantify the broader burden of SH recurrence by applying the Kaplan-Meier-based mean cumulative count (MCC) method to accommodate time-varying SH rates and account for death as a competing event.Methods: We analyzed a random 20% sample of nationwide fee-for-service US Medicare beneficiaries (Parts A/B/D) from 2007-2019. We included adults 65+ yrs with T2D with antihyperglycemic medication use before an “index” SH event that required an ED visit or hospitalization. We estimated MCCs for the expected number of recurrent SH events per person over time after the index event across subgroups defined by medication use.Results: Among 102,098 OA with T2D (38.0% male, 62.7% White, 20.2% Black, 11.3% Hispanic; mean age 77 yrs ± SD 8; 44.2% on insulin, 33.3% on sulfonylureas, 18.5% on both), 1-year mortality was 22.9%. There were 36,718 recurrent SH events over mean follow-up 2.8 years ± SD 2.7 (incidence rate = 12.8 per 100 person-years). Figure 1 shows subgroup differences in SH recurrence and mortality by medication use; both were highest among insulin users.Conclusion: Thirty-day recurrence rates mask how the burden of SH recurrence propagates over time amid high mortality and differs by medication use for OA with T2D.DisclosureA. Kahkoska: None. A. Alexopoulos: None. A. Fruik: None. C.M. Germain: None. A. Ratzki-Leewing: Other Relationship; Abbott, Dexcom, Inc. Consultant; Sanofi. Other Relationship; Sanofi. Consultant; Sanofi-Aventis U.S. Advisory Panel; Sanofi-Aventis U.S. V. Pate: None. A. Kinlaw: None.FundingNorth Carolina Diabetes Research Center (NIDDK P30 DK124723)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-222-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 223-OR: Emulation of the Study of Tirzepatide Compared with Dulaglutide on
Major Cardiovascular Events in Participants with Type 2 Diabetes
(SURPASS-CVOT)-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 223-OR
Abstract: Introduction and Objective: SURPASS-CVOT is an ongoing, randomized, active-controlled trial evaluating the effect of tirzepatide vs. dulaglutide on major adverse cardiovascular events (MACE) in people with type 2 diabetes (T2D) and atherosclerotic cardiovascular disease (ASCVD). We aimed to emulate the SURPASS-CVOT trial using insurance claims data.Methods: Using claims from a private health plan (06/2022 to 08/2024), we identified 15,775 pairs of 1:1 propensity score (PS)-matched adults initiating tirzepatide or dulaglutide, stratified by baseline SGLT2i use. Our primary outcome was MACE (myocardial infarction, stroke, or mortality). We estimated hazard ratios (HRs) and 95% confidence intervals (CI), adjusting for 125 covariates. We also conducted HbA1c-adjusted analyses among those with HbA1c values (54% of population).Results: Over a median follow up of ~6 months, tirzepatide was associated with a 37% reduction in MACE vs. dulaglutide (Table). Results were consistent in the HbA1c-adjusted analysis (HR, 0.77; 95% CI, 0.62 to 0.95) and, in both analyses, irrespective of SGLT2i use.Conclusion: In this observational study emulating SURPASS-CVOT, tirzepatide appeared superior to dulaglutide in preventing MACE events. This study may also inform the design and conduct of future observational studies evaluating GLP-1-based treatments.DisclosureJ. Ostrominski: None. J. Ortega-Montiel: None. H. Tesfaye: None. C. Alix: None. D.J. Wexler: Other Relationship; Novo Nordisk. J.M. Paik: None. E. Patorno: Research Support; National Institute of Diabetes and Digestive and Kidney Diseases, Patient-Centered Outcomes Research Institute, Food and Drug Administration (FDA), Boehringer-Ingelheim. Other Relationship; UpToDate.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-223-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 224-OR: SURMOUNT-5 Tirzepatide vs. Semaglutide for Obesity—Rapid
Responders and Associated Weight Reduction and Safety-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 224-OR
Abstract: Introduction and Objective: A knowledge gap remains in how rate of weight reduction (WR) with new obesity management medications impacts efficacy and safety. This SURMOUNT-5 post hoc aimed to define rapid responders [RR] and to evaluate efficacy and safety in RR vs non-rapid responders (NRR).Methods: Defining RR was informed by tertile analysis of all participants’ WR by week (wk) 24. Proportion of participants achieving WR targets by wk72, and time to ≥15% WR from efficacy analysis set, and safety / GI tolerability measures were summarized by treatment and responder (RR vs NRR) group.Results: RR was defined as ≥15% WR by wk24 (32.3% of all participants). RR included 44% of tirzepatide (TZP) and 21% of semaglutide (Sema) participants. Median time to ≥15% WR was 36 and 52 wk for TZP and Sema, respectively. The proportions of participants achieving WR targets by wk72 were higher for RR vs NRR (Table). Safety trends for TZP and Sema were similar for RR vs NRR. Numerically higher number of GI and hepatobiliary AE were reported in RR. For RR vs NRR, treatment completion was nominally higher for TZP and similar for Sema.Conclusion: In this post hoc, the TZP group had greater proportions of participants that achieved all WR targets in both RR and NRR compared to Sema. With both treatments, RR had nominally more GI and hepatobiliary AE, yet these trends were not associated with ability to complete treatment compared to NRR.Disclosure L.J. Aronne: Consultant; Novo Nordisk. Research Support; Novo Nordisk. Consultant; Lilly USA LLC. Research Support; Lilly USA LLC. D. Horn: Consultant; Eli Lilly and Company. Speaker's Bureau; Eli Lilly and Company. Research Support; Eli Lilly and Company. Consultant; Amgen Inc. Advisory Panel; Novo Nordisk. Consultant; Novo Nordisk. Speaker's Bureau; Novo Nordisk. Research Support; Novo Nordisk. B. Falcon: Employee; Eli Lilly and Company. D. Cao: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. H.T. Hoffmann: Employee; Eli Lilly and Company. C. Lee: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. J.P. Dunn: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-224-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 225-OR: The Oral Apelin Receptor Agonist Azelaprag Enhances Glycemic
Control in Preclinical Models of Diabetic Obesity Both as Monotherapy and
in Combination with Tirzepatide-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 225-OR
Abstract: Introduction and Objective: Obesity with comorbid type 2 diabetes remains a significant therapeutic challenge. Apelin signaling is genetically linked to glucose homeostasis, with apelin knockout mice showing impaired insulin sensitivity. We evaluated whether our oral apelin receptor agonist azelaprag could improve glycemic control in preclinical models of diabetic obesity, alone and in combination with tirzepatide.Methods: Two models of diabetic obesity were used: 1) diet-induced obese (DIO) mice with elevated baseline A1c, and 2) a more severe model combining DIO with low doses of streptozotocin (DIO/STZ) to impair β-cell function. In the DIO study, mice received azelaprag (1.1 g/L) or vehicle for >3 months. In the DIO/STZ study, mice received azelaprag and/or tirzepatide (10 nmol/kg) for 12 days. A1c, OGTT, HOMA-IR), body composition, and metabolic phenotypes were measured.Results: In DIO mice, after 2 months, azelaprag reduced A1c to levels comparable to lean controls and improved oral glucose tolerance (Δ glucose AUC) by 25% relative to vehicle (p<0.05). Metabolic phenotypes were measured after 3 months. Azelaprag increased activity and energy expenditure. During overnight fasting, azelaprag significantly reduced respiratory exchange ratio (RER), indicating increased fat oxidation. In the DIO/STZ model, azelaprag monotherapy reduced A1c by 1.2% (from 6.7% to 5.5%, p<0.05), comparable to the effect of tirzepatide alone (1.3% reduction, from 6.7% to 5.4%, p<0.05). The combination achieved greater improvement in A1c (2.1% reduction, from 6.9% to 4.8%, p<0.05) while increasing weight loss (26.2% vs 11.2% for tirzepatide alone, p<0.05) and improving body composition.Conclusion: Azelaprag demonstrated significant glycemic benefits in preclinical models of diabetic obesity, as monotherapy and in combination with tirzepatide. These results support clinical investigation of azelaprag for the treatment of diabetic obesity.Disclosure Y. Wang: Employee; BioAge Labs. S. Yan: Employee; BioAge. M. Banicki: Employee; BioAge Labs. M. Cochran: Employee; BioAge Labs. C. Portillo: Employee; BioAge Labs. C. Rodriguez: Employee; BioAge Labs. A. Banicki: Employee; BioAge Labs. A. Ritter: Employee; BioAge Labs. G. Guerrero: Employee; BioAge Labs. S. Cowdin: None. C. Patil: Employee; BioAge Labs. J. Rebo: None. R. Montgomery: Employee; BioAge Labs. E. Morgen: Employee; BioAge Labs. K. Fortney: Employee; BioAge. P. Rubin: Employee; BioAge Labs.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-225-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 226-OR: Switching from Dulaglutide to Tirzepatide in T2D—Subgroup
Analyses of the SURPASS-SWITCH Trial-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 226-OR
Abstract: Introduction and Objective: This work investigates the potential benefits of switching from weekly dulaglutide (DU) to weekly tirzepatide (TZP) in adults with T2D across baseline subgroups from SURPASS-SWITCH.Methods: SURPASS-SWITCH was a Phase 4 trial enrolling adults with T2D and inadequate glycemic control treated with weekly DU (0.75 mg/1.5 mg) for at least 6 months plus 0-3 oral antihyperglycemic medications (OAMs). Participants were assigned 1:1 to escalate to DU 4.5 mg/maximally tolerated dose (MTD), or switch with escalation to TZP 15 mg/MTD. Treatment effect on HbA1c and BW were analyzed by baseline subgroups of HbA1c (≤8.5%, >8.5%), duration of T2D (≤5 years, >5-≤10 years, >10 years), baseline DU dose (0.75 mg, 1.5 mg), and duration of DU dose (<1 year, ≥1 year).Results: Switching to TZP versus escalating DU was associated with statistically significant reductions from baseline to week 40 in HbA1c and BW across all baseline subgroups.Conclusion: In SURPASS-SWITCH, switching to TZP 15 mg/MTD from DU 0.75 mg /1.5 mg was associated with significant and consistent improvements in HbA1c and weight reductions versus DU across all baseline subgroups. For those not at treatment goals across a range of baseline characteristics, switching to TZP may be a clinical option when current treatment plans are not yielding desired clinical outcomes.DisclosureR. Violante: None. L. Rose: None. P. Sharma: None. K.K. Chivukula: Employee; Eli Lilly and Company. A. Kwan: Employee; Eli Lilly and Company.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-226-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 227-OR: Patient-Reported Outcomes in People with T2D in the SURPASS-SWITCH
Phase 4 Clinical Trial-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 227-OR
Abstract: Introduction and Objective: Switching from dulaglutide (DU) 0.75 mg/1.5 mg to tirzepatide (TZP) has shown clinically meaningful improvements in HbA1c and body weight (BW) in adults with T2D in SURPASS-SWITCH. These benefits were further explored through patient-reported outcomes (PROs) measuring BW-related self-perception and health-related quality of life (HRQoL), ability to perform daily physical activities, and emotional impact of two treatments for T2D.Methods: Participants were randomized 1:1 to escalate to DU 4.5 mg or maximally tolerated dose (MTD), or switch to tirzepatide with escalation to 15 mg/MTD. PRO measures assessed at baseline and week 40 were IWQOL-Lite-CT, IW-SP, APPADL, and GIEH. Higher scores indicate better perceived outcomes.Results: After switching from DU 0.75 mg/1.5 mg to TZP 15 mg/MTD, a statistically significant improvement in IW-SP score vs. DU was observed. Although not statistically significant vs. DU, improvements in IWQOL-Lite-CT, APPADL, and GIEH were numerically larger in the TZP treatment group.Conclusion: In addition to improvements in key clinical markers, switching from DU 0.75 mg/1.5 mg to TZP 15 mg/MTD was associated with statistically significant improvement vs. DU in BW-related self-perception and non-statistically significant improvements vs. DU in BW-related HRQoL, ability to perform daily physical activities, and global impression of emotional health.DisclosureK. Boye: None. P. Sharma: None. K.K. Chivukula: Employee; Eli Lilly and Company. A. Kwan: Employee; Eli Lilly and Company.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-227-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 228-OR: Effects of Pemvidutide, a GLP-1/Glucagon Dual Receptor Agonist, on
Cardioinflammatory Lipids in Subjects with Obesity or Overweight-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 228-OR
Abstract: Introduction and Objective: Dysregulated lipid profiles in obesity can promote systemic inflammation and increase cardiovascular risk. We previously reported on the effects of pemvidutide, a dual GLP-1/glucagon receptor agonist, on these profiles in a Phase 1 trial in healthy volunteers. The aim of this study was to extend these observations to a Phase 2 clinical trial of pemvidutide in subjects with obesity or overweight.Methods: Subjects with obesity, or overweight and at least 1 obesity-related comorbidity, but without diabetes were randomized 1:1:1:1 to pemvidutide (1.2, 1.8, 2.4 mg) or placebo administered weekly by the subcutaneous route for 48 weeks (N=391; mean BMI 37.4 kg/m2). Metabolomic profiling was conducted in 254 subjects with paired Baseline and Week 48 plasma samples using mass spectrometry or NMR.Results: Pemvidutide reduced body weight by up to 15.6% and atherogenic lipids including total cholesterol, LDL-C, and triglycerides by up to 15.1%, 11.2%, and 34.9%, respectively. Pemvidutide reduced pro-inflammatory lipidomic signatures, including remnant cholesterol, small LDL-C particles, and multiple classes of pro-inflammatory lipids. Reductions in Glyc-A, a biomarker correlated with heart failure, were also observed (Table 1).Conclusion: Pemvidutide elicited significant weight loss and decreases in atherogenic pro-inflammatory lipid species in subjects with obesity or overweight.Disclosure J.J. Suschak: Employee; Altimmune Inc. M. Lucca Andrade: Employee; Altimmune Inc. B. Georges: Employee; Altimmune Inc. C. Alonso: Employee; Rubió Metabolomics, S.L.U. (OWL Metabolomics). M.S. Roberts: Employee; Altimmune Inc. M. Harris: Employee; Altimmune Inc. S.K. Browne: Employee; Altimmune Inc.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-228-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 229-OR: The Accuracy of a Novel Continuous Ketone Monitoring System (CKM)
and Metrics of Ketosis during Ketogenic Diets in Type 1 Diabetes (T1D)-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 229-OR
Abstract: Introduction and Objective: We evaluated i) the accuracy of SiBio CKM and ii) continuous ketone levels during two ketogenic diets, in individuals with T1D on automated insulin delivery (AID).Methods: We compared the readings of the CKM on day 7 of wear age to capillary measurements by FreeStyle Libre 2 ketone meter in adults who underwent 8-hour inpatient insulin suspension experiments. We also assessed metrics of continuous ketone levels using the CKM on two 6-day ketogenic diets: very-low carbohydrate diet (<50 g/day) and intermittent 12-hour fasting in outpatient free-living settings.Results: During insulin suspensions, 181 paired data points were collected from 14 adults (10 female, mean age of 36.5 y, HbA1c 6.9%, insulin dose 0.72 units/kg). The overall mean absolute difference (MAD) between the CKM and capillary readings was 0.2 mmol/L and the relative MAD for ketone values ≥0.6 and ≥1.0 mmol/L were 24% and 20%, respectively. During the ketogenic diets, the percent time with CKM values <0.6 and ≥0.6 mmol/L were 97.9% and 2.1% (30 min/day), respectively. The number of continuous ketosis events >0.6 and >1.0 mmol/L of more than 30 minutes were 51 and 7 events (i.e., 1 event in 2.7 and 20 days), respectively, with an average duration of 77 min/event; all events were asymptomatic.Conclusion: SiBio CKM demonstrated acceptable accuracy and reveals that benign, transient ketosis may be common in T1D.DisclosureN. Sabelli: None. A. Haidar: Research Support; Tandem Diabetes Care, Inc. Consultant; Eli Lilly and Company, Abbott. Research Support; ADOCIA, Dexcom, Inc., Ypsomed AG, Bigfoot Biomedical, Inc. D. Majdpour: None. M. Pasqua: Speaker's Bureau; Abbott, Sanofi, Medtronic. M. Tsoukas: Speaker's Bureau; Novo Nordisk, Eli Lilly and Company, Boehringer-Ingelheim, Janssen Pharmaceuticals, Inc, Sanofi. N. Perz: None. S. Jacobson: None.FundingDiabetes Quebec (Subvention de m'rite)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-229-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 230-OR: A Real-Time Recalibration Algorithm to Improve the Accuracy of CGM
Sensors in Newborns-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 230-OR
Abstract: Introduction and Objective: Over one third of infants in the U.S. are considered at-risk for neonatal hypoglycemia (NH), which is associated with long-term neurodevelopmental sequelae. Currently, neonatal blood glucose is assessed intermittently, missing over 25% of NH events. Continuous glucose monitoring (CGM) sensors, providing glycemic data every 5 minutes, are standard care for individuals with diabetes and represent a possible solution to improve the monitoring of NH. However, CGM sensors are not optimized for the physiology of neonates. Here we present interim data aimed to develop and validate an algorithm that allows the real-time recalibration of CGM sensors when applied to newborns.Methods: Pregnant women with diabetes and non-diabetic controls were recruited in the third trimester to participate in this IRB-approved study. A factory calibrated Dexcom G6 sensor was placed within 2 hours of birth and point of care blood glucoses (POCBG) were measured per standard of care guidelines with an Abbott Freestyle Precision Pro glucometer. We developed a recalibration algorithm, based on a linear regression model, that exploits the first 2 POCBG and can be applied right after the second measurement. The accuracy of original and recalibrated CGM was measured via Mean Absolute Relative Difference (MARD).Results: On the 12 individuals, a total of 59 POCBG references were available to assess sensor accuracy. The MARD of original CGM data was 40.8%, with a mean error (ME) of 25.2 mg/dL. The recalibration algorithm reduced the MARD of CGM to 12.5% and the ME to 3.5 mg/dL, which was a statistically significant improvement (p<0.01).Conclusion: Application of CGM devices for newborns is key for NH management, but original CGM data do not provide sufficient accuracy to guide clinical care. The proposed real-time recalibration algorithm enhances the accuracy of CGM, approaching the approved accuracy of the devices, potentially enabling a better detection of NH and evaluation of glycemic-control metrics.DisclosureF. Prendin: None. S. DelFavero: Research Support; Dexcom, Inc. Other Relationship; Dexcom, Inc. S. Cherkerzian: None. A. Coburn-Sanderson: None. R. Abdel-Rahman: None. C. Monthe-Dreze: None. A. Galderisi: None. S. Sen: Other Relationship; Dexcom, Inc., nova. A. Facchinetti: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-230-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 231-OR: Dexcom G6 Pro Accuracy and Reproducibility in the Intensive Care
Unit-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 231-OR
Abstract: Introduction and Objective: To evaluate the accuracy and reproducibility of the Dexcom G6 Pro sensor in a hospital ICU setting in persons with diabetes or hyperglycemia in the absence of diabetes.Methods: At 5 U.S. academic centers, 9,121 glucose levels obtained with a Dexcom G6 Pro sensor were compared with venous or capillary blood glucose (BG) measurements in 130 adults hospitalized in the ICU (95 with diabetes and 35 with hyperglycemia without diabetes), 124 of whom simultaneously wore 2 sensors.Results: The median relative absolute difference (RAD) was 19% comparing CGM and BG measurements, with 41% of CGM values either within 15% or 15 mg/dL of the corresponding BG value. CGM values were consistency higher than BG values across the entire glucose range, with a median difference (CGM minus BGM) of 25 mg/dL (Table). Median RAD and median difference varied little according to day of sensor wear. For 186,648 paired CGM values from 2 simultaneously worn sensors, median RAD was 11%.Conclusion: In the ICU setting, the G6 Pro sensor tended to be biased high and the median RAD was greater than expected based on prior outpatient studies. It cannot be determined whether this bias and reduced accuracy is a function of the specific sensor or related to the ICU setting.DisclosureJ. Ullal: None. C. Spanbauer: None. J.H. Chao: Research Support; Dexcom, Inc. F.J. Pasquel: Consultant; Insulet Corporation. Research Support; Novo Nordisk, Dexcom, Inc., Ideal Medical Technologies, Tandem Diabetes Care, Inc, Insulet Corporation. Consultant; Dexcom, Inc. M.S. Jones: None. C.C. Low Wang: Research Support; Dexcom, Inc., Virta Health Corp. J.B. Buse: Other Relationship; Corcept Therapeutics, Dexcom, Inc., Novo Nordisk. Consultant; Altimmune Inc, Amgen Inc, ApStem, Aqua Medical, AstraZeneca, Boehringer-Ingelheim, CeQur, Eli Lilly and Company, embecta, GentiBio. Other Relationship; Glyscend Therapeutics. Consultant; Insulet Corporation, Medtronic. Other Relationship; Mellitus Health. Consultant; Metsera. Other Relationship; Pendulum Therapeutics, Praetego, Stability Health. Consultant; Tandem Diabetes Care, Inc, TERNS Pharmaceuticals, Vertex Pharmaceuticals Incorporated, Zealand Pharma A/S. B. Draznin: None. J. Sibayan: None. C. Kollman: Research Support; Dexcom, Inc., Insulet Corporation, MannKind Corporation, Breakthrough T1D (formerly JDRF), Capillary Biomedical, Inc, Hemsley Charitable Trust, National Institute of Diabetes and Digestive and Kidney Diseases, Tandem Diabetes Care, Inc. R.W. Beck: Research Support; Insulet Corporation. Consultant; Insulet Corporation. Research Support; Tandem Diabetes Care, Inc, Beta Bionics, Inc, Dexcom, Inc., Bigfoot Biomedical, Inc, Abbott, embecta, Sequel Med Tech, MannKind Corporation. Consultant; Novo Nordisk, Vertex Pharmaceuticals Incorporated, Hagar, Ypsomed AG, Zucara Therapeutics, Abata Therapeutics, Eli Lilly and Company. I.B. Hirsch: Research Support; Dexcom, Inc., Tandem Diabetes Care, Inc, MannKind Corporation. Consultant; Abbott, Roche Diabetes Care, Hagar.FundingDexcom, Inc
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-231-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 232-OR: Accuracy of Real-Time Continuous Glucose Monitoring in
Hospitalized Patients with Diabetes and Impaired Kidney Function-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 232-OR
Abstract: Introduction and Objective: Continuous glucose monitoring (CGM) systems improve glycemic control in patients with type 1 diabetes (T1D) and type 2 diabetes (T2D) by reducing hypoglycemia and increasing time within target glucose range compared to capillary blood glucose testing. Recent factory-calibrated real-time CGM systems have enhanced usability and accuracy. However, their performance in patients with impaired kidney function, especially those in the hospital where high accuracy is crucial, has not been investigated. This study aimed to evaluate the accuracy of real-time CGM in hospitalized patients with diabetes and impaired kidney function.Methods: A total of 24 patients with diabetes, including T1D (n = 2), T2D (n = 20), and pancreatic diabetes (n = 2), hospitalized in a general ward were enrolled. Participants were categorized into three groups based on estimated glomerular filtration rate (eGFR, mL/min/1.73m²): G1-2 (eGFR ≥60), G3 (eGFR 30-59), and G4-5 (eGFR <30). Capillary glucose values measured using a point of care device (Accu-Chek Guide One, Roche) were compared with the glucose readings from a real-time CGM (G6, Dexcom) recorded at the closest corresponding time. Accuracy was assessed using mean absolute relative difference (MARD), the percentage of readings within ±15% or ±15 mg/dL of reference values (%15/15), and %20/20.Results: The study analyzed 289, 325, and 155 glucose pairs from the G1-2 (n=9), G3 (n=9), and G4-5 (n=6) groups, respectively. Mean HbA1c levels were 9.4% in G1-2, 11.2% in G3, and 7.2% in G4-5, with significant intergroup differences (p = 0.004). The overall MARD was 13.5%, with group-specific values of 15.9% in G1-2, 12.7% in G3, and 10.1% in G4-5, with significant differences among groups (p < 0.001). The intergroup difference was consistent with %15/15 (p < 0.001) and %20/20 (p < 0.001).Conclusion: This study demonstrated the accuracy of real-time CGM in hospitalized patients with diabetes and impaired kidney function.DisclosureY. Kakutani: None. T. Morioka: Research Support; Boehringer-Ingelheim. S. Miyamoto: None. Y. Yamazaki: None. A. Ochi: None. K. Mori: Research Support; Mitsubishi Tanabe Pharma Corporation, Kyowa Kirin Co., Ltd, Sumitomo Dainippon Pharma Co., Ltd. Speaker's Bureau; Mitsubishi Tanabe Pharma Corporation, AstraZeneca, Novo Nordisk, Boehringer-Ingelheim, Kyowa Kirin Co., Ltd, Eli Lilly and Company. T. Shoji: None. M. Emoto: Speaker's Bureau; Novo Nordisk, Kyowa Kirin Co., Ltd. Research Support; Boehringer-Ingelheim.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-232-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 233-OR: Occurrence and Impact of Missing Data on CGM Metrics—Analysis of
Data from Type 1 Diabetes Exercise Initiative (T1DEXI)-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 233-OR
Abstract: Introduction and Objective: Missing CGM data can confound clinical decision making. This study explores the impact of data missingness on CGM metrics from the T1DEXI study.Methods: Study 1: Gaps in CGM data were determined based on time intervals between consecutive readings.Study 2: To evaluate the effect of gap sizes on CGM parameters, a simulation study randomly introduced missing data with gap sizes of 1-10, 11-50, or >50 continuous missing data points while maintaining the same overall missing rate of 20.83% in all groups. CGM glucose metrics including mean, SD, CV, TAR, TIR, and TBR (see Figure B for abbreviations), were compared to a control group with no missing data.Results: In the T1DEXI CGM dataset, gaps of 1-10 account for 15.76% of all missingness but 68.47% of the frequency, gaps of 11-50 account for 41.06% of all missingness and 25.44% of the frequency, and gaps of >50 account for 43.18% of all missingness but only 6.09% of the frequency. The simulation study showed that, compared to smaller missing gaps, larger gaps resulted in higher Mean Absolute Percentage Error (Figure B).Conclusion: Small gaps in CGM data are frequent but cause minimal errors; whereas large data gaps, though less frequent are associated with large errors in CGM metrics particularly in TAR and TBR. These findings highlight the need for accurate prediction of large gaps to improve CGM data interpretation.DisclosureD. Zhan: None. S.J. Fisher: None. X.D. Zhang: None.FundingThis research was supported by US National Institutes of Health (through Grants U01DK135111 and UL1TR001998), the DRC at Washington University (Grant No. P30DK020579), the University of Kentucky Diabetes and Obesity Research Priority Area and the Barnstable Brown Diabetes and Obesity Center. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. This publication is based on the data from the Type 1 Diabetes EXercise Initiative (T1DEXI) Study that has been made available through Vivli, Inc. Vivli has not contributed to or approved, and is not in any way responsible for the contents of this publication.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-233-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 234-OR: Impact of Initiating Continuous Glucose Monitoring in People with
Type 2 Diabetes Not on Insulin—A Randomized Controlled Trial-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 234-OR
Abstract: Introduction and Objective: Nutrition is a cornerstone of diabetes management. The UNITE (Using Nutrition to Improve Time in rangE; NCT05928572) study compared time in range (TIR; glucose 70-180 mg/dL) in people with type 2 diabetes not on insulin (T2NI) who were introduced to CGM using either a nutrition-focused approach (NFA) or a self-directed approach (SDA).Methods: In this two-month study, adults with T2NI completed baseline blinded CGM and dietary assessments and were randomized to start CGM (Dexcom G7) using a NFA or SDA. Both arms participated in one in-person education session and one remote CGM data review session. The NFA emphasized using evidence-based nutrition recommendations to improve TIR, and the SDA encouraged using CGM in any way that felt helpful. Differences in pre-post glycemia and dietary intake were assessed between and within arms.Results: Participants, N=124 (NFA N=64, SDA N=60), were (mean + SD) 65 + 10 years old; took 1.4 + 0.9 diabetes medications; had an A1c of 7.9 + 0.7% and diabetes for 11 + 7 years. TIR improved significantly without medication changes, +25% for NFA and +16% for SDA (p<0.001); no difference in changes by arm (p=0.14). Other CGM metrics and A1c also improved (Table 1). The NFA arm had minor, but significant, pre-post dietary changes.Conclusion: Starting CGM with either a NFA or SDA led to very significant improvements in TIR in people with T2NI.Disclosure H.J. Willis: Research Support; Abbott, Dexcom, Inc. S. Gustafson: None. M. JaKa: None. R.M. Bergenstal: Advisory Panel; Abbott. Research Support; Abbott. Consultant; Abbott. Research Support; Dexcom, Inc. Consultant; Dexcom, Inc., Eli Lilly and Company. Research Support; Eli Lilly and Company. Consultant; Novo Nordisk. Research Support; Novo Nordisk. Consultant; Roche Diabetes Care, Sanofi, Medtronic. Research Support; Medtronic, Insulet Corporation, Hemsley Charitable Trust. Other Relationship; MannKind Corporation. Consultant; Medscape. Research Support; National Institute of Diabetes and Digestive and Kidney Diseases, Tandem Diabetes Care, Inc, UnitedHealth Group. Consultant; Vertex Pharmaceuticals Incorporated, Ascensia Diabetes Care, American Diabetes Association, Hygieia, embecta, Senseonics, Zealand Pharma A/S.FundingAmerican Diabetes Association (7-22-JDFN-27); Dexcom provided glucose monitoring supplies.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-234-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 235-OR: Interleukin-12 Is a Novel Proinflammatory Cytokine Regulating
Insulin Resistance in the Liver-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 235-OR
Abstract: Introduction and Objective: Interleukin (IL)-12 is a pro-inflammatory cytokine that plays a major role in bridging innate and acquired immunity. IL-12 is primarily secreted by macrophages, and serum IL-12 levels are elevated in obesity.Methods: To determine the role of IL-12 in insulin resistance, male C57BL/6J mice were treated with mouse recombinant IL-12 (0.20 ng/uL/g) or saline (control) via osmotic pumps for 2 weeks (n=5/group), and a hyperinsulinemic-euglycemic clamp was performed to measure insulin sensitivity in awake mice.Results: Basal hepatic glucose production (HGP) was not altered, but HGP during clamp was increased in IL-12 treated mice compared to controls (Fig. 1). This resulted in a 39% decrease in hepatic insulin action, indicating IL-12 effects on hepatic insulin resistance (Fig. 1). Next, male C57BL/6J mice were fed a high-fat diet (HFD) for 14 weeks, and mice were treated with anti-IL-12p35 antibody (250 μg) or PBS (control) for 10 days (n=8/group). Anti-IL-12 treatment rescued HFD-fed mice from hepatic insulin resistance as HGP during insulin clamp trended lower compared to controls (Fig. 2). This resulted in a 24% increase in hepatic insulin action in HFD-fed mice following anti-IL-12 treatment (Fig. 2).Conclusion: These results indicate that a chronic elevation of IL-12 causes insulin resistance in the liver, and IL-12 may be a novel therapeutic target for treating hepatic insulin resistance in obesity.DisclosureA. Daryanani: None. M. Sajid: None. H. Choi: None. J. Lim: None. K. Kasina: None. L.A. Tauer: None. J.K. Kim: None.FundingNational Institutes of Health (R01-DK133772, R01-AG085308)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-235-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 236-OR: A New Layer of Endocrine Regulation—Brown Fat–Derived
MicroRNAs Regulate Metabolic Functions in Distal Organs-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 236-OR
Abstract: Introduction and Objective: Numerous studies have shown that brown adipose tissue (BAT) is associated with good cardiometabolic health. We have shown that BAT is a major source of circulating miRNAs, which are released in plasma via extracellular vesicles (sEVs). These miRNAs are taken up by distal organs, regulating glucose uptake and insulin action, thereby participating in the endocrine system. Indeed, miR-99b and miR-378a are released by BAT and can target Fgf21 and p110α in liver, as shown by us and others. However, the study of inter-tissue miRNA trafficking has been limited.Methods: To study directly inter-organ miRNA trafficking, we have now developed a transgenic mouse expressing the microbial enzyme UPRT in BAT, which allows labeling of BAT-produced miRNAs with 4-thiouracil (4TU) and their tracking to distal tissues. Using this approach, we have defined the full complement of BAT-secreted miRNAs and tracked their appearance in plasma, liver, muscle, and hypothalamus.Results: Focusing on the top labeled miRNAs in BAT, we tracked the appearance of 55 4TU-miRNAs in plasma. Of these 18 were primarily in sEVs, 17 were primarily associated with plasma proteins, and 20 were in both compartments. Surprisingly, miR-1a-3p (a miRNA normally associated with muscle) and miR-122-5p (a miRNA normally abundant in liver) were the top 4TU-miRNAs in plasma, providing evidence that some of the most abundant miRNAs in the liver and muscle can in fact originate from BAT. Using this data, we created a roadmap of BAT- sEV-miRNA and non-sEV-miRNAs trafficking to liver, muscle, and hypothalamus, which shows distinct miRNAs accumulating in each organ with remarkable specificity. Using bioinformatic and molecular biology approaches, we showed that the BAT-secreted miRNAs can target Pi3K/Akt and FoxO1 signaling and metabolic function in distal organs.Conclusion: Thus, we have developed a powerful tool to study inter-tissue miRNA transfer from BAT, revealing a previously unknown network of inter-organ communication by BAT-miRNAs.DisclosureM. Lino: None. G. Ruiz: None. Y. Yu: None. B. Brasil Brandao: Employee; Novo Nordisk. A. Nawaz: None. A. Ghosh: None. C. Kahn: Consultant; Novo Nordisk, Cellarity. Advisory Panel; TIXiMED. Board Member; 1825.FundingDK082659
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-236-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 237-OR: Adipocyte–Endothelial Cell Cross Talk in Adipose Tissue—The
Impact of Rho-Associated, Coiled-Coil–Containing Protein Kinase 2 on
Insulin Resistance-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 237-OR
Abstract: Introduction and Objective: The vascular endothelium of adipose tissue plays a crucial role in regulating adipose functions. However, its role in supporting adipose tissue homeostasis under varying metabolic conditions remains unclear. This study aimed to investigate the role of Rho-associated, coiled-coil-containing protein kinase 2 (ROCK2), a key regulator of endothelial inflammation, in insulin resistance.Methods: (1) We generated vascular endothelium-specific ROCK2-deficient mice (ER2KO) and assessed their phenotype under a diet-induced insulin resistance model. (2) The inducible ER2KO mice were developed in order to eliminate the potential effect of ROCK2 deficiency in hematopoietic cells. (3) We deleted ROCK2 in human adipose tissue vascular endothelial cells, cultured adipocytes in conditioned medium, and analyzed the medium using LC-MS/MS. (4) The expression levels of ROCK2 were assessed in white adipose tissue of wild-type mice under cold exposure and fasting conditions.Results: (1) ER2KO mice showed a reduction in weight gain, smaller adipocytes, improved insulin sensitivity, and reduced liver fat accumulation under a high-fat diet. Furthermore, enhanced browning of white adipose tissue and a shift of macrophages toward the M2 type were observed. (2) Inducible ER2KO mice demonstrated similar results, confirming the observed phenotype was independent of hematopoietic ROCK2 deficiency. (3) The conditioned medium from ROCK2-deficient endothelial cells promoted adipocyte browning and increased anti-inflammatory factors, while reducing pro-inflammatory factors. (4) Cold exposure and fasting conditions were shown to reduce ROCK2 expression in the adipose tissue vascular endothelium of wild-type mice.Conclusion: The deficiency of ROCK2 in adipose tissue endothelial cells promotes crosstalk between adipocytes, thereby suppressing the progression of insulin resistance.Disclosure S. Ohashi: Research Support; Novo Nordisk. K. Matoba: None. S. Nagao: None. K. Sekiguchi: None. E. Mitsuyoshi: None. Y. Nagai: None. R. Nishimura: Advisory Panel; Abbott Japan Co., Ltd. Speaker's Bureau; Nipro, Astellas Pharma Inc, AstraZeneca, Boehringer-Ingelheim, Eli Lilly and Company, LifeScan Diabetes Institute, Mitsubishi Tanabe Pharma Corporation, Kowa Company, Ltd, Kissei Pharmaceutical Co., Ltd. Advisory Panel; Novo Nordisk A/S. Speaker's Bureau; Ono Pharmaceutical Co., Ltd. Advisory Panel; Sanofi. Speaker's Bureau; Teijin Pharma Limited, Terumo Corporation. Advisory Panel; Medtronic. Speaker's Bureau; Dexcom, Inc., Taisho Pharmaceutical Holdings Co., Ltd.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-237-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 238-OR: M6A RNA Methylation Regulates Mitochondrial Functions and Exosomal
miR-6126 Signaling in Brown Adipocytes to Improve Systemic Metabolism-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 238-OR
Abstract: Introduction and Objective: Brown adipose tissue (BAT) plays a critical role in regulating systemic metabolism via its thermogenesis and secretory functions. N6-methyladenosine (m6A) has emerged as a critical regulator of BAT thermogenesis and signaling lipid secretion. Here, we focused on the contribution of m6A in modulating BAT mitochondrial function and exosomal miRNA secretion.Methods: AlkB homolog 5 (ALKBH5) floxed mice were crossed with Ucp1-Cre mice to generate BAT-specific ALKBH5 knockout (A5KO) animals.Results: Male A5KO mice exhibited protection against high-fat diet-induced insulin resistance and glucose intolerance with enhanced thermogenesis, independent of body weight changes. Mitochondrial analyses showed improved morphology, oxidative phosphorylation, and respiratory capacity in BAT, suggesting cell-autonomous effects of ALKBH5 deficiency. Vena cava insulin injection revealed increased insulin sensitivity in liver and muscle, indicating inter-organ communication mediated by BAT-derived factor(s). Furthermore, exosomal miRNA sequencing of differentiated ALKBH5-KO human brown adipocytes (A5KO-hBAs) media identified a significant downregulation of micro RNA-6126 (miR-6126), which targets the RAS-PI3K-AKT pathway. Mechanistically, m6A- and RNA-sequencing in A5KO-hBAs revealed MYC proto-oncogene, bHLH transcription factor (MYC) hypermethylation. While MYC mRNA level remained unchanged, m6A hypermethylation promoted its translation via YTHDF1. MYC suppressed miR-6126 expression and upregulated genes related to mitochondrial biogenesis and function in brown adipocytes.Conclusion: These findings reveal a novel m6A-mediated regulatory axis where ALKBH5 deficiency enhances mitochondrial function and miR-6126-mediated inter-organ communication. Targeting ALKBH5 offers a therapeutic strategy to improve systemic metabolic homeostasis in obesity-related disorders.DisclosureL. Xiao: None. S. Wang: None. A. DiStefano-Forti: None. D.F. De Jesus: None. R. Kulkarni: Advisory Panel; Novo Nordisk, Biomea Fusion, REDD Pharma, Inversago Pharma. Research Support; Inversago Pharma. Stock/Shareholder; Biomea Fusion.FundingNational Institutes of Health (R01 DK067536); National Institutes of Health (RC2 139552)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-238-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 239-OR: Bone Marrow Stromal OGT Controls Diabetic Osteoporosis
-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 239-OR
Abstract: Introduction and Objective: Bone disease is a major type of complication of diabetes. However, the molecular and metabolic basis of how insulin deficiency or resistance affects bone is still incompletely known. Here, we tested if O-linked N-Acetylglucosamine (O-GlcNAc) signaling prevents diabetic osteoporosis in preclinical models.Methods: Post-translational modification of intracellular proteins by a single O-GlcNAc moiety at serine or threonine residues is mediated by O-GlcNAc transferase (OGT). We first used single-cell RNA sequencing and Flow Cytometry to examine the levels of Ogt gene expression and protein O-GlcNAc modification in osteogenic bone marrow stromal cells (BMSCs). We then generated adult perivascular BMSC-specific OGT knockout (OgtΔLepr) mice and characterized their bone microstructure at the steady state and during streptozotocin (STZ)-induced diabetes. Finally, we treated cultured BMSCs with chemicals to induce O-GlcNAcylation or overexpressed OGT in BMSCs in mice to test whether O-GlcNAc augmentation alleviates diabetes-induced osteopathy.Results: OGT and protein O-GlcNAcylation are enriched in adipo-osteogenic BMSCs that are marked by the leptin receptor gene (Lepr). LeprCre-mediated deletion of OGT in adult BMSCs (OgtΔLepr) did not evidently change bone microarchitecture or mineral density in young or old mice. Instead, STZ-induced diabetes diminished stromal O-GlcNAcylation and OgtΔLepr mice showed exacerbated bone loss during diabetes. In culture, OGT was required for insulin and intermittent parathyroid hormone (iPTH) to stimulate BMSC proliferation and osteogenic differentiation. In mice, OGT overexpression in BMSCs alleviated induced bone loss. Mechanistically, OGT modified and activated RUNX2 to stimulate osteogenesis.Conclusion: Protein O-GlcNAcylation modulates the differentiation fate and metabolic fitness of BMSCs, thus impeding diabetic osteopathy.DisclosureC. Gu: None. H. Ruan: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-239-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 240-OR: Mirabegron Treatment Reduces Myofibroblasts and Inflammatory NK
Cells in Adipose Tissue in Obesity-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 240-OR
Abstract: Introduction and Objective: Treatment with the β3-adrenergic receptor (β3AR) agonist mirabegron improves insulin sensitivity, β cell function, and glucose tolerance in individuals with obesity, without weight loss or a change in brown adipose tissue (BAT). The objective of this study was to identify changes in the mRNA transcriptome of subcutaneous white adipose tissue (SC WAT) to identify mechanisms for the beneficial effects of mirabegron treatment.Methods: Adipose biopsies were performed on obese subjects before and after treatment with mirabegron 50 mg/day. We utilized RNA seq and enrichment analysis on SC WAT to identify biological pathways changed by mirabegron treatment. We verified these changes by immunohistochemistry and performed mechanistic studies in differentiated human adipocytes in vitro.Results: Mirabegron treatment reduced myofibroblasts, which are fibrotic, and reduced CXCR2, which is involved in inflammation and chemotaxis, in SC WAT. Adipose tissue myofibroblasts were higher with obesity and negatively correlated with β cell function. Mirabegron inhibited TGFβ induction of the adipocyte mesenchymal transition pathway in differentiated adipocytes in vitro. Furthermore, mirabegron treatment reduced expression of snail, a transcription factor which promotes the mesenchymal transition pathway, in vitro and in vivo. We also found that mirabegron treatment reduced CXCR2 expression in SC WAT. CXCR2 was expressed by NK cells and mirabegron treatment reduced CXCR2 and the inflammation marker NK1.1 on NK cells in SC WAT.Conclusion: Together, these results suggest mechanisms for a β3AR agonist to reduce fibrosis and inflammation in human SC WAT, which improves glucose metabolism.DisclosureB. Finlin: None. H. Memetimin: None. P. Westgate: None. J. Chen: None. E.E. Dupont-Versteegden: None. P.A. Kern: None.FundingR01DK124626, RO1DK112282, RO1DK107646, UL1TR001998, P20GM103527
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-240-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 241-OR: Hypoglycemia Prevention in High-Risk Patients with Type 2
Diabetes—A Pragmatic Randomized Controlled Trial-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 241-OR
Abstract: Introduction and Objective: Severe hypoglycemia is a life-threatening diabetes treatment complication associated with increased risks of falls, cardiovascular events, cognitive decline, and mortality. Our objective was to determine whether proactive outreach by a clinical pharmacist applying an evidence-based hypoglycemia prevention algorithm, “Hypoglycemia on a Page” (HOAP) would result in safer diabetes regimens among patients with type 2 diabetes (T2D) at high risk for hypoglycemia.Methods: We conducted a pragmatic, randomized trial in a large, integrated healthcare delivery system. Patients with T2D and at high risk for hypoglycemia (based on a validated hypoglycemia risk tool) were randomized to either (1) protocol-driven outreach by a clinical pharmacist (intervention arm, n=100), or (2) usual care (control arm, n=100). We performed an intention to treat analysis using chi square tests to compare the proportion of patients prescribed safer (less hypoglycemia-prone) diabetes regimens (defined as discontinuation of sulfonylureas, and/or rapid-/short-acting or mixed insulins).Results: Patients in the two study arms were similar at baseline in terms of race, sex, HbA1c, insulin, and sulfonylurea use. At 6 months, patients in the intervention arm were more likely to be prescribed a safer diabetes regimen (28% vs. 16% in control arm, p=0.04). Patients in the intervention arm also experienced fewer hypoglycemia-related ED or inpatient encounters (0% vs. 5.3%, p=0.02). We did not see worsening HbA1c control in the intervention arm, compared to the control arm (62% vs 64% with HbA1c < 8%, p=0.82).Conclusion: We demonstrated that adding clinical pharmacists into collaborative team-based care improves medication optimization and patient outcomes. This approach provides an evidence-based, targeted strategy for preventing severe hypoglycemia in high-risk individuals that enhances patient safety and potentially reduces overall health care cost.DisclosureL.K. Gilliam: None. M. Chen: None. M.M. Parker: Research Support; Dexcom, Inc. R.W. Grant: None. A.J. Karter: Research Support; Dexcom, Inc.FundingKaiser Permanente Delivery Sciences Research Program
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-241-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 242-OR: Effects of Automated Insulin Delivery (AID) on Impaired Awareness
of Hypoglycemia (IAH) in Older Adults with Type 1 Diabetes in the AIDE
Study-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 242-OR
Abstract: Introduction and Objective: One in three older adults with T1D has IAH. Risk factors include longer diabetes duration and recurrent hypoglycemia. In the AIDE study, hybrid closed loop (HCL) and predictive low glucose suspend (PLGS) decreased hypoglycemia in older adults with T1D. In this post-hoc analysis, we determined the effects of AID (HCL/PLGS) on IAH.Methods: We studied adults aged ≥65 years with T1D who underwent two consecutive 12-week periods of AID (HCL followed by PLGS or vice versa). Hypoglycemic awareness was classified as normal (NAH; Gold score <4) or impaired (IAH; Gold score ≥4). We analyzed changes in Gold score after 24 weeks of AID and corresponding changes in CGM metrics in those with persistent IAH, persistent NAH, and in those whose IAH resolved.Results: Of the 64 participants (mean ± SD age, 70.5 ± 4y, diabetes duration 30 ±17y, 52% females, 97% White), 20 (31%) had IAH at baseline (Fig B). After 24 weeks of AID, Gold score decreased significantly in the IAH cohort (5.6±1.1 to 3.95±0.8; P=0.0001; Fig A). Time spent in hypoglycemia (<54 mg/dL) increased in adults with persistent IAH but decreased among those whose IAH resolved (Fig C). In a linear regression model, 1% greater time <54 mg/dL was associated with a 1.36 higher Gold score.Conclusion: Twenty-four weeks of AID improves IAH in older adults with T1D. This could be due to decreased hypoglycemia exposure.DisclosureA. Bilal: None. D.A. Igudesman: None. R. Henderson: None. J.L. Jo Kamimoto: None. K.J. Whitaker: None. S. Rizvi: None. N. Chaytor: None. R.S. Weinstock: Research Support; Amgen Inc, Eli Lilly and Company, Tandem Diabetes Care, Inc, Diasome Pharmaceuticals, Insulet Corporation, MannKind Corporation, Dexcom, Inc. Y.C. Kudva: Advisory Panel; Novo Nordisk, Vertex Pharmaceuticals Incorporated, Tandem Diabetes Care, Inc. Research Support; Dexcom, Inc., Insulet Corporation. M.R. Rickels: Consultant; Vertex Pharmaceuticals Incorporated, Sernova, Corp. Research Support; Dompé, Tandem Diabetes Care, Inc. Consultant; Novo Nordisk. R.E. Pratley: Consultant; AbbVie Inc. Stock/Shareholder; Altanine, Inc. Consultant; Amgen Inc, AstraZeneca. Other Relationship; Bayer AG, Bayer Pharmaceuticals, Inc, Biomea Fusion. Consultant; Boehringer-Ingelheim. Other Relationship; Carmot Therapeutics, Inc, Corcept Therapeutics, Dompé, Eli Lilly and Company, Endogenex. Consultant; Endogenex. Other Relationship; Fractyl Health, Inc., Gasherbrum Bio, Inc. Consultant; Genprex, Getz Pharma, Hanmi Pharm. Co., Ltd, Intas Pharmaceuticals Ltd, Lexicon Pharmaceuticals, Inc, Lilly USA LLC. Speaker's Bureau; Lilly USA LLC. Other Relationship; Metavention, Novo Nordisk, Novo Nordisk. Speaker's Bureau; Novo Nordisk. Other Relationship; Pfizer Inc, Poxel SA. Consultant; Regeneron Pharmaceuticals. Other Relationship; Sanofi. Consultant; Scholar Rock. Other Relationship; Sun Pharmaceutical Industries Ltd. A. Casu: Other Relationship; Enable Bioscience.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-242-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 243-OR: Edaravone Protects the Hippocampus from Brain Damage following
Insulin-Induced Severe Hypoglycemia-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 243-OR
Abstract: Introduction and Objective: To determine if Edaravone, a free radical scavenger and neuroprotective agent with antioxidant properties, could prevent brain damage following insulin-induced severe hypoglycemia.Methods: 10-week-old Sprague-Dawley rats were divided into three treatment cohorts: 1) euglycemic controls, 2) rats treated with insulin-induced (15U mg/kg) severe hypoglycemia (SH: 10-15mg/dL for 90 minutes), and 3) rats treated with SH followed by once daily with Edaravone (3mg/kg) (SH+EDV). After one week animals were euthanized, perfused and brains extracted. Sections from the hippocampus (40µm) were stained using Fluoro-Jade C (FJC), Iba-1/CD68, Cleaved Caspase 3 (CC3), or 4-Hydroxynonenal (4HNE). Stains were analyzed using ImageJ and one-way ANOVA.Results: As compared to euglycemic controls, severe hypoglycemia increased Iba-1/CD68, CC3, and FJC stained cells as well as 4HNE+ areas (Fig. 1). As compared to SH alone, SH+EDV reduced all stained cells to a level not different from controls.Conclusion: Edaravone protected the brain from severe hypoglycemia induced cell death indicated by FJC and CC3 immunohistochemistry staining. Edaravone also reduced neuronal inflammation indicated by reduced Iba-1/CD68 staining, and reduced oxidative stress as indicated by 4HNE staining. In this rodent model, post-hypoglycemia treatment with Edaravone protected against brain damage.DisclosureA. Thompson: None. N.G. Phelps: None. H. Riley: None. M. Wooten: None. A.R. Marksbury: None. E.W. Brockman: None. L.A. Schoeder: None. Z. Beckner: None. M.H. Devore: None. I. Papazoglou: None. S.J. Fisher: None.FundingNational Institute of Diabetes and Digestive and Kidney Diseases (R01DK118082)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-243-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 244-OR: Sotagliflozin Added to Insulin Reduces the Risk of Clinically
Important Hypoglycemic Events in Adults with Type 1 Diabetes Regardless of
Kidney Function-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 244-OR
Abstract: Introduction and Objective: Chronic kidney disease (CKD) is a major risk factor for hypoglycemia. Sotagliflozin (SOTA) was associated with a reduced risk of hypoglycemia events when added to insulin in adults with type 1 diabetes (T1D). The present analysis evaluated the effect of kidney function on hypoglycemia in patients with T1D treated with SOTA.Methods: This analysis was conducted using pooled data of two placebo (PBO)-controlled trials of SOTA in combination with optimized insulin in adults with T1D. Documented hypoglycemia was predefined as blood glucose (BG) ≤70 and ≤55 mg/dL and severe hypoglycemia per Level 3 definition. Results were evaluated in the overall cohort and by eGFR subgroups (<60, 60 to <90, and ≥90 mL/min/1.73 m2).Results: Declining kidney function was associated with an increasing rate of severe hypoglycemic events and events with BG ≤ 70 or ≤ 55 mg/dL in the PBO group. Positively adjudicated severe hypoglycemia occurred in 7.4% of patients on PBO compared to 5.7% and 4.4% on SOTA 200 and 400 mg, respectively. A similar trend was observed across the eGFR. SOTA was associated with a reduction in the risk of events with BG ≤ 55 mg/dL, regardless of dose and eGFR subgroup (Table).Conclusion: SOTA significantly reduced the risk of clinically important BG events ≤55 and ≤70 mg/dL, with a trend towards a reduction in severe hypoglycemic events in patients with T1D regardless of baseline kidney function.Disclosure M.B. Hardin: Employee; Lexicon Pharmaceuticals, Inc. A.K. Carroll: None. P.L. Banks: None. M. Girard: None. M.J. Davies: Employee; Lexicon Pharmaceuticals, Inc.FundingLexicon Pharmaceuticals
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-244-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 245-OR: Plasma Methylglyoxal Is Linked to Nerve Dysfunction and Predicts
Increased Neuropathic Pain Intensity over Six Years in Diabetic
Polyneuropathy-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 245-OR
Abstract: Introduction and Objective: Methylglyoxal, a highly reactive dicarbonyl compound, has been implicated in the pathogenesis of diabetic sensorimotor polyneuropathy (DSPN). Here, we aimed to determine cross-sectional and longitudinal associations of plasma methylglyoxal with peripheral nerve function and symptoms in individuals with DSPN.Methods: Included were 383 individuals from the PROPANE study with type 1 or type 2 (16.2/83.8%) diabetes and asymptomatic, symptomatic painless, or symptomatic painful (9.1/34.2/56.7%) DSPN ([mean±SD] age 65.7±10.2 years, sex: 73% male, BMI: 30.3±5.5 kg/m2, HbA1c: 7.41±1.32%, known diabetes duration: 16.2±12.4 years). Eighty-five participants underwent follow-up examinations after 4-8 (6.14±1.04) years. Peripheral nerve function was assessed by motor and sensory nerve conduction velocities (MNCV, SNCV), sensory nerve action potentials (SNAP), vibration perception threshold (VPT), and cold and warmth detection thresholds (CDT, WDT). Plasma methylglyoxal was determined by tandem mass spectroscopy.Results: After adjustment for age, sex, BMI, smoking, HbA1c, diabetes type, and diabetes duration, plasma methylglyoxal was inversely associated with lower peroneal and tibial MNCV (β=-0.139/-0.152), sural SNAP (β=-0.114), and CDT (β=-0.115), and positively associated with WDT (β=0.155), VPT (β=0.149) and maximum 24h pain intensity (β=0.127; all P<0.05). After additional adjustment for DSPN severity, plasma methylglyoxal was higher in symptomatic compared with asymptomatic DSPN (P<0.05). Baseline plasma methylglyoxal was predictive for increasing 24h average pain intensity and WDT over 6 years.Conclusion: Higher systemic carbonyl stress levels are linked to DSPN and its progression, while methylglyoxal may be involved in the development of symptomatic DSPN entities with and without neuropathic pain, implying direct adverse effects on different types of sensory nerve fibers.DisclosureG.J. Bönhof: None. T.H. Fleming: None. G. Sipola: None. J. Szendroedi: Advisory Panel; Novo Nordisk, Lilly Diabetes, Novartis AG, Boehringer-Ingelheim. M. Roden: Research Support; Boehringer-Ingelheim. Advisory Panel; Echosens. Speaker's Bureau; Madrigal Pharmaceuticals, Inc. Advisory Panel; MSD Life Science Foundation. Board Member; Novo Nordisk. Advisory Panel; TARGET PharmaSolutions, Inc. D. Ziegler: Consultant; Wörwag. Speaker's Bureau; Viatris Inc. Consultant; Nevro Corp. Advisory Panel; Grünenthal. Speaker's Bureau; Sanofi-Aventis Deutschland GmbH, GlaxoSmithKline plc. Consultant; Procter & Gamble. A. Strom: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-245-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 246-OR: Single Nuclei Multiome Sequencing Reveals Subtype-Specific Changes
in Oligodendrocytes Imparted by the Metabolic Syndrome-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 246-OR
Abstract: Introduction and Objective: One in three adults in the United States suffer from the metabolic syndrome (MetS). MetS is associated with neurological complications including cognitive impairments (such as Alzheimer’s Disease and its related Dementias), especially when compounded with aging. However, the mechanisms linking MetS to cognitive impairment are not fully understood. In our project, we aimed to investigate the effects of midlife MetS on cognition and explore the underlying mechanisms linking MetS to cognitive impairment.Methods: We fed 52-week-old C57BL6/J mice standard diet (SD, 10% fat) or high fat diet (HFD, 60% fat) for 24 weeks followed by metabolic and cognitive phenotyping. Terminally, we isolated hippocampal nuclei to conduct single nuclei multiome sequencing, which includes single nuclei RNA sequencing (snRNA-seq) and transposase-accessible chromatin sequencing (snATAC-seq) to assess chromatin accessibility. We validated the discovered targets using IHC and RNAscope.Results: Mice on HFD experienced impaired glucose tolerance and decreased cognition compared to SD-fed mice. Multiome sequencing revealed 41 distinct cell clusters. Of note, neuronal cell clusters in HFD-fed mice showed perturbation of genes involved in synaptic transmission and neurodegeneration. Oligodendrocyte clusters showed differential expression of metabolic and inflammatory genes between HFD- and SD-fed mice. Interestingly, both RNAscope and IHC staining confirmed that oligodendrocyte MCT1 expression was downregulated in hippocampus of HFD mice compared to their SD counterparts, indicating an inhibition of oligodendrocyte-neuronal metabolic support.Conclusion: Collectively, our data indicate that MetS alters the oligodendrocytes epigenomics and transcriptomics in a cell subtype-specific manner suggesting that the metabolic support function of oligodendrocytes is compromised, likely contributing to cognitive impairment.DisclosureM.H. Noureldein: None. S. Elzinga: None. B. Kim: None. S. Teener: None. D.M. Rigan: None. J.M. Hayes: None. W. Rubin: None. V. Dolgachev: None. S.C. Parker: Research Support; Pfizer Inc. E.L. Feldman: None.FundingNIA K99/R00 Pathway to Independence (5K99AG081390)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-246-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 247-OR: Risk Factors for 30-Year Incidence of Two Peripheral Neuropathy
Phenotypes in Type 1 Diabetes (T1D)-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 247-OR
Abstract: Introduction and Objective: Distal symmetric polyneuropathy (DSP) and neuropathic pain (NP) are common T1D complications but data are limited on factors related to long-term risk. We thus aimed to identify factors associated with DSP and NP incidence in Epidemiology of Diabetes Complications (EDC) study of childhood-onset (<17 years) T1D in participants free of both at baseline (n=404, baseline mean age 25 years, T1D duration 17 years).Methods: DSP was defined as ≥2 of: neuropathy symptoms on exam, abnormal sensory exam, reduced tendon reflexes. NP was defined as burning, aching, or stabbing foot pain reported during exam or via MNSI questionnaire. Time-to-event analyses were performed separately for DSP and NP. Baseline risk factors associated at p < 0.1 were eligible for multivariable Cox models with backward selection.Results: Over 30 years, 221 (55%) developed DSP; 155 (38%) developed NP. HbA1c was a stronger risk factor for DSP; white blood cell count was stronger for NP (Table 1). T1D duration, age at T1D onset, hypertension, and height were only associated with DSP, while blood pressure medication, Non-HDLc, and lower education were associated with NP.Conclusion: Risk factors for DSP and NP differ in T1D. Aside from the NP-blood pressure medication association, which may reflect blood pressure severity, associations with Non-HDLc and white blood cells suggest a greater role for inflammation in NP than DSP.DisclosureJ. Zhou: None. T. Costacou: None. T.J. Orchard: None. R.G. Miller: None.FundingNational Institutes of Health (R01-DK034818), Rossi Memorial Fund
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-247-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 248-OR: Thyroid-Stimulating Hormone Aggravates Ferroptosis in Schwann
Cells via Suppression of the Nrf2/GPX4 Pathway—Implications for Diabetic
Peripheral Neuropathy-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 248-OR
Abstract: Introduction and Objective: Diabetic peripheral neuropathy (DPN) is a common and debilitating chronic complication of diabetes, characterized by Schwann cell injury, axonal degeneration, and neurovascular dysfunction. Recent studies suggest that elevated thyroid-stimulating hormone (TSH) levels are strongly associated with the progression of DPN, though the underlying mechanisms remain unclear. Ferroptosis, a regulated cell death driven by iron-dependent lipid peroxidation, may contribute to this process. This study explored the role of TSH in inducing ferroptosis in Schwann cells via the NRF2/GPX4 pathway.Methods: RSC96 Schwann cells were divided into four groups: control (CON), high glucose/palmitic acid (HG/PA), TSH treatment (TSH), and high glucose/palmitic acid with TSH (HG/PA+TSH). Transcriptomic sequencing was performed, and cell viability, proliferation, apoptosis, ROS levels, MDA, GSH, mitochondrial membrane potential (JC-1), and intracellular Fe2+ levels were assessed. Western blot analysis was conducted to evaluate changes in the NRF2/GPX4 pathway.Results: TSH with HG/PA reduced cell viability and proliferation, increased apoptosis, ROS levels, lipid peroxidation, and intracellular Fe2+, depleted GSH, and disrupted mitochondrial function. Transcriptomic analysis showed enrichment in lipid metabolism and oxidative stress pathways. Western blot revealed NRF2/GPX4 suppression.Conclusion: This study demonstrates that TSH induces ferroptosis in Schwann cells by suppressing the NRF2/GPX4 signaling pathway, thereby exacerbating oxidative stress, iron overload, and mitochondrial dysfunction. These findings provide novel insights into the mechanistic link between thyroid dysfunction and the pathogenesis of DPN and highlight potential therapeutic targets for protecting Schwann cells and mitigating disease progression in diabetes.DisclosureS. Fei: None. L. Guo: Research Support; Abbott, AstraZeneca, Bayer Pharmaceuticals, Inc, Eli Lilly and Company, Innovent Biologics, Merck & Co., Inc, MSD Life Science Foundation, Novo Nordisk A/S, Sanofi, Jiangsu Hengrui Pharmaceuticals Co., Ltd, Tonghua Dongbao. Q. Pan: None.FundingThe National Natural Science Foundation of China ( 82270881).
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-248-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 249-OR: Long Noncoding RNA in Mitochondrial Stability in Diabetic
Retinopathy-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 249-OR
Abstract: Introduction and Objective: Mitochondrial dysfunction plays a central role in diabetic retinopathy. Depending on the energy demand, mitochondria constantly fuse and divide, but in diabetic retinopathy, this process is impaired and Mfn2, a fusion gene, is downregulated due to its promoter DNA hypermethylation. Long noncoding RNAs (RNAs with >200 nucleotides) do not have open reading frame, but can regulate gene expression by interacting with DNA, RNA, and proteins. Many LncRNAs are aberrantly expressed in diabetes, and among those, MALAT1 is upregulated in the retina, altering expression of genes associated with inflammation. However, the role of MALAT1 in mitochondrial dynamics is not clear. Our aim was to investigate the role of MALAT1 in mitochondrial stability in diabetic retinopathy.Methods: Using MALAT1-siRNA transfected retinal endothelial cells incubated in 20mM D-glucose, Mfn2 expression (transcripts and protein), and its promoter DNA methylation (5-methyl cytosine by MeDIP) and GTPase activity were quantified. Mitochondrial integrity was evaluated by analyzing mitochondrial fragmentation (MitoTracker green staining), structure (electron microscopy and membrane potential), mtDNA damage (extended length PCR and nucleoids by SYBR green staining), and function (oxygen consumption rate by SeaHorse)Results: Compared to normal glucose, high glucose upregulated MALAT1 expression, and MALAT1-siRNA ameliorated glucose-induced decrease in Mfn2 expression, activity and its promoter DNA hypermethylation. MALAT1-siRNA also protected glucose-induced increase in mitochondrial fragmentation, structural and DNA damage and reduction in oxygen consumption rate.Conclusion: Upregulation of MALAT1 in hyperglycemia hypermethylates Mfn2 promoter DNA and downregulates its transcription, resulting in impaired mitochondrial dynamics, and structural, genomic and functional instability. This opens an avenue to target MALAT1 and restore mitochondrial integrity in diabetic retinopathy.DisclosureR. Kowluru: None. J. Kumar: None.FundingNIH (R01 EY333516)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-249-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 250-OR: Cytokines Differentially Alter Tight Junctional Proteins to
Increase Retinal Microvascular Endothelial Cell Permeability-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 250-OR
Abstract: Introduction and Objective: Inflammation is associated with progression of diabetic retinopathy (DR). Inflammatory cytokines tumor necrosis factor alpha (TNFα), interleukin-1β (IL-1β), and interleukin-6 (IL-6) are elevated in DR and trigger retinal microvascular leakage. RMEC tight junction complexes include the transmembrane proteins occludin and ZO-1. Diabetic relevant stimuli cause changes in occludin and ZO-1 localization and content. Our goal was to compare the effects of TNFα, IL-1β, and IL-6 on ZO-1 and occludin in RMECs and on RMEC permeability.Methods: Human RMECs (HRMECs) were treated with TNFα, or IL-1β, or IL-6 + soluble IL-6 receptor, or vehicle, and used to perform Western blotting for ZO-1 and Occludin. HRMECs treated as above were immunostained for ZO-1 and occludin and imaged at 40x with a confocal microscope. Transendothelial electrical resistance (TEER) of HRMEC monolayers treated as above was measured with the electrical cell-substrate impedance sensing (ECIS) method. Wild-type C57bl6 mice received intravitreal injections of TNFα, or IL-1β, or IL6 + soluble IL-6 receptor, or vehicle and quantitative fluorescein angiography (qFA) was performed to evaluate the effect of cytokines on retinal vascular permeability.Results: TNFα and IL-6 decreased the occludin protein content of HRMECs (TNFα: p= 0.0129, n=8, IL-6: p=0.0162, n=8) without changing the ZO-1 content (TNFα: p= 0.0724, n=8, IL-6: p=0.1706, n=8). IL-1β treatment decreased the ZO-1 protein content of HRMECs (p= 0.0174, n=8) but did not change the occludin protein content (p=0.6073, n=8). ECIS experiments showed decreased barrier resistance of HRMEC monolayers treated with TNFα, IL-1β, and IL-6. All 3 inflammatory cytokines induced retinal vascular hyperpermeability in vivo on qFA.Conclusion: TNFα, IL-1β, and IL-6 differentially alter HRMEC tight junctional complex proteins ZO-1 and occludin to increase retinal microvascular permeability.DisclosureI. De la Huerta: None.FundingNational Institutes of Health (EY032620)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-250-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 251-OR: Differential DNA Methylation Patterns in the Retina and White
Blood Cells Associated with Type 1 Diabetes and Retinopathy-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 251-OR
Abstract: Introduction and Objective: DNA methylation (DNAm) changes have been associated with diabetic retinopathy (DR), but primarily in circulating white blood cells (WBCs). It is critical to determine whether DNAm patterns in WBCs are reflective of those in the retina. We compared DNAm patterns in the retina and WBCs of same individuals of the Joslin Medalist Study with ≥50 years of type 1 diabetes (T1D), 35% with no-mild DR and 50% with severe DR.Methods: DNAm was assessed by whole genome bisulfite sequencing (WGBS, 32.8×coverage, Illumina NovaSeq) of retina and WBCs within the same individuals with no-mild or severe DR (n=5 per group). Retinal proteomics (mass spectrometry) was done in those with or without severe DR (n=10). Principal component analysis (PCA) and linear regression models adjusted by age and sex tested the differential DNAm patterns in severe DR vs. no-mild DR.Results: WGBS output a total of 105M CpG sites. There was dramatic differentiation of DNAm patterns between retina and WBCs on PCA. Within the retina or WBCs, there were clear differential DNAm patterns in people with DR vs. those without, with 487 and 1960 differentially methylated regions (DMR) in the retina and WBCs, respectively (Bonferroni p<1E-8), and 14 and 32 changed KEGG pathways (p<0.05). However, only 23-upregulated and 3-downregulated DMR-related genes and 6 pathways overlapped between retina and WBCs, suggesting DNAm patterns are significantly different between these tissues. In proteomics, 543 proteins were changed (p<0.05) in the retina comparing DR vs. no DR. Three upregulated and 15 downregulated protein targets overlapped with those detected by DMR analysis, some with essential functions in neurovascular retina.Conclusion: DNAm changes induced by T1D and associated with DR severity are very different between retina and leukocytes. Future epigenetic studies on DR need to use retina, rather than surrogate tissues.DisclosureM. Ma: None. S. Jangolla: None. H. Shah: None. K. Park: None. W. Fickweiler: None. J. Dreyfuss: None. H. Pan: None. I. Wu: None. J.K. Sun: Research Support; Optovue, Boehringer-Ingelheim. Other Relationship; Boehringer-Ingelheim. Research Support; Novo Nordisk, Roche Pharmaceuticals. Other Relationship; Roche Pharmaceuticals. Research Support; Physical Sciences, Inc, Boston Micromachines, Adaptive Sensory Technologies. L.P. Aiello: Consultant; Boehringer-Ingelheim, Ceramedix, Inc. Advisory Panel; Novo Nordisk. Stock/Shareholder; KalVista. G.L. King: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-251-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 252-OR: Associations of Serum Lipid Profiles with Diabetic Macular Edema
and Retinal Structural Alterations-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 252-OR
Abstract: Introduction and Objective: To explore the associations between serum lipid profiles and the severity of diabetic macular edema (DME), as well as its relationship with retinal structural alterations in patients with DME.Methods: A total of 275 type 2 diabetes mellitus (T2D) patients with diabetic retinopathy were included. Among them, 95 T2D patients with macular edema (DME group) and 190 T2D patients without macular edema (nDME group) were matched using propensity score matching (PSM). Basic parameters including gender, age, diabetes duration, neutrophil count, systemic immunoinflammatory index (SII), fasting blood glucose, HbA1c, triglycerides (TG), and triglyceride glucose index (TyG index) were collected. Ocular examinations including visual acuity, fundus photography, and OCT were performed. Multifactorial logistic regression was used to explore factors related to DME severity and retinal structural destruction in T2D patients.Results: The differences between neutrophil counts, lymphocyte counts, TG, TyG index, HDL cholesterol, LDL cholesterol, total cholesterol, direct bilirubin, and indirect bilirubin were statistically significant in both the DME and the nDME group (all p < 0.05). After adjusting for potential confounders including age, gender, HbA1c, diabetes duration and SBP, the association between high serum TG levels and the risk of DME remained significant (OR=3.79, 95% CI: 2.15-6.68, p < 0.001). TG and TyG index were significantly higher in the DRIL group than in the no DRIL group (TG: OR = 3.00, 95% CI: 1.60-5.60, p < 0.001; TyG: OR = 3.76, 95% CI: 1.80-7.86, p < 0.001).Conclusion: The association between serum TG levels and the risk of DME development remains significant after multivariable adjustment. High TG levels and high TyG index are associated with retinal inner layer structural abnormalities in DME. Further studies are needed to explore the potential of these lipid markers in predicting the progression of DME.DisclosureY. Wu: None. Z. Gu: None. M. Zhao: None. H. Zhang: None. S. Wang: None. L. Wang: None. X. Zheng: None. J. Weng: None. S. Luo: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-252-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 253-OR: Statin Prescriptions for Prevention of Atherosclerotic
Cardiovascular Disease in Adults 40–75 Years Old with Type 1 Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 253-OR
Abstract: Introduction and Objective: Guidelines recommend statins for prevention of ASCVD in adults 40-75 yrs old with diabetes. This study of real-world statin use in T1D investigates prescribing practices, disparities, and barriers.Methods: A retrospective cross-sectional study was performed in adults 40-75 yrs old with T1D who established with endocrinology (endo) at a large academic center from 2015-2018. Charts were reviewed for prescriptions as of December 2024.Results: We included 266 patients: 55.3% female (N=147), 80.8% (N=215) white, aged 54.4 ± 10.0 yrs with A1c 7.8 ± 1.6%. There were 21.1% (N=56) with prior ASCVD, of which 39.3% (N=22) were on high intensity statin. For primary prevention, 44.3% (N=93/210) were on moderate or high intensity statin. Overall, only 43.2% (N=115) were on guideline-directed statin intensity. Patients prescribed statin by endo (N=56) vs PCP/other provider (N=86) were more often on the recommended intensity (91.1% vs 74.4%, p=0.013). From endo notes, the main reason for statin under-treatment was deference to PCP/other provider in 23.3% (N=62), followed by intolerance in 15.8% (N=42). Women were less likely to get guideline-recommended statin (36.7% vs 51.3%, p=0.017). Endos were more likely to defer to other providers for statins in women (28.6% vs 16.8%, p=0.024) and there was a nonsignificant difference in statin intolerance by gender (18.4% vs 11.7%, p=0.138). Other LDL-lowering agents were rarely used: ezetimibe 4.1% (N=11), PCSK9-inhibitors 0.4% (N=1), and none on bempedoic acid.Conclusion: The majority of patients 40-75 yrs old with T1D are not on guideline-recommended statin therapy for primary nor secondary prevention of ASCVD. Particular disparity is noted for women. Coordination of statin ownership between providers is needed; patients would benefit from endo prescription of statins for greater guideline adherence. Statin intolerance is a barrier, yet other LDL-lowering medications are underutilized.DisclosureM.D. Lundholm: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-253-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 254-OR: GLP-1(32-36) Peptide Promotes Diabetic Ischemia Recovery through
Independent GLP-1R Pathway to Mediate Lipid Transport-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 254-OR
Abstract: Introduction and Objective: GLP-1(32-36), a major end-product of glucagon-like peptide 1 (GLP-1), improves diabetic limb ischemia in mice independent of its insulinotropic effect. However, the mechanisms underlying this effect and its relevance in human ischemic lesions remain unclear.Methods: We used single-cell transcriptomics on the plantar muscles of diabetic foot patients and healthy controls to investigate changes in lipid metabolism genes and pathways. We also applied cellular and spatial metabolomics to evaluate the impact of GLP-1(32-36) on lipid metabolism and lipid accumulation in the gastrocnemius microvasculature in diabetic mice. Adenovirus and lentivirus were used for gene silencing in vivo and in vitro, respectively. Cross orthogonal coupling was employed for drug modification of GLP-1(32-36).Results: High glucose induces lipid metabolism dysregulation in endothelial cells (ECs) and in diabetic mice with limb ischemia. GLP-1(32-36) binds atrial natriuretic peptide receptor A (NPRA) to regulate cholesterol transport via oxysterol-binding protein (OSBP), promoting blood flow in ischemic limbs. NPRA knockdown inhibited GLP-1(32-36)’s pro-angiogenic effects, independent of the GLP-1 receptor (GLP-1R). Single-cell RNA sequencing (scRNA seq) revealed lipid metabolism dysregulation in capillary ECs of diabetic foot patients. To prolong GLP-1(32-36)’s half-life, we synthesized the ROS-responsive prodrug tEC-cRGD-(32-36) for EC-specific delivery, enhancing blood flow recovery and reducing lipid droplet formation.Conclusion: Our findings demonstrate that GLP-1(32-36) regulates lipid metabolism via the NPRA-OSBP axis to alleviate endothelial dysfunction and promote diabetic ischemic recovery, supporting the development of EC-targeting GLP-1(32-36) for treating diabetic ischemia.DisclosureY. Zhang: None. S. Wang: None. Q. Zhou: None. C. Zheng: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-254-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 255-OR: Therapeutic Potential of Intestinal Epithelial Organoids–Derived
Exosomes in Ameliorating Steatohepatitis-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 255-OR
Abstract: Introduction and Objective: Non-alcoholic steatohepatitis is a prevalent metabolic liver disease with limited therapeutic options. This study aimed to investigate the therapeutic potential of intestinal epithelial organoid (IEO)-derived exosomes in treating steatohepatitis.Methods: IEOs were generated from the small intestinal tissue of eight-week-old C57BL/6 mice, and exosomes were isolated from IEO culture supernatants. Human hepatoma HepG2 cells were treated with IEO-derived exosomes and palmitic acid (PA). Additionally, the role of IEO-derived exosomes in macrophages-mediated inflammation was evaluated using human leukemia THP-1 cells treated with PA and lipopolysaccharide (LPS), a model for macrophage-mediated inflammation in steatohepatitis. Experimental analyses included cell viability assays (CCK-8), lipid accumulation assessments (triglycerides content and Oil Red O staining), and quantitative PCR for fibrosis and inflammatory markers.Results: IEO-derived exosome treatment significantly attenuated PA-treated cell death in HepG2 cells, thereby enhancing cell viability. Oil Red O staining and TG content revealed that IEO-derived exosomes significantly attenuated lipotoxicity-induced lipid accumulation in hepatocytes. mRNA expression of fibrosis markers (COL1A1, ACTA2) and inflammatory markers (NLRP3, TNF-α) was significantly downregulated in PA-treated HepG2 cells following exosome treatment. In PA+LPS-treated THP-1 cells, IEO-derived exosomes also reduced the expression of inflammatory cytokines (TNF-α, IL-6, IL-8, CXCL10, and IL-1β) and fibrosis markers (COL1A1, TGF- β1).Conclusion: These findings demonstrate that IEO-derived exosomes attenuate lipotoxicity-induced steatosis, fibrosis, and macrophage-mediated inflammation, highlighting their therapeutic potential for steatohepatitis through modulation of gut-liver axis crosstalk.DisclosureS. Hahn: None. J. Kim: None. G. Kim: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-255-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 256-OR: Omega-6 Fatty Acids in Neonatal Life—Impairing Adipocyte
Metabolism by Programing Adipocyte Stem-Like Cells through NR2F2
Suppression-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 256-OR
Abstract: Introduction and Objective: The Developmental Origins of Health and Disease (DOHaD) hypothesis posits that early-life nutritional exposures shape long-term metabolic health. Here, we show that perinatal excess n6-FA exposure programs neonatal Adipocyte Stem-like Cells (ASCs) toward a lipogenic, metabolically inflexible phenotype, increasing susceptibility to obesity later in life. We hypothesize that n6-FA suppression of NR2F2 underlies these effects.Methods: C57BL/6J dams were provided an n6-FA rich or a balanced n6/n3 (control) diet at pairing. Offspring were evaluated at postnatal day 12 for whole-body metabolic responses, adipose morphology, cellular metabolism, and molecular signatures. ASCs were isolated, and NR2F2 expression was manipulated to assess its role in adipocyte metabolic programming. Metabolic, proteomic, and transcriptomic analyses were conducted.Results: Perinatal high n6-FA exposure reduced fatty acid oxidation (FAO) in both ASC-derived adipocytes and whole-body metabolism, accompanied by mitochondrial dysfunction, increased lipogenesis, and suppressed thermogenic adipocyte markers. Morphological changes included adipocyte hypertrophy, increased triglyceride storage, and greater body fat in exposed pups. Mechanistically, n6-FA exposure suppressed NR2F2 expression in ASCs. ASC-specific deletion of NR2F2 recapitulated the metabolic impairments observed with n6-FA exposure, including reduced fatty acid oxidation and thermogenic gene expression. Conversely, transient activation of NR2F2 in n6-FA-exposed ASCs restored FAO by activating the PPARγ-PGC1α axis and upregulating mitochondrial respiratory chain components.Conclusion: These findings establish NR2F2 as a central regulator of ASC metabolic programming, revealing how early-life n6-FA exposure promotes a pro-adipogenic, metabolically inflexible phenotype. Our study highlights NR2F2 as a potential therapeutic target for mitigating obesity and associated metabolic disorders.DisclosureS. Das: None. R. Varshney: None. G. Kyere-Davies: None. A.E. Martinez: None. K.B. Hill: None. M. Kinter: None. G.P. Mullen: None. M. Rudolph: None.FundingThe Oklahoma Center for Adult Stem Cell Research, Presbyterian Health Foundation Bridge Fund, College of Medicine Alumni Association Support, IDeA National Resource for Quantitative Proteomics (R24GM137786); Oklahoma INBRE (P20GM103447)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-256-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 258-OR: Perioperative Glucose Management and Amputation Outcomes
-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 258-OR
Abstract: Introduction and Objective: Patients with diabetes have a 15-34% lifetime risk of foot ulcerations and complications from these ulcers are a leading cause of nontraumatic amputations in the United States. Elevated perioperative glucose (>140 mg/dL or A1c ≥8%) is associated with complications in elective surgeries, but limited data exists on its impact on nonelective amputations. This study aims to assess the effect of perioperative glucose levels on outcomes in patients with diabetes undergoing lower extremity amputations after infectious cases.Methods: This two-year retrospective chart review at a large tertiary health system identified 186 patients who underwent lower extremity amputations between January 1, 2021, and December 31, 2022. Glucose levels were measured preoperatively (120-30 minutes before incision), intraoperatively, and postoperatively (30-120 minutes after surgery). Non-eligible patients included non-diabetic related amputations, incomplete follow-up (<6 months), and missing glucose measurements. Outcomes such as healing time, postoperative infection, and hospital readmissions were assessed.Results: 65 patients met eligibility. Postoperative glucose >180 mg/dL significantly delayed healing by ~ 1.6 weeks (p= 0.0255). Healing time was also influenced by amputation level, with transmetatarsal amputations delaying healing by ~ 2.9 weeks (p<0.001). Postoperative infection and peripheral arterial disease (PAD) added ~2.1 weeks (p <0.001) and ~ 1.6 weeks (p = 0.0046) respectively to the average healing time. A1c levels and preoperative glucose levels were non-significant.Conclusion: Postoperative glucose levels >180 mg/dL delayed healing in diabetic patients undergoing amputations. Healing time was also influenced by amputation level, post operative infection, and PAD. These findings emphasize tight perioperative glucose control and lay the groundwork for future research to optimize glucose management in high-risk procedures.DisclosureC. Girgis: None. S. Behme: None. I. Gaynanova: None. B.M. Schmidt: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-258-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 259-OR: Evaluating Diabetic Foot Ulcer Recognition Algorithms for Patients
of Color-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 259-OR
Abstract: Introduction and Objective: Computer vision offers an opportunity to automatically analyze foot images to segment diabetic foot ulcers (DFU) and determine clinically relevant characteristics. Although diabetic foot complications take a disproportionate toll on communities of color, these communities are underrepresented in dermatologic image datasets, which may propagate health disparities. Are current state-of-the-art foot ulcer recognition algorithms effective for Black patients living with diabetes (compared to patients with white or pale skin)'Methods: We collected the first known repository of DFU images from patients of color. We train and evaluate five state-of-the-art foot ulcer segmentation models (HarDNet-DFUS, Mask R-CNN, MobileNetV2, U-Net, SegNet) on our dataset, and compare to metrics reported for white or pale skin.Results: Our dataset consists of 3,483 foot images (including 1,652 instances of a DFU or pre-ulcerative lesion) from 248 patients. Images were collected from a diabetes clinic in a safety net hospital in the Southern United States and patients were predominantly (over 80%) Black. The five state-of-the-art ulcer recognition models result in insufficient performance on this new dataset. The best performing baseline model (Mask R-CNN) has been reported to achieve a Dice score (i.e., similarity coefficient indicative of model performance) of 90.2% on a dataset of foot images collected from white patients but achieves a Dice score of only 37.4% on our dataset.Conclusion: Current ulcer recognition models provide lower performance on wound images collected from patients of color. Larger, more diverse datasets will be crucial for the next generation of recognition models. Our work supports more equitable technological interventions for diabetic foot care to improve patient self-monitoring and clinician delivery of care for communities of color. As automated wound recognition may improve clinician delivery of care, it is vital to advance equity for those who face the greatest disease burden.DisclosureC. Baseman: None. Z. Leng: None. T. Ploetz: None. G. Santamarina: None. M.C. Schechter: None. M. Fayfman: Research Support; Abbott, Dexcom, Inc. R.I. Arriaga: None.FundingAmerican Diabetes Association (11-22-ICTSHD-09)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-259-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 260-OR: Differential Effect of GLP-1RA and SGLT2 Inhibitors on Lower
Extremity Amputation Outcomes in Type 2 Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 260-OR
Abstract: Introduction and Objective: Patients with diabetes mellitus are at increased risk of lower extremity amputations (LEAs), a severe complication affecting morbidity and quality of life. This study evaluates the association between glucagon-like peptide-1 receptor agonists (GLP-1 RA) versus sodium-glucose cotransporter-2 inhibitors (SGLT2i) and risk of LEAs in patients with type 2 diabetes (T2D).Methods: We conducted a retrospective cohort study using TriNetX, a federated electronic health records network, including adults with T2D who initiated GLP-1 RA or SGLT2i after May 2013. Outcomes included incident diabetic foot ulcer (DFU), major LEA, and minor LEA. Propensity score matching (1:1 ratio) adjusted for demographics, comorbidities, medications, and laboratory values. Results were reported as hazard ratio (HR) with 95% confidence intervals (CIs).Results: The matched cohort included 106,649 patients receiving GLP-1 RA and 106,649 patients receiving SGLT2i. Compared with SGLT2i, GLP-1 RA cohort was associated with a lower risk of major (HR 0.73, 95% CI 0.60-0.90) and minor LEA (HR 0.86, 95% CI 0.74-0.99) at 3 years, but no differences in DFU risk.Conclusion: In this real-world study, GLP-1 RA treatment was linked to a reduced risk of amputations compared with SGLT2i in T2D. Prospective studies are needed to confirm these findings and guide glucose-lowering therapy for at-risk patients.DisclosureA.T. Hong: None. I.Y. Luu: None. F. Lin: None. L. Shin: None. C. Hsu: None. D.G. Armstrong: None. T. Tan: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-260-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 261-OR: Validation of Mitraa, a GPT-Based Conversational Model for
Enhancing Diabetes Self-Management and Education-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 261-OR
Abstract: Introduction and Objective: The growing prevalence of diabetes underscores the need for scalable, patient-centric tools to support diabetes self-management and education (DSME). Mitraa, a GPT-based conversational AI model, was developed to provide personalized diabetes care, including guidance on nutrition, medication adherence, glucose monitoring, and lifestyle adjustments. This study validates Mitraa’s effectiveness in delivering accurate, patient-relevant recommendations compared to certified diabetes educators (CDEs).Methods: A cohort of 250 adults with diabetes (both Type 1 and Type 2) participated in a validation study. Participants interacted with Mitraa and a certified diabetes educator on identical scenarios covering glucose management, dietary advice, and medication adjustments. The accuracy of Mitraa’s responses was assessed using a predefined scoring rubric (accuracy, relevance, and safety) by an independent panel of diabetes specialists. Secondary outcomes included patient satisfaction, usability (via System Usability Scale, SUS), and comprehension of provided recommendations.Results: Mitraa achieved an 89% accuracy score in providing safe and clinically relevant recommendations, comparable to CDEs (92%, p=0.08). Patient satisfaction with Mitraa was high, with a mean SUS score of 82. Time efficiency was superior with Mitraa, reducing interaction time by 35% compared to CDE consultations. Additionally, 95% of participants reported understanding Mitraa’s recommendations, indicating its suitability for patient education. Feedback highlighted Mitraa’s empathetic tone and adaptability to diverse cultural contexts as strengths.Conclusion: Mitraa demonstrates high accuracy, usability, and patient satisfaction in supporting diabetes management. Its scalability and cost-effectiveness position it as a promising adjunct to healthcare providers in delivering DSME. Further integration with electronic medical records and real-time glucose data could enhance its clinical utility.DisclosureB. Saboo: None. S. Saboo: None. H.A. Hirani: None. A.D. Modi: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-261-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 262-OR: A Digital Health Study—The Quality of TikTok-Based Diabetes
Self-Management Education in English and Spanish-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 262-OR
Abstract: Introduction and Objective: Overcoming limited reach with traditional in-person diabetes education, social media platforms are becoming popular sources for self-management information. This study evaluated TikTok videos on Type 2 Diabetes (T2DM) self-management to assess the quality of the information provided and determine whether the content aligns with the Association of Diabetes Care & Education Specialists’ 7 key areas of diabetes self-care (ADCES7).Methods: We analyzed top TikTok videos under popular diabetes-related hashtags in English and Spanish (N = 300) using the Global Quality Scale (GQS), ranging from 1 (poor) to 5 (excellent), based on the content creator—healthcare professionals, personal accounts, or companies. We further examined the extent to which the videos incorporated the ADCES7 behaviors.Results: Results showed significant differences in GQS scores by source (F(2, 297) = 12.93, p <.001). Videos posted by healthcare professionals (M = 2.63+0.80) had significantly higher GQS scores compared to personal accounts (M = 2.22+0.82, p <.001) and companies (M = 2.07+0.82, p <.001). However, the overall mean GQS score was low (M = 2.32; range: 2.00 to 2.67), with only 4% exceeding a score of four (4). “Healthy eating” was the most discussed ADCES7 behavior (61%), while “problem-solving” and “healthy coping” were the least mentioned.Conclusion: Future studies should investigate ways to improve the quality of diabetes information in social media, as it is crucial to prioritize accurate, evidence-based information. Collaboration with healthcare professionals may benefit the efforts to ensure high-quality content across social media platforms.DisclosureL. Diaz: None. D.A. Tolentino: None. S.E. Choi: None.FundingGraduate Student Research Mentorship (UCLA)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-262-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 263-OR: Impact of Pharmacist-Led Digital Education Program on Diabetes
Medication Adherence—A Large-Scale Retrospective Cohort Study in Japan-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 263-OR
Abstract: Introduction and Objective: Medication adherence is critical for glycemic control in diabetes, but is limited by provider workload. This study evaluated the impact of pharmacist-delivered digital education on medication adherence.Methods: A retrospective cohort study using data from Japanese pharmacies (July-December 2023) via the electronic medication history system Musubi (KAKEHASHI Inc.) for diabetes patients. Medication counseling included optional Health Advice (HA), digital content based on the Health Belief Model displayed on digital device via Musubi. Patients were divided into HA and non-HA groups. Propensity score matching was used to adjust for background differences. Primary outcome was the proportion of days covered (PDC) over 180 days as medication adherence, analyzed using multilevel logistic regression analysis for PDC ≥ 80%.Results: Of 399,022 patients, 45,721 were matched in each group, confirming similar backgrounds by standardized mean differences. HA was a significant independent factor for PDC ≥ 80% (OR 1.98 [95% CI 1.88-2.08]) (Figure). Antihypertensive and antihyperlipidemic medications were also significant factors.Conclusion: Pharmacist-led counseling using digital content may improve medication adherence in diabetes, supporting standardization and broader implementation.DisclosureM. Sakamoto: None. T. Saika: Employee; KAKEHASHI Inc. S. Shimayoshi: Employee; KAKEHASHI Inc. M. Yamazaki: Employee; KAKEHASHI Inc. T. Takebe: Employee; KAKEHASHI Inc. S. Ikeda: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-263-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 264-OR: Carbohydrate Nutritional Knowledge and Diabetes Outcomes According
to Different Mode of Insulin Administration in Patients Living with Type 1
Diabetes from the French SFDT1 Cohort-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 264-OR
Abstract: Introduction and Objective: Carbohydrate counting is essential for determining prandial insulin doses and is, therefore, a key component of education for patients with type 1 diabetes (T1D). This study aimed to evaluate the relationship between carbohydrate knowledge and glycemic control in T1D patients according to different treatment options.Methods: Carbohydrate knowledge was assessed using GluciQuizz, a validated self-administered questionnaire totaling 36 points [(1,2)], and exploring five domains: carbohydrate recognition, carb-counting in simple foods, label reading, hypoglycemia management, and meal carb-counting. The questionnaire was submitted to participants in the SFDT1 cohort. Glycemic control was determined using time in range (TIR) during the 14 days preceding questionnaire completion. Linear regression was performed to assess the association between carbohydrate knowledge and glycemic control.Results: The median age of the 656 participants was 43 [IQR 32-54] years, with a T1D duration of 25 [14-36] years. The median total GluciQuizz score was 26 [23-28] in the overall sample: 24 [21-27] among the 158 participants treated with multiple daily injections (MDI), 25 [22-27] among the 261 users of continuous subcutaneous insulin infusion (CSII), and 26 [25-28] among the 237 users of automated insulin delivery (AID) systems. Median TIR (in %) was as follows: overall 68 [55-77]; MDI 60 [49-72]; CSII 60 [49-72]; AID 75.5 [69-82.2].The total GluciQuizz score was positively associated with TIR in the overall population (β ± SE = 0.04 ± 0.01; p < 0.001). This association was observed in the CSII subgroup (β ± SE = 0.04 ± 0.01; p = 0.004) but not in the MDI (p > 0.9) or AID (p = 0.29) subgroups.Conclusion: Better carbohydrate knowledge is associated with improved glycemic control in T1D patients using CSII but not in those using MDI or AID systems.DisclosureS. Tatulashvili: None. J. Riveline: Consultant; Abbott, Lilly Diabetes, Novo Nordisk, Sanofi, Dexcom, Inc., Air Liquide, Insulet Corporation. Research Support; Tandem Diabetes Care, Inc, Juvenile Diabetes Research Foundation (JDRF). M. Joubert: Board Member; Abbott, Medtronic, Insulet Corporation, Dexcom, Inc., Ypsomed AG, Lilly Diabetes, Novo Nordisk, Sanofi. E. Cosson: Board Member; Abbott Diagnostics, Amgen Inc, Bayer Pharmaceuticals, Inc, Boehringer-Ingelheim, Dexcom, Inc., Lilly Diabetes, Medtronic, Novartis AG, Novo Nordisk, Roche Diagnostics, Sanofi.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-264-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 265-OR: Exercise-Induced Lactylation of WDR41 Initiates Autophagy and
Improves MASLD-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 265-OR
Abstract: Introduction and Objective: A sedentary lifestyle is associated with diabetes and MASLD (metabolic dysfunction-associated steatotic liver disease), but the causal mechanisms and preventive methods are not fully understood. Autophagy is a lysosomal degradation pathway robustly induced by physical exercise. This study is to determine how exercise activates autophagy systemically, and whether exercise-induced autophagy regulates hepatic glucose and lipid metabolism and plays a preventative role against MASLD.Methods: Animal exercise was carried out using a mouse treadmill. WDR41-depleted cells and mice, and cells expressing the WDR41 loss-of-lactylation mutant (WDR41K319R), were used to study the role and mechanism of WDR41 lactylation in autophagy activation and glucose and lipid metabolism. Liver samples from patients with MASLD, MASH or cirrhosis were collected and analyzed for expression and lactylation levels of WDR41. Statistical analysis was performed using one-way or two-way ANOVA with Tukey-Kramer test.Results: Via a proteomic screen we identified WDR41 as a pro-autophagy protein that undergoes lactylation under autophagy-inducing conditions, such as exercise. WDR41 is lactylated at lysine (K) 319, and lactylated WDR41 promotes autophagy initiation by directly binding to the autophagy proteins ATG13 and FIP200 and driving the ULK1 kinase complex assembly. Physiologically, WDR41, and WDR41 K319 lactylation, is essential for exercise-induced improvements in insulin sensitivity and lipid metabolism against excess lipid accumulation in the liver. A negative correlation between expression and lactylation of WDR41 was also discovered in patients with various hepatic metabolic dysfunctions.Conclusion: Exercise-induced WDR41 lactylation at K319 is an important regulatory mechanism by which exercise regulates autophagy and hepatic glucose and lipid metabolism. Lactylated WDR41 is a key player and potentially a biomarker of the pathogenesis of diabetes and MASLD.DisclosureC. He: None.FundingNational Institutes of Health (R01 DK123447)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-265-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 266-OR: Blood-Flow Restriction Resistance Training Improves Muscle
Mitochondrial Function in Type 2 Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 266-OR
Abstract: Introduction and Objective: Impaired muscle strength and mitochondrial function are hallmarks of type 2 diabetes (T2D). While classical resistance training (CT) enhances muscle strength, effects on mitochondrial function are less studied. Low-load blood flow restriction training (BFRT) may, by enhancing metabolic stress, confer comparable hypertrophic benefits and potentially improve mitochondrial function. This study aims to compare performance and metabolic effects of BFRT compared to CT in individuals with type 2 diabetes (T2D).Methods: Sedentary individuals with T2D matched for age and BMI allocated to either BFRT (n=10, 10% female) or CT (n=10, 30% female) completed a 12-week, thrice weekly supervised training and underwent comprehensive phenotyping including hyperinsulinemic-euglycemic clamps and body composition measurement by magnetic resonance imaging. Muscle strength was assessed by dynamometry and mitochondrial function by high-resolution respirometry from vastus lateralis and subcutaneous adipose tissue biopsies before and 72 hours after the last training session.Results: Both CT and BRFT decreased diastolic blood pressure and resting heart rate, but enhanced muscle cross sectional area (all p<0.05) and isometric leg strength (30% vs. 19%, both p<0.01). CT decreased whole-body adipose tissue volumes by 5%, while BFRT selectively reduced visceral adipose tissue by 13% (both p<0.05). Only BFRT raised muscle mitochondrial content as well as muscle and adipose ADP sensitivity (all p<0.01). Of note, neither CT nor BRFT significantly affected glycemia and insulinemia.Conclusion: In conclusion, both forms of resistance training effectively improve muscle quality and cardiovascular risk factors in T2D. However, BFRT uniquely enhances muscle and adipose tissue mitochondrial functionality. These findings suggest that BFRT may be an effective alternative to CT for improving mitochondrial function and muscle mass in individuals with T2D.DisclosureN. Trinks: None. S. Gancheva: None. M. Schön: None. K. Pafili: None. L. Mastrototaro: None. C. Herder: None. K. Strassburger: None. O.P. Zaharia: None. S. Trenkamp: None. V. Schrauwen-Hinderling: None. M. Roden: Research Support; Boehringer-Ingelheim. Advisory Panel; Echosens. Speaker's Bureau; Madrigal Pharmaceuticals, Inc. Advisory Panel; MSD Life Science Foundation. Board Member; Novo Nordisk. Advisory Panel; TARGET PharmaSolutions, Inc. D. Pesta: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-266-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 267-OR: Acute Effects of Resistance Exercise on Blood Glucose Levels in
Postmenopausal Females with Type 1 Diabetes—A Pilot Study-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 267-OR
Abstract: Introduction and Objective: Post-menopausal females with type 1 diabetes (PFT1D) are at elevated risk of cardiovascular disease, osteoporosis, and frailty. In other populations, resistance exercise (RE) reduces these risks, but its safety for PFT1D remains unexplored. We compared the glycemic effects of high-repetition/low resistance exercise (HL), or moderate-repetition/moderate resistance exercise (MM) in PFT1D.Methods: We compared capillary blood glucose concentrations (BG) before, during, and after RE between HL (3 sets of 16 repetitions at 40% 1 repetition maximum [1RM]) and MM (3 sets of 8 repetitions at 80% 1RM) across 7 exercises targeting all major muscle groups. MM and HL were matched for total exercise volume, completed post-prandially at 4:00pm, at least 72 hours apart, in a randomized order, with similar food intake.Results: Seven PFT1D (mean±SD: age 58±6 years, diabetes duration 28±19 years, HbA1C 7.3±0.7%) completed both HL and MM. Average BG (mmol/L) was 7.1±0.9 (HL) and 7.7±1.1 (MM) before exercise, 6.8±2.1 (HL) and 7.0±0.7 (MM) after exercise, and 6.8±2.6 (HL) and 7.7±1.8 (MM) one hour after exercise. There were no differences in BG or in BG changes between HL and MM. No BG readings < 4.0mmol/L (hypoglycemic) were measured during or in the hour following exercise. According to continuous glucose monitor data, participants spent little time in hypoglycemia (BG < 3.9mmol/L) overnight (HL: 0.9%, MM: 2.5%, p=0.18) and in the 24 hours following RE (HL: 0.8%, MM: 1.1%, p=0.31). In qualitative interviews, participants indicated a strong interest in longer-term training studies, with their largest barriers to participation being time and motivation.Conclusion: BG responses to HL and MM were similar and participants maintained safe BG levels during and after both sessions. RE should cause a safe glycemic profile for PFT1D for future long-term training to test the impacts on HbA1C, bone mineral density, muscle mass, and overall long-term health.DisclosureJ.E. Logan: None. Z. Momeni: None. N.G. Boulé: Research Support; Roche Diabetes Care, Dexcom, Inc. J.E. Yardley: Research Support; Diabetes Canada, Canadian Institutes of Health Research. Speaker's Bureau; Dexcom, Inc.FundingAlberta Diabetes Institute
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-267-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 268-OR: Modeling Metabolic Changes in Glucose Physiology during Physical
Activity in T1D-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 268-OR
Abstract: Introduction and Objective: In individuals with T1D, increased change in CGM (ΔG) is common during physical activity (PA) due to 3 main factors: impaired endogenous glucose production (ΔGegp), increased insulin-dependent glucose utilization (ΔGid), and increased insulin-independent glucose clearance (ΔGii) by skeletal muscles. To understand how the factors affect ΔG during PA, we identify a data-driven weighted sum model using the 4 most common PAs from the T1DEXI dataset.Methods: To account for glucose dynamics with a scalar value, we used the glucose area under the curve (AUC) of ΔG of each component. We estimated the 3 component weights by minimizing the difference between the sum of the 3 AUCs and the measured total AUC of ΔG. For identification, we used PA sessions with positive net insulin on board (netIOB) at PA onset, where netIOB was defined as the changes in insulin delivery relative to the basal rate.Results: We used 175 sessions of strength training, 201 biking, 123 jogging, and 515 walking. For small netIOB at the PA onset, ΔGii is predominant over the ΔGid, while ΔGii becomes more pronounced for increasing netIOB (Fig. 1). For PA >120 min, both ΔGii and ΔGid heavily contributed to overall ΔG for increasing netIOB. ΔGegp was much smaller than ΔGii or ΔGid.Conclusion: The proposed model constitutes a tool to reproduce real-life scenarios in simulation and is appealing for control design due to its simplicity.Disclosure E. Aiello: Research Support; Hemsley Charitable Trust. K. Tang: Research Support; Hemsley Charitable Trust. M.P. Dhaliwal: Research Support; Hemsley Charitable Trust. R. Lal: Consultant; Abbott, Biolinq, Capillary Biomedical, Inc, Gluroo, PhysioLogic Devices, Portal Insulin, Sanofi, Tidepool. Advisory Panel; Provention Bio, Inc, Provention Bio, Inc, Microbion, Microbion, Lilly Diabetes. Research Support; Insulet Corporation, Medtronic, Tandem Diabetes Care, Inc, Sinocare Inc. C. Summers: Consultant; Tidepool. M. Connolly: Employee; Tidepool. D.P. Zaharieva: Research Support; Hemsley Charitable Trust. Speaker's Bureau; Dexcom, Inc. Research Support; Insulet Corporation, International Society for Pediatric and Adolescent Diabetes. B. Arbiter: Stock/Shareholder; Eli Lilly and Company, Dexcom, Inc. Employee; Tidepool. K. Watson: Employee; Tidepool. M. Friedman: None. L. Figg: None. A.L. Cortes-Navarro: None. I. Balistreri: None. R.S. Kingman: None. B. Suh: None. M.C. Riddell: Advisory Panel; Zucara Therapeutics, embecta. Consultant; Dexcom, Inc., Insulet Corporation, Eli Lilly and Company, Novo Nordisk. Speaker's Bureau; Novo Nordisk, Dexcom, Inc., Sanofi, Eli Lilly and Company. Stock/Shareholder; Zucara Therapeutics. Research Support; Dexcom, Inc., Insulet Corporation, Eli Lilly and Company. Y. Qin: None.FundingThe Leona M. & Harry B. Helmsley Charitable Trust Grant (2404-06905)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-268-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 269-OR: Glucagon Antagonism Improves Insulin Sensitivity and Increases
Lean Body Mass in Patients with Type 1 Diabetes—A Twelve-Week
Double-Blind, Randomized, Placebo-Controlled Trial-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 269-OR
Abstract: Introduction and Objective: Glucagon has underappreciated effects on lipid, glucose, and amino acid metabolism. This study aimed to assess the comprehensive metabolic effects of glucagon antagonism in type 1 diabetes (T1D).Methods: 30 adults with T1D were randomized 1:1 to receive the glucagon receptor antagonist (GRA) volagidemab via once weekly subq injection for 12 weeks vs. placebo. A 2-stage hyperinsulinemic-euglycemic clamp (8 and 40 mU/m2/min) with indirect calorimetry was conducted at baseline and after 12-weeks to determine changes in insulin sensitivity and substrate oxidation.Results: GRA therapy decreased exogenous insulin use by 16% while maintaining glucose control (no Δ in A1c or CGM metrics). Compared to baseline, GRA decreased circulating FFA concentrations by 30% in the fasting state and 39% in the 1st stage of the insulin clamp, suggesting an increase in adipose tissue insulin sensitivity (p < 0.05). During the high dose step of the clamp, which is representative of skeletal muscle insulin action, glucose disposal increased by 33% (p = 0.052) and respiratory quotient by indirect calorimetry increased by 5% (p = 0.013). Thus, GRA therapy significantly increased glucose utilization and showed a strong trend toward improving skeletal muscle insulin sensitivity. Finally, bioimpedance data showed a significant increase in lean body mass of 1.5 kg after GRA therapy (p < 0.001) with no change in total body weight. As a potential explanation for this finding, GRA therapy significantly increased circulating amino acid concentrations (~2-fold) which may provide additional substrate for muscle tissue synthesis.Conclusion: GRA therapy decreased lipolysis, improved peripheral glucose disposal, increased glucose oxidation, and increased lean body mass. These data highlight the profound effects that glucagon action has on multiple aspects of metabolism that extend far beyond glucose control.Disclosure S.C. Boeder: Consultant; Cecelia Health. Advisory Panel; Novo Nordisk. Consultant; Lexicon Pharmaceuticals, Inc, Persperion Diagnostics. Research Support; Eli Lilly and Company, Carmot Therapeutics, Inc, REMD Therapeutics, Dexcom, Inc., Lexicon Pharmaceuticals, Inc. R.L. Thomas: Research Support; REMD Therapeutics, Carmot Therapeutics. V. Hamidi: None. E.R. Giovannetti: Advisory Panel; Eli Lilly and Company, Sanofi. A. Armstrong: None. L. Carter: None. T.P. Ciaraldi: None. J.H. Pettus: None.FundingBreakthrough T1D and the Helmsley Charitable Trust (3-SRA-2021-1066-M-B)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-269-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 270-OR: Risk of Severe Hypoglycemia Associated with Concomitant Use of
Sulfonylurea and Amiodarone-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 270-OR
Abstract: Introduction and Objective: Sulfonylureas (SU), commonly used for type 2 diabetes, are metabolized by liver cytochrome P450 2C9 (CYP 2C9), which is inhibited by amiodarone. Given their frequent co-administration in patients with diabetes and arrhythmia, we evaluated the risk of severe hypoglycemia associated with their concomitant use.Methods: Using South Korean health insurance claims data (2010-2022), we identified cohorts of adult patients with type 2 diabetes aged ≥18 years. These patients initiated antiarrhythmic drugs, either amiodarone or other antiarrhythmics (flecainide, sotalol, and propafenone), while on SU. The risk of severe hypoglycemia was evaluated using hazard ratios (HR) with 95% confidence intervals (CI). Propensity-score matching weights were applied to ensure balance between groups.Results: Among 26,611 patients, 20,756 (78.0%) initiated amiodarone (mean age 71.3 years, 61% male), and 5,855 (22.0%) initiated other antiarrhythmics (mean age 68.7 years, 56% male). The weighted HR for severe hypoglycemia associated with amiodarone was 1.68 (95% CI 1.14-2.48). This increased risk remained consistent across various sensitivity analyses.Conclusion: Initiation of amiodarone while on sulfonylureas was associated with an increased risk of hypoglycemia, warranting attention and monitoring when sulfonylureas and amiodarone are used concomitantly.DisclosureS. Bea: None. H. Lee: None. K. Bykov: None. J. Shin: None.FundingAmerican Diabetes Association (1-25-PDF-66); National Institutes of Health (K01AG068365)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-270-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 271-OR: Randomized Phase 1 Single-Ascending Dose Study of ENT-03 in
Healthy Obese Subjects and Subjects with Type 2 Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 271-OR
Abstract: Introduction and Objective: Although GLP-1 agonists show efficacy treating obesity and T2D, significant side effects and high discontinuation rates occur. Drugs with different mechanisms of actions are needed for mono- and combination therapy. ENT-03 is a subcutaneously administered aminosterol antagonist of PTP1B that acts in the hypothalamus to decrease weight.Methods: This was a first-in-human, randomized, placebo-controlled Phase 1a study to evaluate the safety, tolerability, and pharmacokinetics and pharmacodynamic profile of single doses of ENT-03 from 3.0 mg to 75 mg in healthy obese subjects (BMI 30-35) and obese subjects with T2D (HbA1c 6.6%-8.5%). Although not powered for statistical significance, clinical efficacy was assessed with exploratory endpoints.Results: Forty-nine subjects were enrolled and randomized to either ENT-03 or placebo at a 5:2 (active: placebo) ratio. In healthy obese (n=27) and obese subjects with diabetes (n=8), ENT-03 was well-tolerated, with no safety signals, no treatment-emergent adverse events (TEAEs) ≥3, no SAEs and no TEAEs leading to study discontinuation. No vital sign, clinical lab or ECG changes were observed compared to baseline. All TEAEs were reported as mild (grade 1) or moderate (Grade 2), indicating a favorable AE profile. Mild nausea was observed in 4 patients, and 2 patients had moderate vomiting (3 mg dose and 50 mg dose). Four mild injection site reactions were observed and did not require intervention. t1/2 increased as doses increased in each treatment group with mean t1/2 of 72.3 hr (+7.1) at a dose of 75 mg. Of the 10 subjects receiving a single 50 mg dose, 8 lost an average of 0.99 kg on day 8 (p<0.04). All 8 subjects returned to baseline weight on day 14. In obese patients with type 2 diabetes, there was a trend toward decreased insulin, decreased Matsuda index, and decreased HOMA-IR.Conclusion: ENT-03 with a novel mechanism of action to treat obesity and/or T2D appears safe and well-tolerated in this Phase 1a study.Disclosure R.S. Larson: Employee; Metabolics Pharma, Enterin Inc. G. Fleming: Advisory Panel; Abvance Therapeutics. Consultant; AdipoPharm, ADOCIA, Aerami Therapeutics, Biocon. Stock/Shareholder; Diasome Pharmaceuticals. Consultant; Biomea Fusion, Glyscend Therapeutics, Intarcia Therapeutics, Inc, Kriya Therapeutics. Other Relationship; Juvenile Diabetes Research Foundation (JDRF). Consultant; Oramed Pharmaceuticals, Regor Therapeutics, Rhythm Pharmaceuticals, Inc, Rivus Pharmaceuticals Inc, TIXiMED, vTv Therapeutics, Zealand Pharma A/S, Zucara Therapeutics. M.B. Zemel: Consultant; AdipoPharm, Aerami Therapeutics, Diasome Pharmaceuticals, Glyscend Therapeutics, Intercept Pharmaceuticals, Inc, NeuroBo Pharmaceuticals, Inc, Rhythm Pharmaceuticals, Inc, TIXiMED, Zealand Pharma A/S, Enterin. A.C. Moses: Consultant; Vertex Pharmaceuticals Incorporated, Virta Health Corp, Alnylam Pharmaceuticals, Inc. Board Member; diaTribe. Stock/Shareholder; Minutia, Inc. Consultant; Scholar Rock. Advisory Panel; TIXiMED.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-271-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 272-OR: COVALENT-111: 26-Week Efficacy and Safety after 8 and 12 Weeks of
Daily Oral Icovamenib in Patients with Poorly Controlled Type 2 Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 272-OR
Abstract: Introduction and Objective: Icovamenib, an oral covalent menin inhibitor, is in development for the treatment of diabetes. In the MAD phase of the COVALENT-111 trial, 4 wks of daily icovamenib in patients with T2D significantly improved A1C at 26 wks. This was most pronounced in insulin deficient T2D subtypes (mild age-related diabetes [MARD] and severe insulin-deficient diabetes [SIDD]). Here we report 26-wk results of the expansion phase of COVALENT-111.Methods: This 52-wk, double-blind, randomized, PBO-controlled trial enrolled adults with T2D (A1C 7.0-10.5%, BMI 25-40 kg/m², up to 3 antidiabetics). Icovamenib or PBO (3:1) was administered in 3 arms: Arm A (100 mg QD for 8 wks), Arm B (100 mg QD for 12 wks), and Arm C (100 mg QD for 8 wks then 100 mg BID for 4 wks). Primary endpoint was change in A1C at 26 wks.Results: The per protocol population consisted of 115 icovamenib- (age 54±8 yr, T2D duration 4.4±1.9 yr, A1C 8.2±0.96%, BMI 31.9±4.7 kg/m2, mean±SD) and 50 PBO-treated (age 55±7 yr, T2D duration 4.3±2.0 yr, A1C 8.3±0.93%, BMI 32.6±4.1 kg/m2) patients. Across the 3 arms, icovamenib demonstrated a PBO-corrected A1C change of -0.36% (p=0.022) at Wk 26. Patients receiving 12 wks of icovamenib (Arms B and C) had a greater change in A1C (-0.42%, p=0.015) than 8 wks of treatment (Arm A, -0.27%, p=NS). In a prespecified analysis of MARD and SIDD subtype patients, PBO-corrected change in A1C was -0.73% (p=0.009). SIDD patients treated for 12 wks (Arms B and C) had a -1.17% change in A1C (p=0.038), with those in Arm B having the greatest PBO-corrected A1C change (-1.47%, p=0.022). Icovamenib was well-tolerated, with no serious AEs or discontinuations due to AEs.Conclusion: Icovamenib for 8 or 12 wks resulted in significant improvements in A1C at 26 wks in poorly controlled T2D. As expected, based on icovamenib’s mechanism of action, this effect was most pronounced in insulin-deficient T2D. These results support icovamenib as a potential first-in-class menin inhibitor for the management of T2D.DisclosureS. Mourya: None. B. Munneke: Employee; Biomea Fusion. J. Kim: None. T. Butler: Employee; Biomea Fusion. J.P. Frias: Employee; Biomea Fusion. Stock/Shareholder; Biomea Fusion. Board Member; T1D Exchange. Consultant; Eli Lilly and Company. Speaker's Bureau; Eli Lilly and Company. Research Support; Eli Lilly and Company. Consultant; Novo Nordisk. Research Support; Novo Nordisk. Advisory Panel; Novo Nordisk, Sanofi. Research Support; Sanofi. Consultant; Sanofi. Speaker's Bureau; Sanofi. Research Support; Boehringer-Ingelheim. Advisory Panel; Boehringer-Ingelheim. Consultant; Carmot Therapeutics, Inc, Altimmune Inc. Research Support; Altimmune Inc, Novartis Pharmaceuticals Corporation, Pfizer Inc. Consultant; Pfizer Inc. Research Support; Merck & Co., Inc. Consultant; Merck & Co., Inc. Speaker's Bureau; Merck & Co., Inc. Consultant; Akero Therapeutics, Inc. Research Support; Akero Therapeutics, Inc, 89bio, Inc. Consultant; 89bio, Inc.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-272-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 273-OR: Moving the Goalposts—Do Adults with Type 1 Diabetes (T1D) Want
Time in Tight Range'-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 273-OR
Abstract: Introduction and Objective: Clinical recommendations advise most adults living with T1D to target >70% time in range (TIR 70-180 mg/dL). Recent discussions have suggested narrowing the clinical target to time in tight range (TITR 70-140 mg/dL) for improved long term health outcomes.Methods: We held focus groups with adults with T1D using continuous glucose monitors (CGM) to elicit feedback on TITR.Results: Thirty-three adults (age 43±17 years; 55% female; 91% non-Hispanic White; 23±16 years with T1D; 88% using automated insulin delivery, AID) participated. Table 1 shows themes and example quotes. Several participants wanted TITR for improved health and some were already working toward TITR. However, many participants raised concerns about TITR including risks of increased management burden, anxiety, hypoglycemia, disordered eating, and feelings of failure. Participants conveyed a preference for flexible, personalized clinical targets and customizable CGM data visualization. Participants advocated for advances in diabetes care (technologies, insulins, access) to make TITR achievable.Conclusion: With increasing adoption of AID systems, TITR may be realistic for some. However, introducing narrower clinical targets may pose added risks and management burdens. Further input from people with T1D will be essential in considering education about CGM/AID metrics to increase success of introducing new goals.DisclosureM.L. Tanenbaum: None. E. Pang: None. M.B. Pasmooij: None. R. Tam: None. F.K. Bishop: None. M. Basina: None. M.S. Hughes: Consultant; Dexcom, Inc. Research Support; Tandem Diabetes Care, Inc, Medtronic, Insulet Corporation, Sinocare Inc. D.M. Maahs: Advisory Panel; Abbott, Medtronic. Research Support; Dexcom, Inc. Consultant; Sanofi.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-273-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 274-OR: Association between Continuous Glucose Monitoring–Derived
Metrics and Diabetes Complications—Data from People with Type 1 Diabetes
in Saudi Arabia-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 274-OR
Abstract: Introduction and Objective: Continuous glucose monitors (CGMs) are the standard of care for people with type 1 diabetes (PWT1D), yet studies linking CGM metrics with diabetes complications in PWT1D are scarce. We examined the association between CGM metrics and microvascular complications in PWT1D in Saudi Arabia.Methods: We analyzed CGM data and medical records of 253 PWT1D at two Saudi tertiary diabetes centers. We included PWT1D who had retinal exams, one-month CGM data within 3 months of the retinal exam, and sensor active time ≥70%. Risk factors of diabetic retinopathy (DR), albuminuria, and a composite microvascular complication (CMC) of DR and/or albuminuria were evaluated using multivariable logistic regression.Results: Those with TIR>80% had lower rates of DR (0% vs 26.9%, p=0.02), albuminuria (7.7% vs 20%, p=0.27), and CMC (7.7% vs 40.7%, p=.02) than those with TIR≤80. Likewise, PWT1D with TIR>50% had lower rates of DR (20.2% vs 29.9%, p=0.08), albuminuria (11.5% vs 25.8%, p<0.01), and CMC (31.1% vs 45.3%, p=.03) than those with TIR≤50%. Increasing glycemia risk index (GRI) levels (0-20, 21-60, >60) corresponded with higher prevalence of DR (0, 24.2, and 28.1%, p=0.09), albuminuria (11.1, 10.7, and 25.2%, p=0.03), and CMC (11.1, 33.3, and 44.2%, p=0.06). Duration of diabetes ≥10 years, TIR≤60%, and SBP>126 mmHg were significant predictors of retinopathy after adjusting for age, gender, duration of diabetes, CGM CV, TIR, hemoglobin A1C, systolic blood pressure (SBP), triglycerides, and HDL when appropriate. The only significant predictors of albuminuria in the adjusted model were duration of diabetes ≥10 years, SBP>126 mmHg, and TG>1.22. Hemoglobin A1C was not associated with any microvascular complications in the adjusted model.Conclusion: Our findings support the association between microvascular complications and lower TIR, longer diabetes duration, and higher GRI, SBP, and TG in PWT1D in Saudi ArabiaDisclosure M. Al-Sofiani: Advisory Panel; Medtronic. Speaker's Bureau; Insulet Corporation, Abbott, Lilly Diabetes. Advisory Panel; Dexcom, Inc., Roche Diabetes Care. Speaker's Bureau; Sanofi. Research Support; Medtronic. Speaker's Bureau; Vitalaire. A.M. Shadid: None. A. Shadid: None. M. Makkawi: None. A.B. Albacker: None. O. Aldosari: None. R.J. Alshareef: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-274-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 275-OR: Change in Hypoglycemia Fear and Frequency with the Use of
Automated Insulin Delivery—A Prospective Analysis of the Type 1 Diabetes
Better Registry-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 275-OR
Abstract: Introduction and Objective: Automated insulin delivery (AID) is expected to reduce the burden of hypoglycemia including fear of hypoglycemia (FOH) in type 1 diabetes (T1D). This study aimed to evaluate the change in hypoglycemia fear survey-II (HFS-II) scores and hypoglycemia frequency after AID initiation in usual-living conditions.Methods: Adults (≥18years) living with T1D from the Canadian Type1BETTER registry who started using an AID system during the follow-up period were included. Data included demographics, diabetes specific variables, and the validated HFS-II. Data were collected annually for three years.Results: A total of 115 participants (mean age 42.1±14.5 years; T1D duration 24.4±13.9 years; 77% identified as women) were included. At baseline, 49% of participants reported HbA1c ≤7.0%, which increased to 63% after AID initiation (p=0.047).Participants reported fewer hypoglycemia episodes over the previous month after starting AID compared to baseline. Specifically, the number of monthly level 2 hypoglycemia episodes (<3.0mmol/L with autonomous treatment) decreased from 6.0±7.0 to 4.1±4.5, p=0.022 and symptomatic nocturnal hypoglycemia decreased from 2.3±4.1 episodes to 1.6±2.6, p=0.012.Similarly, average HFS-II scores decreased after using AID: total from 34.0±17.6 at baseline to 30.0±19.4 (p=0.006), HFS-II Behavior subscale 15.9±7.5 to 14.0±8.0 (p=0.012), and HFS-II Worry subscale 18.2±13.3 to 15.9±13.4 (p=0.027).Conclusion: AID initiation was associated with improved HbA1c, reduced hypoglycemia frequency, and lowered HFS-II scores in adults with T1D in usual-living conditions. These findings support the potential of AID to reduce the burden of hypoglycemia without compromising overall glycemic management.Disclosure M.K. Talbo: Other Relationship; Dexcom, Inc. T. Peters: None. C. South: None. A. Katz: None. J. Yale: Advisory Panel; Eli Lilly and Company. Speaker's Bureau; Eli Lilly and Company. Advisory Panel; Novo Nordisk. Speaker's Bureau; Novo Nordisk. Advisory Panel; Abbott. Speaker's Bureau; Abbott, GlaxoSmithKline plc. Advisory Panel; Sanofi. Speaker's Bureau; Bayer Pharmaceuticals, Inc, Dexcom, Inc. Advisory Panel; Dexcom, Inc., Ypsomed AG, Bayer Pharmaceuticals, Inc. Speaker's Bureau; Insulet Corporation. R.P. Rabasa-Lhoret: Advisory Panel; Abbott, Eli Lilly and Company, Novo Nordisk, Sanofi, Insulet Corporation. Other Relationship; Medtronic. Advisory Panel; Bayer Pharmaceuticals, Inc. A. Brazeau: Speaker's Bureau; Dexcom, Inc. Research Support; Canadian Institutes of Health Research. Speaker's Bureau; Juvenile Diabetes Research Foundation (JDRF). Research Support; Juvenile Diabetes Research Foundation (JDRF), Diabète Québec, Fonds de recherches du Québec-Santé, Mitacs.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-275-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 276-OR: T1D Exchange Multicenter Study—Increasing CGM Adoption in
Type 2 Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 276-OR
Abstract: Introduction and Objective: Most published studies have demonstrated the value of continuous glucose monitors (CGM) in type 1 diabetes. Type 2 diabetes involves more varied management approaches, ranging from oral medications to insulin therapy. Significant disparities exist in CGM adoption among people with type 2 diabetes (PwT2D). Non-Hispanic Black and Hispanic PwT2D, those with lower household income, or public insurance, are less likely to be on a CGM. The aim of this study is to highlight strategies that effectively increase CGM adoption equitably.Methods: Three centers in the T1D Exchange Quality Improvement Collaborative used the 10-step equity framework, including the Ishikawa diagram, process map, effort/impact matrix tool, and PDSA cycles to test interventions in their centers to increase CGM use among all PwT2D. The coordinating center used statistical process control charts to evaluate the effectiveness of the interventions.Results: Participating centers improved their CGM adoption, equitably, by 11% over 20 months impacting 3219 PwT2D (Figure 1). Successful strategies highlighted include redesigning of CGM prescription workflows, use of technology navigators, audio- visual educational materials in multiple languages, use of electronic health records to screen for CGM use and to track CGM use.Conclusion: This project demonstrates that cross-learning and the use of QI and health equity principles can increase CGM use for all PwT2D.DisclosureT.R. Bol: None. O. Odugbesan: None. T. Wright: None. N. Rioles: None. K. Fantasia: Stock/Shareholder; Eli Lilly and Company. M. Zupa: None. J. Haw: None. O. Ebekozien: Research Support; Abbott. Advisory Panel; Sanofi. Research Support; Sanofi, Lilly Diabetes, Medtronic.FundingThe Leona M. and Harry B. Helmsley Charitable Trust
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-276-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 277-OR: OCT1 and TCF7L2 Variants Modulate Metformin–Liraglutide
Pharmacokinetics and Glycemia in African American Youth-Onset Type 2
Diabetes—The MIGHTY Study-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 277-OR
Abstract: Introduction and Objective: Combination metformin (Met) and liraglutide (Lira) improves glycemia in African American (AA) youth with type 2 diabetes (Y-T2D), but factors influencing medication response are unknown. We constructed the first Met population pharmacokinetic (PK) model for AA Y-T2D and evaluated the relationship of pharmacogenetic (PG) variants of Met+Lira with glycemia.Methods: In a 3-month parallel arm trial of standard release Met (n=12) and Met+Lira (n=10), we measured HbA1c, fasting plasma glucose (FPG), and fractional gluconeogenesis (GNG) pre- and post-intervention. Plasma Met and Lira concentrations were analyzed by LC-MS and dose adjusted. Common PG variants were genotyped in OCT1 (rs628031 and rs622342, Met transporter) and TCF7L2 (rs7903146, transcription factor). A one-compartment first-order absorption and elimination Met PK model was constructed. Linear regression models assessed relationships of PK variables, glycemic outcomes, and PG variants, adjusted for age, sex, and treatment.Results: The Met PK parameters absorption rate constant, clearance (Cl), and volume of distribution were similar by group and not related to glycemia. However, Met+Lira reduced HbA1c more than Met (Δ 1.2±0.8 vs 0.1±0.6%, mean±SD, P < 0.01). OCT1 variants were associated with lower Met Cl (rs628031 G>A, β = -39 L/hr, Adj. R2 = 0.4, P < 0.02) and lower fractional rates of GNG (rs622342 A>C, β = -7.6%, Adj. R2 = 0.5, P < 0.003). TCF7L2 rs7903146 C>T was associated with lower Lira concentrations (β = -36 ng/mL * mg-1, Adj. R2 = 0.4, P = 0.03) and reduced FPG (β = -1.4 mmol/L, Adj. R2 = 0.8, P < 0.002).Conclusion: In AA Y-T2D, genetic variants modulated therapeutic response and glycemic outcomes. OCT1 variants explained up to 50% of the variability in Met Cl and GNG response but did not predict overall glycemia. TCF7L2 variant rs7903146 modulated Lira concentrations and glycemia. Genotyping OCT1 and TCF7L2 in Y-T2D may enable optimization of patient-specific Met and Lira medication regimens.DisclosureS.L. Cantor: None. Y. Zeng: None. F.S. Davis: None. G.P. Thota: None. S.B. Glaros: None. N.A. Macheret: None. I.N. Kacker: None. N. Malandrino: None. L. Mabundo: None. W.D. Figg: None. A.R. Bentley: None. S.T. Chung: None.FundingNational Institute of Diabetes & Digestive & Kidney Diseases (ZIA DK 075133)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-277-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 278-OR: Higher Static Phase Insulin Secretory Rate Compensates for Lower
Insulin Sensitivity in South Asian Youth—The Charisma Study-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 278-OR
Abstract: Introduction and Objective: South Asian (SA) adult studies suggest insulin deficiency contributes to increased T2D risk. Our prior data found higher OGTT insulin in SA vs. White (W) and African American (AA) adolescents and young adults (AYA). Using mathematical modeling, we aim to investigate this finding by characterizing insulin sensitivity (Si), 1st pass hepatic extraction (HE), and the β-cell’s biphasic insulin secretory rates (ISR).Methods: SA, W, and AA AYA with BMI ≥80%ile (≥23kg/m2 if ≥18y) without diabetes underwent 180-min OGTT with derivation of Si by the oral minimal model, HE by the insulin clearance model, and ISR dynamic (1st phase) and static (2nd phase) by the beta-cell function model. ISR AUC for both phases at 180 min were calculated using the trapezoidal method. Disposition index (DI) for both phases: Si x ISR AUC. Ancestry differences were tested with age, sex, and BMIZ-adjusted robust linear regression.Results: AYA [49 SA of mean age: 19.8y, 52 W: 18.9y, 47 AA: 18.8y, p=0.02] did not differ by sex or BMIZ. SA had lower Si [marginal mean (SE): 5.14 (0.77) 104mu/L-1*min-1] vs W [8.25 (0.74); p=0.004] but not vs AA. SA had borderline higher dynamic ISR AUC vs W (p=0.051) but did not differ from AA. Static ISR AUC was 44.7% higher in SA [marginal mean (SE): 27984 (1267) pmol/l] vs W [19334 (1219), p=0.0001] and 66.0% higher in SA vs AA [16858 (1297), p=0.0001]. HE did not differ for SA vs W, but was 13.8% lower in AA vs SA (p=0.0001). DI for both insulin secretory phases did not differ between SA vs W or vs AA.Conclusion: Higher postprandial hyperinsulinemia in SA AYA is due to hypersecretion rather than lower HE. Static phase insulin hypersecretion in SA AYA may precede β-cell failure and T2D in SA adults. Dynamic phase insulin secretion, which typically compensates for lower Si to preserve DI, was unchanged in SA AYA. Future studies can interrogate the roles of alterations in each insulin secretion phase in the progression to β-cell failure and the emergence of T2D in SA.DisclosureT.A. Hitt: None. D. Stefanovski: None. B.S. Zemel: Consultant; Incyte. A. Kelly: None. S.N. Magge: None.FundingNIH NDDK (R01DK115648); CTSA NIH support (UL1TR001878, UL1TR00107)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-278-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 279-OR: The Relationship of Relative Fat Mass (RFM) to In Vivo Peripheral,
Hepatic, and Adipose Insulin Sensitivity (IS) and Cardiometabolic Risk
Factors in Youth across the Adiposity Spectrum-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 279-OR
Abstract: Introduction and Objective: Calculated RFM, a simple alternative to imaging-based body composition, reflects total and abdominal adiposity. We examined if RFM relates to global IS and cardiometabolic risk factors in youth along the adiposity spectrum from normal weight (NW) to obesity.Methods: A total of 304 youth (age 14.4±1.9 yrs; 146 boys/158 girls; 140 black/164 white) with NW=81 and overweight/obesity=223, were included. Spearman correlation analyses examined the relationships of RFM to a) in vivo IS, including peripheral (PIS), hepatic (HIS), and adipose tissue (ATIS), measured by a hyperinsulinemic-euglycemic clamp combined with [6,6-2H2]glucose and [2H5]glycerol tracers, and b) cardiometabolic risk factors including HbA1c, blood pressure (BP), and lipids.Results: RFM correlated inversely with PIS, HIS, ATIS, and HDL (r=-.75, -.34, -.53, and -.29, respectively; all P<.001) (Image), and positively with HbA1c, triglycerides, non-HDL-C, and systolic BP (r=.23, .31, .19, and .20, respectively; all P<.001).Conclusion: Expanding RFM is associated with worsening IS and cardiometabolic risk in youth from NW to obesity. RFM can be a useful tool that reflects changes in IS & cardiometabolic risk over time in large-scale youth cohorts receiving anti-obesity pharmacotherapy for weight and health management.DisclosureW. Cho: None. J. Kim: None. S.A. Arslanian: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-279-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 280-OR: Insulin Sensitivity following an In-Home Sleep and Circadian
Intervention for Habitually Short-Sleeping Adolescents-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 280-OR
Abstract: Introduction and Objective: Insufficient sleep and late circadian timing are common in adolescence and associated with impaired insulin sensitivity (Si). The aim of this study was to evaluate associations among and change in sleep, circadian, and Si variables following a one-week in-home sleep and circadian intervention in habitually short-sleeping adolescents.Methods: A randomized crossover trial was conducted in adolescents with sleep ≤7h on school nights (N=28, 15.9±1.3y, 71% female, 89.3% non-Hispanic White, BMI%=65.9±29.0). Participants completed one week each of typical sleep (TS) and a combined sleep extension and circadian manipulation (EXT+; ≥1h additional time in bed, PM melatonin [500mcg 2h], and AM light therapy [30min]. Sleep was measured with wrist actigraphy, circadian variables with salivary dim-light melatonin, and Si with HOMA-IR and an intravenous glucose tolerance test (IVGTT) following each condition. Spearman and Kendall correlations assessed associations and paired samples t-tests and Wilcoxon signed-rank tests examined change between TS and EXT+.Results: At TS, later dim light melatonin onset and offset (DLMOn and DLMOff) were significantly associated with poorer IVGTT-assessed Si. During EXT+ compared to TS, sleep duration significantly increased by 1.1h (0.9,1.3; p<0.001) and bedtime and DLMOn significantly advanced by 1.2h (0.8,1.6; p<0.001) and 1.1h (0.4,1.9; p=0.005). There was no significant change in waketime, DLMOff, or Si from TS to EXT+. However, greater change in DLMOn from TS to EXT+ was correlated with lower HOMA-IR at EXT+ (r=-0.8, p=0.001).Conclusion: Greater change in circadian rhythms following a sleep and circadian timing manipulation was associated with better post-intervention fasting Si in a sample of habitually short-sleeping adolescents. Future research should utilize larger, more diverse samples and evaluate a longer duration of intervention.DisclosureS.L. Simon: None. E. Cooper: Research Support; Boehringer-Ingelheim. A.R. Bernard: None. J. Brinton: None. S.M.M. Hawkins: Consultant; Ionis Pharmaceuticals. M.G. Cree: None. K.J. Nadeau: None.FundingNational Institutes of Health (K23DK117021, R03DK131225, 2K12HD057022, CTSA UL1TR002535)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-280-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 281-OR: Time-Restricted Feeding Prevents Deleterious Effects of
Diet-Induced Obesity on Circadian Regulation of β-Cell Function and
Transcription-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 281-OR
Abstract: Introduction and Objective: Disruptions in circadian fasting/feeding cycles contribute to β-cell dysfunction in diabetes. Diet-induced obesity (DIO) (modeled by a high-fat diet) adversely affects circadian glucose homeostasis partly through dysregulation of fasting/feeding cycles. However, its impact on circadian β-cell function and gene expression remains unknown.Methods: To address this, we exposed male/female C57BL/6 mice to chow or DIO for 8 weeks and evaluated behavioral (feeding/activity), physiological (glucose tolerance/insulin secretion), transcriptomic (RNA-seq), and epigenomic (ATAC-seq) circadian rhythms. Additionally, we tested whether normalization of fasting/feeding cycles by time-restricted feeding (tRF) mitigates the effects of DIO.Results: DIO disrupted circadian regulation of fasting/feeding cycles, with the extent of disruption greater in males vs. females (p<0.05). Also, DIO led to the loss of circadian regulation of glucose tolerance and in vivo glucose-stimulated insulin secretion (GSIS) (p<0.05 vs. chow) in males, whereas circadian glucose homeostasis was preserved in female mice. RNA-seq analysis of male islets revealed a ~ 50% reduction in circadian-regulated transcripts under DIO (p<0.05 vs. chow), with attenuated circadian rhythms in key pathways (e.g., Protein processing in ER and cAMP signaling). Importantly, normalization of fasting/feeding cycles in DIO male mice by tRF restored circadian glucose tolerance, GSIS, and islet gene expression (p<0.05 vs. chow). Motif analysis identified transcription factors DBP and NRF1 as mediators of beneficial effects of tRF in DIO islets.Conclusion: Our study demonstrates that 1) DIO perturbs circadian regulation of β cell function and gene expression through dysregulation of fasting/feeding cycles, and 2) highlights notable sex differences in how DIO impacts circadian control of glucose homeostasis and β-cell function.DisclosureL. Zhang: None. S.K. Sen: None. T. Nguyen: None. K. Omori: None. A. Bharath: None. A. Matveyenko: None.FundingNational Institutes of Health (R01DK098468)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-281-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 282-OR: Pancreatic Alpha Cells Integrate Neuronal and Immune Stimuli for
Insulin Secretion-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 282-OR
Abstract: Introduction and Objective: Neuronal stimulation can trigger insulin secretion, as seen in the cephalic phase insulin response (CPIR). The CPIR is the release of insulin in the anticipation of a meal and occurs prior to meal-derived changes in blood glucose. We have demonstrated that blocking IL-1β signaling impairs the CPIR, yet how neuronally-mediated insulin release from beta cells in the fasted, low glucose state is regulated is still unclear. Alpha cells have been shown to fine-tune beta cell responses; therefore we hypothesized that alpha cells help integrate neuronal and immune stimuli in order to facilitate the CPIR.Methods: We administered acute injections of glucagon and L-1β in fasted mice to assess insulin secretion and performed cephalic phase experiments with alpha-cell KO mice (a-KO). By stimulating isolated islets with a muscarinic receptor agonist (carbachol) and IL-1β at 3.5mM glucose we could mimic cephalic stimulation in vitro. Using a-KO islets, GCGR and GLP-1R antagonists, we investigated glucagon action in the context of cephalic phase. We treated cephalic stimulated islets with diazoxide or 2-APB to block Ca2+ mobilization. Further, we repeated glucagon stimulated insulin secretion and in vitro cephalic stimulation in HFD-fed mice.Results: Glucagon stimulated insulin secretion was suppressed in mice pre-treated with atropine and plasma insulin and glucagon levels were elevated after IL-1β injection in vivo. a-KO mice had suppressed CPIR both in vivo and in vitro. Blocking GCGR and GLP-1R strongly reduced cephalic stimulated insulin release in vitro. Blocking intracellular Ca2+ mobilization with 2-APB abolished CPIR in vitro. HFD disrupted glucagon stimulated insulin secretion and increased beta cell responsiveness to cholinergic stimulation.Conclusion: Alpha cells are essential for cephalic phase insulin secretion and this neuronally-mediated beta cell response relies on glucagon, thereby positioning alpha cells as integrators of cholinergic and IL-1β-stimulated insulin secretion at fasting glucose.DisclosureK. Trimigliozzi: None. S.J. Wiedemann: None. L. Rachid: None. H. Mereau: None. M. Boeni-Schnetzler: None. D.T. Meier: None. M.Y. Donath: Advisory Panel; Abbott, AstraZeneca, Boehringer-Ingelheim, Eli Lilly and Company, Novo Nordisk, Novartis AG, Roche Pharmaceuticals, Sanofi-Aventis Deutschland GmbH. Research Support; Olatec.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-282-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 283-OR: β-Cell 14-3-3ζ Ablation Protects against Metabolic
Stress in Mice-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 283-OR
Abstract: Introduction and Objective: Crosstalk between α-cells and β-cells is vital for healthy islet function. While α-cells typically produce glucagon, under pathophysiological conditions such as diabetes and obesity, they can produce active glucagon-like peptide-1 (GLP-1). However, the mechanisms regulating α-cell GLP-1 production remain poorly understood. We find that β-cell 14-3-3ζ ablation increases glucose-stimulated insulin secretion, and inhibition of 14-3-3 proteins activates α-cell active GLP-1 production in mouse and human islets. Therefore, we tested the hypothesis that β-cell 14-3-3ζ ablation will protect against metabolic disease by increasing α-cell GLP-1 production.Methods: We assessed the impact of β-cell 14-3-3ζ ablation on glycemic regulation by performing a mixed meal tolerance test (MMTT) in high fat diet (HFD)-fed wild-type (WT) and β-cell-specific 14-3-3ζ knockout (KO) littermates. We further assessed GLP-1 secretion from islets isolated from these mice. To test the role of α-cell GLP-1 in glycemic regulation we performed an oral glucose tolerance test (OGTT) in WT and α-cell GLP-1 KO littermates maintained on a low-fat diet (LFD) or HFD.Results: β-cell 14-3-3ζ ablation improved glucose tolerance compared to WT mice during a MMTT in mice. Further, β-cell 14-3-3ζ ablation increased active GLP-1 secretion from isolated islets in response to high glucose plus glutamine, compared to WT. While glucose tolerance was similar between WT and α-cell GLP-1 KO mice, α-cell GLP-1 ablation in HFD-fed mice lowered insulin secretion compared to WT during an OGTT.Conclusion: These findings demonstrate that β-cell 14-3-3ζ ablation protects against HFD-induced metabolic stress and increases α-cell GLP-1 secretion. Further, we find that α-cell GLP-1 secretion facilitates β-cell compensation in response to metabolic stress. Together, these data highlight a role for 14-3-3ζ in regulating islet cell crosstalk that may offer therapeutic potential for improving islet function.DisclosureR. Shishani: None. R. Moreno: None. M. Tucker: None. S. Dinglasan: None. G.E. Lim: Research Support; Inversago Pharma. Consultant; DiogenX, Ambagon. B. Cummings: None.FundingNational Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health under award numbers (R56DK124853, R01DK139200 & F31DK139734); the NIH T32 Predoctoral Training in Pharmacological Sciences award GM099608 and the Hartwell Foundation.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-283-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 284-OR: Physiologic Compensation to Metabolic Stress following Islet
α-Cell Loss-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 284-OR
Abstract: Introduction and Objective: Islet endocrine cells rely on efficient prohormone synthesis and elimination of misfolded peptides for proper function. We recently found that endoplasmic reticulum-associated degradation (ERAD) and autophagy are essential protein quality control systems that maintain α cell identity, ER homeostasis, and glucagon (Gcg) production.Methods: To investigate whether ERAD and autophagy serve overlapping roles in α cells, we inactivated both systems in mice by deleting the key components Sel1L and Atg7 in Gcg+ cells, then evaluated islet morphology and function.Results: Intriguingly, Sel1L;Atg7ΔGcg mice showed a dramatic loss of α cells after birth, with a decline in Gcg+ islet cells between 2-4 weeks of age, resulting in a 79% reduction in pancreatic glucagon content. Surviving α cells appeared normal by immunolabeling for markers of ER dysfunction, suggesting escape from Cre-loxP recombination. Adult Sel1L;Atg7ΔGcg mice had significantly impaired glucagon secretion in vivo in response to fasting or hypoglycemia, but normal glucose tolerance. We then evaluated whether loss of α cells in Sel1L;Atg7ΔGcg mice affected their response to metabolic stress by examining islet function in late gestation or after high-fat diet (HFD) feeding. Pregnant Sel1L;Atg7ΔGcg mice given a mixed meal had similar blood glucose, insulin, and GLP-1 responses as pregnant littermate controls. Likewise, HFD-fed Sel1L;Atg7ΔGcg mice had similar mixed meal responses as controls after two and six weeks on HFD. Neither pregnancy nor HFD normalized the impaired glucagon secretion or low pancreatic glucagon content in Sel1L;Atg7ΔGcg mice, suggesting against α cell mass expansion with these stressors.Conclusion: Collectively, these data demonstrate that cellular protein quality control, maintained by ERAD and autophagy, is required for α cell survival. However, mice can compensate for low intrapancreatic proglucagon and maintain normal β cell function in vivo during pregnancy and nutritional stress.DisclosureW. Zhu: None. B. Pederson: None. R.B. Reinert: None.FundingNational Institutes of Health (K08DK129719)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-284-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 285-OR: A Kinase-Mediated Signaling and Glucose Uptake Defect in Human
Insulin Resistance-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 285-OR
Abstract: Introduction and Objective: Insulin resistance is a major risk factor in the development of type 2 diabetes (T2D) and metabolic syndrome. Although ~25% of people within the general non-diabetic population are insulin resistant, the primary underlying cause of insulin resistance remains elusive.Methods: In this study, we have used induced pluripotent stem cells (iPSC) derived from non-diabetic humans at both ends of the insulin sensitivity spectrum, i.e., the top 20% of insulin resistance vs. the top 20% of insulin sensitivity differentiated into myoblasts (iMyos) to model insulin resistance in vitro.Results: Global phosphoproteomics analysis of these cells showed a large network of protein phosphorylations linked to differences in insulin sensitivity including 378 up-regulated and 393 down-regulated insulin stimulated phosphosites in I-Res iMyos. To identify drivers of altered phosphorylation in insulin resistance, we used an in silico AI kinome analysis to query which of the 300+ Ser/Thr kinases encoded in the human genome might be responsible for the protein phosphorylation changes. We could identify 16 kinases whose predicted activities were significantly increased in I-Res iMyos, suggesting their potential link to the pathogenesis of insulin resistance. To functionally link these altered kinases to the downstream defect of impaired glucose uptake associated with insulin resistance, we conducted a loss-of-function screen using a CRISPR-based approach to identify candidate kinases, or phosphatases that regulate glucose uptake in I-Res iMyos. Among the 16 kinases predicted to have increased activity in insulin resistance, one kinase, DYRK2, was identified as a potential modulator of insulin resistance by being both increased in predicted activity in I-Res iMyos and associated with rescued glucose uptake in I-Res iMyos by CRISPR-mediated knockdown.Conclusion: In summary, combining a Kinome analysis with CRISPR screening and population genetics reveals DYRK2 as an important upstream regulator of human insulin resistance.DisclosureN. Haider: None. T. Yaron-Barir: Other Relationship; DeStroke. J.L. Johnson: None. L. Cantley: Stock/Shareholder; Larkspur, Volastra, Cell Signaling Technologies. Consultant; Manas. P. Yi: None. C. Kahn: Consultant; Novo Nordisk, Cellarity. Advisory Panel; TIXiMED. Board Member; 1825.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-285-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 286-OR: Spatial Regulation of Glucose and Lipid Metabolism by Hepatic
Insulin Signaling-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 286-OR
Abstract: Introduction and Objective: Hepatic insulin sensitivity is critical for systemic glucose and lipid homeostasis. The liver is spatially organized into zones in which hepatocytes express distinct metabolic enzymes; however, the functional significance of this zonation to metabolic dysregulation caused by insulin resistance is undetermined.Methods: Here, we used CreER mice to selectively disrupt insulin signaling in periportal (PP) and pericentral (PC) hepatocytes.Results: PP-insulin resistance has been suggested to drive combined hyperglycemia and excess lipogenesis in type 2 diabetes. However, we found that PP-insulin resistance in mice impaired lipogenesis and suppressed high-fat diet (HFD)-induced hepatosteatosis, despite elevating blood glucose and insulin. Conversely, PC-insulin resistance reduced HFD-induced pericentral steatosis while preserving normal glucose homeostasis, in part by shifting glycolytic metabolism from the liver to muscle.Conclusion: These results demonstrate distinct roles of insulin in PP versus PC, and suggest that PC-insulin resistance might be therapeutically useful to combat hepatosteatosis without compromising glucose homeostasis.DisclosureB. He: None. K.D. Copps: None. M.F. White: Board Member; HPRL (Housey Pharmaceutical Research Laboratory). R. Tao: None.FundingNIH grants DK133388
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-286-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 287-OR: Physiological and Cellular Effects of Ligand and Kinase
Independent Action of the Insulin Receptors in Liver-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 287-OR
Abstract: Introduction and Objective: Insulin signals through the insulin receptor (IR) tyrosine kinase to mediate its well-known metabolic and mitogenic functions. Recently, we have identified a second IR signaling pathway in preadipocytes that is dependent on intracellular domain of IR, but is ligand and tyrosine kinase-independent (LYK-I). Here, we studied this pathway in liver using liver specific IR-KO mice (LIRKO), since liver naturally contains almost no IGF1R.Methods: We have re-expressed either wildtype (WT) or kinase-dead (K1030R) -IR in LIRKO mice using adenoviral over-expression.Results: As expected, infection of LIRKO hepatocytes with the WT-IR, but not the kinase-dead IR, restored classical insulin signaling. In vivo, re-expression of WT-IR in liver of LIRKO mice normalized fed hyperglycemia, glucose tolerance, insulin sensitivity, reduced plasma insulin levels and increased liver weight, compared to mock-infected LIRKO mice. By contrast, somewhat surprisingly, expressing K1030R mutant IR in LIRKO mice worsened these parameters, despite the absence of endogenous IR and minimal IGF1R to inhibit. In isolated LIRKO hepatocytes, expression of either WT-IR or the K1030R mutant increased etoposide induced apoptosis and reduced NFκB expression compared to mock infected cells, similar to LYK-I effects observed in preadipocytes. Cholesterol biosynthesis genes (e.g. Hmgcs1), were upregulated by the expression of either WT-IR or the K1030R mutant, while inflammatory markers (Tnfα, Cxcl10) were downregulated compared to mock infected mice.Mechanistically, using LC-MS/MS proteomics we have shown that both WT-IR and kinase dead IR can interact with several inflammatory mediators, including IFITM2/3, which may partially contribute to apoptosis and inflammatory responses related to LYK-I actions of IR.Conclusion: Thus, LYK-I actions of IR in liver could modulate several cellular actions including cholesterol biosynthesis, inflammation, and apoptosis.DisclosureA. Ghosh: None. V.R. Muñoz: None. A. Gattu: None. Y. Watanabe: None. M. Lino: None. G. Ruiz: None. C. Kahn: Consultant; Novo Nordisk, Cellarity. Advisory Panel; TIXiMED. Board Member; 1825.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-287-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 288-OR: Increased Insulin Signaling Is Associated with a Proatherogenic
Lipoprotein Profile-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 288-OR
Abstract: Introduction and Objective: Type 2 diabetes (T2D) is associated with insulin resistance (IR), a risk factor for cardiovascular disease (CVD). In T2D, IR affects only a subset of insulin signaling (IS) pathways, with preserved IS in others. Thus, patients with T2D develop both hypertriglyceridemia from excess IS and hyperglycemia from insufficient IS. As IR involves biology mediated by both increased and decreased IS, we used rare disease models to determine if CVD in states of IR is driven by excessive IS, insufficient IS, or both.Methods: We compared NMR lipoprotein profiles (markers of CVD risk) in 14 patients with type B IR (TBIR), a disorder where autoantibodies against the insulin receptor block IS (low IS), which is restored in remission (normal IS). Patients with lipodystrophy (LD) were included to represent high IS.Results: Across the spectrum of IS, from lowest (TBIR active) to intermediate (TBIR remission), to highest (LD) there were increases in all atherogenic TRLs (Table). Likewise, there was an atherogenic shift in HDL subfractions with decreases in protective large HDL-P and increases in harmful small HDL-P across groups. LDLs did not show a direct relationship between IS and CVD risk as inflammation in patients with active TBIR can cause elevations in highly atherogenic small LDL-P resulting in reduced mean LDL particle size.Conclusion: Excess IS contributes to a pro-atherogenic lipoprotein profile.DisclosureM. Hwang: None. R. Brown: Research Support; Chiesi, Regeneron Pharmaceuticals, Marea.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-288-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 289-OR: Insulin Receptor Regulation across Adipose Tissues and Its Impact
on Systemic Metabolism-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 289-OR
Abstract: Introduction and Objective: Adipose tissue dysfunction is strongly associated with insulin resistance and type 2 diabetes (T2D). Insulin signaling plays crucial roles in maintaining adipose homeostasis. In humans, insulin receptor (INSR) expression is decreased in white adipose tissue (WAT) from aged, obese, and T2D individuals.Methods: To define the role of insulin receptor reduction in fat in whole-body physiology, we generated mice with heterozygote loss of Insr in adipocyte (IR-HET) by crossing adiponectin-Cre+/- and Insr-flox+/- mice.Results: The resultant mice exhibited ~20% to ~50% reductions in Insr in epididymal WAT (eWAT), inguinal WAT (iWAT), and brown adipose tissue (BAT). This was paralleled by a similar reduction in insulin signaling in these fats, but not in liver and muscle, as manifest by decreased phosphorylation of Insr Tyr1150/1151, Akt Ser473, and Erk Thr202/204. IR-HET mice showed significant reductions of BAT and iWAT weight, but a mild decrease of eWAT and body weight. IR-HET mice maintained normal plasma triglyceride and glucose levels but exhibited insulin resistance and hyperinsulinemia. This reduction in Insr also resulted in significant and distinct changes in gene expression across eWAT, iWAT, and BAT with 224 to 931 genes upregulated and 814 to 1205 genes downregulated. Interestingly, only 6 upregulated and 5 downregulated genes were present in all 3 fats, indicating the unique role of Insr in each depot. Differentially expressed genes in eWAT were most enriched in cilium movement, whereas in iWAT they were in the adaptive immune response and in BAT in fatty acid synthesis. Single nuclei sequencing of human WAT also showed more than 500 genes that correlated with INSR dosage.Conclusion: Thus, the reduction in adipocyte Insr in rodents and humans alters gene expression and fat function, highlighting its critical role in maintaining fat and whole-body homeostasis. Identification of these dose-dependent Insr-regulated genes provides new insights into the complex nature of insulin resistance response in different fats.DisclosureY. Yu: None. X. Liu: None. H. Camara: None. Y. Tseng: Consultant; Paratus Sciences. Other Relationship; Novo Nordisk, ATCC, Biohaven. Consultant; LyGenesis. C. Kahn: Consultant; Novo Nordisk, Cellarity. Advisory Panel; TIXiMED. Board Member; 1825.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-289-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 290-OR: Association of Pathophysiological Markers with Type 2 Diabetes
Subtypes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 290-OR
Abstract: Introduction and Objective: Pathophysiological markers preceding type 2 diabetes (T2D) diagnosis may inform future membership in T2D subtypes (Severe Insulin Deficient Diabetes [SIDD], Severe Insulin Resistant Diabetes [SIRD], Mild Obesity-related Diabetes [MOD], Mild Age-related Diabetes [MARD]). Using prospective cohort studies, we evaluated the association of key markers with T2D subtypes.Methods: We followed 9,610 participants (78,752 observations; median: 10.0 years [range: 0.2-15.0]) from three cohort studies (DPP control arm and outcome study, JHS, MESA) without T2D at their initial visit till T2D diagnosis, or for 15 years. New T2D were classified into four subtypes. Cause-specific hazards of seven pathophysiological markers (Figure) with subtypes were estimated using Time-Dependent Cox Models.Results: In the 15 years after the first visit (Figure), 18.0% (n = 1,731) were newly diagnosed with T2D, with higher crude incidence of MOD and MARD compared to SIDD and SIRD. Higher HOMA2-IR was associated with membership in SIRD (HR: 1.70 [95%CI: 1.54, 1.89]), higher HbA1c was associated with SIDD (HR: 1.21 [95%CI: 0.73, 1.99]), and higher BMI was associated with MOD (HR: 1.04 [95%CI: 1.04, 1.05]) and SIRD (HR: 1.01 [95%CI: 1.00, 1.03]). SBP, LDL, eGFR and HOMA2-%B were not associated with subtype membership.Conclusion: HOMA2-IR, HbA1c, and BMI were prospectively associated with membership in subtypes of type 2 diabetes.DisclosureJ. Guo: None. J. Varghese: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-290-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 291-OR: Effect of Type 2 Diabetes Characteristics on Semaglutide Treatment
in People with Type 2 Diabetes and Peripheral Artery Disease—A Post Hoc
Analysis of the STRIDE Trial-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 291-OR
Abstract: Introduction and Objective: The STRIDE trial (NCT04560998) demonstrated that once weekly semaglutide 1.0 mg significantly improved maximum walking distance (MWD) in people with type 2 diabetes (T2D) and symptomatic peripheral artery disease (PAD) vs. placebo. Whether the benefits are consistent across T2D characteristics has not been described.Methods: The primary outcome in STRIDE, MWD measured on a constant load treadmill at 52 weeks, was analyzed by T2D duration (≥10 vs. <10 years), obesity status (BMI (≥30 vs. <30 kg/m2)), glycemic control (HbA1c (≥7% vs. <7%)), and concomitant T2D medications (SGLT2i or insulin). A mixed model for repeated measurements was employed, incorporating treatment, region, and subgroup as fixed factors, along with the treatment-by-subgroup interaction. Baseline values were used as covariates, all nested within each visit.Results: Among 792 randomized STRIDE participants at baseline, median T2D duration was 12.2 years, BMI 28.7 kg/m2, HbA1c 7.1%, with 35.1% on SGLT2i and 31.7% on insulin. Semaglutide significantly improved MWD regardless of T2D duration, BMI, HbA1c and concomitant SGLT2i or insulin use (Figure).Conclusion: These findings support the efficacy of semaglutide in patients with symptomatic PAD across the spectrum of T2D including non-obese participants and those with HbA1c <7%.Disclosure N. Rasouli: Advisory Panel; Novo Nordisk. Research Support; Novo Nordisk. Advisory Panel; Eli Lilly and Company. Research Support; Eli Lilly and Company. E. Guder Arslan: Employee; Novo Nordisk A/S, Sanofi. A. Catarig: Employee; Novo Nordisk A/S. Stock/Shareholder; Novo Nordisk A/S. K. Houlind: Consultant; LeMaitre, Novo Nordisk. B. Ludvik: Research Support; Novo Nordisk. Speaker's Bureau; Novo Nordisk. Advisory Panel; Novo Nordisk, Boehringer-Ingelheim. Speaker's Bureau; Boehringer-Ingelheim. Research Support; Amgen Inc. Speaker's Bureau; AstraZeneca. Research Support; Eli Lilly and Company. Advisory Panel; Eli Lilly and Company. Speaker's Bureau; Eli Lilly and Company. J. Nordanstig: Advisory Panel; AstraZeneca, Novo Nordisk. Other Relationship; Novo Nordisk. H. Sourij: Advisory Panel; Eli Lilly and Company. Speaker's Bureau; Eli Lilly and Company. Research Support; Eli Lilly and Company. Advisory Panel; Boehringer-Ingelheim. Speaker's Bureau; Daiichi Sankyo. Advisory Panel; Novo Nordisk A/S. Speaker's Bureau; Novo Nordisk A/S. Advisory Panel; Novartis AG, Amarin Corporation, Amgen Inc. S. Thomas: None. S. Verma: Other Relationship; Various. M.P. Bonaca: Other Relationship; CPC Clinical Research.FundingThe STRIDE trial was funded by Novo Nordisk A/S
PubDate: Sat, 21 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-291-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 292-OR: Oral Semaglutide and Cardiovascular Outcomes by Baseline A1C and
BMI in People with Type 2 Diabetes in the SOUL Trial-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 292-OR
Abstract: Introduction and Objective: In SOUL (NCT03914326), oral semaglutide (sema) 14 mg QD, a GLP-1 receptor agonist, reduced major adverse cardiovascular (CV) event (MACE) risk by 14%. GLP-1RAs are routinely prescribed to reduce A1c and BMI in type 2 diabetes (T2D). Whether the CV benefits of oral sema are influenced by baseline A1c or BMI is not fully known.Methods: SOUL’s primary outcome was time to first MACE, assessed for this post hoc analysis by baseline A1c, BMI and body weight using Cox regression.Results: People with T2D (n=9650; A1c 6.5–10%) and known atherosclerotic CV disease (ASCVD) or chronic kidney disease (CKD) were randomized to oral sema or placebo and followed for a mean of 47.5 months. We found significant differences in MACE outcomes associated with oral sema use by baseline A1c, with greater effects apparent with A1c >8.0% (Fig.). When the data were further analyzed across four A1c strata, the MACE benefit from oral sema appeared to apply to those with A1c >7%. The effects of oral sema on MACE were the same in those with BMI above / below 30 kg/m2, as well as across all four BMI strata, and above / below the mean body weight (87.9 kg) (Fig.).Conclusion: In SOUL, the CV benefits of oral sema appeared more pronounced with higher A1c levels at baseline but were consistent across various BMI categories. These data may help inform the individualized use of oral sema in people with T2D and ASCVD and/or CKD.Disclosure S.E. Inzucchi: Consultant; Novo Nordisk, AstraZeneca, Boehringer-Ingelheim, Merck & Co., Inc, Pfizer Inc, Bayer Pharmaceuticals, Inc. R. Abdul Ghani: None. J. Deanfield: Other Relationship; Aegerion Pharmaceuticals, Amgen Inc, AstraZeneca, Bayer Pharmaceuticals, Inc, Boehringer-Ingelheim, Merck & Co., Inc, Novartis Pharmaceuticals Corporation, Novo Nordisk A/S, Novo Nordisk A/S, Pfizer Inc. M.D.M. Engelmann: Employee; Novo Nordisk. G. Hovingh: Employee; Novo Nordisk. Stock/Shareholder; Novo Nordisk. O.K. Jeppesen: None. M. Kellerer: Advisory Panel; Abbott, Bayer Pharmaceuticals, Inc. Speaker's Bureau; Boehringer-Ingelheim, Johnson & Johnson Medical Devices Companies. Advisory Panel; Lilly Diabetes. Speaker's Bureau; Lilly Diabetes. Advisory Panel; Novo Nordisk. Speaker's Bureau; Novo Nordisk. Advisory Panel; Sanofi. K. Mandavya: Employee; Novo Nordisk. J.F. Mann: Other Relationship; AstraZeneca, Bayer Pharmaceuticals, Inc. Advisory Panel; Novo Nordisk. Board Member; AstraZeneca, Bayer Pharmaceuticals, Inc, Boehringer-Ingelheim, Novo Nordisk. Other Relationship; Sanofi. Consultant; AstraZeneca, Bayer Pharmaceuticals, Inc, Novo Nordisk. Research Support; AstraZeneca. Other Relationship; Boehringer-Ingelheim. Research Support; Novo Nordisk, Sanofi. Speaker's Bureau; AstraZeneca, Bayer Pharmaceuticals, Inc, Novo Nordisk, Novartis AG. Other Relationship; UpToDate Inc / KDIGO. N. Marx: Speaker's Bureau; Abbott, Amgen Inc, AstraZeneca. Advisory Panel; AstraZeneca. Speaker's Bureau; Bayer Pharmaceuticals, Inc. Advisory Panel; Bayer Pharmaceuticals, Inc. Speaker's Bureau; Boehringer-Ingelheim. Advisory Panel; Boehringer-Ingelheim. Speaker's Bureau; Daiichi Sankyo. Advisory Panel; Merck Sharp & Dohme Corp. Speaker's Bureau; Novo Nordisk. Advisory Panel; Novo Nordisk. Speaker's Bureau; Sanofi. Advisory Panel; Sanofi. Speaker's Bureau; Lilly Diabetes. C. Mathieu: Advisory Panel; Novo Nordisk, Sanofi, Eli Lilly and Company, Abbott, Medtronic, SAB Biotherapeutics, Inc, Roche Diabetes Care, Vertex Pharmaceuticals Incorporated, Biomea Fusion, Bayer Pharmaceuticals, Inc. D.K. McGuire: Consultant; Novo Nordisk. Advisory Panel; Novo Nordisk. Consultant; Lilly USA LLC. Advisory Panel; Lilly USA LLC. Consultant; Boehringer-Ingelheim. Advisory Panel; Boehringer-Ingelheim, AstraZeneca, ESPERION Therapeutics, Inc., NewAmsterdam Pharma, Pfizer Inc. Consultant; Applied Therapeutics, Lexicon Pharmaceuticals, Inc, Bayer Pharmaceuticals, Inc, Amgen Inc, Kailera, Idorsia, Alveus, Metsera. V. Mohan: Speaker's Bureau; Novo Nordisk. Advisory Panel; Abbott. Research Support; Servier Laboratories. Speaker's Bureau; USV Private Limited, Sanofi, Medtronic, Eli Lilly and Company. S.L. Mulvagh: Advisory Panel; Novo Nordisk, Merck & Co., Inc. R. Pop-Busui: Board Member; American Diabetes Association. Consultant; Averitas Pharma, Inc. Research Support; Bayer Pharmaceuticals, Inc. Other Relationship; Biogen. Research Support; Juvenile Diabetes Research Foundation (JDRF). Advisory Panel; Lexicon Pharmaceuticals, Inc, Novo Nordisk. Research Support; Novo Nordisk, National Institute of Diabetes and Digestive and Kidney Diseases. Consultant; Roche Diagnostics. N.R. Poulter: Consultant; Servier Laboratories, Alnylam Pharmaceuticals, Inc. Research Support; Servier Laboratories. Speaker's Bureau; AstraZeneca. Consultant; Aktiia. M. Ripa: Employee; Novo Nordisk. G. Roman: Advisory Panel; AstraZeneca. Consultant; Berlin-Chemie AG. Research Support; AstraZeneca. Advisory Panel; Boehringer-Ingelheim, Medtronic, Lilly Diabetes, Novo Nordisk. Research Support; Novo Nordisk. Advisory Panel; Roche Diabetes Care, Sanofi, Viatris Inc. R. Sánchez García: None. M. Shechter: None. J.B. Buse: Other Relationship; Corcept Therapeutics, Dexcom, Inc., Novo Nordisk. Consultant; Altimmune Inc, Amgen Inc, ApStem, Aqua Medical, AstraZeneca, Boehringer-Ingelheim, CeQur, Eli Lilly and Company, embecta, GentiBio. Other Relationship; Glyscend Therapeutics. Consultant; Insulet Corporation, Medtronic. Othe...
PubDate: Mon, 23 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-292-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 293-OR: The Antistenotic Effect of Liraglutide Is Abolished in Vascular
Smooth Muscle Cell-Specific Insulin-Receptor Knockout Mice-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 293-OR
Abstract: Introduction and Objective: Percutaneous intervention to treat atherosclerotic vessels can result in restenosis. Although drug-eluting stents have decreased rates of restenosis, insulin resistant patients with type-2 diabetes remain at risk. Our laboratory found that insulin has an anti-stenotic effect in rodent models of restenosis. However, the insulin effect is abolished in insulin resistant rodents fed high-fat diet. GLP-1 receptor agonists (GLP-1RA) are a new class of anti-diabetic drug that have anti-stenotic effects mediated by endothelial nitric-oxide synthase (eNOS) — like insulin — and we have shown are effective in insulin resistant rodents. Although GLP-1RAs may have a direct anti-stenotic effect mediated by GLP-1 receptors, GLP-1 receptor expression in vascular cells is low, thus GLP1-RA may act via stimulating insulin secretion. Previously, we have shown that the anti-stenotic effects of liraglutide (GLP-1RA) is abolished in endothelial-specific insulin receptor (IR) knockout mice. The objective of this study was to investigate the effect of GLP-1RA in mice with IR-knockout in vascular smooth muscle cells (SMCs).Methods: We used the tamoxifen-inducible CreERT2-loxP system utilizing smooth muscle myosin heavy chain (SMMHC)-Cre to generate SMC-specific IR knockout mice. Liraglutide (107nmol/kg/day)/vehicle was delivered s.c. by an osmotic pump implanted 3 days before femoral artery injury.Results: We found that liraglutide decreased neointimal growth evaluated 28 days after injury in SMMHC-IR floxed control mice and this effect was abolished in SMC-specific IR knockout mice.Conclusion: These data suggest that like IR in endothelial cells, IR in vascular SMCs is also important for liraglutide’s anti-stenotic effect.DisclosureT.A. Chaudhry: None. J. Yoo: None. A. Giacca: None.FundingHeart and Stroke (G-18-0022151)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-293-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 294-OR: Tirzepatide Prevents Palmitate-Induced Apoptosis, Autophagy, and
Senescence in Human Cardiac Progenitor Cells-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 294-OR
Abstract: Introduction and Objective: Tissue turnover in the human heart requires the recruitment of multipotent cardiac progenitor cells (hCPC). Defective hCPC number and pro-angiogenic capacity contribute to diabetes- and obesity-related heart failure in humans. Evidence supports potential cardiovascular benefits of dual GIP/GLP-1 receptor agonists. The aim of this study was to evaluate whether hCPC express functional GLP-1R and GIPR, and to investigate the ability of the GIP/GLP-1 receptor agonist tirzepatide to prevent palmitate-induces apoptosis, autophagy, and senescence in hCPC.Methods: hCPC were obtained from right auricle biopsies of non-obese, non-diabetic subjects undergoing elective cardiac surgery. GLP-1R and GIPR mRNA and protein expression were demonstrated by quantitative real-time PCR and immunoblotting, respectively. hCPC, pretreated or not with 100 nM tirzepatide for 1 h, were exposed to 0.25 mM palmitate for 16 h. CREB phosphorylation was evaluated by immunoblotting. Apoptosis, autophagy and senescence, were evaluated by cleaved caspase-3, LC3-II and p21Cip1/WAF1 immunoblotting, respectively.Results: hCPC express both functional GLP-1R and GIPR. Exposure of hCPC to tirzepatide for 5 min activated CREB (p<0.05). Treatment of hCPC with palmitate induced apoptosis, autophagy and senescence (p<0.05). Pretreatment of hCPC with tirzepatide prevented palmitate-induced apoptosis, autophagy, and senescence (p<0.05). Conversely, the GLP-1R agonist exendin-4 prevented palmitate-induced apoptosis and autophagy, whereas GIP prevented apoptosis, but not autophagy.Conclusion: hCPC express functional GLP-1R and GIPR that mediate partially overlapping bioeffects. Tirzepatide prevents palmitate-induced apoptosis, autophagy, and senescence of hCPC, showing that dual pharmacological targeting through both GLP-1R and GIPR might be required to exert full beneficial effects on hCPC survival and function.DisclosureC. Colabufo: None. I. Calderoni: None. R. Doria: None. C. Caccioppoli: None. G. Palma: None. G. Santarpino: None. T. Bottio: None. A.D. Milano: None. A. Leonardini: None. A. Natalicchio: Speaker's Bureau; AstraZeneca, Lilly Diabetes, Novo Nordisk, Sanofi. S. Perrini: None. A. Cignarelli: None. F. Giorgino: Advisory Panel; Abbott. Consultant; Amgen Inc. Advisory Panel; AstraZeneca, Bayer Pharmaceuticals, Inc, Biomea Fusion, Boehringer-Ingelheim, Daiichi Sankyo, Eli Lilly and Company. Research Support; Eli Lilly and Company. Board Member; European Association for the Study of Diabetes. Consultant; Medtronic. Advisory Panel; Mundipharma, Novo Nordisk, Roche Diabetes Care. Research Support; Roche Diabetes Care. Advisory Panel; Sanofi. L. Laviola: Speaker's Bureau; A. Menarini Diagnostics, Abbott, AlfaSigma, Ascensia Diabetes Care, AstraZeneca. Advisory Panel; Boehringer-Ingelheim, Eli Lilly and Company. Speaker's Bureau; Boehringer-Ingelheim, Eli Lilly and Company. Research Support; Medtronic. Speaker's Bureau; Medtronic. Advisory Panel; Novo Nordisk. Speaker's Bureau; Novo Nordisk. Advisory Panel; Roche Diabetes Care. Speaker's Bureau; Roche Diabetes Care. Advisory Panel; Sanofi. Speaker's Bureau; Sanofi.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-294-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 295-OR: Cardiovascular Events in Patients Treated with
Sulfonylureas—A Target Trial Emulation-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 295-OR
Abstract: Introduction and Objective: Sulfonylureas are a common choice in treatment of type 2 diabetes (T2D). Cardiovascular safety of sulfonylureas is unknown.Methods: We emulated a target trial using observational data from 12 health systems and insurance plans across the US. Eligible individuals were patients with T2D and hyperglycemia (HbA1c 7.0-11.0% or equivalent glucose levels) at moderate CV risk (no prior CV disease) on metformin monotherapy who initiated a second T2D medication between 01/01/13 and 12/31/22, with eGFR ≥ 45 ml/min/1.73m2 and with no contraindications to study medications. We compared patients initiating individual sulfonylureas (glimepiride, glipizide and glyburide) to patients initiating DPP4i (which were shown in multiple controlled trials to have CV risk similar to placebo). In each treatment arm we estimated the 5-year risk of a composite outcome (MI, ischemic CVA, HF hospitalization or CV death) after adjustment for demographics, comorbidities and laboratory values at baseline.Results: We studied 48,165 patients followed for a median of 37 (IQR 20-64) months, with a median age of 61 (IQR 52-69) years and median baseline HbA1c of 7.8% (IQR 7.3-8.5%). Of these, 13,849 patients initiated a DPP4i; 14,282 initiated glimepiride; 18,147 initiated glipizide; and 1,887 initiated glyburide. A total of 3,158 (6.6%) of patients experienced the primary outcome endpoint. The estimated 5-year risk ratios (95% CI), compared to DPP4i, were 1.04 (95% CI 0.83 to 1.24) for glyburide, 1.07 (95% CI 0.96 to 1.16) for glimepiride and 1.13 (95% CI 1.03 to 1.23) for glipizide. Sensitivity analysis excluding saxagliptin from the reference DPP4i category showed similar results.Conclusion: Patients with T2D treated with glipizide as a second agent after metformin had the highest incidence of MACE-4 events compared with patients treated with DPP4i among those initiating a sulfonylurea. Glipizide may not be the optimal agent in treatment of patients with T2D at elevated CV risk.Disclosure A. Turchin: Consultant; Novo Nordisk. Research Support; Eli Lilly and Company. Consultant; Proteomics International. L. Petito: Advisory Panel; Patient-Centered Outcomes Research Institute. Research Support; Omron Healthcare Co., Ltd. Consultant; Ciconia Medical. E. Hegermiller: None. R.M. Carnahan: None. A.R. Devries: None. S. Goel: None. M.E. McDonnell: Research Support; Dexcom, Inc. M. Lansang: Research Support; Abbott, Dexcom, Inc., Neuro Solutions 100. V. Nair: None. E.L. Priest: Research Support; Boehringer-Ingelheim, AstraZeneca, Vifor Pharma, Owkin. V. Willey: Other Relationship; Carelon Research. A.F. Kaul: None. M. Hernan: None.FundingPCORI (DB-2020C2-20308)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-295-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 296-OR: Underutilization of High-Intensity Statin Therapy in Patients with
Type 2 Diabetes and Elevated Coronary Artery Inflammation Detected on
Coronary CT Angiography-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 296-OR
Abstract: Introduction and Objective: Pericoronary adipose tissue (PCAT) attenuation, assessed using coronary computed tomography angiography (CCTA), is a novel biomarker for coronary artery inflammation. A mean attenuation above -70.5 Hounsfield Units (HU) is associated with higher rate of myocardial infarction. This study aims to identify treatment patterns in patients with type 2 diabetes (T2DM) who had elevated PCAT attenuation on CCTA.Methods: We retrospectively analyzed 168 scans in consecutive patients with T2DM who underwent CCTA from 1/1/2021 to 9/1/2024 and met these key criteria: age 40-80 years, HbA1C ≤8.0%, BMI ≤35.0, evidence of coronary atherosclerosis on CCTA, treatment with ≥1 oral hypoglycemic agent, and no history of prior coronary interventions. The scans were performed on Siemens Somatom FORCE dual-source scanner. PCAT attenuation was assessed in the proximal 1-5cm portion of the right coronary artery on TeraRecon Aquarius Intuition software. Patients were classified as having elevated (E-PCAT) or non-elevated (N-PCAT) PCAT attenuation based on a -70.5 HU cutoff.Results: E-PCAT (n=63) and N-PCAT (n=105) patients had similar age (66.9±9.1 vs 65.3±10.2, respectively; p=0.28) and HbA1C (6.5±0.7 vs 6.7±0.7; p=0.15). Compared to N-PCAT patients, E-PCAT patients had lower rate of being on high-intensity statins (30% vs 48%, p=0.03) and similar rate of being on metformin (93.7% vs 92.4%, p>0.99), SGLT-2 inhibitors (19.1% vs 26.7%, p=0.35) and GLP-1 agonists (12.7% vs 20% p=0.29). E-PCAT patients had lower HDL level (42.7±13.2 mg/dL vs 49.6±15.5 mg/dL, p=0.006), while both groups' LDL levels were similar (E-PCAT: 74.0±33.2 mg/dL vs N-PCAT: 75.4±34.0 mg/dL, p=0.79).Conclusion: CCTA-based evidence of elevated coronary inflammation is associated with underutilization of high-intensity statin therapy in patients with T2DM, despite guideline-based indications for aggressive preventive treatment.DisclosureB. Wu: None. K. Nieman: Research Support; Siemens Healthcare Diagnostics. Consultant; Novartis Pharmaceuticals Corporation, Cleerly, RapidAI, Artrya. B. Arnold: None. R. Sandoval: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-296-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 297-OR: Interactive Virtual Assistant for Health Promotion and Diabetes
Care in Older Adults with Diabetes—A Randomized Controlled Trial-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 297-OR
Abstract: Introduction and Objective: This study evaluated the impact of an interactive virtual assistant device, programmed with a behavioral intervention model, on mental-health and diabetes-related outcomes in older adults with type 2 diabetes (T2D)Methods: We conducted a randomized controlled trial enrolling participants aged 65 years or older with T2D. Participants were randomized to receive a Smart Speaker EchoDot 3rd Gen device, programmed with a behavioral intervention that included automatic medication reminders and health tips, or to continue with usual care for 12 weeks. The primary outcome was mental distress, assessed using the SRQ-20 scale. Secondary outcomes included quality of life (measured with the SF-36 scale), adherence to diabetes self-care behaviors (assessed with the SCI-R scale), and HbA1c. An analysis of covariance model was used to evaluate the impact of the intervention on study outcomes. Between-group mean differences after the intervention period, adjusted for baseline data and relevant covariates, were reported, with statistical significance set at an alpha level of 0.05Results: A total of 112 participants (63% female, 63% white; mean age: 72.5 years; mean T2D duration: 16.9 years; mean HbA1c: 7.9%) were randomized, with 103 completing the trial. At 12 weeks, participants in the intervention group showed a reduction in mental distress (mean difference: -1.46; 95% CI -2.73 to -0.19; p=0.024), an increase in quality of life (mean difference: 9.46; 95% CI 3.65 to 15.26; p=0.001), greater adherence to diabetes self-care behaviors (mean difference: 3.40; 95% CI 1.61 to 5.19; p<0.001), and lower HbA1c (mean difference: -0.48; 95% CI -0.85 to -0.11; p=0.011) when compared to those in the usual care groupConclusion: In this randomized controlled trial, a smart-speaker-based intervention was associated with significant improvements in mental health, quality of life, diabetes self-care behaviors, and HbA1c in older adults with T2DDisclosureL.S. Matzenbacher: None. F.L. da Costa: None. L.G.B. de Barros: None. V. Gheno: None. I.S. Maia: None. L.M. Blank: None. M.B. Brum: None. L.F. Fontoura: None. J. Alessi: None. G.H. Telo: None.FundingBrazilian National Council for Scientific and Technological Development (CNPq/MCTI/FNDCT 18/2021 grant)
PubDate: Mon, 23 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-297-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 298-OR: Reducing Diabetes Distress Leads to Positive Glycemic
Change—Results from the EMBARK Trial-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 298-OR
Abstract: Introduction and Objective: We asked how a diabetes distress (DD) intervention fostered changes in diabetes-related emotion management, diabetes problem solving, and HbA1C; and to test a hypothesized 4-Stage, sequential pathway whereby reductions in DD were linked with improved glycemic outcomes.Methods: PWDs with T1D (n=276) with elevated DD and HbA1cwere assigned to: StreamLine, a diabetes self-management program; TunedIn, an ACT-based (Acceptance and Commitment Therapy), emotion-focused DD program; or FixIt, an integration of Streamline and TunedIn. 12-month changes in DD (Stage 1), diabetes-related emotion management (Stage 2), diabetes-related problem solving (Stage 3), and HbA1C (Stage 4) were each evaluated. A structural equation model was then specified to evaluate the hypothesized 4-Stage sequence of change over time.Results: Improvements occurred in all 3 groups at all 4 stages. However, TunedIn and FixIt, compared to StreamLine, displayed significantly greater improvements in Stages 1, 2 and 3; while StreamLine and TunedIn displayed greater improvements in HbA1C (Stage 4) than FixIt. The structural equation model supported the hypothesized 4-Stage sequence, such that associations between reductions in DD and glycemic change were explained through improvements in emotion management and problem solving. Two plausible, alternative models also were tested: reversing Stages 1 and 2; reversing stages 3 and 4. In both cases, the model fit indices indicated worse fit, thus supporting the original 4-Stage model.Conclusion: Overall, TunedIn an emotion-focused intervention, demonstrated the most comprehensive, impactful intervention benefits. The model demonstrated how reductions in DD are linked with improved glycemic outcomes through changes in emotion management, which then allow for improved diabetes-related problem solving. This sequence can assist in designing effective intervention programs to reduce DD and improve overall diabetes management.DisclosureL. Fisher: None. S. Guzman: Consultant; Abbott. W.H. Polonsky: Consultant; Abbott. Research Support; Abbott. Consultant; Dexcom, Inc. Research Support; Dexcom, Inc. Other Relationship; Ascensia Diabetes Care. L.A. Strycker: None. K. Greenberg: None. D.M. Hessler: None.FundingDiabetes and Digestive and Kidney Diseases (R01DK121241)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-298-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 299-OR: Outcomes of Type 1 Diabetes and Life (T1DAL) Behavioral
Intervention Pilot Targeting Health-Related Quality of Life (HRQOL)-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 299-OR
Abstract: Introduction and Objective: Individualized behavioral support is recommended during routine diabetes care to address T1D challenges. This non-randomized pilot study tested a brief behavioral intervention targeting HRQOL for people with T1D across the lifespan and their parents or partners.Methods: We recruited youth and adults receiving T1D care at specialty diabetes clinics or in adult primary care. Participants completed the Type 1 Diabetes and Life (T1DAL) measure of T1D-specific HRQOL and HbA1c was collected at pre- and post-intervention. A certified diabetes care and education specialist delivered 2 remote intervention sessions over 6 months, tailored to HRQOL domains identified by participants’ T1DAL responses.Results: We enrolled 120 participants (39 pediatric T1D clinic, 41 adult T1D clinic, 40 primary care) with 37 parents and 25 partners. Mean T1DAL scores increased from pre- to post-intervention (Table) with variable changes in HbA1c. Satisfaction themes included: felt supported/non-judgmental, program emphasized stress management/positive perspectives, and learned new skills.Conclusion: The T1DAL intervention was feasible to conduct across settings and participants were largely satisfied. Improvements in HRQOL suggest potential psychosocial benefits. Integration with a medical intervention may be needed to improve glycemic outcomes.DisclosureM.E. Hilliard: None. R.S. Weinstock: Research Support; Amgen Inc, Eli Lilly and Company, Tandem Diabetes Care, Inc, Diasome Pharmaceuticals, Insulet Corporation, MannKind Corporation, Dexcom, Inc. K.K. Hood: Consultant; Sanofi. Advisory Panel; MannKind Corporation. Consultant; Havas Health. Research Support; embecta. P.M. Trief: None. S. Kim: None. D. DeSalvo: Consultant; Dexcom, Inc. Advisory Panel; Insulet Corporation. Y. Rojas: None. W. Levy: None. S.S. Eshtehardi: None. K. Holland: None. A.K. Schneider-Utaka: None. L.M. Agostini: None. M. de Wit: Speaker's Bureau; Medtronic. Consultant; Sanofi. L.H. Messer: Employee; Tandem Diabetes Care, Inc. B.J. Anderson-Thomas: None.FundingThe Leona M. and Harry B. Helmsley Charitable Trust, 2012-04197 (PI: Hilliard); NIH 1K26DK138332 (PI: Hilliard)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-299-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 300-OR: Mechanisms of Behavior Change in Diabetes Prevention—Evidence
from a Randomized Trial in Women with a History of Gestational Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 300-OR
Abstract: Introduction and Objective: Women with a history of gestational diabetes mellitus (GDM) face a preference-sensitive decision for diabetes prevention. Their commitment to adhere to a given strategy (e.g., lifestyle change and/or metformin use) may be bolstered with the use of shared decision-making (SDM).Methods: We conducted a pragmatic RCT examining effectiveness of SDM on uptake of diabetes prevention strategies among women with GDM, overweight/obesity, and prediabetes within two large health care systems. In this interim, ancillary study, we evaluated motivational factors (informed by the Capability, Opportunity, Motivation, and Behavior model) as mechanisms to explain “why, how, and for whom” SDM may be effective for achieving behavior change. We used mixed effects regression and the Sobel test to test if the effect of the SDM intervention on outcomes are mediated by patient activation (Altarum Consumer Engagement Measure).Results: We included 226 women with 12-months of follow-up data (mean age 40.7±5.8 years, Hgb A1c 5.8±0.2, BMI 32.5±7.0; 61% non-white). Women randomized to SDM intervention had significantly greater increases in total activation (SDM baseline 71.1±9.5, follow-up 72.2±9.0 vs. control baseline 70.4±9.1, follow-up 70.5±8.7), driven mostly by an increase in the commitment subscale, which reflects the patient's dedication to maintaining healthy behaviors. Higher scores on the commitment subscale were also associated with greater 12-month weight loss (p=0.049), any physical activity (p<.001), higher intensity physical activity (p=0.016), and reduced processed food consumption (p<.001). Although SDM improved patient activation, we find limited evidence to support mediation (p>0.05).Conclusion: Our study found that SDM bolsters women’s commitment to engage in diabetes prevention health behavior changes, which independently improves core outcomes. SDM should be used to enhance engagement in evidence-based strategies to lower diabetes risk among high-risk groups.DisclosureL.E. Wisk: None. T. Tibbe: None. R. Maranon: None. A.V. Moss: None. R. Madievsky: None. S.J. Liu: None. S.C. Thomas: Employee; PocketRN. J. Page: None. W.M. Andrews: None. J. Krong: None. C. Mangione: None. O. Duru: None. T. Moin: None.FundingThis work was generously supported by the National Institute of Diabetes and Digestive and Kidney Diseases (R01DK127733) (PIs: Moin and Duru).
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-300-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 301-OR: Findings from a Culturally Adapted Community Health Worker
Intervention to Improve Diabetes Management among South Asian Patients in
New York City-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 301-OR
Abstract: Introduction and Objective: Research suggests that type 2 diabetes disproportionately affects South Asian Americans compared to other racial and ethnic groups.Methods: The DREAM Initiative was a multi-level, community health worker (CHW)-led intervention to improve diabetes management among South Asian patients. Participants were recruited from NYC primary care practices from 2019-2022. Individuals randomized to the intervention group received five CHW-led education sessions, goal setting activities, and referrals to specialists and social services over six months; control group individuals were not contacted. The primary outcome was a decrease in HbA1c of ≥0.5% from baseline to endpoint; secondary outcomes included a decrease in weight and body mass index (BMI). Generalized mixed effects models were run, adjusting for age, sex, and collection of data during COVID, and accounted for correlation of patients nested within primary care practices.Results: Among 592 individuals with an HbA1c measurement within +/-180 days of the primary 6-month endpoint, 36.7% of the intervention group and 29.3% of the control group had a reduction in HbA1c≥0.5%; the group difference was not significant (p=0.110). Weight decreased from 160.3 lbs. to 156.8 lbs. in the treatment group, and from 160.7 lbs. to 159.6 lbs. in the control group. BMI decreased from 27.7 to 27.1 in the treatment group, and from 27.9 to 27.7 in the control group. Reduction in weight and BMI was statistically significant between groups (p<0.001).Conclusion: While a significant difference was not seen for HbA1c reduction between groups, weight and BMI were found to be statistically significant in favor of the intervention arm at endpoint. This suggests that a culturally tailored intervention may be effective in managing diabetes in this population.DisclosureL. Wyatt: None. S. Lim: None. H. Belli: None. S. Mammen: None. J. Zanowiak: None. S. Hussain: None. N. Islam: None.FundingNIH NIDDK (R01DK11048)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-301-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 302-OR: Financial Incentives and Nurse Coaching to Enhance Diabetes
Outcomes—A Randomized Controlled Trial-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 302-OR
Abstract: Introduction and Objective: Evaluate efficacy of financial incentives and nurse coaching on glycemic control at 12 months in a diverse group of adults with type 2 diabetes.Methods: We randomized 450 participants into a structured financial incentives intervention (FINANCE-DM) comprised of: 1) diabetes education/skills training, 2) home telemonitoring, and 3) structured financial incentives and compared them to an active control group (nurse education and home telemonitoring alone). The financial incentive structure included incentives for uploading glucose measurements, participating in telephone delivered educational sessions, and absolute percentage drop in HbA1c from baseline at 3-month intervals. In preliminary analyses, longitudinal mixed model with treatment, time, and treatment x time interactions for change in HbA1c from baseline were run for each arm.Results: Mean age was 57.7 (sd=29.3), mean duration of diabetes was 13.7 years, 51.3% female, 32.4% Black, 10% Hispanic, 25.8% with income <$20,000, 40.4% Medicare, and 21.8% Medicaid. We found statistically significant differences within both groups (at 6-months -1.30% drop for those randomized to FINANCE-DM intervention and -0.93% for control). See Figure 1.Conclusion: Financial incentives resulted in a clinically significant drop of over 1% in HbA1c at 6-months in a diverse sample based on racial/ethnic, sociodemographic, and gender characteristics.DisclosureL.E. Egede: None. J.A. Campbell: None. R.J. Walker: None.FundingThis study is funded by grant number R01DK120861 from the National Institute of Diabetes and Digestive Kidney Disease.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-302-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 303-OR: Efficacy and Safety of BGM0504 in Chinese Patients with Type 2
Diabetes—A Multicenter, Randomized, Double-Blind, Placebo-Controlled and
Semaglutide Positive-Controlled Phase 2 Trial-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 303-OR
Abstract: Introduction and Objective: BGM0504 is a dual agonist targeting the glucagon-like peptide-1 receptor (GLP-1R) and glucose-dependent insulinotropic polypeptide receptor (GIPR). This study aimed to evaluate the safety and efficacy of BGM0504 in Chinese adults with type 2 diabetes mellitus (T2DM) and compare its performance to Semaglutide through multiple subcutaneous injections.Methods: This multicenter, randomized, placebo-controlled, and Semaglutide positive-controlled trial included 64 Chinese adults with T2DM. Participants were randomized into five groups: BGM0504 5 mg (n=12), 10 mg (n=12), 15 mg (n=12), placebo (n=12), and Semaglutide 1.0 mg (n=16). The study consisted of a titration phase (2-6 weeks), 12 weeks of once-weekly treatment, and a 2-week follow-up. The trial was registered with the Chinese NMPA (CTR20232464).Results: Changes in HbA1c from baseline to week 12 relative to placebo were as follows (LSM, 95% CI): <ul> <li>5 mg group: −1.82% (−2.83 to −0.81)</li> <li>10 mg group: −2.05% (−3.27 to −0.82)</li> <li>15 mg group: −2.56% (−3.58 to −1.54)</li> <li>Semaglutide 1.0 mg: −1.86% (−2.83 to −0.90)</li> </ul> The 15 mg dose was superior to Semaglutide (p=0.0327). Improvements in FPG and 2h-PPG relative to placebo ranged from −3.18 to −1.63 mmol/L and −6.16 to −4.76 mmol/L, respectively (p < 0.05). The percentage of participants achieving HbA1c <7.0% was:<ul><li>5 mg group: 76.9%</li><li>10 mg group: 81.8%</li><li>15 mg group: 91.7%</li><li>Semaglutide 1.0 mg: 75.0%</li><li>Placebo: 16.7%</li></ul>All BGM0504 doses were superior to placebo in achieving this target (p < 0.05). The 15 mg group also demonstrated significantly greater weight reduction compared to Semaglutide (p < 0.001). All doses of BGM0504 were well tolerated, with common adverse events.Conclusion: BGM0504 was safe and well-tolerated, with the 15 mg dose showing the most substantial effects. It is a promising treatment option for improving glycemic control and achieving weight reduction in patients with T2DM.Disclosure J. Yuan: Employee; BrightGene Bio-Medical Technology Co., Ltd. Y. Huang: Employee; BrightGene Bio-Medical Technology Co., Ltd. H. Ding: Employee; BrightGene Bio-Medical Technology Co., Ltd. D. Xie: Employee; BrightGene Bio-Medical Technology Co., Ltd. X. Jiang: Consultant; BrightGene Bio-Medical Technology Co., Ltd. X. Yuan: None. Z. Cao: None. P. Jin: None. L. Ji: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-303-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 304-OR: Leveraging Real-World Evidence to Analyze Changes in Prescribing
of GLP-1 Receptor Agonists in the United States-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 304-OR
Abstract: Introduction and Objective: GLP-1 receptor agonists (GLP-1 RAs) have revolutionized type 2 diabetes (T2D) and obesity management but are costly, raising equity concerns. This study examines prescribing disparities for GLP-1 RAs among White, Black, and Hispanic patients using a national EHR database.Methods: This retrospective study analyzed adults with uncomplicated T2D (ICD-10: E11.9) from the TriNetX national EHR repository. Prescription trends were summarized from 2019 to 2023. Adjusted odds ratios (aOR) for semaglutide and tirzepatide prescriptions in 2022-2023 were calculated by race/ethnicity, adjusting for age, sex, and Charlson Comorbidity Index.Results: The study included 14,196 White, 13,982 Black, and 11,974 Hispanic patients. Semaglutide, tirzepatide, and dulaglutide were the most frequently prescribed GLP-1 RAs. In 2022-2023, compared to White patients, Black patients had an aOR of 0.7 (95% CI: 0.6-0.9) for tirzepatide and 0.8 (95% CI: 0.7-0.9) for semaglutide. Hispanic patients had an aOR of 0.4 (95% CI: 0.3-0.5) for tirzepatide and 0.6 (95% CI: 0.6-0.7) for semaglutide.Conclusion: EHR databases are effective tools for monitoring prescribing trends and identifying disparities. White patients are being prescribed the latest-generation GLP-1 RAs (semaglutide and tirzepatide) more frequently than Black and Hispanic patients, highlighting the need for equitable access to GLP-1 RA therapies.DisclosureP. Kukhareva: None. K. Kawamoto: Consultant; Pfizer Inc. Other Relationship; Beckman Coulter.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-304-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 305-OR: Tirzepatide in Type 1 Diabetes—Safety, Tolerability, and
Clinical Outcomes—Real-World Experience from a Large UK Center-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 305-OR
Abstract: Introduction and Objective: Tirzepatide is licensed for type 2 diabetes and weight management. Obesity is an increasing problem in people with type 1 diabetes (T1D), exposing them to an elevated cardiometabolic risk. We aimed to evaluate the safety, tolerability and efficacy of tirzepatide in people with T1D and obesity.Methods: We conducted a longitudinal, retrospective study, including all people with T1D started on tirzepatide at Sheffield Teaching Hospitals (UK). Case notes were reviewed for tolerability, side effects, hospitalizations and clinic weights. Glycemic metrics were obtained from the respective CGM cloud applications. Two-tailed paired t-tests compared variables before and after 3 months of tirzepatide use. Data are presented as median (IQR) and mean (95%CI).Results: Fifty-eight participants were identified (65.5% female). Median age 39.5 years (26.0-51.8), weight 101.5 kg (92.7-123.3), body mass index 36.3 kg/m2 (33.2-40.5) and HbA1c 7.7% (6.9-8.3%.) Mean weight significantly reduced by 6.7 kg (6.7%) after 3 months (5.4-8.0 kg, p<0.001, n=36.) Mean total daily insulin dose reduced by 21.6 units (12.8-30.4, p<0.001, n=28), skewed towards a reduction in bolus doses (14.4 units, 6.6-22.2, p=0.001, n=26.) Time in range (70-180 mg/dl) significantly increased from 54.9% to 60.8% (0-11.8, p=0.048, n=36), mean sensor glucose decreased from 185 to 173 mg/dl (2-23, p=0.019) and the coefficient of variation decreased from 35.4% to 32.5% (1.5-4.3, p<0.001). Side effects were reported by 29 participants (32.8%), with nausea or vomiting the most common (22.4%), but 53 participants (91.4%) continued on tirzepatide at 3 months. There were three unplanned admissions related to tirzepatide (median one day length of stay.)Conclusion: Tirzepatide showed promising results in terms of safety, tolerability, and clinical benefits in people with T1D. Definitive data from RCTs in T1D are urgently needed to confirm these findings.Disclosure S.A. Berry: Research Support; Tandem Diabetes Care, Inc. E. McNally: None. I. Goodman: None. J. Elliott: Speaker's Bureau; Abbott. Research Support; Dexcom, Inc. Advisory Panel; Dexcom, Inc. Speaker's Bureau; Dexcom, Inc., Boehringer-Ingelheim, Eli Lilly and Company. Advisory Panel; Glooko, Inc. Speaker's Bureau; Insulet Corporation. Advisory Panel; Roche Diabetes Care. Speaker's Bureau; Sanofi. Advisory Panel; Ypsomed AG. A. Iqbal: Speaker's Bureau; Lilly Diabetes. Research Support; Abbott, Dexcom, Inc. Speaker's Bureau; AstraZeneca, Boehringer-Ingelheim. Research Support; Tandem Diabetes Care, Inc.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-305-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 306-OR: Mazdutide vs. Placebo as Monotherapy in Patients with Type 2
Diabetes (DREAMS-1)-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 306-OR
Abstract: Introduction and Objective: Mazdutide (MAZ) is a once-weekly GLP-1 and glucagon receptor dual agonist in development for type 2 diabetes (T2D). This trial assessed the efficacy and safety of MAZ vs placebo (PBO) in patients with T2D inadequately controlled by diet and exercise alone.Methods: In this randomized, 24-week double-blind, placebo-controlled phase 3 trial, 320 patients with T2D (mean baseline HbA1c 8.24%, age 50.4 yrs, diabetes duration 1.9 yrs, body weight 77.7 kg) were randomised 1:1:1 to receive MAZ 4 mg, 6 mg or PBO. Primary endpoint was mean change in HbA1c from baseline at week 24. Secondary endpoints included proportion of patients achieving HbA1c and weight reduction targets and mean percentage change in weight from baseline at week 24.Results: At week 24, MAZ was superior to PBO in mean HbA1c change from baseline (LSM treatment difference: −1.43% [95% CI −1.73, −1.13] for MAZ 4 mg; −2.02% [−2.32, −1.72] for MAZ 6 mg; both p<0.0001). MAZ was superior to PBO in proportion of patients achieving HbA1c <7.0%, weight reduction ≥5%, both HbA1c <7.0% and body weight reduction ≥5%, as well as mean percentage change in weight from baseline at week 24 (Table). The most common adverse events were gastrointestinal and mostly mild to moderate in severity. No severe hypoglycemia was reported.Conclusion: In Chinese patients with T2D, MAZ as monotherapy demonstrated robust and clinical meaningful HbA1c and body weight reduction.Disclosure D. Zhu: Consultant; Innovent Biologics. J. Zhao: None. H. Cai: None. X. Chu: Consultant; Innovent Biologics. S. Xiu: Consultant; Innovent Biologics. C. Song: Consultant; Innovent Biologics. Z. Cheng: None. H. Cao: None. H. Jiang: None. L. Zhang: None. F. Xue: None. H. Deng: Employee; Innovent Biologics. H. Li: None. L. Li: Employee; Innovent Biologics. Stock/Shareholder; Innovent Biologics. L. Qian: Employee; Innovent Biologics.FundingInnovent Biologics, Inc.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-306-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 307-OR: Effect of Oral Small Molecule GLP-1 Receptor Agonist TERN-601 in
Healthy Participants with Obesity or Overweight—A First-in-Human Study-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 307-OR
Abstract: Introduction and Objective: TERN-601 is a novel once-daily oral small molecule GLP-1 receptor agonist, in development for chronic weight management. This first-in-human (FIH) study evaluated the safety, tolerability, and effect on body weight of TERN-601 in participants with obesity or overweight.Methods: Participants (N=12/cohort) with BMI ≥27 to <40 kg/m2 were randomized 3:1 to receive TERN-601 or placebo once daily for 28 days in 3 cohorts. TERN-601 was titrated within 2 weeks from 100 mg to target doses of 240, 500, or 740 mg. Safety assessments were performed throughout the study.Results: There were no treatment-related dose interruptions, reductions, or discontinuations. Despite rapid titration, most adverse events (AEs) were mild and gastrointestinal; no Grade ≥3 AEs were reported. No nausea/vomiting in 240 mg group. There were no clinically meaningful changes in HR, BP or ECGs. All TERN-601 doses showed continuous mean weight loss (up to -5.5%) over 28 days (Figure). At TERN-601 740 mg, 67% of participants achieved ≥5% weight loss.Conclusion: TERN-601 demonstrated favorable safety and tolerability in this FIH study in participants with obesity or overweight. TERN-601 led to clinically meaningful reductions in body weight. These results support further clinical development of TERN-601 for chronic weight management.Disclosure C.H. Nelson: Employee; TERNS Pharmaceuticals. Stock/Shareholder; TERNS Pharmaceuticals, Gilead Sciences, Inc. C. Jones: Employee; TERNS Pharmaceuticals. E. Kwan: Employee; TERNS Pharmaceuticals. E.N. Castelloe: Consultant; TERNS Pharmaceuticals, Ascendis Pharma A/S, Artelo Biosciences, Dianthus Therapeutics, Soleno Therapeutics, Plexium, Sustained Therapeutics, Virogenics, Nobias Therapeutics. T. Marmon: None. E.T. Kuriakose: Employee; TERNS Pharmaceuticals.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-307-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 308-OR: Risk of New Cancer Diagnoses with GLP-1 Receptor Agonist, SGLT2
Inhibitor, DPP-4 Inhibitor, and Sulfonylurea Use in Type 2 Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 308-OR
Abstract: Introduction and Objective: Concerns have been raised about potentially harmful cancer-related effects of certain medications used to manage type 2 diabetes (T2D). However, there is limited evidence from head-to-head comparisons between commonly used second-line T2D medications with respect to incident cancer risk.Methods: In a retrospective target trial emulation, we compared glucagon-like peptide-1 receptor agonists (GLP-1RA), sodium-glucose cotransporter 2 inhibitors (SGLT2i), dipeptidyl peptidase-4 inhibitors (DPP4i), and sulfonylureas with respect to incident cancer risk among adults with T2D and moderate CVD risk. We used de-identified administrative claims from the OptumLabs Data Warehouse and the Medicare fee-for-service 100% sample to identify adults ≥21 years with T2D between 2014-2021 with an estimated 1-5% annualized risk of a major adverse cardiovascular event who initiated these drugs. We then compared rates of any incident cancer (excluding non-melanoma skin cancer) and each cancer type using propensity score inverse probability of treatment weighted Cox proportional hazards models.Results: We identified 40,956 patients starting GLP-1RA (mean age 65.1 ± 8.3 years, 51.1% male), 52,050 starting SGLT2i (mean age 65.1 ± 8.4 years, 50.6% male), 74,314 starting DPP4i (mean age 65.44 ± 8.5 years, 50.9% male), and 187,960 starting sulfonylurea (mean age 65.4 ± 8.5 years, 51.0% male). Treatment with GLP-1RA was associated with a 12% higher risk of incident cancer compared to SGLT2i (HR 1.12, 95% CI 1.04-1.22), 12% higher risk compared to DPP4i (HR 1.12, 95% CI 1.05-1.20), and 15% higher risk compared to sulfonylurea (HR 1.15, 95% CI 1.08-1.22). This increase in risk was driven primarily by higher incidence of melanoma, male reproductive, and female breast cancers.Conclusion: This increased risk of some cancers observed with GLP-1RA warrants further investigation and cautious use among individuals at risk for these malignancies.DisclosureS. Sklepinski: None. J. Herrin: None. K. Swarna: None. J.J. Neumiller: Advisory Panel; Proteomics International. R.J. Galindo: Consultant; Abbott, AstraZeneca. Advisory Panel; Bayer Pharmaceuticals, Inc, Boehringer-Ingelheim. Consultant; Dexcom, Inc., Eli Lilly and Company, Medtronic. Research Support; National Institute of Diabetes and Digestive and Kidney Diseases. Consultant; Novo Nordisk. Research Support; Novo Nordisk, Boehringer, Dexcom. G. Umpierrez: Research Support; Abbott, Dexcom, Inc., Bayer Pharmaceuticals, Inc, Corcept Therapeutics. Advisory Panel; Dexcom, Inc., GlyCare Health. J. Ross: Research Support; Janssen Pharmaceuticals, Inc. Y. Deng: None. E. Polley: None. M. Mickelson: None. R.G. McCoy: Consultant; Wolters Kluwer Health, Yale New Haven Health System. Research Support; American Diabetes Association. Other Relationship; American Diabetes Association.FundingPCORI Award (PCS-1409-24099)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-308-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 309-OR: Improvement in Day and Night Glycemic Outcomes with an AI-Based
Fully Closed Loop (FCL) System Compared with Hybrid Closed Loop (HCL) in
Adults, Young Adults, and Adolescents with Type 1 Diabetes (T1D)-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 309-OR
Abstract: Introduction and Objective: HCL has become standard therapy for T1D, with particular glycemic improvements overnight. These systems require meal announcement for optimal daytime glycemia. FCL therapy will reduce daytime diabetes management burden and may further improve nighttime glycemia.Methods: Adolescents (14-17yrs), young adults (18-25yrs), and adults (26-60yrs) were enrolled at 3 sites to evaluate a novel FCL system (Automated Insulin Delivery as an Adaptive NETwork [AIDANET]). AIDENET was initiated in a supervised hotel setting, followed by 7 days at home. Results were analyzed by time of day (nighttime: 12am-6am) and compared to usual care with HCL. T-tests were used to assess non-inferiority and difference of glycemic metrics with a primary outcome of mean sensor glucose.Results: 34 subjects (25.4±12.6 yrs, HbA1c 8.0±1.1%, 62% F) participated. Daytime FCL use was non-inferior, but not different, to HCL for all glycemic metrics except coefficient of variation (Table). Nighttime FCL wear was both non-inferior and significantly different (p<0.05) for most glycemic metrics.Conclusion: The AIDANET FCL system significantly improved nighttime glycemia and was equivalent during the daytime compared to HCL. Longer use studies are necessary to determine sustainability in the home setting.Disclosure E.C. Cobry: Advisory Panel; Dexcom, Inc. M. Moscoso-Vasquez: Other Relationship; Dexcom, Inc. Research Support; Tandem Diabetes Care, Inc, National Institute of Diabetes and Digestive and Kidney Diseases. L. Towers: None. J.C. Wong: Research Support; Abbott, Dexcom, Inc., Tandem Diabetes Care, Inc. S.A. Brown: Research Support; Dexcom, Inc., Insulet Corporation, Tandem Diabetes Care, Inc, Tolerion, Roche Diabetes Care. Other Relationship; MannKind Corporation. L. Ekhlaspour: Other Relationship; Medtronic. Advisory Panel; Abbott, Medtronic. Consultant; Jaeb Center for Health Research. Research Support; MannKind Corporation. Speaker's Bureau; Insulet Corporation. Advisory Panel; Sequel Med Tech. Other Relationship; Tandem Diabetes Care, Inc. Research Support; Abbott. Other Relationship; Sanofi.FundingBreakthrough T1D (2-SRA-2023-1275-M-B)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-309-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 310-OR: Randomized Controlled Study of Algorithmic CGM-Based Degludec
Titration in People with Type 2 Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 310-OR
Abstract: Introduction and Objective: People with type 2 diabetes (T2D) may require insulin therapy. As CGM is increasingly used in T2D, this study evaluated the feasibility of a CGM titration algorithm for basal insulin treatment.Methods: We conducted a 16-week, two-site, randomized controlled trial (NCT06111508) involving CGM-naïve adults with T2D (≥18yo, HbA1c: 7-9%) using degludec and other antidiabetic medications. Participants were randomized 2:1 to weekly CGM-based titration (EXP) or a standard of care SMBG-based titration with blinded CGM (CTR). Both groups received dose notifications via a phone app. The primary endpoint was the change in CGM time in range (TIR: 70-180 mg/dL) from baseline to week 16, tested for non-inferiority (5% margin).Results: Thirty participants were randomized (EXP: 20, CTR: 10). At week 16, estimated mean changes in TIR were higher in EXP (+20.3%) compared to CTR (+8.3%) with adjusted difference +14.6% [4.0; +∞] (non-inferiority p=0.001). The overall rate of confirmed hypoglycemia (SMBG < 70 mg/dL) was similar (17±20 vs 14±18 events per patient-year, p=0.67). Clinically significant hypoglycemia events (SMBG < 54 mg/dL) were low (7 in each group). No severe hypoglycemia was reported.Conclusion: This CGM-based titration algorithm is a feasible alternative to standard approaches in adults with T2D. Outcomes favored participants using open CGM with CGM-based titration.DisclosureA. El Fathi: None. R. Nass: None. C.J. Levy: Research Support; Tandem Diabetes Care, Inc. Advisory Panel; Tandem Diabetes Care, Inc. Research Support; MannKind Corporation, Dexcom, Inc., Novo Nordisk, Eli Lilly and Company. C. Levister: Research Support; Dexcom, Inc., Tandem Diabetes Care, Inc. G. O'Malley: Research Support; Dexcom, Inc., Tandem Diabetes Care, Inc, Novo Nordisk, MannKind Corporation. N. Shah: None. E. Emory: None. D. Flanagan: None. P.W. Hansen: Employee; Novo Nordisk A/S. M.D. Breton: Speaker's Bureau; Sinocare Inc, Tandem Diabetes Care, Inc. Consultant; Roche Diabetes Care, Boydsense.FundingNovo Nordisk
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-310-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 311-OR: Adapting Automated Insulin Delivery for Menstrual Cycle
Variability in Type 1 Diabetes—Insights from a Combined Quantitative and
Qualitative Study-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 311-OR
Abstract: Introduction and Objective: Premenopausal women with type 1 diabetes (T1D) experience fluctuations in glucose levels related to their menstrual cycles. Research and anecdotal reports from the diabetes community indicate that insulin needs change across cycle phases, and many women make manual adjustments to Automated Insulin Delivery (AID) systems to ensure appropriate insulin delivery. However, the specifics of these adjustments and the reasoning for adopted strategies to manage cycle-induced changes on glucose control are not yet well understood and warrant further research.Methods: In collaboration with Tidepool, we analyzed 354 menstrual cycles from donated data provided by 70 women with T1D using an AID system. This quantitative study was complemented by qualitative research consisting of 7 focus groups with semi-structured interviews involving 38 women.Results: Both studies confirmed significant variability in insulin requirements throughout the menstrual cycle, with no consistent patterns across individuals or AID systems. In the quantitative study, 43% of the women regularly adjusted their insulin delivery settings to counteract hormone-related fluctuations. Women who adjusted their insulin settings achieved a statistically significant higher Time-in-Range, increasing by 5 percentage points compared to those who did not make adjustments. To address cycle-induced glycemic fluctuations, women primarily adjusted basal rates, target glucose levels, and correction factors, often supplementing with ad-hoc strategies such as fake carbs or under-bolusing.Conclusion: Our findings highlight the limitations of current AID systems to fully automate glucose control for premenopausal women. As AID systems play an increasing role in diabetes care, it is crucial that they can appropriately adapt to factors affecting glucose levels.DisclosureS. Hossmann: None. S. Bühler-Häfliger: None. S. Khan-Gallo: Employee; Tidepool. Advisory Panel; Diabetes Center Berne. M. Friedman: None. L. Burlando: None. S. Krutisch: Employee; Abbott. H. Ballhausen: None. S. Rossi: None. A. Lizoain: None. V.S. Braunack-Mayer: None. M. Rothenbühler: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-311-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 312-OR: Real-World Differences in Glycemia According to Automated Insulin
Delivery System in Youth with Low Bolus Frequency-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 312-OR
Abstract: Introduction and Objective: Prior real-world studies of youth with type 1 diabetes (T1D) did not identify significant differences in time in range (TIR) between Insulet Omnipod 5 (OP5) and Tandem Control IQ (CIQ) users. In this follow-up study, we assessed differences in glycemia between youth with low bolus frequency.Methods: This single center, retrospective study included youth managing T1D with OP5 or CIQ who averaged ≤3 boluses/day over a 90-day period (6/15/24-9/12/24). Propensity scores following nearest-neighbor 1:1 matching with a caliper width requirement of 0.2 were used to account for between group differences. A multiple linear regression model adjusting for covariates (race/ethnicity, insurance, sex, T1D duration, CGM active time, manual boluses/day) assessed for differences in TIR by AID system in the propensity matched sample.Results: A total of 202 youth had low bolus frequency (CIQ n=75, OP5 n=127). CIQ users had a longer T1D duration (8.8 vs 7.9yrs, p=0.0001), higher CGM active time (91.7% vs 80.4%, p=0.0001), higher time in automated mode (81.3% vs 62%, p=0.0001), and higher total daily insulin dose (59.6 vs 49.5 units/day, p=0.0001).Propensity score matching paired CIQ users (n=49) with OP5 users (n=49). All between group differences were eliminated with propensity matching, with the exception of time in automated mode which remained higher for CIQ users (80% vs 64.0%, p=0.01). Demographics of the matched sample included: age 17.0yrs, 54.1% female, 68.4% NHW, 32.7% publicly insured. Median CGM active time was 87.7% and median manual bolus frequency was 2.2 boluses/day. Adjusted TIR was 8.0% higher (95% CI 2.9-13.1 p=0.002) in CIQ (54.9%) vs OP5 users (46.9%).Conclusion: In youth with T1D who bolus infrequently, CIQ use was associated with greater time in automated mode and greater TIR though neither group attained TIR goals. This information should be discussed when counseling families choosing an AID system.DisclosureP. Chatty: None. R.J. Gallop: None. A. Rearson: None. S. Gera: None. J.N. Mountain: None. N. Alicea-Trelles: None. B.E. Marks: Consultant; Insulet Corporation. Board Member; International Society for Pediatric and Adolescent Diabetes. Research Support; Tandem Diabetes Care, Inc, Dexcom, Inc., Medtronic. Advisory Panel; T1D Exchange.FundingB.E.M. is supported by the National Institutes of Health (PI: Marks, NIH: K23DK129827).
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-312-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 313-OR: Outpatient Real-World Use of an Automated Insulin Delivery (AID)
System That Automatically Doses for Meals Compared with Hybrid Commercial
AID Systems-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 313-OR
Abstract: Introduction and Objective: Most commercial AIDs require entry of carbohydrates before meals. This is burdensome for people with type 1 diabetes (T1D) with many forgetting to report or incorrectly estimating carbohydrates. We developed the OHSU AID with automated, machine-learning based meal detection and dosing that can be used with or without carbohydrate announcements.Methods: This multisite study evaluated 7 days of real-world use of the OHSU AID in 25 people (13 female, mean age 32.4, mean A1c 7.5%) with T1D currently using Control-IQ (24) or Omnipod5 (1) with baseline A1c or GMI above 7.5%. The OHSU AID uses the iPancreas platform, Insulet pods, and Dexcom G6 CGM. The primary outcome was to evaluate non-inferiority (7% margin) of OHSU AID (intervention) compared with usual care (control) in randomized order.Results: The OHSU AID achieved non-inferior time-in-range (70-180 mg/dL) compared to control (intervention 56.0% SD 12.0 vs. control 56.8% SD 12.7, mean within-person difference -0.8% SD 10.4). Other CGM metrics were also non-inferior. No severe adverse outcomes occurred.Conclusion: This study demonstrates potential for AIDs that maintain safety and efficacy while reducing burden for the person with diabetes by allowing automated meal dosing with flexibility to enter meal carbohydrates.DisclosureL.M. Wilson: None. C.M. Mosquera-Lopez: None. D.K. Aby-Daniel: None. S. Trikudanathan: None. J.H. Eom: None. D. Branigan: None. H. Ling: None. D. Chen: None. M. Howard: None. J.A. Leitschuh: None. W. Hilts: None. K. Ramsey: None. R. Dodier: None. J. Pinsonault: None. J. Castle: Employee; Dexcom, Inc. Stock/Shareholder; Dexcom, Inc. P.G. Jacobs: Research Support; Dexcom, Inc. Speaker's Bureau; Dexcom, Inc. Advisory Panel; Eli Lilly and Company. Stock/Shareholder; Pacific Diabetes Technologies. Research Support; SFC Fluidics, Eli Lilly and Company.FundingNational Institutes of Health (R01DK120367)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-313-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 314-OR: Improved Outcomes across Baseline Time-in-Range Levels with the
Omnipod 5 AID System Compared with Multiple Daily Injections (MDI) in Type
1 Diabetes (T1D)—Analysis of the RADIANT Study-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 314-OR
Abstract: Introduction and Objective: Despite advances in technology, many people living with T1D continue to use MDI, with glycemic outcomes remaining at suboptimal levels. This subgroup analysis of a recent randomized controlled trial of the Omnipod® 5 Automated Insulin Delivery (AID) System compared with MDI and CGM use evaluated outcomes according to baseline time in range (TIR; 70-180 mg/dL) in children and adults with T1D.Methods: This multinational trial enrolled participants aged 4-70y with T1D and screening A1C 7.5-11% currently using MDI with a FreeStyle Libre 2 CGM (study CGM) for ≥3 months. Participants completed 14 days of data collection with MDI + CGM, then were randomized 2:1 to intervention (Omnipod 5 + CGM) or continued with MDI + CGM (control) for 13 weeks.Results: A total of 188 participants (<18y: 58%) were randomized, 125 to intervention and 63 to control. TIR during the 13-week trial period was greater with AID compared with control across all baseline TIR levels (Figure), with the largest difference among participants with baseline TIR <30% (unadjusted difference: 30%).Conclusion: These results demonstrate the efficacy of the Omnipod 5 System compared with MDI in people with T1D across all baseline levels of TIR, demonstrating the feasibility of direct transition from MDI to AID regardless of baseline glycemia.Disclosure E.G. Wilmot: Research Support; Abbott. Speaker's Bureau; Abbott. Advisory Panel; Abbott. Speaker's Bureau; AstraZeneca. Advisory Panel; Dexcom, Inc. Speaker's Bureau; Dexcom, Inc., Eli Lilly and Company. Advisory Panel; Eli Lilly and Company. Research Support; embecta. Advisory Panel; embecta. Research Support; Insulet Corporation. Speaker's Bureau; Insulet Corporation. Advisory Panel; Insulet Corporation, Medtronic. Speaker's Bureau; Novo Nordisk. Advisory Panel; Novo Nordisk. Research Support; Novo Nordisk. Advisory Panel; Roche Diabetes Care, Sanofi. Speaker's Bureau; Sanofi. Advisory Panel; Sinocare Inc. Speaker's Bureau; Ypsomed AG. J. Beltrand: Board Member; Sanofi, Insulet Corporation. Speaker's Bureau; Lilly Diabetes, Sanofi. Board Member; Ypsomed AG. Speaker's Bureau; Abbott. B. Guerci: Research Support; Abbott Diagnostics. Advisory Panel; Insulet Corporation. Research Support; Eli Lilly and Company. Advisory Panel; Novo Nordisk, Boehringer-Ingelheim, AstraZeneca, Bayer Pharmaceuticals, Inc, Medtronic. Research Support; Dexcom, Inc. Advisory Panel; Air Liquide. A. Berot: None. H. Hanaire: Consultant; Abbott, Dexcom, Inc. Advisory Panel; Medtronic, Insulet Corporation. Consultant; Tandem Diabetes Care, Inc, Novo Nordisk, Sanofi. E. Bismuth: Other Relationship; Abbott, Eli Lilly and Company. Advisory Panel; Insulet Corporation. Other Relationship; Insulet Corporation, Novo Nordisk. Advisory Panel; Medtronic, Sanofi. Other Relationship; Sanofi, Dexcom, Inc. P. Gillard: Research Support; Novo Nordisk A/S, Sanofi, Dexcom, Inc., Tandem Diabetes Care, Inc, Medtronic. Speaker's Bureau; Abbott, Bayer Pharmaceuticals, Inc. Advisory Panel; Ypsomed AG. Speaker's Bureau; Air Liquide. Research Support; Roche Diabetes Care. M. Saade: Other Relationship; Medtronic. M. Joubert: Board Member; Abbott, Medtronic, Insulet Corporation, Dexcom, Inc., Ypsomed AG, Lilly Diabetes, Novo Nordisk, Sanofi. R. Salet: None. P. Choudhary: Speaker's Bureau; Abbott. Advisory Panel; Dexcom, Inc. Consultant; Insulet Corporation. Advisory Panel; Ypsomed AG, embecta, Sanofi. Speaker's Bureau; Lilly Diabetes, Medtronic. Advisory Panel; Roche Diabetes Care. Consultant; Cambridge Mechatronics. R. Reynaud: Other Relationship; Novo Nordisk. Speaker's Bureau; Lilly Diabetes, Sanofi. L. Leelarathna: Research Support; Abbott. Consultant; Abbott. Research Support; Insulet Corporation. Speaker's Bureau; Insulet Corporation. Advisory Panel; Medtronic. E. Renard: Consultant; Sanofi. Other Relationship; Ypsomed AG. S. Lablanche: Board Member; Insulet Corporation, Abbott, Dexcom, Inc., Sanofi, Medtronic. C. Gouillard Darnaud: Other Relationship; Pfizer Inc, Sanofi. S.M. Ng: None. P.A. Lysy: None. N. Daskas: None. K. Perge: None. T.S. Crabtree: Other Relationship; Abbott, Dexcom, Inc., Eli Lilly and Company, Insulet Corporation. T.T. Ly: Employee; Insulet Corporation. Stock/Shareholder; Insulet Corporation. M. Nicolino: Board Member; Novo Nordisk, Merck & Co., Inc. Research Support; IPSEN. Board Member; Pfizer Inc. Advisory Panel; Sanofi. Board Member; Rhythm Pharmaceuticals, Inc.FundingThis study was funded by Insulet Corporation.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-314-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 315-OR: Effect of Telemonitoring Using Connected Devices on Insulin
Injection Adherence in People Living with T2D-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 315-OR
Abstract: Introduction and Objective: The DiaMonT trial compared glycemic outcomes seen with a telemonitoring intervention (Fig) vs standard of care in adults with T2D treated with insulin. This post hoc analysis of the DiaMonT trial explored insulin injection patterns.Methods: Participants (n=331) were randomized 1:1 to telemonitoring (treatment arm) or standard of care (control arm) for 13 weeks. Injection adherence (defined as number of missed doses) and number of bolus correction doses were assessed using linear mixed models with patient as a random effect.Results: Both basal and bolus adherence was significantly higher in the treatment arm vs the control arm (p<0.001 and p=0.015, respectively). Estimated LS-mean [95% CI] probability of skipping a basal dose was 1.3% [1.0; 1.7] in the treatment arm and 3.0% [2.4; 3.8] in the control arm. Mean [95% CI] probability of a day with ≥1 missing bolus dose was lower in the treatment arm (43.6% [38.6; 48.7]) than the control arm (56.5% [48.0; 64.7]). Correction doses were more frequently administered in the treatment arm (3.5% [95% CI 2.7; 4.7] of days) than in the control arm (1.3% [95% CI 0.8; 2.1] of days).Conclusion: Telemonitoring was associated with better injection adherence and higher frequency of correction doses than standard of care. These data suggest that telemonitoring using connected devices could help support adults with T2D optimize insulin treatment.DisclosureT. Kronborg: None. S. Hangaard: None. N.V. Hartvig: Employee; Novo Nordisk. Stock/Shareholder; Novo Nordisk. A. Kaas: Employee; Novo Nordisk A/S. S.N. Slobodziuk Kristensen: Employee; Novo Nordisk A/S. Stock/Shareholder; Novo Nordisk A/S, Dexcom, Inc., Abbott. R. Kosmina: Employee; Novo Nordisk A/S. P. Vestergaard: None.FundingNovo Nordisk A/S and Innovation Fund Denmark
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-315-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 316-OR: Natriuretic Peptide Screening Predicts Survival Outcomes in
Individuals with Diabetes without Known Heart Failure-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 316-OR
Abstract: Introduction and Objective: Heart failure (HF) is common in diabetes and may be asymptomatic in earlier stages. NT-proBNP and BNP [collectively natriuretic peptides (NP)] detect early HF in asymptomatic individuals who could benefit from disease-modifying therapies. We examined the prognostic value of NP levels in people with type 1 (T1D) or type 2 (T2D) diabetes without known HF.Methods: We retrospectively evaluated adults (≥18 years) with T1D or T2D using Optum’s de-identified Market Clarity Data who received an outpatient NP test between 2017-2023 without known HF at time of testing. We categorized BNP levels as <50, 50-100 or >100 and NT-proBNP levels as <125, 125-300 or >300. We assessed the association between NP levels and HF development or death using Cox proportional hazard models, adjusting for age, sex, race, ethnicity, comorbidities and region.Results: Among 116,439 people (3,284 with T1D and 113,155 with T2D) who met inclusion criteria and were followed up to 7 years, 54% were female, had a median (IQR) age of 64 (55-74) and a mean (SD) A1c of 7.2% (1.8) at baseline. Overall, 28,239 individuals (24%) had incident HF or death during follow-up (median 26 months). Roughly 18% of people with T1D and 19% with T2D had BNP 50-100 or NT-proBNP 125-300; 22% of those with T1D and 23% with T2D had BNP >100 or NT-proBNP >300. In adjusted Cox models, increased NT-ProBNP was significantly associated with increased risk of HF development or mortality among individuals with T1D (HR [95% CI] NT-ProBNP 125-300: 2.06 [1.40-3.06]; >300: 5.25 [3.75-7.36], ref: NT-ProBNP<125) and T2D (HR [95% CI] NT-ProBNP 125-300: 1.90 [1.79-2.02]; >300: 3.70 [3.51-3.91]). BNP showed a similar prognostic pattern.Conclusion: These data demonstrate that NP test results in individuals with diabetes without HF are highly prognostic for future risk of HF or mortality. The study supports implementation of NP testing for HF risk assessment in people with T1D and T2D for optimal management and improved outcomes.Disclosure R. Pop-Busui: Board Member; American Diabetes Association. Consultant; Averitas Pharma, Inc. Research Support; Bayer Pharmaceuticals, Inc. Other Relationship; Biogen. Research Support; Juvenile Diabetes Research Foundation (JDRF). Advisory Panel; Lexicon Pharmaceuticals, Inc, Novo Nordisk. Research Support; Novo Nordisk, National Institute of Diabetes and Digestive and Kidney Diseases. Consultant; Roche Diagnostics. E. Repetto: Employee; Roche Diagnostics. J.M. Baron: Employee; Roche Diagnostics. Stock/Shareholder; Roche Diagnostics. D. Schumacher: Employee; Roche Diagnostics. M. Vaduganathan: Advisory Panel; American Regent, Amgen, AstraZeneca, Bayer AG, Baxter Healthcare, BMS, Boehringer Ingelheim, Chiesi, Cytokinetics, Fresenius Medical Care, Idorsia Pharmaceuticals, Lexicon Pharmaceuticals, Merck, Mile, Pharmacosmos, Relypsa, Roche Diagnostics, Sanofi, and Tricog Health. Research Support; AstraZeneca, Galmed, Novartis, Bayer AG, Occlutech, and Impulse Dynamics. A. Pandey: Consultant; Roche Diagnostics. Advisory Panel; Bayer Pharmaceuticals, Inc, Novo Nordisk. Other Relationship; Lilly USA LLC. Consultant; Edwards Lifesciences. Other Relationship; Merck & Co., Inc, Rivus Pharmaceuticals Inc, Ultromics. Consultant; Tricog Health, Sarfez Pharma, Axon Therapies. Other Relationship; Alleviant.FundingA part of the work was funded by Roche Diagnostics Corporation (Indianapolis, IN, USA); RPB was supported by 1-R01-DK126837-01A1
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-316-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 317-OR: Causes and Consequence of Diabetes Supply Distress—Qualitative
Analysis of T1D Exchange Survey Responses-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 317-OR
Abstract: Introduction and Objective: Diabetes devices (continuous glucose monitors, insulin pumps/supplies) offer glycemic and quality of life benefits to people with type 1 diabetes (T1D). Challenges acquiring and maintaining access to prescribed supplies are common and pose an additional psychosocial burden that we refer to as Diabetes Supply Distress (DSD). To gain insight and identify themes of DSD we performed a qualitative analysis of free-text responses from a T1D Exchange survey of US adults with T1D.Methods: We analyzed 349 free-text responses (age 51±17 years; T1D duration 29.5±18 years; 70% female; 97% White, 71% private insurance) to the question: ‘What else do you want to tell us about obtaining diabetes supplies'’ and identified themes of DSD.Results: Qualitative data analysis identified 4 sources of DSD: unpredictability and unreliability of access, shipping, and insurance; burden of navigating complex systems; perception of apathetic diabetes supply stakeholders; and financial burden. Consequences of DSD included: anxiety about losing health insurance and fear of running out of supplies leading to stockpiling (Table 1).Conclusion: The complex challenges adults with T1D in the US face to maintain access to prescribed diabetes supplies can be a significant source of distress and burden. More qualitative research on DSD is needed to inform actionable improvements in policy and practice.DisclosureA.A. Welch: None. M.B. Pasmooij: None. T. Knoerl: None. E.J. Kopras: None. M. Falciglia: None. M.L. Tanenbaum: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-317-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 318-OR: The Effectiveness of Care Coordination on Medication Adherence
among High-Need, High-Cost Commercially Insured Beneficiaries—A
Randomized Controlled Trial-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 318-OR
Abstract: Introduction and Objective: Care coordination programs may improve medication adherence for high-need, high-cost (HNHC) beneficiaries. We analyzed data from an RCT of a care coordination program conducted by a large national insurer, to assess impacts on medication adherence.Methods: We performed intention-to-treat (ITT) and instrumental variable (IV) analyses using claims data for HNHC beneficiaries from 2019-2022. Comparing intervention to control arms, we examined adherence to metformin in diabetes (n=2,875), statins in diabetes (n=3,057), direct oral anticoagulants (DOACs) in atrial fibrillation (n=267), and levothyroxine in hypothyroidism (n=1,983). To define adherence, we calculated mean proportion of days covered (PDC) for each medication as well as a binary adherence measure of PDC ≥ 80%. We used multivariate linear and logistic regression models, respectively. For the IV analyses, we used randomization status as the instrument. Covariates included age, gender, geographic location, plan type, and 18 comorbidity indicators.Results: In the primary ITT analyses, we did not observe significant differences in mean PDC for any comparisons. The adjusted mean PDC for beneficiaries randomized to intervention versus control was 0.80 vs. 0.81 (p = 0.31) for metformin, 0.82 vs. 0.82 (p = 0.66) for statins, 0.80 vs 0.81 (p = 0.78) for DOACs, and 0.86 vs. 0.85 (p = 0.17) for levothyroxine. In the ITT analyses and the IV analyses examining PDC as a binary variable, we observed a similar pattern of no difference between arms other than improved adherence in beneficiaries with hypothyroidism who were prescribed levothyroxine.Conclusion: Our results align with prior studies showing that care coordination delivered to HNHC beneficiaries by care managers may not consistently improve medication adherence, and emphasize the challenges of improving adherence within a complex HNHC beneficiary population.DisclosureR. Saju: None. C. Tseng: None. T. Moin: None. C. Mangione: None. S. Takada: None. O. Duru: None.FundingCenters for Disease Control and Prevention, under Cooperative Agreement U18DP006535.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-318-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 319-OR: Clinical Decision Support System for Insulin Management in a
Remote Diabetes Care Model-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 319-OR
Abstract: Introduction and Objective: A clinical decision support system (CDSS) was integrated into a remote diabetes care model that demonstrated clinical benefits. These analyses assess insulin dose adjustment agreement between the CDSS and remote providers and examine the related app usage within the telemonitoring framework.Methods: Participants (N=234) were onboarded to the CDSS platform and accessed a connected app to receive treatment updates from their remote provider, log events, and use a bolus calculator. The provider could use the CDSS for insulin dose adjustments, modify them if desired, and share the updated plan with the participant. Individuals who had ≥1 recommendation were included in analyses. Clinical agreement was defined as both indicating the same direction of insulin adjustment or one indicating no change while the other suggested a change, all within 20%.Results: Among 185 (79%) adults included in the analyses, 134 had T1D and 51 had T2D. The mean number of recommendations per individual was 5.2±2.2. For the pump population (288 recommendations), there was clinical agreement between the provider and CDSS an average of 99%, 96%, and 95% over a 24-hour period for basal rates, CR, and CF, respectively. The recommendations were identical for an average of 64%, 71%, and 67% and differed by >20% for an average of 1%, 3%, and 5% for basal rates, CR, and CF, respectively. For MDI users (665 recommendations), clinical agreement was 94% for basal, 86% for CR, and 93% for CF. Identical recommendations were observed in approximately half of the comparisons for basal and CR, and in over 75% for CF. 9% of comparisons showed a difference >20% in the recommended dose adjustments. The CDSS app was used by 161 (69%) participants at least once. An average of 3.8 ± 3.5 events/day were logged, with insulin dose entries being the most frequent.Conclusion: In a comprehensive remote care model, the CDSS provided recommendations closely aligned with providers, accompanied by high app usage among participants.DisclosureL. Kanapka: None. Y. Shtrit: Employee; DreaMed Diabetes. R.L. Gal: None. C. Kollman: Research Support; Dexcom, Inc., Insulet Corporation, MannKind Corporation, Breakthrough T1D (formerly JDRF), Capillary Biomedical, Inc, Hemsley Charitable Trust, National Institute of Diabetes and Digestive and Kidney Diseases, Tandem Diabetes Care, Inc. I. Muller: Employee; DreaMed. M. Phillip: Advisory Panel; Medtronic. Other Relationship; Eli Lilly and Company, Sanofi. Advisory Panel; Sanofi. Other Relationship; Novo Nordisk. Advisory Panel; Novo Nordisk. Other Relationship; Pfizer Inc. Advisory Panel; Pfizer Inc, Insulet Corporation. Other Relationship; AstraZeneca. Advisory Panel; LifeScan Diabetes Institute. Other Relationship; Dompé, Provention Bio, Inc, Provention Bio, Inc, Microbion, Microbion, OPKO, LUMOS. Advisory Panel; embecta, Tandem Diabetes Care, Inc. Consultant; Qulab Medical. Stock/Shareholder; Dreamed Diabetes. Other Relationship; Dreamed Diabetes. Stock/Shareholder; NG Solutions. Other Relationship; NG Solutions. R. Nimri: Advisory Panel; Tandem Diabetes Care, Inc. Speaker's Bureau; Novo Nordisk, Sanofi, Insulet Corporation, Medscape. Stock/Shareholder; DreaMed Diabetes. Employee; DreaMed Diabetes. Research Support; Geffen Medical.FundingThe Leona M. and Harry B. Helmsley Charitable Trust
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-319-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 320-OR: CGM Initiation prior to Hospital Discharge Is Associated with
Improved Glycemic Control and Patient Satisfaction-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 320-OR
Abstract: Introduction and Objective: Continuous Glucose Monitoring (CGM) is established to improve glycemic control and quality of life (QoL), reduce diabetes-related hospitalization and utilization of the emergency department in people with diabetes (PWD). While guidelines have recommended CGM, there are multiple known barriers including cost, insurance coverage and access to specialized education and clinical care that supports use. We designed and implemented an interdisciplinary Diabetes Technology Transition of Care Program in an urban academic medical center to address barriers and leverage hospital resources to target patients most likely to benefit from CGM.Methods: Hospitalized patients with plan for insulin use at discharge were offered CGM through a pharmacy-led Meds to Beds Program that included bedside education, sensor placement, device set up and transition of care planning by a pharmacist or inpatient diabetes team member. Participants were offered a one-time follow up visit with a diabetes clinician after discharge, and were contacted post discharge to identify and address barriers to CGM use and remote data sharing. We assessed individual change in glycemic control by comparing baseline A1c with the CGM-derived glucose management indicator (GMI) and measured patient satisfaction using CGM Satisfaction Survey (CGM-SAT).Results: Baseline characteristics (N=43): 65% female, mean age 46.3 (±15.9), A1c 9.9% (±2.4). The mean GMI was lower than baseline mean A1c at 2 weeks (N=26, -3.1% (±2.8), p<0.001); 3 months (N=12, -2.7% (±2.3), p<0.01); and 6 months (N=5, -3.3% (±1.4), p<0.01). CGM-SAT at baseline and 6 months confirm patient reported benefit with greatest impact on domains of trust and openness.Conclusion: Employing a hospital-based interdisciplinary service to initiate CGM in insulin-treated patients for use upon discharge was feasible and associated with improvement in glycemic control and patient satisfaction over 6 months.Disclosure N.E. Palermo: Other Relationship; Dexcom, Inc. E.G. Thurber: Other Relationship; SimulConsult. G.M. Rickards: None. J. Harrod: None. B. Altshuler: None. A. Shahani: None. M.E. McDonnell: Research Support; Dexcom, Inc.FundingBrigham and Women's Hospital Department of Medicine Health Equity Innovation Pilot Grant
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-320-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 321-OR: ADA Presidents' Select Abstract: FOXO1 Is Vital for Gestational
Beta-Cell Compensation to Protect Against Gestational Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 321-OR
Abstract: Introduction and Objective: Gestational beta-cell compensation is an adaptive mechanism by which maternal islets are conditioned to secrete more insulin for maintaining normoglycemia during pregnancy. Inept beta-cell compensation contributes to gestational diabetes mellitus (GDM).Methods: We generated beta-cell FoxO1 knockout (FoxO1-KO) mice, followed by determining the effect of FoxO1 depletion on beta-cell mass and function in female mice. We determined the effect of prolactin on FoxO1 signaling in primary islets of mice and humans.Results: FoxO1-KO mice, relative to WT littermates, developed GDM, as evidenced by impaired glucose tolerance and reduced glucose-stimulated insulin secretion during pregnancy. The severity of GDM, as indexed by the amplitude of glucose intolerance, was pronounced in FoxO1-KO dams with multiparity. Mechanistically, FoxO1 acts as a substrate of JAK2, a key kinase that mediates the proliferative effect of prolactin on beta-cells. In response to prolactin, FoxO1 at Tyr162 was phosphorylated by JAK2. This phosphorylation augmented FoxO1 activity in stimulating beta-cell expression of TPH1, a major isoform of tryptophan hydroxylase responsible for serotonin production in maternal islets. This translated into the stimulatory effect of prolactin on beta-cell compensation, as reflected by 2- to 3-fold expansion of beta-cell mass in WT dams. However, these effects were abrogated by beta-cell FoxO1 depletion, contributing to beta-cell decompensation and GDM in FoxO1-KO dams.Conclusion: We revealed a new prolactin-JAK2-FoxO1-serotonin pathway in priming maternal islets to undergo beta-cell compensation for pregnancy. Of clinical significance, we validated this pathway in human islets. We suggest that FoxO1 is vital for gestational beta-cell compensation to protect against GDM.DisclosureT. Usman: None. T. Zhang: None. G. Chhetri: None. H. Yeh: None. G. Lu: None. A. Garcia-Ocana: Consultant; Sun Pharmaceutical Industries Ltd. H. Dong: None.FundingThis study was supported by National Institutes of Health (1R01DK125001-01A1)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-321-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 322-OR: Higher Placental GKN1 Expression Is Associated with Reduced
Pregnancy Beta-Cell Function-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 322-OR
Abstract: Introduction and Objective: We aimed to identify candidate placental proteins that impact beta-cell function in human pregnancy through transcriptome-wide placental gene expression analysis.Methods: In the Gen3G cohort, we measured glucose and insulin levels fasting, 1, and 2 hours after a 75-gram oral glucose load given at 24-30 weeks’ gestation. We calculated the Pregnancy Insulin Physiology (PIP) Index, a measure of pregnancy beta-cell function. We performed bulk RNA sequencing of placental samples (N=15,216 RNA transcripts) and analyzed differential gene expression to identify transcripts most strongly associated with beta-cell function (PIP index, box-cox transformed, standardized) after adjustment for maternal age, gravidity, body mass index (BMI), gestational age at delivery, and offspring sex. We used the false discovery rate (FDR) to adjust P-values. We then quantified nominal associations (P<0.05) between identified transcripts and other glycemia-related traits with weighted linear regression models.Results: In 433 cohort participants, we identified GKN1, encoding gastrokinin 1, as the top differentially expressed gene in relation to the PIP index. Gastrokinin 1, a secreted protein highly expressed in the stomach, has putative roles in mucosal homeostasis and fat metabolism. Higher placental GKN1 expression was associated with lower beta-cell function (log2 change in GKN1 expression per SD change in beta-cell function=-0.44, FDR=8.1×10-6). Placentas from pregnancies with gestational diabetes had higher GKN1 expression compared to unaffected pregnancies (log2 fold change=1.13, FDR= 4.2×10-3). Higher GKN1 expression was associated with higher BMI (β=0.2, P=0.04), post-load glucose (β=0.3, P=3.5×10-5) and insulin (β=0.2, P=0.007), and lower insulin sensitivity-adjusted Stumvoll first phase estimate (β=-0.2, P=0.001).Conclusion: Higher placental GKN1 expression is associated with reduced beta-cell function in pregnancy and gestational diabetes.Disclosure C.E. Powe: Research Support; Dexcom, Inc. Other Relationship; Mediflix, Wolters Kluwer Health. F. White: None. C. Allard: None. L. Shook: None. F. Aguet: Employee; Predicta Biosciences, Illumina, Inc. K. Ardlie: None. A. Edlow: Research Support; Merck Sharp & Dohme Corp. Consultant; Merck Sharp & Dohme Corp, Mirvie, Inc. L. Bouchard: None. P. Jacques: None. J.C. Florez: Research Support; Novo Nordisk. S. Karumanchi: Consultant; Thermofisher Scientific, Comanche Biopharma. Stock/Shareholder; Aggamin Therapeutics, Roche Diagnostics. Other Relationship; Beth Israel Deaconess Medical Center, Cedars-Sinai Medical Center. M. Hivert: None.FundingNational Institutes of Health (R01HD094150)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-322-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 323-OR: Elucidating the Epigenetic Landscape of Hepatic HKDC1 during
Pregnancy-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 323-OR
Abstract: Introduction and Objective: Gestational Diabetes mellitus (GDM) is a serious health condition that affects 3 to 8 % of all pregnant women in the US. This condition is diagnosed around 28 weeks of pregnancy through an oral glucose tolerance test (OGTT) and increases the likelihood of Type II diabetes in the mothers later in life and multiple complications during pregnancy for the mother and the unborn child. HKDC1 is genetically linked to gestational glucose levels and GDM, and we have previously shown that hepatic HKDC1 expression is important in gestational glucose homeostasis. In this study, we sought to understand the regulation of its expression in the liver through the transcription factor, TFEB, which has been identified to regulate HKDC1’s expression.Methods: We have employed chromatin immunoprecipitation (ChIP) coupled to qPCR to analyze changes in levels of chromatin binding of TFEB over the entire proximal promoter of HKDC1.Results: Our data shows that binding of TFEB on HKDC1 promoter in liver is significantly higher in gestational day 15 (G15) female mice compared to gestational day 0 (G0) and decreases with increasing distance from transcription start site (TSS). The increase in levels of TFEB binding at G15 correlates with an increase in HKDC1 expression. Furthermore, alterations in this binding are linked to loss of HKDC1 expression and progression of GDM.Conclusion: A complex interaction of genetic and environmental factors underlies GDM which alters the epigenetic landscape of key tissues. Here, we describe alteration of binding of a master transcriptional regulator TFEB on hexokinase gene HKDC1 in diet-induced GDM mice at different gestation stages (G0-G15). Integration of gene expression and transcription factor binding data is vital for providing clues in identifying epigenetic driver modifications responsible for pre-disposition and diagnosis of various conditions. In the future, we will perform blood-based screening for histone modifications (H3K4me3, H3K14ac, H3K9me3) for early diagnosis of GDM to improve maternal and fetal outcomes.DisclosureZ. Farooq: None. V. Ilievski: None. J.E. Boyett: Stock/Shareholder; CVS Caremark. B.T. Layden: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-323-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 324-OR: Targeting Triglycerides to Prevent Fetal Overgrowth—High
Agreement between Plasma and a Portable Triglyceride Meter Similar to a
Glucometer-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 324-OR
Abstract: Introduction and Objective: Fasting and postprandial triglycerides (PPTG) in obese pregnancies may be stronger predictors of fetal overgrowth than glucose, making them a potential novel treatment target. Measurement of TG currently requires venipuncture in a laboratory, a barrier for collecting repeated measures to understand contributions to fetal growth. Our aim was to evaluate agreement between fingerstick capillary TG using an FDA-approved point-of-care (POC) meter and venipuncture plasma TG (vTG).Methods: Pregnant patients (n=35) with obesity (59%) and GDM (41%) (BMI 33±4) had fasting vTG at 25±9 wks’ gestation. A subset (n=23) had PPTG collected at 1- and 2-hrs after a controlled breakfast (35±2 wks’). POC TG and vTG were collected simultaneously. Venipuncture TG were measured enzymatically in a lab. Two-way mixed effects intraclass correlations (ICC) and Bland-Altman plots were used to determine agreement. Paired t-tests were used to compare vTG and POC TG (mean±SD).Results: 68 paired fasting TG and 52 paired 1- and 2-hr PPTG were collected. Fasting vTG were slightly lower than POC TG (181±66 vs192±81 mg/dL), as were 1-hr (225±65 vs 260±76) and 2-hr PPTG (227±70 vs 249±77; p<0.05 all). The ICC for fasting TG was 0.86 and 0.84 for PPTG. The mean %difference (vTG minus POC TG) was -4.6±17.8% for fasting and -12.0±12.0% for PPTG.Conclusion: These data suggest good agreement between vTG and POC TG in fasting and PPTG during pregnancy. Agreement was higher for fasting TG (11 mg/dL difference). The %difference was likely higher in PPTG due to rapidly changing TG concentrations after meals, with closer agreement in 2-hr PPTG (22 mg/dL difference). These data are comparable to agreement between plasma and POC glucose and support utilizing a POC TG meter, similar to a glucometer, to discern the contribution of TG and their potential targets in optimizing fetal growth in patients with a metabolic syndrome and elevated TG.DisclosureS.S. Farabi: None. E.Z. Dunn: None. L.A. Barbour: None. C. Ingram: None. E.M. Lopez: None. J. Hinojosa: None. E. Phillips: None. N. Hirsch: None. K.P. Rolloff: None. J.E. Friedman: None. T.L. Hernandez: Research Support; Dexcom, Inc., PTS Diagnostics.FundingNational Institute of Diabetes and Digestive and Kidney Diseases (R01DK101659); National Institute of Child Health and Human Development (R01HD102726) and University of Oklahoma/Harold Hamm Diabetes Center (RS20201450)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-324-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 325-OR: Gestational Diabetes Mellitus (GDM) Is Associated with Higher Fat
Mass (FM) Accretion in Male Infants during Early Postnatal Period-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 325-OR
Abstract: Introduction and Objective: Infants of women with GDM can exhibit higher FM accretion in the early postnatal period, but sex-specific trajectories of FM and fat-free mass (FFM) remains unknownMethods: In a UK multi-ethnic cohort of 925 mother-infant pairs (18.5% GDM), body composition was assessed using air displacement plethysmography (PEAPOD) at birth, 4 weeks, and 5 months. Complete dataset with PEAPOD measurements were available for 325 infants (18.5% GDM). Linear mixed-effects models were used to analyse the percent FM, FFM, FM index (FMI) and FFM index (FFMI) trajectories normalised for lengthResults: At birth, infants born to GDM mothers had similar FM, but lower FFM compared to non-GDM (mean±SD: FM=0.33±0.17 vs 0.36±0.17; p=0.11 and FFM=2.82±0.30 vs 2.97±0.39; p=0.001). Infants exposed to GDM gained 177g more FM with a 21.1% faster growth rate compared to non-GDM. This was mainly observed in male infants born to GDM mothers (FMI mean difference:1.25 kg/m2; 95% CI: 0.68, 1.81) from birth to 5 months compared to non-GDM, after adjusting for maternal and infant covariates, including breastfeeding. However, no significant differences in FFM or FFMI growth rates were observed between male infants exposed to GDM and non-GDM (FFMI mean difference: 0.05 kg/m²; 95% CI: -0.77 to 0.87)Conclusion: Male infants exposed to GDM gained faster and higher FM accretion compared non-GDM. Despite lower FFM at birth in GDM, there was no catch up of FFM DisclosureN. Periyathambi: None. C. Bagias: None. Y. Ghebremichael-Weldeselassie: None. N. Sukumar: None. P. Saravanan: None.FundingPartly supported by: Medical Research Council, UK (MR/N006232/1)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-325-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 326-OR: Dietary Macronutrient Substitutions Are Associated with
Cardiometabolic Benefits in Children Exposed to Gestational Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 326-OR
Abstract: Introduction and Objective: Children exposed to gestational diabetes in utero face an increased risk of cardiometabolic disorders, underscoring the need for effective preventive intervention. We used isocaloric substitution modeling to examine the impact of macronutrient substitution on cardiometabolic outcomes in GDM-exposed and unexposed children.Methods: Data from 191 BrainChild participants aged 7-11 years (53% GDM-exposed, 40% male) were analyzed. Assessments included a 24-hour dietary recall, fasting blood draw, anthropometrics, and blood pressure measurements. Isocaloric substitution modeling assessed the effects of replacing primary macronutrients (protein, fat, carbohydrates) on fasting plasma glucose (PG), insulin, total body fat (BF), waist circumference (WC), and systolic/diastolic blood pressure (BP).Results: GDM-exposed vs. unexposed children were younger (8.6±1.0 vs 8.9±1.0, p=0.02) but had similar fasting PG (83.58.9 vs 84.58.8 mg/dl, p=0.40), insulin (7.010.5 vs 7.38.6 uU/ml, p=0.82), BF (26.89.4 vs 24.88.6%, p=0.14), WC (67.09.4 vs 65.410.9 cm, p=0.38) and BP (102.89.8/ 64.16.6 vs 102.99.8/63.66.6 mm/HG, p=0.95). GDM-exposed vs. unexposed children consumed more daily calories (1838.3±533.5 vs 1713.0±407.7 kcal, p=0.07), driven by higher carbohydrate intake (953.8±290.8 vs 872±208 kcal, p=0.03), with no differences in protein (266.691.7 vs 257.793.9 kcal, p=0.5) or fat (644.6234.3 vs 607.4188.9 kcal, p=0.23). In GDM-exposed children, replacing 5% of daily calories from carbohydrates with protein significantly reduced fasting glucose (β=-11.9, p=0.02) and diastolic BP (β=-8.0, p=0.04), adjusting for total caloric intake, age, race, sex, and BMI. In unexposed children, replacing 5% of daily calories from fat with carbohydrates (β=-5.1, p=0.04) or protein (β=-8.8, p=0.04) lowered diastolic BP.Conclusion: Dietary macronutrient adjustments show promise for improving cardiometabolic health, particularly in GDM-exposed children.DisclosureJ.M. Alves: None. B.R. Belcher: None. T. Chow: None. A. Xiang: None. K.A. Page: None.FundingAmerican Diabetes Association(1-14-ACE-36); National Institute of Diabetes and Digestive and Kidney Diseases(R01DK116858)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-326-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 327-OR: A Multistate Analysis of Cardiovascular, Renal, and
Neuropsychiatric Outcomes in Patients with Type 1 and Type 2 Diabetes
Using Two Independent Nationwide Cohorts-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 327-OR
Abstract: Introduction and Objective: Heart failure (HF), myocardial infarction (MI), stroke, cancer, depression, dementia, and end-stage renal disease (ESRD) are critical complications associated with diabetes. This study aimed to evaluate transition probabilities between these conditions in patients with type 1 diabetes (T1D) and type 2 diabetes (T2D) compared to the general population (GP).Methods: We conducted a retrospective analysis using two independent nationwide cohorts: 11,115 patients with new-onset T1D matched by age and sex with 55,575 new-onset T2D patients (1:5) and 111,150 individuals from the GP (1:10). A multi-state modeling approach was used to define transitions, with the initial state progressing to first intermediate states (HF/MI, stroke, depression, and cancer), second intermediate states (dementia and ESRD), and the absorbing state (death). Transition probabilities were estimated using the Aalen-Johansen method to calculate 10-year probabilities with 95% confidence intervals (CIs).Results: The median age of participants was 57 years, with a median follow-up of 8.6 years for those with T1D and 5.0 years for those with T2D. The 10-year probability (95% CI) of HF/MI was highest in T2D (7%, 5-8), followed by T1D (5%, 3-7), and GP (4%, 4-4). Depression probability was highest in T1D (9%, 7-10), compared to GP (2%, 0-3) and T2D (1%, 1-1). The probability of dementia was significantly higher in T1D (30%, 27-33) than in T2D (17%, 15-19) and GP (13%, 12-13). In T1D, the 10-year mortality was highest for the ESRD-to-death pathway (52%, 43-61), while in T2D, the stroke-to-death pathway had the highest probability (65%, 61-69).Conclusion: Patients with T1D showed higher risks for neuro-psychiatric and renal outcomes, while T2D patients exhibited higher risks for cardiovascular outcomes. These distinct complication patterns highlight the need for tailored screening and management strategies.DisclosureS. Kim: None. S. Park: None. J. Kim: None. G. Kim: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-327-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 328-OR: Impact of Diabetes and Chemotherapy on Cardiovascular Outcomes in
Breast Cancer Survivors—A Population-Based Study-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 328-OR
Abstract: Introduction and Objective: Older breast cancer (BC) survivors with diabetes mellitus (DM) have worse mortality outcomes than survivors without DM. DM is a major risk factor for cardiovascular disease (CVD), now the leading cause of death in BC survivors. Anthracycline chemotherapy (AC), a widely used BC treatment, also increases CVD risk. We assessed the impact of DM and AC, and their interaction, on specific CVD outcomes in older BC survivors.Methods: We analyzed Surveillance, Epidemiology and End Results cancer data linked to Medicare, a US population-based dataset. We included patients ≥66 years old diagnosed with Stage 2-3 BC between 2008-2017 and excluded patients with preexisting CVD. DM and incident CVD (myocardial infarction [MI], coronary artery disease [CAD], congestive heart failure [CHF]), and AC were ascertained from claims. We used inverse probability treatment weighting with propensity scores to balance baseline sociodemographic characteristics and comorbidities in patients who received AC vs. no AC. Cox regression was used to assess the impact of DM, AC and their interaction on CVD incidence.Results: In 7,182 included BC survivors with median 5 years follow up and median age 72, 1235 (17%) received AC, 1408 had preexisting DM (20%), 332 (4.6%) developed MI, 1289 (18.0%) developed CAD, and 1101 (15.3%) developed CHF. DM increased the risk of MI (hazard ratio [HR] 1.98, 95% confidence interval [CI] 1.53-2.55), CAD (HR 1.63, 95% CI 1.41-1.86), and CHF (HR 1.91, 95% CI 1.65-2.21). AC also increased risk of CAD (HR 1.23, 95% CI 1.12-1.35) and CHF (HR 1.29, 95% CI 1.16-1.44)), but not MI (HR 0.99, 95% CI 0.81-1.23). There were no significant interactions between DM and AC in increasing any CVD event risk.Conclusion: In older BC survivors, both DM and AC significantly increase CVD risk separately, but do not interact to further increase CVD risk. Future research should focus on mitigating CVD risk in BC survivors with DM receiving AC, a particularly high-risk group.DisclosureA. Leiter: None. J.J. Lin: None. C. Kong: None. J. Wisnivesky: Other Relationship; PPD, Banook, American Medical Association, Sanofi, Biontech. Research Support; Axella, Regeneron Pharmaceuticals, Sanofi.FundingNIDDK/NIH (K08DK137022)NCI/NIH (R01CA271604)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-328-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 329-OR: Cardiovascular Effectiveness of SGLT2i and GLP-1RA vs.
Sulfonylureas by Socioeconomic Status—Analysis of U.S. and UK Health
Care Systems-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 329-OR
Abstract: Introduction and Objective: The extent to which differences in socioeconomic backgrounds of patients with type 2 diabetes (T2D) may influence the comparative effectiveness of newer, costlier vs. older, cheaper T2D medications is unclear.Methods: Within the US and UK healthcare systems [Medicare and Clinical Practice Research Datalink (CPRD) (2013-20)], we identified adults with T2D aged >65 years (>18 in CPRD) who initiated sodium-glucose cotransporter 2 inhibitors (SGLT2i) or glucagon-like peptide-1 receptor agonists (GLP-1RA) vs. sulfonylureas (SU). We used dipeptidyl peptidase-4 inhibitors (DPP-4i) vs. SU as a negative control comparison. After propensity matching accounting for social deprivation and other indicators of socioeconomic status (SES), we estimated hazard ratios (HR) and rate differences (RD) of 3-point MACE and hospitalized heart failure (HHF) events per 1,000 person-years, overall and stratified by SES.Results: SGLT2i and GLP-1RA were associated with lower MACE and HHF risks vs. SU in both Medicare and CPRD (Table). HR and RD were similar across different SES. We did not observe large differences in MACE or HHF risks for DPP-4i vs. SU, in line with CAROLINA trial estimates.Conclusion: For adults with T2D in the US and UK, initiating SGLT2i or GLP-1RA vs. SU resulted in lower MACE and HHF risk regardless of socioeconomic backgrounds.DisclosureP.T. Htoo: None. S. Cromer: Other Relationship; Johnson & Johnson Medical Devices Companies. Advisory Panel; Alexion Pharmaceuticals, Inc. Consultant; Wolters Kluwer Health, Patient Square Capital. J.M. Paik: None. D.J. Wexler: Other Relationship; Novo Nordisk. L. Azoulay: Consultant; Roche Diagnostics, Pfizer Inc, Boehringer-Ingelheim. E. Patorno: Research Support; National Institute of Diabetes and Digestive and Kidney Diseases, Patient-Centered Outcomes Research Institute, Food and Drug Administration (FDA), Boehringer-Ingelheim. Other Relationship; UpToDate.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-329-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 330-OR: Enhancing Cardiovascular Disease (CVD) Risk Prediction Using
Metabolic Profiling in the UK Biobank—Pooled Cohort Equations vs.
Retinal Imaging Based Dr. Noon CVD-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 330-OR
Abstract: Introduction and Objective: Circulating metabolites hold potential for improving cardiovascular disease (CVD) risk prediction. However, their added value to existing risk calculators like the Pooled Cohort Equations (PCE) and retina based artificial intelligence (AI) tool like Dr Noon CVD remains uncertain.Methods: This study used UK Biobank, a prospective cohort of 0.5 million participants aged 40-69 years. 17447 participants with available blood metabolic profiling and no history of CVD at baseline were included. Cox LASSO model identified a set of metabolites possibly associated with incident CVD events over 10-year follow-up in a training set of UK Biobank (50% of the individuals). The predictive performance of the PCE and Dr Noon CVD was assessed using Cox regression before and after adding the metabolites.Results: At 10 year follow-up, 563 participants had CVD events. Among the 168 metabolites - glucose, lactate, albumin, phospholipids in medium HDL, triglycerides in chylomicrons and extremely large VLDL and triglycerides in large LDL were associated with CVD events. For metabolites alone baseline Harrell’s C-index= 0.667 (95% CI: 0.635-0.699). After adding selected metabolites C-index for Dr Noon CVD improved by 2.72% from 0.711 (95% CI: 0.683-0.738) to 0.738 (95% CI: 0.712-0.765). For PCE, the performance increased by 2.93% from 0.710 (95% CI: 0.682-0.738) to 0.739 (95% CI: 0.713-0.766). For individuals with prediabetes and diabetes, the C-index improved by 5.11% (from 0.684 to 0.735) for PCE as compared to 2.86% (from 0.706 to 0.735) for Dr Noon CVD.Conclusion: Integration of metabolic profiling with CVD risk prediction models enhances performance, with similar improvements for Dr. Noon CVD and PCE. In diabetics and prediabetics, the PCE model showed a larger improvement, however, both models achieved comparable overall performance after incorporating metabolites, indicating similar final predictive performance for both approaches.Disclosure S. Thakur: Employee; Mediwhale Inc. S. Nusinovici: Employee; mediwhale. J. Cho: Employee; Mediwhale. J. Park: Employee; Mediwhale. H. Kim: Employee; Mediwhale. T. Rim: Employee; Mediwhale Inc. Stock/Shareholder; Mediwhale Inc.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-330-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 331-OR: Modelling the Legacy Effect of Glycaemic Exposure on Long-Term
Cardiovascular Disease in Newly Diagnosed Type 2 Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 331-OR
Abstract: Introduction and Objective: Glycaemic exposures throughout the diabetes continuum may have lasting effects on clinical outcomes, but this legacy effect on cardiovascular disease (CVD) remains poorly understood. This study evaluated the legacy effect of glycaemic exposure on long-term CVD risk in newly diagnosed type 2 diabetes (T2D).Methods: We retrospectively analysed a territory-wide cohort of Hong Kong Chinese adults newly diagnosed with T2D between 2000 and 2019. We examined the contribution of historical HbA1c exposures to incident CVD risk by applying a weighted cumulative exposure model that captures time-varying influences of glycaemia over different periods and adjusts for potential confounders.Results: Among 50,548 newly-diagnosed T2D patients (mean age: 58±11 years; 46% female; mean HbA1c at diagnosis: 9.0%±2.5%), 1,972 developed CVD over a median follow-up of 6.2 years. Early-stage historical HbA1c exposures contributed most significantly to long-term CVD risk, while the impact of later exposures gradually diminished over time. Within a hypothetical 10-year window, a sustained 1% reduction in HbA1c was associated with a 23% lower CVD risk at 10 years (hazard ratio [HR]=0.77; 95% confidence interval [CI]: 0.73-0.81). The risk reductions for achieving 1% HbA1c reduction during the specific time frames were 12% (HR=0.88, 0.86-0.90) for 1-2 years and 6% (HR=0.94, 0.93-0.95) for the 3-4 years after diagnosis. The reductions within the first 4 years post-diagnosis accounted for approximately 78.3% of the overall benefits achievable through a 1% HbA1c reduction over the entire 10-year period.Conclusion: Glycaemic management in newly diagnosed T2D patients has lasting cardiovascular effects. Prompt initiation and sustained glycaemic control after diagnosis can achieve the greatest benefits.DisclosureX. Zhang: None. A. Yang: None. H. Wu: None. E. Lau: None. M. Shi: None. B. Fan: None. J. Yu: None. Y. Huang: None. J.N. Lui: None. A.P. Kong: Advisory Panel; Abbott. Speaker's Bureau; Abbott, AstraZeneca, Zuellig Pharma. Advisory Panel; Biomea Fusion. Speaker's Bureau; Dexcom, Inc. Advisory Panel; Eli Lilly and Company. Other Relationship; Elsevier. Research Support; Sanofi. Advisory Panel; Kyowa Kirin Co., Ltd. J.C. Chan: Consultant; Servier Laboratories, Bayer Pharmaceuticals, Inc, Roche Diabetes Care, Lilly Diabetes. Research Support; AstraZeneca. Other Relationship; Novo Nordisk Foundation. Research Support; Hua Medicine. Speaker's Bureau; Zuellig Pharma. Research Support; Biolingus. Board Member; Asia Diabetes Foundation. Stock/Shareholder; GemVCare. Other Relationship; KDIGO. Research Support; Applied Therapeutics. Other Relationship; European Association for the Study of Diabetes. Consultant; Sanofi. E. Chow: Speaker's Bureau; AstraZeneca, Boehringer-Ingelheim, Bayer Pharmaceuticals, Inc. Research Support; Medtronic. Speaker's Bureau; Zuellig Pharma, Sinocare Inc. Research Support; Hua Medicine. Speaker's Bureau; Procter & Gamble. R.C. Ma: Advisory Panel; AstraZeneca. Other Relationship; AstraZeneca, Bayer Pharmaceuticals, Inc. Advisory Panel; Boehringer-Ingelheim. Other Relationship; Boehringer-Ingelheim. Advisory Panel; Eli Lilly and Company. Research Support; Novo Nordisk, Boehringer-Ingelheim, Roche Diagnostics. Advisory Panel; Merck & Co., Inc. A. Luk: Research Support; Roche Pharmaceuticals. Other Relationship; Eli Lilly and Company. Research Support; Merck Sharp & Dohme Corp, AstraZeneca. Other Relationship; Novo Nordisk. Research Support; Amgen Inc.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-331-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 332-OR: Social Isolation and Loneliness and Stroke Risk in Men and Women
with Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 332-OR
Abstract: Introduction and Objective: We evaluated the association between social isolation, loneliness, and stroke risk in individuals with diabetes (DM) (vs. euglycemia) and assessed sex differences in the association.Methods: We included participants with DM (N=40,684) (defined by self-reported DM diagnosis, DM medication, HbA1c>6.5%, ICD codes) and sex-, race-, age-, and center-matched euglycemic individuals (1:1) from the UK Biobank. Isolation and loneliness were measured using validated 3-item scales. We used Cox regression to examine the association between social isolation, loneliness and stroke risk (ICD codes for ischemic and hemorrhagic strokes) in the DM and euglycemic groups separately, adjusting for common cardiovascular risk factors and psychosocial comorbidities. We tested for sex differences by adding a sex-exposure interaction to the models and estimated the stroke absolute risk reduction (ARR) associated with improved isolation and loneliness.Results: During a median follow-up of 10 years, low social isolation and low loneliness (score=0 vs. score≥2) were associated with a reduced risk of stroke (isolation 0.83, 0.72-0.97; loneliness 0.73, 0.62-0.86) in the DM group, especially in men with DM (men isolation 0.79, 0.65-0.95, women 0.93, 0.72-1.22, p-interaction=0.05; loneliness men 0.63, 0.52-0.77, women, 0.96, 0.72-1.29, p-interaction=0.02). ARR associated with improved isolation and loneliness was 0.7% and 1.3% (equivalent to 7 and 13 stroke cases per 1000 people with DM, respectively, during the 10-year period). The association between isolation, loneliness and stroke risk was not significant in the euglycemic group.Conclusion: Improved social isolation and loneliness attenuate excess stroke risk in individuals with DM, particularly in men with DM.DisclosureX. Wu: None. Y. Zu: None. X. Wang: None. Y. Yoshida: None.Fundingthe National Institute of GeneralMedical Sciences of the National Institutes of Health (1P20GM152305)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-332-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 333-OR: Genetic Variants Associated with Weight Change in Response to
Glucose-Lowering Medications—Results from the GRADE Study-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 333-OR
Abstract: Introduction and Objective: Obesity management is an integral part of type 2 diabetes (T2D) treatment, as weight reduction significantly improves glycemic control and accordingly may ameliorate diabetes complications. Many glucose-lowering medications also affect weight. Understanding genetic factors that predict weight changes can enhance precision in T2D management by aligning treatments with each patient’s genetic profile.Methods: In the GRADE Study, we conducted a genome-wide association study to identify variants associated with weight change after 1 and 4 years of treatment with liraglutide, glargine, glimepiride, or sitagliptin. Our cohort included 4,689 participants of diverse ancestries. We modeled weight change as a continuous outcome, adjusting for age, sex, baseline weight, and the first 10 principal components to account for differences in genetic ancestries.Results: We identified treatment-specific associations between genetic variants and weight change. Five variants were associated with weight change for liraglutide, one for glargine, one for glimepiride, and none for sitagliptin (P<5×10-8). Of particular interest is rs6026781 near EDN3, associated with weight change for liraglutide. The A allele of rs6026781 was associated with reduced weight loss at year 1, with carriers losing on average 3.87 kg less than noncarriers (P=3.5×10-9) and showed a trend toward smaller average weight loss over 4 years. The variant is rare across most ancestry groups but has a higher prevalence in individuals of African ancestry (minor allele frequency=8.8%). EDN3 encodes endothelin-3, a peptide known to stimulate GLP-1 secretion, inhibit gluconeogenesis, and promote browning of white adipose tissue.Conclusion: Our study identified novel loci associated with weight response to T2D treatments. These findings, pending validation, could inform personalized T2D management by optimizing weight response across diverse populations.DisclosureL. Szczerbinski: None. T.Y. Wangden: None. M. Tripputi: None. A. Huerta: None. A.J. Kretowski: None. S.E. Kahn: Advisory Panel; Amgen Inc, AltPep, Biomea Fusion. Research Support; Corcept Therapeutics. Advisory Panel; Eli Lilly and Company, Merck & Co., Inc. Consultant; Neurimmune. Advisory Panel; Novo Nordisk, Oramed Pharmaceuticals. N. Younes: None. J.H. Li: None. J.M. Mercader: None. J.C. Florez: Research Support; Novo Nordisk.FundingAmerican Diabetes Association (11-22-PDFPM-03); The National Institute of Diabetes and Digestive and Kidney Diseases (U01DK098246; R01DK123019; U34DK088043); The National Heart, Lung, and Blood Institute; The Centers for Disease Control and Prevention
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-333-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 334-OR: Comparison of T2D Genetic Clusters Highlights Robustness across
Clustering Approaches-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 334-OR
Abstract: Introduction and Objective: Clustering type 2 diabetes (T2D) genetic loci based on phenotype associations is a powerful approach for uncovering disease mechanisms. Here, we compared two recent efforts from the T2D Global Genomics Initiative (TGGI) and Mass General Hospital (MGH) groups, which used distinct input matrices and clustering methods (k-means vs Bayesian non-negative matrix factorization, bNMF). Our goal was to identify robust and biologically meaningful clusters that transcend methodological differences.Methods: To compare the published clusters, we assessed: i) cluster-specific partitioned polygenic risk scores (pPS) in individuals from the Mass General Brigham Biobank (MGBB, N=64k), ii) ) variant overlap, iii) colocalization analyses, and iv) a cross-clustering analysis, where each clustering method was applied to the opposing study’s matrix.Results: In MGBB, we identified four cluster pairs with correlated pPS (MGH/TGGI): Beta Cell 2/Beta Cell PI+; Lipodystrophy 1/Lipodystrophy; Obesity/Obesity, Cholesterol/Liver Lipid Metabolism (R>0.4, p<1e-200). Phenotypic associations with cluster pPS reinforced these findings, such as both MGH/TGGI Lipodystrophy clusters with increased triglycerides and decreased BMI and HDL. These same cluster pairs had strong overlap of shared variants (Fisher’s p< 1e-10). In colocalization analyses, loci that overlapped between matrices and belonged to one of the above four cluster pairs were enriched for quantitative trait loci signals in metabolites, proteins, and GWAS traits (Chi-square p<0.002). When bNMF was applied to the TGGI matrix, >90% of variants from the four robust clusters still clustered together (excluding those that went unclustered).Conclusion: Our analysis demonstrates that while clustering results are influenced by inputs and methods, certain T2D genetic clusters emerge consistently, indicating robust biological signatures. These findings support cluster reproducibility and highlight key clusters for further investigation into T2D pathophysiology.DisclosureK. Smith: None. A.J. Deutsch: None. J.E. Gervis: None. K. Lorenz: None. H.J. Taylor: None. R. Mandla: None. B.F. Voight: Other Relationship; Eli Lilly and Company. J.I. Rotter: None. C. Yap: None. C.N. Spracklen: None. E. Zeggini: None. J.M. Mercader: None. A. Morris: None. M. Udler: Research Support; Novo Nordisk.FundingDoris Duke (241537)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-334-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 335-OR: Polygenic Score Predicts Faster Kidney Function Decline in
Individuals with and without Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 335-OR
Abstract: Introduction and Objective: Diabetes, the major cause of chronic kidney disease (CKD), accounts for half of end-stage kidney disease cases worldwide. This study evaluates whether polygenic score (PS) predicts estimated glomerular filtration rate (eGFR) trajectories in people with and without diabetes.Methods: We analyzed 7,163 participants (2,496 with diabetes) from the Korean Genome and Epidemiology Study (KoGES) and validated in 749 individuals with diabetes from an independent cohort of Seoul National University Hospital (SNUH). eGFR was calculated using CKD-EPI equation, and PRS-CSx generated a multi-ancestry PS for eGFR using CKDGen, UK Biobank, and Japan Biobank data. Participants were stratified into high, intermediate, and low PS groups by quartiles. A longitudinal linear mixed model assessed PS and diabetes status interactions on eGFR decline, while Cox regression evaluated the association of PS with CKD risk.Results: Baseline eGFR varied significantly by PS groups, with lower PS linked to worse kidney function in the KoGES cohort. In the diabetes group, annual eGFR decline was steepest in the low PS group (-0.71mL/min/1.73m2), followed by intermediate (-0.70) and high (-0.58) groups, with significant differences (p ≤ 6.7e-7) and comparable trends observed in the non-diabetes group. Validation in the SNUH cohort showed similar declines (-0.64, -0.46, -0.21mL/min/1.73m2; p ≤ 1.4e-2). Decline rates differed significantly by diabetes status in intermediate and low PS groups, with wider gaps as PS decreased. Lower PS was also linked to higher CKD risk, with hazard ratios (HRs) of 1.4 (1.2-1.5) and 2.2 (1.9-2.4) for intermediate and low PS groups compared to the high PS group. SNUH cohort exhibited similar HR patterns with 1.5 (1.2-1.8) and 2.5 (2.0-3.0), respectively.Conclusion: Our study demonstrates that PS for eGFR effectively predicts eGFR decline, especially in people with diabetes. Integrating PS into clinical practice could improve CKD diagnosis and management.DisclosureY. Jo: None. H. Lee: None. J. Park: None. J. Park: None. J. Choi: None. J. Lee: None. S. Lee: None. S. Kwak: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-335-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 336-OR: Diabetogenic Processes for Increased Insulin Resistance with
Concomitant Hyperinsulinemia Are Associated with Increased Colorectal
Cancer Risk-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 336-OR
Abstract: Introduction and Objective: Type 2 diabetes (T2D) has been associated with an increased risk of colorectal cancer (CRC), potentially through distinct mechanisms including hyperinsulinemia, insulin resistance, and hyperglycemia. This study aimed at investigating the relationship between polygenic scores for these pathophysiological processes and CRC risk.Methods: We analyzed data from participants of European ancestry in the Genetics and Epidemiology of Colorectal Cancer Consortium and the Colon Cancer Family Registry, including 62,292 with incident CRC cases and 62,708 controls. Eight pathway-specific polygenic scores characterizing distinct diabetogenic processes were generated using data from the largest genome-wide association study for T2D. Conditional logistic regression was used to estimate odds ratios (ORs) for CRC after adjusting for potential confounders.Results: The four pathway-specific polygenic scores reflecting increased insulin resistance with concomitant hyperinsulinemia were associated with increased CRC risk (P < 0.001 for lipodystrophy, body fat, obesity, and metabolic syndrome scores). Individuals in the highest decile of these four pathway-specific polygenic had elevated CRC risk compared to those in the lowest decile, with adjusted ORs ranging from 1.08 (95% CI 1.06-1.09) for the metabolic syndrome score to 1.25 (95% CI 1.23-1.26) for the obesity score. No significant associations were observed for scores reflecting other diabetogenic processes such as beta-cell dysfunction, insulin resistance mediated through impaired liver and lipid metabolism, or residual glycemic effects.Conclusion: These findings link specific T2D-related pathophysiological processes characterized by insulin resistance with concomitant hyperinsulinemia to increased CRC risk and may inform the development of more targeted CRC prevention strategies.DisclosureX. Zhou: None. M. Sevilla-Gonzalez: None. U. Peters: Consultant; ABGIL. Stock/Shareholder; Amazon, ARM Holdings, BioNTech, Microsoft, Crowdstrike Holdings Inc, CureVac, Google/Alphabet. Other Relationship; Stellantis. Stock/Shareholder; NVIDIA Corp. A. Phipps: None. M. Udler: Research Support; Novo Nordisk. A.T. Chan: None. J.C. Florez: Research Support; Novo Nordisk. E. Giovannucci: None. M. Song: Consultant; Etiome, Inc. J. Merino: None.FundingEFSD/Lilly European Diabetes Research Programme Novo Nordisk Foundation ( NNF23SA0084103, NNF18CC0034900)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-336-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 337-OR: Associations of Polygenic Risk Scores for Type 2 Diabetes with
Metabolic Measures in Pacific Islanders from Guam and Saipan-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 337-OR
Abstract: Introduction and Objective: Several polygenic risk scores (PRSs) for type 2 diabetes (T2D) have been derived from genome-wide association studies (GWASs), but Pacific populations have little representation in these studies. The aim of this study was to examine the association of PRS for T2D with clinical measures in Pacific Islander populations from Guam and Saipan.Methods: We analyzed seven constructions of PRSs using publicly available GWAS summary statistics in 2,022 participants in a GWAS from a community-based cross-sectional study of diabetes. Associations of T2D PRS with diabetes, maximum body mass index (BMI), fasting glucose, and HbA1c were examined with adjustment for age, sex, and the first four genetic principal components (PCs) from the GWAS (to account for population stratification). Insulin resistance/secretion measures (HOMA-IR/HOMA-B) were also analyzed in 998 non-diabetic participants.Results: All seven PRSs were strongly associated with T2D (p<6×10-9 for each); a 1-SD increase in the PRS was associated with 40-81% increase in the odds of T2D (i.e., standardized odds ratio [OR] ranging from 1.40-1.81) adjusting for age, sex, and PCs. We also found that each 1-SD increase in the PRS was associated with 5.28-8.23 mg/dL higher fasting glucose, and with 0.24-0.41% higher HbA1c adjusting for age, sex, and PCs. We found no associations of PRSs with maximum BMI or insulin measures. Among the seven different PRSs, a score composed of ~1.1M variants, derived from a European GWAS (Mars, AJHG, 2022) provided the strongest associations with T2D; the OR for a difference of 5000 risk alleles was 2.11 (95% CI, 1.78-2.49). For comparison, the OR in European Americans from the ARIC study was 2.32 (95% CI, 2.16-2.49).Conclusion: All seven of the T2D PRSs evaluated associated significantly and strongly with diabetes, fasting glucose and HbA1c. These analyses suggest that T2D polygenic scores have high transferability to individuals from Pacific populations.DisclosureM.J. Ramirez-Luzuriaga: None. S. Safabakhsh: None. R. Salehi: None. S. Kobes: None. J. Curran: None. W. Hsueh: None. R.L. Hanson: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-337-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 338-OR: Loss of LAMA4 as a Novel Causative Defect for Lipodystrophy
-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 338-OR
Abstract: Introduction and Objective: Lipodystrophy (LD) is characterized by partial or complete loss of adipose tissue (AT) and concomitant ectopic lipid storage, IR and dyslipidemia. Variants in >15 genes have been reported to cause recessive or dominant LD forms, but often there is no genetic cause identified for familial LD. Furthermore, studying causality of novel variants is further complicated by mouse models of human LD presenting with lean but metabolically healthy phenotypes.Methods: Two female siblings from a consanguineous Turkish family were diagnosed as teenagers with partial LD characterized by AT loss on the extremities and excessive AT on the neck and trunk in addition to diabetes. The females, aged 33, BMI 21.3 kg/m2, HOMA-IR 4.7 and 26, BMI 25.3 kg/m2, HOMA-IR 23.8 present with hepatic steatosis, hypertriglyceridemia and (in one) recurrent acute pancreatitis. WES was interrogated for the presence of rare (gnomAD MAF < 0.1%) shared homozygous or compound heterozygous variants.Results: Whilst no variants in known LD genes were identified, an early nonsense mutation (Q45*) in LAMA4 was revealed as a potential causal variant of the partial LD and metabolic phenotype. Complete loss of LAMA4 was confirmed in the white AT (WAT) of the patients. Laminin-α4 (LAMA4) is a trimeric extracellular matrix protein present in basement membranes, with LAMA4 being highly expressed in human WAT. To examine the role of heterozygous LAMA4 variants in LD, we sequenced LAMA4 in a Spanish cohort of familial partial LD patients (n=89) and controls (n=58). No enrichment of potentially damaging heterozygous variants (CADD >25) in the FPLD1 cohort was observed. Consistent with an important role for LAMA4 in AT function, mice lacking LAMA4 exhibited reduced body weight and decreased adipose mass in inguinal and gonadal depots.Conclusion: We have identified loss of LAMA4 as a potential causative defect underlying partial LD and associated metabolic dysfunction, additionally emphasising the importance of laminin in healthy adipose physiology.DisclosureY. Karusheva: None. M. Muso: None. J. Shen: None. J.A. Tadross: None. B. Lam: None. K. Rainbow: None. S. Lockhart: Consultant; Eolas. Stock/Shareholder; Verve therapeutics. S. Gancheva: None. D. Savage: None. D. Araujo-Vilar: Consultant; Amryt Pharma. M. Roden: Research Support; Boehringer-Ingelheim. Advisory Panel; Echosens. Speaker's Bureau; Madrigal Pharmaceuticals, Inc. Advisory Panel; MSD Life Science Foundation. Board Member; Novo Nordisk. Advisory Panel; TARGET PharmaSolutions, Inc. S.P. O'Rahilly: Advisory Panel; Pfizer Inc. Consultant; AstraZeneca.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-338-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 339-OR: UNC119B: A Novel Target for the Treatment of Type 2 Diabetes
-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 339-OR
Abstract: Introduction and Objective: Following our discovery of compound C59 as a new insulin sensitizer, we identified Unc119b as its molecular target. The role of Unc119b in insulin signaling had not previously been shown. Here we investigate how Unc119b regulates GLUT4 translocation and validate Unc119b as a novel promising target to improve insulin sensitivity.Methods: To test insulin action, we measured glucose tolerance, insulin tolerance and glucose uptake. Unc119b expression was measured by qPCR and western blot. Activity of Rac1 was measured through PAK1 pull down and PAK1 phosphorylation assays.Results: We found that Unc119b silencing enhances insulin-stimulated GLUT4-translocation in cells and that deletion of Unc119b significantly improves glucose tolerance and glucose uptake in skeletal muscle and BAT of rodent models of insulin resistance. Of note, we show that Unc119b expression is increased in those tissues in obese animals. Mechanistically, we show that Unc119b binds to Rac1, a small Rho-GTPase which facilitates GLUT4 translocation. Inhibition of Unc119b using C59 results in increased activation of Rac1 by insulin and increased phosphorylation of its downstream effector PAK1.Conclusion: These results suggest that Unc119b impairs insulin action through inhibition of Rac1and that the increased expression of Unc119b in obese individuals likely contributes to the development of insulin resistance. Genetic or pharmacological inhibition of Unc119b significantly improved insulin sensitivity and glucose tolerance through enhanced Rac1 signaling and increased GLUT4 translocation in skeletal muscle and BAT. Together, these data establish Unc119b as a promising new target for the treatment of insulin resistance and type II diabetes.DisclosureA. Mittal: None. P. Buscaglia: None. J. Sebag: None.FundingNational Institutes of Health (RO1DK138932)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-339-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 340-OR: Posttranslational Modification of Adipose Tissue Aging and
Metabolic Dysregulation by the Methyltransferase SETD2-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 340-OR
Abstract: Introduction and Objective: Aging is a complex biological process with pronounced metabolic dysfunction, which is exacerbated by obesity. During aging, adipose tissue is vulnerable and functions as a driver of age-related diseases. Adipose tissue progenitors are responsive to aged environment. However, the key regulator involved in adipose aging process remains obscure.Methods: Progenitor-specific SETD2 knockout mice, adipocyte-specific SETD2 knockout mice and littermates were fed with chow or HFHS diet for 16 weeks. The glucose tolerance test and insulin tolerance test were performed. H&E staining, Sirius red staining and immunohistochemical staining were used for adipose tissue analysis. Coimmunoprecipitations were used for identification of C/EBPα as a SETD2 binding protein.Results: We show that lysine methyltransferase SETD2 is an essential regulator of adipose tissue aging via maintaining differentiation capacity of progenitors and metabolic function of mature adipocytes. Compared with young mice, SETD2 was significantly decreased in white adipose tissue of 20 months aged mice. Progenitor-specific SETD2 deficiency remarkably reduced body weight, caused defective development of adipocytes and exacerbated systemic metabolic disorders. Adipocyte-specific SETD2 deficiency aggravated age-related adipose hypertrophy, inflammation, fibrosis and expression levels of aging markers, p16 and p21, in obese mice fed with HFHS. Mechanistically, SETD2 is sufficient to interact with C/EBPα, thereby facilitating genes related to differentiation and development. Importantly, SETD2 is decreased in adipose tissues of obese humans and positively associated with improved metabolic function.Conclusion: Collectively, this study uncovered a novel mechanism in adipose tissue aging process, targeting SETD2 may provide therapeutic strategies for the treatment of age-related metabolic diseases, such as type 2 diabetes and obesity.DisclosureD. Ding: None. Z. Zheng: None. S. Wei: None. W. Li: None. J. Shen: None. J. Lin: None. M. Huang: None. L. Li: None. Z. Liu: None. K. Qian: None. T. Zhang: None. J. Zhao: None. Y. Jiang: None. W. Su: None. Y. Li: None. A. Cui: None.FundingNational Key R&D Program of China (2019YFA0802502, 2023YFA1801100), National Natural Science Foundation of China (81925008, 32130047), Project supported by Shanghai Municipal Science and Technology Major Project, Open Project Program of Metabolic Vascular Diseases Key Laboratory of Sichuan Province (2022MVDKL-K2)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-340-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 341-OR: PLA2G7 Governs Adipocyte Hypertrophy and Metabolic Regulation
through HIF1α/Glycolysis/Adipogenesis Pathway-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 341-OR
Abstract: Introduction and Objective: Adipocyte hypertrophy contributes to adipose tissue dysfunction and global metabolic disorders. PLA2G7 is known as an vital mediator of the immune changes of aging, however, it remains unclear whether PLA2G7 mediates dysregulation of adipocytes and metabolism.Methods: We generate adipocyte-specific PLA2G7 KO (PLA2G7AKO) and overexpression mice (PLA2G7OE) and subject them to a chow diet (NCD) or high fat diet (HFD). We performed various molecular, biochemical, immunohistochemical analyses, and primary cell culture studies to evaluate the role of PLA2G7 in adipocytes and elucidate the underlying mechanisms.Results:PLA2G7AKOmice are protected against diet-induced obesity, insulin resistance, glucose dysregulation and hepatic steatosis. In contrast, PLA2G7OE mice exhibit adipocyte hypertrophy and metabolic dysfunctions. Gain- and loss-of-function studies with primary adipocytes reveal a role for PLA2G7 in promotion of HIF1α/glycolysis/adipogenesis axis. The serum level of LP-PLA2 (encoded by PLA2G7) and the expression of PLA2G7 in human adipose tissues are both positively correlated with human obesity and related disorders, indicated by the adipogenic marker PPARγ, BMI, fasting insulin and glucose levels and HOMA-IR.Conclusion: we reveal a novel role for adipocyte PLA2G7 in diet-induced hypertrophic obesity. Targeting PLA2G7 could be a promising therapy against obesity and metabolic dysfunctions.DisclosureJ. Zheng: None. Y. Shu: None. X. Lyu: None. J. Yan: None. C. Hu: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-341-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 342-OR: Cell-State Dependent Regulation of PPARγ Signaling by the
Transcription Factor ZBTB9 in Adipocytes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 342-OR
Abstract: Introduction and Objective: ZBTB9 is a widely expressed but poorly studied transcription factor that interacts with the key adipocyte regulator PPARγ. In addition, genetic variants in ZBTB9 are associated with BMI, T2D risk, and HbA1c levels. Thus, we sought to investigate the role of Zbtb9 in adipocyte function and metabolic health.Methods: We combined genomic, biochemical, and cell biology approaches in both human and mouse adipocyte cell lines as well as in vivo studies of a floxed Zbtb9 allele to investigate the function of Zbtb9.Results: We discovered that Zbtb9 deficiency in adipocytes decreased PPARγ activity and protein level. In contrast, Zbtb9 deficiency in preadipocytes increased PPARγ levels and enhanced adipogenesis. Transcriptomic analyses of Zbtb9 deficient preadipocytes revealed that the E2F pathway was among the most upregulated pathways, and RB phosphorylation (pRB) was likewise increased, which in turn regulates E2F activity. Inhibition of the E2F pathway blocked the effects of Zbtb9 deficiency on adipogenesis. Collectively, these results demonstrate that Zbtb9 inhibits adipogenesis as a negative regulator of Pparg expression via pRB-E2F signaling in preadipocytes while positively regulating PPARγ signaling in mature adipocytes by increasing levels of PPARγ protein. Adipocyte-specific deletion of Zbtb9, using a newly generated floxed allele, resulted in impaired glucose homeostasis without altering fat pad morphology, particularly in mice fed a high-fat diet, whereas deletion of Zbtb9 in preadipocytes altered fat pad morphology resulting in smaller adipocytes, confirming the in vivo importance of Zbtb9 in metabolic health.Conclusion: Our findings reveal cell-state dependent roles of ZBTB9 in adipocytes, identifying a new molecule that regulates adipocyte biology as both a positive and negative regulator of PPARγ signaling depending on the cellular context, and thus may be important in the pathogenesis of obesity and T2D.DisclosureX. Xu: None. J. Ockunzzi: None. D. Buchner: None.FundingNational Institute of Diabetes and Digestive and Kidney Diseases (DK119305)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-342-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 343-OR: The Mitochondrial Protein OPA1 Governs Preadipocyte Proliferation
and Metabolic Homeostasis through Ca2+ Mechanical Force/Glycolysis Pathway
-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 343-OR
Abstract: Introduction and Objective: The proliferation of preadipocytes favors global metabolic homeostasis. Our study aims to explore the role of mitochondrial protein Optic atrophy 1 (OPA1) in preadipocytes in regulating metabolic disorders and elucidate underlying mechanisms.Methods: We generate preadipocyte-specific KO mice (OPA1PKO) with OPA1flox/flox and Pdgfrα-Cre mice and overexpression mice (OPA1OE) by AAV-DIO injection in Pdgfrα-Cre mice. Mice are subjected to an HFD to monitor preadipocyte proliferation and metabolic phenotypes. Seahorse assays, Ca2+and mechanical force measurements are performed in primary preadipocytes.Results:OPA1PKO mice are protected from glucose and insulin intolerance after HFD. It is due to the increased proliferation of Pdgfrα+ cells that promotes hyperplasia. In contrast, OPA1OE mice exhibit decreased hyperplasia and severe metabolic disorders. Mechanistically, OPA1 KO increases glycolysis to promote the proliferation of preadipocytes through intracellular Ca2+ / mechanical force pathways. Inhibition of Ca2+ and glycolysis reverse these effects. Finally, OPA1 in Pdgfrα+cells from human visceral fat is positively correlated with HOMA-IR and serum TG.Conclusion: we uncover a novel function of OPA1 as a regulator of preadipocyte proliferation and adipose hyperplasia in metabolic homeostasis.DisclosureY. Shu: None. J. Zheng: None. X. Lyu: None. H. Yu: None. J. Yan: None. C. Hu: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-343-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 344-OR: Understanding the Dynamic Roles of Ketone Body Metabolism of
Mesenchymal Stromal Cells in the Regulation of Adipose Tissue Inflammation
and Insulin Resistance-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 344-OR
Abstract: Introduction and Objective: Mesenchymal stromal cells (MSCs), including adipocyte progenitor cells and other types of fibroblasts, contribute to adipose tissue remodeling and function through various mechanisms. In addition to providing a source of new adipocytes, MSCs regulate adipose tissue inflammation in response to nutritional and environmental challenges such as cold exposure. Ketone bodies serve as an alternative energy source when glucose is not readily available. Recent studies indicate that ketone bodies influence brown adipogenesis. This study investigates the roles of ketone body metabolism in adipose tissue MSCs in the regulation of adipose tissue remodeling and energy metabolism.Methods: To address the question, we deleted a key enzyme of ketolysis, 3-oxoacid CoA-transferase 1 (Oxct1), selectively in PDGFRα+ MSCs of mice. To assess the role of ketone body metabolism in response to environmental cold, control and knockout (KO) mice were exposed to cold (6°C) or thermoneutral (TN; 30°C) conditions, followed by assessment of adipose tissues and metabolic phenotypes, including metabolomic profiling.Results: Oxct1 KO mice exposed to a cold environment showed increased levels of adipose tissue inflammation and impaired glucose tolerance. Surprisingly, these inflammatory responses were reversed in mice housed under TN conditions. At TN, Oxct1 KO mice showed lower levels of inflammation and improved glucose tolerance. Comprehensive metabolomic analyses of adipose tissue revealed that the levels of methylglyoxal (MG), an inflammatory metabolite, were reciprocally regulated, with KO mice exhibiting higher MG levels in the cold and lower levels at TN, relative to control mice.Conclusion: Collectively, these results indicate that ketone body metabolism in MSCs is critical for controlling adipose inflammation and metabolic homeostasis.DisclosureI. Hwang: None. J. Jung: None. Z. Arany: Consultant; nanophoria, abrax, Biohaven, Pfizer Inc, scipher. P. Seale: Advisory Panel; iTeos. Consultant; Merck & Co., Inc.FundingAmerican Diabetes Association (1-25-PDF-28)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-344-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 345-OR: Recombinant AAV-Mediated Gene Therapy for the Treatment of
Streptozotocin-Induced Diabetes in Nonhuman Primates-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 345-OR
Abstract: Introduction and Objective: Diabetes mellitus, caused by beta cell loss and insulin insufficiency, affects over 300 million people worldwide, with limited curative therapies available. Gene therapy using recombinant adeno-associated virus (rAAV) offers a promising alternative for sustained therapeutic effects. Building on prior success in murine models, we applied retrograde intraductal infusion of rAAV6 to deliver Pdx1 and MafA, converting alpha cells into beta-like cells in non-human primates (NHPs).Methods: Diabetes was induced with streptozotocin (STZ) in cynomolgus macaques. NHPs received retrograde intraductal infusion of rAAV via laparotomy. rAAV capsids were chosen based on tropism and pre-existing neutralizing antibody titers (NAbs). Temporary immunosuppression (IS) was found to be necessary to prevent antiviral immunity, using various combinations of rituximab, anti-thymocyte globulin, mycophenolate, rapamycin, and steroids. Blood work, IV GTTs, NAbs, ELISpot assays, and immunophenotyping were performed for up to 3 months post-infusion. Pancreatic tissues were analyzed using IHC and RNA-scope for beta cell markers, as well as single-cell RNA transcriptomics.Results: One-month post-infusion, NHPs showed improved glucose tolerance and reduced insulin requirements. The AAV6 capsid with endocrine-specific promoters driving Pdx1 and MafA showed durable effects. By 3 months, improvements declined, likely due to anti-viral immunity, evidenced by ELISpot-positive cytotoxic T cells and neutralizing antibodies. Effective IS regimens, including rituximab, steroids, and rapamycin, suppressed immune responses, rescued beta-like cell populations, and improved glucose control.Conclusion: We developed a novel rAAV gene therapy and demonstrated that ectopic expression of Pdx1 and MafA in alpha cells enables regeneration of beta-like cells, production of endogenous insulin, and attenuation of the diabetic phenotype in NHPs.Disclosure H.N. Rinehardt: Research Support; Genprex, Burrough's Wellcome Fund. E.R. Jozwiak: None. V. Dhamotharan: None. M. Takeda: None. A. Martyn: None. M. Saleh: None. K. Prasadan: None. T. Zhang: None. G. Gittes: None.FundingNIH (R01DK120377)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-345-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 346-OR: Pharmacologic Stimulation of Insulin Granule Acidification
Increases β-Cell Zinc and Augments β-Cell-Targeted Drug Delivery-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 346-OR
Abstract: Introduction and Objective: Loss of insulin-producing pancreatic β-cells is a pathologic hallmark of diabetes that could be reversed by regenerative therapy. However, existing replication-promoting compounds lack β-cell specificity, presenting a major barrier to their clinical application. To achieve β-cell restricted bioactivity, we previously generated a zinc-chelating hybrid compound of GNF-4877 (βRepZnC), which leverages the uniquely high zinc content of β-cells for targeted action. Herein, we aimed to identify pharmacological agents that boost β-cell zinc and improve targeted βRepZnC delivery and bioactivity.Methods: To identify compounds that augment β-cell zinc content, chemical screening and automated image analysis was performed using a turn-on zinc probe (TSQ) fluorescence intensity (a zinc content surrogate) analysis in R7T1 β-cells. Hit compound effects on βRepZnC delivery and bioactivity were evaluated by measuring cellular drug accumulation (LC-MS/MS) and β-cell replication (BrdU and Ki-67 immunostaining), respectively, in primary islets isolated from human and mice.Results: We identified GR-46611 as an enhancer of β-cell zinc content. Zinc enhancement increased β-cell-specific accumulation and retention of βRepZnC by 160-fold in human islets and 103-fold in mouse islets, relative to the parent molecule GNF-4877; accordingly, boosting selective β-cell replication (but not non-β-cell) in rodent and human islets. Mechanistic studies revealed that GR-46611 increased zinc flux into insulin granules, in a ZnT8-dependent fashion, by promoting V-ATPase-driven granule acidification via inhibition of cAMP-PKA signaling.Conclusion: Our findings uncover a novel interplay between β-cell zinc and insulin granule regulation, advancing a versatile zinc-powered strategy for β-cell-targeted therapeutic delivery for diabetes treatments.DisclosureS. Lee: None. H.P. Moeller: Employee; Genentech, Inc. J.P. Annes: None.FundingNational Institute of Diabetes and Digestive and Kidney Diseases (R01DK101530, U01DK136965, R01DK119955)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-346-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 347-OR: ILV-001, a Myokine of Interest to Potentiate the Success of
Pancreatic Islet Transplantation and Treat a Maximum Number of People with
T1DM-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 347-OR
Abstract: Introduction and Objective: Islet transplantation is a promising therapeutic approach for people with unstable T1DM. The main challenge is to reduce the number of pancreases needed to treat a single person. In this context, we have recently demonstrated that ILV-001, a component of the muscle secretome, enables rapid uptake and lasting function of the graft. The aim of the project was to determine whether ILV-001 could reduce the quantity of pancreatic islets to be transplanted in order to normalize glycaemia in diabetic rats.Methods: Syngeneic rats rendered diabetic with streptozotocin were given or not (SHAM group) an intra-portal infusion of 5000 IEQ/kg untreated (control group) or pre-treated with 1µg/ml ILV-001. Transplanted animals either received or did not receive a daily intraperitoneal injection of ILV-001. Weight gain, glycemia, c-peptidemia, graft function and insulin requirements were assessed for 3 months.Results: Contrary to control group, transplantation of 5000IEQ/kg+ILV-001 improved glycemic control in diabetic rats and this from 3 days after islet injection. Moreover, whatever ILV-001 administration modality, c-peptidemia increased compared with the control group from 7 days post-injection. In addition, IPGTT tests showed an improvement in graft functionality with ILV-001 versus control group throughout the study. Finally, insulin requirements were significantly reduced in ILV-001-treated diabetic rats during metabolic follow-up.Conclusion: ILV-001 is a promising therapeutic agent to potentiate the effectiveness of islet transplantation. It reduces by at least half the number of islets needed to normalize glycemic control in people with T1DM.DisclosureA. Langlois: None. M. Pinget: None. C. Siobhan: None. K. Bouzakri: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-347-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 348-OR: Diabetes Induces Complex Dysfunction of Intrinsic Mesenchymal Stem
Cells That Can Be Repaired by Healthy Mesenchymal Stem Cells-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 348-OR
Abstract: Introduction and Objective: Mesenchymal Stem Cells' (MSCs) immunemodulatory & anti-inflammatory actions make them effective Regenerative Medicine tools for Diabetes and its complications. MSCs can be used allogeneically, but patients prefer to use their own cells. Intrinsic MSCs from T1 & T2DM subjects exhibit dysfunctions that may contribute to the comorbidities and inflammation associated with DM. Culture expansion in a non-diabetic milieu does not repair the dysfunctions, suggesting that DM “reprograms” these cells. We and others showed that MSCs from healthy donors are renoprotective and beneficial to patients with DM suggesting they may affect the patient's own MSCs (see also abstract this meeting).We assessed here whether conditioned medium (CM) from healthy MSCs could restore the functions of MSCs from diabetic patients.Methods: MSCs from healthy, T1 & T2DM donors were culture expanded in low glucose DMEM, or CM from either healthy or T1 DM MSCs. Inflammatory responses were assessed pre and post INFγ exposure (rtPCR & ELISA).Results: IDO-1 and IL6 protein expression are 2-4-fold higher at baseline in T1 & T2DM MSCs vs. control. IDO-1, CCL8, IL6, and IGF1 are elevated 10-40-fold at baseline; IDO1, CXCL-9, CXCL10, IL6, FGF-2, and PD-L1 are elevated 10-200-fold upon stimulation with INFγ in T1 & T2 DM MSCs vs. healthy MSCs. Culture of T1DM & T2DM MSCs in CM from healthy MSCs restores expression of all but IGF1 & IL6 to near normal, while CM from T1DM MSCs does not. When healthy MSCs are cultured in CM from T1DM MSCs, the expression of CXCL10 in healthy MSCs increases by 8.5-fold, suggesting that secreted factors influence these genes' expression.Conclusion: We demonstrate that healthy MSCs can influence and significantly reset the inflammatory phenotype exhibited by T1 & T2DM MSCs, likely by its secretome. These data identify a novel mechanism whereby administration of healthy MSCs is an effective therapy in T1 & T2DM patients.Disclosure A. Gooch: Board Member; SymbioCellTech, LLC. Employee; SymbioCellTech, LLC. Stock/Shareholder; SymbioCellTech, LLC. C. Westenfelder: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-348-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 349-OR: Type 2 and Type 3C Diabetes Are Not Contraindications for Total
Pancreatectomy with Islet Autotransplantation-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 349-OR
Abstract: Introduction and Objective: Although total pancreatectomy with islet auto-transplantation (TPIAT) is a standard of care for chronic pancreatitis (CP) patients, selection criteria are key to obtaining successful primary outcomes, which are reduction in pain and narcotic usage. Several patients with CP also have underlying diabetes, Type 2 or type 3c, which is considered a contraindication in many centers. A comparative analysis of the outcomes (metabolic and pain management) after the TPIAT procedure in our pre-transplant diabetic and non-diabetic patient cohorts was performed.Methods: This retrospective analysis of 100 CP patients who underwent TPIAT at VCU has been rigorously analyzed. 26 diabetic and 74 non-diabetic patients underwent the procedure and they were categorized as diabetic either by insulin-dependent or diabetic medications or having an HbA1c of more than 6.0%. Outcomes of isolation including islet mass, quality, and viability followed by metabolic outcomes and data on pain management post-transplantation were analyzed. Maintenance of hypoglycemic awareness was also assessed in these patients.Results:: Islet yields in diabetic and non-diabetic patients undergoing transplantation differed significantly as we would have imagined, due to the reduction in islet mass in diabetic patients. All Patients who were diabetic before the TPIAT procedure continued to be insulin-dependent, whereas 40% of non-diabetic patients became insulin-independent at 1 year post-transplantation. Most interestingly, the primary outcomes such as narcotic dependence were reduced by more than 50% in 1 year in patients with diabetes which was similar to non-diabetic patients. Similarly, pain scores were also reduced in patients equally regardless of their diabetic status before transplantation.Conclusion: Pre-transplant diabetes should not be considered a contra-indication for TPIAT, as this procedure can provide essential pain relief along with modest glycemic control that can be managed with exogenous insulin.DisclosureM.A. Kanak: None. J. Kalivarathan: None. P. Saravanan: None. A. Khan: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-349-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 350-OR: Role of Type 1 and Type 2 Diabetes Genetics in Diabetes Outcomes
after Islet Autotransplantation-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 350-OR
Abstract: Introduction and Objective: One-third of chronic pancreatitis (CP) patients who undergo total pancreatectomy with islet autotransplantation (TPIAT) achieve insulin independence. Little is known regarding diabetes (DM) related genetics on TPIAT. Genetic risk scores (GRS) are utilized in type 1 (T1D) and type 2 (T2D) DM to predict C-peptide (Cpep) before diagnosis.Methods: We genotyped 384 patients with CP who underwent TPIAT enrolled in the multicenter “POST” study using the Global Screening Array to assess the influence of T1D and T2D GRS and 14 pre-specified SNPs associated with Cpep preservation on 1 year TPIAT outcomes.Results: Patients were 30 ± 17 years, 62% female, 92% Caucasian, 13% previously had DM and received 4294 ± 3458 IEQ/kg during TPIAT. One year post TPIAT 80% required insulin, fasting Cpep was 0.98 ± 0.79 ng/mL and insulin dose adjusted A1c (IDAA1C) was 8.4 ± 2.8. Having diabetes before TPIAT was associated with higher T1D GRS1 (mean Z-score 0.27 ± 0.8 vs -0.04 ± 1.0 in non-DM, p=0.03) and higher T2D GRS (mean Z-score 0.52 ± 1.2 vs -0.07 ± 1.0, p=0.003). At 1 year after TPIAT higher T2D GRS was associated with a lower fasting Cpep (β=-0.09 per 1 SD, p=0.04) and higher IDAA1C (β=0.45 per 1 SD, p=0.009). Several pre-selected SNPs had a trend of lower mean fasting Cpep 1 year post TPIAT (Table).Conclusion: Genetic risk factors for T1D and T2D may impact the risk for DM in CP and insulin secretion after TPIAT.DisclosureT.M. Triolo: None. A. Eaton: None. W. Chen: None. S. Onengut-Gumuscu: None. A. Steck: Advisory Panel; Sanofi-Aventis U.S. M. Bellin: Advisory Panel; Vertex Pharmaceuticals Incorporated. Research Support; ViaCyte, Inc. Advisory Panel; Novo Nordisk. Consultant; Soleno. Research Support; Dexcom, Inc. Advisory Panel; bridgebio.FundingNIDDK (K23 DK136931)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-350-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 351-OR: Plasticity in Proglucagon Processing and Secretion by Alpha Cells
-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 351-OR
Abstract: Introduction and Objective: Glucagon-like peptide (GLP-1) and glucagon stimulate insulin secretion by engaging β-cell GLP-1 receptors. The degree to which alpha-cells produce GLP-1 from proglucagon remains debatable. We hypothesized that alpha-cells are able to vary proglucagon processing from glucagon to GLP-1, providing a more potent GLP-1R ligand to enhance insulin secretion.Methods: To test this, we developed a novel assay to accurately quantify GLP-1 levels in islets and generated mouse models with alpha-cell deletion of either Pcsk1 (which generates GLP-1) or Pcsk2 (which generates glucagon), alone and in combination.Results: Using a mass-spectrometry based assay, active GLP-1 was measurable in both mouse and human islets, and levels increased in models of metabolic stress. Deletion of Pcsk1 in alpha-cells nearly eliminated active GLP-1 from mouse islets, but these animals had insulin secretion and glucose tolerance comparable to controls, even with high-fat feeding. Deletion of Pcsk2 reduced islet and plasma glucagon levels and increased Pcsk1 expression and islet GLP-1 levels. However, insulin secretion and glucose tolerance were improved. The enhanced insulin secretion was eliminated by the GLP-1R antagonist exendin-9, supporting greater GLP-1 production as the mechanism for improved β-cell function. With α-cell knockout of both Pcsk1 and Pcsk2, islet GLP-1 and glucagon were substantially reduced, leading to impaired insulin secretion and glucose intolerance. Human islets had nearly 10-fold greater GLP-1 content than mouse islets and levels correlated with glucose-stimulated insulin secretion across age, sex, BMI, and A1C.Conclusion: These results indicate that islet proglucagon peptides are necessary for normal glucose tolerance and support a model whereby varying amounts of islet proglucagon peptides regulate insulin secretion.DisclosureC. Cui: None. S.M. Gray: Employee; Sage Therapeutics. Stock/Shareholder; Sage Therapeutics, Fractyl Health, Inc. P.A. Grimsrud: None. D.C. Leander: None. K.M. El: None. J. Becker: None. A. Hoofnagle: None. G. Zhang: None. D. D'Alessio: Consultant; Arrowhead Pharmaceuticals, Inc. Other Relationship; Eli Lilly and Company. Consultant; Gasherbrum Bio, Inc. Stock/Shareholder; MBX Biosciences. Consultant; Structure Therapeutics, Inc. Advisory Panel; Sun Pharmaceutical Industries Ltd. J. Campbell: Research Support; Eli Lilly and Company, Novo Nordisk. Advisory Panel; Structure Therapeutics, Inc. Research Support; Structure Therapeutics, Inc. Consultant; Arrowhead Pharmaceuticals, Inc. Advisory Panel; Boehringer-Ingelheim, Neurocrine, Roche Pharmaceuticals, Prostasis. Research Support; Merck & Co., Inc.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-351-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 352-OR: GABA Modulates Pancreatic Beta-Cell Function through Ca2+
Signaling-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 352-OR
Abstract: Introduction and Objective: Gamma-aminobutyric acid (GABA) is an inhibitory neurotransmitter uniquely found outside the central nervous system at high concentrations in pancreatic beta cells. Understanding the functional role of GABA in the islet has been challenging due to conflicting results that often relied on supraphysiological concentrations of exogenous GABA. Surprisingly, a genetic model to delete GABA from the islet has not been developed. Here, we generated and characterized a beta-cell specific knockout of both GABA-synthesizing enzymes (GAD65 and GAD67) (β-Gad1,2-/-).Methods: Pancreatic beta cell function was analyzed in vivo by glucose tolerance test and in vitro using isolated islets.Results: We confirmed deletion of GAD65/GAD67 by western blot and showed that the knockout islets were devoid of GABA by HPLC. β-Gad1,2-/- mice exhibited hypersecretion of insulin, with normal islet size, number, and endocrine cell ratio. In vivo, male β-Gad1,2-/- mice showed impaired glucose tolerance, increased insulin and c-peptide secretion, and faster weight gain. Ca2+ imaging showed that β-Gad1,2-/- islets had a shorter delay to initiate Ca2+ mobilization in response to glucose, sustained longer maximal Ca2+ activation, and altered Ca2+ oscillations with a prolonged active phase of Ca2+ wave and reduced differences between maximal and minimal Ca2+ levels, suggesting impaired ability to generate distinct active and silent phases critical for pulsatile insulin secretion. Pharmacological inhibition of GABA signaling in control islets with a GABAAR antagonist mimicked the effect of the GAD knockout, indicating that GABA functions via the GABAAR.Conclusion: We conclude that GABA's principal role in beta cells is to regulate insulin secretion by inhibiting beta cell excitability. These findings identify the functional role for GABA in the islet is to ensure proper beta cell stimulus-secretion coupling by regulating the strength and speed of the initial Ca2+ response followed by enforcing symmetry and enhancing the amplitude of subsequent Ca2+ oscillations.DisclosureS. Ferreira: None. A.E. Stis: None. A. Widener: None. A.E. Cuaycal: None. E. Phelps: Research Support; Immunocore, Ltd, Meso Scale Diagnostics, LLC.FundingNIH (R01DK124267); DRC (AWD11953)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-352-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 353-OR: Silencing of Mitochondrial Transaminase GPT2 in β-Cells Enhances
Response to Antidiabetic Incretins-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 353-OR
Abstract: Introduction and Objective: Despite promising incretin therapies for type 2 diabetes (T2D), many humans with T2D respond poorly to incretins, and the underlying mechanism is unclear.Methods: Human islets with GPT2 silencing and β-cell-specific Gpt2 knockout mice (Gpt2βKO) were used to study incretin response and β-cell survival.Results: We report that mitochondrial transaminase GPT2 was induced in glucolipotoxicity (GLT)-exposed non-diabetic (ND) islets and T2D islets (1.8 and 13.8-fold, respectively, P ≤0.01). Silencing GPT2 enhanced β-cell sensitivity to the GLP-1 receptor agonist Exendin4 (Ex4) (1.6 and 2.6-fold in ND and T2D islets, respectively, P≤0.01). Gpt2βKO mice had improved oral, but not intraperitoneal (IP), glucose tolerance and in vivo GSIS, highlighting improved incretin effect. Ex4 had a greater impact on IP GTT and GSIS in Gpt2βKO than Gpt2f/f mice (P≤0.05). Gpt2βKO islets showed enhanced response to Ex4 and GIP but not acetylcholine in static GSIS and in perifusion with 8 mM glucose and stepwise increase in [Ex-4] (EC50=169 nM vs 356 nM). Random blood glucose was lower in high-fat diet (HFD) fed Gpt2βKO mice (P≤0.01). HFD fed Gpt2βKO mice exhibited mildly improved IP GTT with no change in acute GSIS whereas OGTT and oral GSIS were markedly improved. After IP Ex4, HFD-fed Gpt2βKO mice exhibited lower glucose excursion than HFD-fed Gpt2f/f mice (-37%, P≤0.05). RNASeq revealed a reversal of metabolic stress-induced gene expression and upregulation of pro-survival genes in Gpt2βKO islets. β-cell silencing of human GPT2 reduced %TUNEL+ β-cells under GLT (1.3±0.2 vs 0.5±0.1, P ≤ 0.05) and T2D (1.2±0.2 vs 0.6±0.1, P≤0.05) conditions. Similarly, %TUNEL+ β-cells were reduced in GLT-exposed Gpt2βKO comparedto Gpt2f/f islets (0.15±0.06 vs. 0.05±0.01, P ≤ 0.01) and Gpt2βKO mice showed improved β-cell mass (3.8±0.9 mg vs. 2.5±0.4 mg, P≤0.05) after HFD.Conclusion: GPT2 depletion enhances incretin sensitivity and supports β-cell survival, raising it as a therapeutic target to mitigate β-cell dysfunction in T2DDisclosureS. Sen: None. A.V. Rozo: None. M.W. Haemmerle: None. J. Roman: None. C. Juliana: None. S.A. Tersey: None. C.B. Newgard: Advisory Panel; Eli Lilly and Company, Novo Nordisk. Research Support; Boehringer-Ingelheim. D.A. Stoffers: Other Relationship; Amylyx.FundingNational Institute of Diabetes and Digestive and Kidney Diseases (5R01DK121175-03)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-353-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 354-OR: Differential Mirroring between In Vivo Insulin Secretion and Ex
Vivo Islet Function in Humans with and without Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 354-OR
Abstract: Introduction and Objective: While β cell dysfunction represents a key pathogenetic factor in T2D onset, collecting appropriate pancreatic samples from metabolically profiled donors has proven challenging. In this study, we investigate possible mirroring between in vivo insulin secretion and ex vivo islet function of subjects with and without T2D.Methods: 36 subjects in list for pancreatectomy underwent OGTT and hyperglycemic clamp (HC) and were divided in: non-diabetic (ND n=23) and diabetics (DM n=13). Parameters of β cell function were calculated by C-peptide deconvolution. Islets were isolated from tissues collected during surgery by collagenase P digestion, followed by Lympholyte separation. Islets were stimulated with 3.3 and 16.7 mM glucose (G) and 20 mM arginine (Arg). Insulin levels were assessed by ELISA. SI16.7 was the ratio of insulin at 16.7 and 3.3 mM G stimulation; SIArg was the ratio of insulin at 20 mM Arg and 3.3 G stimulationResults: DM displayed reduced SI16.7 compared to ND (p=0.02). In ND, SIArg was negatively correlated to basal glucose (r=0.45, p=0.03). In DM, SI16.7 was associated with C-peptide AUC during OGTT (r=0.45 p=0.02) and with the following parameters: total and basal insulin secretion rate (tISR, r=0.66 p=0.01; bISR r=0,67 p<0.01), Glucose Sensitivity (r=0.59, p=0.02) and with standardized insulin secretion at 8 mmol/L glucose (r=0.55, p=0.04). Additionally, in DM but not in ND, SI16.7 was positively correlated with HC-derived second phase insulin secretion (ISR2nd r=0.82 p<0.01).Conclusion: In ND, ex vivo stimulation reflects poorly in vivo function, illuminating the role of other players beyond β cells in normal glucose homeostasis. Conversely, in DM, the surprisingly preserved ability to respond to high glucose is closely correlated with functional parameters in vivo, suggesting an heightened β cell autonomous role in metabolic control under T2D conditions, and the extreme heterogeneity in ex vivo functional responses.DisclosureG. Di Giuseppe: None. G. Gliozzo: None. E. Di Piazza: None. L. Carciero: None. G. Ciccarelli: None. L. Soldovieri: None. M. Brunetti: None. F. Cinti: None. A. Mari: Consultant; Lilly USA LLC, Novo Nordisk, Sanofi. A. Giaccari: Board Member; Novo Nordisk A/S. Speaker's Bureau; AstraZeneca, Sanofi. Advisory Panel; Sanofi. Speaker's Bureau; Guidotti. G. Pani: None. T. Mezza: None.FundingThe Italian Ministry of Education, University, and Research GR-2018-12365577; PRIN 2020SH2ZZA); The Italian Ministry of Health (RF-2019–12369293)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-354-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 355-OR: Deletion of 4E-BP1 in α-Cells Reduces Mass and Impairs
Glucagon Secretion-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 355-OR
Abstract: Introduction and Objective: mTORC1 is a central regulator of α-cell mass and glucagon secretion, modulating protein synthesis through downstream targets such 4E-BPs and S6Ks. mTORC1-mediated phosphorylation of 4E-BP promotes cap-dependent translation initiation, a process often dysregulated in metabolic diseases. The isoform 4E-BP1 has been implicated in metabolic regulation, stress adaptation, and cell survival, but its role in α-cells remains poorly understood.Methods: To investigate the role of mTORC1 target 4E-BP1 in α-cells, we generated an α-cell-specific 4E-BP1 knockout mouse (α4EBP1ko). The effects of 4E-BP1 deletion on glucose homeostasis, α-cell mass, and glucagon secretion were assessed in male and female mice. In vivo, glucose, glucagon, and insulin levels were measured under basal conditions and during glucose and insulin tolerance tests. In vitro, isolated islets were analyzed for hormone content, secretion, and cell morphometry.Results: Male α4EBP1ko mice exhibited normal glycemia and plasma glucagon levels, while females showed significantly lower fed glycemia and plasma glucagon levels. Plasma insulin was unaltered in α4EBP1ko mice. Both sexes showed impaired glucagon secretion following insulin or 2-deoxy-D-glucose challenges, with normal glucose excursions. In vitro, glucose-stimulated glucagon response was unaffected, but glucagon secretion and content were markedly reduced in α4EBP1ko islets. Insulin secretion and content in α4EBP1ko islets remained unaffected. Morphological analysis revealed that α4EBP1ko islets have fewer α-cells and a lower α/β-cell ratio.Conclusion: In summary, the loss of 4E-BP1 in α-cells disrupts glucagon secretion, likely due to a reduced α-cell mass. These findings highlight the protective role of the 4E-BP1 in α-cell survival and function. Future studies will explore the mechanisms of alpha cell loss in α4EBP1ko.DisclosureA.F. Neves: None. C. Rossetti: None. R. Andrade Louzada Neto: None. E. Bernal-Mizrachi: None.FundingNational Institutes of Health (R01DK133183), United States Department of Veterans Affairs (I01BX002728)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-355-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 356-OR: IL-1 and IL-6 Impair Proinsulin Maturation in Aging Mice via
Downregulation of Prohormone Convertases-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 356-OR
Abstract: Introduction and Objective: Aging is associated with increased immune activity and of metabolic diseases. We have shown that aging mice display increased expression of IL-1β in pancreatic islets and that inhibition of its signaling preserves β-cell function during aging. Similarly, IL-6 is upregulated in metabolically stressful conditions. Based on these observations, we hypothesized that pro-inflammatory cytokines disrupt proinsulin processing and hence diminish β-cell function.Methods: A series of in vivo and ex vivo experiments were conducted to address our hypothesis. We utilized wt and β-cell-specific IL-1 receptor ko mice and isolated islets. Additionally, isolated islets were treated with the drug anakinra to evaluate its therapeutic potential. The expression levels of key prohormone convertases, PC1/3 and PC2, were assessed following cytokine exposure.Results: Exposure of isolated islets to IL-1β or IL-6 significantly reduced the levels of PC1/3 and PC2 in a dose-dependent manner. Pharmacological inhibition of IL-1 signaling or genetic ablation of the IL-1 receptor in β-cells effectively prevented IL-1β-mediated downregulation of PC1/3 but did not mitigate the reduction caused by IL-6. General inhibition of IL-1 signaling, but not β-cell-specific IL-1 receptor deletion, prevented PC2 downregulation. In aging mice, the expression of PC1/3 and PC2 in islets was markedly reduced, accompanied by an increased proinsulin-to-insulin ratio in circulation, indicative of impaired proinsulin processing.Conclusion: These findings underscore the role of age-related islet inflammation in disrupting proinsulin processing. Increased levels of IL-1β and IL-6 during aging impair the expression of prohormone convertases, leading to reduced production of mature insulin and an accumulation of immature proinsulin. Targeting the IL-1β and IL-6 signaling pathways may offer therapeutic strategies to mitigate age-associated β-cell dysfunction and prevent diabetes.DisclosureK. Sifoniou: None. L. Rachid: None. D.T. Meier: None. M.Y. Donath: Advisory Panel; Abbott, AstraZeneca, Boehringer-Ingelheim, Eli Lilly and Company, Novo Nordisk, Novartis AG, Roche Pharmaceuticals, Sanofi-Aventis Deutschland GmbH. Research Support; Olatec.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-356-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 357-OR: Excessive Dietary N-6 Polyunsaturated Fatty Acids in Obese
Patients Drive Lgr5+ Cell–Derived Gastric Mucosal Spasmolytic
Polypeptide-Expressing Metaplasia-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 357-OR
Abstract: Introduction and Objective: Spasmolytic polypeptide expressing metaplasia (SPEM), which is considered as origin of gastric cancer, is associated with obesity. However, the fundamental determinants and mechanisms underlying obesity-associated SPEM remain poorly understood.Methods: Our metabolomics study analyzed 42 obese patients to assess the association between n-6 polyunsaturated fatty acids (PUFAs) and SPEM. Gastric organoids and mouse models were used to evaluate the effects of n-6 PUFAs supplementation on SPEM formation. Lineage tracing assays and single-cell RNA-sequencing analysis were performed to identify the cellular origins of SPEM.Results: High levels of n-6 PUFAs were significantly associated with SPEM in obese patients. Supplemental n-6 PUFAs induced SPEM derived from quiescent Lgr5+ stem cells (ISCs) at the mucosal base. Mechanistically, downregulated stearyl CoA desaturase 1 (SCD1) activated the ERK pathway, promoting SPEM development. SCD1 was found to bind Prohibitin 1 (PHB1), enhancing PHB1's degradation via ubiquitin E3 ligase tripartite-motif-containing 21 (TRIM21), thereby suppressing the ERK pathway. A novel diagnostic model based on SCD1, PHB1, and ERK expression was developed, and dietary intervention with low-linoleic acid or ERK inhibition effectively reduced SPEM.Conclusion: Dietary enrichment with n-6 PUFAs represents a new aetiology of SPEM, driven by the activation of the ERK pathway via the SCD1-PHB1-TRIM21/ERK axis. Strategies targeting n-6 PUFAs dietary intervention and the SCD1-PHB1-TRIM21/ERK pathway offer promising therapeutic potential for SPEM.DisclosureX. Wen: None. H. You: None. X. Wang: None. H. Chen: None. L. Bu: None. S. Qu: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-357-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 358-OR: Acute Fatty Acid Elevation Does Not Alter Brain Glucose Uptake in
Humans-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 358-OR
Abstract: Introduction and Objective: Acute elevation of non-esterified fatty acids (NEFA) can induce peripheral insulin resistance and impair glucose uptake in muscle. Rodent studies have shown that elevation of NEFA through a high-fat diet impairs brain glucose uptake, and prior observational studies by our group have reported that higher NEFA levels correlate with lower brain glucose. Here, we test whether acute elevations in circulating NEFA in lean individuals can induce impairment in brain glucose uptake.Methods: Lean, healthy adults underwent either intravenous infusion of saline or Intralipid 20% at 60 mL/hr for 4 hours followed by hyperglycemic clamp (target 180 mg/dL) and 1H MRS scanning to measure changes in brain glucose on two separate occasions. Saline/Intralipid infusion was continued throughout the hyperglycemic clamp and MRS scanning. Brain glucose was measured by 1H MRS at 3 Tesla.Results: Five lean, healthy adults completed the study (age 24.8 ± 6.8 years, BMI 22.9 ± 1.2 kg/m2, A1c 5.0 ± 0.2%). Four hours of Intralipid infusion led to a ~2.5-fold elevation in circulating NEFA at the beginning of the hyperglycemic clamp (Intralipid 1.4 ± 0.5 vs. saline 0.59 ± 0.08 mmol/L, p=0.04). NEFA levels differed between treatments during the hyperglycemic clamp (p<0.01, two-way mixed ANOVA). Between saline vs. Intralipid infusion, there were no differences in plasma glucose (183 ± 7 vs. 181 ± 7 mg/dL, p=0.31), plasma insulin (41 ± 15 vs. 44 ± 17 mU/L, p=0.64), glucose infusion rate (4.4 ± 1.2 vs. 4.8 ± 1.6 mg/kg*min, p=0.44), or change in brain glucose (0.26 ± 0.03 vs. 0.28 ± 0.07 mmol/L, p=0.67) during steady state hyperglycemia (average 60-120 minutes of clamp).Conclusion: Despite significantly higher NEFA levels, there were no differences in measures of insulin sensitivity following Intralipid. We conclude that elevation of circulating NEFA for hours (to levels higher than normal physiologic conditions) in the presence of hyperglycemia and absence of insulin resistance has no impact on brain glucose uptake.DisclosureB.C. Matson: None. W. Chang: None. J.J. Palmiotto: None. D.L. Rothman: None. R. Belfort De Aguiar: None. G.F. Mason: Consultant; Merck & Co., Inc. Research Support; Pfizer Inc. Consultant; Leal Therapeutics. J.J. Hwang: None.FundingNational Institutes of Health (R01DK123227)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-358-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 359-OR: Effect of GLP-1 Receptor Antagonism or Incretin Enhancer on
Ad-Libitum Energy Intake in Subjects with and without Bariatric Surgery-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 359-OR
Abstract: Introduction and Objective: Roux-en-Y gastric bypass (GB) and sleeve gastrectomy (SG) promote a significant and durable weight loss. Rerouted gut after these procedures exaggerates prandial glucagon-like peptide-1 (GLP-1) secretion. Whether an augmented GLP-1 response to meal ingestion following GB or SG would change the food behavior remains unknown. We compared the acute effects of increased incretin concentrations or GLP-1R blockade on ad-libitum energy intake (AdLibEI) among 3 BMI- and age-matched non-diabetic obese cohorts of GB (n=7), SG (n=9), and non-operated controls (CN, n=7).Methods: Participants were studied with 3-h meal test on 4 separate days: (A) 50-gram glucose ingestion with (OGT+S) and without (OGT) 200 mg sitagliptin (S) taken orally 2-h prior to OGT; (B) 50-gram whey protein ingestion with (OPT+Ex9) and without intravenous infusion of GLP-1R antagonist (exendin-(9-39) [Ex9], 750 pm/kg/min). After the 3-h meal studies, AdLibEI of a mixed-meal lunch (1736 kcal, 52% carbohydrate, 13% protein, 35% fat) and perception of appetite were measured.Results: As expected, AdLibEI was significantly lower in GB or SG compared to CN (p=0.001). Among 3 groups, post-OGT AdLibEI was reduced only in CN by sitagliptin (p=0.05 for interaction, ANOVA), due to a reduction in AdLib protein. Similarly, post-OPT AdLibEI tended to be lower in CN by prior Ex9 infusion but not in GB or SG (p=0.06), due to a diminished AdLib carbohydrate intake. While sitagliptin administration did not change the appetite scores among 3 cohorts, Ex9 infusion reduced desire to eat in CN but not in surgical subjects (p=0.014).Conclusion: These data indicate that, in the current model, enhancing or blocking endogenous GLP-1R signal has an acute affect on food intake in humans with intact gastrointestinal system. Unaffected energy intake by GLP-1R manipulation in GB and SG subjects, however, undermines a significant role for GLP-1 in mediating surgical-induced weight loss.DisclosureG. Della Pepa: None. S. Sabatini: None. A. Alamdari: None. A. Gastaldelli: Advisory Panel; Boehringer-Ingelheim. Consultant; Boehringer-Ingelheim, Novo Nordisk, Merck Sharp & Dohme Corp, Regeneron Pharmaceuticals. Other Relationship; Pfizer Inc, Madrigal Pharmaceuticals, Inc, Echosens, Eli Lilly and Company. Speaker's Bureau; Merck Sharp & Dohme Corp, Eli Lilly and Company, Novo Nordisk. M. Salehi: Advisory Panel; Vognex, Amylyx.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-359-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 360-OR: Mixed Meals Containing Complex Carbohydrates Improves Insulin
Sensitivity and Disposition Index in Type 2 Diabetes—Mechanistic
Insights Using Minimal Model Analyses-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 360-OR
Abstract: Introduction and Objective: A novel tracer method using natural [13C]-enrichment of polysaccharides in commercially available grains was developed previously to measure postprandial insulin sensitivity and β-cell function, using Minimal Model analysis. This study was conducted to determine whether complex carbohydrate-based meals can improve insulin resistance in Type 2 diabetes (T2D).Methods: Seven T2D were studied twice following isocaloric mixed meals with identical macronutrient compositions (50% carb, 20% protein, 30% fat). The carbohydrate was either glucose (simple carb, SC) or sorghum (complex carb, CC). Oral antidiabetes medications were withheld prior to meal study. We estimated Si, a marker of whole-body insulin sensitivity, and beta cell responsiveness (Phitotal) in response to meal stimuli. Disposition index (DI; beta cell responsivity appropriate to the degree of insulin resistance) was computed as well.Results: Results are shown in Figure 1. Post meal glucose concentrations were lower with CC than SC meal. Si and DI were significantly higher (p<0.05) with CC vs SC meal while Phitotal increased but was not statistically different (p=0.21).Conclusion: Results suggest that CC meals significantly improve insulin resistance in people with T2D. We provide mechanistic insights as to why glucose tolerance improves with CC meals and should be preferred over SC meals in T2D.Disclosure S. Perazzolo: Consultant; Abbott Diagnostics. U.S. Unni: None. C. Lane: None. B. Gran: None. A. Basu: None. R. Basu: Advisory Panel; Novo Nordisk, Boehringer-Ingelheim.FundingNational Institute of Health (R01 DK029953, R01 DK085516, DK059637 (MMPC)) and (DK020593 (DRTC))
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-360-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 361-OR: The Alpha-Cell Response to Hyperglycemia Is Modulated by
Circulating Amino Acid Concentrations in the Presence of Obesity and
Hepatic Fat-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 361-OR
Abstract: Introduction and Objective: Pre-diabetes is characterized by abnormal postprandial suppression of glucagon and circulating amino acid (AA) concentrations. It is unknown if hyperglucagonemia arises from a defective α-cell response to AA or from abnormal metabolism resulting in elevated AA.Methods: Lean (BMI: 23 ± 0.5 Kg/M2, n = 10) and obese (BMI 31 ± 0.5 Kg/M2, n = 20) subjects underwent hepatic MRI to quantify fat content using Proton Density Fat Fraction (PDFF). They were then studied on two occasions in random order after an overnight fast using a graded glucose infusion. On one occasion saline was infused (Saline Day) and on the other an AA mixture [Clinisol (15%, 0.003ml/kg/min); Baxter, Healthcare, Deerfield, IL - AA day]. The glucagon secretion rate (GSR) was derived from peripheral glucagon concentrations using a mathematical model, which also provided G50 - the change in glucose required to reduce GSR by 50% - for each subject. AA and their metabolites (n = 42) were measured by mass spectrometry at 0, 120 and 240 mins.Results: On both occasions, experimental conditions produced a progressive rise in insulin secretion and an inverse-exponential suppression of glucagon. AA infusion did not change G50 (1.4 ± 0.2 vs. 1.3 ± 0.3 mmol/L, AA vs. saline respectively, p = 0.20) in lean subjects. This was not the case in the obese group (2.3 ± 0.4 vs. 1.3 ± 0.2 mmol/L, p = 0.02). On the AA day G50 correlated with alanine (R2 = 0.34) and cysteine (R2 = 0.25) concentrations. Concentrations of alanine (R2 = 0.38), α-aminoadipic acid (R2 = 0.14) and lysine (R2 = 0.34) positively correlated with PDFF irrespective of changing insulin and glucagon concentrations throughout both study days.Conclusion: These experiments demonstrate that α-cell function is modulated by circulating AA. Increased PDFF is associated with increased AA concentrations, but these differences are present regardless of islet hormone concentrations at 0, 120 and 240 mins.DisclosureS. Mohan: None. F. Boscolo: None. H.E. Christie: None. A.M. Pipkins: None. A.M. Egan: None. M.C. Laurenti: Employee; Angelini Pharma. C. Dalla Man: None. A. Vella: Research Support; Novo Nordisk A/S, Dexcom, Inc. Advisory Panel; Boehringer-Ingelheim, Rezolute.FundingNIH NIDDK (DK116723)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-361-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 362-OR: Morning Elevation in Insulin Enhances Afternoon Postprandial
Insulin Action and Glucose Effectiveness-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 362-OR
Abstract: Introduction and Objective: The 2nd meal phenomenon refers to the improved glycemic response observed after consuming a 2nd identical meal. It is well known that postprandial hepatic glucose uptake (HGU) is determined by the combined effects of three regulatory factors: insulin action (hyperinsulinemia; HI), glucose effectiveness (hyperglycemia; GE), and glucose delivery into the hepatoportal circulation (portal glucose signal; PGS). While our previous studies demonstrated the importance of morning (AM) hyperinsulinemia in priming the liver for increased HGU later in the day, the question remains as to which aspect of the afternoon (PM) response explains the augmented HGU. Thus, to provide insight into the underlying mechanism of the 2nd meal effect, we sought to determine the extent to which PM HI, GE, and the PGS are impacted by AM hyperinsulinemia.Methods: Dogs underwent an AM clamp with either a 4h hyperinsulinemic prime (Prime, n=8) or basal insulin delivery (NoPrime, n=8). After a 1.5h non-clamp period, both groups were challenged with a PM hyperglycemic clamp (with the PGS) in the presence of basal insulin.Results: During the PM clamp, net HGU was significantly elevated in Prime vs. NoPrime groups (mean of 2.2±0.4 vs. 0.1±0.3 mg/kg/min, respectively, P<0.005), indicating an enhancement of GE and/or the PGS. There was no difference in PM non-HGU (4.5±0.3 vs. 4.4±0.4 mg/kg/min). In previous experiments when all three factors (HI, GE, PGS) were present in the PM, net HGU was 6.3±1.7 vs. 2.4±1.1 mg/kg/min in groups receiving an AM insulin prime vs. basal insulin, respectively. Therefore, the AM insulin prime enhanced the effects of HI, GE, and the PGS on PM HGU by 3.9 mg/kg/min, whereas it enhanced the effects of glucose (GE and the PGS), in the absence of a rise in insulin, by 2.1 mg/kg/min.Conclusion: Taken together, the data show that AM HI enhanced PM insulin action and GE (including the PGS) to an equal extent. This suggests that AM insulin priming enhances cellular targets common to both insulin and glucose signaling in the PM.DisclosureH.L. Waterman: None. M.S. Smith: None. K. Yankey: None. B. Farmer: None. T.R. Howard: None. A.D. Cherrington: Other Relationship; Abvance Therapeutics. Advisory Panel; AdipoPharm. Research Support; Alnylam Pharmaceuticals, Inc. Other Relationship; Fractyl Health, Inc., Novo Nordisk. Advisory Panel; Portal Insulin, Sekkei Bio, Sensulin Labs, LLC. Research Support; SFC Fludics, Inc. Consultant; Thetis Pharmaceuticals, LLC. D.S. Edgerton: None.FundingNational Institutes of Health (1F31DK142297); National Institutes of Health (R01DK131082); National Institutes of Health (5T32DK007563); National Institutes of Health (DK020593); National Institutes of Health (DK059637)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-362-OR
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 363-P: Disproportionate Hypoglycemia Fear and Time-Below-Range in
Individuals with Type 1 and Type 2 Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 363-P
Abstract: Introduction and Objective: Fear of Hypoglycemia (FOH) has been demonstrated to have a weak relationship with Time Below Range (TBR) in previous studies. We explored this relationship in the HypoMETRICS population and identified patients who FOH was discordant with their TBR.Methods: HypoMETRICS participants wore blinded continuous glucose monitors (CGM) for 10 weeks and completed the Hypoglycemia Fear Score questionnaire (HFS). We categorized participants into high (>4% TBR) and low (<4%) risk of hypoglycaemia and high (>23) and low (<23) HFS.Results: We included 576 participants (257 T1D; mean TIR: 62%, mean TBR: 5.8%, CGM use: 75%; 319 T2D: mean TIR: 65%, mean TBR: 2.4%, CGM use: 40%). There was a very weak correlation between FOH and TBR in type 1 (r = 0.005) and in type 2 (r = - 0.026).In T1D, 36% had low TBR and low FOH and 14% had high TBR and high FOH. 11% had high FOH with low TBR whilst 39% had a high TBR and low FOH.In T2D, 66% had low TBR and low FOH and 4% had high TBR and high FOH. 16% had high FOH with a low TBR whilst 13% had a high TBR and low FOH.Conclusion: Our findings suggest that 50% of T1D and 30% of T2D had disproportionate FOH in relation to their TBR. Exploring the reasons for this may be helpful where this is causing a clinical problem such as raised glucose levels or severe hypoglycemia risk.DisclosureJ.J. Thomas: None. A.M. McCarthy: None. V. Koutroukas: Other Relationship; Kelcon GmbH. P. Choudhary: Speaker's Bureau; Abbott. Advisory Panel; Dexcom, Inc. Consultant; Insulet Corporation. Advisory Panel; Ypsomed AG, embecta, Sanofi. Speaker's Bureau; Lilly Diabetes, Medtronic. Advisory Panel; Roche Diabetes Care. Consultant; Cambridge Mechatronics.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-363-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 364-P: Hypoglycemic Counterregulation Is Impaired following Exposure to 72
Hours of Fasting in Male and Female Rats-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 364-P
Abstract: Introduction and Objective: Hypoglycemia-associated autonomic failure (HAAF), a common complication of diabetes, is caused by recurrent exposure to treatment-induced hypoglycemia. Starvation is the only normal physiological process which induces prolonged exposure to hypoglycemia similar to the antecedent of HAAF. This study tested whether exposure to starvation in rats would lead to impairments in hypoglycemic counterregulation following short-term refeeding.Methods: Two groups of rats were used, an ad libitum fed group and a 72-h fasted group. Following an 8-h refeeding period in fasted rats, both groups were fasted for 8-10 hours and then subjected to a hyperinsulinemic-hypoglycemic clamp procedure and blood was collected for determination of plasma levels of the counterregulatory hormones glucagon (GCG) and epinephrine (EPI). The experiment was conducted in both male and female rats (n=7-8/group and n=4/group, respectively). A two-way ANOVA was used to test the effect of exposure to 72 h of fasting on hypoglycemia-induced GCG and EPI levels during the clamp procedure.Results: As expected, male and female rats exposed to the 72-h fast lost ≈20 % of their initial body weight and experienced a gradual fall in blood glucose. Clamp glucose levels following insulin administration were well matched in each of the groups. Male rats exposed to the 72-h fast had significantly reduced GCG and EPI levels during the clamp relative to controls (11.3 vs 25.9 pg/mL, p=0.003; 1321 vs 2077 pg/mL, p=0.018, respectively). Clamp GCG levels were also significantly reduced in female rats exposed to the 72-h fast relative to controls (7.8 vs 19.3 pg/mL, p=0.048).Conclusion: Our results reveal that exposure to starvation induces a HAAF-like syndrome in both male and female rats following refeeding. Our data suggests that HAAF may result from an adaptive response to starvation which is inappropriately elicited by diabetes treatments. Future studies will be needed to determine how starvation leads to impairment of hypoglycemic counterregulation.DisclosureL. DePrimo: None. A. Narez: None. A. Bui: None. S. Junot: None. C.R. Meaux: None. D. McDougal: None.FundingNIH (R01DK131165)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-364-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 365-P: Comparative Analysis of Hypoglycemia at Admission and during
Hospitalization—Insights from the DEKODE Surveillance Registry-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 365-P
Abstract: Introduction and Objective: Severe hypoglycemia poses a critical risk to people with diabetes, with episodes during hospitalization reflecting potential failures in patient safety. This study aimed to evaluate the clinical characteristics, precipitants, management and outcomes of hypoglycemic events in those occurring at admission (outpatient) or during the hospital stay (inpatient).Methods: This retrospective study utilized data from the DEKODE Hypoglycemia Surveillance Registry, encompassing level 2 and 3 hypoglycemic episodes as per the International Hypoglycemia Study Group (IHSG). Data was collected for adults (>18 years) admitted from October 2023 to July 2024 in 9 UK hospitals. Variables analyzed included precipitants, treatment modalities and outcomes. Statistical analyses involved chi-square tests for categorical data and Mann-Whitney U tests for continuous variables.Results: Of the 1,451 episodes analyzed, 77.1% (73.2% Level 2 vs 26.8% Level 3) occurred during hospitalization. Inpatients exhibited a higher prevalence of cognitive impairment (72.6% vs. 50.2%, p<0.0001). Fasting/missed meals more frequently precipitated hypoglycemia in inpatients (42.9% vs. 29.5%, p<0.0001) and intercurrent illness was more common in inpatients than outpatients (44.0% vs. 35.8%, p=0.0094). Treatment modalities also varied; inpatients primarily received oral glucose (70.5% vs. 79.5%, p=0.0045), while glucagon administration was higher among outpatients (45.7% vs 4.6% p<0.0001). Hospital stays were longer for inpatients (median: 9 days vs. 1 day, p<0.0001). Discharge outcomes showed notable disparities, with higher mortality observed in inpatients (23.5% vs. 4.2%, p<0.0001).Conclusion: Our findings underscore the need for targeted strategies to mitigate hypoglycemia risks during hospitalization. Future research should focus on developing predictive tools and interventions tailored to high-risk inpatient populations.DisclosureK. Persad: None. A. Buchipudi: None. S. Sherratt-Mayhew: None. M. Idrissi: None. A. Rakkar: None. S. Rafi: None. C. Page: None. A. Iqbal: Speaker's Bureau; Lilly Diabetes. Research Support; Abbott, Dexcom, Inc. Speaker's Bureau; AstraZeneca, Boehringer-Ingelheim. Research Support; Tandem Diabetes Care, Inc. A. Lubina Solomon: None. P. Kempegowda: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-365-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 366-P: Machine Learning Reveals CGM Superiority over Hypoglycemia
Awareness Questionnaires in Discriminating Individuals with Severe
Hypoglycemia-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 366-P
Abstract: Introduction and Objective: This study compares the use of CGM metrics to hypoglycemia awareness (HA) questionnaires in discriminating individuals having severe hypoglycemia (SH) events among the CGM users with type 1 diabetes (T1D).Methods: Spearman correlation analyses were performed among CGM metrics tied to time ranges, Gold score, Clarke HA factor (ClarkeHAF) and the number of self-reported SH events over six months in 708 adults with T1D. Logistic regression and random forest (RF) models were performed to discriminate individuals with ≥1 SH events. Model performance was compared using area under the ROC curve (AUC).Results: SH events showed the highest absolute correlation coefficient with TIR (0.198), being higher than those of both Gold (0.129) and ClarkeHAF (0.187) scores (p<0.001 for each, Fig 1A). Logistic regression (Fig 1B) and RF (Fig 1C) models using only CGM metrics (Model 3) obtained greater AUC than those using Gold (Model 1) or Clarke (Model 2) scores alone. Enhanced models combining CGM metrics with questionnaire scores (Models 4 and 5) provided slight improvements over CGM-only models.Conclusion: Machine learning analyses highlight the superiority of CGM metrics over HA questionnaires in discriminating individuals having SH events. Incorporating CGM data analysis into clinical practice can enhance hypoglycemia risk stratification.DisclosureX.D. Zhang: None. Y. Lin: None. R.D. Wang: None. D. Zhan: None. S.J. Fisher: None.FundingNational Institutes of Health (U01DK135111, K23DK129724, UL1TR001998, P30DK020579)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-366-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 367-P: Cross Talk between Gs and Gq Signaling Is Essential for Proper
α‐Cell Function-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 367-P
Abstract: Introduction and Objective: Glucagon (GCG), a polypeptide hormone released from pancreatic α-cells, regulates glucose homeostasis by stimulating hepatic glucose production during hypoglycemia. GCG secretion is dysregulated in type 1 and 2 diabetes, yet the molecular mechanisms underlying this phenomenon remain incompletely understood. Pancreatic α-cells express many G protein-coupled receptors (GPCRs) coupled to various functional classes of heterotrimeric G proteins (Gs, Gq/11, Gi/o, and G12/13). In this study, we investigated the role of different GPCR/G protein signaling pathways in modulating GCG release and glucose homeostasis.Methods: To investigate the role of α-cell Gs and Gq/11 signaling, we ablated Gαs or Gαq/11 in α-cells of adult mice (α-GsKO and α-Gq/11KO mice, respectively).Results: Both α-GsKO and α-Gq/11KO mice showed reduced circulating GCG levels, due to decreased Gcg expression and islet GCG content. Additionally, disruption of α-cell Gs or Gq/11 signaling impaired GCG secretion under hypoglycemic or glucopenia conditions. Unexpectedly, α-GsKO islets exhibited reduced GCG secretion not only in response to Gs-coupled receptor agonists but also to Gq/11-linked receptor agonists, suggesting that Gq/11-mediated GCG release requires functional Gs. Conversely, α-Gq/11KO islets failed to respond to Gs-coupled receptor agonists, indicating that proper α-cell function requires crosstalk between Gs and Gq/11signaling.Conclusion: Both α-cell Gs and Gq/11 signaling play critical roles in stimulating GCG secretion during hypoglycemia and glucopenia. Moreover, crosstalk between Gs and Gq/11 signaling is essential for proper α-cell function. These new findings may inform the development of novel therapeutic strategies aimed at restoring normal α-cell function in certain metabolic disorders.DisclosureL. Liu: None. K.M. El: None. Y. Cui: None. L. Weinstein: None. J. Campbell: Research Support; Eli Lilly and Company, Novo Nordisk. Advisory Panel; Structure Therapeutics, Inc. Research Support; Structure Therapeutics, Inc. Consultant; Arrowhead Pharmaceuticals, Inc. Advisory Panel; Boehringer-Ingelheim, Neurocrine, Roche Pharmaceuticals, Prostasis. Research Support; Merck & Co., Inc. J. Wess: None.FundingNIH
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-367-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 368-P: Perceived AID Algorithm Performance and Hypoglycemia Prevalence in
PWD-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 368-P
Abstract: Introduction and Objective: Hypoglycemia, defined as blood glucose (BG) below 70 mg/dL, poses significant risks for people with diabetes (PWD) using insulin. Despite growing adoption of Automated Insulin Delivery (AID) systems, hypoglycemia among their users remains understudied. This study assessed hypoglycemia experiences alongside perceived AID algorithm performance.Methods: In November 2024, US PWD (n=1,384 Type 1 and n=107 Type 2) using AID systems completed an online survey. Respondents rated their AID algorithms as “too conservative,” “just right,” or “too aggressive” in treating high BG. They also reported frequencies of mild (55-70 mg/dL) and moderate (40-54 mg/dL) hypoglycemia and their BG thresholds for treating lows and highs. In analysis, highly impacted individuals were defined as experiencing near-daily milds and occasional (weekly) moderates. Hypoglycemia impact and BG thresholds were compared across algorithm rating groups.Results: Differences in prevalence of “highly impacted” PWD occurred across all algorithm groups (p<0.05). PWD rating algorithms as “just right” had the lowest impact (12%), followed by “too conservative” (17%) and “too aggressive” (35%). The “too conservative” group treated low BG at a lower mean threshold (70.4 mg/dL) than “just right” (72.2, p<0.01) and “too aggressive” (72.2, p<0.05). They also treated high BG at a lower mean threshold (174.1 mg/dL) than “just right” (183.9, p<0.01) and “too aggressive” (185.2, p<0.01).Conclusion: PWD rating their AID algorithms as “just right” experience the lowest hypoglycemia impact. Those perceiving algorithms as “too aggressive” report the highest, suggesting they need more cautious settings/algorithms. The “too conservative” group treats lows and highs at lower mean thresholds than others, suggesting they’re less proactive with lows and/or “rebound” after preemptively correcting highs, leading to hypoglycemia. These findings emphasize the nuances of managing hypoglycemia on an AID system and the importance of aligning patients to optimal settings/algorithms.Disclosure A. Beltran: Research Support; Abbott, Dexcom, Inc., Eli Lilly and Company, diaTribe, Insulet Corporation, Medtronic, Ascensia Diabetes Care, Tandem Diabetes Care, Inc, Sequel Med Tech, Beta Bionics, Inc, Zucara Therapeutics. J. Lee: Employee; dQ&A. T. Bell: Research Support; Abbott, Dexcom, Inc., Tandem Diabetes Care, Inc, Medtronic, MannKind Corporation, Insulet Corporation, CeQur, Beta Bionics, Inc, Eli Lilly and Company, Ypsomed AG. T.L. Bristow: None. R. Wood: Other Relationship; Abbott, diaTribe, Glooko, Inc, Dexcom, Inc., Medtronic, Lilly Diabetes, Insulet Corporation, Sanofi-Aventis U.S., Tandem Diabetes Care, Inc, Zucara Therapeutics.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-368-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 369-P: Exposure to Recurrent Hypoglycemia Does Not Alter Brain Glucose
Transport Kinetics in Type 1 Diabetes (T1D)-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 369-P
Abstract: Introduction and Objective: Mechanisms of impaired awareness of hypoglycemia (IAH) upon exposure to recurrent hypoglycemia (HG) in people with T1D are unknown. We tested the hypothesis that brain glucose transport is upregulated in response to recurrent HG, obviating the need to mount a counterregulatory response during subsequent HG.Methods: Glucose concentrations in the hypothalamus (HTL) and prefrontal cortex (PFC) were measured during hyperglycemic clamps in 45 people with T1D who were aware of HG using 1H MRS at 3T before and after the induction of IAH by exposure to 3 two-hour HG clamps over 2 days. Steady state brain glucose transport kinetics were determined using reversible Michaelis-Menton model. Epinephrine samples and the Towler symptom questionnaire were collected at the 1st and 3rd HG clamp. We present data from 30 who completed the entire study (14 males, age 30.4(±9.3), A1c 6.8(±0.7)).Results: Data collected during HG clamps 1 and 3 are in table. During hyperglycemia, brain glucose concentrations increased as a function of the target glycemia, but no differences were found in steady state glucose transport kinetics before vs after IAH-induction (Tmax/CMRgluc, before vs after, HTL:1.81±0.14 vs 1.88±0.13; PFC: 1.94±0.07 vs 1.91±0.06).Conclusion: We conclude that exposure to recurrent HG did not alter glucose transport kinetics in the HTL or PFC in subjects with T1D.DisclosureE.R. Seaquist: None. Y. Park: None. A. Kumar: None. L. Zhang: None. B. Strong: None. L.E. Eberly: None. A. Moheet: Other Relationship; Sanofi-Aventis U.S. P. Henry: None. G. Oz: Research Support; Biogen. Consultant; Servier Laboratories, UCB Biopharma SRL / Lacerta Therapeutics Inc, Sanofi.FundingNational Institutes of Health (NS035192)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-369-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 370-P: Interoception Mitigates the Impact of Hypoglycemia Exposure on
Symptom Recognition in Adults with Type 1 Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 370-P
Abstract: Introduction and Objective: Hypoglycemia exposure lowers the glycemic threshold for symptom recognition (i.e., Symptom Level), contributing to impaired awareness of hypoglycemia (IAH). Interoception—the ability to sense and interpret bodily signals— is related to lower IAH risk. We tested the hypothesis that interoception moderates the association between hypoglycemia exposure and autonomic Symptom Level.Methods: Adults with type 1 diabetes (T1D) completed 30-day continuous glucose monitoring and assessments of interoception (MAIA-2) and Symptom Level (HypoA-Q). Proportional odds logistic regression tested if interoception moderated the association between hypoglycemia exposure (%Time <60 mg/dL) and Symptom Level, adjusting for covariates.Results: Among 717 adults with T1D (mean age: 44 ± 15 years; T1D duration: 25 ± 15 years), hypoglycemia exposure (%Time <60 mg/dL) was 0.8 ± 1.4%. Higher exposure was associated with lower Symptom Levels (OR: 0.48, CI: 0.33-0.71, p < 0.001). Interoception was not associated with Symptom Level (OR: 0.90, CI: 0.75-1.08). However, greater interoception reduced the impact of hypoglycemia exposure on Symptom Level (OR: 1.13, CI: 1.01-1.26, p < 0.05).Conclusion: Interoception moderated the association between hypoglycemia exposure and Symptom Level. Targeting interoception may offer a novel approach for prevention and management of IAH.DisclosureA.M. Matus: None. A. Agni: None. E. Hepworth: None. S.A. Amiel: Advisory Panel; Vertex Pharmaceuticals Incorporated. Other Relationship; Vertex Pharmaceuticals Incorporated. Research Support; National Institutes of Health. M.R. Rickels: Consultant; Vertex Pharmaceuticals Incorporated, Sernova, Corp. Research Support; Dompé, Tandem Diabetes Care, Inc. Consultant; Novo Nordisk. B. Riegel: None. J.A. Shaw: None. J. Speight: Advisory Panel; Vertex Pharmaceuticals Incorporated. Y. Lin: None.FundingNational Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases (T32DK007314); National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases (U01DK135120); National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases (K23DK129724)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-370-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 371-P: Sex, Age, and Diabetes Type—Dissecting Patterns of Real-World
Level 3 Hypoglycemia (iNPHORM, USA)-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 371-P
Abstract: Introduction and Objective: Large-scale, real-world data on age- and sex-specific Level 3 hypoglycemia rates in type 1 or 2 diabetes (T1D, T2D) remain critically sparse. We aimed to address this gap using prospective data from the iNPHORM study.Methods: Adults (≥18 years) with T1D or T2D on insulin and/or secretagogues recruited from a US-wide probability-based internet panel completed an online screener, baseline, and up to 12 monthly follow-up questionnaires. For complete cases with ≥1 follow-up, we calculated annualized Level 3 hypoglycemia rates overall and by age, sex (assigned-at-birth), and diabetes type.Results: N=978 participants were analyzed; Table 1 reports overall and group-specific Level 3 hypoglycemia rates. Across diabetes types, adults aged 18-39 years—particularly males—reported the highest event rates, which sharply dropped after age 39, regardless of sex. In T1D, females aged 40-49 years had higher rates than males (p=0.04), a trend that persisted (non-significantly) in cohorts aged ≥60 years. In T2D, males had higher Level 3 hypoglycemia rates than females until after age 59, when increasing female rates surpassed (non-significantly) declining male rates.Conclusion: Our results reveal age- and sex-based disparities in Level 3 hypoglycemia, suggesting that younger males and older females are key at-risk groups. Targeted prevention strategies are crucial to ensure equitable outcomes across diverse populations with diabetes.Disclosure A. Ratzki-Leewing: Other Relationship; Abbott, Dexcom, Inc. Consultant; Sanofi. Other Relationship; Sanofi. Consultant; Sanofi-Aventis U.S. Advisory Panel; Sanofi-Aventis U.S. J.E. Black: None. A. Kahkoska: None. K. Gandhi: None. B.L. Ryan: None. G. Zou: None. S.B. Harris: Advisory Panel; Abbott. Consultant; Abbott. Research Support; Boehringer-Ingelheim. Advisory Panel; Dexcom, Inc. Consultant; Dexcom, Inc. Research Support; Canadian Institutes of Health Research. Advisory Panel; Eli Lilly and Company. Research Support; Eli Lilly and Company. Consultant; Medscape. Advisory Panel; Novo Nordisk. Research Support; Novo Nordisk, Novartis Pharmaceuticals Corporation. Advisory Panel; Sanofi. Consultant; Sanofi.FundingThe iNPHORM study was funded through an investigator-initiated grant from Sanofi Global.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-371-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 372-P: Risk of Hypoglycemia Associated with Nondiabetes Medications in
Older Adults on Sulfonylureas-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 372-P
Abstract: Introduction and Objective: Sulfonylureas (SU) are widely used for diabetes management but can cause hypoglycemia, worsened by drug interactions. We used high-throughput data mining to identify non-diabetes medications that may increase hypoglycemia risk when added to SU.Methods: Using Medicare, MarketScan, and Optum Clinformatics (2003-2022), we identified patients ≥65 years who experienced severe hypoglycemia after at least 90 days on SU. We evaluated all non-diabetes medications dispensed in the 90 days before a hypoglycemic event using a case-crossover design, with metformin as the reference group to adjust for time-varying confounding. Odds ratios (OR) quantified the association between each medication and hypoglycemia risk. False discovery rate was controlled at 0.05 to adjust for multiple testing.Results: We identified a total of 571,789 hypoglycemic events. After adjustment, four medications showed significant associations: sulfamethoxazole/trimethoprim (OR 1.47, p<0.01), metronidazole (OR 1.62, p=0.01), loperamide (OR 1.78, p=0.02), and clarithromycin (OR 2.11, p=0.02). After adjusting for multiple testing, only sulfamethoxazole/trimethoprim retained statistical significance.Conclusion: This data mining approach validated known but rare associations and further screened for non-diabetes medications that could potentially increase hypoglycemic risk when added to SU.DisclosureS. Bea: None. E. Patorno: Research Support; National Institute of Diabetes and Digestive and Kidney Diseases, Patient-Centered Outcomes Research Institute, Food and Drug Administration (FDA), Boehringer-Ingelheim. Other Relationship; UpToDate. G. Hahn: None. J.M. Paik: None. D.J. Wexler: Other Relationship; Novo Nordisk. K. Bykov: None.FundingAmerican Diabetes Association (1-25-PDF-66); National Institute of Health (K01AG068365)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-372-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 373-P: Effect of Automated Insulin Delivery Systems Initiation on
Reduction of Hypoglycemia in People with Type 1 Diabetes—Retrospective
Single-Centre Study-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 373-P
Abstract: Introduction and Objective: Automated Insulin Delivery systems (AID) improve glycemic outcomes and reduce hypoglycemia in people with type 1 diabetes (PwT1D). We assessed the effect of AID initiation (MiniMed 780G, Tandem t:slim X2, CamAPS FX hybrid closed-loop system) in PwT1D on reduction of hypoglycemia in real-world settings.Methods: CGM data from our local registry (entered once yearly at the last clinic visit of the corresponding year) were used for the analysis. All PwT1D who were initiated on any AID in our center throughout the year 2023 were included in the study. CGM data the year before and after AID initiation were compared.Results: Altogether 219 PwT1D (121/219, 55% women) with mean (SD) age 42 (15) years, diabetes duration 24 (12) years were analyzed. Of these, 168/219 (77%) were previously on non-AID pumps and 51/219 (33%) were on MDI regimen. Following AID initiation, TBR reduced (mean paired difference [95%CI]) (-2.6 [-3.4, -1.8] %, p < 0.001), level 1 hypoglycemia (-1.7 [-2.4, -1.1] %, p < 0.001) and level 2 hypoglycemia (-0.9 [-1.2, -0.6] %, p < 0.001) reduced. Reductions in TBR, level 1 and level 2 hypoglycemia occurred with all 3 AIDs: for MiniMed 780G (n = 86) (-3.6 [-5.1, -2.1] %, p < 0.001), (-2.5 [-3.9, -1.2] %, p < 0.001) and (-1.0 [-1.6, -0.5] %, p < 0.001); for Tandem t:slim X2 (n = 94) (-2.1 [-3.2, -1.0] %, p < 0.001), (-1.3 [-2.0, -0.5] %, p < 0.001) and (-0.8 [-1.4, -0.3] %, p = 0.005), and for CamAPS FX system (n = 39) (-1.9 [-3.6, -0.3] %, p < 0.001), (-1.2 [-2.3, -0.1] %, p = 0.016) and (-0.7 [-1.4, -0.1] %, p = 0.033). The difference in hypoglycemia reduction between MiniMed 780G and CamAPS FX was statistically significant for TBR (-1.7 [-3.1, -0.2] %, p = 0.016) and level 2 hypoglycemia (-0.5 [-0.9, -0.1] %, p = 0.006) in favor of MiniMed 780G.Conclusion: Initiation of all three AIDs in PwT1D statistically significantly and clinically meaningfully reduced hypoglycemia in our cohort. Highest reductions were observed with the MiniMed 780G.Disclosure P. Novodvorsky: Advisory Panel; Novo Nordisk A/S. Speaker's Bureau; Novo Nordisk A/S, Sanofi, Abbott, AstraZeneca, Boehringer-Ingelheim. R. Bem: None. K. Sochorova: Consultant; Medtronic, Ypsomed AG. R. Koznarova: None. D. Vávra: None. K. Cechová: None. F. Hrubý: None. P. Girman: Speaker's Bureau; Neovii. M. Dubsky: None. M. Haluzik: Research Support; Sanofi. Advisory Panel; Eli Lilly and Company. Speaker's Bureau; Novo Nordisk, Abbott. Advisory Panel; AstraZeneca. Speaker's Bureau; GlaxoSmithKline plc, Amgen Inc. Advisory Panel; Bausch Health.FundingCarDia (Programme EXCELES, Project No. LX22NPO5104) - Funded by the European Union - Next Generation EU Grant: G7301
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-373-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 374-P: MiR-1181 Ameliorates Renal Fibrosis by Alleviating High
Glucose-Induced Oxidative Stress In Vitro-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 374-P
Abstract: Introduction and Objective: Diabetic renal fibrosis (DRF) is an irreversible pathological change of the kidney in the end-stage of diabetic kidney disease (DKD). Studies have shown microRNAs (miRNAs) play an important role in the development and progression of DKD. In our study, plasma miR-1181 levels were significantly lower in DKD patients compared to healthy individuals, as revealed by miRNA microarray analysis. However, the involvement of miR-1181 in DKD pathogenesis remains unclear.Methods: Since miR-1181 is not expressed in rodents, experiments in vitro were used to construct a DKD model in vitro by treating human renal tubular epithelial cells (HK-2) and human renal glomerular endothelial cells (HRGECs) under high glucose (HG) conditions in our study.Results: The experimental results showed that HG significantly downregulated the expression of miR-1181 in a concentration-independent manner. Our further study found that miR-1181 inhibition exacerbated HG (40mM)-induced oxidative stress, reduced cell proliferation, and enhanced inflammatory responses. In contrast, miR-1181 overexpression significantly reversed HG-induced damage in HK-2 and HRGECs. Transwell migration and scratch assays demonstrated that upregulating miR-1181 reduced the migration ability of HG-treated HK-2 and HRGEC cells, thereby mitigating HG-induced epithelial-mesenchymal transition (EMT) and endothelial-mesenchymal transition (EndMT), ultimately improving renal fibrosis. Additionally, our study revealed that the expression of miR-1181 inhibited the p38 mitogen activated protein kinases (P38 MAPK) signaling pathway.Conclusion: In conclusion, this study suggests that miR-1181 alleviate HG-induced renal fibrosis via the P38 MAPK pathway and offer potential protection against DKD, making it a promising therapeutic target.DisclosureS. Wan: None. J. Luo: None. F. Li: None. L. Zhang: None.FundingHealth Science and Technology Program of Yunnan Province (202301AY070001-092); Yunnan health training project of high level talents (L-2024011); Priority Union Foundation of Yunnan Provincial Science and Technology Department and Kunming Medical University (202201AY070001-061)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-374-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 375-P: DYRK1A Regulates Kidney Fibrosis Induced by TGF-β by
Modulating Phospho-SMAD3 Levels-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 375-P
Abstract: Introduction and Objective: DYRK1A is a serine/threonine kinase that plays a key role in the development and function of the central nervous system, and is associated with degenerative diseases and cancer progression. While recent studies have shown that knocking down DYRK1B reduces fatty liver and fibrosis caused by a high-fat diet, and harmine inhibits DYRK1B to reduce TGF-β-induced collagen expression in liver fibrosis, the role of DYRK1A in kidney fibrosis is still not well understood. Additionally, DYRK1A inhibition has been shown to promote renal epithelial cell proliferation after kidney injury. This study aims to investigate how DYRK expression affects kidney fibrosis and uncover the mechanisms underlying this process.Methods: UUO surgery was performed as follows: the left ureter was ligated with 5.0 silk at two separate points. HK-2 cells were maintained with keratinocyte-free medium according to the supplier’s recommendations. To elucidate the effect of DYRK1A and DYRK1B, knockdown experiments were conducted by transfecting HK-2 cells with small interfering RNA targeting DYRK1A and DYRK1B for 24 hours. Cells were infected with adenovirus in serum-free medium for 2 hours, after which the medium was changed to conditioned medium for 24 hours.Results: The expression of DYRK1A and DYRK1B was increased in the kidney fibrosis model through UUO. In the knockdown study using siRNA, the kidney fibrosis induced by TGF-β was more effectively reduced by the inhibition of DYRK1A compared to the inhibition of DYRK1B. Upon overexpression of DYRK1A via adenovirus, kidney fibrosis and phosphorylation of Smad3, a key downstream mechanism of TGF-β, were increased. Furthermore, kidney fibrosis and phospho-Smad3 induced by TGF-β were reduced upon the inhibition of DYRK1A expression through sh-DYRK1A adenovirus.Conclusion: These results indicate that DYRK1A regulates kidney fibrosis induced by TGF-β in cultured human proximal tubular epithelial cells, by increasing the levels of phospho-Smad3.DisclosureG. Jung: None.FundingNational Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT: Ministry of Science and ICT) (No. RS-202300252005)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-375-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 376-P: The Relationship of Mitochondrial DNA Copy Number with
Cardiovascular and Microvascular Complications in Patients with Type 2
Diabetes—A Field Substudy-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 376-P
Abstract: Introduction and Objective: Mitochondrial dysfunction contributes to cardiovascular and microvascular disease risks in type 2 diabetes (T2D). This study investigates whether mitochondrial DNA copy number (mtDNA-CN) in whole blood can serve as a biomarker for these complications.Methods: mtDNA-CN was measured in the DNA extracted from whole blood samples of 497 T2D adults from the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) trial. The relationship of mtDNA-CN with cardiovascular and microvascular complications over 5 years was assessed.Results: The cohort (29.8 % women, mean(SD) age 62(7) years, HbA1c 7.1(1.4)%) showed no variation in mtDNA-CN by sex. There were no significant associations of mtDNA-CN with traditional risk factors of age, BMI, HbA1c, diabetic duration (P>0.05), but mtDNA-CN correlated with eGFR (Pearson r = 0.117, P = 0.009) and plasma uric acid (Pearson r = -0.114, P = 0.012). mtDNA-CN was not related to new on-trial total CVD events, but inversely associated with new on-trial total microvascular events (Table 1).Conclusion: Mitochondrial DNA copy number could serve as a biomarker for assessing microvascular disease risk in T2D patients.DisclosureA. Mangani: None. A.S. Januszewski: None. K. Ong: None. H. Francis: None. R.L. O'Connell: None. L. Li: None. D. Sullivan: Other Relationship; Amgen Inc. Research Support; Arrowhead Pharmaceuticals, Inc. Other Relationship; Novartis Pharmaceuticals Corporation, Merck Sharp & Dohme Corp. Research Support; Ionis Pharmaceuticals. R.S. Scott: None. P.G. Colman: None. A. Jenkins: Advisory Panel; Abbott. Speaker's Bureau; GlaxoSmithKline plc. Research Support; Abbott, Metronics, Ypsomed AG, Insulet Corporation, Jaeb Center for Health Research, Endogenex, Hemsley Charitable Trust. Speaker's Bureau; CSL Seqirus. Research Support; AbbVie Inc, National Institutes of Health, Juvenile Diabetes Research Foundation (JDRF). A.C. Keech: Research Support; Abbott, Amgen Inc, ASPEN Australia, Mylan. Speaker's Bureau; Novartis AG, Pfizer Inc. Research Support; Kowa Company, Ltd. Speaker's Bureau; Sanofi. Research Support; AbbVie Inc, Viatris Inc.FundingLaboratoires Fournier, Dijon, France and the National Health and MedicalResearch Council of Australia (457103, 1024105, 1037786, 1105467, 1121272, 1137071 and 2018537)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-376-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 377-P: Diabetes Reduces Endothelial Glycocalyx via Matrix Remodeling
-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 377-P
Abstract: Introduction and Objective: Diabetic Kidney Disease (DKD) occurs commonly in people with diabetes and often presents with albuminuria resulting from glomerular filtration barrier injury. The glycocalyx, an extracellular matrix (ECM) produced by endothelial cells, plays a critical role in regulating glomerular filtration.Methods: To test if diabetes induces ECM changes, we examined the abundance of glomerular glycocalyx in a mouse model of DKD (BTBR Lepob; OB) and in nondiabetic (ND) mice. Glycocalyx abundance was assessed using wheat germ agglutinin (WGA) staining, which selectively marks glycocalyx, quantified through immunohistochemistry and flow cytometry. Single-cell RNA sequencing (scRNA-seq) was used to examine the expression of genes involved in ECM remodeling.Results: Diabetes significantly reduced glomerular glycocalyx in OB vs ND mice. Glomerular WGA accumulation was 27.1±2.7% (mean±SEM) of glomerular area in ND compared to 19.6±2.7% in OB mice (p=4.5x10-2; n=20-21). Flow cytometric analysis of cortical endothelial cells similarly showed diabetes decreased endothelial cell WGA binding by 19.8±4.7% compared to ND mice (p=4.2x10-3; n=17-21), indicating a reduction in the glycocalyx in DKD. Gene Set Enrichment analysis of scRNA-seq data from adults with DKD from the Kidney Precision Medicine Project and our data from OB vs ND mice indicated ECM remodeling is a key pathway altered in human and mouse endothelial cells in DKD. Consistent with an increased turnover of the ECM, expression of enzymes such as Adamts6, a protease that cleaves ECM components, was increased in the scRNA-seq dataset (1.6-fold, p=2.1x10-6) and in isolated endothelial cells from diabetic mice (2.5±0.5-fold, p=2.9x10-2; n=4).Conclusion: ECM remodeling may be induced by increased expression of ECM-degrading enzymes in diabetes, contributing to the glomerular filtration barrier breakdown seen in DKD.DisclosureA.E. Reed: None. F. Kramer: None. J. Cervantes: None. C. Limonte: None. J.E. Kanter: None.FundingAmerican Diabetes Association (11-22-IBSPM-09); National Institutes of Health (R01DK121756)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-377-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 378-P: Enhanced Renal Protective Effects of Tirzepatide in T2D People
-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 378-P
Abstract: Introduction and Objective: In Japan, 1/400 diabetes people undergo hemodialysis. Chronic Kidney Disease (CKD) can lead to cardiovascular events (CV). Early detection and protection against renal failure is paramount. A report has revealed GLP-1RAg provides renal protection and decreases CV in Type 2 Diabetes (T2D) people. However, effects of GIP, another incretin hormone, on renal function are unknown. This study analyzed whether Tirzepatide (Tir), GLP-1RAg/GIPR agonist, has enhanced renal protection compared to GLP-1RAg therapy alone in real-world long duration applications.Methods: Retrospective univariate and multivariate analyses regarding HbA1c, eGFR, body weight and age were performed on three groups, A) eGFR >60, B) eGFR 59~30, and C) eGFR <30, of T2D cases receiving Tir or GLP1RAg for 12 months or more from 04/2023. Adverse events were monitored.Results: Of 367 T2D cases new to Tir (male 209, age 66.8±14.4, starting HbA1c 8.0±1.5%), 267 were analyzed (male 150, age 62±15, BMI 25.9±7.2, starting HbA1c 8.2±3.4%) and achieved HbA1c 6.7±2.4 % (P<0.01) over more than 1 years. In group B (70 cases/male 50, HbA1c 7.9 ± 1.5%, eGFR 42.2 ± 7.4), 43 improved significantly (eGFR 50 ± 8.7 was 50.1 ± 11.4 (P < 0.01)), 3 were unchanged and 24 worsened (eGFR 50 ± 8.7 was 5.1 ± 11.4 (P < 0.01)). Tir eGFR provided significant favorable changes compared to semagletide injections, GLP-1RAg alone (P<0.01). No significant difference in weight loss occured. Group A (187 cases/male 92, HbA1c 8.1±1.6%, eGFR 85.5±18.1) and C (16 cases/male 11, HbA1c 8.7±1.3%, eGFR 20.9±6.6) had no significant changes. Reasons for discontinuation were excessive weight loss, appetite loss or nausea/vomiting.Conclusion: This study suggests addition of GIP to GLP-1 signaling enhances reno-protective effects and prevents renal impairment more than GLP1RAg alone without serious side effects and may lead to comparable reductions in CVs. This could result in greater general well-being and immense medical cost savings. Observations in larger numbers are needed.Disclosure S. Kaneko: Speaker's Bureau; Mitsubishi Tanabe Pharma Corporation, Novo Nordisk. Research Support; Novo Nordisk. Consultant; Novo Nordisk. Speaker's Bureau; AstraZeneca, Kowa Company, Ltd, Eli Lilly and Company. Research Support; Eli Lilly and Company. Speaker's Bureau; Novartis Pharmaceuticals Corporation, Sumitomo Dainippon Pharma Co., Ltd, Otsuka Pharmaceutical. T. Hirobata: Consultant; OtsukaPharmaceutical Co.,Ltd, Kowa Company, Ltd, Sanofi, Sumitomo Dainippon Pharma Co., Ltd, Taisho Pharmaceutical Holdings Co., Ltd, Novartis Pharmaceuticals Corporation, Novo Nordisk, Bayer Pharmaceuticals, Inc, Boehringer-Ingelheim, Mochida pharmaceutical Co., Ltd. Research Support; Novo Nordisk.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-378-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 379-P: Imeglimin May Improve Inflammation and Fibrosis in Diabetic Kidney
Disease-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 379-P
Abstract: Introduction and Objective: Imeglimin is an oral hypoglycemic agent marketed from Japan and has shown glucose-lowering effects in Japanese patients with type 2 diabetes in TIMES trials. However, it is not well known whether imeglimin can affect diabetic kidney disease (DKD). To clarify this, we investigated the protective effects of imeglimin on DKD by using diabetic mice and culture cells (HUVEC).Methods: In vivo study, 8-week-age C57BL/6 mice were fed with control diet or high-fat diet (HFD). For HFD-fed mice, streptozocin (STZ) was single intraperitoneally injected at 12 weeks of age, and STZ-induced diabetic mice were orally administered with vehicle or imeglimin from 16 to 24 weeks of age, resulting in three experimental groups: non-diabetes (NDM), diabetes (DM), and DM+Imeglimin. Urinary albumin excretion was measured at 20 and 24 weeks of age, and mice were sacrificed at 24 weeks of age. In vitro study, the effects of imeglimin on high glucose (HG, 25mM)-induced inflammation were tested. HUVEC were stimulated by HG for 72 hours, and vehicle or imeglimin was co-administered. Total RNA was isolated from mouse renal tissue and HUVEC, and mRNA expression was measured by real-time qPCR.Results: At 24 weeks of age, imeglimin did not affect random glucose level and body weight between DM and DM+Imeglimin. Urinary albumin excretion was increased in DM compared with NDM, which was decreased in DM+Imeglimin. The mRNA expression of Nlrp3, Tlr-4, F4/80, inflammatory cytokines (Il-1b, Icam-1, Tnfa), and fibronectin were increased in DM compared with NDM, which were also decreased in DM+Imeglimin. In vitro study, the mRNA expressions of Nlrp3 and Vcam-1 were upregulated by HG stimulation compared with low glucose (5mM) in HUVEC, which were reduced by imeglimin administration.Conclusion: Imeglimin could improve albuminuria in DKD via anti-inflammation and anti-fibrotic actions and may prevent from the progression of DKD.DisclosureY. Muta: None. H. Yokomizo: None. T. Kawanami: None. Y. Hamaguchi: None. D. Kawanami: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-379-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 380-P: Dual Roles of Renal Tubular Mitochondrial AKT1 in Improving Whole
Body Glucose Metabolism and Protecting Against Diabetic Nephropathy-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 380-P
Abstract: Introduction and Objective: Diabetic nephropathy (DN) is a major cause of end-stage renal disease. We have recently shown that activation of mitochondrial Akt1 in proximal tubules played a renoprotective role in murine acute ischemia-reperfusion injury. However, whether activation of mitochondrial Akt1 in renal proximal tubules can protect against the development of DN remains to be elucidated.Methods: We have generated a transgenic mouse model harboring a renal proximal tubule-specific tamoxifen-inducible mitochondria-targeting constitutively active Akt1 (KMCAKT).Results: High fat+fructose diet (HFFD) induced DN, but KMCAKT mice attenuated renal dysfunction induced by HFFD. Urinary albumin/creatinine ratio, fasting plasma creatinine, glomerular mesangial expansion and fibrosis were all improved compared to controls. To dissect the underlying mechanism, we have determined the contents of renal αSMA and TGFβ1 and both were lower in KMCAKT mice than in controls (p<0.001). This indicated that activation of mitochondrial Akt1 in renal tubule protected against the development of DN induced by HFFD. Interestingly, HFFD-fed KMCAKT mice showed significant reduction in fasting plasma glucose and urinary glucose excretion with an improvement of oral glucose tolerance compared to controls. Fasting plasma insulin levels were higher in HFFD-fed KMCAKT mice as compared to controls, whereas insulin resistance (HOMA-IR) were unchanged from controls, suggesting that renal mitochondrial Akt1 positively modulated systemic glucose metabolism, at least partially, by enhancing beta cell function.Conclusion: These data demonstrated novel roles of renal tubular mitochondrial Akt1 in the regulation of whole-body glucose metabolism and insulin secretion beyond its local effect on kidney function in DN, which suggests renal function and glucose homeostasis could be mediated through a common pathway in renal tubular mitochondria.DisclosureE. Salem: None. A. Ta: None. P.T. Fueger: None. P.H. Wang: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-380-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 381-P: Identification and Functional Analysis of ZFP36, the Hub
Ferroptosis-Related Factor in Diabetic Kidney Disease-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 381-P
Abstract: Introduction and Objective: Diabetic Kidney Disease (DKD) is a leading cause of end-stage renal disease (ESRD). Extensive studies suggest that ferroptosis is a key factor in DKD progression. Our research aims to investigate whether ferroptosis-related factor ZFP36 can alleviate diabetic kidney injury.Methods: We extracted differentially expressed genes from the GEO database and conducted GO enrichment, GSEA, GSVA, plus machine learning techniques like RF, SVM-RFE, and Lasso Cox regression to identify ferroptosis-related genes. Expression differences of ZFP36 and its interacting proteins were validated in HK-2 cells and DKD mouse models. Additionally, ZFP36's interaction with traditional Chinese herbal components was assessed using AutoDock Tools to evaluate their impact on DKD ferroptosis.Results: We identified 9 genes significantly associated with both ferroptosis and DKD. Further machine learning marked ZFP36 as a central gene. In vivo experiments showed that compared to the control group, the expression of ZFP36 is reduced in the DKD model group. In vitro, overexpression of ZFP36 alleviates high-glucose-induced ferroptosis and reduce the formation of extracellular matrix components such as FN1 and α-SMA.ZFP36 interacts with Nrf2, reducing ROS and MDA levels, and increasing GSH levels, indicates that ZFP36 can alleviate oxidative stress. Molecular docking analysis shows that traditional Chinese herbs like Berberine and Jatrorrhizine positively regulating ferroptosis in DKD, exhibit high affinity for ZFP36, suggesting it mediates their renal protective effect.Conclusion: This study illuminates the emerging role of ZFP36 in ferroptosis in DKD, emphasizing its potential as a therapeutic target. This provides new insights for the development of targeted therapies for DKD.DisclosureA. Li: None. M. Shi: None. W. Gu: None. Y. Chen: None. Y. Liu: None. J. Zhang: None. Y. Yuxuan: None. C. Huimin: None. J. Chen: None. H. Zhang: None.FundingHuai'an Science and Technology Bureau (BE2023745), Jiangsu Provincial Health Commission (H2023137)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-381-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 382-P: Metallothionein-1/2 Alleviates Inflammation-Driven Progression of
Diabetic Kidney-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 382-P
Abstract: Introduction and Objective: Diabetic nephropathy associated with type 2 diabetes (T2DN) involves inflammation as a key mechanism contributing to kidney dysfunction. However, no targeted agents to effectively control this process have been developed. This study aimed to investigate the role of metallothioneins-1/2 (MT-1/2) in the inflammation-driven progression of T2DN.Methods: MT-1/2 expression was assessed in kidney tissues from patients with T2DN and T2D using single-cell and spatial transcriptomic analyses. Cell line and animal experiments (e.g., high-fat diet, streptozotocin, and adenine-mixed diet models) were conducted to identify transcription factors, inflammatory mediators, and inducers associated with MT-1/2 expression.Results: Patients with high tubular MT-1/2 expression exhibited slower T2DN progression than those with low expression. Single-cell and spatial transcriptomic analyses revealed that MT-12 genes were upregulated in the proximal tubules of T2DN patients with stable kidney function. Ligand-receptor analysis identified transforming growth factor-β as an inducer of MT-1/2, while single-nucleus epigenomics integrated cell analysis confirmed nuclear receptor subfamily 1 group I member 3 as a key transcription factor. These findings were validated using human proximal tubular cell lines and mouse models. Sodium-glucose cotransporter 2 inhibitors enhanced tubular MT-1/2 expression, particularly under conditions of heightened inflammation in a mouse model.Conclusion: Elevated MT-1/2 expression in the proximal tubules provides protective effects in T2DN, especially when inflammation drives disease progression. While existing therapies primarily focus on reducing albuminuria, agents that induce MT-1/2 expression represent a novel therapeutic strategy by directly preserving tubular function.DisclosureJ. Hwang: None. H. Yoon: None. M. Hong: None. B. Jang: None. D. Yun: None. C. Kang: None. S. Han: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-382-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 383-P: WTAP-Induced M6A Methylation of ATOH8 Promotes Cell Proliferation
and Fibrosis in Diabetic Nephropathy-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 383-P
Abstract: Introduction and Objective: N6-methyladenosine(m6A) RNA methylation is involved in governing the mechanism of Diabetic nephropathy(DN). We aimed to investigate the biological role and mechanism of the m6Amethyltransferase WT1-associatedprotein(WTAP) in DN.Methods: We analyzed m6A modification levels in mouse mesangial cells cultured under high-glucose conditions and in renal tissues from db/db mice. siRNAs was used to knock down WTAP in mouse mesangial cells(MMCs), MeRIP-Seq and RNA-Seq were utilized to identify downstream targets of WTAP-induced m6A modification, with a particular focus on the gene Atoh8. Then the influences of WTAP or Atoh8 on the proliferation and fibrosis were tested through CCK-8, qRT-PCR, flow cytometry and western blot.Results: Our findings indicate that m6A modification levels are up-regulated in high-glucose conditions and DN renal tissues, with WTAP being a key contributor to this increase. Knockdown of WTAP significantly reduced the proliferation and fibrosis of mouse mesangial cells. We first revealed that Atoh8 was lowly expressed in renal tissues of DN modelmice and HG-induced mesangial cells. We identified Atoh8 as a target of WTAP-induced m6A modification, with WTAP reducing Atoh8 expression by destabilizing its mRNA. Overexpression of Atoh8 was found to suppress mesangial cell proliferation and fibrosis.Conclusion: This study provides novel insights into the role of m6A modification in DN and suggests that WTAP and Atoh8 could serve as potential therapeutic targets for this condition.DisclosureS. Wang: None. M. Zhang: None.FundingThe Improvement of Clinical Ability Project of Jiangsu Province Hospital (JSPH-MA-2021-3); Postgraduate Research & Practice Innovation Program of Jiangsu Province (SJCX23_0697)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-383-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 384-P: The Role of ROCK Isoform in the Impairment of Tubular Fatty Acid
Metabolism-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 384-P
Abstract: Introduction and Objective: Diabetic nephropathy is the leading cause of end stage of kidney disease requiring dialysis, or kidney replacement. Therefore, the development of effective treatments is of paramount significance. Rho-associated, coiled-coil-containing protein kinase (ROCK) is a downstream molecule of the small G-protein Rho, playing a key role in cell motility and cell polarity. Two isoforms of ROCK, ROCK1 and ROCK2, are widely distributed in kidney cells. While previous reports have shown that activation of both isoforms in the glomerulus leads to impaired energy metabolism, their roles in tubular function are not fully understood. Since fatty acid metabolism is the primary source of ATP production in kidney tubules, the present study aimed to investigate the effects of ROCK isoforms on tubular fatty acid metabolism.Methods: Human kidney 2 (HK-2) cells were stimulated with transforming growth factor-β (TGF-β). To evaluate the role of ROCK, a ROCK inhibitor was administered or siRNA was used to knock down ROCK1 and ROCK2. The expression levels of genes involved in fatty acid metabolism were analyzed using qPCR and Western blotting.Results: TGF-β stimulation reduced the expression levels of peroxisome proliferator-activated receptor-α (PPARα) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α), key regulators of lipid energy metabolism in tubular cells. ROCK1 gene expression showed a tendency to increase under TGF-β stimulation. The addition of ROCK inhibitor significantly attenuated the reduction in PPARα gene expression caused by TGF-β. Similarly, the knockdown of ROCK1 using siRNA in the presence of TGF-β significantly mitigated the suppression of PPARα expression. The expression levels of PPARα and PGC1α remained unchanged following siRNA treatment targeting the ROCK2 gene.Conclusion: The results suggest that ROCK1 plays a suppressive role in fatty acid energy metabolism in kidney tubules by regulating the expression of PPARα and PGC1α.DisclosureS. Nagao: None. K. Matoba: None. S. Ohashi: Research Support; Novo Nordisk. K. Sekiguchi: None. E. Mitsuyoshi: None. Y. Nagai: None. R. Nishimura: Advisory Panel; Abbott Japan Co., Ltd. Speaker's Bureau; Nipro, Astellas Pharma Inc, AstraZeneca, Boehringer-Ingelheim, Eli Lilly and Company, LifeScan Diabetes Institute, Mitsubishi Tanabe Pharma Corporation, Kowa Company, Ltd, Kissei Pharmaceutical Co., Ltd. Advisory Panel; Novo Nordisk A/S. Speaker's Bureau; Ono Pharmaceutical Co., Ltd. Advisory Panel; Sanofi. Speaker's Bureau; Teijin Pharma Limited, Terumo Corporation. Advisory Panel; Medtronic. Speaker's Bureau; Dexcom, Inc., Taisho Pharmaceutical Holdings Co., Ltd.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-384-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 385-P: Association between Triglyceride, Glucose, Body Mass Index, and
Kidney Impairment in Type 2 Diabetes Mellitus-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 385-P
Abstract: Introduction and Objective: Insulin resistance is associated with kidney impairment in patients with type 2 diabetes mellitus (T2DM). The triglyceride glucose-body mass index (TyG-BMI), which combines the TyG index with body mass index (BMI), has received significant attention as a tool for evaluating insulin resistance. This study aims to explore the association between TyG-BMI and kidney impairment in patients with type 2 diabetes mellitus (T2DM).Methods: The cross-sectional analysis included 100 patients with T2DM, and data were collected from Medicine outdoor of Vedantaa Institute Of Medical Sciences, Dahanu, India. TyG-BMI was calculated by fasting blood glucose, triglyceride, and body mass index. History, physical examination and relevant investigations were done.Results: TyG-BMI was significantly higher in T2DM patients with albuminuria than those without albuminuria (242.2 [199.4- 288.2] vs 221.9 [188.1- 248.7], p =0.013). T2DM patients with chronic kidney disease (CKD) showed a significantly higher value of TyG-BMI compared with those without CKD (239.23 [200.5- 277.3] vs 218.73 [191.2- 247.5], p=0.011). Correlation analysis showed a significantly positive association between TyG-BMI and metabolic parameters including BMI, TG, TC, HDL-C, FBG, and HbA1c in patients with T2DM. The binary logistic regression analysis found that TyG-BMI was an independent factor for albuminuria and CKD in patients with T2DM respectively.Conclusion: The study suggests that TyG-BMI is associated with kidney impairment in patients with T2DM. Given that TyG-BMI is a novel parameter of insulin resistance, the study results indicate that clinicians should pay close attention to screening for kidney impairment in T2DM patients with insulin resistance.DisclosureV.M. Rathod: None. D. Raval: None. S. Bhatt: None. K.R. Rana: None. M. Subhan: None. A. Bhattacharya: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-385-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 386-P: Pyruvate Kinase M2 (PKM2) Activation in Podocytes Prevents
Diabetes-Induced Changes in Glomerular Cell Subset Differentiation-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 386-P
Abstract: Introduction and Objective: Diabetic nephropathy (DN) exhibits metabolic and structural changes in the glomeruli. PKM2 activation in glomerular cells protect against DN by improving glomerular mitochondrial function. We investigated the role of PKM2 in glomerular cell differentiation induced by diabetes using single-cell RNA sequencing (scRNA-seq).Methods: Glomerular cells were isolated from mice with PKM2 overexpression in podocytes (PPKM2Tg) and wild-type (WT) after 7 months of diabetes. scRNA-seq was performed on 87,283 cells, with >98% from glomeruli, including podocytes (31%), and endothelial (EC; 43%), mesangial (MC; 14%), parietal epithelial (PEC; 2%), and immune cells (8%). Cell subsets were analyzed for phenotypic and gene expression changes in response to diabetes and PKM2 overexpression.Results: Diabetes increased immune cells; macrophages (2.2 to 4.8%) and B cells (0.35 to 1%). While diabetes or PKM2 overexpression did not alter the overall percentages of EC, MC, and podocytes, significant phenotypic shifts were observed within their subsets. In podocytes, diabetes increased subsets associated with stress proteins and reduced cells involved in extracellular matrix production and CDC42 GTPase activity, crucial for cytoskeleton and foot process formation, which were reversed in PPKM2Tg mice and in patients with type 1 diabetes and protected from DN. Knockdown of PKM1/2 in podocytes increased CDC42 activation by promoting the expression of CDC42-GTP and decrease stress proteins. Similarly, diabetes reduced MC subsets enriched for mitochondrial activity, and EC subsets with anti-inflammatory phenotypes, both of which were restored in PPKM2Tg mice.Conclusion: ScRNA-seq showed that PKM2 overexpression in podocytes modulated the differentiation of podocyte, MC, and EC subsets, mitigating the adverse effects of diabetes on foot process in podocytes, inflammatory EC and mitochondrial activities in MC, to protect against DN.DisclosureJ. Fu: None. Q. Li: None. K. Park: None. T. Shinjo: None. Q. Huang: None. I. Wu: None. G.L. King: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-386-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 387-P: A High-Fat Diet during Pregnancy and Lactation Alters Renal Glut2
Gene Expression in Male Offspring in Mice-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 387-P
Abstract: Introduction and Objective: A high fat diet (HF) during pregnancy (P) and lactation (L) induces kidney disease in offspring. In diabetic kidney disease renal GLUT2 is increased. Mice with a genetic heterozygous deletion of GLUT4 (G4+/-), a model of insulin resistance, develop renal disease if exposed to HF during P/L. This study investigates the effect of a HF during P/L on the metabolic phenotype and expression of glucose homeostasis genes in kidney in male G4+/- and wild type (WT) offspring.Methods: Female CD1 mice were fed either a HF or control diet (C) prior to mating with G4+/- males and throughout P/L. After weaning male offspring were fed a C diet. Body weight (BW), kidney weights and blood glucose were measured. Mice were sacrificed at 5 or 13 wks, respectively, and renal GLUT1, 2 and 8 mRNA was measured by qRT-PCR (n=4-6).Results: BW of G4+/- mice on HF during P/L was lower by 11.7% at 5 wks and by 17.4% at 13 wks compared to G4+/- mice on C whereas BW of WT mice on HF during P/L was lower by 18.5% compared to WT on C during P/L at 13wks only (P<0.05). Kidney weight was reduced in both G4+/- on C (10.5%) and on HF (11.2%) during P/L compared to WT controls at 5 wks but was increased at 13 wks in G4+/- (1.15-fold) and in WT (1.22-fold) on HF during P/L compared to their genotype on C during P/L (P<0.05). No differences in blood glucose were observed. For GLUT2 gene expression, an increase in G4+/- mice on C during P/L (1.69- fold and 1.52- fold compared to WT on C and G4+/- on HF during P/L, respectively) was observed at 5 wks whereas at 13 wks an increase was observed for WT on HF during P/L compared to G4+/- (1.34-fold) and to WT (1.55-fold) on C during P/L (P<0.05). A decrease in GLUT8 gene expression by 47.3% compared to WT on C during P/L (P=0.001) was observed at 5 wks. No differences in GLUT1 gene expression were observed.Conclusion: A HF diet during P/L alters renal morphology and expression of GLUT2 which both indicate renal dysfunction, already early in post-weaning life in the absence of alterations in blood glucose levels.DisclosureM. Kruse: None. Y. Seki: None. X. Du: None. M.J. Charron: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-387-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 388-P: Keap1-Nrf2 Modulation and SLC7A11 Restoration—Bardoxolone Methyl
as a Ferroptosis Inhibitor in Renal Tubular Epithelial Cells-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 388-P
Abstract: Introduction and Objective: Ferroptosis of renal tubular epithelial cells (RTECs) is implicated in the pathogenesis of diabetic kidney disease (DKD). Bardoxolone methyl (BM), a synthetic triterpenoid with antioxidant and anti-inflammatory properties, has shown promise in clinical trials for preventing DKD-related renal decline but carries a risk of heart failure. Recent studies revealed that 2-deoxy-D-ribose (dRib) induces ferroptosis in RTECs by degrading system χc- (SLC7A11). This study investigates whether BM inhibits dRib-induced ferroptosis and elucidates the mechanisms involved.Methods: Using NRK-52E cells and primary RTECs, the researchers assessed cystine uptake, GSH and iron levels, cell viability, lipid peroxidation, and ferroptosis-related markers. Nrf2 and Keap1 interactions were evaluated using co-immunoprecipitation, and Nrf2 nuclear translocation was observed via confocal microscopy.Results: BM pretreatment dose-dependently restored cystine uptake, GSH levels, and cell viability while reducing intracellular iron and lipid peroxidation caused by dRib. The effects were diminished by Nrf2 inhibitors, indicating BM's dependence on Nrf2 activation. BM enhanced Nrf2 protein expression, upregulated SLC7A11, and increased expression of Nrf2-ARE target genes (HO1, NQO1, GCLC), while suppressing ferroptosis-related markers (ACSL4, CHAC1, PTGS2). BM disrupted the Nrf2-Keap1 interaction, promoting Nrf2 nuclear translocation.Conclusion: BM inhibits dRib-induced ferroptosis in RTECs by disrupting the association between Nrf2 and Keap1, thereby enhancing Nrf2 nuclear translocation and increasing SLC7A11 gene expression. These findings highlight the therapeutic potential of targeting the Keap1-Nrf2/SLC7A11 axis for DKD treatment without heart failure risk.DisclosureJ. Han: None. J. Bae: None. S. Yoo: None. S. Lee: None. G. Koh: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-388-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 389-P: The Ketone Body β-hydroxybutyrate Mitigates Diabetic Kidney
Disease through Metabolic Reprogramming-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 389-P
Abstract: Introduction and Objective: Diabetic kidney disease (DKD) is the most common cause of end-stage kidney disease and need for renal replacement therapy. Metabolic dysregulation plays a pivotal role in the pathogenesis of DKD, and recent research has highlighted the ketone body beta-hydroxybutyrate (BHB) as a potential link between the reno-protective effects of SGLT2 inhibitors in humans and animal models of DKD. However, how BHB exerts its reno-protective effects is unknown and the focus of this work.Methods: We collected the plasma, urine, and kidney from 24-weeks-old diabetic db/db mice and control db/+ mice. BHB was measured by LC-MS. To determine whether further increases in BHB impact DKD, db/db mice were fed with 5% 1,3-Butanediol (v/v in drinking water; 1,3-BD), as a precursor of BHB. DKD metrics including albuminuria were quantified in addition to post-translational beta-hydroxybutyrylation (BHBylation) of proteins. In HK-2 cells, BHB’s effect on mitochondrial function was assessed by metabolic flux analysis (MFA) of TCA cycle metabolites using LC-MS.Results: We found that BHB levels are significantly higher in plasma, urine, and kidney cortex of diabetic mice. Feeding 1,3-BD markedly reduced albuminuria in diabetic mice compared to controls. Diabetic mice were also found to have significantly higher BHBylated lysine levels compared to non-diabetic controls. In HK-2 cells, MFA showed BHB was the preferred fuel source compared to glucose and palmitate.Conclusion: To summarize, BHB and BHBylated protein levels were higher in diabetic condition, and supplementation with the 1,3-Butanediol, led to lower urinary albumin excretion consistent with improved DKD. Increased in BHBylation associated with this protection suggests key role of this posttranslational modification in mediating improved metabolic rewiring in DKD and associated renoprotection.DisclosureS. Chakraborty: None. M.S. Arnipalli: None. K. Saum: None. J. Baek: None. S.S. Garapati: None. P. Kayampilly: None. S. Pennathur: Research Support; Aurinia.FundingJDRF
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-389-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 390-P: NCOA4-FTH1 Axis Regulates Iron Homeostasis and Ferroptosis in
Diabetic Kidney Disease-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 390-P
Abstract: Introduction and Objective: To investigate the role of the NCOA4-FTH1 axis in regulating iron metabolism, ferroptosis, and fibrosis in diabetic kidney disease (DKD) and explore its potential as a therapeutic target.Methods: We utilized db/db mice and renal cells cultured under high-glucose and high-fat conditions to establish in vivo and in vitro DKD models. Oxidative stress, ferrous iron, lipid peroxidation, iron metabolism genes, and fibrosis markers were evaluated using biochemical assays, immunofluorescence, and Western blotting. The effects of NCOA4 knockdown, FTH1 deficiency, and treatment with HIF-1 inhibitors (YC-1) or metformin were assessed on ferroptosis and fibrosis.Results: Renal tissues from DKD mice and DKD cell model exhibited iron overload, especially ferrous iron, along with elevated lipid peroxidation and mitochondrial changes indicative of ferroptosis, and dysregulated NCOA4 and FTH1 expression. Knocking down FTH1 promoted ferroptosis and fibrosis, while NCOA4 knockdown under high glucose and lipid conditions restored FTH1 levels, inhibiting ferroptosis and fibrosis. Elevated NCOA4 in DKD mice correlated with HIF-1αexpression, and in vitro hypoxia increased HIF-1α and NCOA4. Treatment with YC-1 or metformin reduced HIF-1α and NCOA4 expression, attenuating intracellular lipid peroxidation and ferroptosis in renal tubular cells.Conclusion: This study identifies the NCOA4-FTH1 axis as a critical regulator of iron metabolism and ferroptosis in DKD. Targeting this pathway can mitigate oxidative stress and fibrosis, providing a novel therapeutic strategy for DKD.DisclosureX. Chen: None. M. Zhang: None.FundingNational Natural Science Foundation of China (82370828); the Improvement of Clinical Ability Project of Jiangsu Province Hospital (JSPH-MA-2021-3)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-390-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 391-P: Suppression of Glucokinase Mitigated Renal Injury Induced by ABCC8
Mutation-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 391-P
Abstract: Introduction and Objective: Glucokinase (GCK) maintains glucose homeostasis. Gck heterozygous inactivation mutation leads to maturity onset diabetes of the young 2 with clinical features of mild hyperglycemia and low insulin levels, and the incidence of microvascular complications is significantly low. ATP-Sensitive K+ Channel (K-ATP) is vital in regulating insulin secretion. Inactivated variants of Abcc8 encoding SUR1 subunit of the K-ATP can lead to hyperinsulinemia and kidney injury. Our study aims to elucidate the role of GCK and hyperinsulinemia in the development of kidney injury.Methods:Gck knockout mouse (Gck+/-) and Abcc8 R306C mutation mouse (Abcc8mut/+) were constructed using CRISPR-Cas9. After hybridization, we obtained Gck knockout and Abcc8 mutant heterozygote mouse (G&A), observed metabolic phenotype and evaluated the kidney injury.Results:Gck+/- mice showed hyperglycemia and impaired glucose toleranc. Abcc8mut/+ mice showed normal blood sugar, elevated fasting insulin, and significant kidney injury. Compared to Abcc8mut/+ mice, G&A mice developed elevated fasting blood glucose but lower insulin levels, and alleviated kidney injury. (Figure 1)Conclusion: Hyperinsulinemia leads to severe renal injury independent of hyperglycemia. Suppression of glucokinase on the basis of hyperinsulinemia can partially alleviate renal injury.DisclosureH. Lian: None. C. Yang: None. L. Ji: None. X. Han: None.FundingNational Natural Science Foundation of China (82170814)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-391-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 392-P: Metabotypes to Define Cardiorenal Risk in People with Type 1
Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 392-P
Abstract: Introduction and Objective: Cardio-renal complications are the leading source of morbidity in people with type 1 diabetes (T1D). While previous metabolomic studies have characterized incident and predictive metabolic signatures (metabotypes) of diabetic kidney disease (DKD) and cardiovascular autonomic neuropathy (CAN) in separate T1D cohorts, no previous study has investigated CAN and DKD in the same subset of T1D patients. In this study we sought to identify shared and unique metabotypes of T1DKD and CAN in 120 T1D subjects.Methods: Baseline blood samples were processed for central carbon and lipidomic LC/MS analysis. DKD and CAN were defined as eGFR < 60 mL/min/1.73m2 and/or elevated albumin/creatinine (ACR), and prior validated cut-offs for indices of heart rate variability (SDNN, RMSSD). We used logistic regression to assess ability of metabolic feature/classes associating with incident and progression of DKD and CAN before and after adjusting for age, gender, race, diabetes duration and BMI.Results: Among 120 T1D subjects (mean age 48 years, mean A1c 8.2%; 42 % women) a unique panel of metabolites associated with incident DKD (with amino acids showing AUC of > 0.7 for eGFR and ACR) and CAN (peptides AUC > 0.7). In a subset of subjects with available follow-up data in adjusted analysis baseline azolines and glycerophosphoinositols were associated DKD progression (new decline in eGFR at follow-up < 60 or elevation of ACR compared with baseline). Unadjusted data showed baseline azolines, peptides and steroids may associate with progression of CAN while in adjusted analysis this was no longer significant presumably due to small numbers of subjects that exhibited progression.Conclusion: These data suggest that distinct metabotypes associate with T1D DKD and CAN at baseline, a subset of which associate with DKD progression. Ongoing studies will focus on identifying predictive CAN progression markers as more follow-up data becomes available for risk stratification in people with T1D.DisclosureL. Ang: None. Y. Huang: None. F. Afshinnia: None. M. Banerjee: None. C. Martin: None. P. Ramkumar: None. M. Kretzler: Research Support; AstraZeneca, Boehringer-Ingelheim, Chinook Therapeutics, Inc, Eli Lilly and Company, Moderna, Inc, Janssen Pharmaceuticals, Inc, National Institutes of Health, European Union. Advisory Panel; Novartis Pharmaceuticals Corporation. Research Support; Novo Nordisk. Advisory Panel; Otsuka America Pharmaceutical, Inc. Research Support; Regeneron Pharmaceuticals, Renalytix, Roche Pharmaceuticals, Sanofi, Travere, Certa, Dimerix. S. Pennathur: Research Support; Aurinia. R. Pop-Busui: Board Member; American Diabetes Association. Consultant; Averitas Pharma, Inc. Research Support; Bayer Pharmaceuticals, Inc. Other Relationship; Biogen. Research Support; Juvenile Diabetes Research Foundation (JDRF). Advisory Panel; Lexicon Pharmaceuticals, Inc, Novo Nordisk. Research Support; Novo Nordisk, National Institute of Diabetes and Digestive and Kidney Diseases. Consultant; Roche Diagnostics.FundingSupported by Breakthrough T1D (former JDRF) Center of Excellence grant 2019-861RPB was also supported by 1-R01-DK126837-01A1
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-392-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 393-P: Epigenome-Wide Association Applied in Early Prediction of Kidney
Disease in Diabetes (DKD)—A Pilot Study-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 393-P
Abstract: Introduction and Objective: Epigenetic modifications, such as DNA methylation(DNAm), can provide a composite measurement of environmental/genetic influence on gene expression. A significant gap remains in defining DNAm profiles in diabetes, prior to DKD diagnosis. We determined blood-derived DNAm profiles, in type-2 diabetes(T2D) people with normal kidney function, that were predictive of DKD incidence in the DARE cohort.Methods: Blood-derived DNAm was measured at 850,000 genomic loci (CpGs) using the Infinium EPIC V2-BeadChip (Illumina), in 42 people with T2D, with >10 years detailed clinical follow up data, including renal function. All had normal ACR at baseline. The ‘ChAMP package’ in R was used to identify differentially methylated CpGs in T2D individuals who developed urine ACR>3mg/mmol)) vs no increase in ACR (n=21), after 10 years. Age range was 42-79 years (20 female/22 male), with equal split between case/control groups. Bulk RNA sequencing data from the human kidney was extracted from the ‘Nephroseq’ database.Results: Our Epigenome-wide Association study (EWAS) identified 127 differentially methylated CpG sites (p<9x10-5) associated with UACR>3mg/mmol incidence in the DARE cohort, after adjustment for age/sex. Cross-tissue comparisons identified associations between methylation at cg08494812 (sitting within 200bp of AF1B transcription start site) and UACR>3mg/mmol consistent between both blood-derived and kidney-derived DNA. RNA sequencing data (‘Nephroseq’) indicated that TAF1B expression in the kidney tubule was reduced in DKD, and suggested that kidney TAF1B expression correlated with renal function preservation.Conclusion: Our pilot study identified pre-diagnosis DNAm changes predictive of albuminuria incidence and highlights that increased methylation at the TAF1B gene (cg08494812) is associated with decreased TAF1B expression in kidney and rise in ACR. Future work aims to confirm the significance of these findings and to extend our EWAS to the larger DARE cohort.DisclosureA.C. Lay: None. A.H. Heald: None. J.M. Gibson: None. P. Kalra: Speaker's Bureau; Pharmacosmos. Advisory Panel; Medice, CSL Vifor.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-393-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 394-P: Severe Insulin-Deficient Diabetes in Chile—A Contributor to
Diabetic Kidney Disease Risk'-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 394-P
Abstract: Introduction and Objective: Understanding diabetes heterogeneity across diverse populations is critical for advancing precision medicine. However, data on diabetes subphenotypes in South America remains limited. Here we analyze the distribution of Ahlqvist clusters among a nationally representative cohort of Chilean individuals with diabetes and their relation to chronic kidney disease (CKD).Methods: This cross-sectional analysis included 627 adults with diabetes mellitus from the Chilean National Health Survey (NHS) 2009-2010 and 2016-2017 with BMI 31 ± 6 kg/m2, HbA1c of 7.8 ± 2.2% and diabetes duration of 10 ± 10 years. They were assigned to the Mild Age-Related Diabetes (MARD), Mild Obesity-Related Diabetes (MOD), Severe Insulin-Resistant Diabetes (SIRD), and Severe Insulin-Deficient Diabetes (SIDD) clusters using the approach proposed by Bello-Chavolla et al., that relies on BMI, HDL, triglycerides, waist circumference, age at diagnosis and NHS, sex, glucose, and HbA1c. CKD markers (GFR and albumin-to-creatinine ratio, ACR) and self-reported complications (retinopathy, diabetic foot ulcers) were assessed.Results: Clusters were distributed as follows: MARD 24.2 %, MOD 31.6 %, SIRD 11.5 %, and SIDD 32.7 %. Both MARD and SIRD had lower GFR and higher rates of stage 3 CKD compared to MOD. SIDD exhibited the highest HbA1c and 2-5 times higher ACR (p < 0.01 vs. all other clusters). Rates of retinopathy and diabetic foot ulcers did not differ among clusters. In a subgroup with recent diagnosis (<3 years, n=193), SIDD represented a smaller proportion (15.5 %), but CKD marker disparities across clusters were consistent.Conclusion: SIDD accounts for a substantial segment of Chilean diabetes cases, characterized by poor glycemic control and markedly elevated proteinuria. This contrasts with findings from Caucasian cohorts where SIRD is tightly linked to CKD, underscoring the importance of population-specific data for developing equitable precision medicine strategies.DisclosureS. Gancheva: None. V. Serrano: None. G. Echeverría: None. A. Rigotti: Advisory Panel; Merck Sharp & Dohme Corp. Research Support; Merck Sharp & Dohme Corp.FundingThis research used information from the Health Surveys for epidemiological surveillance of the Undersecretariat of Public Health. The author thanks the Ministry of Health of Chile for allowing him/her to use the database. All results obtained from the study or research are the responsibility of the author and do not in any way compromise said institution.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-394-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 395-P: Dynamically Predicting Renal Failure after Development of Diabetes
for Millions across Biobanks-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 395-P
Abstract: Introduction and Objective: Despite advances in diabetes (DM) care, complications remain high, underscoring the need for better risk prediction. We developed a risk engine in the Veterans Health Administration (VA), validated it in All of Us (AoU), and compared it with Risk Equations for Complications Of Type 2 Diabetes (RECODe).Methods: We analyzed newly diagnosed VA patients using Fine-Gray sub-distribution hazard models for renal failure at 1, 5, and 10-year landmarks (LM), with all-cause mortality as a competing risk. We used a two-step feature selection (logistic regression followed by a minimax concave penalty) to choose variables at LM1, then re-fitted unpenalized models at LM5 and LM10. Medication/comorbidity histories, baseline covariates, and biomarker trends were included.Results: Of the 815,429 newly diagnosed patients at LM1, 3.27% developed renal failure (median age 62; time to renal failure 8.0 years from DM), while 29.2% died without renal failure. At LM1, AUROCs for predicting 1-/5-/10-year renal failure were 0.86, 0.82, and 0.79 in VHA; 0.86, 0.85, and 0.80 in AoU; and 0.87, 0.76, and 0.69 for RECODe in AoU. Other landmarks showed similar performance.Conclusion: Our dynamic risk engine, which continuously updates patient risk at key intervals, significantly improves renal failure prediction among those with diabetes. Its superior discrimination compared to RECODe, with validation in AoU, suggests broad applicability for care optimization.DisclosureA. Jensen: None. S. Dhaubhadel: None. G. Li: None. H. Zhou: Consultant; Merck & Co., Inc. B. McMahon: None. P. Reaven: Research Support; Dexcom, Inc. J. Zhou: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-395-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 396-P: Association between Body Roundness Index and Chronic Kidney Disease
Risk in Diabetic Patients—Insights from NHANES 1999–2018-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 396-P
Abstract: Introduction and Objective: Chronic kidney disease (CKD) is a common and severe complication of diabetes. Early identification of CKD risk factors is essential for timely intervention. Body Roundness Index (BRI), a novel obesity measure reflecting body shape, may have a stronger association with metabolic disorders compared to traditional metrics like BMI. This study aimed to evaluate the relationship between BRI and CKD risk in diabetic patients.Methods: Data from the National Health and Nutrition Examination Survey 1999-2018 were analyzed, including 6,971 diabetic participants. Baseline differences between the CKD and non-CKD groups were compared. Weighted multivariable logistic regression models were used to evaluate the association between BRI and CKD, adjusting for demographic, metabolic, and medication-related covariates. Subgroup analyses were conducted to explore potential effect modifiers, and mediation analysis assessed the role of HbA1c and other factors in the relationship between BRI and CKD.Results: BRI was significantly higher in the CKD group compared to the non-CKD group (P<0.001). Logistic regression showed a positive association between BRI and CKD risk (Model 1 OR=1.047, P=0.003), which remained significant after adjusting for demographics (Model 2 OR=1.087, P<0.001), clinical factors (Model 3 OR=1.095, P=0.005), and medication use (Model 4 OR=1.105, P=0.003). Subgroup analyses revealed stronger associations in younger patients, those with poorer metabolic profiles, or higher uric acid levels. Mediation analysis demonstrated that HbA1c served as a significant positive mediator in the relationship between BRI and CKD risk, whereas ALB showed a protective mediation effect.Conclusion: BRI is an independent predictor of CKD risk in diabetic patients and may be mediated through metabolic abnormalities (HbA1c) and nutritional status (ALB), suggesting its potential utility for early CKD risk assessment.DisclosureS. Fei: None. L. Guo: Research Support; Abbott, AstraZeneca, Bayer Pharmaceuticals, Inc, Eli Lilly and Company, Innovent Biologics, Merck & Co., Inc, MSD Life Science Foundation, Novo Nordisk A/S, Sanofi, Jiangsu Hengrui Pharmaceuticals Co., Ltd, Tonghua Dongbao. Q. Pan: None.FundingCapital's Funds for Health Improvement and Research (2024-1-4053)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-396-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 397-P: Association of Visit-to-Visit Variability of Metabolic Indicators
with the Progress of Proteinuria in Chinese Patients with Type 2 Diabetes
Mellitus-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 397-P
Abstract: Introduction and Objective: To explore the relationship between the variability of metabolic parameters and the development of proteinuria in patients with type 2 diabetes mellitus (T2DM).Methods: 1453 T2DM patients (median follow-up: 26 months) with at least 3 measurements of metabolic parameters and urinary albumin creatinine ratio (UACR) were analyzed from a cohort of 3297. Variability was assessed using standard deviation of serial measurements. Proteinuria progression was defined as UACR increase from normal (<30 mg/g) to microalbuminuria (30-299 mg/g) or macroalbuminuria (≥300 mg/g), or from microalbuminuria to macroalbuminuria.Results: T2DM patients with proteinuria progress exhibited significantly higher baseline age, body mass index (BMI), systolic blood pressure (SBP), waist circumference, prevalence of hypertension and stroke, UACR, C-reactive protein (CRP) levels, and proportion of GLP-1 receptor agonist use, as well as longer diabetes duration, compared to those without proteinuria progress. Conversely, they showed lower smoking and alcohol consumption rates, family history of diabetes, 1-hour postprandial blood glucose, serum creatinine, total cholesterol, and low-density lipoprotein levels. T2DM patients with proteinuria progress demonstrated significantly greater variability in BMI, SBP, diastolic blood pressure (DBP), uric acid, creatinine, and fasting blood glucose levels during follow-up. Furthermore, we found that high variability in creatinine levels was an independent risk factor for progressive proteinuria in T2DM patients during follow-up, even after adjusting for mean BMI, SBP, DBP, triglycerides (TG), uric acid (UA), and HbA1c levels.Conclusion: Creatinine level fluctuations independently predict proteinuria development and progression in T2DM. Close monitoring of creatinine variability and its stabilization are crucial for mitigating proteinuria risk.DisclosureY. Ma: None. L. Gu: None. G. Liang: None. R. Wang: None. Y. Wang: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-397-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 398-P: Renal Intraparenchymal Fat Is Linked to Renal Function Decline in
People with Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 398-P
Abstract: Introduction and Objective: People with diabetes have an increased risk to develop chronic kidney disease (CKD). How the ectopic accumulation of lipids in the renal compartments is related to nephropathy is not yet clear. In this study, we investigated the relationship of renal intra-parenchymal fat (RIPF) and kidney function as assessed from glomerular filtration rate (eGFR).Methods: Participants (n=221) from the German Diabetes Study (GDS), including people with type 1 (n=66), type 2 diabetes (n=55) and participants with normoglycemia (n=26) were retrospectively assessed for RIPF content by abdominal chemical-shift-encoded magnetic resonance imaging (MRI) and the water- and fat-reconstructed images were used to calculate fat fraction maps. The association of fat fraction with renal function was tested by multiple linear regression (n=145), adjusting for sex, age, body mass index (BMI), mean arterial pressure (MAP) and subcutaneous (SAT) and visceral adipose tissue (VAT) volumes. Further, the association of the fat fraction with the eGFR slope over follow-up (7.0±4.0 years) was tested (n=121).Results: An increase of 1% in MRI-based fat fraction was inversely associated with a 3.95±1.21 ml/min/1.73 m2 lower eGFR, independently of sex, age, BMI, MAP, VAT and SAT. Further, RIPF content was associated with a faster decline of eGFR (β=-0.57, *p=0.001) over a mean follow-up duration of 7.5 years, independent from all the included confounders.Conclusion: Renal intra-parenchymal fat is linked to lower eGFR and its decline, highlighting its potential as a biomarker for CKD in diabetes. Further studies are required to determine whether RIPF plays a causal role in diabetic nephropathy.DisclosureF.C. Michelotti: None. C. Möser: None. R. Koshiba: None. K.S. Massold: Stock/Shareholder; Dexcom, Inc., Sernova, Corp. O.P. Zaharia: None. M. Schön: None. K. Prystupa: None. K. Bódis: None. S. Trenkamp: None. Y. Kupriyanova: None. J. Meister: None. K. Jandeleit-Dahm: None. M. Roden: Research Support; Boehringer-Ingelheim. Advisory Panel; Echosens. Speaker's Bureau; Madrigal Pharmaceuticals, Inc. Advisory Panel; MSD Life Science Foundation. Board Member; Novo Nordisk. Advisory Panel; TARGET PharmaSolutions, Inc. V. Schrauwen-Hinderling: None. R. Wagner: Speaker's Bureau; Boehringer-Ingelheim, Novo Nordisk. Advisory Panel; Sanofi. Speaker's Bureau; Sanofi. Advisory Panel; Lilly Diabetes.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-398-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 399-P: Towards a Digital Twin Model for Predicting Renal Function Decline
in Type 2 Diabetes Using Longitudinal Electronic Health Records-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 399-P
Abstract: Introduction and Objective: T2D is a public health crisis and a leading cause of end-stage kidney disease (ESKD). This study aims to develop T2DTwin, a digital twin model to simulate T2D progression and predict complications, with a focus on modeling diabetic kidney disease progression using longitudinal electronic health records (EHRs).Methods: We identified adult T2D patients from the 2012-2021 OneFlorida+ longitudinal EHR data via a validated computable phenotyping algorithm, including those with at least 2 eGFR values during follow-up. Our T2DTwin model utilizes an Operator-Regression-based machine learning (ML) approach to learn complex dynamical systems from data, integrating time-varying and time-invariant information (e.g., sociodemographic, vitals, lab values, comorbidities, and medications). We implemented neural operators to model GFR to (1) forecast renal function trajectories (e.g., eGFR decline), and (2) assess the impact of modifiable predictors, like SGLT2 inhibitors.Results: Among 251,305 T2D patients (mean age 58.3 years), baseline eGFR ranged from 30.0 to 126.8 mL/min/1.73 m2, with a mean (SD) of 72.5 (23.6). T2DTwin showed strong predictive utility for eGFR changes over one year, achieving SMAPE of 10.6% (i.e., 10.6% off from the actual eGFR). We predicted risks of significant renal function decline (e.g., 30% eGFR reduction within 1, 3, and 5 years) and CKD stage changes (1-5), with F1 score, precision, and sensitivity of 0.78. SHAP analysis identified triglycerides and low density lipoprotein as important modifiable factors.Conclusion: T2DTwin leverages Operator-Regression to model complex dynamic systems like human body, offering scalability and adaptability over traditional ML methods. Its accurate predictions of renal function decline in T2D patients using longitudinal EHR have significant potential to enhance diabetic kidney disease management.DisclosureH. Chen: None. Y. Huang: None. L. Sun: None. A. Chen: None. J. Guo: None. J. Bian: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-399-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 400-P: A Novel Genetic Risk Score Can Identify People at Risk of Diabetes
Complications-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 400-P
Abstract: Introduction and Objective: Identifying risk of diabetes complications at diabetes onset is vital to a precision medicine approach to managing diabetes. A genetic risk score (GRS) could do this decades before positive biochemical tests. Therefore, we developed a novel GRS for predicting diabetic kidney disease (DKD), assessed its performance and analyzed clinical differences between genetic risk groups.Methods: The GRS was developed with data from >2000 subjects. Its performance was tested on 429 adults with type 1 or type 2 diabetes attending a tertiary hospital. Cases were those with eGFR <30 mL/min. Controls had diabetes for >10 years and eGFR >60 mL/min. Clinical differences between GRS groups were tested with sample t-test, Fisher’s exact or Chi2 test, as appropriate.Results: People with a high GRS had an OR of 9.40 for developing DKD (95% CI 5.78-17.57, p<0.0001). Those with low GRS and DKD were more likely to have a history of smoking, dyslipidaemia, hypertension, and other diabetes complications. Those with high GRS and DKD were also more likely to have other diabetes complications including cardiovascular disease. This group developed DKD more rapidly than those with low GRS and DKD. There were no statistically significant differences in HbA1c, BMI and duration of diabetes between those with and without DKD, in either risk group. A lower HbA1c throughout follow up did not affect progression to DKD.Conclusion: The GRS performed well in identifying risk of DKD. It also identified those with high risk of other diabetes complications.DisclosureA. Ali: None. K. Kishore: None. S. Golub: None. G. Morahan: Stock/Shareholder; Advanced Genetic Diagnostics. E.I. Ekinci: Research Support; Amgen Inc, Novo Nordisk, Lilly Diabetes, AstraZeneca, Endogenex, Versanis. Advisory Panel; Lilly Diabetes, Novo Nordisk.FundingDiabetes Australia Research Grant (Y22G-ALIA)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-400-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 401-P: The Diagnostic Efficacy of Optical Coherence Tomography
Angiographyin Detecting Diabetic Kidney Disease-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 401-P
Abstract: Introduction and Objective: This study aims to evaluate the diagnostic value of OCTA in DKD confirmed by renal biopsy pathology.Methods: This study employed a multicenter case-control study design. One hundred patients with type 2 diabetes from 3 hospitals in Beijing were selected and divided into DKD group (63 cases) and non-DKD group (37 cases) based on renal biopsy results. All patients underwent OCTA, digital fundus photography, medical history, and biochemical blood and urine tests. Compare the differences of parameters between two groups, and analyze the diagnostic efficacy of DKD through ROC curve analysis.Results: The study found that OCTA has high sensitivity and specificity in identifying diabetic retinopathy. The combination of OCTA and fundus photography significantly increased the detection rate of diabetic kidney disease, with a diagnostic efficacy greater than 85%. There were significant differences in the foveal arch circularity ratio, shallow and deep layer vascular linear density, shallow and deep layer blood flow perfusion density between the diabetic kidney disease group and the non-DKD group, with AUC values all greater than 70%.Conclusion: OCTA combination with fundus photography can effectively increase the detection rate of diabetic kidney disease.DisclosureL. Zhang: None. X. Zhu: None. T. Wei: None. J. Lu: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-401-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 402-P: Relationship between Average Glucose and HbA1c across GFR Stages
-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 402-P
Abstract: Introduction and Objective: HbA1c’s accuracy and precision decline in advanced CKD, commonly attributed to anemia. Whether other CKD factors influence its relationship with glycemia in those with preserved GFR is unclear. We examined the relationship between CGM-derived average glucose and HbA1c across GFR stages.Methods: We conducted a retrospective cohort study linking Dexcom/Libre CGM data to EHR from a large academic health system. Adults with diabetes were included if they had: (1) HbA1c measurements, (2) ≥10 days of CGM data within the preceding 3 months, and (3) ≥1 creatinine within 6 months. Linear mixed-effects models with participant-specific random intercepts were used to examine the longitudinal association of CGM-derived average glucose and HbA1c, adjusting for age, sex, and race. Interactions with GFR and hemoglobin were tested.Results: We included 1,598 patients (692 GFR Stage G1, 532 G2, 285 G3, 89 G4-5) with 4,662 CGM periods. Mean age was 57, 45% female, 74% White, and mean HbA1c was 7.1%. Spearman correlations between average glucose and HbA1c declined from 0.7 (G1) to 0.44 (G4-5), and slopes flattened with advancing GFR stages (Fig). In adjusted models, the association between average glucose and HbA1c was modified by GFR (P-interaction=0.001), but not by hemoglobin (P-interaction=0.5).Conclusion: The association between CGM-derived mean glucose and HbA1c weakens as GFR declines, independent of hemoglobin levels.Disclosure M. Tang: Research Support; Dexcom, Inc., American Heart Association. M.S. Putman: Consultant; Anagram Therapeutics. Research Support; Dexcom, Inc. Other Relationship; Vertex Pharmaceuticals Incorporated. D.M. Nathan: Advisory Panel; Lexicon Pharmaceuticals, Inc. D.J. Wexler: Other Relationship; Novo Nordisk. H. Zheng: None. S. Sanzone: None. A. Doria: Research Support; Abbott, Lexicon Pharmaceuticals, Inc, Dexcom, Inc. I. de Boer: Consultant; Alnylam Pharmaceuticals, Inc, Jaeb Center for Health Research, Boehringer-Ingelheim, Lilly USA LLC, Dexcom, Inc. Research Support; Dexcom, Inc. Consultant; Lexicon Pharmaceuticals, Inc, Novo Nordisk. Research Support; Novo Nordisk. S. Kalim: Consultant; Fresenius. Speaker's Bureau; Vistera.FundingAmerican Heart Association (AHA23POST1010825)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-402-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 403-P: Evaluating the Effect of Finerenone on Renal Markers in Patients
with Diabetic Nephropathy (Stage 1–3) Receiving Angiotensin Receptor
Blockers and SGLT2i Therapy-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 403-P
Abstract: Introduction and Objective: Evaluate the additional role of Finerenone (Fi) on renal markers (RM) in T2DM patients with diabetic nephropathy (DN) Stages 1-3, receiving angiotensin receptors blocker (ARB) [Valsartan {V} or Telmisartan {Tm}], SGLT2i (dapagliflozin) {D} & optimized for Blood Pressure (BP) <130/80mm for at least 1 yr.Methods: Between Oct’ 22 & Mar’ 23, 60 T2DM pt’s with DN irrespective of A1c, on regular F/U receiving D, ARB, Fi & optimized for BP (using CCB &/or Beta-blocker) were retrospectively analyzed. Pt’s were followed for 6 months. Weight-kg (W), BMI-kg/m2, SBP/DBP (mm Hg), lipid profile mg/dL (TC, LDL, TG, HDL), hs-CRP mg/L, NT-ProBNP pg/ml, eGFR (Cr & Cyst-C), K+ mEq/L & UACR μg/mg were analyzed every 2-3 moths. Exclusion: H/O any revascularization, IHD, hospitalization in last 1 year, eGFR < 30 & K+ > 5.5 mEq/L. Statistical analysis: Paired ‘t’ test assessed within-group comparisons. P-value < 0.05 was considered significant (S).Results: Baseline (B): 80% (eGFR > 60.0). 86.66% patients (UACR 30 - 300). Mean age-yrs (60.05 ± 10.21), W (74.25 ± 15.14), SBP (124.4 ± 13.7), DBP (78.32 ± 10.51), A1c (7.16 ±0.169), eGFRCr (88.96 ± 33.15), eGFRCy (65.2 ± 22.115), K+ (4.576 ± 0.45), UACR (170.76 ± 241.84), hsCRP (1.35 ± 1.13), NTProBNP (106.87 ± 100.68). Avg doses: V (112 ± 39.2), Tm (87.43 ± 43.37), Fi (12.67 ± 4.43). ARBs (66.66%), ARNI (33.33%), CCBs (33.33%), Beta-blockers (30%). B-6 mths: S reduction in UACR (101.348 ± 33.93, p<0.001) S increase in W (-0.8 ± 0.294, p = 0.025) were seen. Non-S reductions in SBP (1.33 ± 1.671, p = 1), DBP (1.9 ± 1.34, p = 0.486), A1c (0.038 ± 0.105, p = 1.000), eGFRCr (-0.713 ± 2.22, p = 1), eGFRCy (-6.0 ±3.26, p=0.063) K+ (-0.007 ± 0.048, p = 0.1), NTProBNP (11.018 ± 5.69, p = 0.174). Avg doses: V (96 ± 32), Tm (111.43 ± 55.42), Fi (16.70 ± 4.92).Conclusion: In T2DM pt’s with stage 1-3 nephropathy receiving SGLT2i (D), ARB & optimized for BP, the addition of Fi over 6 months led to significant 59.35% reduction in UACR.DisclosureV. Gupta: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-403-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 404-P: Long-Term HbA1c Variability and Risk of Hospitalization and
Mortality in End-Stage Kidney Disease Patients Undergoing Dialysis-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 404-P
Abstract: Introduction and Objective: HbA1c is recommended as the gold standard for assessing glycemic control; however, HbA1c is not a reliable indicator of glycemic control and outcomes in ESKD. We report the predictive value of HbA1c variability on hospitalizations and all-cause mortality in patients on dialysis.Methods: Patients with diabetes on dialysis >90 days at an academic institution from 1/2010 to 12/2023, and with >3 HbA1c measures, were included. HbA1c was measured quarterly. Coefficient of variation (CV, standard deviation divided by mean HbA1c) and variability index (VI, change of 0.5% compared to previous value) were used as predictors of outcome. The association between HbA1c variability, hospitalization, and all-cause mortality was assessed using Cox hazard models, with HbA1c values as continued variables and tertiles of distribution.Results: Of 979 included patients, T2D: 92.5%, age: 56±13 years, male: 52.5%, African American: 88.7%, hemodialysis: 80.9%, and mean follow-up: 4.9±2.9 years. Both HbA1c variability indices- CV (p<0.001) and VI (p=0.002), at their highest tertiles- CV (HR 1.42, CI: 1.10-1.83) and VI (HR 1.44, CI: 1.12-1.85) were associated with increased hospitalizations and all-cause mortality (Figure).Conclusion: Glycemic variability was strongly associated with hospitalizations and all-cause mortality in ESKD patients on dialysis.DisclosureP.H. Kim: None. I.A. Castro-Revoredo: None. G. Umpierrez: Research Support; Abbott, Dexcom, Inc., Bayer Pharmaceuticals, Inc, Corcept Therapeutics. Advisory Panel; Dexcom, Inc., GlyCare Health. J.E. Navarrete: None.FundingDexcom, Inc. (00004617)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-404-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 405-P: Weight-Adjusted Insulin Dose Is Positively Associated with
Estimated GFR (eGFR) in Type 1 Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 405-P
Abstract: Introduction and Objective: EGFR is one of the current clinical methods for identifying risk for diabetic kidney disease in patients with type 1 diabetes (T1D). Initiating insulin infusion in T1D has been shown to increase overall sodium reabsorption within the renal tubules. However, the potential association between the magnitude of insulin dosage and eGFR has not been evaluated. We used 30-year data from the Epidemiology of Diabetes Complications (EDC) cohort of T1D to assess the hypothesis that weight-adjusted mean daily insulin dose (insulin dose per weight, INSWT) is positively associated with eGFR.Methods: Measurements of INSWT (self-reported total daily insulin units divided by measured weight) and eGFR (calculated using the CKD-EPI formula) were taken at baseline and at 2, 4, 6, 8, 10, 18, 25, and 30 years of follow-up. Eligibility comprised age >=18 years, eGFR >=60 mL/min/1.73 m² at baseline (1986-88), and availability of at least two INSWT and eGFR measurements.Results: INSWT was generally lower in women vs men throughout follow-up (0.65 vs. 0.71, p<0.0001). In linear mixed model analysis (n=510, mean age: 28.3 years, T1D duration: 19.7 years) adjusting for sex, HbA1c, diabetes duration, hypertension, and non-HDL cholesterol, a positive association was observed between INSWT and eGFR (β±SE: 0.13±0.02 per 0.23 u/Kg of insulin per body weight, p<0.0001). A significant sex by INSWT interaction was found (p=0.0009) such that the INSWT-eGFR association was stronger in women.Conclusion: In our longitudinal cohort of T1D, weight-adjusted insulin dose was positively associated with eGFR, independent of glycemic control. Although challenging to confirm with observational data, the presence of such an association may impede the accurate detection of early diabetic nephropathy in T1D due to variability in insulin titration, particularly in females. Future studies should investigate the potential causal impact of long-term exogenous insulin dosing on kidney function.DisclosureM. Mosslemi: None. R.G. Miller: None. T.J. Orchard: None. T. Costacou: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-405-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 406-P: The Risk Factor Changes for Diabetic Kidney in T2DM during 13-Year
Period in Beijing Community-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 406-P
Abstract: Introduction and Objective: It is well known that diabetic kidney (DN) disease is a risk factor for cardiovascular diseases (CVD) in patients with type 2 diabetes mellitus (T2DM). The aim of this study is to investigate the risk factor changes for DN in T2DM during 13-year period in Beijing community.Methods: 1,428 patients with T2DM in the Beijing community were enrolled in 2008, while 1,267 patients were enrolled in 2021. All patients were divided into two groups. Patients without DN were named as the Non-DN group; Patients with DN were named as the DN group. Chronic kidney disease staging was categorized using AER (mg/d) and eGFR (mL/min/1.73 m2).Results: In 2008, there were significant differences between Non-DN group and DN group in comparison of demographic and clinical characteristics, such as age, gender, the proportion of people with smoker, the duration of DM, BMI, WHR, neck circumstance, SBP, DBP, the levels of HbAlc, HDL-c and uric acid (P<0.05). In 2021, when compared with the Non-DN group, the proportion of people with smoker, BMI, heart rate, DBP, the levels of PPG and uric acid were higher in the DN group (P<0.05). The potential confounding factors for DN progression showed that SBP and PPG were independent risk factors in 2008, while neck circumstance, total cholesterol and LDL-c were independent risk factors for DN in 2021.Conclusion: In 2008, blood pressure and blood glucose were the main risk factor for DN progression. From 2008 to 2021, the risk factors of DN changed to clinical characteristics reflecting obese and lipid profiles for T2DM in the community. Interventions should be more up-to-date and focus on weight and lipid management.DisclosureX. Zhang: None. M. Lu: None. S. Yuan: None.FundingA Capital Medical Development Foundation of China (2007-1035), a Grant of Special Scientific Research on Capital Health Development (2011-2005-01,2016-1-2057), Beijing Municipal Science & Technology Commission (Z151100004015021), BRIDGES Grant from the International Diabetes Federation.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-406-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 407-P: Higher Serum Adiponectin Levels Predict Poorer Outcomes in Patients
Undergoing Hemodialysis-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 407-P
Abstract: Introduction and Objective: While adiponectin (ADPN) has anti-inflammatory and anti-atherosclerotic effects, many studies have shown that higher serum ADPN levels predict poorer prognosis in patients with cardiovascular disease (CVD) or chronic kidney disease (CKD). This study investigated the relationship between serum ADPN levels and survival in CKD patients undergoing hemodialysis.Methods: Total ADPN levels were measured using serum from 518 patients who participated in a prospective observational cohort study, and the associations with all-cause mortality, CVD mortality, non-CVD mortality, new CVD events and subsequent mortality, and hospitalization due to infection and subsequent mortality were analyzed using the Kaplan-Meier method and multivariate Cox proportional hazards model.Results: The median serum ADPN level was 18.3 μg/mL at baseline. During the 5-year follow-up, 107 deaths occurred, with 39 deaths due to CVD, 48 deaths due to non-CVD, and 20 deaths due to unknown causes. Higher ADPN levels were predictors of all-cause mortality (hazard ratio (HR) [95% CI] 2.17 [1.41-3.33]), CVD mortality (HR 4.78 [2.26-10.13]), and non-CVD mortality (HR 2.19 [1.11-4.45]). Regarding CVD mortality, higher ADPN levels were associated with both new CVD events (HR 1.51 [1.11-2.05]) and subsequent death (HR 2.28 [1.30-4.05]). On the other hand, higher ADPN levels were not associated with hospitalization for infection (HR 1.01 [0.74-1.39]), the main cause of non-CVD mortality, but were associated with mortality after hospitalization for infection (HR 2.30 [1.17-4.63]).Conclusion: Higher ADPN levels were associated with higher risk of all-cause mortality in CKD patients undergoing hemodialysis. Since ADPN was associated with both death after CVD and infection events, a higher ADPN may be a marker for fragility/frailty or lower resilience.Disclosure T. Morioka: Research Support; Boehringer-Ingelheim. T. Shoji: None. Y. Natsuki: None. Y. Kakutani: None. A. Ochi: None. S. Nakatani: None. K. Mori: Research Support; Mitsubishi Tanabe Pharma Corporation, Kyowa Kirin Co., Ltd, Sumitomo Dainippon Pharma Co., Ltd. Speaker's Bureau; Mitsubishi Tanabe Pharma Corporation, AstraZeneca, Novo Nordisk, Boehringer-Ingelheim, Kyowa Kirin Co., Ltd, Eli Lilly and Company. Y. Tsujimoto: None. M. Emoto: Speaker's Bureau; Novo Nordisk, Kyowa Kirin Co., Ltd. Research Support; Boehringer-Ingelheim.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-407-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 408-P: Assessing Individual Estimated GFR Trajectory on GLP-1RA Use for
Kidney Protection-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 408-P
Abstract: Introduction and Objective: After landmark FLOW trial, GLP-1RA might be considered 4th pillar approach in people with type 2 diabetes (T2D) for kidney protection. But algorithms how we should use these therapies are not yet known. We evaluated add-on effects of GLP-1RA in persons with T2D treated by SGLT2i by assessing individual eGFR trajectory.Methods: Individual eGFR slopes in persons with T2D on CKD stage 3-4 (n=75) treated by SGLT2i were analyzed. By tracing eGFR slopes, the most rapid slopes were calculated individually from the data for 46±20 months before using SGLT2i and 58±25 months after adding it. GLP-1RA (semaglutide in 15%, liraglutide or duraglutide) was initially or additionally used in 55% (41/75). Characteristics at baseline; average age was 69.1±12.2 yr-old, the duration of diabetes was 15.4±10.1 yrs, and macroalbuminuria (Macro-Alb) existed in 49%. Observation period was extended from the previous study.Results: 1) Proportion of responders to SGLT2i (defined as their ratios of slopes are less than 1.0 after addition of SGLT2i) in each stage were as follows: stage 3a; (21/29), stage 3b; (23/28), stage 4; (16/18). Slopes in responders (60/75) were improved as follows, -7.5±9.7 to -0.8±2.8ml/min/1.73m2/year (P<0.01) with GLP-1RA use in 55%. Slopes in non-responders (15/75) were worsened as follows, -1.7±2.0 to -3.3±3.3ml/min/1.73m2/year (P<0.01), despite GLP-1RA use in 53%. 2) Slopes in rapid decliners (defined as the most rapid individual eGFR slope greater than -10.0ml/min/1.73m2/y) (13/75) were improved from -18.9±16.4 to -1.2±3.2ml/min/1.73m2/year (P<0.01) by combined use of GLP-1RA in 85% (11/13). 3) Sub-analysis; stepwise use of GLP-1RA and SGLT2i to the persons with nephrosis in 46% (5/11), Macro-Alb in 82% (9/11), baseline slopes -16.7±19.8 were improved to -5.0±5.8 (P<0.05) by adding GLP-1RA, then to -2.5±3.8 ml/min/1.73m2/year (vs baseline: P<0.03) by adding SGLT2i.Conclusion: On GLP-1RA use, assessing individual eGFR trajectory is important for renal benefits.DisclosureK. Kashima: None. H. Shimizu: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-408-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 409-P: The Prevalence and Factors Associated with CKD Remission in
Patients with Type 2 Diabetes Mellitus-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 409-P
Abstract: Introduction and Objective: Chronic kidney disease (CKD) in patients with diabetes is well known to become the major leading cause of end stage renal disease and was believed to be an irreversible and progressive process. Yet, massive evidence indicated that new therapeutic regiments may induce remission in patients with type 2 diabetes mellitus (T2DM).Methods: A retrospective longitudinal study was performed in T2DM patients who had been followed-up for at least 3 years in diabetes-specific polyclinics. The CKD stage was defined according to the KDIGO definition. The definition of CKD remission was defined as patients present evidence of decreased eGFR (<=60 ml/min/1.73m2) or albuminuria (> 30 mg/gm) in at least two out of three consecutive measurement without any accompanied kidney disease, their eGFR returned to > 60 ml/min/1.73m2 and UACR < 30 mg/gm sustained at least for 1 year during follow-up after management. Multivariate Cox proportional hazard model analyses were used to identify independent factors associated with change in CKD.Results: A total of 7,761 patients were enrolled into the study with a mean follow-up for 7.1 years. The prevalence of CKD was 43.1%. Of these patients with CKD, progression was observed in 27.3%, regression was 11.0% and 23.1% got remission. Factors associated with a decreased likelihood of CKD remission, as identified through multivariate Cox proportional hazard model analysis, included male gender, HbA1c, uACR, and body mass index (BMI). Conversely, healthy diabetic self-management behaviors, statin prescription, and insulin treatment were positive factors associated with remission. The prescription of, ACEI/ARB, SGLT2i, MRA (finerenone), and GLP1RA were not associated with CKD remission.Conclusion: Our data indicates that CKD remission is common in real-world practice. This finding underscores the critical role of lifestyle interventions, effective metabolic control may induce CKD remission among patients with T2DM.DisclosureT. Lee: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-409-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 410-P: Development and Validation of a Risk Score for Predicting the
Initiation of Dialysis in People with and without Diabetes Mellitus-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 410-P
Abstract: Introduction and Objective: Dialysis is known to predispose patients to a lower quality of life as well as higher rates of cardiovascular events and mortality, regardless of diabetes. Identifying predictors for starting dialysis is of relevance in clinical practice and care. Therefore, we sought to determine whether a risk score could be developed and validated to predict the initiation of dialysis in a Japanese population.Methods: We analyzed data from a nationwide claim database involving 792,956 participants during 2008-19. We weighted risk according to the following variables: men, BMI ≥25, systolic blood pressure (SBP) (130-139, ≥140mmHg), smoker, no regular breakfast, not sleeping well, no regular exercise, HbA1c (7.5-7.9%, ≥8%), LDLC ≥140mg/dL, HDLC <40mg/dL, eGFR (75-89, 60-74, 45-59, 35-44, 30-34, <30 mL/min/1.73 m²), and proteinuria (UP; low, moderate, and severe levels) according to logistic regression in a derivation cohort and validated using the same cohort.Results: Low eGFR and the presence of UP had a strong effect on the incidence of dialysis, followed by high HbA1c and SBP levels. The area under the curve (AUC) for the derivation cohort was 0.95 (95% CI, 0.93-0.98). The AUC for the validation cohort was 0.95 (0.92-0.98). The absolute estimated probability of dialysis in people with a score ≥30 was more than 10%.Conclusion: In summary, our results indicated that a simple risk score was useful in predicting the initiation of dialysis in a Japanese population. The use of risk scores may enable lifestyle modification and risk management from an early stage to prevent the initiation of dialysis.DisclosureT. Osawa: None. K. Fujihara: None. M.H. Yamada: None. T. Sato: None. M. Kitazawa: None. Y. Matsubayashi: None. T. Yamada: None. S. Kodama: None. H. Sone: Research Support; Novo Nordisk, Astellas Pharma Inc, Kyowa Kirin Co., Ltd, Sumitomo Dainippon Pharma Co., Ltd, HITACHI, NEC, NTT, KDDI, Healthbit, Niigata Prefecture, Agano City, JMDC.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-410-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 411-P: Renal Arteriolar Hyalinosis Predicts Progressive Renal Functional
Decline in Persons with Type 2 Diabetes Showing Macroalbuminuria prior to
Impaired Glomerular Filtration-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 411-P
Abstract: Introduction and Objective: Clinical course of diabetic kidney disease (DKD) is diverse. Previously, we reported that renal arteriolar hyalinosis (AH) predicted the onset of macroalbuminuria prior to the onset of eGFR<60 ml/min/1.73m2 in persons with type 2 diabetes. However, it remains unclear whether individuals who develop macroalbuminuria before eGFR<60 ml/min/1.73m2 have more progressive decline in renal function compared to those in whom eGFR declines < 60 prior to macroalbuminuria.Methods: Thirty-three persons with type 2 diabetes (22 men; age, 46±10 years; eGFR, 92.7±18.4 mL/min/1.73 m2, 17 normoalbuminuria, 16 microalbuminuria) underwent percutaneous renal biopsy and were divided into 3 groups, onset of macroalbuminuria in advance (MA; n=9), onset of eGFR<60 in advance (G; n=11) and no onset of CKD (C; n=13) during the observation period (21±6 year). Light and electron microscopy-based morphometric analyses were performed to quantitatively evaluate glomerular and interstitial structural changes.Results: All of study subjects had typical histological changes of diabetic nephropathy. During observation period, induction of hemodialysis (n=3) was observed in only MA group. The slope of eGFR in the MA group (-4.34±2.16 ml/min/1.73m2/year) was significantly higher than the G (-1.48±0.90, p<0.0001) and C (-0.66±0.69, p<0.0001) groups. The slope of eGFR was not different between G and C groups. Multiple regression analysis showed that both AH (p=0.0129) and MA (p<0.0001) independently affected the slope of eGFR after renal biopsy.Conclusion: Persons with type 2 diabetes having increased AH exhibited macroalbuminuria prior to eGFR decline experienced a more progressive decline in renal function. It is necessary to closely monitor the slope of eGFR in persons with type 2 diabetes once they develop macroalbuminuria.DisclosureT. Moriya: None. A. Suzuki: None. A. Hayashi: None. T. Miyatsuka: Speaker's Bureau; Eli Lilly and Company, Novo Nordisk, Sumitomo Dainippon Pharma Co., Ltd, Kowa Company, Ltd, Mitsubishi Tanabe Pharma Corporation, Abbott Japan Co., Ltd, Novartis Pharmaceuticals Corporation, Ono Pharmaceutical Co., Ltd.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-411-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 412-P: Nutritional Risk as a Predictor of Hypoglycemia in People with Type
2 Diabetes Undergoing Hemodialysis-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 412-P
Abstract: Introduction and Objective: People with type 2 diabetes undergoing hemodialysis (T2HD) are reported to exhibit distinct glucose profiles. However, the relationship between these profiles and nutritional status remains unclear.Methods: We analyzed sensor glucose levels (SGL) from continuous glucose monitoring (CGM) data collected in 116 T2HD (80 males, age 61 years, HbA1c 6.5%, glycated albumin [GA] 21.1%). Patients were stratified into two groups based on the Geriatric Nutritional Risk Index (GNRI): those without nutritional risk (GNRI > 98, n = 60) and those with suspected nutritional risk (GNRI ≤ 98, n = 56). Clinical parameters and CGM metrics were compared between the groups.Results: The GNRI ≤ 98 group was older (64 vs. 58 years, P = 0.0099) with lower BMI (21.0 vs. 27.1, P < 0.0001), hemoglobin (10.2 g/dL vs. 11.1 g/dL, P = 0.0018), albumin (3.4 g/dL vs. 3.9 g/dL, P < 0.0001), and HbA1c (6.2% vs. 6.9%, P = 0.0033). GA levels were similar (22.0% vs. 20.2%, P = 0.1608). No differences were observed in CGM metrics, including mean SGL, standard deviation (SD), coefficient of variation (%CV), time in range (TIR, 70-180 mg/dL), time below range (TBR, < 70 mg/dL), or time above range (TAR, > 180 mg/dL). The incidence of all-cause hypoglycemia was higher in the GNRI ≤ 98 group (39.3% vs. 23.3%; P = 0.0628). Hemodialysis (HD)-induced hypoglycemia was more frequent in the GNRI ≤ 98 group (30.4% vs. 13.3%; P = 0.0248).Conclusion: In T2HD with GNRI ≤ 98, HbA1c levels were significantly lower than in those with GNRI > 98 despite comparable GA and mean SGL. Furthermore, HD-induced hypoglycemia was significantly more frequent, indicating that nutritional risk is associated with greater vulnerability to hypoglycemia in T2HD.DisclosureA. Hayashi: None. H. Sogabe: None. R. Takaesu: None. S. Tsuji: None. T. Moriya: None. T. Miyatsuka: Speaker's Bureau; Eli Lilly and Company, Novo Nordisk, Sumitomo Dainippon Pharma Co., Ltd, Kowa Company, Ltd, Mitsubishi Tanabe Pharma Corporation, Abbott Japan Co., Ltd, Novartis Pharmaceuticals Corporation, Ono Pharmaceutical Co., Ltd.FundingJSPS KAKENHI (JP22K15674); Grants from Japan Association for Diabetes Education and Care (2023-FND-012 )
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-412-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 413-P: MASLD in Adults with Type 1 Diabetes Mellitus—Association
with Hyperglycemia-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 413-P
Abstract: Introduction and Objective: Metabolic dysfunction-associated steatotic liver disease (MASLD) is associated with cirrhosis, cardiovascular disease (CVD) and increased mortality in type 2 diabetes. Data in type 1 diabetes (T1D) are limited. We examined the prevalence of and risk factors for MASLD in adults with T1D in the Epidemiology of Diabetes Interventions and Complications (EDIC) study.Methods: Hepatic steatosis (controlled attenuation parameter [CAP] score ≥274 dB/m) and clinically significant fibrosis (liver stiffness measurement ≥8.0 kPa) were evaluated in 746 participants by vibration-controlled transient elastography (FibroScan®). Clinical signs of peripheral neuropathy were defined as a score >2 on the Michigan Neuropathy Screening Instrument. CVD events were adjudicated using standardized measures.Results: Current mean age and T1D duration were 64 and 43 yrs, respectively; 53% were male; mean BMI was 29.1 kg/m2 and HbA1c 7.2%. Prevalence of steatosis was 38% (8% mild, CAP 274-287; 8% moderate, 288-302; 22% severe, ≥302) and 12% had fibrosis. Male sex, higher BMI, mean chronic HbA1c and triglycerides, and lower HDL-C were associated with higher risk of both steatosis and fibrosis. In age and sex adjusted models, neuropathy was associated with higher odds of steatosis (OR [95% CI] 1.66 [1.21, 2.28]), while CVD and mean chronic HbA1c were associated with higher odds of fibrosis (1.86 [1.05, 3.29] and 1.47 [1.12, 1.93] per 1% increase in HbA1c, respectively). Only the association of fibrosis with mean chronic HbA1c (1.37 [1.02, 1.83]) remained significant after further BMI adjustment.Conclusion: MASLD affects over one-third of the individuals with long-duration T1D included in this study; 12% have clinically significant fibrosis, a predictor of hepatic decompensation, mortality, and liver cancer. These findings support the ADA recommendations to screen for MASLD in T1D in the face of obesity and other risk factors, and highlight the association between glycemic control and fibrosis.Disclosure K. Cusi: Research Support; Boehringer-Ingelheim, Echosens, Inventiva, Perspectum Ltd, LabCorp. Consultant; Arrowhead Pharmaceuticals, Inc, AstraZeneca, TERNS Pharmaceuticals, 89bio, Inc, Boehringer-Ingelheim, Eli Lilly and Company, Novo Nordisk A/S, Sagimet Biosciences. V.R. Trapani: None. H. Karanchi: None. B.H. Braffett: None. I. Bebu: None. R. Gubitosi-Klug: None. M. Bott: None. G.M. Lorenzi: None. V. Arends: None. C.K. Lovell: None. D.M. Nathan: Advisory Panel; Lexicon Pharmaceuticals, Inc. A. Sanchez: Advisory Panel; Madrigal Pharmaceuticals, Inc, IPSEN. Research Support; AbbVie Inc, Gilead Sciences, Inc, Takeda Pharmaceutical Company, Merck & Co., Inc, Inventiva Pharma, Boehringer-Ingelheim. W. Sivitz: None.FundingNational Institutes of Health (U01 DK094176 and U01 DK094157)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-413-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 414-P: The Efficacy and Safety of Dapaglifrozin in Type 1 Diabetic
Patients with Diabetic Kidney Disease in Zhongshan, China-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 414-P
Abstract: Introduction and Objective: Limited treatment of diabetic kidney disease (DKD) for patients with type 1 diabetes (T1D) was obtained at present. It was shown in previous studies that SGLT-2 inhibitor contributed to improving the albuminuria in patients with T2D, but the benefits and safety of it in T1D were still undefined.Methods: A total of 33 type 1 diabetic patients with DKD aged 18 to 75 from the Registry Study of T1D in Zhongshan, China participated in this randomized controlled trial. With originally existing treatments of insulin therapy and ACEI/ARB, patients randomly assigned to be treated with dapagliflozin (DAPA group, n = 18, 5mg/day of dapagliflozin for the first 8 weeks and 10 mg/day for the following 12 weeks) were compared against those treated without SGLT-2 inhibitor (control group, n=15).Results: At baseline, there were no significant differences in age, duration of T1D, daily insulin dosage, HbA1c, urine albumin-creatinine ratio (UACR), serum creatinine (SR), eGFR and the incidence of hypoglycemia between the two groups. After 20 weeks’ follow-up, changes of the daily insulin dosage, HbA1c, SR and eGFR were not significantly different between the two groups. While the UACR decreased in DAPA group [102.7 (29.3, 331.1) mg/g vs. 169.6 (84.3, 504.1) mg/g, p = 0.001)] but did not change significantly in the control group [228.5 (62.6, 1149.5) mg/g vs. 251.3 (72.9, 561.5) mg/g, p = 0.363)], and the changes of the UACR were significantly different between the DAPA group and the control group [-86.65 (-177.65, -15.25) mg/g vs. 11.2 (-52.7, 65.4) mg/g, p = 0.001]. There were 2 cases of urinary tract infection in the DAPA group, but no increase in the incidence of DKA or hypoglecmia was observed in both groups.Conclusion: The results indicated that dapaglifrozin is effective in improving the albuminuria but neither improve the glycemic control nor increase the incidence of DKA or hypoglycemia in T1D. Further study is necessary to explore its efficacy and safety in T1D.DisclosureB. Zhu: None. L. Qiu: None. Q. Ye: None. W. Wu: None. C. Yang: None.FundingZhongshan Social Commonweal Science and Technology Research Project (2021B1021)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-414-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 415-P: Proteinuria and Progression of Kidney Disease in Patients with T2D
Treated with SGLT2i and GLP-1RA—A Target Trial Emulation-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 415-P
Abstract: Introduction and Objective: Several clinical trials have shown that SGLT2i and GLP1-RA reduce progression of kidney disease in patients with T2D. It is not known whether these medications have renoprotective effects both in patients with and without proteinuria.Methods: We emulated a target trial using nationwide dataset from 12 US health systems and insurance plans for patients with T2D at moderate CV risk, hyperglycemia (HbA1c 7.0-11.0%) and with eGFR ≥ 45 ml/min/1.73m2 who initiated a second T2D medication after metformin between 1/1/13 and 12/31/22. We compared patients initiating a) SGLT2i or GLP1-RA or b) sulfonylureas to patients initiating DPP4i, stratifying by the presence of proteinuria (ACR ≥ 30 mg/g). We estimated 5-year risk of a composite nephropathy outcome (doubling of serum creatinine or eGFR < 15) after adjustment for demographics, comorbidities and laboratory values.Results: We studied 76,263 patients (14,067 with and 62,196 without baseline proteinuria) followed for a median of 32 (IQR 18-57) months, with a median age of 60 (IQR 51 - 68) years and median baseline HbA1c of 7.8% (IQR 7.3% - 8.5%) Of these, 26,306 patients initiated either an SGLT2i or a GLP1-RA, 36,059 initiated a sulfonylurea and 13,898 initiated a DPP4i. A total of 1,512 (2.0%) of patients experienced the composite nephropathy endpoint. The estimated 5-year risk ratios (95% CI), compared to DPP4i, were 0.57 (95% CI 0.40-0.79) for the combined SGLT2i-GLP1-RA arm among patients with proteinuria and 1.07 (95% CI 0.86-1.32) for patients without proteinuria. Sensitivity analyses among patients with a baseline eGFR < 60 showed similar results. There was no evidence of effect modification by proteinuria for sulfonylureas vs. DPP4i.Conclusion: Patients with T2D treated with an SGLT2i or GLP1-RA as a second agent after metformin had a lower risk of incident / worsening nephropathy compared with patients treated with DPP4i only if they had baseline proteinuria.Disclosure A. Turchin: Consultant; Novo Nordisk. Research Support; Eli Lilly and Company. Consultant; Proteomics International. L. Petito: Advisory Panel; Patient-Centered Outcomes Research Institute. Research Support; Omron Healthcare Co., Ltd. Consultant; Ciconia Medical. E. Hegermiller: None. R.M. Carnahan: None. A.R. Devries: None. S. Goel: None. M. Lansang: Research Support; Abbott, Dexcom, Inc., Neuro Solutions 100. M.E. McDonnell: Research Support; Dexcom, Inc. V. Nair: None. E.L. Priest: Research Support; Boehringer-Ingelheim, AstraZeneca, Vifor Pharma, Owkin. V. Willey: Other Relationship; Carelon Research. A.F. Kaul: None. M. Hernan: None.FundingPCORI DB-2020C2-20308
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-415-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 416-P: Relationship of Free Light Chains and Polymorphisms of the
Endocannabinoid Receptor CNR1 and Fatty Acid Amide Hydrolase to Chronic
Kidney Disease-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 416-P
Abstract: Introduction and Objective: Endocannabinoidsystem (ECS) mediates metabolism and inflammation in multiple organs. Polymorphisms in EC receptor type 1 (CNR1) gene 3813A/G and 4895A/G and in fatty acid amide hydrolase (FAAH) C385CA are associated with obesity, a cause of chronic kidney disease (CKD). ECS signaling is linked to CKD due to tubulo-glomerular damage and fibrosis, specifically, viaCNR1. Free light chains (FLCs), kappa (κ) and lambda (λ) are a marker of tubular dysfunction. Objective was to explore whether polymorphisms in CNR13813A/G, CNR14895A/G, or FAAH C385CA were associated with urinary and plasma κ and λ FLCs in those with CKD (eGFR < 60 mL/min/1.73 m2) and without CKD (eGFR > 60 mL/min/1.73 m2); and assess their correlation to CKD.Methods: This cross-sectional study enrolled 637 subjects (53. 7% female, 49.2% AAs; 69.7% had body mass index ≥30 kg/m2). Plasma FLC and urinary FLC (UFLC) levels were compared in those with and without CKD with Wilcoxon rank-sum tests. Logistic regression models were performed to assess associations between the polymorphisms, FLC, and CKD.Results: Plasma κ LC (PκLC) was significantly higher in those with CKD (median 21.7 mg/L, IQR = 17.3, 33.3 mg/L, P=0.0002) compared to those without CKD (13.7 mg/L, IQR = 10.5, 17.9 mg/L). Plasma λ LC levels were significantly higher in those with CKD (16.54 mg/L, IQR = 14.54, 23.99 mg/L, P=0.017). Logistic regression between CKD and PκLC suggested in those with eGFR < 60 mL/min/1.73 m2 PκLC are higher by 20% (odds ratio [OR] = 1.05, 95% CI: 1.01, 1.10, P =0.021). Logistic regression analysis did not reveal a significant association between CNR113813A/G, CNR14895A/G, FAAHC385CA and CKD or between CKD and ULC.Conclusion: In a population with high prevalence of obesity, PκLC and PλLC were higher in those with CKD, likely due to decreased renal clearance. Polymorphisms in ECS genes CNR13813A/G, CNR14895A/G, and FAAHC385CA were not significantly associated with CKD.Disclosure T.K. Thethi: Speaker's Bureau; Eli Lilly and Company. Consultant; Novo Nordisk. Research Support; Fractyl Health, Inc., Novo Nordisk. S. Tye: None. A. Bilal: None. S. Liu: None. R.E. Pratley: Consultant; AbbVie Inc. Stock/Shareholder; Altanine, Inc. Consultant; Amgen Inc, AstraZeneca. Other Relationship; Bayer AG, Bayer Pharmaceuticals, Inc, Biomea Fusion. Consultant; Boehringer-Ingelheim. Other Relationship; Carmot Therapeutics, Inc, Corcept Therapeutics, Dompé, Eli Lilly and Company, Endogenex. Consultant; Endogenex. Other Relationship; Fractyl Health, Inc., Gasherbrum Bio, Inc. Consultant; Genprex, Getz Pharma, Hanmi Pharm. Co., Ltd, Intas Pharmaceuticals Ltd, Lexicon Pharmaceuticals, Inc, Lilly USA LLC. Speaker's Bureau; Lilly USA LLC. Other Relationship; Metavention, Novo Nordisk, Novo Nordisk. Speaker's Bureau; Novo Nordisk. Other Relationship; Pfizer Inc, Poxel SA. Consultant; Regeneron Pharmaceuticals. Other Relationship; Sanofi. Consultant; Scholar Rock. Other Relationship; Sun Pharmaceutical Industries Ltd. V. Fonseca: Stock/Shareholder; Amgen Inc. Consultant; Corcept Therapeutics. Speaker's Bureau; Eli Lilly and Company. Consultant; Regeneron Pharmaceuticals, Abbott Diagnostics. V. Batuman: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-416-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 417-P: Increasing Pyruvate Flux to Attenuate UUO-Induced Kidney Fibrosis
and Improve Mitochondrial Dysfunction-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 417-P
Abstract: Introduction and Objective: Chronic kidney disease (CKD) is characterized by increased reliance on glycolysis and reduced oxidative phosphorylation, leading to mitochondrial dysfunction. This study investigates whether enhancing pyruvate flux can shift metabolism from glycolysis to mitochondrial pathways, improving CKD outcomes.Methods: Mice with enhanced pyruvate flux were subjected to unilateral ureteral obstruction (UUO). After 14 days, kidneys were collected for analysis. Mitochondrial function was evaluated by measuring mitochondrial ROS markers (nitrotyrosine, 4-HNE) via immunohistochemistry, mitochondrial membrane potential (TMRM staining), and oxygen consumption rate (XF analyzer). Fibrosis markers (collagen I, α-SMA, PAI-1, fibronectin) were assessed at RNA and protein levels. TGF-β-treated kidney cells were used to mimic in vivo conditions.Results: Enhanced pyruvate flux significantly reduced fibrosis markers in UUO-treated mice compared with controls. Glycolytic activity decreased, while mitochondrial function improved, as evidenced by reductions in ROS (nitrotyrosine, 4-HNE), increased mitochondrial membrane potential, and enhanced oxygen consumption.Conclusion: Enhancing pyruvate flux restores mitochondrial function and attenuates kidney fibrosis in CKD. This metabolic approach offers a promising therapeutic strategy for CKD management.DisclosureM. Kim: None. C. Oh: None. W. Choi: None. I. Lee: None. J. Jeon: None.FundingKorean Health Industry Development Institute (KHIDI) (HR22C1832, RS-2024-00437643); National Research Foundation of Korea (2022R1A2B5B03001929, 2021R1A5A2021614, 2022R1C1C101089811)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-417-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 418-P: Impact of Intensive Lifestyle Intervention on Kidney Disease
Progression in People with Type 2 Diabetes—The Look AHEAD Study-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 418-P
Abstract: Introduction and Objective: T2DM increases CKD risk by 2-3 fold. While lifestyle intervention (ILI) is shown to reduce very high-risk CKD in individuals with T2DM, its impact on earlier CKD progression and kidney function vs diabetes support and education (DSE) is less clear.Methods: This Look AHEAD ancillary study included males and postmenopausal females with T2DM and BMI ≥25 kg/m2 over 8 years. High-risk CKD is defined as eGFR ≤60 mL/min/1.73 m² or urine albumin to creatinine ratio (ACR) >300 mg/g. Cox regression assessed CKD progression, while mixed-effects models analyzed longitudinal eGFR trajectories, adjusting for age and baseline diabetes duration.Results: At baseline, participants had a mean age of 60.2 ± 6.2 years, eGFR of 90.5 ± 15.0 mL/min/1.73 m², median ACR 8.9 mg/g (5.4-19.0), and diabetes duration of 5 years (2-10). Over 8 years, 20% (N=468) progressed to high-risk CKD. ILI reduced CKD risk vs DSE (HR: 0.80; 95% CI: 0.67-0.96). ILI slowed eGFR decline vs DSE (-1.45 vs. -1.59 mL/min/1.73 m² annually, p=0.07). The eGFR difference between groups widened over time, suggesting cumulative ILI benefit on kidney function (Fig.1). After adjustment, annual eGFR decline was -0.66 vs. -0.52 mL/min/1.73 m² for DSE and ILI, respectively (p=0.07).Conclusion: ILI preserves kidney function in T2DM by maintaining higher eGFR and slowing CKD progression, emphasizing its importance in mitigating early renal decline and preventing CKD.DisclosureN. Srialluri: None. J. He: None. J. Ma: None. C.P. Oyeka: None. T. Gisinger: None. R. Kalyani: None. E. Michos: Consultant; Amgen Inc, Boehringer-Ingelheim, Novo Nordisk, Edwards Lifesciences, Eli Lilly and Company, Ionis Pharmaceuticals, NewAmsterdam Pharma, Bayer Pharmaceuticals, Inc, ESPERION Therapeutics, Inc., Arrowhead Pharmaceuticals, Inc. M. Woodward: None. D. Vaidya: None. W.L. Bennett: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-418-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 419-P: AI-Based Noninvasive Retinal Imaging for CKD Risk Prediction in DM
Patients without Established CKD-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 419-P
Abstract: Introduction and Objective: Dr.Noon CKD is a deep-learning model analyzing retinal images to predict the likelihood of eGFR ≤ 60mL/min/1.73m² (reti-eGFR) and estimate 5-year CKD risk using age, sex, and reti-eGFR in a Cox regression model. This study evaluates its utility in DM patients without CKD by comparing CKD risk predictions between hypertensive and normotensive patients.Methods: After excluding patients with CKD (eGFR ≤ 60 or UACR ≥ 30mg/g), UK Biobank data were used for 1:1 propensity score matching. Matching criteria included age, sex, UACR, BMI, LDL-C, HDL-C, BP, and smoking status for reti-eGFR and eGFR analyses. For 5-year CKD risk prediction, age and sex were excluded from the criteria. Dr.Noon CKD scores were averaged across both eyes. Statistical analyses included Wilcoxon rank-sum tests, Holm-adjusted p-values, and odds ratios (OR) with 95% confidence intervals (CI).Results: While eGFR values were similar between groups, hypertensive patients had higher reti-eGFR and Dr.Noon 5-year CKD risk scores, as shown in Figure 1. The 5-year CKD risk score (OR: 4.19, 95% CI: 1.19-15.12) and reti-eGFR (OR: 3.70, 95% CI: 1.15-12.16) were strong predictors, with males showing higher risk than females (OR: 1.55, 95% CI: 1.08-2.23).Conclusion: In DM patients without CKD, Dr.Noon CKD offers a non-invasive approach for CKD risk stratification, complementing eGFR in identifying risk differences.Disclosure D. Nam: Employee; Mediwhale. H. Kim: Employee; Mediwhale. S. Thakur: Employee; Mediwhale Inc. T. Rim: Employee; Mediwhale Inc. Stock/Shareholder; Mediwhale Inc. H. Ko: Employee; mediwhale. Y. Jung: Employee; Mediwhale. M. Yoon: None. Y. Lee: Other Relationship; Mediwhale Inc.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-419-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 420-P: Baseline Risk and Longitudinal Changes in KidneyIntelX Scores and
Their Association with Kidney Outcomes in the CANVAS and CREDENCE Trials-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 420-P
Abstract: Introduction and Objective: KidneyIntelX is a composite risk score incorporating biomarkers and clinical variables at baseline for diabetic kidney disease (DKD) progression. We sought to determine the clinical relevance of KidneyIntelX and thresholds in a large cohort of patients with type 2 diabetes and a broad range of CKD.Methods: We measured tumor necrosis factor receptor (TNFR)-1), TNFR-2, and kidney injury molecule (KIM-1) on banked plasma samples from CANVAS and CREDENCE participants, and executed kidneyintelX.dkd at baseline and year 1. We assessed the association of baseline and changes in kidneyintelX.dkd with a composite kidney outcome of 40% decline in eGFR or kidney failure. Hazard ratios were estimated using multivariate Cox regression.Results: There were 4677 participants (mean eGFR 69.4 mL/min/1.73m2; median UACR 77.0 mg/g) with available plasma samples. At baseline, kidneyintelX.dkd scored 867 (18.5%) as high, 1520 (32.5%) as moderate, and 2290 (49.0%) as low risk. The adjusted HR per doubling in predicted probability was 2.26 (95% CI 1.80-2.84). At year 1, the median change in KidneyIntelX predicted probabilities was 0.0%, with >10% reduction in 25.6% of canagliflozin- vs. 17.0% of placebo-treated patients. The adjusted HR for the change in predicted probability from baseline to year 1 was 2.24 (95% CI 1.65-3.04).Canagliflozin led to more patients shifting to lower risk at year 1 (32.1% vs. 16.2% moderate to low; 38.9% vs 19.7% high to moderate or low). Low risk at year 1 was associated with very low kidney outcome risk of 0.3 events per 100 person-years, while staying at moderate had 1.4, moving from high to moderate had 2.2, and high risk at year 1 had 8.9.Conclusion: Baseline and year 1 KidneyIntelX risk assessments in patients with type 2 diabetes and CKD robustly stratified patients for DKD progression independently of classic predictors and should be considered for enriching clinical trials and assessing treatment response.DisclosureE. Moedt: None. S. Coca: Consultant; Renalytix, Bayer Pharmaceuticals, Inc, Alexion Pharmaceuticals, Inc, Vera Therapeutics, Mylan. F. Fleming: Employee; Renalytix. H.L. Heerspink: Consultant; Alnylam Pharmaceuticals, Inc, Alexion Pharmaceuticals, Inc, AstraZeneca, Bayer Pharmaceuticals, Inc, Boehringer-Ingelheim, Eli Lilly and Company, Janssen Pharmaceuticals, Inc, Novartis AG, Novo Nordisk A/S, Roche Pharmaceuticals, Traveere Pharmaceuticals, Menarini.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-420-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 421-P: Development and Validation of a Risk Prediction Model for Diabetic
-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 421-P
Abstract: Introduction and Objective: To develop and validate a risk prediction model for diabetic kidney disease (DKD) in overweight/obese patients with type 2 diabetes mellitus (T2DM) in Guangdong Province, China.Methods: The study enrolled 1,453 overweight/obese patients with T2DM who were treated at the Department of Endocrinology and Metabolism, the Third Affiliated Hospital of Sun Yat-sen University between January 2021 and December 2023. The data was randomly assigned to form a training set comprising 70% of the patients and a validation set containing the remaining 30%, which included the non-DKD group (n=1,214) and the DKD group (n=239). We developed a predictive nomogram using multivariate logistic regression, incorporating variables from Least Absolute Shrinkage and Selection Operator (LASSO) models. The model's performance was assessed using C-index, calibration plots, and decision curve analysis for both internal and external validation, ensuring its discriminative power, calibration, and clinical utility.Results: The prevalence of DKD was 16.4%, and the risk prediction model included five predictors, namely, diabetes duration, systolic blood pressure(SBP), albumin(ALB), total cholesterol(TC), and cystatin C(CysC). ALB was a protective factor for DKD in overweight/obese patients with T2DM [OR=0.900, (0.861~0.940), P< 0.001]. The model showed high discrimination ability and the area under the curve (AUC) was 0.783 (95% CI: 0.743~0.822, P < 0.001). It showed superb calibration against actual DKD rates, with a c-index of 0.783 for internal and 0.763 for external validation. Decision curve analysis also indicated that this new nomogram is clinically useful.Conclusion: ALB might be a protective factor for DKD in overweight/obese patients with T2DM. The risk prediction model is a useful tool for predicting DKD in overweight/obese patients with T2DM at an early stage, and facilitate prompt and effective intervention.DisclosureY. Zhang: None. H. Li: None. X. Hu: None. F. Xu: None. M. Cai: None. Y. Chen: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-421-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 422-P: Type 2 Diabetes and the Individual Perception of Risk for
Cardiovascular Death in Coronary Artery Disease Patients-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 422-P
Abstract: Introduction and Objective: Subjective feelings of patients regarding the likelihood of undesired disease outcomes can influence their behavior and medication adherence. We investigated the individual risk perception for cardiovascular (CV) death within 10 years in patients with coronary artery disease (CAD) confirmed at coronary angiography.Methods: We included 445 consecutive patients with angiographically confirmed CAD in a tertiary care setting in central Europe. Prior to coronary angiography, patients were asked to rate their individual risk for CV death within the following 10 years in the categories very high, high, moderate or low, and to estimate a risk percentage between 0 and 100%.Results: A response rate of 81.3% was achieved for the question with a categorial and 69.4% for that with a continuous response variable. From our patients, 155 (34.8%) had T2DM according to ADA criteria. Overall, patients with T2DM assessed their risk for CV death higher compared to those without diabetes, with allocations in the categories very high in 11.5% vs. 3.0%, high in 20.0% vs. 18.5%, moderate in 43.1% vs. 38.8% and low 25.4% vs. 39.7%, with a significant trend towards higher risk perception categories in T2DM (p=0.002). The median self-estimated risk for CV death over 10 years was 40% [IQR:15-50] vs. 20% [IQR:10-50] in patients with versus those without T2DM (p<0.001). In analysis of covariance, T2DM (F=5.55; p=0.019) besides age (F=20.262; p<0.001) and the number of drugs (F=9.65; p=0.002) independently predicted the risk perception of CV death after multivariable adjustment.Conclusion: We conclude that CAD patients with T2DM estimate their individual risk for CV death higher than those without T2DM. Irrespective of T2DM status, there is a remarkable discrepancy between the level of risk CAD patients regard to represent very high, high, moderate or low risk and the definition of these risk categories in current guidelines.DisclosureM. Neyer: None. J. Vogel: None. P. Elsner: None. T. Plattner: None. A. Vonbank: None. B. Larcher: None. A. Mader: None. L. Schnetzer: None. A. Leiherer: None. M. Frick: None. A. Muendlein: None. A. Festa: None. H. Drexel: None. C.H. Saely: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-422-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 423-P: Three Decades of Glucose-Lowering Therapy in Patients with
Established Coronary Artery Disease—A Real-World Analysis-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 423-P
Abstract: Introduction and Objective: We aimed to assess long-term trends in glucose-lowering therapy (GLT) among patients with type 2 diabetes (T2DM) with proven coronary artery disease (CAD).Methods: We investigated T2DM patients (n=590) referred to elective coronary angiography and diagnosed with CAD in one of three observational cohort studies (OS): OS1: 1999-2000 (n=190); OS2: 2005-2008 (n=241); OS3: 2022-2023 (n=159). These studies were conducted in a tertiary care hospital in central Europe.Results: From patients with T2DM, 43.2% in OS1, 27.8% in OS2 and 28.3% in OS3 were newly diagnosed at admission and had no GLT (ptrend=0.002). Patients with known T2DM (OS1: n=108, OS2: n=174, OS3: n=114) had a median diabetes duration of 5 years (IQR:1-13), 4 years (IQR:2-8) and 4 years (IQR:<1-17) in OS1, OS2 and OS3, respectively (p=0.343). These patients reported to have some oral GLT in 50.0% (OS1), 72.4% (OS2) and 77.2% (OS3) of cases (ptrend<0.001). A wider array of glucose-lowering drugs was used over time (OS1: 11, OS2: 21, OS3: 24). SGLT2 inhibitors were the most frequently reported class in OS3 (34.0% of reported glucose-lowering drugs) while not available in OS1 and OS2. Sulfonylureas were largely replaced (OS1: 32.1%, OS2: 26.8%, OS3: 2.0%, ptrend<0.001), while metformin remained a key component of therapy (OS1: 31.2%, OS2: 42.1%, OS3: 31.0%). The use of incretin mimetics remained low in OS3: 4.6%; they were not used in OS1 and OS2. The proportion of patients on insulin showed no significant trend through the OS (OS1: 28.7%, OS2: 26.4%, OS3: 17.5%; ptrend>0.05). Achievement of an HbA1c target <7.0% was higher in OS3 (67.9%) than in OS1 (49.2%, p<0.001) and in OS2 (53.9%, p=0.005); ptrend<0.001.Conclusion: Our data show an upward trend in GLT intensity and complexity in T2DM patients with CAD. Significantly more patients reached HbA1c targets in the most recent cohort. However, the use of incretin mimetics remained very low, despite current guideline recommendations.DisclosureM. Neyer: None. J. Vogel: None. P. Elsner: None. T. Plattner: None. A. Vonbank: None. B. Larcher: None. A. Mader: None. L. Schnetzer: None. A. Leiherer: None. M. Frick: None. A. Muendlein: None. A. Festa: None. H. Drexel: None. C.H. Saely: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-423-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 424-P: The Relationship between Hepatic Steatosis and Bone Mineral Density
across Glycemic States-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 424-P
Abstract: Introduction and Objective: The relationship between hepatic steatosis and bone mineral density (BMD) across glycemic states remains incompletely understood. This study investigated these correlations in patients with varying glycemic status using comprehensive metabolic screening data.Methods: Cross-sectional analysis of 591 participants underwent metabolic screening including HbA1c, hepatic fibroscan (LSM & CAP), BMD, and comprehensive metabolic profiling. Statistical analysis included correlation studies and glycemic status stratification (non-diabetic, pre-diabetic, diabetic), with multivariate regression for confounding factorsResults: CAP scores (151-444 dB/m) showed significant inverse correlation with BMD (r=-0.42, p<0.001), with 43% participants showing grade II-III fatty liver. Glycemic status analysis revealed progressive deterioration: non-diabetic group (n=89; mean CAP: 245 dB/m; normal BMD: 58%), pre-diabetic group (n=43; mean CAP: 267 dB/m; normal BMD: 48%), and diabetic group (n=180; mean CAP: 289 dB/m; normal BMD: 39%). LSM values (2.1-51.0 kPa) showed moderate correlation with bone health markers across all groups.Conclusion: This study demonstrates significant associations between hepatic steatosis severity and declining bone health across glycemic states, with strongest correlation in individuals with diabetes. These findings suggest the need for integrated screening protocols and early preventive interventions in metabolic health management.DisclosureS.M. Patil: None. S.K. Singla: None. A. Maheshwari: None. A.A. Shaikh: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-424-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 425-P: Machine Learning Identifies Glypican 4 as Key Predictor of
Five-Year Mortality in Heart Failure Patients with Prediabetes or Diabetes
-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 425-P
Abstract: Introduction and Objective: The rise of Big Data necessitates artificial intelligence-driven analyses to extract valuable insights, particularly for risk prediction in high-risk patient populations. This observational study applied machine learning (ML) algorithms to predict 5-year overall mortality in heart failure patients with type 2 diabetes mellitus (T2DM) or prediabetes.Methods: A cohort of 290 heart failure patients with T2DM or prediabetes was followed for 5 years, during which 54% of participants died. The dataset comprised 470 variables, e.g. anthropometric, clinical, social, family history, and lifestyle factors. After preprocessing, the data were analyzed using ML techniques implemented in R’s caret package. The dataset was split into training (75%) and test (25%) subsets.Results: Among the ML models tested, the Random Forest algorithm demonstrated the best predictive performance, with a sensitivity of 82%, specificity of 89%, and overall accuracy of 85%. Clinical parameters were the most significant predictors, with the multimorbidity marker Glypican-4, hemoglobin, and glomerular filtration rate identified as the top three contributors.Conclusion: In conclusion, ML-based Big Data analysis holds great potential for predicting mortality risk in pre-/diabetic heart failure patients, paving the way for personalized and timely interventions.DisclosureA. Leiherer: None. A. Muendlein: None. L. Schnetzer: None. S. Mink: None. C. Heinzle: None. E. Brandtner: None. K. Geiger: None. S. Gaenger: None. B. Bermeitinger: None. T. Plattner: None. A. Vonbank: None. A. Mader: None. B. Larcher: None. C.H. Saely: None. P. Fraunberger: None. H. Drexel: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-425-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 426-P: Predicting Coronary Stenoses Using Machine Learning to Reduce
Unnecessary Angiographies-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 426-P
Abstract: Introduction and Objective: Coronary angiography is the gold standard for diagnosing coronary artery stenoses, but is invasive and confers potential risks. This study aimed to develop a Machine Learning (ML) model to predict significant stenoses while minimizing false negatives, ensuring accurate risk stratification and better patient selection.Methods: Data from 2,310 patients undergoing coronary angiography were analyzed, with outcomes classified as no stenoses (X0), non-significant stenoses (X1), or significant stenoses (X2).Results: XGBoost, optimized through grid search and 5-fold cross-validation, emerged as the top-performing ML algorithm. Of 114 clinical and laboratory variables, fibrinogen, HbA1c, BMI, waist-hip ratio, TyG index, FGF23, ceramides, and vitamin D - all associated with insulin resistance and diabetes - were identified as key contributors to the ML model (figure). Overall, the model achieved 62.9% accuracy (95% CI: 57.8-67.9). Sensitivity, precision, and F1 score for X2 were 94.7%, 62.7%, and 74.5%. For X0, sensitivity was 37.3%, with precision and F1 scores of 67.6% and 48.1%.Conclusion: This ML-based approach has the potential to reduce unnecessary angiographies and optimize patient selection in clinical practice. Highlighting the relevance of diabetes-linked variables, the study also underscores the potential of metabolic profiling in coronary risk stratification.DisclosureA. Leiherer: None. L. Schnetzer: None. S. Mink: None. A. Muendlein: None. B. Bermeitinger: None. T. Plattner: None. A. Vonbank: None. A. Mader: None. B. Larcher: None. C.H. Saely: None. P. Fraunberger: None. H. Drexel: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-426-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 427-P: Elevated Body Mass Index at Type 2 Diabetes Diagnosis Is Associated
with Increased Risk of Cardiovascular Disease and Kidney Outcomes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 427-P
Abstract: Introduction and Objective: Type 2 diabetes (T2D) and obesity are independently associated with increased risk of cardiovascular disease (CVD) and kidney outcomes. This study aimed to explore the impact of body mass index (BMI) at T2D diagnosis on CVD and kidney outcomes, which is less understood.Methods: Data from people diagnosed with T2D from January 2010 to March 2021 were extracted from Clinical Practice Research Datalink Aurum and linked Hospital Episode Statistics datasets in England. Ten-year incidence of CVD and kidney outcomes were estimated in males and females by BMI subgroup using parametric survival models.Results: Data from 161,109 people (60.6% male) with T2D were included. Ten-year incidence of CVD [and kidney outcomes] in males with BMI 35-40 and 40-50 kg/m2 were 43.1% and 47.9% [23.6% and 26.6%] respectively (vs 38.7% [20.6%] in BMI 18-30 kg/m2; p<0.05; Fig 1). Females with BMI 40-50 kg/m2 had higher 10-year incidence of CVD [and kidney outcomes] of 33.6% [27.8%] (vs 28.2% [22.5%] in BMI 18-30 kg/m2; p<0.05).Conclusion: Males with BMI > 35 kg/m2 and females > 40 kg/m2 at T2D diagnosis have higher risk and earlier manifestation of CVD and kidney outcomes. Timely screening and appropriate weight management in these populations could support management of this increased risk and potentially reduce healthcare burden associated with CVD and kidney complications.Disclosure A.B. Jain: Advisory Panel; Abbott. Speaker's Bureau; Abbott. Research Support; Abbott. Advisory Panel; Novo Nordisk. Research Support; Novo Nordisk. Speaker's Bureau; Novo Nordisk. Research Support; AstraZeneca, Amgen Inc. Speaker's Bureau; Amgen Inc. Advisory Panel; Amgen Inc. Research Support; Sanofi. Advisory Panel; Bausch Health. Speaker's Bureau; Bausch Health. Advisory Panel; Bayer Pharmaceuticals, Inc. Speaker's Bureau; Bayer Pharmaceuticals, Inc, Boehringer-Ingelheim. Advisory Panel; Dexcom, Inc. Speaker's Bureau; Dexcom, Inc. Advisory Panel; Eli Lilly and Company. Speaker's Bureau; Eli Lilly and Company. Advisory Panel; HLS Therapeutics. Speaker's Bureau; HLS Therapeutics, Medtronic. Advisory Panel; Insulet Corporation. Speaker's Bureau; Insulet Corporation. Advisory Panel; Sandoz. P.N. Kristensen: Stock/Shareholder; Novo Nordisk. Employee; Novo Nordisk. R. Wasehuus: Employee; Novo Nordisk A/S. J. Hollinghurst: Consultant; Novo Nordisk A/S, AbbVie Inc, AstraZeneca, GlaxoSmithKline plc, Pfizer Inc, Shionogi & Co., Ltd, Galapagos, Rocket Pharma, ViiV Healthcare. E. Noertoft: Employee; Novo Nordisk A/S.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-427-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 428-P: Association between the Use of Alpha-lipoic Acid and Macrovascular
Complications in Patients with Diabetic Neuropathy-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 428-P
Abstract: Introduction and Objective: Alpha-lipoic acid (ALA) is used for diabetic neuropathy, but their potential impact on macrovascular complications remains unclear. This study aimed to investigate the association between ALA use and the risk of cardiovascular outcomes and mortalityMethods: We conducted a retrospective cohort study using the Korean National Health Insurance Service Health Screening Cohort. Participants aged 40-79 who were diagnosed with diabetic neuropathy from 2011 to 2015 were followed up to December, 2019. ALA users were defined as those prescribed ALA for ≥6 months. Propensity score matching was performed to balance baseline characteristics, and Cox proportional hazards models were used to evaluate associations between ALA use and myocardial infarction (MI), stroke, diabetic foot ulcers (DFU), amputation, and all-cause mortality.Results: A total of 8,740 participants (4,370 ALA users and 4,370 non-users) were included after matching. Over a median follow-up of 8 years, ALA use was significantly associated with a lower risk of MI (Hazard ratio [HR] 0.85, 95% confidence interval [CI] 0.74-0.98) and all-cause mortality (HR 0.82, 95% CI 0.72-0.93), while no significant associations were observed for stroke, diabetic foot ulcer, or amputation. Subgroup analyses revealed a pronounced MI risk reduction in individuals with high comorbidity index (HR 0.38, 95% CI 0.22-0.65). In a 'user-only design' analysis, longer use of ALA (>2 years) was associated with a stronger MI risk reduction (HR 0.48, 95% CI 0.40-0.59, p for trend < 0.001).Conclusion: ALA use, particularly long-term use, was associated with a reduced risk of MI and all-cause mortality in individuals with diabetic neuropathy. These findings highlight the potential role of antioxidant as adjuncts in managing macrovascular complications in diabetes.DisclosureS. Kim: None. Y. Cho: None. H. Park: None. D. Seo: None. S. Hong: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-428-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 429-P: The Difference between Cystatin C- and Creatinine-Based Estimated
Glomerular Filtration Rate in Relation to Carotid Plaque Score in Patients
with Type 2 Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 429-P
Abstract: Introduction and Objective: The difference between cystatin C (cys)- and creatinine (cr)-based estimated glomerular filtration rate (eGFRdiff) is recently documented to be associated with adverse cardiovascular outcomes and diabetes microvascular complications. We examined association between eGFRdiff and carotid plaque score (PS) in patients with type 2 diabetes (T2D).Methods: We enrolled 1,576 patients with T2D. The eGFRdiff was defined as follows: eGFRcys - eGFRcr. Participants were categorized into 3 groups by the sex-specific eGFRdiff tertile. Carotid PS was ranged from 0 to 12 and high PS was defined as ≥ 3.Results: Patients with high PS were 626 (39.7%). They were more likely to be old and male and had higher diabetes duration, hypertension, systolic blood pressure (BP), cys, and cr, but lower body mass index (BMI), diastolic BP (DBP), HDL cholesterol, eGFRcys, and eGFRcr than those without high PS. Subjects in the 1st sex-specific eGFRdiff tertile group were older and had higher BMI, waist circumference (WC), C-reactive protein (CRP), eGFRcr, and PS, but lower DBP, fasting glucose (FG), HbA1c, LDL cholesterol, eGFRcys, and cr than those in the 3rd tertile group. The prevalence of high PS was proportionally increased with decreasing the eGFRdiff tertile (3rd vs. 2nd vs. 1st = 30.7% vs. 41.3% vs. 47.1%, p < 0.001). The odds ratios (ORs) and 95% confidence intervals (CIs) for the presence of high PS after adjusted for age and sex, were 1.20 (0.91 - 1.59, p = 0.20) in the 2nd and 1.69 (1.28 - 2.23, p < 0.001) in the 1st tertile groups. The ORs and 95% CIs in the 1st tertile group remained significant after further adjusted for current smoker, WC, BMI, DBP, CRP, HDL and LDL cholesterol, FG, and HbA1c (p < 0.01).Conclusion: Large negative eGFRdiff was independently associated with high PS. These findings proposed that monitoring eGFRdiff in patients with T2D may be beneficial for the detection of early atherosclerosis.DisclosureJ. Shin: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-429-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 430-P: Sleep Disorders and Cardiometabolic Markers in Type 1 Diabetes
-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 430-P
Abstract: Introduction and Objective: Type 1 diabetes (DM1) is associated with poor sleep quality and increased prevalence of obstructive sleep apnea (OSA), leading to worse glycemic control. We aim to assess the impact of sleep disorders on cardio metabolic markers in DM1.Methods: Our retrospective cross-sectional study included patients with DM1 from our endocrinology clinic who underwent polysomnography (PSG). Sleep-related diagnoses were obtained from sleep clinic notes and PSG results, and were not mutually exclusive. For each sleep diagnosis, we created 2 subgroups, with and without the diagnosis. We calculated averages for metabolic markers and compared them between subgroups using two-sample one-tailed t-tests.Results: We included 45 patients (21 male and 24 female), average age of 52 years, total daily insulin dose (TDD) of 65 units, BMI of 32, systolic blood pressure (SBP) of 129 mmHg, A1C of 7.8%, LDL of 81, and triglycerides (TAG) of 117. The most common sleep diagnoses were OSA (n=29), insomnia (n=21), and periodic limb movement disorder (PLMD) (n=12). Patients with OSA had a higher A1C (M=8.1, SD=1.6 vs M=7.3, SD=1.1; p=0.043), SBP (M=133, SD=17 vs M=121, SD=11; p=0.006), and TAG (M=133, SD=100 vs M=82, SD=39; p=0.036) than those who did not. Patients with insomnia had a higher TAG (M=141, SD=121 vs M=96, SD=32; p=0.046) than those without it, but this difference disappeared after excluding OSA. Patients with PLMD used less daily insulin (M=43, SD=14 vs M=72, SD=40; p=0.009) and BMI (M=29, SD=4.9 vs M=34, SD=9.1; p=0.044) than those without it, though more patients with PLMD had OSA (83%) than those without PLMD (58%). With nested case-control analysis, this relationship remained significant for TDD (M=48, SD=15 vs M=65, SD=25; p=0.036).Conclusion: Patients with DM1 and OSA had poor metabolic health and glycemic control. In DM1 patients with insomnia, OSA was the driver of metabolic disturbances. PLMD was associated to lower BMI, even though OSA was more common.DisclosureF. Chagani: None. A.T.F. Kessler: None. A. Danyluk: None. K. Tuna: None. J.A. Leey: None.FundingNational Institutes of Health (UL1TR001427)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-430-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 431-P: Gut and Oral Microbiome Characteristics Associated with Chronic
Complications in Type 1 Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 431-P
Abstract: Introduction and Objective: This study aims to examine the gut and oral microbiome characteristics associated with chronic complications in T1D and explore potential links between these microbiomes.Methods: We conducted a cross-sectional study with 74 T1D patients (disease duration >10 years) and 43 healthy controls. Clinical data such as blood glucose, lipids, and complication-related tests were collected. Fecal and mouthwash samples were taken for metagenomic sequencing. Patients were grouped based on the number of chronic complications (diabetic nephropathy, retinopathy, peripheral neuropathy, and macrovascular complications) into three groups: no complications, one complication, and two or more complications. The differences in gut and oral microbiomes among the groups were analyzed.Results: β-diversity analysis showed significant differences in microbiome structure across groups (p = 0.001). Specific gut bacteria (Candidatus Propionivibrio aalborgensis, Eubacterium ventriosum, Faecalibacterium prausnitzii) and oral bacteria (Microlunatus antarcticus, Streptococcus gordonii, Corynebacterium durum) were linked to the number of complications. Gut and oral microbiota showed positive correlations with each other, particularly, Candidatus Propionivibrio aalborgensis and Microlunatus antarcticus. Further analysis showed, Additionally, Eubacterium ventriosum was negatively correlated with blood glucose and vascular complications, while Microlunatus antarcticus was positively correlated with disease duration and blood glucose levels.Conclusion: Distinct oral and gut microbiome characteristics associated with varying severities of chronic complications in T1D, and the differences in oral and gut microbiome species are correlated. This study offers new insights into T1D complications and potential strategies for their management.DisclosureX. Li: None. R. Tang: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-431-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 432-P: Association between Neck-to-Limb Length and Neck-to-Height Ratios
and Cardiovascular Events in a Chinese Population-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 432-P
Abstract: Introduction and Objective: This study explored anthropometric indicators to improve body mass index (BMI)'s predictive value for cardiovascular (CV) events in individuals without carotid plaques, improving early risk stratification in subclinical populations.Methods: The study included 1043 participants (aged 50-80) from a 2013-2014 community cohort, followed for CV events (2021-2022). Carotid plaque was excluded using ultrasound. Visceral fat area (VFA) was assessed via MRI. The neck circumference [NC], neck-to-height ratio [NHtR], waist-to-height ratio [WHtR], waist-to-hip ratio [WHR], neck-to-limb length ratio [NLR], and waist-to-limb length ratios [WLR] were calculated.Results: Obesity indices (BMI, waist circumference, NC, NHtR, WHtR, WHR, NLR, and WLR) were significantly correlated with VFA (all P < 0.001). During 7.6 years of follow-up, 97 CV events (9.3%) were recorded. NHtR and NLR emerged as significant CV risk predictors, with hazard ratios of 1.33 and 1.31, respectively. NLR notably improved predictive accuracy (C-statistic= 0.671 [95% CI: 0.616-0.726], P = 0.002).Conclusion: Anthropometric indices incorporating NC (NHtR and NLR) improved BMI’s predictive value for CV risk and were strongly associated with visceral fat. NHtR and NLR could refine CV risk assessment in individuals without carotid plaques.DisclosureX. Li: None. T. Hu: None. Y. Xu: None. X. Ma: None. Y. Bao: None.FundingNational Natural Science Foundation of China (82400999); China Postdoctoral Science Foundation (2024M762052); Shanghai Research Center for Endocrine and Metabolic Diseases (2022ZZ01002); Clinical Research Project of Health Industry of Shanghai Municipal Health Commission (20224Y0155); Shanghai Rising Star of Medical Talent Youth Development Program (YYXX202302)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-432-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 433-P: Comparative Evaluation of Current Therapeutic Agents for Heart
Failure with Preserved Ejection Fraction (HFPEF)—A Systematic Review and
Network Meta-analysis-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 433-P
Abstract: Introduction and Objective: To evaluate and compare the therapeutic effects of current agents for heart failure with preserved ejection fraction (HFpEF).Methods: Literature retrieval was conducted in PubMed, Embase, the Cochrane Central Register of Controlled Trials and Clinicaltrial.gov between inception and December 2024. Randomized controlled trials (RCTs) in patients with HFpEF, which intercompared current therapeutic agents and reported the cardiovascular outcomes were included. Network meta-analyses regarding these studies were implemented.Results: A total of 17 RCTs with 52,934 participants were included. Compared with non-users, GLP-1/GIP dual receptor agonists, GLP-1RA, SGLT-2i, MRA, and ARNI were all associated with reduced risk of the composite outcome of worsening heart failure and cardiovascular death in patients with HFpEF. The surface under the cumulative ranking curve (SUCRA) evaluation conferred a rank order as GLP-1/GIP dual agonists> GLP-1RA > SGLT-2i > MRA > ARNI in terms of the risk reduction in the composite cardiovascular outcome. Meanwhile, compared with non-users, GLP-1/GIP dual receptor agonists and MRA were all associated with significantly improved score of Kansas City Cardiomyopathy Questionnaire (KCCQ). And the corresponding rank order of SUCRA was GLP-1/GIP dual agonists> MRA > SGLT-2i > GLP-1RA.Conclusion: Compared with non-users, GLP-1/GIP dual receptor agonists, GLP-1RA, SGLT-2i, MRA and ARNI were associated with reduced risk of worsening heart failure and cardiovascular death in patients with HFpEF. Moreover, patients receiving GLP-1/GIP dual receptor agonists and MRA were with significantly improved score of KCCQ. GLP-1/GIP dual receptor agonists may serve as promising candidates in HFpEF treatment with exceptional cardiovascular benefits.DisclosureZ. Li: None. C. Lin: None. X. Cai: None. F. Lyu: None. W. Yang: None. L. Ji: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-433-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 434-P: Coronary Artery Calcification Incidence in Individuals with
Diabetes and BMI <30 kg/m 2-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 434-P
Abstract: Introduction and Objective: Coronary artery calcification (CAC), a proxy of atherosclerosis, has increased incidence and prevalence in individuals with diabetes. It is also known that CAC predicts future coronary heart disease, along with mortality in this population. We aimed to evaluate whether the association between diabetes and CAC incidence holds in individuals with diabetes and BMI < 30 kg/m2.Methods: We analyzed data of 2,105 asymptomatic individuals with BMI < 30 kg/m2 and no prior cardiovascular disease from the ELSA-Brasil cohort. The association between diabetes at baseline and CAC incidence was examined by multivariable logistic regression adjusted for age, sex, race, tobacco use, hypertension, triglycerides, LDL-c, and HDL. CAC incidence was defined by initial CAC = 0 and repeated CAC > 0. The mean interscan period was 5.2 years.Results: At baseline, the mean age was 48 ± 7.5 years, 60.7% of individuals were female, and 58.9% were White, with a mean BMI of 25 ± 2.8 kg/m2, diabetes prevalence of 10.7% and hypertension prevalence of 18.3%. Diabetes was associated with CAC incidence, odds ratio (OR) 1.82 (95% CI 1.3-2.55, p<0.001) in the crude model and in the model adjusted for age, sex, race, and tobacco, OR 1.79 (95% CI 1.26 -2.52, p: 0.001). In the fully adjusted model, the OR was 1.4 (95% CI 0.97-2.02, p:0.07). The overall CAC incidence was 15.1%, 14.1% in individuals without diabetes and 23% in individuals with diabetes (chi square p< 0.001).Conclusion: Individuals with BMI < 30 kg/m2 and diabetes have increased incidence of CAC, a proxy of coronary atherosclerosis. Diabetes is associated with increased odds of incident coronary calcification even after adjustment for several confounders. In the fully adjusted model, there was a trend towards significance that did not reach the classic statistical significance as the OR was attenuated by other factors, such as hypertension and dyslipidemia.DisclosureT.B. Mendes: None. C.C. Janovsky: None. G. Generoso: None. B. Halpern: Other Relationship; Eli Lilly and Company, AstraZeneca, Novo Nordisk, Merck & Co., Inc, Boehringer-Ingelheim. Advisory Panel; Currax. R. Correa Fabiano: None. R. Santos: Research Support; Amgen Inc, Sanofi. Consultant; ESPERION Therapeutics, Inc., Daiichi Sankyo. Speaker's Bureau; Daiichi Sankyo. Research Support; Eli Lilly and Company. Speaker's Bureau; Eli Lilly and Company. Research Support; Kowa Company, Ltd, Novartis Pharmaceuticals Corporation. Speaker's Bureau; Novo Nordisk. Research Support; Ionis Pharmaceuticals. Speaker's Bureau; Novartis Pharmaceuticals Corporation. I.M. Bensenor: None. P.A. Lotufo: None. M.S. Bittencourt: Speaker's Bureau; Cleerly. Board Member; Elucid.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-434-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 435-P: Endothelial Dysfunction in T1D—A Spotlight for Obesity
-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 435-P
Abstract: Introduction and Objective: Overweight/obesity (ow/ob) is increasingly prevalent in T1D, but its impact on vascular complications remains unclear. This study aims to investigate endothelial function in lean (lean T1D) and ow/ob subjects with T1D (T1D+ow/ob), compared to healthy controls.Methods: Endothelial dysfunction was evaluated by flow-mediated dilation (FMD) of the brachial artery and advanced glycation end-products (AGE) by AGE reader in 23 T1D+ow/ob and 23 lean T1D, matched 1:1 for sex, age, and disease duration. A control group of healthy volunteers (n=14) was also evaluated.Results: FMD was significantly lower in T1D than in controls (p=0.02). T1D+ow/ob had a further reduced FMD than lean T1D (9.8[4.9-15.1] vs 15.4[7.4-29.0] %; p=0.05), despite similar classic CV risk factors (Table). AGE levels were higher among T1D than among controls (p=0.016), and negatively associated with FMD (β= -0.31; p= 0.027), independently from confounders. However, AGE did not differ between lean and ow/ob people with T1D.Conclusion: Overweight and obesity further exacerbate endothelial function in people with T1D. Given the increasing prevalence of ow/ob in T1D, further studies are warranted to characterize its impact on vascular and other complications.DisclosureR. Amendolara: None. R. Risi: None. L. D'Onofrio: None. F. Barbaro: None. F. De Vita: None. A. Carafa: None. D. Luverà: None. R. Buzzetti: Other Relationship; Abbott, Eli Lilly and Company, Sanofi, Novo Nordisk A/S, Boehringer-Ingelheim, AstraZeneca, Novartis Pharmaceuticals Corporation. E. Maddaloni: Speaker's Bureau; Abbott, AstraZeneca. Advisory Panel; Novo Nordisk, Merck Sharp & Dohme Corp. Speaker's Bureau; Eli Lilly and Company, Medicat Technologies and Devices (MTD). Other Relationship; Guidotti, Theras. Speaker's Bureau; Aurora Biopharma.FundingEuropean Union through Italian Ministry of University and Research, PRIN project (2022NS7PRM); Sapienza University of Rome Grants 2022 (RP1221816784D0A1)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-435-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 436-P: The Association between Glycemic Control, Normal Weight, and
Long-Term Macrovascular Outcomes in People with T2D in China-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 436-P
Abstract: Introduction and Objective: The Chinese diabetes guideline recommends a normal BMI as a component of comprehensive management of T2D. However, evidence on the independent or combined effects of glycemic control and normal BMI on long-term macrovascular outcomes is limited.Methods: Regional electronic health record data from Yinzhou Ningbo China (2006/1/1 - 2021/10/30) was used. Adult patients with T2D and no prior cardiovascular events who had ≥ 1 HbA1c record between 2007/1/1 and 2016/10/31 were included to ensure ≥ 5 years follow-up. The index date was the first HbA1c occurring ≥ 90 days after initial T2D diagnosis. Glycemic control was defined as HbA1c ≤ 6.5% or <7.0%. The BMI closest to the index date was identified with a normal range of 18.5-24 kg/m². Patients were categorized by the attainment of the two targets. For weight effect alone, BMI was categorized by Chinese cut-offs. Cox proportional hazards model was used to analyze the incidence of 3-point major adverse cardiovascular events (3P-MACE).Results: Among 5,757 patients (mean age 61.6 years; 52.5% female) observed for a median of 6.8 years, 1,188 (20.6%) experienced 3P-MACE with an incidence rate of 3.1/100 person-years. Compared to patients achieving neither strict glycemic control (HbA1c≤ 6.5%) nor normal weight, lower 3P-MACE risk was observed in patients achieving only normal weight (0.850 [hazard ratio], 0.737-0.980 [95% confidence interval]), only glycemic control (0.762, 0.644-0.901) and both targets (0.759, 0.642-0.898). A more consistent trend was observed when HbA1c target was set at < 7.0%. In the weight alone analysis, after adjusting HbA1c and other confounders, patients with underweight (1.153, 0.802-1.658), overweight (1.069, 0.943-1.211), and obesity (1.270, 1.058-1.524) had higher risks compared to those with normal weight.Conclusion: Glycemic control and normal weight were associated with a significantly lower risk of long-term macrovascular outcomes in patients with T2D.DisclosureQ. Pan: None. F. Sun: None. M. Zhang: None. S. Zhan: None. L. Guo: Research Support; Abbott, AstraZeneca, Bayer Pharmaceuticals, Inc, Eli Lilly and Company, Innovent Biologics, Merck & Co., Inc, MSD Life Science Foundation, Novo Nordisk A/S, Sanofi, Jiangsu Hengrui Pharmaceuticals Co., Ltd, Tonghua Dongbao.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-436-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 437-P: Coronary Calcium Score and Cardiovascular Events in Ketosis-Prone
Diabetes Compared with T2DM-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 437-P
Abstract: Introduction and Objective: Coronary artery calcium score (CACS) is an effective marker to stratify cardiovascular risk. Compared to type 2 diabetes (T2D) Ketosis Prone Diabetes (KPD) has an atypical presentation marked by ketosis during decompensation. We compared CACS and cardiovascular events (CVE) in KPD and T2D.Methods: It is a retrospective observational study (2014-2024) of KPD and T2D patients attending the diabetology day hospital and undergoing CACS evaluation. We recorded CVE occurring after CACS evaluation: non-fatal myocardial infarction (MI), coronary revascularization (CR), heart failure (HF), obliterative arteriopathy of the lower limbs (OA).Results: A total of 1244 patients (106 KPD and 1138 T2DM) were included in the analysis. Their characteristics are presented in Table 1. In the study population, 66.8% had CACS <100 and 16.2% >400. Median KPD CACS compared to T2D was lower (p<0.0001). Percentage of KPD with CACS <100 was higher and CACS >400 lower compared to T2D (p=0.001). Odds ratio (OR) for CACS <400 was 5 times higher for KPD 5.37 (1.95 - 14.75, p<0.0001) (95% CI). In multivariate logistic regression, OA, limb amputation and albumin/creatinine ratio (ACR) were significantly associated to CACS >400 (p<0.05)Conclusion: KPD showed lower CACS and lower frequency of OA occurrence compared to T2D. However recorded MI were similar in both groups.DisclosureJ. Nguewa: None. J. Kevorkian: None. J. Julla: Other Relationship; Lilly Diabetes. Board Member; Sanofi. Other Relationship; Novo Nordisk. F. Féron: None. M. Laloi-Michelin: None. L. Akl: None. R. Badawi: None. K. Chafai: None. J. Riveline: Consultant; Abbott, Lilly Diabetes, Novo Nordisk, Sanofi, Dexcom, Inc., Air Liquide, Insulet Corporation. Research Support; Tandem Diabetes Care, Inc, Juvenile Diabetes Research Foundation (JDRF). J. Gautier: Board Member; Sanofi. Advisory Panel; Pfizer Inc, Novo Nordisk. Other Relationship; Eli Lilly and Company.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-437-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 438-P: Adipose-Tissue Insulin Resistance Predicts Mortality in Persons at
Risk for Cardiac Diseases-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 438-P
Abstract: Introduction and Objective: Insulin resistance (IR) significantly contributes to cardiovascular mortality in type 2 diabetes (T2D). Whether organ-specific IR (skeletal muscle, adipose tissue, liver) independently associates with structural and functional cardiac morbidity and mortality is unclear.Methods: This study included 850 Europeans with and 2243 without T2D of the LUdwigshafen RIsk and Cardiovascular Health (LURIC) cohort undergoing echocardio- and coronary angiography for suspected acute coronary syndrome. IR was assessed at whole-body level (HOMA2-IR), adipose tissue (Adipo-IR by fasting non-esterified fatty acids and C-peptide) and liver (HIR: 0.45+0.23*log(insulin)+0.24*(AUC0-120 (insulin))-0.24*log(adiponectin)). All results were adjusted for age, sex, BMI, HbA1c and T2D status. Mortality was assessed by telephone interviews and population registers over 15 [IQR: 9, 18] yrs and Cox models also adjusted for coronary artery disease (CAD) and heart failure (HF).Results: Participants (63 [56, 70] yrs, 30% female) were mostly overweight and well-controlled (BMI 27 [25, 30] kg/m², HbA1c 6.0 [5.6, 6.4]%). HOMA2-IR, Adipo-IR and HIR were 6%, 6% and 1% higher in people with than without CAD (all p<0.001). Compared to people without HF, those with HF and preserved ejection fraction (HFpEF) and with reduced EF (HFrEF) had 8% and 11% higher HOMA2-IR (p<0.001), 17% and 16% higher Adipo-IR (p<0.001), and both 1% higher HIR (p<0.05). Adipo-IR was 4% higher in HFpEF than HFrEF (p<0.05). Higher HOMA2-IR increased mortality independent of HF by 9% (p<0.01), but not independent of CAD or HbA1c. Higher Adipo-IR increased mortality by 18% and 13% independently of CAD or HF (p<0.001). Higher HIR did not increase mortality. CAD or HF status did not interact with IR indices on mortality.Conclusion: The Adipo-IR independently predicts mortality in people at risk for cardiac diseases, emphasizing the relevance of integrating this index into clinical practice for precision medicine.DisclosureK. Bódis: None. S. Goh: None. C. Binsch: None. K. Prystupa: None. O.P. Zaharia: None. M. Schön: None. P. Wischmann: None. H. Busch: None. M. Heni: Advisory Panel; Amryt Pharma. Speaker's Bureau; Amryt Pharma, AstraZeneca, Boehringer-Ingelheim. Advisory Panel; Boehringer-Ingelheim. Speaker's Bureau; Lilly Diabetes, Novartis AG, Novo Nordisk, Sanofi. M. Kelm: None. A. Niessner: None. M. Roden: Research Support; Boehringer-Ingelheim. Advisory Panel; Echosens. Speaker's Bureau; Madrigal Pharmaceuticals, Inc. Advisory Panel; MSD Life Science Foundation. Board Member; Novo Nordisk. Advisory Panel; TARGET PharmaSolutions, Inc. W. März: None. R. Wagner: Speaker's Bureau; Boehringer-Ingelheim, Novo Nordisk. Advisory Panel; Sanofi. Speaker's Bureau; Sanofi. Advisory Panel; Lilly Diabetes.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-438-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 439-P: Investigation of Wall Shear Stress (WSS) in Patients with Type 2
Diabetes Mellitus-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 439-P
Abstract: Introduction and Objective: Wall shear stress (WSS), the force exerted by blood flow on vessel walls, is considered an early indicator of atherosclerosis, as moderate WSS supports endothelial function. It has been reported that WSS is associated with cerebral small vessel disease (SVD). Traditional methods like MRI and computational fluid dynamics assess WSS but are impractical for routine use. Recently, vector flow mapping (VFM) by carotid echography has emerged as a simpler method to visualize blood flow and calculate WSS, providing a more accurate blood velocity distribution reflecting flow dynamics in vivo. VFM, combined with morphological evaluation such as intima-media thickness (IMT) assessment in carotid artery ultrasound, offers an approach for evaluating atherosclerosis in clinical practice. This study investigated the association between WSS using VFM during carotid artery ultrasound and atherosclerosis in patients with type 2 diabetes (T2D).Methods: We measured WSS, IMT, and FMD (Flow-mediated dilation) using brachial artery echography within a few days in hospitalized patients with T2D. We also analyzed the relationship between WSS and atherosclerotic diseases.Results: In this study, 83 patients with T2D (51 men and 32 women, mean age = 67.6±11.7 years) were included. The mean HbA1c level was 8.3±1.5%. WSS and FMD were significantly positively correlated in simple correlation analyses (r=0.37, p=0.0006) and multiple regression analyses adjusted by age, gender, BMI, smoking status, HbA1c, hypertension, dyslipidemia, and IMT (β=0.34, p=0.004). WSS showed a significant negative association between IMT (r=-0.38, p= 0.0004) and age (r=-0.39, p=0.0003). Furthermore, WSS was notably lower in patients who had diabetic microangiopathy and heart failure.Conclusion: This study showed that WSS was significantly associated with FMD, suggesting that, carotid WSS may be a useful, simple method for evaluating the early stage of atherosclerosis.DisclosureY.O. Ohata: None. K. Saito: None. R. Koezuka: None. T. Tamanaha: None. M. Noguchi: None. H. Makino: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-439-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 440-P: Associated Factors with Cardiovascular Disease in Patients with
Type 2 Diabetes Mellitus in iCaReMe China Registry-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 440-P
Abstract: Introduction and Objective: We use data from iCaReMe China Registry to analysis the associated factors with cardiovascular disease (CVD) in patients with type 2 diabetes (T2D) in China.Methods: iCaReMe China Registry study is an ongoing prospective, multicentric, observational registry. 9000 patients with T2D were recruited from 60 sites in China from July 2023 to March 2024 with three years of follow-up. The primary outcome is to describe the socio-demographic, clinical characteristics, disease management patterns, healthcare resource utilization, and clinical outcomes in Chinese T2D patients.Results: 1515(16.8%) patients reported CVD at baseline. Multivariate logistic regression analysis showed that advanced age, widowhood, family history of CVD, and disease history (stroke, hypertension, chronic kidney disease, and heart failure) were significantly associated with the increased risk of CVD. Patients with CVD were associated with more use of SGLT2 inhibitors, or GLP1RA, or antihypertensive drugs, or anti heart failure drugs, or antiplatelet drugs. Lower level of blood glucose and lipid levels were also associated with the increased risk of CVD.Conclusion: This study outlined the current risk factors associated with CVD in patients with T2D in China, providing the evidence for the strategies in the management of macrovascular disease with type 2 diabetes.DisclosureX. Cai: None. J. Yan: None. W. Yang: None. N. Tong: None. M. Liu: None. Y. Li: None. B. Feng: None. L. Ji: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-440-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 441-P: Different Diagnostic Categories and Prediction of Complications in
Chinese Hospitalized Diabetic Patients Based on Artificial Intelligence-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 441-P
Abstract: Introduction and Objective: The current study aimed to assess the applicability of different clustering methods in an extensive range of Chinese inpatients with diabetesMethods: We performed hard and soft clustering diagnosis and prediction of complications in two follow-up visits among Chinese inpatients with diabetes in Heilongjiang. Furthermore, the hard and soft clustering model was validated using data from Chinese inpatients with diabetes in Beijing.Results: The results between the Heilongjiang cohort and the Beijing Hospital cohort were consistent, with the highest proportion of participants in the mild obesity-related diabetes (MOD) subgroup, followed by severe insulin-resistant diabetes (SIRD). In the K-means model of two follow-up visits with Heilongjiang data, the mild age-related diabetes (MARD) subgroup had the highest prevalence of distal symmetric polyneuropathy (DSPN) and coronary heart disease (CHD), the severe insulin-deficient diabetes (SIDD) subgroup had the highest prevalence of diabetic ketosis (DK) and the highest level of TG and eGFR (all P value <0.001), and the MOD subgroup had the highest prevalence of hypertension (P value<0.001). In the Gaussian mixture model of two visits with Heilongjiang data, the MOD subgroup had the highest prevalence of hypertension (P value<0.001), severe insulin-deficient diabetes (SIDD) subgroup had the highest value of LDL-C (P value <0.05), and the MIX subgroup had the highest the percentage of alcohol drinking (P value <0.05)Conclusion: Both hard and soft clustering methods were applicable to a comprehensive range of Chinese inpatients with diabetesDisclosureJ. Zhang: None. W. Wang: None. L. Guo: Research Support; Abbott, AstraZeneca, Bayer Pharmaceuticals, Inc, Eli Lilly and Company, Innovent Biologics, Merck & Co., Inc, MSD Life Science Foundation, Novo Nordisk A/S, Sanofi, Jiangsu Hengrui Pharmaceuticals Co., Ltd, Tonghua Dongbao. Q. Pan: None.FundingCapital's Funds for Health Improvement and Research (2024-1-4053); National High Level Hospital Clinical Research Funding (BJ-2024-144)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-441-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 442-P: Statin Therapy in Type 1 Diabetes—Adherence to NICE Guidelines
for Primary Prevention of Cardiovascular Disease-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 442-P
Abstract: Introduction and Objective: Cardiovascular disease (CVD) is the leading cause of mortality in Type 1 diabetes mellitus (T1DM) patients, with a two-fold increase in death rates. This study aimed to determine the adherence to National Institute for Health and Care Excellence (NICE) guidelines for statin therapy in T1DM patients for primary prevention of CVD.Methods: A retrospective analysis was conducted on electronic health records of T1DM patients from a single healthcare trust. Patients were stratified into two age groups: ≥40 years and <40 years. Inclusion criteria were based on NICE guidelines: age >40 years, diabetes duration >10 years, established nephropathy, or other modifiable risk factors. The primary outcome was the proportion of eligible patients prescribed statins. Descriptive statistics were used to analyze the data.Results: Of 1,229 patients ≥40 years, 73% (896/1,229) were prescribed statins, while 27% (333/1,229) were not. Among 192 patients <40 years with indications for statin use, prescription rates were low: 35% (6/17) in nephropathy patients, 15% (2/15) in retinopathy patients, and 47% (75/160) in patients with both risk factors. Overall, in the <40 years group with indications, only 43% (83/192) were prescribed statins.Conclusion: There is a substantial gap between NICE recommendations and actual statin prescription practices for primary CVD prevention in T1DM patients, particularly in those <40 years with additional risk factors. These findings highlight the need for improved adherence to guidelines in clinical practice to reduce CVD risk in this high-risk population.DisclosureM. Riasat: None. S. Nafees: None. S. Akbar: None. K. Bakht: None. F. Ahmad: None. K. Zamari: None. M. Tufail: None. H. Javed: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-442-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 443-P: The LDL-C/Apo B Ratio Predicts Mortality in Heart Failure Patients
both with and without Type 2 Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 443-P
Abstract: Introduction and Objective: A low LDL-C/Apo B ratio reflects small LDL particle size which like type 2 diabetes (T2DM) is associated with insulin resistance and reflects an unfavorable lipid profile. The LDL-C/Apo B ratio has been shown to be predictive of cardiovascular events in patients with atherosclerotic disease and of cardiovascular and overall mortality in the general population. Whether the LDL-C/ApoB ratio predicts mortality in patients with heart failure independently of the presence of T2DM is unclear and is investigated in the present study.Methods: We enrolled a cohort of 349 patients with clinically evident heart failure, including patients with HFpEF, HFmrEF and HFrEF. T2DM was diagnosed in 140 (40.1%) of these patients according to current ADA guidelines. Prospectively, mortality was recorded over a mean follow-up period of 3.0 ± 2.5 years.Results: At baseline, the LDL-C/Apo B ratio was significantly lower in patients with T2DM than in subjects who did not have T2DM (0.93 ± 0.21 vs. 1.04 ± 0.19, p<0.001). During follow-up, 158 patients died; the mortality rate was higher in patients with than in those without T2DM (55.0 % vs. 40.2%; p<0.001). The LDL-C/ApoB ratio predicted mortality in univariate analysis (HR 0.73 [0.62-0.86]; p<0.001) and after adjustment for age, gender, BMI, hypertension, smoking, LDL-C, HDL-C, triglycerides, NT-proBNP and T2DM (HR 0.55 [0.42-0.75]; p<0.001). In this multivariate adjusted Cox regression model, the LDL-C/Apo B ratio significantly predicted mortality in patients with T2DM (HR 0.51 [0.33-0.79]; p=0.003) as well as in those without T2DM (HR 0.61 [0.39-0.93]; p=0.022)Conclusion: Our findings indicate that the LDL-C/Apo B ratio is a robust predictor of mortality in heart failure patients, irrespective of T2DM state.DisclosureB. Larcher: None. A. Festa: None. A. Mader: None. A. Vonbank: None. A. Leiherer: None. A. Muendlein: None. H. Drexel: None. L. Schnetzer: None. T. Plattner: None. C.H. Saely: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-443-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 444-P: Protein and mRNA Comparison in Complications of Type 2
Diabetes—Integrating Proteomics with Transcriptomics-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 444-P
Abstract: Introduction and Objective: We have previously identified 50 proteins associated with T2D vascular complications (CX). We now measured their mRNA expression in T2D patients with and without CX.Methods: RNA was extracted from citrate plasma samples of 542 people with T2D from the Fenofibrate Intervention and Event Lowering in Diabetes trial (Age: 62±7 yrs; T2D duration: 6±6 yrs; HbA1c: 6.8±1.3%). There were n=179 participants with CX at baseline, n=142 developing first CX during follow-up (FUP) and n=221 who had no CX. OpenArray was used to measure mRNA with normalisation using housekeeping gene (MT-ATP6). For differences between groups ΔΔCT values were used.Results: Seven genes had circulating mRNA levels below the detection limit in all samples, 32 were detected in < 20% of samples. The remaining 11 genes were detected in 23-90% of samples. Genes differentially expressed between T2D patients with and without CX were involved in vascular repair and extracellular matrix remodeling. E.g. FERMT3 mRNA was 1.8-fold higher in those developing macroCX during FUP vs. no CX group. Clusterin mRNA was 1.1-1.5-fold higher with CX during FUP and 1.3-1.7-fold higher with baseline CX vs. no CX. Comparisons of proteomic and mRNA levels across the study groups revealed that in 32% of cases differences in mRNA levels were paralleled in protein level differences. E.g. TLN1 exhibited reduced mRNA and protein expression in subjects who developed both micro- and/or macroCX during FUP. In contrast, in 45% of instances, differences in mRNA were not paralleled by the same differences in protein expression, suggesting potential post-transcriptional regulation in those pathways.Conclusion: These findings underscore the importance of integrating transcriptomic and proteomic analyses to better understand the molecular mechanisms driving vascular complications in T2D and to identify potential therapeutic targets.DisclosureH. Francis: None. A.S. Januszewski: None. M. O'Rourke: None. M.L. Huang: None. F. Ema: None. A.A. Hardikar: None. M.V. Joglekar: None. D. Sullivan: Other Relationship; Amgen Inc. Research Support; Arrowhead Pharmaceuticals, Inc. Other Relationship; Novartis Pharmaceuticals Corporation, Merck Sharp & Dohme Corp. Research Support; Ionis Pharmaceuticals. R.S. Scott: None. A. Jenkins: Advisory Panel; Abbott. Speaker's Bureau; GlaxoSmithKline plc. Research Support; Abbott, Metronics, Ypsomed AG, Insulet Corporation, Jaeb Center for Health Research, Endogenex, Hemsley Charitable Trust. Speaker's Bureau; CSL Seqirus. Research Support; AbbVie Inc, National Institutes of Health, Juvenile Diabetes Research Foundation (JDRF). M.P. Molloy: None. A.C. Keech: Research Support; Abbott, Amgen Inc, ASPEN Australia, Mylan. Speaker's Bureau; Novartis AG, Pfizer Inc. Research Support; Kowa Company, Ltd. Speaker's Bureau; Sanofi. Research Support; AbbVie Inc, Viatris Inc.FundingNational Health and Medical Research Council of Australia (GNT1147879)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-444-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 445-P: Heterogeneous Treatment Effects of Intensive Blood Pressure Control
(IBP) on Major Adverse Cardiovascular Events (MACE) and
Cardiovascular-Kidney-Metabolic (CKM) Syndrome in People with Hypertension
-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 445-P
Abstract: Introduction and Objective: IBP reduced cardiovascular events; however individual treatment benefits may vary by clinical characteristics and co-morbidities. We quantified the variation in IBP benefits across different subgroups to develop strategies for targeted treatment.Methods: We analyzed SPRINT data (n=9,361) using a causal survival forest algorithm and Shapley Additive exPlanations values to identify effect modifiers driving heterogeneity in IBP benefits. Outcomes included MACE onset in the overall population and CKM progression in the stage 2 subsample. A scoring algorithm categorized patients into benefit tertiles based on predicted treatment effects.Results: Baseline characteristics were similar between treatment groups. Key modifiers for MACE were eGFR, logical memory, Framingham risk score, and cognitive scores, while CKM progression modifiers were Sokolow-Lyon index, standing heart rate, and cholesterol levels (Figure). In the high-benefit tertiles, IBP reduced MACE risk by 35% (95% CI: [13%, 51%]) and CKM progression by 28% (95% CI: [10%, 43%]), nearly doubling the overall treatment effects.Conclusion: Our tool identifies subgroups achieving twice the average IBP benefit, highlighting its potential to inform personalized BP management in clinical settings.DisclosureJ. Lee: None. Q. Xue: None. P. Li: None. E. Staton: None. Y. Hong: Consultant; Weight Watchers International. J. Guo: None. M.K. Ali: Advisory Panel; Eli Lilly and Company. H. Shao: None.FundingNational Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health (R01DK133465)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-445-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 446-P: Associations between Insulin Secretory Function and Atherosclerotic
Cardiovascular Disease Risk-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 446-P
Abstract: Introduction and Objective: The relevance of β-cell function in atherosclerotic cardiovascular disease (ASCVD) risk prediction is understudied. We investigated the association of HOMA2β with incident ASCVD outcomes.Methods: We pooled participants' data from 5 cohorts (ARIC, CARDIA, CHS, JHS and MESA) without diabetes or ASCVD at baseline who were followed up for incident ASCVD (any, CHD, stroke and non-fatal MI). We calculated 10-year ASCVD risk using the pooled cohort equation (PCE) and participants were categorized as low (<5%), intermediate (5 - <20%) and high risk (≥20%). HOMA2β was estimated using fasting glucose and insulin, and participants were categorized as low and normal using a pre-specified cut-off (47.64%). Effect modification of PCE risk by HOMA2β categories on incident ASCVD was assessed using Cox proportional hazards regressions.Results: Over 10 years of follow-up, 2397 (13.1%) of 18,230 individuals aged 40-79 years (mean: 57.9 (9.5) years, 45.1% men) developed ASCVD. Across PCE risk categories, individuals with low HOMA2β had higher incidence of ASCVD than individuals with normal HOMA2β (Figure; p for trend <0.001). Results were similar for all cardiovascular outcomes and for groups based on ASCVD risk estimated using PREVENT equations.Conclusion: β-cell function identifies individuals at higher risk of ASCVD events in the general population independent of estimated ASCVD risk.DisclosureA.S. Oguntade: None. J. Varghese: None. J. Guo: None. M.K. Ali: Advisory Panel; Eli Lilly and Company. K. Narayan: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-446-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 447-P: Twenty-Five Years Longitudinal Real-World Analysis of Statin
Therapy Outcomes in People with Diabetes on Telemedicine Follow-up and
Predictors of Cardiovascular Events-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 447-P
Abstract: Introduction and Objective: Longitudinal analysis: data from Diabetes Tele-Management System (DTMS®) over 25 years (1997 to present) to assess impact of telemedicine (TM)-based follow-up on achieving lipid targets & averting events.Methods: N=7,780 PWD. Baseline and longitudinal lipid parameters analyzed, predictors of CV events identified using Generalized Estimating Equations (GEE) model. Median survival times for follow-up durations calculated for each gender.Results: Follow-up rates showed sharp dropout after 1-2 visits (33%), stabilizing thereafter. Baseline LDL 118 ± 40 mg/dL, dropped significantly (sig) to 56 ± 10.38 mg/dL. 91% achieved ADA lipid targets. Median survival times for follow-up: 3.16 y for females & 2.37 y for males. (Fig 1) 53% on high-intensity statins, 37% on moderate-intensity. Top 3 statins: atorvastatin 10 mg (mean LDL = 78 ± 20.3 mg/dL), atorvastatin 5 mg (mean LDL = 57 ± 9 mg/dL), and rosuvastatin 5 mg (mean LDL = 67 ± 24 mg/dL). Only 3% had CV events. GEE analysis: sig predictors of CV events: age (OR = 1.00093, p < 0.001) and low HDL (OR = 0.99995, p = 0.009). Female sex protective (OR = 0.9958, p = 0.015), while A1C (p = 0.051), SBP (p = 0.095), and high-dose statin (p = 0.093) showed marginal associations. BMI, TG, and diabetes duration were not sig predictors.Conclusion: 25-y analysis highlights critical role of TM follow-up in achieving lipid targets and lower CV events.DisclosureJ. Kesavadev: None. A. Shankar: None. G. Krishnan: None. S. Jothydev: None. A. David: None. A. Basanth: None. B.D. Saboo: None. S. Joshi: Advisory Panel; USV Private Limited, Marico, Glenmark Pharmaceuticals, Franco Indian, Twin Health, Biocon, Zydus Lifesciences. Speaker's Bureau; Abbott, Novo Nordisk, MSD.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-447-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 448-P: Dynamic Shifts in Metabolic Pathways Linked to Hyperglycemia under
Surgical Stress-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 448-P
Abstract: Introduction and Objective: Stress hyperglycemia (SH) commonly occurs after coronary artery bypass surgery (CABG), but its underlying metabolic perturbations remain unclear.Methods: We studied 48 participants (12.5% female, mean age 64±10 years) undergoing CABG. SH was defined as three glucose measurements >140 mg/dL or one >180 mg/dL within 4-28 hours post-surgery. High-resolution metabolomics (HRM) analyses were performed at four timepoints: pre-surgery baseline, 2-hours after surgery start, and 24- and 72-hours post-surgery [8,631 metabolites (C18 column)]. Two non-linear mixed-effects models were compared, one incorporating interaction terms for SH status and one without, to identify significant metabolite features. Pathway enrichment analysis was performed using Mummichog V2.Results: Twenty-eight participants developed SH. Seven significant pathways emerged, highlighting alterations in amino acid, pyrimidine, lipid, and microbiome metabolism. As shown in the Figure, key metabolites with the lowest p-values included imidazolelactic acid (histidine breakdown), orotidine (pyrimidine catabolism), sphingosine-1-phosphate (lipid signaling), and dihydroxybutyric acid (propanoate metabolism).Conclusion: Distinct metabolic changes were associated with SH in CABG patients, suggesting potential targets for monitoring, prevention, and therapeutic intervention during perioperative stress.DisclosureD. Ku: None. J. Bartelt: None. S. Kollipara: None. J. Feeley: None. H. Huneault: None. M.R. Smith: None. J. Li: None. F.J. Pasquel: Consultant; Insulet Corporation. Research Support; Novo Nordisk, Dexcom, Inc., Ideal Medical Technologies, Tandem Diabetes Care, Inc, Insulet Corporation. Consultant; Dexcom, Inc.FundingNational Institutes of Health (K23GM128221)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-448-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 449-P: Glycation of the Lipoprotein ApoA-I Is a Novel Biomarker for Early
Predicting of Diabetic Cardiovascular Risk-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 449-P
Abstract: Introduction and Objective: Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in diabetes, primarily driven by chronically elevated blood glucose levels. Diabetes reduces HDL levels and impairs HDL function, both contributing to CVD risk. Glycation of HDL proteins, particularly Amadori-glycation adducts (AGAs), may play a role in HDL dysfunction and CVD development in diabetes. This study tested the hypothesis that hyperglycemia-induced glycation impairs HDL function and promotes CVD in type 2 diabetes (T2D).Methods: HDL was isolated from T2D patients and healthy controls (n=10/group) to assess antioxidant and cholesterol efflux functions. We analyzed HDL proteome composition and post-translational modifications and measured proteome dynamics using ²H2O labeling. Inflammatory markers, including VCAM-1 and TNF-α expressions, were evaluated in human aortic endothelial cells (HAECs).Results: Despite similar lipid profiles, HDL from T2D patients showed reduced antioxidant activity and cholesterol efflux capacity (P<0.05). T2D HDL was enriched with glycated ApoAI, correlating with HbA1c levels. Glycated ApoAI showed increased degradation, with a half-life of 3-5 days, and reduced cholesterol efflux capacity. Diabetic HDL with glycated ApoAI also elevated VCAM-1 expression and TNF-α secretion in HAECs, indicating heightened endothelial inflammation. Higher AGA levels were observed in T2D patients with CVD compared to those without, linking AGAs to CVD in diabetes.Conclusion: Glycated ApoAI may be a novel marker for short-term glycemic control and CVD risk in diabetes. With a shorter half-life than HbA1c, it may reflect hyperglycemia and therapeutic response. These findings suggest glycation-specific targets to manage CVD risk in diabetic and prediabetic populations. Further studies in larger cohorts are needed to validate these results.DisclosureA. Kasumova: None. C. Kim: None. S.R. Kashyap: Research Support; Fractyl Health, Inc. Advisory Panel; GI Dynamics. Research Support; Janssen Pharmaceuticals, Inc, Novartis Pharmaceuticals Corporation. T. Kasumov: None.FundingNational Institutes of Health (1R21AG085590-01); National Institutes of Health (1R21AA029784)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-449-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 450-P: Serum Osteopontin Is Independently Associated with Cardiovascular
Outcomes in Renoprotected, Long-Duration Type 1 Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 450-P
Abstract: Introduction and Objective: Cardiovascular disease (CVD) is a major cause of mortality in people with long-duration Type 1 diabetes (T1D), even among those with excellent cardiometabolic control and without nephropathy (DN). We assessed circulating factors that may be associated with CVD risks in the renoprotected Joslin “Medalists”, with T1D≥50 years.Methods: Medalists were evaluated for self-reported CVD (n=1043), with subsets undergoing coronary artery calcium (CAC; n=142) and cardiac magnetic resonance (CMR; n=111) imaging. Circulating factors such as cytokines and osteopontin (OPN; n=300) were analyzed for associations with CVD outcomes, independent of DN and other cardiometabolic and glycemic risk factors, including HbA1c, continuous glucose monitor (CGM; n=102) metrics, and advanced glycation end products (AGEs; n=200).Results: Only 13% of Medalists have DN, but 40% have CVD. Despite having excellent median HbA1c (7.1%), blood pressure (132/64), HDL (63), and LDL (78), Medalists exhibited high CAC burden (median 937) compared to CMR abnormalities, even without DN. In multivariable analysis, including other inflammatory cytokines, OPN associated with CVD (p<0.01), but not with CAC or CMR parameters. OPN also associated with the AGE, CML (p=0.01), but not with HbA1c or CGM metrics; and was borderline significant with TNF-a (p=0.06). After stratifying by DN, OPN remained associated with CVD only in the non-DN group (p<0.01); and with CML (p<0.01) and TNF-a (p=0.02) only in the DN group.Conclusion: Our results showed that aging people with long-duration T1D, no DN, and excellent cardiometabolic control still possess high atherosclerotic CVD risks. Among the various circulating factors, only elevated OPN levels provided independent CVD risks. Since OPN is expressed in arterial cells in response to hyperglycemia, we speculate that it could be a potential CVD biomarker and may contribute to inflammation and atherosclerosis.DisclosureM. Yu: None. S. Jangolla: None. I. Wu: None. J. Gauthier: None. E. Viebranz: None. Q. Li: None. H. Shah: None. G.L. King: None.FundingAmerican Diabetes Association (9-18-CVD1-005); NHLBI (R01 HL161864-01); Thomas Beatson. Jr. Foundation
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-450-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 451-P: Association of the Genetic Variant Rs10911021 with Coronary Artery
Calcium Score Is Mediated by Alterations of Glutamic Acid Metabolism in
Individuals with Type 2 Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 451-P
Abstract: Introduction and Objective: The risk allele C of genetic variant rs10911021, at the glutamate-ammonia ligase (GLUL) locus, was previously associated with increased risk of coronary artery disease (CAD) and with alterations of glutamic acid (Glu) metabolism/gamma-glutamyl cycle in individuals with type 2 diabetes (T2D). Our aim was to evaluate the association between rs10911021 and subclinical CAD (measured by coronary artery calcium [CAC] score) and assess whether this can be explained by the association of this variant with alterations of Glu metabolism.Methods: 295 individuals with recently diagnosed T2D were genotyped for rs10911021 and underwent CAC evaluation by computed tomography. A targeted metabolomic profile was assessed.Results: Participants' mean age at examination and diabetes duration were 56.8±7.8 and 6.2±2.5 years, respectively. Mean BMI was 32.4±6.5 kg/m2; mean HbA1c was 7.3±1.3%; most participants were treated only with oral antidiabetic medications (73%). The C allele of rs10911021 was associated with increased log(CAC) (beta 0.45, p=0.05, corresponding to a linear CAC increase of 57% per allele copy) and with CAC>10 (as a dichotomous variable, OR 1.45 per allele copy, p=0.03) as well as with higher serum Glu levels (beta 0.10, p-value 0.0009). Glu levels were associated with an increase in log(CAC) (beta 1.85, p=0.00002) and with CAC>10 (OR 4.29, p=0.00004). By contrast, glutamine (Gln) was not associated with either rs10911021 (p=0.59) or log(CAC) (p=0.10). Mediation analysis showed 53% of the effect of rs10911021 on CAC to be mediated by its association with Glu levels (p-value by bootstrapping 0.044).Conclusion: rs10911021 is associated with subclinical coronary artery disease (as assessed by CAC) in the early stages of T2D. This association is partly mediated by Glu serum levels, pointing to a modulatory role of glutamic acid metabolism in the increased risk of CAD observed in T2D.DisclosureF.M. Giuffrida: None. C. Bulcão: None. C. Mendonca: None. C. He: Employee; Agilent Technologies. A. Inoki: None. S. Pennathur: Research Support; Aurinia. A. Doria: Research Support; Abbott, Lexicon Pharmaceuticals, Inc, Dexcom, Inc.Funding5R01HL132254
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-451-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 452-P: Metabolome-Wide Association Study Links an Immunoinflammatory
Response with Metabolic Stress after Coronary Artery Bypass Graft Surgery
(CABG)-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 452-P
Abstract: Introduction and Objective: Stress hyperglycemia (SH) post-CABG is common and associated with post-surgical complications. We analyzed metabolic and inflammatory profiles of participants undergoing CABG.Methods: Participants without diabetes undergoing CABG were recruited. SH was defined as three measurements >140 mg/dL or one >180 mg/dL post-surgery. Soluble urokinase-type plasminogen activator receptor (SuPAR), brain-type natriuretic peptide (BNP), high-sensitivity troponin (HsTn), and C-reactive protein (CRP) were measured along with high-resolution metabolomics (HRM) before and during the perioperative period. We conducted a metabolome-wide association study (MWAS) including clinical and metabolic data layers (R-package xMWAS).Results: A total of 48 participants were included (12.5% female, mean age 64±10 years, BMI 28.3±4.5 kg/m2. Using HRM, 18,055 metabolic features were extracted. In those with SH, 764 features correlated with clinical biomarkers (SuPAR, CRP, and BNP) while for those without SH, only 50 features correlated with BNP, CRP, and HsTn. Increased SH-related pathways included a predominance in fatty acid (SuPAR, CRP), arachidonic acid (CRP), and Urea cycle/amino group (BNP) metabolism.Conclusion: Post-surgical systemic metabolic perturbations are closely linked to a marked immunoinflammatory (SuPAR and CRP) response.DisclosureJ. Feeley: None. D. Ku: None. J. Bartelt: None. S. Kollipara: None. H. Huneault: None. J. Li: None. F.J. Pasquel: Consultant; Insulet Corporation. Research Support; Novo Nordisk, Dexcom, Inc., Ideal Medical Technologies, Tandem Diabetes Care, Inc, Insulet Corporation. Consultant; Dexcom, Inc. M.R. Smith: None.FundingNational Institutes of Health (K23GM128221)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-452-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 453-P: Association between Triglyceride, Glucose, and Body Mass Index and
Long-Term Adverse Outcomes in Heart Failure Patients with Coronary Heart
Disease-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 453-P
Abstract: Introduction and Objective: The triglyceride glucose-body mass index (TyG-BMI) is a reliable surrogate marker of insulin resistance and an emerging predictor of cardiovascular diseases. However, its role in predicting adverse outcomes in heart failure (HF) patients with coronary heart disease (CHD) remains poorly understood. This study is aimed to investigate the association between the TyG-BMI index and long-term adverse outcomes, including all-cause mortality and HF rehospitalization, in patients with HF and CHD.Methods: A single-center, cross-sectional study was conducted on 50 HF patients with CHD. The TyG-BMI index was calculated as: Ln [fasting triglyceride (mg/dL) × fasting blood glucose (mg/dL)/2]×BMI Patients were followed from January 2022 to May 2024 for all-cause mortality and HF rehospitalization. Multivariate Cox regression models and restricted cubic splines with threshold analysis were employed to examine nonlinear associations between TyG-BMI values and outcomes.Results: Over the study period, 5 patients died, and 18 were rehospitalized due to HF. Threshold analysis identified a significant reverse "J"-shaped relationship between the TyG-BMI index and all-cause mortality, with reduced mortality risk observed at higher TyG-BMI values below 250.0. Additionally, a "U"-shaped nonlinear relationship was observed with HF rehospitalization, with an inflection point at a TyG-BMI index of 230.Conclusion: This study demonstrates a nonlinear association between the TyG-BMI index and adverse outcomes in HF patients with CHD. These findings suggest that the TyG-BMI index is a valuable prognostic marker for risk stratification and may inform therapeutic strategies to improve long-term outcomes in this high-risk population.DisclosureD. Raval: None. K.R. Rana: None. F.N. Shaikh: None. V.M. Rathod: None. A. Bhattacharya: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-453-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 454-P: Impact of Exercise Training on Cardiac Function in Individuals with
Obesity with and without Type 2 Diabetes Using Cardiac and 4D Flow MRI-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 454-P
Abstract: Introduction and Objective: Type 2 diabetes (T2D) and obesity are associated with left ventricular (LV) dysfunction, but the impact of exercise interventions on LV function remains unclear. This study aims to assess LV function in individuals with obesity, with and without T2D via supervised aerobic exercise training, using cardiac MRI and time-resolved three-dimensional phase-contrast MRI (4D flow MRI).Methods: 16 overweight controls (OWC; HbA1c = 5.3 ± 0.2%; age = 42.8 ± 6.0 years; 56% female) and 7 individuals with obesity and T2D (HbA1c = 6.8 ± 0.8%; age = 48.3 ± 6.0 years; 57%) completed 15 weeks of exercise training. Maximal oxygen consumption was measured as a marker of cardiorespiratory fitness. Global LV function and strain were analyzed using cardiac MRI. E/A velocity, a standard echocardiographic marker, was assessed using 4D flow MRI. Participants were categorized into low SVi (20.5 ± 3.0 mL/m2) and high SVi groups (30.1 ± 3.6 mL/m2) based on an SVi threshold of 25 mL/m2. Pre- and post-exercise data were compared using paired t-tests.Results: Reclassifying the cohort by SVi showed a significant increase in E/A velocity only in the high SVi group after exercise, with no other biomarkers showing significant changes in either group.Conclusion: Early LV function changes via exercise intervention may be detectable in E/A velocity in individuals with high SVi.DisclosureS. Park: None. E.K. Englund: None. T. Fujiwara: None. D. Enge: Employee; Epic. M. Schäfer: None. B.M. Fonseca: Consultant; Siemens Healthcare Diagnostics. K.S. Hunter: None. J.G. Regensteiner: None. J.E.B. Reusch: Advisory Panel; Medtronic. A.J. Barker: None.FundingAmerican Diabetes Association (4-24-PDF-51)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-454-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 455-P: Role of 3-Hydroxyisobutyrate in Cardiometabolic Disease
-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 455-P
Abstract: Introduction and Objective: The valine catabolite 3-hydroxyisobutyrate (3HIB) was shown to promote insulin resistance in skeletal muscle by increasing lipid content in vivo. Translating this finding to cardiovascular system, it might be hypothesized that 3HIB deranges trans-endothelial fatty acid transport with potential clinical implications.Methods: To measure the impact of 3HIB on the development and progression of atherosclerotic lesions in vivo, ApoE-/- mice were fed a standard laboratory diet (SD) or a Western Diet (WD) for 12 weeks starting at 8 weeks of age to induce atherosclerosis, in presence or not of 3HIB (300mg/kg, i.p injected 3 times a week) (n=6 per group).Results: After the treatment WD+3HIB mice showed a significant reduction in weight and serum triglycerides content and in aortic mean plaque areas compare to WD mice. To investigate the molecular mechanisms involved in the effect of 3HIB, aorta RNA seq analysis was performed (n=6 per group). Biological process enrichment analysis revealed significant modulation of several pathways, including circadian rhythm, calcium signalling, membrane potential regulation. Preliminary RT-PCR experiments confirmed the significant increase of NR1D2 and decrease of CCL2 and NOS2 expression in WD+3HIB mice compared to WD. Next, mRNA expression levels of oxidative stress, lipid metabolism and circadian rhythm genes were evaluated in liver. The preliminary results suggest a significant improvement of liver functions induced by 3HIB treatment under WD conditions and confirmed the modulation of genes involved in circadian rhythm. Finally, preliminary results show that, in HepG2 cells, 3HIB treatment lowered FA uptake and induced the modulation of circadian genes expression, suggesting a direct link that is under investigation.Conclusion: In contrast to elevated levels of endogenous 3HIB serum levels during metabolic and cardiovascular diseases, the 3HIB treatment induces protective effects involving at least in part the modulation of circadian genes.DisclosureV. Casagrande: None. L. Panarello: None. A. Quatrana: None. L. Antonetti: None. C. Internò: None. A. Lepri: None. M. Cardellini: None. M. Federici: None. R. Menghini: None.FundingEFSD/Sanofi 2022
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-455-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 456-P: Effects of Hyperinsulinemia on Fibrinolysis in Insulin Resistant
States-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 456-P
Abstract: Introduction and Objective: Insulin resistance (IR) is associated with atherogenesis. In vitro, insulin induces plasminogen activator inhibitor-1 (PAI-1), an inhibitor of clot breakdown, through a signaling pathway downstream of the insulin receptor. In lipodystrophy (LD) and obesity, IR is pathway selective, meaning insulin signaling is increased in some signal transduction pathways and decreased in others. By contrast, rare mutations of the insulin receptor gene (INSR) block all insulin signal transduction pathways. We hypothesized that PAI-1 is higher in LD vs INSR and healthy controls (HC).Methods: Fasting blood samples from age and sex matched subjects with LD (N=15), INSR (N=10) and HC (N=14) were analyzed for PAI-1, and correlated with A1c and insulin.Results: Mean age was 31±9 years; 72% were female. A1c and insulin were higher in LD and INSR vs HC (HbA1c 7.9±2.6 vs 9.3±3.3 vs 5.3±0.3%, p=0.005; insulin 46[22,79] vs 112[24,298] vs 3[2,4] mcU/mL, p<0.0001). Active PAI-1 was higher in LD vs both INSR and HC. PAI-1 correlated positively with insulin in LD (p=0.007) and negatively in INSR (p=0.048) but did not correlate with A1c.Conclusion: Patients with LD have increased PAI-1 that correlates with insulin, conferring higher risk of impaired fibrinolysis. Patients with INSR, despite the most severe IR, had comparable PAI-1 to HC. This suggest that excess, rather than deficient, insulin signaling impairs thrombolysis in states of post-receptor insulin resistance such as LD and obesity.DisclosureM. Lightbourne: None. L. Metuge: None. M. Startzell: None. M. Walter: None. R. Brown: Research Support; Chiesi, Regeneron Pharmaceuticals, Marea.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-456-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 457-P: Overexpression of SOD2 and P53 Gene Silencing in BM-MSCs–Rescued
Hyperglycemic Endothelial Cells-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 457-P
Abstract: Introduction and Objective:Diabetes is associated with endothelial dysfunction. Studies have demonstrated that CD34+ve endothelial progenitor cells (EPCs) and mature endothelial cells such as HUVEC, both are susceptible to apoptosis in hyperglycemic (HG) environment. EPC more than HUVEC. EPCs are critical for revascularization and p53 gene silencing prevents EPC senescence and helps vascular regeneration, as shown by our group. Our goal was to test whether conditioned media (CM) rather than cells itself would help regeneration. SOD2 upregulation also helps EC regeneration in HG by reducing mito-toxic ROS. We hypothesized that, CM obtained from both p53 silenced and SOD2 overexpressed human stem cells such as bone marrow derived mesenchymal stromal cells (BMMSCs) can improve EC regeneration.Methods: Ad-human-P53 (TP53)-shRNA is used to silence P53, Ad-humanSOD2 is used to overexpress SOD2 and Ad-scrambled-null-shRNA was used as control in BM-MSCs. After transduction, cells were grown in media containing 2% exosome free FBS for only 48h and the collected supernatant was concentrated 10-fold to obtain the conditioned media (CM). Endothelial regeneration was tested using endothelial wound healing assay kit ( from Cell Biolabs # CBA-120-T).Results: Both CM and exosomes derived from CM from BMMSCs achieved EC rescue in HG compared to control CM. However, the two experimental conditions did not show significant difference in the number of cells in the scratch area. Interestingly, in both the conditions there was an increase in SOD2 gene expression, on CM or related exosome addition.Conclusion: Both exosomes and unfractionated CM from SOD2 overexpression plus p53 gene silenced BM MSCs rescued the endothelial cells in hyperglycemic conditions., which further emphasizes exosomes from modified stem cells, play a therapeutic role in rescuing endothelial cells from hyperglycemic conditions by increased mitochondrial functional genes such as SOD2.DisclosureS. Nandula: None. S. Sen: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-457-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 458-P: Exploring the Momentary Lived Experience of Painful Diabetic
Neuropathy in Type 1 Diabetes—A Mixed-Methods Study-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 458-P
Abstract: Introduction and Objective: Painful diabetic peripheral neuropathy (pDPN) is a debilitating condition that worsens quality of life. Mixed methods allow for a deeper exploration of the lived experience of pDPN.Methods: A convenience sample of adults with T1D and pDPN were enrolled. Participants completed a 7 day ecological momentary assessment (EMA) bedtime diary to assess the following pain domains: symptoms, interference, self-efficacy, social support, and relief. Participants were also asked to upload a digital photograph (photo) and caption representing their pDPN experience for that day. Follow-up semi-structured interviews explored the daily pain experience and were analyzed using inductive thematic analysis. EMA and qualitative data were merged to summarize each participant’s pDPN experience.Results: Six participants (67% female, mean age 54 years (SD 8.5), 50% with comorbid depression) completed this study. The EMA response rate was 83.3% and photo upload rate was 80.1%. EMA, interview and photo data showed heterogeneity in pDPN experience, as shown for Participant 2 in Figure 1. Interviews highlighted participants’ fear of developing complications of pDPN.Conclusion: In this study, mixed methods allowed for a personal portrayal of the lived experience of pPDN in T1D. Further studies are needed to better understand how to support the psychosocial needs of patients with pPDN.DisclosureK. Kinger: None. M. DeJonckheere: None. Y. Huang: None. L. Ang: None. C. Martin: None. D. Albright: None. E.L. Reynolds: Employee; Michigan State University, University of Michigan. Research Support; National Institutes of Health, Juvenile Diabetes Research Foundation (JDRF). Other Relationship; American Diabetes Association, Ohio State University. B.C. Callaghan: None. E. Hirschfeld: None. J.J. Iyengar: None. H. Centola: None. J.M. Lee: Advisory Panel; GoodRx. R. Pop-Busui: Board Member; American Diabetes Association. Consultant; Averitas Pharma, Inc. Research Support; Bayer Pharmaceuticals, Inc. Other Relationship; Biogen. Research Support; Juvenile Diabetes Research Foundation (JDRF). Advisory Panel; Lexicon Pharmaceuticals, Inc, Novo Nordisk. Research Support; Novo Nordisk, National Institute of Diabetes and Digestive and Kidney Diseases. Consultant; Roche Diagnostics. K.R. Mizokami-Stout: None.FundingBreakthrough T1D and University of Michigan's Center of Diabetes Excellence; NIDDK (K23DK13129601A13, K01DK134766)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-458-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 459-P: SYW06, a Small-Molecule Modulator of GPCRs, Improves Nerve
Conduction Velocity in a Rhesus Monkey Model of Diabetic Peripheral
Neuropathy-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 459-P
Abstract: Introduction and Objective: Electrophysiological abnormalities, including reduced sensory nerve conduction velocity observed in some diabetic monkeys, are similar to those described in humans with diabetes. This study aims to evaluate the efficacy of SYW06 in improving nerve conduction velocity (NCV) in diabetic monkeys with electrophysiological abnormalities.Methods: Twelve rhesus monkeys diagnosed with diabetic peripheral neuropathy (DPN), aged 13-25 years and with a diabetes duration of 3-7 years, were randomly divided into three groups. One group received vehicle treatment, another group received oral SYW06 twice daily for 8 weeks, and the third group received oral epalrestat once daily for 8 weeks. Nerve conduction studies were conducted before and after the treatment period.Results: In the SYW06 group, compared to baseline values, 17 nerves with abnormal conduction velocities showed a significant increase in sensory conduction velocity (SCV) after 8 weeks of administration, with a mean increase of 4.3 ± 3.4 m/s (P < 0.05 vs. baseline), which was significantly greater than the placebo group (P < 0.01 vs. placebo). In the epalrestat group, 13 nerves with abnormal conduction velocities also showed a significant increase in SCV after 8 weeks, with a mean increase of 4.2 ± 4.0 m/s, which was also significantly higher than the placebo group (P < 0.01 vs. placebo).Conclusion: The results indicate that SYW06 significantly improves NCV in diabetic monkeys. Its efficacy is comparable to that of the commonly used first-line clinical drug, epalrestat, suggesting its potential as an effective therapeutic option for controlling and alleviating DPN progression.DisclosureZ. Yang: None. L. Gong: None. Y. Liang: None. Z. Yao: None. L. Zeng: None. M. Wu: None. Z. Yang: None. W. Zeng: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-459-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 460-P: Gender Differences in Nonlinear Cerebrovascular CO 2 Reactivity for
Type 2 Diabetes Mellitus-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 460-P
Abstract: Introduction and Objective: To study gender differences in nonlinear cerebrovascular responses to CO2 in type 2 diabetes mellitus.Methods: The subjects’ data included 131 T2DM patients, 93 men and 38 women, and 11 normal healthy elderly subjects. The breath-to-breath signals, including CBFV, ABP, and PETCO2, were processed and calculated with the percentage change from baseline to reveal the nonlinear CBFV and CVCi responses to CO2 under hyperventilation. The nonlinear cerebrovascular responses were modeled with a four-parameter sigmoid function (Battisti-Charbonney et al., 2011).Results: The sigmoidal curves of CBFV (Fig. (a)) and CVCi (Fig. (b)) responses and their cerebral vasoreactivity (CVMR) were reconstructed based on the group averaged curve-fit parameters. In both the CBFV and CVCi responses, all T2DM groups (including females and males) showed significant differences (p<0.05) in b, CBFVmax(%), in comparison with the normal elders. Significant differences between male and female DM groups existed exclusively in parameter d(p=0.03), PETCO2 range, of the CVCi responses. This also suggested the CBFV regulation of male DM responded to a wider CO2 range (DM-m: d=1.58±1.86; DM-f: d=0.81±0.5 mmHg), and female DM accessed higher sensitivity to the change of CO2.Conclusion: Gender differences in DM patients notably appeared in their CO2 range of the CVCi responses to CO2 under hyperventilation.DisclosureS. Lin: None. S. Yeh: None. C. Chen: None. H. Tsai: None.FundingNational Science and Technology Council, Taiwan (NSTC 112-2629-E-035-001, NSTC 113-2629-E-035-001)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-460-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 461-P: Diagnostic Accuracy of One Physical Examination Test vs. Three for
Diabetic Peripheral Neuropathy Screening-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 461-P
Abstract: Introduction and Objective: ADA guidelines recommend using three physical examination tests (temperature or pinprick for small-fiber function, vibration for large-fiber function, and monofilament) for annual neuropathy screening. As some guidelines recommend choice of one test, we aimed to determine if the ADA strategy has better cross-sectional diagnostic accuracy over one test in adults with diabetes.Methods: We performed an updated analysis on baseline data from the Toronto Diabetic Neuropathy longitudinal cohort (N=478, 70 (15%) with T1D). 345(72%) participants had neuropathy according to the ‘Toronto Criteria’ nerve conduction study-based classification. Simultaneously, all underwent blinded assessment by independent examiners for pinprick, vibration (by the on-off method), and monofilament. Logistic regression and Area Under the receiver operating characteristic Curve (AUC) determined diagnostic accuracy for each testing strategy.Results: AUC for the combined three-test multiple logistic regression model was 0.84. Each of monofilament, pain, and vibration had slightly lower AUC (0.79, 0.75, and 0.74, respectively, p<0.001 for all comparisons). The optimal cut-point for the three-test model (predicted probability of 0.70) had sensitivity 80%, specificity 75%, likelihood ratio positive (LR+) 3.16, likelihood ratio negative (LR-) 0.27, and Diagnostic Odds Ratio (DOR) 11.7. The optimal cut-point for the single test with highest AUC (3 or fewer sensate monofilament responses out of 8) had sensitivity 67%, specificity 78%, LR+ 3.01, LR- 0.42, and DOR 7.2.Conclusion: The combined three-test ADA strategy had the best overall diagnostic accuracy. However, use of a single physical examination maneuver, such as the monofilament, had acceptable diagnostic performance. Future work should focus on the best strategy for prediction of future neuropathy onset.DisclosureA. Al Mulla: None. E. Parikh: None. L. Lovblom: None. A. Orszag: None. V. Bril: None. B.A. Perkins: Other Relationship; Abbott, Novo Nordisk, Sanofi. Advisory Panel; Abbott, Insulet Corporation, Sanofi, Novo Nordisk, Nephris, Vertex Pharmaceuticals Incorporated. Research Support; Novo Nordisk.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-461-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 462-P: A Study on the Relationship between Microcirculatory Dysfunction
and the Risk of Microvascular Complications in Elderly Patients with Type
2 Diabetes Mellitus-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 462-P
Abstract: Introduction and Objective: This study used non-invasive techniques to assess microcirculatory dysfunction, investigate its influencing factors, and explore its correlation with diabetic microvascular complications.Methods: A retrospective analysis of 323 elderly T2DM patients admitted to Beijing Hospital between March and November 2024 was conducted. Patients were categorized into two groups based on abnormal TcPO2 and/or increased blood flow in lower extremities measured by temperature-controlled LDF. Statistical differences were analyzed using Mann-Whitney U and χ2 tests, while multifactorial logistic regression was used to identify influencing factors.Results: Multivariate regression analysis revealed that female sex was a protective factor for microcirculation dysfunction (OR = 0.542, 95% CI: 0.335-0.878, P = 0.013). Gender-stratified analysis indicated that in elderly male T2DM patients, diabetes duration (OR = 1.071, 95% CI: 1.020-1.126, P = 0.006), hemoglobin A1c (OR = 1.418, 95% CI: 1.147-1.754, P = 0.001), and body mass index (OR = 1.199, 95% CI: 1.059-1.358, P = 0.004) were significant risk factors for microcirculation dysfunction. In elderly female T2DM patients, clinically diagnosed diabetic peripheral neuropathy (OR = 2.475, 95% CI: 1.151-5.325, P = 0.020), abnormal nerve conduction study (OR = 2.148, 95% CI: 1.063-4.340, P = 0.033), and diabetic nephropathy (OR = 3.534, 95% CI: 1.451-8.605, P = 0.005) were identified as significant risk factors.Conclusion: A gender disparity exists in microcirculatory dysfunction among elderly T2DM patients, with higher prevalence in males. In elderly males, diabetes duration, hemoglobin A1c levels, and body mass index are key risk factors. In elderly females, microcirculatory dysfunction is closely associated with diabetic peripheral neuropathy, abnormal nerve conduction, and nephropathy.DisclosureP. Zhao: None. Q. Pan: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-462-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 464-P: Non–high-density Lipoprotein-Cholesterol to High-Density
Lipoprotein-Cholesterol Ratio (NHHR) as a Predictor of All-Cause and
Cardiovascular Mortality in U.S. Adults with Diabetic Peripheral
Neuropathy: NHANES 1999–2004-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 464-P
Abstract: Introduction and Objective: Diabetes and diabetic complications, especially diabetic peripheral neuropathy (DPN), are major causes of death and disability worldwide. The NHHR has emerged as a marker of lipid metabolism and cardiovascular risk. However, the prognostic value of the NHHR in patients with DPN has not been established.Methods: This cohort study used data from the NHANES and analyzed 304 adults with DPN. Participants were categorized based on NHHR tertiles and Cox proportional hazards models were used to assess the association between NHHR and all-cause and cardiovascular mortality. Restricted cubic splines were used to determine non-linear associations and subgroup analyses assessed differences in demographic and clinical characteristics.Results: NHHR exhibited a U-shaped association with all-cause mortality. There was an inverse relationship between all-cause mortality and an NHHR ≤ 3.27 (HR: 0.46, 95% CI: 0.31-0.68) and a positive association between all-cause mortality and an NHHR > 3.27 (HR: 1.25, 95% CI: 1.02-1.52). Subgroup analyses showed that the protective effect of an NHHR ≤ 3.27 was stronger in younger, male, non-obese, and adults with hypertension or CKD. An inverse association with cardiovascular mortality was observed (HR: 0.55, 95% CI: 0.30-0.99) for an NHHR ≤ 3.27, but the inverse association did not exist for an NHHR > 3.27. The inverse association was only observed in BMI subgroups and individuals with hypertension or CKD.Conclusion: The NHHR was shown to have a U-shaped association with all-cause mortality and an L-shaped association with cardiovascular mortality in adults with DPN. Targeted lipid management to maintain an NHHR of 3.27 may reduce the risk of all-cause and cardiovascular mortality, especially in specific populations, such as women and individuals with hypertension or CKD.DisclosureQ. Cai: None. S. Fei: None. W. Wang: None. L. Guo: Research Support; Abbott, AstraZeneca, Bayer Pharmaceuticals, Inc, Eli Lilly and Company, Innovent Biologics, Merck & Co., Inc, MSD Life Science Foundation, Novo Nordisk A/S, Sanofi, Jiangsu Hengrui Pharmaceuticals Co., Ltd, Tonghua Dongbao. Q. Pan: None.FundingNational Natural Science Foundation of China (82270881)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-464-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 465-P: The Sweet Sting—Momentary Neuropathic Pain and Glucose
Elevations-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 465-P
Abstract: Introduction and Objective: Poor glycemic control as assessed by glycated hemoglobin (A1c) is a strong risk factor for painful diabetic peripheral neuropathy (pDPN) in type 1 diabetes (T1D). However, the relationship between momentary glucose elevations and momentary increased neuropathic pain (NP) is unclear. In this study, glucose elevations prior to and following momentary NP was evaluated in T1D.Methods: Continuous glucose monitoring-derived (CGM) elevations prior to and following momentary NP symptoms were evaluated in 40 participants with T1D (62.5% with known pDPN, mean age 56 years (SD 14), 45% female, mean A1c 7.3% (SD 1.3)) who completed a 14-day ecological momentary assessment (EMA) battery of neuropathic and overall pain symptoms 4 times daily (morning, afternoon, evening, bedtime) while simultaneously wearing a personal CGM. Linear mixed models adjusted for age, sex, smoking, and 14-day mean glucose were used to evaluate inter- and intra-person associations between glucose elevations (defined as mean of the 4-hour glucose > mean of the 14-day CGM period) prior to and following EMA neuropathic and generalized pain prompts to determine if glucose elevations precede or follow elevations in pain (defined as momentary neuropathic or generalized pain scores >14-day mean).Results: Regression models revealed higher NP levels associated with subsequent CGM-derived glucose elevations (point estimate [PE]: 0.03 (95% CI 0.01-0.07)). In contrast, there were no associations between CGM-derived glucose elevations and subsequent momentary NP (PE: 0.07 (95% CI -0.02-0.17)). Similarly, there were no associations between CGM-derived glucose elevations and momentary generalized pain in either direction.Conclusion: This study suggests that, within T1D individuals, increased momentary NP precedes glucose elevations. Further studies are needed to understand the mechanisms linking NP to glucose elevations as well as whether pain reduction leads to improvements in momentary glucose.DisclosureK.R. Mizokami-Stout: None. M. Plegue: None. E. Hirschfeld: None. L. Ang: None. J.J. Iyengar: None. H. Centola: None. D. Albright: None. E.L. Reynolds: Employee; Michigan State University, University of Michigan. Research Support; National Institutes of Health, Juvenile Diabetes Research Foundation (JDRF). Other Relationship; American Diabetes Association, Ohio State University. B.C. Callaghan: None. R. Pop-Busui: Board Member; American Diabetes Association. Consultant; Averitas Pharma, Inc. Research Support; Bayer Pharmaceuticals, Inc. Other Relationship; Biogen. Research Support; Juvenile Diabetes Research Foundation (JDRF). Advisory Panel; Lexicon Pharmaceuticals, Inc, Novo Nordisk. Research Support; Novo Nordisk, National Institute of Diabetes and Digestive and Kidney Diseases. Consultant; Roche Diagnostics. J.M. Lee: Advisory Panel; GoodRx.FundingBreakthrough T1D; University of Michigan's Center of Diabetes Excellence; NIDDK (1K23DK13129601A1)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-465-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 466-P: Exploration of Single Nucleotide Polymorphisms Associated with
Small-Fiber Neuropathy-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 466-P
Abstract: Introduction and Objective: Introduction & Objective: Small fiber neuropathy (SFN) is known to develop early in the course of diabetic polyneuropathy (DPN). It has been shown that single nucleotide polymorphisms (SNPs) are involved in DPN, but how SNPs correlate with SFN has not yet been investigated. In the present study, we explored the correlation in Japanese health check cohort.Methods: Methods: 906 participants, including 785 controls, 121 fasting hyperglycaemia (IFG) subjects and 76 type 2 diabetes subjects (DM), in the 2017 Iwaki Health Promotion Project were evaluated. Pain threshold reflecting SFN was evaluated by Pain Threshold Induced by Intra-epidermal Electrical Stimulation (PINT) method. The weakest stimulation value in the PINT test was defined as the PINT index. A PINT index of 0.15 mA or less was defined as a low PINT index group and others as a high PINT index group. Genomic association analysis (GWAS) was performed using extracted DNA to examine the SNPs by Japonica array.Results: RESULTS: PINT index was significantly increased in IFG compared to healthy subjects (0.21 ± 0.22 mA vs. 0.15 ± 0.13 mA, p < 0.01). In GWAS, the obtained p-values were plotted in Manhattan plots and quantile-quantile plots, which revealed 10 SNPs with log10(p) > 5. Among them, rs482912 was further studied. rs482912 was divided into CC variant (143 cases), CT variant (420 cases) and TT variant (343 cases), in which there were no significant differences in weight and metabolic parameters. PINT index was significantly lower in CC than in the others (CC: 0.13 ± 0.13 mA, CT: 0.14 ± 0.13 mA, TT: 0.17 ± 0.16 mA, p < 0.01, respectively). When restricted to diabetic patients, the PINT index was significantly lower in the CC group than in the other groups (CC: 0.07±0.02 mA, CT: 0.19 ± 0.18 mA, TT: 0.17 ± 0.12 mA, p < 0.01, respectively).Conclusion: CONCLUSION: The CC variant of rs482912 may have an suppressive effect on the deterioration of pain threshold evoked by type 2 diabetes.DisclosureH. Mizukami: None. S. Ogasawara: None. Z. Wang: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-466-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 467-P: Hyperglyceamia-Indued Oxidative Stress Inflicted Enteric Glial
Cells of Mice via the Novel Pathway Redoxosomes/p66shc Activation In Vivo
and In Vitro-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 467-P
Abstract: Introduction and Objective: Diabetic gastrointestinal dysfunction is a enteric nervous system impairment. We explored the pathogenesis of mice enteric-glial cell (EGC) damages via the oxidative stress pathway-redoxosomes/p66SHCactivation in diabetes models.Methods: STZ-diabetic C57BL/6J mice were intestinal-intramuscularlly injected with RAC1/NOX inhibitors or p66SHC-silencing AAVs, respectively. Enteric glial cell line were cultured and transfected. The cell viability was determined using the MTT assay and cell apoptosis using the TUNEL. With ntracellular ROS generation assessment, NOX activity and western blot were determined. Immunofluorescence images were analyzed.Results: Week-6 diabetic mice with hyperglycemia showed the increased cell apoptosis of EGCs in the duodenum, with the increased MDA levels and the decreased SOD activities. Hyperglycemia significantly reduced cell viability and induced cell apoptosis with increased ROS generation and MDA levels, reduced SOD activities and the increased NOX4 expression in EGCs of the duodenum. Pre-treatment with RAC1 inhibitor (NSC23766) or NOX inhibitor (VAS2870) to deactivate redoxosomes under hyperglycemic stress attenuated hyperglycemic stress-induced cytotoxic effect in EGCs, via decreasing ROS generation and MDA level, and increasing SOD activity. Intestinal intramuscular injection of NSC23766 or VAS2870 decreased cell apoptosis in EGCs of the duodenum. RAC1 inhibitor or NOX inhibitor pre-treatment blocked hyperglycemia-induced serine36 phosphorylation and mitochondrial translocation of p66SHC in EGCs of the duodenum. The p66SHC knockdown reduced cell apoptosis of EGCs in the duodenum with decreased MDA levels and increased SOD activities.Conclusion: Our findings suggest that the redoxosomes/p66SHC signaling is involved in the oxidative damage of EGCs during the pathological process of diabetic gastrointestinal dysfunction.DisclosureJ. Li: None. Y. Jiang: None. X. Zhu: None. X. Zhu: None.FundingNational Natural Science Foundation of China ( 820708320); Cohort and Clinical Research Program of Wuxi Medical Center, Nanjing Medical University (WMCC202308, WMCC202322); and Wuxi Science and Technology Development Fund (N20202006)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-467-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 468-P: The Course of Cardiac Autonomic Function in Recently Diagnosed Type
2 Diabetes over the Next Five Years Is Determined by Glycemic Control-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 468-P
Abstract: Introduction and Objective: Cardiovascular autonomic diabetic neuropathy (CADN) is characterized by reduced heart rate variability (HRV), but the course of HRV in people with type 2 diabetes compared to those with normal glucose tolerance (NGT) and its key determinants remain unclear. We aimed to evaluate changes in HRV after the first five to six years of type 2 diabetes compared with NGT.Methods: Included were 238 individuals with recently diagnosed type 2 diabetes (known diabetes duration ≤1 year) and 53 with NGT from the German Diabetes Study (GDS): age: 52.2 (45.3; 59.8)/49.9 (38.3; 59.7) years, male: 72/74%, BMI: 30.7 (26.5; 34.9)/26.7 (23.9; 29.0) kg/m², HbA1c: 44.3 (39.9; 49.7)/34.4 (32.2; 35.8) mmol/mol. HRV was assessed during a hyperinsulinemic-euglycemic clamp including eight time and frequency domain indices.Results: At baseline, 2 of 8 HRV measures were lower in type 2 diabetes compared to NGT after adjustment for sex, age, BMI, and antihypertensive treatment. After five years, five HRV measures deteriorated in type 2 diabetes, compared to one in NGT. Stratifying type 2 diabetes participants by HbA1c levels and changes revealed group differences: very-low-frequency (VLF) power improved in well-controlled type 2 diabetes (ΔHbA1c<5.46 mol/mmol and HbA1c<53 mol/mmol) compared to NGT (β=0.187, P<0.05), whereas low-frequency (LF) power deteriorated in those with HbA1c ≥53 mol/mmol or ≥Δ5.46 mol/mmol compared to NGT (β=-0.174, P<0.05). Five HRV measures deteriorated in participants with poorly versus well-controlled type 2 diabetes (e.g. LF power -212 (-582; -23) vs -82 (-367; 94) ms², all P<0.05). The decline in HRV was associated with changes in glycemia in the type 2 diabetes and NGT group (e.g. ΔVLF and Δfasting glucose (β=-0.207, P<0.05) and ΔVLF and waist circumference (β=-0.199, P<0.05) in type 2 diabetes).Conclusion: Near-normal glycemic control may prevent or delay the onset of CADN in people with recently diagnosed type 2 diabetes.DisclosureA. Strom: None. D. Ziegler: Consultant; Wörwag. Speaker's Bureau; Viatris Inc. Consultant; Nevro Corp. Advisory Panel; Grünenthal. Speaker's Bureau; Sanofi-Aventis Deutschland GmbH, GlaxoSmithKline plc. Consultant; Procter & Gamble. G. Sipola: None. R. Wagner: Speaker's Bureau; Boehringer-Ingelheim, Novo Nordisk. Advisory Panel; Sanofi. Speaker's Bureau; Sanofi. Advisory Panel; Lilly Diabetes. M. Roden: Research Support; Boehringer-Ingelheim. Advisory Panel; Echosens. Speaker's Bureau; Madrigal Pharmaceuticals, Inc. Advisory Panel; MSD Life Science Foundation. Board Member; Novo Nordisk. Advisory Panel; TARGET PharmaSolutions, Inc. G.J. Bönhof: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-468-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 469-P: Therapeutic Potential of Imeglimin for Diabetic
Neuropathy—Neuroprotective Effects in Type 1 Diabetic Rats-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 469-P
Abstract: Introduction and Objective: Imeglimin is an oral antidiabetic agent with beneficial effects on mitochondrial function. Studies have shown that imeglimin reduces gluconeogenesis and stimulates muscle glucose uptake, thereby improving insulin resistance. Additionally, it promotes insulin secretion by increasing NAD+ levels in pancreatic β-cells. Studies have also demonstrated that imeglimin reduces mitochondrial oxidative stress and the activity of mitochondrial complex I in hepatic mitochondria of mice fed high-fat or high-sucrose diets. However, the effects of imeglimin on diabetic neuropathy remain unclear. Therefore, we investigated the effects of imeglimin on diabetic neuropathy in streptozotocin (STZ)-induced diabetic rats.Methods: Male Wistar rats were injected intraperitoneally with vehicle or STZ to induce diabetes. Four weeks after STZ injection, rats were orally gavaged with vehicle or imeglimin (200 mg/kg) twice daily for four weeks. Subsequently, assessments of mortor nerve conduction velocity (MNCV), sciatic nerve conduction velocity (SNCV), sciatic nerve blood flow (SNBF) were performed.Results: Imeglimin did not significantly affect body weight or blood glucose levels. Compared to controls, diabetic rats exhibited a trend toward decreased MNCV, which was attenuated by imeglimin. Diabetic rats also showed significant reductions in SNCV, and SNBF compared to controls. Imeglimin treatment significantly ameliorated the reduction in SNCV and SNBF.Conclusion: These findings from STZ-induced diabetic rats indicate the therapeutic potential of imeglimin for diabetic neuropathy.DisclosureW. Nihei: None. A. Kato: None. T. Sato: None. T. Himeno: None. N. Nakamura: None. K. Sango: None. K. Naruse: None. J. Nakamura: Speaker's Bureau; Daiichi Sankyo, Novo Nordisk. H. Kamiya: Research Support; Sumitomo Dainippon Pharma Co., Ltd. Speaker's Bureau; Sumitomo Dainippon Pharma Co., Ltd. K. Kato: Speaker's Bureau; Daiichi Sankyo.FundingJSPS KAKENHI (24K09971)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-469-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 470-P: Alterations in NMJ-Associated Stromal Cells in Diaphragms of Mice
with Obesity and Type 2 Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 470-P
Abstract: Introduction and Objective: Pulmonary disorders impact 40-80% of individuals with obesity and include dyspnea on exertion, which reduces exercise tolerance, and obesity hypoventilation syndrome (OHS), which doubles 5-year mortality rate. Type 2 diabetes confers an increased risk of chronic respiratory failure, with phrenic neuropathy implicated in its pathogenesis. Fibro-adipogenic progenitors (FAPs) are muscle mesenchymal cells recently shown to be critical for maintenance of neuromuscular junctions (NMJs). Notably, an FAP subpopulation marked by Hsd11b1 and Mme expression, geographically associates with NMJs, suggesting a functional link. Our previous work demonstrated high fat diet feeding to significantly alter diaphragm FAP profiles; however, the impact of obesity and diabetes on diaphragm NMJ-associated FAPs remains uninvestigated.Methods: We evaluated this in a model of long-standing obesity/ type 2 diabetes by subjecting mice to a 12-month diet-induced obesity (DIO) protocol beginning at 2-months old–analyzing NMJ morphology by confocal microscopy and diaphragm FAPs by single cell RNA sequencing (scRNA-seq).Results: 12-month DIO mice developed respiratory dysfunction, as indicated by whole body plethysmography (tidal volume reduction during hypoxic and hypercapnic challenges) and non-invasive ultrasound (reduced diaphragm excursion amplitude). NMJs of DIO mice exhibited an abnormal crumpled morphology and increased peri-NMJ extracellular matrix deposition. Hsd11b1/ Mme-expressing NMJ-associated FAPs assumed a fibro-inflammatory phenotype with enhanced expression of the genes encoding NF-kB, interleukin-6, and fibronectin.Conclusion: These data demonstrate that alterations in respiratory function and diaphragm NMJ architecture correspond with the emergence of fibro-inflammatory NMJ-associated FAPs in a model of long-term obesity and type 2 diabetes.DisclosureJ. Cumbum Syed: None. S.K. Patterson: None. J. Yang: None. M. Woo: None. E.D. Buras: None.Funding5 K08 HL14737701-05
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-470-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 471-P: Establishment and Validation of Rodent Models for Diabetic
Neuropathy—A Robust Platform for Therapeutic Evaluation-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 471-P
Abstract: Introduction and Objective: Diabetic neuropathy, affecting about 50% of diabetic patients, leads to chronic pain, sensory loss, and increased risks of foot ulcers and amputations, significantly impacting quality of life and healthcare costs. Robust animal models are essential for research and therapeutic development, despite the challenges in replicating human pathophysiology and ensuring reproducibility. In this study, we developed diabetic neuropathy models using db/db mice and STZ-induced diabetic animals, completing efficacy testing on multiple agents to evaluate their therapeutic potential.Methods: Diabetic neuropathy models were established using male db/db mice and STZ-induced Type I diabetic rats (single STZ injection, 65 mg/kg). Gabapentin (100 mg/kg for mice, 50 mg/kg for rats) was administered orally one hour before testing. Evaluations included paw withdrawal threshold (Von Frey test), sciatic nerve conduction velocity, intra-epidermal nerve fiber quantification (PGP9.5), and CGRP immunostaining.Results: Both db/db mice and STZ-induced diabetic rats exhibited a significantly decreased paw withdrawal threshold, confirming successful development of diabetic neuropathy. Gabapentin alleviated pain sensitivity in db/db mice. Positive control drugs, including pregabalin, gabapentin, naproxen, SB-705498, meloxicam, rimegepant, sumatriptan, and carbamazepine, showed efficacy in STZ-induced diabetic rats. Sciatic nerve conduction velocity was significantly reduced in both models. Additionally, intra-epidermal nerve fibers were significantly decreased in db/db mice, indicating small fiber neuropathy.Conclusion: Our study successfully established models of diabetic neuropathy, demonstrating significant neuropathic pain and impaired nerve conduction. Positive control treatments, including Gabapentin, effectively alleviated these complications, highlighting their potential therapeutic benefits.DisclosureT. Hu: None. H. Huang: None. C. Zhang: None. T. Li: None. Y. Li: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-471-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 472-P: Development and Validation of STZ-Induced Diabetic Retinopathy
Models for Therapeutic Evaluation-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 472-P
Abstract: Introduction and Objective: Diabetic retinopathy affects about 35% of diabetic patients and is a leading cause of adult blindness, significantly impacting quality of life and healthcare costs. Developing robust animal models for research and therapeutic development is challenging due to the need to replicate human pathophysiology and ensure reproducibility. In this study, we developed diabetic retinopathy models using STZ-induced diabetic animals and tested a reference agent to evaluate therapeutic potential.Methods: Diabetic retinopathy model was developed using STZ-induced type I diabetic rats. A single intraperitoneal (i.p.) injection of STZ (150 mg/kg; Sigma, S0130-1G) was administered for the induction of diabetes on day 1. Aflibercept (25 mg/kg, Eylea, Bayer) was intraperitoneally injected once a week from the 4th week after STZ modeling (Day 28). In-life and terminal readouts include retinal thickness by Optical coherence tomography (OCT), retinal function by ERG, and retinal pathology by CD45 immunohistochemistry (IHC) analysis.Results: Diabetic retinopathy was assessed using full-field electroretinogram (ERG) in STZ-induced diabetic mice. STZ mice exhibited significantly increased latency and reduced amplitude of a- and b-waves, indicating retinal functional deficits. Aflibercept (25 mg/kg, i.p., weekly in the last 4 weeks) significantly improved these ERG parameters. OCT showed reduced retinal thickness in STZ mice, which increased significantly with Aflibercept treatment. CD45 IHC analysis revealed increased CD45-positive cells, indicating inflammation, which was significantly reduced by Aflibercept.Conclusion: Our study successfully established a model of diabetic retinopathy, demonstrating significant retinal dysfunction and inflammation. Aflibercept effectively alleviated these complications, highlighting its potential therapeutic benefits.DisclosureT. Hu: None. H. Huang: None. C. Zhang: None. T. Li: None. Y. Li: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-472-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 473-P: Predicting Diabetic Retinopathy Using Saudi Insurance Claims
Data—Development and Validation of a Real-Time Risk Stratification
System-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 473-P
Abstract: Introduction and Objective: Diabetic retinopathy (DR) is a leading cause of visual impairment and can be prevented with early detection. While most predictive models use electronic health records (EHRs), their accessibility and scalability can be limited. This study aims to develop and validate a real-time risk stratification system for DR using Saudi insurance claims data, an underutilized resource in predictive health analytics.Methods: A retrospective cohort with Type 2 diabetes, insured by MEDGULF, was analyzed using claims data from July 2022 to July 2024. The observation period (July 2022-July 2023) was used to train the system, and the prediction period (July 2023-July 2024) was reserved for validation. Key input features included ICD-10 diagnosis codes, unstructured clinical notes on reason of visit and chief complaint and demographic and healthcare utilization data. The system’s performance was evaluated using AUROC and sensitivity at a fixed threshold of 80%, with calibration assessed for robustness.Results: The system achieved an AUROC of 0.720 (95% CI: 0.708-0.736) on a validation set of 7,410 patients, demonstrating reliable discrimination and solid performance in identifying high-risk patients. Stratification into risk categories allowed for targeted interventions, ensuring timely management of patients at risk of DR.Conclusion: This real-time system demonstrates the feasibility and clinical utility of using Saudi insurance claims data for DR risk prediction, offering a scalable solution with strong potential for reducing diabetic complications. Future work will include prospective validation and integration into clinical care pathways to optimize patient outcomes.Disclosure G. Ghosheh: Employee; iO Health. M. Ghosheh: Employee; iO Health. W. Afzal: Employee; MEDGULF Insurance & Reinsurance Company. M.A. Mohamed: Employee; MEDGULF Insurance & Reinsurance Company. A. Kheir: Employee; MEDGULF Insurance & Reinsurance company.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-473-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 474-P: Progression of Diabetic Retinopathy in Wales during the COVID-19
Pandemic-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 474-P
Abstract: Introduction and Objective: Between March and September 2020, routine healthcare in the UK, including diabetic retinopathy (DR) screening, was paused due to the COVID-19 pandemic. This created a natural experiment to explore the impact of extended screening intervals.Methods: Data from Diabetic Eye Screening Wales (DESW) and primary care were linked using the Secure Anonymised Information Linkage databank (SAIL). Individuals screened within 12 months pre-lockdown and rescreened between March 2020 and August 2022 were included.Results: Of 12,424 individuals with no DR pre-lockdown, 84.3% remained free of retinopathy post-lockdown, 15.8% progressed to background retinopathy, and 0.3% to referable retinopathy. Background Retinopathy (Pre-Lockdown): Of 11,694 individuals with background DR pre-lockdown, 30.8% regressed to no retinopathy, 64.9% remained with background DR, and 4.4% progressed to referable diabetic retinopathy (RDR). Of 731 individuals with RDR pre-lockdown, 3.3% had no DR post-lockdown, 36.0% regressed to background DR, and 60.7% remained at referable level. Of 24,866 individuals with no maculopathy pre-lockdown, 94% remained maculopathy-free, while 6.0% developed diabetic maculopathy. Diabetic Of 257 individuals with diabetic maculopathy pre-lockdown, 50.6% regressed to no maculopathy, while 49.4% remained unchanged.Conclusion: The risk of progression from no DR to RDR or maculopathy was low (0.3% and 6.0%, respectively). Only 10% of those referred with suggested maculopathy required treatment. This study provides further evidence that screening biennially is considered safe for those without DRDisclosureR.L. Thomas: None. W. Cheung: None. J. Rafferty: None. L. Pratt: None. J. Cherry: None. R. Reynolds: None. G. Williams: None. S.C. Bain: Research Support; Novo Nordisk A/S, Lilly Diabetes. Speaker's Bureau; Menarini, AstraZeneca. Research Support; Boehringer-Ingelheim, Abbott Diagnostics, Amgen Inc. D.R. Owens: None.FundingHealth and Care Research Wales (HRG-20-1776(P))
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-474-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 475-P: Screening for Diabetes-Related Retinopathy in Bermuda—An
Observational Study with the Bermuda Diabetes Association-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 475-P
Abstract: Introduction and Objective: This pilot study aimed to assess the burden of diabetic retinopathy (DR) amongst a small cohort of people with diabetes in Bermuda.Methods: People with diabetes mellitus (DM) were invited (social media, posters, radio) to attend diabetic eye-screening free of charge at the Bermuda Diabetes Association (BDA) or the Patient-Centred Medical Home (PCMH), King Edward VII Memorial Hospital. Lifestyle and diabetes questionnaires were undertaken, and blood pressure, HbA1c, and Body Mass Index (BMI) determined. Following visual acuity testing using the Snellen chart, eyes were dilated (1% tropicamide) and images taken with Optomed Aurora (Finland) handheld non-mydriatic cameras. A macula-centred and an optic disc-centred image were taken per eye where possible. These were then graded by 2 experienced graders and an adjudicator. Results letters were sent to GPs for all attendees.Results: Altogether, 172 people with diabetes were screened (132 at BDA, 40 at PCMH), 61% were female, 88% had type 2 DM. mean age was 65.5 years (range 15-89), mean diabetes duration 13.3 years (1-50), mean HbA1c 7.6% (5.1-13.1) and mean BMI 31 kg/m2 (18-56.3). Initial grading revealed that 58% had no DR, 19% had background DR and 23% were recommended to their GP for onward referral, of which 34% required laser treatment for diabetes related eye disease. Most were unaware of their condition.Those with BDR or RDR had significantly longer duration of diabetes (mean 15.5, 15.0 vs 8.0 years) and higher HbA1c levels (mean 7.5, 7.9 vs 6.8%) compared to those without DR, respectively.Conclusion: This pilot screening study revealed a relatively high rate of referrals to ophthalmologists. However, a more extensive study is required to determine the true prevalence of DR in Bermuda to provide a basis for establishing a systematic screening program to prevent sight loss and blindness, in this vulnerable population.DisclosureR.L. Thomas: None. C. Jamison: None. E. Setzu: None. P. Huhtinen: Employee; Optomed. L. Rockhead: None. D. Jones: None. T. Peto: Advisory Panel; Bayer Pharmaceuticals, Inc. D.R. Owens: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-475-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 476-P: Serum EG-VEGF Levels in Patients with Diabetes with and without
Retinopathy-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 476-P
Abstract: Introduction and Objective: Diabetic retinopathy (DR) is associated with hyperglycemia and inflammatory biomarkers such as Vascular Endothelial Growth Factor. Another molecule, Endocrine Gland-derived Vascular Endothelial Growth Factor (EG-VEGF) is present in human sera and is hypothesized to play a role in angiogenesis. We aim to determine whether DR severity is correlated to circulating levels of biomarkers associated with inflammation and vascular proliferation such as EG-VEGF.Methods: We examined 143 patients with diabetes and being seen by a retina specialist. Patients received a blood draw and were split into cohorts based on their retinal findings: Diabetes No Retinopathy (DNR), Non-proliferative DR (NPDR), or Proliferative DR (PDR), (n=47, n=49, and n=53 respectively). Serum was analyzed for biomarker concentrations of EG-VEGF using an enzyme-linked immunosorbent assay (ELISA).Results: Samples were run in duplicate. The means of the log EG-VEGF concentrations for DNR, NPDR, and PDR were 1.95, 2.22, and 1.91 respectively. A Kruskal-Wallis test was performed with a p-value >0.05 (0.93). In each of the cohorts, approximately half of the samples were below baseline value.Conclusion: Although EG-VEGF has been characterized with angiogenic capacities, we found no correlation regarding DR severity and the concentration of serum EG-VEGF. Further studies with additional angiogenesis-related biomarkers and subgroup analyses may offer deeper insights.DisclosureJ. Stroumza: None. J. Lee: None. C.M. Sooranahalli: None. F. De Alba: None. O.M. Iqbal: None.FundingIllinois Society for the Prevention of Blindness
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-476-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 477-P: Semaglutide Is Associated with Lower Risk of Diabetic Retinopathy
in a Saudi Cohort with Type 2 Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 477-P
Abstract: Introduction and Objective: Glucagon-like peptide-1 Receptor Agonists (GLP-1RA) are effective glucose-lowering medications that also promote weight loss and reduce cardiovascular risk in patients with Type 2 diabetes(T2DM), however, in SUSTAIN -6, the development of retinopathy related complications were significantly higher in the Semaglutide group compared to the placebo group. Therefore, still more data is needed to assess the risk of retinopathy in different populations. The aim of the current study was to assess the prevalence of diabetic retinopathy (DR) in Saudi patients with type 2 diabetes who were prescribed Semaglutide compared to those who were not on GLP-1RA.Methods: This was a cross-sectional study that was done in 833 patients with type 2 diabetes, of whom 317 patients were on Semaglutide and 516 who were not on GLP-1RA treatment. Ethical approval was obtained from King Fahad Medical City Committee. SPSS was used for statistical analysis. Chi square test was used to compare the frequencies of DR between the two groups. Binary regression was used to determine the independent predictors of diabetic retinopathy.Results: The prevalence of DR in the whole group was 24.8 % ( 207/833). The prevalence of DR in those who were on Semaglutide was 18.3 % ( 58/317) compared to 28.9 % (149/516) in those who were not on GLP1RA, respectively, P < 0.001. Logistic regression analysis showed that age (P 0.03), diabetes duration (P <0.001), HbA1c ( P <0.001), Semaglutide treatment (P< 0.001) and estimated GFR ( P < 0.001) were the independent predictors of DR in a model that also included BMI, gender, LDL cholesterol, Empagliflozin treatment and BP. The odds ratio for the risk of DR was 1.48 for HbA1c and 0.49 for Semaglutide treatment,Conclusion: Semaglutide treatment was associated with 51 % lower risk of DR in our cohort after adjusting for all possible confounding factors. These data are reassuring regarding the risk of retinopathy with GLP-1RA, however, further larger studies are needed.DisclosureI. Brema: None. L.R. AlMazrou: None. M. Almehthel: Advisory Panel; Novo Nordisk. Speaker's Bureau; Novo Nordisk. Research Support; Novo Nordisk. Advisory Panel; Sanofi. Speaker's Bureau; Sanofi. Research Support; Sanofi. Speaker's Bureau; Lilly Diabetes. Advisory Panel; Abbott. Speaker's Bureau; Abbott. Advisory Panel; Dexcom, Inc. Speaker's Bureau; Bayer Pharmaceuticals, Inc.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-477-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 478-P: Application of Plasma Proteomics to Explore Potential Biomarkers of
Diabetic Macular Edema-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 478-P
Abstract: Introduction and Objective: Diabetic macular edema (DME), a sight-threatening retinopathy, is a leading cause of vision loss in persons with diabetes mellitus. Despite strict control of systemic risk factors, a fraction of patients with diabetes developed DME, suggesting the existence of other potential pathogenic factors underlying DME. This study aimed to explore the difference of protein expression between patients with DME and diabetes patients without DME by using isobaric tag for relative and absolute quantification (iTRAQ) proteomics, and to identify potential biomarkers of DME.Methods: To match clinical parameters between case and control subjects, patients with DME (DME, n=30) or those with diabetes but without DME (Control, n=30) were assigned to the present case-control study. Distinct proteomic profiles of serum were examined using liquid chromatograph-mass spectrometer and mass spectrometer (LC-MS/MS).Results: A total of 17 distinct proteins between DME and Control groups were identified (VIP > 1, Fold Change > 1.2 or < 0.83, and P < 0.05). Among them, 15 proteins were upregulated, and 2 proteins were downregulated in the DME group. The distinct metabolites between DME and Control groups were enriched in 16 Reactome pathways, and top 3 pathways were Hyaluronan metabolism (P=5.34E-05), Glycosaminoglycan metabolism (P=0.001) and Immune System (P=0.002). Eventually, four upregulated proteins that participated in the aforementioned three pathways were singled out as candidate biomarkers for DME. These comprised Lymphatic vessel endothelial hyaluronic acid receptor 1, Leucine-rich alpha-2-glycoprotein, CD44 antigen, and Polymeric immunoglobulin receptor.Conclusion: This study identified differential expressed proteins between the DME group and the control group and 4 upregulated proteins emerged as potential serum diagnostic biomarkers. This discovery may offer valuable insights into potential new pathogenic pathways associated with DME.DisclosureX. Zhu: None. J. Lu: None. T. Wei: None. L. Zhang: None.FundingNoncommunicable Chronic Diseases-National Science and Technology Major Project (2023ZD0509300)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-478-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 479-P: Isoleucine-Tryptophan Dipeptide Mitigates Gut Dysbiosis and
Diabetic Retinopathy in T2D Mice-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 479-P
Abstract: Introduction and Objective: Tryptophan (Trp) is absorbed via angiotensin converting enzyme 2 (ACE2) dependent and independent mechanisms. In chronic diabetes a reduction of ACE2 and of its dimerization partner the Trp transporter BOAT1 limits Trp absorption. Loss of ACE2 and BOAT1 supports the need for alternative mechanisms for Trp absorption. We sought to bypass ACE2 by using the dipeptide isoleucine-tryptophan (IW). Di- and tripeptides are absorbed via SLC15A1, an alternative amino acid transporter that is minimally affected by diabetes. This study examined IW’s therapeutic potential in prevention of gut dysbiosis and diabetic retinopathy in the model of type 2 diabetes, db/db mice.Methods: ACE2 dependent Trp absorption was achieved using oral gavage of genetically modified Lactobacillus paracasei expressing soluble ACE2 (LP-ACE2) and was compared to ACE2 independent absorption using oral administration of IW (5 mg/kg/day. Acellular capillaries, a marker of retinal vasodegeneration, were the diabetic retinopathy endpoint. Gut barrier integrity and dysbiosis were assessed at 2 and 6 months of diabetes.Results: Metatranscriptomic analysis revealed that both IW and LP-ACE2 corrected gut dysbiosis. IW and LP-ACE2 treatments restored gut barrier integrity, reduced plasma gut microbial antigens, and corrected diabetes-induced dysbiosis. Both treatments decreased gut inflammation (IL-1β, IL-2, IL-6, and IFN-γ), with reductions in acellular capillaries by 40.9% (LP-ACE2) and 43.18% (IW). IW increased levels of the beneficial Trp derived bacterial metabolite, indole proprionic acid (IPA) which enhances AhR/PXR signaling in intestinal epithelial cells, improving gut barrier function. Both treatments doubled intestinal GLP-1 and GIP levels compared to untreated db/db mice.Conclusion: IW and microbiota-derived metabolites address diabetes-induced dysbiosis, inflammation, and vascular damage. By activating indole/AhR/PXR signaling pathways, they preserve gut and retinal health.DisclosureM.B. Grant: None. R. Prasad: None.FundingNEI (033620, 012601)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-479-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 480-P: Endothelia-Targeting Eye Drops Delivery of a STING Inhibitor Reduce
Retinal Neovascularization in Ischemic Retinopathy-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 480-P
Abstract: Introduction and Objective: Retinal neovascularization is the main pathologic feature of ischemic retinopathy such as proliferative diabetic retinopathy, which eventually leads to vision loss and even blindness. Current treatments like laser photocoagulation and intravitreal injection of anti-vascular endothelial growth factor drugs are invasive and incompetent. Therefore, it is urgent to explore convenient and non-invasive therapies, particularly eye drops, to improve treatment effects. Abnormal activation of the stimulator of interferon genes (STING) is closely associated with retinal vascular diseases, and it is highly enriched in retinal ECs with retinopathy. Our research aimed to investigate the potential effect of endothelial Sting on ischemic retinopathy and develop endothelia-targeting eye drops loaded with STING inhibitor to reduce retinal neovascularization.Methods: Endothelial cell-specific Sting knockout mice were constructed and subjected to oxygen-induced retinopathy (OIR) treatment. In addition, iRGD and TAT decorated nanoparticles (NPs) loaded with C-176 (I/T-C-NP) were eye dropped to OIR mice. Fluorescein fundus angiography and retinal immunofluorescence staining were used to examine vascular tortuosity and neovascularization.Results: Activation of STING was detected in the vascular endothelium of the retina of OIR mice, knockout of endothelial Sting reduced vascular tortuosity and area of neovascularization. I/T-C-NP targeted vascular endothelial, suppressed STING pathway and alleviated retinal neovascularization.Conclusion: Inhibition of endothelial Sting reduces retinal neovascularization.DisclosureS. Wen: None. X. He: None. J. Wang: None. Z. Xiao: None. Y. Chen: None.FundingNational Natural Science Foundation of China (82270886); Science and Technology Plan Project of Guangzhou City (2024A03J0002)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-480-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 481-P: Chronic Kidney Disease Amplifies Dementia Risk in Patients with
Diabetic Retinopathy—A Korean National Health Information Data-Based
Study-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 481-P
Abstract: Introduction and Objective: Diabetes mellitus (DM) and its complications are global health problem. Dementia, which also causes substantial morbidity and mortality among the elderly, has been shown to be associated with diabetic retinopathy (DR) and chronic kidney disease (CKD). However, the combined impact of these conditions on dementia risk remains unclear. This study aims to investigate the individual and combined effects of DR and CKD on dementia risk.Methods: Using the nationwide database of National Health Insurance Service in South Korea, 2,356,298 patients aged 40 years or older with diabetes who underwent routine health examination from 2015 to 2016 were included. The mean follow-up duration was 5.63 years. Dementia incidence was defined using International Classification of Diseases 10th revision codes (ICD-10). Cox proportional hazards analysis was used to calculate hazard ratios (HR) of dementia in patients with CKD or DR, adjusting for covariates such as age, sex, BMI, income, smoking, alcohol consumption, and comorbidities.Results: The incidence rate (IR) of dementia was increased in patients with CKD (HR 1.16, 95% CI: 1.15-1.18). Similarly, DR patients showed higher dementia risk compared to non-DR patients, with proliferative diabetic retinopathy (PDR) associated with higher HR of 1.26 (95% CI: 1.21-1.31) compared to 1.09 (95% CI 1.08-1.10) in non-PDR patients. Furthermore, CKD amplified dementia risk in DR patients. Compared to patients without CKD or DR, patients with CKD and PDR had an HR of 1.57 (95% CI 1.49-1.64), higher than the HR in PDR patients without CKD (HR 1.26, 95% CI 1.21-1.31). Subgroup analysis showed that younger patients (age 40-64 years) had higher HRs than older patients (≥65 years) within the same disease groups.Conclusion: This study suggests the synergistic effect of CKD in DR patients on dementia risk, emphasizing the need of early screening and integrated care for diabetes-related complications.DisclosureN. Song: None. Y. Park: None. M. Moon: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-481-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 482-P: Eicosapentaenoic Acid (EPA) Alleviates LPS-Induced Oxidative Stress
via the PPARα-NF-κB Axis-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 482-P
Abstract: Introduction and Objective: Metabolic endotoxemia, fueled by lipopolysaccharide (LPS) translocation, promotes chronic inflammation and insulin resistance in obesity and type 2 diabetes. Eicosapentaenoic acid (EPA/C20:5) exhibits anti-inflammatory and antioxidative effects, yet its precise mechanism against LPS-induced oxidative stress in macrophages remains unclear. This study investigates EPA’s protective role via the FABP5/PPARα/NF-κB axis.Methods: THP-1 monocytes were differentiated into macrophages and pretreated with EPA or vehicle for 24 hours, followed by overnight LPS stimulation. Gene expression was analyzed by TaqMan; protein levels by Western blot, flow cytometry, and ELISA. Mitochondrial membrane potential and ROS were measured with JC-1 and DCFH-DA assays, respectively. Pharmacological inhibition of PPARα was performed with GW9662.Results: EPA pretreatment significantly dampened LPS-induced inflammatory responses, as evidenced by reduced IL-1β and IL-6 expression, decreased IL-1β secretion, and a lower percentage of HLA-DR+ macrophages. Concomitantly, ER stress markers (ATF4, DDIT3, HSPA5/GRP78, BIP, and CHOP) were downregulated at both gene and protein levels. EPA also mitigated oxidative stress, indicated by lower expression of HIF1α, decreased ROS levels, and preserved mitochondrial membrane potential. Mechanistically, EPA stimulated PPARα and FABP5 expression while inhibiting NF-κB activation, independent of TLR4-IRF5 signaling. Notably, blocking PPARα with GW9662 abolished these protective effects, underscoring the necessity of PPARα activation in EPA-mediated cytoprotection.Conclusion: EPA ameliorates LPS-induced oxidative stress and inflammation in macrophages by activating PPARα and FABP5 while inhibiting NF-κB, offering a potential therapeutic strategy to counter inflammation in metabolic disorders.DisclosureH. Alabduljader: None. H. AlSaeed: None. A. Alrabeea: None. F. Almulla: None. R. Ahmad: None. F. Alrashed: None.FundingKuwait Foundation for the Advancement of Sciences (KFAS) RA CB-2019-002
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-482-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 483-P: Prevalence and Associated Factors of High Lipoprotein(a) Level in
Patients with Type 2 Diabetes Mellitus-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 483-P
Abstract: Introduction and Objective: High lipoprotein(a) (Lp(a)) levels are the causal risk factors for atherosclerotic cardiovascular disease (ASCVD) and aortic stenosis. Type 2 diabetes is also an important risk factor for ASCVD. This study was aimed to evaluate the prevalence and associated factors of high Lp(a) levels in Thai adults with type 2 diabetes.Methods: The observational, cross-sectional study was done by collecting data from medical records in Thai adults with type 2 diabetes who had had Lp(a) level blood tested by immunoturbidimetric method during 2021-2024. The data was reviewed to explore the prevalence and associated factors of high Lp(a) levels among persons with diabetes. High Lp(a) levels were defined as Lp(a) levels greater than or equal to 50 mg/dl.Results: Among 563 subjects, 396 (70.3%) were women, and the median age was 64.9 +/- 13.0 years. Almost half of the subjects (48.7%) have had diabetes for more than 20 years. Mean HbA1c was 7.27 +/- 1.54%. The mean and median Lp(a) levels were 30.24 mg/dl and 16.30 mg/dl, respectively. The prevalence of high Lp(a) levels in persons with diabetes was 20.1%. No association had been found between high Lp(a) levels with age, sex, lipid profile, HbA1c, and vascular complications. However, when using an Lp(a) level cut-off of 30 mg/dl, urine microalbumin level was found to be significantly higher in subjects with Lp(a) levels greater than or equal to 30 mg/dl, adjusted OR 1.00024, 95% CI 1.00003- 1.0004); p-value 0.025. Our study did not find an association between high Lp(a) levels and cardiovascular disease because only 5.7% of subjects had cardiovascular disease.Conclusion: The prevalence of high Lp(a) levels in persons with type 2 diabetes is 20.1%. No factors were found to be associated with Lp(a) levels except for urine microalbumin level when using an Lp(a) level cut-off of 30 mg/dl. The addition of Lp(a) level in ASCVD risk assessment led to better risk stratification and thus helped to reclassify patients to a higher risk category.DisclosureP. Manomongkolkul: None. C. Deerochanawong: None. T. Treesaranuwattana: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-483-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 484-P: Altered Pro- and Anti-inflammatory Lipid Mediator Response to Mixed
Meal in Post-bariatric Hypoglycemia-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 484-P
Abstract: Introduction and Objective: Post-bariatric hypoglycemia (PBH) is characterized by postprandial increases in insulin secretion and altered metabolites, including lipids. We aimed to determine if signaling lipids are altered in PBH vs. asymptomatic post-RYGB (RNonH) and non-surgical controls (CON).Methods: Three groups were recruited: PBH (n=8, 88% F, age 63±7), RNonH (n=8, 100% F, age 52±11), and CON (n=8, 50% F, age 47±16). Plasma was collected for LC-MS lipidomics analysis after overnight fast (0 min) and at 30 and 120 minutes after mixed meal.Results: At 0 min, HDHA was 2-fold higher in PBH vs. RNonH (p=0.04), while 5-HETrE was elevated in both surgical groups (p<0.02) and 8-HDHA was higher in PBH vs. CON (p=0.036). At 30 min, pro-inflammatory linoleic acid-derived mediators (9,10-epOME, 9-HODE, 13-HODE) were significantly lower in PBH vs. CON (p<0.01), and 13-HODE was also lower in RNonH vs. CON (p=0.01). At 120 min, anti-inflammatory mediators, including 11-HEPE, remained significantly reduced in PBH vs. CON (p=0.01), and 13-HOTrE was lower in both surgical groups (p<0.01). 20-HETE was correlated with fasting insulin in PBH (r=0.82, p=0.01).Conclusion: PBH is characterized by a distinct temporal pattern of lipid mediators, with elevated baseline oxidative stress marker 4-HDHA, followed by suppressed early pro-inflammatory response and diminished late anti-inflammatory response vs. CON.DisclosureH. Saeed: None. R. Ferraz-Bannitz: None. L. Pei: Stock/Shareholder; Eli Lilly and Company. C.J. Cummings: None. A.L. Sheehan: None. A.E. Amore: None. D.C. Simonson: Stock/Shareholder; GI Windows. Consultant; Phase V Technologies. M.A. Kiebish: None. J. Aristizabal-Henao: None. M. Patti: Research Support; Dexcom, Inc. Other Relationship; Recordati, Fractyl Health, Inc. Consultant; Spruce Biosciences, Premier, Cello, Alpha sight, Boxer Capital. Other Relationship; Amylyx.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-484-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 485-P: Cholesterol Efflux Capacity of HDL Is Impaired in Metabolic
Dysfunction–Associated Steatotic Liver Disease.-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 485-P
Abstract: Introduction and Objective: Metabolic dysfunction-associated steatotic liver disease (MASLD), defined as steatotic liver disease associated with metabolic syndrome, has become the most prevalent chronic liver disease. Since dyslipidemia is common in metabolic syndrome, we have evaluated HDL functionality in subjects with MASLD by measuring the cholesterol efflux capacity (CEC) of HDL.Methods: CCEC was assessed by measuring the efflux of [3H]cholesterol from RAW264.7 macrophages to apolipoprotein B-depleted serum in 591 MASLD subjects and 197 age-matched healthy controls. Serum concentrations of high sensitivity C-reactive protein (hsCRP) and adiponectin (as an indicator of insulin sensitivity) were measured by ELISA. Vibration-controlled transient elastography was performed to determine the degree of liver steatosis and fibrosis by measuring controlled attenuation parameter (CAP) and liver stiffness (LS) respectively. The presence of steatosis was defined as CAP ≥ 248 dB/m.Results: CEC was reduced in MASLD individuals compared with healthy controls (18.9% ± 6.1 versus 22.2% ± 7.4, respectively; p<0.01). They also had higher hsCRP (p<0.01) and lower adiponectin levels than control (p<0.01). CEC correlated with HDL-C (r= 0.33, p<0.01), log(CAP) (r=-0.20, p<0.01), log(LS) (r=-0.21, p<0.01), log(hsCRP) (r=-0.10, p<0.01) and log(adiponectin) (r=0.17, p<0.01). Linear regression analysis showed that age, HDL-C and LS were significant and independent determinants of CEC, in a model including sex, BMI, smoking, glycated haemoglobin, the use of lipid lowering therapy, hsCRP, adiponectin and CAP.Conclusion: CEC of HDL was impaired in patients with MASLD. Hepatic fibrosis was a significant determinant of CEC independent of inflammation and insulin sensitivity in these individuals.DisclosureK.C.B. Tan: None. S. Lam: None. C. Lee: Other Relationship; AstraZeneca, Echosens, Boehringer-Ingelheim, Eli Lilly and Company. H. Fong: None. S. Shiu: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-485-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 486-P: Haptoglobin Phenotype and HDL Function in Adults with Type 1
Diabetes (Prospective InlipoDiab1 Study)-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 486-P
Abstract: Introduction and Objective: People with type 1 diabetes (T1DM) have high HDL cholesterol. This not translate into a better cardiovascular (CVD) prognosis but rather reflect impaired HDL function. The antiatherosclerotic function of HDL is related to reverse cholesterol transport from macrophages in arterial walls (cholesterol efflux capacity-CEC). CEC is CVD risk factor. HDL dysfunction may be related to copy number variants in haptoglobin (Hp), a strong antioxidant. Hp 2-2 enhances dysfunctional ApoA-I and increases CVD risk. There are no prospective data about Hp and CEC in newly diagnosed T1DM. We aimed to evaluate the relationship between Hp phenotype and CEC in adults with T1DM in a prospective longitudinal studyMethods: The analysis comprised 118 adults (64% men) with T1DM confirmed by the autoantibodies, recruited to the Insulin Therapy and Lipoproteins' Profile in Type 1 Diabetes (InLipoDiab1) study. The median age at onset was 26 (IQR: 22-32) years. CEC was assessed by the efflux of radiolabeled cholesterol from murine J774 macrophages to apolipoprotein B-depleted serum. Hp phenotype was assessed with ELISA (Savyon Diagnostics, Ltd). The endpoint was the assessment of CEC at one year after diagnosisResults: Among adults with T1DM Hp 1-1, 1-2, and 2-2 were respectively in 11%, 53% and 36%. At time of diagnosis, Hp phenotype was not associated with CEC. However, after one year of observation, the group with Hp 2-2 had significantly lower CEC in comparison with other phenotypes [(1.2(1.0-1.3) vs 1.3(1.2-1.4), p=0.03)]. Moreover, Hp 2-2 remained independently associated with lower CEC at one year (beta=-0.21, p=0.02), adjusted for sex, age, and HbA1c. Other phenotypes have no relationship with CECConclusion: The Hp 2-2 is related to worse CEC, a key antiatherosclerotic HDL function, in adults with T1DM, assessed after the first year of DM diagnosis. Evaluation of Hp can improve the CVD risk assessment with implementation of interventions in this group from the onset of the diseaseDisclosure A. Uruska: Other Relationship; Boehringer-Ingelheim, Eli Lilly and Company, AstraZeneca. M. Mietkiewska-Dolecka: None. A. Grzelka-Wozniak: Other Relationship; Novo Nordisk, Sanofi, Boehringer-Ingelheim, Roche Diabetes Care, Eli Lilly and Company. A. Gangwar: None. J. Flotynska: None. A. Rohatgi: Research Support; CSL Behring, Quest Diagnostics. Consultant; Raydel, JP Morgan, HDL Diagnostics. Other Relationship; Novartis Pharmaceuticals Corporation, Eli Lilly and Company. D. Zozulinska-Ziolkiewicz: Speaker's Bureau; Abbott. Advisory Panel; Abbott. Speaker's Bureau; Ascensia Diabetes Care, Lilly Diabetes, Boehringer-Ingelheim, AstraZeneca, Novo Nordisk, Sanofi, Servier Laboratories.FundingNational Science Center (Narodowe Centrum Nauki) (2023/50/E/NZ5/00278); Polish National Agency for Academic Exchange Walczak Programe (BPN/WAL/2022/1/00020)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-486-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 487-P: Lipocalin-2 Regulates the Function of Phosphatidic Acid in
Senescence and mTOR Signaling in Adipose Stromal-Vascular Cells-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 487-P
Abstract: Introduction and Objective: Phosphatidic acid (PA), a key intermediate in phospholipid synthesis, regulates mTOR, a nutrient-sensing pathway critical for metabolism, growth and development. However, PA's role in aging and cellular senescence, and its regulatory mechanisms, remain unclear. Lipocalin 2 (LCN2), an adipocyte secreted protein, was identified as a PA-binding protein. Lcn2 deficiency is shown to increase the risk of obesity, diabetes, and reduces adipose tissue PA species, including PA 16:0 18:1 (PA1) and PA 16:0 18:2 (PA2). This study explores LCN2's role in PA-mediated regulation of cellular senescence and mTOR signaling.Methods: Stromal-vascular (SV) cells from inguinal white adipose tissue (Ing-WAT) of wild-type (WT) and Lcn2 knockout (KO) mice were treated with PA1, mouse recombinant LCN2 (apoLCN2), or PA1+LCN2 (holoLCN2) for two days. Additionally, WT SV cells were treated with PA1 and PA2. Cellular senescence and mTOR signaling were assessed via β-galactosidase staining, and gene/protein expression analyses.Results: In WT SV cells, PA1 or PA2 significantly reduced β-galactosidase-positive senescent cells as well as downregulated of senescence and senescence-associated secretory phenotype (SASP) marker genes, including p16, Cebpb, Il1b, Il18, and Tnfa.Lcn2 deficiency in Ing SV cells resulted in increased senescence shown in β-galactosidase staining. Gene expression analysis revealed a significant upregulation of senescence markers in Lcn2 KO SV cells. While neither PA1 alone nor apo-LCN2 (LCN2 alone) had a significant effect on mTOR signaling activation, holo-LCN2 markedly enhanced mTOR signaling pathway activation in both WT and Lcn2 KO SV cells.Conclusion: Our findings show PA is protective against cellular senescence, while Lcn2 deficiency exacerbates it by reducing PA levels. LCN2 is essential for the PA-mediated mTOR activation, highlighting the functional interplay between PA and LCN2 in regulating adipose tissue metabolism and aging.DisclosureX. Jin: None. H. Su: None. X. Chen: None.FundingNIDDK Grant (R01 DK123042)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-487-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 488-P: Correlation of HbA1c Levels with Lipid Profile in Type 2 Diabetes
Mellitus Patients—A Retrospective Cross-Sectional Study-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 488-P
Abstract: Introduction and Objective: Type 2 diabetes mellitus (T2DM) is a major global health concern, significantly increasing the risk of dyslipidemia, which contributes to macrovascular complications. This study aims to explore the correlation between HbA1c levels and lipid parameters in elderly T2DM patients, emphasizing the implications for managing dyslipidemia in this population.Methods: This retrospective cross-sectional study analyzed clinical data from 300 T2DM patients (60% male) who visited Parul Sevashram Hospital, Vadodara, Gujarat, between January and April 2025. Sociodemographic information and laboratory values, including HbA1c and lipid profiles, were extracted from hospital records. Dyslipidemia was defined using standard lipid profile thresholds. Statistical analysis was performed to evaluate correlations between HbA1c levels and lipid parameters, including total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), and triglycerides (TGs).Results: The study population had a mean age of 62 years, with 43% aged between 55 and 64 years. Dyslipidemia was prevalent, with 60% of patients having elevated LDL-c, 40% with low HDL-c, and 35% each with elevated triglycerides and total cholesterol levels. A statistically significant positive correlation was observed between HbA1c and TC (p<0.01) as well as TGs (p<0.01), indicating that poor glycemic control is closely associated with dyslipidemia in T2DM patients.Conclusion: This study highlights a significant association between HbA1c levels and dyslipidemia, particularly with cholesterol and triglyceride levels, in T2DM patients. These findings underscore the need for integrated management strategies targeting both glycemic control and lipid abnormalities to mitigate cardiovascular and microvascular risks in this population. Further research is warranted to establish causality and optimize therapeutic interventions.DisclosureV.M. Rathod: None. D. Raval: None. P. Thammireddy: None. M. Subhan: None. A. Bhattacharya: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-488-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 489-P: Familial Hypercholesterolemia Is Not Associated with Type 2
Diabetes Presence in Patients Undergoing a Genetic Cascade Screening
Program-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 489-P
Abstract: Introduction and Objective: Epidemiological and genetic studies have shown an inverse association between hypercholesterolemia and type 2 diabetes (T2DM), particularly in Familial Hypercholesterolemia (FH). Defects in LDL receptor gene (LDLR) may lead to beta-cell apoptosis, and statin therapy might complicate it. The study evaluated biomarkers related to T2DM severe hypercholesterolemic patients in a genetic FH cascade screening program.Methods: Cross-sectional study, 1,431 patients with severe hypercholesterolemia, with FH-causing genes or not. T2DM was diagnosed by ADA criteria or by the use of antidiabetic medications.Results: A total of 797 patients with genetically confirmed FH (96.6% with variations in the LDLR, 47.7 ± 15.0 years; 56.7% female; baseline LDL-C 199 ± 74 mg/dL, body mass index (BMI) 27.55 ± 4.85 kg/m², 27.1% with previous cardiovascular disease, (CVD)) and 634 patients without FH variants (56.04 ± 12.6 years; 67.4% female; baseline LDL-C 191 ± 66 mg/dL, BMI: 26.91 ± 5.05 kg/m², 25.1% CVD were analyzed. FH patients were younger (p<0.001), leaner (p=0.004), and had a higher proportion of males (p< 0.001). At baseline, 67.8% of FH received statin therapy, compared to 87.4% of non-FH patients (p<0.001). The prevalence of T2DM at baseline was 13.4% in the FH group vs. 21.8% (odds ratio-OR 0.555, 95%CI 0.420-0.732, p<0.001). However, this association lost significance after multivariate analysis. Factors independently associated with T2DM included age (OR: 1.049, 95% CI: 1.032-1.066, p < 0.001), BMI (OR: 1.111, 95% CI: 1.073-1.151, p < 0.001), triglycerides (OR: 1.003, 95% CI: 1.001-1.005, p< 0.001), hypertension (OR: 2.845, 95% CI: 1.886-4.292, p < 0.001), and previous CVD (OR: 1.901, 95% CI: 1.324-2.729, p < 0.001). No association was observed with genetic defects or statin therapy.Conclusion: Among this group of hypercholesterolemic individuals, T2DM was not less prevalent in those with molecularly confirmed FH.Disclosure F.C.P. Maia: Other Relationship; Eli Lilly and Company. Speaker's Bureau; Amgen Inc, Novo Nordisk. M.H. Miname: Speaker's Bureau; Novartis Pharmaceuticals Corporation, Ache, Novo Nordisk. K.A.P. Maia: Research Support; Lilly USA LLC. Speaker's Bureau; Novo Nordisk, Novartis Pharmaceuticals Corporation, Servier Laboratories. H. Takematsu: None. P.G. Lorente: None. M.H. Mizuta: None. R. Santos: Research Support; Amgen Inc, Sanofi. Consultant; ESPERION Therapeutics, Inc., Daiichi Sankyo. Speaker's Bureau; Daiichi Sankyo. Research Support; Eli Lilly and Company. Speaker's Bureau; Eli Lilly and Company. Research Support; Kowa Company, Ltd, Novartis Pharmaceuticals Corporation. Speaker's Bureau; Novo Nordisk. Research Support; Ionis Pharmaceuticals. Speaker's Bureau; Novartis Pharmaceuticals Corporation.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-489-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 490-P: Well-Formulated Ketogenic Diet (WFKD) Reduces Hypertriglyceridemia
-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 490-P
Abstract: Introduction and Objective: Hypertriglyceridemia (HTG) is an independent risk factor for cardiovascular (CV) disease with few pharmacologic options. Current dietary management of HTG includes whole grains, oats, legumes, and fruits, however restricting these carb-rich foods reduces triglycerides (Trigs) in the context of WFKD. The magnitude of reduction of Trigs with WKFD at different levels of baseline HTG is not known.Methods: Virta remotely offers WKFD to patients with metabolic disease. From among our real-world population, a random sample of patients with enrollment (E) Trigs 150 to 499 mg/dl (ETrigs150, n=500) and ≥500 mg/dl (ETrigs500, n=500) with 6 month (6m) follow-up labs were identified to explore changes in dyslipidemia, weight, A1c over time.Results: The table shows the characteristics of each cohort at E, and weight, A1c, and lipids at E and 6m. Trigs, nonHDL, and Tg-HDL ratio dropped 30.4%, 6.5%, and 34.2% in ETrigs150, and 56.2%, 22.7%, and 49.8% in ETrigs500, respectively (p-values<0.001). There was no change in LDLc in ETrigs150, and LDLc increased slightly within the normal range in ETrigs500, while non-HDL and total cholesterol dropped significantly. These changes suggest improved lipid metabolism.Conclusion: WKFD delivered remotely improves HTG, and appears to be a highly effective way to address both CV risk and insulin resistance non-pharmacologically. Studies of clinical CV endpoints are warranted.Disclosure C.G.P. Roberts: Employee; Virta Health Corp. Stock/Shareholder; Virta Health Corp. S.J. Athinarayanan: Employee; Virta Health Corp.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-490-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 491-P: Factors of Mortality among Adult Diabetic Foot Patients in a
Tertiary Government Hospital-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 491-P
Abstract: Introduction and Objective: The Philippine healthcare system faces challenges in addressing mortality among adult patients with diabetic foot disease, despite advancements in medical care. Globally, the increasing prevalence of diabetes, projected to rise in the next two decades, may exacerbate complications such as diabetic foot, raising morbidity and mortality rates. This study aims to identify risk factors associated with mortality among adult Filipino inpatients with diabetic foot disease in a tertiary government hospital.Methods: A retrospective, analytical, descriptive study design was employed, using medical chart reviews. Binary logistic regression was applied to analyze predictive factors.Results: Among 247 cases (mean age 58.4±10.5 years), 56.7% were male. Most underwent Doppler ultrasound (97.6%), but 87% experienced surgical delays exceeding 12 hours. Early antibiotic therapy was given in 23.5%, while 76.5% had delays over 24 hours. Ankle-brachial index was not assessed in any case. Mortality occurred in 27.6% of cases. Delayed antibiotic therapy significantly predicted mortality (OR 2.93, 95% CI 1.31-6.57, p=0.007), while delayed surgical intervention was not predictive (p=0.725).Conclusion: The study highlighted a middle-aged, male-dominant population with high mortality rates and delayed antibiotic therapy as a key predictor of mortality. Routine ankle-brachial index measurement and timely management, including antibiotic therapy, are recommended.DisclosureA.G. Rabadan: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-491-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 492-P: Validation of Compliance Monitoring Algorithm for RCWs and
Contralateral Limb Lift Equalizer-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 492-P
Abstract: Introduction and Objective: Offloading adherence (OA) to removable cast walker (RCW) is traditionally assessed through potentially inaccurate self-reported data like diaries and surveys. Understanding OA is crucial, as higher adherence correlates with reduced plantar stress. Previous research only focused on ambulation and overlooked standing or whether contralateral footwear was worn. Our project validates a methodology for objectively monitoring offloading OA using activity monitors.Methods: 30 healthy participants wore an ActivPAL4 monitor on their ipsilateral thigh to detect activity with two hidden sensors—(inside RCW and on contralateral lift). Participants engaged in various activities (walking, sitting, standing, etc.) in the lab and wore sensors for 24 hours outside, maintaining a diary. A LabVIEW program compared thigh sensor data with RCW and lift data to calculate OA percentages during walking and standing. A cross-validation approach used in-lab data to train the algorithm used for the outside lab data.Results: Three subjects were removed due to data collection errors, leaving 27 participants. The algorithm's in-lab validation showed a 100% accuracy in detecting walking OA % based on thigh sensor activity compared to the RCW, and 99.84% accuracy with the lift. During standing, OA accuracy was 99.72% with the RCW and 98% with the lift. Intraclass correlation coefficients (ICCs) were highly significant, showing perfect agreement (ICC = 1, p < 0.05) for in-lab validation. For outside lab data, ICCs were 0.99 (p < 0.05) during walking and 0.95 (p < 0.05) during standing, indicating strong agreement between the log sheets and the LabVIEW algorithm.Conclusion: The LabVIEW algorithm, using activity sensors at the thigh to detect standing and walking, and calculating OA with sensors concealed in the RCW and contralateral lift, has been successfully validated both in the lab and outdoors, showing strong agreement with log sheets. This approach is clinically applicable for quantifying OA during treatments in diabetic subjects.DisclosureS.V. Yalla: None. N. Negron-Fernandez: None. N.J. Rosenblatt: None. R.T. Crews: None.FundingNational Institutes of Health (R01DK131303)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-492-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 493-P: Risk Factors for Failure of Autologous Cell Therapy in Patients
with Diabetes and Chronic Limb-Threatening Ischemia-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 493-P
Abstract: Introduction and Objective: Autologous cell therapy (ACT) is a revascularision method for patients with no-option chronic limb-threatening ischemia (CLTI). The aim of our study was to identify patients who benefit most from ACT and to analyze factors responsible of failure of this therapy.Methods: We performed 159 treatments of 145 limbs in 132 patients with no-option CLTI treated in our center over 15 years. During ACT the patient's bone marrow is harvested to manufacture the final cell product, which is injected into the calf muscles of the ischemic limb. We analyzed all baseline parameters obtained before ACT and compared them with amputation-free survival (AFS). Baseline parameters (BP) were divided into three groups: patent-related BP, ischemia-related BP and ulcer - related BP. Risk factors were analyzed using Kaplan-Meier estimate and Cox proportional-hazard model.Results: Major amputations were necessary to perform in 48 limbs (33.1 %) and 60 (45,5 %) patients died during a 15-year follow-up. The most significant baseline factors for shorter AFS were severe stages of chronic kidney disease (HR 1.23, CI 1.08 - 1.39), severe stages of foot infection in accordance with WIfI classification (HR 1.31, CI 1.05 - 1.64), and the presence of bacteria resistant to oral antibiotics (HR 1.65, CI 1.14 - 2.39).Conclusion: Our study showed that ACT is an effective method for diabetic patients with CLTI. Patients with no kidney damage, without infected diabetic foot, and without resistant bacteria have the greatest chance of success with this treatment.DisclosureD. Sojáková: None. M. Kahle: None. J. Husáková: None. V. Fejfarova: None. R. Jarosikova: None. K. Sutoris: Speaker's Bureau; Bonalive Biomaterials. M. Dubsky: None.FundingSupported by the project CarDia (Programme EXCELES, Project No. LX22NPO5104) - Funded by the European Union - Next Generation EU.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-493-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 494-P: Differences in Foot Care Skills and Foot Care Education between
Veterans with Diabetic Neuropathy Alone and Veterans with a Healed
Diabetic Foot Ulcer-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 494-P
Abstract: Introduction and Objective: Prevention of foot ulcers and amputations in patients with diabetes requires consistent, comprehensive foot care. We compared foot care skills (FCS) and foot care education (FCE) in patients with healed diabetic foot ulcers (DFU) to those with diabetic neuropathy (DN) alone to identify preventive gaps and prevent foot complications.Methods: Data were from two RCTs: PATRIOT for primary prevention of DFU and STEP UP for secondary prevention. Key assessments in both RCTs were FCS and FCE, measured via the validated VA Foot Care Survey. FCS (basic: look at bottom of feet, check between toes, wash feet, test water temp, dry between toes, check shoes; extended: + soak feet 10 min, use lubricants, file calluses, trim nails) ranged from 1 (not at all) to 5 (daily). FCE (basic: education to check feet, keep feet clean, choose proper shoes, always wear footwear, keep skin moist; extended: + use mirror to see bottom of feet, avoid very hot and cold, gently file calluses, cut nails, cut corns/calluses, avoid drugstore chemicals, when to call, whom to call) scored from 1 (nothing) to 4 (enough). Ordinal outcomes were compared using Wilcoxon Rank-Sum tests.Results: Participants in PATRIOT (n = 406) and STEP UP (n = 241) were from the New York area, median age 67.4 years, 97.8% male, 48.4% black. At baseline, the STEP UP vs. PATRIOT participant comparisons were: FCS basic (median = 4.0 vs 3.9, p = 0.008), FCS extended (median = 2.3 vs 2.3, p = 0.33), FCE basic (median = 3.2 vs 3.0, p<0.001), and FCE extended (median = 2.7 vs 2.4, p<0.001).Conclusion: Veterans with healed DFU scored significantly higher on FCS basic and FCE basic and extended. The relationship between behavior, DFU, and amputations is being evaluated in the RCTs. If good foot care among Veterans lowers DFU and amputations, these should be emphasized. If not, newer approaches (thermometry, reducing foot pressures, etc.) should be evaluated rigorously to lower DFU and amputations.DisclosureT. Chen: None. D. Ingerman: None. L. Haley: None. A. Nicholson: None. M. Rodriguez: None. N. Illenberger: None. S. Natarajan: None.FundingVA Rehabilitation, Research and Development Service, Office of Research and Development (E1858-R); Health Services Research and Development Service, VA Office of Research and Development (IIR 14-009)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-494-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 495-P: Prospective, Randomized, Phase IV Clinical Trial Comparing a Novel
Transforming Powder Dressing vs. Standard of Care in Treatment of Wagner
Grade 1 and 2 Diabetic Foot Ulcers-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 495-P
Abstract: Introduction and Objective: Diabetic foot ulcers (DU) affect 19-34% of the 537 million diabetic patients worldwide!Despite recommended evidence-based strategies for DFU management', no standardized wound dressing is consistently used. Our aim is to compare a transforming powder dressing (TPD) to standard of care (SOC) in the treatment of chronic (>30 days)Wagner Grade 1 and 2 DFUs.Methods: The prospective, randomized clinical trial is funded by the Naval Medical Research Command-Naval Advanced Medical Development via the Medical Technology Enterprise Consortium. The primary aim is to assess TPD's wound healing efficacy compared to SOC over 12 weeks, using statistical analyses like Kaplan-Meier survival curves to evaluate healing rates. Healing is defined as wound closure without recurrence for two weeks. Secondary outcomes include changes in wound surface area (WSA), dressing frequency, debridements, and adverse events. TPD upon hydration forms a moist, oxygen-permeable barrier lasting up to 30 days.Results: To date, 137 patients (mean age 62 years; 82% male) were evaluated across 12 U.S. sites. TPD significantly reduced WA at weeks 4, 8, and 12 (p<0.05). Dressing changes were 67% lower (p<0.001), and debridements were 33% lower (p=0.013) compared to SOC. No significant differences in adverse events were observed.Conclusion: Findings suggest that TPD resulted in faster healing with reduced dressing changes and debridements compared to SOC in Wagner Grade 1 and 2 DFUs, without increasing adverse events.Disclosure S. Rolniak St. John: Consultant; Altrazeal Life Sciences Inc. J.V. Stjohn: Employee; Altrazeal Life Sciences. J. Saxe: Consultant; Altrazeal Life Sciences Inc. L.A. Lavery: Consultant; Limflow, enerenesis Medical, Clyra Medical technologies, Blue Sky, Tissue Health Plus. Stock/Shareholder; Xilas Medical. Consultant; Altrazeal.FundingClinical trial funded by the Naval Medical Research Command (NMRC)-Naval Advanced Medical Development (NAMD) via the Medical Technology Enterprise Consortium (MTEC)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-495-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 496-P: Diabetic Foot Ulcer—Value of Bedside Blind Bone Biopsy and
Bedside Toe Amputation Practiced by a Diabetologist on Major Inferior Limb
Amputation Incidence-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 496-P
Abstract: Introduction and Objective: In case of diabetic foot ulcer (DFU), major inferior limb amputation (MILA, complete transmetatarsal, tibial, femoral) is closely related to underlying osteitis and necrosis. Since 2016, in our diabetology unit, medical physicians have been performing bedside blind bone biopsy (B4) and bedside toe amputation surgery (BAS).Methods: In this monocentric, observational study, we compare rates of MILA during 2015, reference period with no B4 or BAS, to 2023.Results: In 2015 and 2023, 105 and 129 patients were respectively hospitalized for a DFU. Patients’ characteristics (age/sex ratio/diabetes mellitus type/duration/DFU history/tobacco smoking/renal function) and DFU severity score (SINBAD) were not significantly different (except for higher HbA1c in 2015, p=0.03). In 2023, B4 and BAS were respectively performed in 45 and 18%. Significantly more inferior distal limb revascularizations (RVZ) have been peformed in 2023 (24vs49%, p=0.0001). MILA rate was significantly lower in 2023 (8.5vs21%, -61%, p=0.006). By multivariate logistic regression analysis, only B4 was associated with this result (figure 1).Conclusion: B4 improves prognosis by reducing MILA rate. The lack of statistical power might explain the lack of benefit from BAS and/or RVZ. A long term analysis of B4/BAS/RVZ practice is required.DisclosureF. Féron: None. J. Julla: Other Relationship; Lilly Diabetes. Board Member; Sanofi. Other Relationship; Novo Nordisk. J. Nguewa: None. J. Gautier: Board Member; Sanofi. Advisory Panel; Pfizer Inc, Novo Nordisk. Other Relationship; Eli Lilly and Company. J. Kevorkian: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-496-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 497-P: Longitudinal Evaluation of Metabolic and Biomechanical Changes in
Type 2 Diabetes Mellitus—Insights from Follow-up Assessments-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 497-P
Abstract: Introduction and Objective: Effective diabetes management involves monitoring clinical and biomechanical parameters to reduce complications. This study analyzed changes in metabolic, cardiovascular, and biomechanical metrics during follow-up visits in patients with Type 2 Diabetes Mellitus (T2DM).Methods: A retrospective study was conducted on patients (N = 365) with paired baseline and follow-up after one year. Parameters included HbA1c, LDL, cholesterol, weight, plantar pressure distribution, and foot deformities. Plantar pressure was assessed using the Presscam hybrid pressure-posturology platform. Statistical comparisons were made using paired t-tests, with significance set at p < 0.05.Results:Significant differences were observed: Metabolic Metrics: HbA1c decreased significantly (-0.52%; p = 0.045), indicating improved glycemic control. LDL and cholesterol levels also showed marked reductions (-11.83 mg/dL and -17.75 mg/dL, respectively), while weight changes were minimal (p = 0.13). Biomechanical Metrics: Maximal pressure was higher in the right foot (7.9 N/cm² vs. 7.1 N/cm²; p < 0.0001), and average pressure also differed (3.46 N/cm² vs. 3.3 N/cm²; p = 0.03). Flattened arches (n=80) and corns (n=110) were the most common deformities, emphasizing biomechanical challenges in T2DM.Conclusion: This study highlights significant improvements in glycemic and lipid profiles during follow-up visits, demonstrating the effectiveness of current treatment strategies. However, plantar pressure asymmetries and frequent foot deformities suggest the need for targeted biomechanical interventions to prevent complications. These findings highlight the importance of integrating metabolic and biomechanical assessments into follow-up protocols for T2DM patients. Larger studies are needed to confirm these results and optimize management strategies.DisclosureR.M. Rohatgi: None. P. Kudkar: None. D. Antao: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-497-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 498-P: A Patient Navigator Program for Post-discharge Diabetic Foot Care
-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 498-P
Abstract: Introduction and Objective: Diabetic foot ulcer (DFUs) are a major cause of hospitalizations, yet post-discharge care coordination remains suboptimal. Effective care organization among specialists is crucial for limb salvage. Patient navigators are an effective model for chronic disease management, but their impact on DFU care is understudied. Here, we evaluated the use of certified diabetes care and education specialist (CDCES) to improve post-hospitalization DFU care.Methods: We conducted this study at a safety-net hospital in Atlanta, GA where the historical 30-day post-hospital discharge outpatient clinic attendance rate among patients with DFUs is 55%. In December 2023, we enrolled participants hospitalized with DFUs and assigned them a CDCES who conducted weekly calls for 4 weeks. These calls consisted of diabetes management, outpatient care coordination, appointment reminders, and addressing DFU-related concerns.Results: Twelve participants were enrolled. The median (IQR) age was 53 (42-59) years; 8 (73%) were male and 8 (73%) identified as non-Hispanic Black. The median (IQR) baseline HbA1c was 8.2% (7.7-11.1). Diabetes distress scores were high [median (IQR): 2.9 (1.7-3.2)]. All participants attended a DFU-related outpatient visit within 30 days post-hospital discharge. Ten of the 12 participants used a CDCES intervention aside from appointment reminders, including setting up transportation (n=1), wound care plan clarification (n=1), antibiotic adverse effect management (n=1), rescheduling appointments (n=3), severe hyper/hypoglycemia management (n=2), and insulin education and dose - modification (n=6).Conclusion: A CDCES-led patient navigator program was associated with substantial improvement in 30 days post-discharge clinic attendance rates for patients hospitalized with DFUs and the CDCES provided comprehensive care, addressing multiple aspects of diabetes and wound management. Ongoing work will determine if this intervention improves DFU healing.DisclosureJ. Flores: None. K. Zamudio-Coronado: None. M.C. Schechter: None. M. Fayfman: Research Support; Abbott, Dexcom, Inc. N.Y. Chaudhry: None. N. Soleimanmanesh: None. I.C. Flores: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-498-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 499-P: Metformin Stimulates Human Adipose-Derived Stem Cells to Promote
Angiogenesis—A Strategy for Diabetic Wound Treatment-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 499-P
Abstract: Introduction and Objective: Metformin (MTF) has pro-angiogenic effects. Adipose-derived stem cells (ASCs) exhibit pro-angiogenic properties and promote healing by secreting cytokines, growth factors and differentiating into endothelial cells. This study evaluates the effects of MTF on ASCs and the potential of MTF-treated ASCs applied within a matrix scaffold for diabetic wound treatment.Methods: Human ASCs were treated with MTF (0.1, 1, 5, 10 mM) +/- glucose (25 mM). Cell viability, proliferation, and migration were measured using MTT, growth curves, trans-well, and wound healing assays with 3D-printed inserts. Endothelial differentiation of ASCs, their adherence, and angiogenic potential on small intestinal submucosa (SIS) scaffolds were evaluated via qPCR, ELISA, and immunofluorescence staining. RNA sequencing characterized gene expression differences between treatment groups.Results: MTF increased ASC proliferation (1.8-fold, p<0.05) and stimulated ASCs to promote fibroblast migration in co-culture (35%, p<0.05). Under high glucose, fibroblast migration increased with MTF but did not reach statistical significance (25%, NS). MTF elevated ASC secretion of FGF (1.8-fold, p<0.01) and VEGF (1.2-fold, p<0.05) and increased mRNA levels of CD31 during ASC differentiation (1.6-fold, p=0.05). Immunofluorescence showed that MTF-treated ASCs enhanced cell attachment, and retention and increased CD31 expression on SIS scaffolds. RNA-seq revealed MTF altered ASC gene expression including transcription factors and specific signaling pathways linked to pro-angiogenesis and wound healing.Conclusion: Metformin shows promise for ASC-based therapies in diabetic wound healing by promoting endothelial cell differentiation, proliferation, migration, and enhanced adhesion upon delivery to the matrix membrane of SIS scaffolds. Our results support the use of MTF and SIS scaffolds as a strategy to improve wound healing in people with diabetes.DisclosureM. von Suskil: None. K. Khaw: None. A. Bohner: None. R.J. Buono: None. S.C. Bonawitz: None. K. Behling: None. M.E. DiSanto: None. P. Zhang: None.FundingNew Jersey Health Foundation (PC-213-24)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-499-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 500-P: Assessment of MRI Markers of Foot Perfusion and Microvascular
Function in People with Diabetic Foot Ulcers (DFU) and Wound Healing-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 500-P
Abstract: Introduction and Objective: Prediction of wound healing in DFU is clinically important to stratify risk of amputation and target limb salvage interventions. Basic and clinical studies show both initiation of ulcers and incomplete wound healing arising from reduced tissue perfusion and ischemia due to macro- and microvascular disease. Current vascular diagnostic modalities in clinical practice are inadequate in predicting wound healing with 16% of patients having unresolved wounds after one year despite normal vascular indicators. Here, we present preliminary results assessing perfusion with advanced quantitative MRI measures in people with DFUs as it relates to wound healing.Methods: This ongoing prospective observational study enrolled 17 people with unhealed plantar forefoot ulcers for at least 30 days. The affected foot was studied using a non-contrast MRI protocol to quantify resting perfusion. Microvascular function was assessed using a dynamic MRI-cuff-occlusion protocol. Study volunteers received standard wound care, and healing was followed prospectively for 12 weeks post-MRI. MRI perfusion markers were compared between healers and non-healers.Results: Ulcers healed within 12 weeks in 47% (n=8) of volunteers. Qualitatively, MRI markers suggest elevated resting perfusion in non-healers compared with healers. Non-healers showed a trend towards reduced tissue oxygen reserve capacity (-6.5% vs -3.2%; p=.06) in the medial plantar compartment and reduced microvascular reactivity (i.e. increased time to peak hyperemia; 171sec vs 101sec; p=.03) compared with healers.Conclusion: Markers of reduced microvascular function show sensitivity to poor wound healing. Combined use of MRI markers for resting perfusion and microvascular function provides additional information on the microvascular involvement in individuals with DFU and could help stratify risk of poor wound healing. Ongoing work is examining their use in combination with clinical and blood markers to prognosticate DFU healing.DisclosureD.A. Reiter: None. S. Edwards: None. N. Soleimanmanesh: None. J. Flores: None. N.Y. Chaudhry: None. G. Santamarina: None. M.C. Schechter: None. M. Fayfman: Research Support; Abbott, Dexcom, Inc.FundingNIDDK Diabetic Complications Consortium (DK076169 and DK115255); NIH (DK136983)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-500-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 501-P: The Infected Diabetic Foot—Risk Factors and Clinical Outcomes for
Nonhealing Foot Wounds-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 501-P
Abstract: Introduction and Objective: To identify risk factors and clinical outcomes for non-healing surgical wounds in patients admitted to the hospital for moderate and severe diabetic foot infections.Methods: This was a pooled analysis of patient level data from 2 RTCs. Moderate and severe diabetic foot infection (DFI) was based on criteria of the International Working Group on the Diabetic Foot infection classification. Non-healing was defined as failure of complete epithelialization of wound. We used χ2 and t-test to compare clinical outcomes, with alpha of <0.05.Results: We evaluated 233 patients that required foot surgery for DFI; 31.3% (n=73) failed to heal at 1 year. Risk factors identified for not healing includes higher baseline CRP, ESR, vibration perception threshold, ankle brachial index <0.9, history of Charcot, severe infection, and wound size (Figure 1). Re-infection was 2.6 times more common (NHW 43.8% vs HW 22.5%, p=0.001) and amputations were 8.7 times more common (NHW 31.5%, HW 5.0% p=0.001) in people with wounds that did not heal. People that did not heal had significantly longer antibiotic therapy (NHW 56.7 ± 35.5 vs. HW 47.4 ± 35.1 days, p=0.01) and longer hospitalizations (NHW 25.4 ± 17.8 vs. HW 18.5 ± 14.3 days, p=0.001). There was no difference in all cause hospitalizations (57.1% vs 61.5% p=0.67).Conclusion: After surgery for infection, failure to heal remains common (31.3%). During follow up, reinfection and amputation are more common in wounds that do not heal.DisclosureM.C. Reyes: None. A. Tarricone: None. O.K. Oz: None. L.A. Lavery: Consultant; Limflow, enerenesis Medical, Clyra Medical technologies, Blue Sky, Tissue Health Plus. Stock/Shareholder; Xilas Medical. Consultant; Altrazeal.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-501-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 502-P: A Prospective Study of Incident Diabetic Foot Ulcer and Risk of
Lower Extremity Amputation-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 502-P
Abstract: Introduction and Objective: While the causes of lower-extremity amputation (LEA) are well-studied, the role of incident diabetic foot ulcer (DFU) has not been prospectively assessed. We evaluated the independent impact of DFU, alongside other factors, on LEA risk in a cohort of Veterans with diabetes at a single Department of Veterans Affairs clinic.Methods: A total of 1,458 male veterans with 2,893 lower limbs without DFU were followed between 1990 and 2002 (mean follow-up: 4.9 years). Risk factors were assessed using a flexible parametric survival model based on data from interviews (demographics, diabetes characteristics), physical exams (blood pressure, weight, Charcot deformity, visual acuity), and blood (albumin, HbA1c, eGFR) and neurovascular tests (10-g monofilament, TcPO2, ABI).Results: During follow-up, 227 DFUs (7.8%) and 72 LEAs (2.5%) occurred. Predictors of LEA (p < 0.05) in the final model adjusted for time-updated measurements (HR, 95% CI) included age ≥70 years [0.29, 0.08-0.97], prior amputation [2.31, 1.13-4.74], lower eGFR [1.16, 1.02-1.32], systolic BP [1.40, 1.11-1.78], ABI ≤0.5 [3.94, 2.03-7.62], and incident DFU [10.44, 6.01-18.15].Conclusion: In this prospective study, incident DFU emerged as having a substantial independent power in predicting LEA among other person- and limb-specific risk factors. Preventing DFU occurrence is critical to reducing the burden of LEA.DisclosureI.S. Al-Busaidi: None. A.D. Seelig: None. E.J. Boyko: None.FundingU.S. Department of Veterans Affairs Rehabilitation Research and Development Program.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-502-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 503-P: Demographic Comparison of Patients with Diabetic Foot Infection
between Adjacent Health Care Systems-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 503-P
Abstract: Introduction and Objective: Diabetic foot infection (DFI) is a common and significant complication of diabetes, with racial, ethnic, and age disparities potentially influencing clinical outcomes. We analyzed 7,769 patients evaluated for DFI at Parkland Health (PHHS), a large tertiary county system, and UT Southwestern (UTSW), a university center, to examine demographic differences between these adjacent healthcare facilities.Methods: The study population included 6,187 PHHS and 1,582 UTSW patients that were seen between 2013 to 2024. Each patient underwent biopsy, surgical resection, or amputation with accompanying histopathology.Results: UTSW patients were predominantly Non-Hispanic White, while PHHS patients were mainly Hispanic White. Slightly more females were seen at UTSW (33%) compared to PHHS (30%). PHHS patients tended to be younger, with most aged 51-60 years, compared to 61-70 years at UTSW. A subset of 3,181 subjects also had microbial cultures associated with their histopathology (2,271 PHHS and 910 UTSW patients). The top five pathogens observed at both facilities included S. aureus, S. agalactiae, MRSA, P. aeruginosa, and E. faecalis, with S. aureus being the most frequently identified microbe.Conclusion: These findings highlight how institutions in close geographical proximity can serve demographically distinct populations, emphasizing the need to consider these differences to tailor care and advance personalized medicine.DisclosureA. Sherwood: None. P.A. Crisologo: None. L.A. Lavery: Consultant; Limflow, enerenesis Medical, Clyra Medical technologies, Blue Sky, Tissue Health Plus. Stock/Shareholder; Xilas Medical. Consultant; Altrazeal. O.K. Oz: None.FundingAmerican Diabetes Association (11-22-ICTSPM-05)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-503-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 505-P: A Formative Evaluation to Improve Study Processes and Optimize a
Tailored Intervention to Prevent Diabetic Foot Ulcer Recurrence—The Step
Up to Avert Amputation Randomized Trial-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 505-P
Abstract: Introduction and Objective: Lower extremity amputation (LEA), a devastating complication of diabetes, is preceded in more than 80% of cases by a diabetic foot ulcer (DFU). Foot-specific care and general diabetes care are necessary to prevent LEA. During the STEP UP randomized clinical trial (RCT), formative evaluation interviews (FEIs) with study participants were conducted to help refine study processes and optimize a tailored behavioral intervention (TI) to prevent DFU recurrence.Methods: At four distinct points in the trial, four to five unique participants were invited to complete an FEI focused on the counseling call, plantar thermometer, foot temperature logbook and foot-care checklist. Once the FEIs were complete, the study team analyzed the interviews to immediately identify actionable feedback to improve the pre-intervention and intervention procedures. Formal thematic analysis was conducted by three independent coders using ATLAS.ti software.Results: Overall, of the 18 participants, most expressed satisfaction with the intervention as it emphasized the importance of foot health and supported adherence to self-monitoring behaviors to prevent DFUs. Primary reasons for participation were gaining accountability, health education, and awareness of their condition. Many found the logbook and checklist straightforward and “easy to use”. Common barriers to adherence were repetitiveness of the calls, difficulties with thermometer use, and forgetfulness. To address these concerns, the questionnaire was shortened, thermometer modifications to improve accessibility were discussed with the manufacturer, and the team worked with participants to devise easy reminders for intervention adherence.Conclusion: Iterative FEIs provided critical information to optimize the STEP UP intervention and study processes, and enhance the participant experience through active troubleshooting.DisclosureP.K. Salovaara: None. S. Gunawan: None. M. Rodriguez: None. A. Nicholson: None. S. Natarajan: None.FundingVA Rehabilitation R&D (I01RX001858)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-505-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 507-P: Diabetic Foot Ulcer Outcomes between Patients with Type 1 (T1D) and
Type 2 Diabetes (T2D)—A Retrospective Analysis-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 507-P
Abstract: Introduction and Objective: Diabetic foot ulcers (DFUs) are a common complication of diabetes, presenting in patients with T1D and T2D. We aimed to compare DFU characteristics and outcomes stratified by T1 vs T2DM.Methods: All patients with a DFU hospitalized in an Atlanta Hospital between 01/2019 - 12/2021 were included. T1D and T2D status were determined using manual chart review. Diabetes due to pancreatic insufficiency or pancreatitis were excluded. The primary outcome was a composite of either major or minor amputation or death.Results: Among 696 patients, 33 (5%) had T1D and 663 (95%) had T2D. Eight (24%) patients with T1D and 135 (20%) patients with T2D experienced the primary outcome (p=0.35). Patients with T1D were significantly younger and had a higher HbA1c than those with T2D. Moreover, patients with T1D seldom had PAD or ESRD at the time of DFU-related hospitalization or when they experienced limb loss or death.Conclusion: We observed no difference in the risk of experiencing amputation or death in patients with T1D and T2D. In our study sample, patients with T1D had higher HbA1c than those with T2D and experienced amputation or death approximately 10 years before those with T2D.DisclosureJ.E. Tyrrell: None. M.C. Schechter: None. R.R. DSouza: None. H.H. Chang: None. M. Fayfman: Research Support; Abbott, Dexcom, Inc.FundingNational Institute of Diabetes and Digestive and Kidney Disease (5R21MD017943-02)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-507-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 508-P: Are Patients with Diabetic Foot Disease Safe at Home' Foot-Loading
Changes in Association with Varied Flooring Surfaces-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 508-P
Abstract: Introduction and Objective: Adherence to offloading footwear for prevention of diabetic foot ulcers (DFU) is often suboptimal, particularly in the home environment. The fact that many individuals at risk of DFU engage in more physical activity in their homes than outside of the home further emphasizes the challenge to DFU prevention. Some individuals at risk for DFU likely perceive carpeting on floors as affording protection to their feet. This study assessed plantar foot loading in association with varied home flooring surfaces.Methods: Eleven subjects at risk for DFU conducted shod and unshod walking trials on three surfaces: hard tile, low pile carpet + carpet padding, and high pile (plush) carpet + carpet padding. For 12 strides per trial, peak plantar pressure was assessed across the entire foot as well as four masks (regions) of the forefoot via pressure insoles. Peak pressure data was analyzed for each foot region via a multifactor repeated measures ANOVA with main effects of footwear status and flooring surface. A Sidak post hoc test was used for pairwise comparisons.Results: The main effect of footwear was significant (p<0.05) for each of the three masks corresponding to metatarsal head regions (mean differences: 64, 85, 64 kPa) and for the total foot (mean difference 128kPa). However, the main effect of footwear was not significant for the hallux mask (mean difference 26 kPa). The interaction of footwear and flooring surface was significant for all foot regions. Within the barefoot condition, the carpet conditions consistently yielded significantly lower pressure than the tile condition. Within the shod condition, flooring type generally did not alter pressures.Conclusion: Shod walking yielded consistently lower peak pressures than unshod walking. Although pressures were significantly reduced while walking unshod on both carpeting options compared to tile, it should be noted that subjects still frequently experienced peak pressures exceeding a previously established target threshold of 200 kPa for preventing DFU.DisclosureR.T. Crews: None. S. Chuang: None. M. Sanchez: None. S. Jhaveri: None. B.W. Donovan: None. N.H. Rak: None.FundingThis project was partially supported by grant number T35DK074390 from the National Institute of Diabetes and Digestive and Kidney disease. The content is solely the responsibility of the authors and does not represent the official views of the National Institute of Diabetes and Digestive Kidney Diseases of the National Institutes of Health.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-508-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 509-P: WoundSCAtlas—A Comprehensive Single-Cell Atlas for Comparative
Analysis of Wound Healing-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 509-P
Abstract: Introduction and Objective: Single cell profiling has advanced our understanding of wound healing, particularly in diabetic foot ulcers (DFUs) and chronic wounds. We present WoundSCAtlas, a resource to explore genomic signatures across human and mouse wound models. This atlas highlights diversity among wound types and enables cross-species expression comparisonsMethods: WoundSCAtlas integrates single cell data from diverse wound types and normal skin samples in humans and mice, including quality control, normalization, and dimensionality reduction. Unsupervised analysis identified cellular clusters from transcriptomic profiles. Differential expression analyses compared wound types and healing outcomes.Results: WoundSCAtlas offers single-cell gene expression data across wound types, healing outcomes, and skin cell populations in humans and mice. It includes over 200k human cells from healing and non-healing DFUs, chronic wounds, diabetic skin, and normal skin, along with >200k cells from mouse models for comparative analysis. Users can explore expression patterns across samples and species using annotated UMAPs and a biomarker gene tool.Conclusion: WoundSCAtlas is a resource for identifying biomarkers, analyzing wound heterogeneity, and understanding transcriptomic profiles in diverse wound across human and mouse models. The atlas offers insights into wound healing processes and translational implications through comparative data.DisclosureD. Choi: None. M.K. Bhasin: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-509-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 510-P: Educational Attainment and Inpatient Diabetic Foot Ulceration
-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 510-P
Abstract: Introduction and Objective: Diabetic foot ulceration is a severe complication of diabetes associated with significant morbidity due to lower extremity amputation. In Barbados, which has been characterized as "the amputation capital of the world”, the impact of social determinants such as educational attainment on ulceration outcomes remains poorly understood. This study investigates the relationship between educational attainment and diabetic foot ulceration outcomes in hospitalized patients.Methods: A prospective cohort study of 176 participants was conducted at Barbados' sole public hospital over six months. Data collection included baseline characteristics, ulcer characteristics, comorbidities, and SINBAD (Site, Ischemia, Neuropathy, Bacterial Infection, Area, and Depth) scoring. Random forest modeling was employed to predict complete healing at 6 weeks post-admission, with SINBAD scoring stratified by educational level.Results: Of the cohort, 17.5% completed primary education only, while 56.8% completed secondary education only. This distribution differs notably from the general Barbadian population, where primary education net enrollment was 96.7% in 2019. Mean SINBAD scores were comparable between primary-only (2.45) and secondary-only (2.51) education groups. No statistically significant association was found between educational attainment and healing outcomes at six weeks.Conclusion: While educational attainment in the study cohort was lower than the general population, it did not significantly influence either SINBAD scores or six-week healing outcomes for diabetic foot ulcers. Future research should focus on developing targeted educational interventions for foot care that are accessible and effective across all educational levels.DisclosureL. Lovell: None. P.S. Chami: None. N.K. Davies: None. N. Chockalingam: None. N.S. Greaves: Research Support; Pfizer Inc.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-510-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 511-P: Red Light Green Light 1-2-3—Creating a Novel Health Education
Tool for Reaching Diabetic Foot Ulceration in Afro-caribbean Communities-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 511-P
Abstract: Introduction and Objective: Diabetic foot ulceration is a complication of diabetes which may lead to lower extremity amputation and disability with impaired quality of life. It disproportionately affects persons of minority ethnic backgrounds who also have poorer outcomes. This study aims to develop a culturally appropriate diabetic foot education tool for foot ulcer prevention and early treatment in an Afro-Caribbean community in BarbadosMethods: An equal arms mixed methods approach was used. This included: 1) a quantitative prospective six-month inpatient cohort study which analyzed demographic and ulcer characteristics of persons admitted with foot ulcer to the island’s lone tertiary- level hospital; and 2) A qualitative study at the primary care level using focus groups, dyads and triads with health care professional and persons living with diabetes (PLWD) and foot ulcer to identify preferred methods for receiving health education to inform design of a scalable ulcer prevention education interventionResults: Inpatient characteristics determined that persons most needing the intervention were average age of 63.4 + 11.2 years and of lower socio-economic groups (Income level $ US 0-25000 annual income and those on social services benefits). Video-based ulcer prevention information given by a medical doctor, using short, culturally relatable speech was viewed as most reliable and useful by the population. Data iteratively informed the design of an educational tool based on a traditional childhood Caribbean game; “Red Light, Green Light 1-2-3”.Conclusion: Culturally accessible video-based health education tools are desirable to PLWD in Barbados, and may be useful in similar Caribbean populations including American diasporic populations, who may have poorer uptake with traditional self-management programmes.DisclosureL. Lovell: None. M.V. Barrow: None. J.P. Niles-Morris: None. N.S. Greaves: Research Support; Pfizer Inc.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-511-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 512-P: A Medical Student–Run Initiative to Improve Glycemic Control in
Prediabetic and Type 2 Diabetic Patients at Free Clinics in South Carolina
-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 512-P
Abstract: Introduction and Objective: Medical Students Making Change (MSMC) is a student-led organization at the University of South Carolina School of Medicine that collaborates with local free medical clinics to improve patient control of T2DM. South Carolina’s adult population has a high rate of diabetes (13.2%) and diabetes-related complications, including the highest rate of foot amputations. This project aims to promote prevention strategies for T2DM within underserved areas.Methods: Student volunteers review HbA1c values to screen and enroll patients that are ≥ 18 years old with diagnosed T2DM or prediabetes. Patients enrolled receive biweekly counseling calls to discuss diet, exercise, and barriers to healthcare, as well as an HbA1c check every 3 months. Patients who meet criteria for continuous glucose monitoring (CGM) are given a CGM and monitored by an endocrinologist.Results: The mean initial HbA1c value for participants (n = 71) was 9.63%. With our lifestyle and educational strategies, HbA1c levels decreased by an average of 0.64% (p=0.2230 with 95% CI -0.427 to 1.705). Average blood glucose decreased from 154 mg/dL to 148 mg/dL in patients utilizing the CGM (p=0.2361 with 95% CI -7.21 to 19.71).Conclusion: These promising data indicate that patient education and access to resources can improve T2DM management in underserved areas.DisclosureB. Franz: None. M.E. Becker: None. A. Lunt: None. K. Borglum: None. C.A. Hensing: None. M. Hotchkin: None. S. Litzenberger: None. S. Varanasi: None. L.P. Reagan: None. D. Keen: None.FundingSC Physicians Care Charity, Free Diabetes SC
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-512-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 513-P: Comparative Analysis of Health Care Utilization between Diabetes
Self-Management Education and Support (DSMES) Program Participants and a
Matched Comparison Group-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 513-P
Abstract: Introduction and Objective: Following standards of care for diabetes management is important for reducing risk of health complications and better health outcomes for persons with diabetes. DSMES programs provide guidance supportive of routine and preventive healthcare as part of active diabetes management. This study examined the impact of DSMES on healthcare utilization, specifically ER visits, hospital admissions after ER visits, and preventive care visits (primary, podiatry, and vision) among group-based DSMES program participants, compared to a matched comparison group.Methods: A quasi-experimental study was conducted using EHR data from 2022-2023, comparing DSMES program participants to a propensity scored matched comparison group (N=604) who received care at a health center. Participants were matched 1-1 on demographics and health indicators including diabetes diagnosis, biometric pre- and posttest measurements (A1C, BMI, LDL), and presence of diabetes-related comorbidities. A two-sample t-test compared healthcare utilization at 6 months and 1 year post program completion.Results: ER visits and hospital admissions after ER visits were significantly lower for DSMES group (24% and 4%) compared to matched comparison group (32% and 8%, p<.05). Healthcare visits were higher for DSMES group at both 6 months (90% vs. 62%, p<.01) and 1 year follow-up (95% vs. 72%, p<.01) for primary care visits related to diabetes (p<.001). Podiatry and vision care visits indicated an increase in preventive care for participants compared to non-participants.Conclusion: Participation in a DSMES program may lead to fewer ER visits and hospital admissions and greater utilization of preventive care visits (primary, podiatry, and vision) for persons with diabetes. Future research could further investigate ways to increase participation in DSMES and explore factors like SDOH that influence healthcare utilization.DisclosureL. Boyce: None. C. Lesesne: None. A. Weckenman: None. J. Halvorson: None. E. Malone: None. A.L. Carter: None. E. Dawkins: None. M.M. Ayala-Perales: None. A. Mickens: None. K.D. Farris: None.FundingCenters for Disease Control and Prevention Division of Diabetes Translation (75D30122C14706)'
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-513-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 514-P: The Role of Peer Support in Diabetes Self-Management Education and
Support (DSMES) Services-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 514-P
Abstract: Introduction and Objective: DSMES is underutilized by people with diabetes (T2D). We adapted the Peers for Progress peer support curriculum to support patients referred to DSMES classes.Methods: As part of a pilot to increase attendance and completion of DSMES, we conducted a 2-day training for peer supporters with peer support experts. Sessions included a diabetes refresher, communication and support skills, and protocols. We met with peer supporters at least quarterly during the pilot. Peer supporters contacted participants and collected quantitative and qualitative data about attendance and reflections on DSMES classes. They also recorded the communication type, the duration of phone calls and support offered.Results: Fourteen patients were randomized to peer support after referral to DSMES services. The average number of contacts with peer supporters was 2.8 (range 1-9) for a total of 42 contacts. Contact types included phone (45.2%), email (30.9%) and text (21.4%). Phone call length was short with most contacts lasting less than 5 min (52.6%), 5-10 min (42.1%), and one over 15 min (5.2%). Peers provided support during contacts around encouraging DSMES class attendance (38%), emotional support (7%), encouragement or motivational support (40%), and problem-solving (10%). The main discussion topics included positive comments about the class curriculum (n=8) and supporting adherence to diabetes self-management activities. Communication challenges were common, with difficulties reaching participants by phone (35.7%). When reflecting on providing support, peer supporters recommended creating a positive relationship with the study participants to ‘help them help themselves’ and encouraging the healthcare providers to support DSMES services during their visits with patients.Conclusion: Peer support is a potential strategy to increase attendance and completion of DSMES classes. Future research should optimize communication methods between peers and participants.Disclosure L.A. Young: Research Support; Novo Nordisk, Rhythm Pharmaceuticals, Inc, Lilly Diabetes, vTv Therapeutics, Carmot Therapeutics, Inc, Insulet Corporation, Corcept Therapeutics, Diasome Pharmaceuticals, MannKind Corporation, Fractyl Health, Inc. J. Halladay: None. M.B. Vu: None. K.M. Mottus: None. J. Rees: None. P. Chen: None. K. Hammond: None. K.K. Goeke-Austin: None. K. Donahue: None.FundingNational Institutes of Diabetes and Digestive and Kidney Diseases (NIDDK) (1-R34-DK132571-01)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-514-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 515-P: T1D Index with Subnational Modelling
-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 515-P
Abstract: Introduction and Objective: Our global model provides accurate estimates on Type 1 Diabetes (T1D) prevalence, incidence and associated mortality and life expectancy across the globe, and now includes additional functionality has been added to the T1D Index, and data at sub national levels for selected countries and simulations to model the impact of T1D interventions.Methods: The T1D Index utilizes a Markov Model and machine learning techniques that use data on T1D incidence and T1D-associated mortality to produce prevalence, incidence and associated mortality and life expectancy estimates (published in the Lancet Diabetes and Endocrinology). We developed a subnational modelling framework that categorizes countries into three tiers based on data availability, with each tier employing a distinct approach to estimate type 1 diabetes incidence.Results: Subnational incidence varies substantially within countries. For both the USA and New Zealand, where we estimated incidence using ethnicity-specific indices, a distinct pattern emerges on the subnational map.Conclusion: The burden of type 1 diabetes in 2025 is vast and is expected to increase rapidly, especially in resource-limited countries across Asia. Moreover, subnational modeling offers a granular perspective, facilitating more effective resource allocation and better-informed decision-making.DisclosureF. Wang: None. S. Pearson: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-515-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 516-P: Health Literacy in Younger and in Older Patients with Type 2
Diabetes Undergoing Coronary Angiography-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 516-P
Abstract: Introduction and Objective: Health literacy reflects the ability to make appropriate health decisions and affects health outcomes. It therefore is an important parameter in patient care. Health literacy in patients undergoing coronary angiography is unclear and is addressed in the present study.Methods: We enrolled 697 consecutive patients undergoing coronary angiography for the evaluation of established or suspected stable CAD in a tertiary care setting in central Europe. Health literacy was measured using the validated HLS-EU-Q16 questionnaire.Results: A response rate of 79.5% was achieved. Overall, 222 patients (31.9%) had type 2 diabetes (T2DM). The mean age was 67.6±10.9 years, 272 patients were <65 years and 425 patients ≥65 years. Comparing T2DM patients to those who did not have diabetes, overall median health literacy scores (HLS) were 12.0 [IQR:10-15] vs. 13 [IQR:10-15] among patients <65 years (p=0.655) and 12 [IQR:10-16] vs. 13 [IQR:11-15] among older patients ≥65 years (p=0.856). Prevalence rates of adequate (HLS 13-16), problematic (HLS 9-12) and inadequate (HLS 0-8) health literacy did not differ significantly in patients with T2DM vs. subjects without T2DM in both age groups: 49.2% vs. 56.1%, 34.4% vs. 27.8% and 16.4% vs. 16.1% among patients <65 years and 49.5% vs. 56.4%, 36.0% vs. 30.7% and 14.4% vs. 12.9% among patients ≥65 years, respectively.Conclusion: We conclude that among patients undergoing coronary angiography for the evaluation of established or suspected stable CAD health literacy is suboptimal, regardless of diabetes status and age.DisclosureM. Neyer: None. J. Vogel: None. P. Elsner: None. T. Plattner: None. A. Vonbank: None. B. Larcher: None. A. Mader: None. L. Schnetzer: None. A. Leiherer: None. M. Frick: None. A. Muendlein: None. A. Festa: None. H. Drexel: None. C.H. Saely: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-516-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 517-P: Satisfaction with Information Regarding Pharmaceutic Therapy in
Younger and Older Patients with Type 2 Diabetes Undergoing Coronary
Angiography-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 517-P
Abstract: Introduction and Objective: Satisfaction with medical information plays a critical role in appropriate medication use and is fundamental to pharmacotherapy. This study addresses the lack of data on this important issue in the clinically important population of patients with type 2 diabetes (T2DM) undergoing coronary angiography.Methods: We consecutively enrolled 697 patients who underwent coronary angiography for the evaluation of suspected or established stable coronary artery disease. Satisfaction with information regarding pharmacotherapy was measured using the validated Satisfaction with Information about Medicines Scale (SIMS-D) consisting of two sub-scales covering action and usage or potential problems. Further, health literacy, which includes the ability to understand and follow instructions for treatment, was determined using the EU-HLS-Q16 questionnaire.Results: For SIMS-D, a response rate of 67.9% was achieved. Overall, 31.9% had T2DM according to ADA criteria. Mean age was 67.6±10.9 years (272 patients <65 years, 425 patients ≥65 years). SIMS-D scores did not differ significantly between T2DM patients and those without diabetes among patients <65 years (9 [IQR:6-15] vs. 9 [IQR:5-14], p=0.903) nor among patients ≥65 years (12 [IQR:7-16] vs. 10 [IQR:6-16], p=0.385). Independently of age categories and diabetes status, patients scored significantly lower on items targeting satisfaction with information about potential problems than in the sub-scale for action and usage of medication (p<0.001). In analysis of covariance, health literacy independently of T2DM, gender and age predicted SIMS-D (F=62.648; p<0.001).Conclusion: From our findings we conclude that satisfaction with information regarding pharmacotherapy in angiographied coronary patients does not depend on the presence of T2DM or age, but is significantly associated with health literacy.DisclosureM. Neyer: None. J. Vogel: None. P. Elsner: None. T. Plattner: None. A. Vonbank: None. B. Larcher: None. A. Mader: None. L. Schnetzer: None. A. Leiherer: None. M. Frick: None. A. Muendlein: None. A. Festa: None. H. Drexel: None. C.H. Saely: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-517-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 518-P: Enhancing CGM Utilization in Primary Care—Outcomes of a
Comprehensive Education and Training Program in an Academic Institution-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 518-P
Abstract: Introduction and Objective: Despite the proven benefits of continuous glucose monitoring (CGM) in improving diabetes management, its adoption remains limited, particularly in primary care (PC) settings. This underutilization represents a critical gap in healthcare delivery.Methods: A CGM implementation program was launched within a large academic network to educate, train, and support primary care professionals—including residents, faculty, nursing staff, and ancillary personnel—on using CGM for insulin-treated patients with type 1 and type 2 diabetes. Spanning over 25 PC clinics between February 2023 and December 2024, the program combined live and virtual conferences and hands-on clinic-based education sessions covering CGM placement, ordering, data interpretation, and workflow integration. After training, participants completed an anonymous, retrospective pre-post survey with a 4-point Likert scale and free-response questionsResults: A total of 650 healthcare professionals participated in the training program, comprising 42.9% providers and 57.1% support staff. Of them, 67.1% attended live conferences, and 32.9% participated in clinic-based face-to-face sessions. Level of comfort and expertise after training increased on CGM placement (67% to 92%), understanding benefits (68% to 93%), sensor-device ordering (53% to 77%), sensor-device connectivity (72% to 91%), and linking patients to the clinic’s data management platforms (53% to 74%); all p < 0.0001. All providers expressed interest, with 93% demonstrating strong interest for implementing CGM into their practice. Participants cited insurance challenges (29%), time constraints (18%), and insufficient training (16%) as the most significant barriers.Conclusion: Primary care professionals are eager to implement CGM but face several challenges when prescribing it. This study reinforces the need for improved clinician education on CGM technology, improving care for patients with diabetes.DisclosureI.C. Flores Shih: None. R. Celedon-Garcia: None. K. Zamudio-Coronado: None. B. Marshall: None. I.A. Castro-Revoredo: None. S. Kantipudi: None. A. Isaacs: None. G. Umpierrez: Research Support; Abbott, Dexcom, Inc., Bayer Pharmaceuticals, Inc, Corcept Therapeutics. Advisory Panel; Dexcom, Inc., GlyCare Health.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-518-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 519-P: Impact of Dose Adjustment for Normal Eating Courses on Glycemic
Control, Severe Hypoglycemia, and Diabetic Ketoacidosis in People with
Type 1 Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 519-P
Abstract: Introduction and Objective: Structured education for type 1 diabetes (T1D) aims to empower individuals to manage their condition effectively. However, limited research has explored the long-term effects of structured education on glycemic improvement, severe hypoglycemia, or diabetic ketoacidosis (DKA). This study assessed the 12-year impact of dose adjustment for normal eating (DAFNE) courses on glycemic levels, the incidence of hypoglycemia requiring emergency medical assistance, and episodes of DKA in people with T1D.Methods: This is a 12-year follow-up study of people with T1D who attended a series of DAFNE courses at Dasman Diabetes Institute. The study included clinical data from the DAFNE registry collected between 2009 and 2024.Results: A total of 925 people with T1D attended the DAFNE course with a mean (±SD) HbAIc 69.3 ± 18.3 mmol/mol. After 1 year, the mean HbA1c decreased to 63.1 ± 15.9 mmol/mol and further decreased to 61.0± 13.8 mmol/mol at year 6, and 59.1 ± 11.2 mmol/mol at year 12 (p<0.001). At baseline, DKA was reported by 13.5% of attendees and after 1 year reported by 4.6% of attendees. Over the 12-year follow up period, DKA was reported by less than 1% of attendees (p<0.001). At baseline, 7.8% of attendees reported hypoglycemic events requiring emergency medical services and after one year reported only by 1% of attendees and over the 12-year follow up period, reported by less than 1% of attendees (p=0.001).Conclusion: The DAFNE program can lead to reduction in glycemia, severe hypoglycemia and DKA with sustained improvements and benefits observed over a 12-year follow-up period.DisclosureJ. AlKandari: None. E. Taghadom: None. M. Irshad: None. A. Megahed: None. L.G. Sojan: None. A. Abdullah: None. S. Murad: None. A. Alattar: None. D. Alroudhan: None. E. Al-Ozairi: None.FundingKuwait Foundation for the Advancement of Sciences (KFAS), Kuwait
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-519-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 520-P: School Day Disruptions in Type 1 Diabetes (T1D) Management—Early
Experiences from the School-Partnered Collaborative Care (SPACE) Study
Highlight an Unmet T1D Education Need-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 520-P
Abstract: Introduction and Objective: T1D management may require frequent interventions which disrupt the school day, though the missed class time and impact on students are not described. We aimed to determine the frequency, duration, and type of school disruptions for students with T1D.Methods: We analyzed data for 16 children (age 9.0±1.8 years, 62% female, 31% public insurance, mean HbA1c 7.5±1.1%, T1D duration 3.7±2.4 years) from 9 districts in SPACE, a school-based T1D intervention, in 2024. Nearly all students used devices (94% CGM, 75% AID). School nurses reported T1D management outside of routine dosing, including the reason, time to resolve, and parent/clinic contact. We calculated an event rate per student, accounting for the number of in-person school days for each district during active study duration.Results: In 3 months, 350 events were reported (2-89/student) with a median of 1.2 events/week (IQR 0.5, 2.8, min: 0.6, max: 6.5). Median event time was 5 minutes (IQR 3, 13, min:1, max:65), though 72 (21%) required ≥15 minutes. Impending or true hypoglycemia were reported most often (218, 62%), followed by hyperglycemia (109, 31%). Few (<5%) were related to device issues or ketones. Most events required presentation to the nurse (307, 87%). Half (167, 48%) of events resulted in parent contact, whereas only 4 (1%) required contact with the medical team. Nearly all (99%) events were handled in school. There were no associations between event rates and age, T1D duration, or HbA1c.Conclusion: Young students with T1D have on average at least one school disruption related to acute management weekly. As our findings do not include routine care or parent/student communication, this is an underestimate. Medical teams may be unaware of these experiences, as parents are usually the point of contact. Diabetes education should include strategies to mitigate school day disruptions to benefit student learning and well-being.DisclosureC. March: None. V. Stouffer: None. E. Naame: None. C. Moon: None. I. Libman: None.FundingNational Institutes of Health (1K23DK135800)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-520-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 521-P: Greater Participation in Diabetes Management Coaching Program
Improves Glycemic Control and Diabetes Distress-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 521-P
Abstract: Introduction and Objective: Virtual diabetes management platforms can be used to improve glycemic control for people with diabetes. The objective of this study was to evaluate the effectiveness of the Diabetes Care Management coaching program in the Wellworks for You© (WW) chronic disease management virtual platform.Methods: A cohort of people with diabetes enrolled in the WW Diabetes Management Program between Sept 2021-2024 were evaluated. At entry, participants completed a biometric screen including blood pressure, A1c, fasting glucose & lipids, and a diabetes distress questionnaire (DDQ). The DDQ was completed every 90 days. Participants entered home glucose levels and A1c into the WW platform. Coaching calls were with certified diabetes educators (CDEs). Main outcomes were change in A1c and DDQ score, stratified by number of calls completed.Results: Of the 651 people enrolled, 479 (74%) were female, 56% white, 14% Hispanic, 10% black. At entry, mean age was 49±13 years, BMI 34.4±8 kg/m2, BP 124±14/77±9 mmHg, HR 75±11, fasting glucose 128±53 mg/dL, TC 178±41 mg/dL, LDL 99±34 mg/dL, HDL 50±13 mg/dL, TG 153±94 mg/dL, A1c 7.4±1.7%, and DDQ score 51.0±12.1. Mean A1c decreased to 6.6±1.2% (Δ -0.8%). Mean DDQ score decreased to 47.4±12.6 (Δ -3.6). In those completing 2-4 coach calls, A1c decreased by -1.2% and DDS by -1.1. In those completing ≥5 coach calls, A1c decreased -1.8% and DDS -8.9. More contact with diabetes management coaches was associated with greater improvements in glycemic control and diabetes distress.Conclusion: Participants engaging with trained CDE coaches experience measurable improvements in health outcomes. Notably, those who completed ≥5 coaching sessions achieved a mean reduction in A1c of 1.8% compared to 1.2% with less participation. These results underscore the value of personalized coaching in managing diabetes and suggest that sustained engagement with coaching interventions can significantly enhance health metrics.Disclosure A.D. Coviello: Advisory Panel; Novo Nordisk. Consultant; Intuitive Surgical. Other Relationship; GI Dynamics. Consultant; Hanmi Pharm. Co., Ltd. Advisory Panel; NewAmsterdam Pharma. R. Fox: None. M. Wolf: None. T. Jones: None. R. Powers: None. C. Whitton: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-521-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 522-P: Utilization of Personal Continuous Glucose Monitoring (CGM) Systems
in the Inpatient Setting-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 522-P
Abstract: Introduction and Objective: This pilot study sought to compare glucose outcomes and provider insulin dosing confidence in individuals using personal CGM while in the hospital compared to those receiving point of care blood glucose (POC BG) monitoring only.Methods: Hospitalized individuals followed by the diabetes service and expected to be discharged on insulin were included. Diabetes service providers completed a short Insulin Dosing Confidence Survey after daily rounds. POC BG values were recorded.Results: A total of 247 patient days were included in the survey. POC BG monitoring only = 200, stand-alone CGM =27, and automated insulin delivery systems = 20.Conclusion: Individuals in the standalone CGM and POC BG only groups had similar mean glucose values and percent of glucose values in target range, however no hypoglycemia was observed in either group utilizing CGM compared to 5.4% in the POC BG monitoring only group. This suggests personal CGM may have a role in limiting hypoglycemia in hospitalized individuals. Further study is needed, and efforts should be made to empower individuals to start or continue use of personal CGM while hospitalized.Disclosure R. Longo: Advisory Panel; Dexcom, Inc.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-522-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 523-P: Seeking Methods to Engage Emerging Adults (EAs) with Type 1
Diabetes (T1D) in Diabetes Self-Management Education and Support
(DSMES)—A Human-Centered Design Approach-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 523-P
Abstract: Introduction and Objective: DSMES is considered a cornerstone of diabetes care. EAs with T1D are reported to have alarmingly low DSMES participation rates yet doing most of their self-care. In its present form, DSMES has been cited for not meeting EAs’ needs. Our objective was to discover factors affecting DSMES engagement and use a collaborative approach to build a DSMES intervention considerate of factors important to EAs with T1D.Methods: EAs with T1D (n=32;18-35y, 56% female, 97% White Non-Hispanic, residing in 4 states) participated in semi-structured interviews (n=22) and a design sprint (n=11), an intervention co-design process grounded in human-centered design. Transcribed interviews were coded using an inductively developed codebook for content and thematic analyses. Design sprint sessions were summarized.Results: Themes about factors important to engaging EAs in DSMES were identified: 1.Continuity in care, particularly interpersonal relationships with T1D care team. 2.Empathetic interactions with diabetes care and education specialists (DCESs) who demonstrate an understanding of real-life experiences of EAs. Several EAs referred to a DCES with T1D lived experience. 3.Person-centered education tailored to issues relevant to EA and life stage. 4.DSMES emphasis on how to transfer from pediatric to adult care. 5.Peer support; EAs described desire to connect with other EAs with T1D. In the design sprint, EAs advised tactics to address these factors, designing a DSMES program in which a DCES who conveyed T1D lived experience would guide interactive group sessions on topics selected by each group, from which EAs would emerge with concrete T1D care goals and ongoing access to relevant DSMES digital resources.Conclusion: Findings provide insight into what EAs with T1D desire from DSMES. Designing DSMES programs considerate of user feedback may improve DSMES participation by EAs and, in turn, T1D outcomes.Disclosure J.S. Krall: Research Support; Sanofi, Becton, Dickinson and Company. M. Hamm: Research Support; Pfizer Inc. L. Funair: Other Relationship; Medtronic, Insulet Corporation, Beta Bionics, Inc. F. Cameron: Research Support; Pfizer Inc. J. Ng: Research Support; Sanofi-Aventis U.S. I. Libman: None. L.M. Siminerio: None.FundingNational Institutes of Diabetes and Digestive and Kidney Diseases (5R34DK136020)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-523-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 524-P: Culturally Competent Diabetes Management—Addressing Access for
Limited English Proficient Patients-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 524-P
Abstract: Introduction and Objective: Diabetes affects all cultures, yet inequities persist, especially among minority groups who often receive lower-quality care. Language barriers lead to inadequate blood sugar control and reduced engagement in Diabetes Self-Management Education (DSME). This report evaluates the effectiveness of a DSME team in integrating culturally competent translated care into primary care, enhancing services for patients with language barriers using best practices and a patient-centered approach to provide materials in their preferred languages.Methods: Eligible patients aged 18-75 with Type 2 Diabetes (T2D) and a language preference classified as "other" were included, with exclusions for Type 1 Diabetes and out-of-state residency. Data from 110 participants (mean age 45 years, SD = 18) included 53% female, with language preferences: 49% Spanish, 10% Vietnamese, 16% Chinese, 7% Russian, 6% Arabic, 5% Farsi, and others. A chi-squared test compared appointment completion rates (scheduled vs. completed) and no-show rates between standard scheduling with translation services and culturally competent outreach involving initial assessments by the CDCES and the translation team.Results: The DSME team had a 55.45% completion rate (73 of 110), while standard practice had 4.55% (5 of 110). The chi-squared test indicated a significant difference ('' = 77.84, df = 1), showing that the DSME approach significantly enhances appointment completion. Additionally, 87% of DSME participants completed their follow-up lab results within 6 months, compared to only 6% of non-participants.Conclusion: These findings highlight the crucial role of culturally competent translated DSME outreach and care in improving health outcomes and reducing disparities among diverse populations.DisclosureA. Simos: None. J. Ringrose: Employee; Insulet Corporation. J. Hong: None. M. Gabriel: None. S. Tsai: None. M. Basina: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-524-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 525-P: Effectiveness of a T1D Patient and Health Professional Codesigned
Diabetic Ketoacidosis (DKA) Prevention Infographic-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 525-P
Abstract: Introduction and Objective: To meet an urgent need, with 68 patients and health professionals we co-designed and refined a DKA education infographic (Figure 1, Infographic Facepage). We aimed to evaluate its effectiveness on changes in patient behaviour, knowledge, beliefs and attitudes.Methods: Through national practice-based recruitment in our project network, we administered two effectiveness outcome questionnaires (‘DKA Behavior’ and DKA Knowledge) before providing the DKA Infographic (‘Day 0’), one day after (‘Day 1’), and one month later (‘Day 30’). Scores were compared by paired t-tests or McNemar’s tests for all subjects from Day 0 to Day 1 (N=20), and explored Day 0 to 30 (n=10).Results: The study recruited a total of 20 participants (11 females, 9 males, mean age 46 (range 31-70), mean A1c 6.8 percent). Mean DKA Behavior summary scores improved from 44.3 to 52.9 (out of 70, p=0.002) on Day 1, and to 53.5 on Day 30 (p=0.021). Mean DKA Knowledge summary scores improved from 5.3 to 7.7 (out of 10, p<0.001) on Day 1, and to 7.9 on Day 30 (p=0.033). 12/20 (60%) reported willingness to test ketones on sick days and/or with ketoacidosis symptoms on Day 0, 20/20 (100%, p=0.013) on Day 1, and 9/10 (90%) on Day 30.Conclusion: A dramatically simplified patient and professional co-designed DKA education infographic in preliminary analysis improves knowledge and behavior for sick day management.DisclosureW. Cheema: None. M. Waniss: None. M.T. Cheema: None. D. Mumford: None. A. Al Mulla: None. N. Verhoeff: None. A. Orszag: None. A. Weisman: None. L. Lovblom: None. N. Ivers: None. B.A. Perkins: Other Relationship; Abbott, Novo Nordisk, Sanofi. Advisory Panel; Abbott, Insulet Corporation, Sanofi, Novo Nordisk, Nephris, Vertex Pharmaceuticals Incorporated. Research Support; Novo Nordisk.FundingDiabetes Canada Operating Grant (OG-3-21-5572-BP)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-525-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 526-P: A Patient and Health Care Professional Codesigned Diabetic
Ketoacidosis Educational Infographic for Type 1 Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 526-P
Abstract: Introduction and Objective: Diabetic Ketoacidosis (DKA) prevention protocols are underused and difficult to understand by patients. We aimed to co-create with people living with T1D, caregivers, and healthcare professionals a core DKA education infographic.Methods: Focus groups were recruited through purposive sampling. In a user-centered design process involving oversight by a User Advisory Panel, participants were shown iterative versions of the infographic in semi-structured interviews. Thematic analysis of coded transcripts informed iterative refinements until convergence was achieved.Results: Following focus groups that defined barriers and behaviours for DKA prevention, a total of 20 diverse participants and 10 members of a User Advisory Panel were involved in seven iterative design sessions. A final draft of the infographic (Figure 1, Faceplate) emerged that incorporated key actions and barriers. Findings emphasized the importance of simplification compared to existing resources; use of clear and accessible language defining the necessary actions. Main design themes were flow of the infographic, legibility, and use of visuals that enhance understanding.Conclusion: A dramatically simplified patient co-created DKA education infographic that addressed known barriers and behaviours is ready for evaluation of DKA prevention knowledge in an intervention study.DisclosureW. Cheema: None. D. Mumford: None. N. Ivers: None. M.T. Cheema: None. N. Verhoeff: None. A. Al Mulla: None. A. Orszag: None. L. Lovblom: None. A. Weisman: None. B.A. Perkins: Other Relationship; Abbott, Novo Nordisk, Sanofi. Advisory Panel; Abbott, Insulet Corporation, Sanofi, Novo Nordisk, Nephris, Vertex Pharmaceuticals Incorporated. Research Support; Novo Nordisk.FundingDiabetes Canada Operating Grant (OG-3-21-5572-BP)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-526-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 527-P: Mapping the Educational Infrastructure Required for Successful
Remote CGM Implementation in Older Adults-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 527-P
Abstract: Introduction and Objective: The REST (Readiness, Education and Sustainability for CGM Technology adoption) study utilized remote education to facilitate continuous glucose monitoring (CGM) adoption in older adults on complex insulin regimens, while building a framework for sustained use. Medicare allows limited diabetes education hours, and little is known about the educational support requirements and implementation challenges in this age group. We interviewed certified diabetes care and education specialists (CDCES) to assess the challenges and facilitators of remote CGM education in older adults.Methods: Semi-structured interviews were conducted with 6 CDCES. Interviews were recorded, transcribed verbatim, and analyzed using MaxQDA by a multidisciplinary team.Results: Four main themes were explored: (1) clinical workflow (100% reported needing to significantly adapt their teaching approaches, requiring 2-3X more time than standard diabetes education visits); (2) age-related adaptations: 3 approaches were developed based on participant cognitive/physical/technological competencies and support system: standard remote delivery, enhanced remote support including caregivers, hybrid remote/in-person visits. Teaching was modified using simplified instructions, more repetition, and multi-modal formats (written, visual, hands-on); (3) resource requirements (83% extended sessions and more comprehension checks); (4) implementation barriers (video platform difficulties (83%), CGM device setup issues (67%), and time requirements (100%)).Conclusion: Successful CGM implementation in older adults requires substantial adaptation of traditional education approaches using simplified, multi-modal teaching methods. These adaptations demand significantly more educator time than currently supported by Medicare. Our findings suggest a critical need to realign reimbursement with the education requirements of older adults adopting diabetes technology.DisclosureA. Adam: None. H. Brabant: None. C. Slyne: None. M. Savory: None. N. Krakoff: None. J.D. Bulger: None. S. Kasetti: None. M. Munshi: Advisory Panel; Abbott, Medtronic. Research Support; Dexcom, Inc. Advisory Panel; Sanofi. R.S. Weinstock: Research Support; Amgen Inc, Eli Lilly and Company, Tandem Diabetes Care, Inc, Diasome Pharmaceuticals, Insulet Corporation, MannKind Corporation, Dexcom, Inc. E. Toschi: Consultant; Vertex Pharmaceuticals Incorporated, Sequel Med Tech. Research Support; Dexcom, Inc.FundingThis work was supported by a grant from The Leona M. and Harry B. Helmsley Charitable Trust
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-527-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 528-P: Awareness of MASLD among People with Diabetes in Four Major U.S.
Cities-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 528-P
Abstract: Introduction and Objective: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease globally, affecting ~60% of people with T2DM, yet remains under-recognized. This study aims to assess awareness of the new term MASLD and liver disease risk factors among people with diabetes.Methods: This was randomized, weighted cross-sectional online survey of adult residents from Chicago, Houston, Los Angeles (LA), and NYC. Participants were recruited from Sept. 5-13, 2024 via river sampling, phone, mail, and opt-in methods. Three weighted samples were created: general adults (n=4,000), adults with diabetes (n=1,000) and PCPs (n=800). Exposures included age, gender, ethnicity, education, PCP visits, liver enzyme testing history, and city. Logistic regression models assessed awareness of MASLD, fatty liver disease, and related risk factors.Results: In the general population, 18.7% had heard of MASLD. Among adults with diabetes, 37.8% had heard of MASLD, with highest awareness in LA (45.7%) and lowest in Houston (30.2%). Awareness was higher in people with type 1 (60.8%) than type 2 diabetes (26.7%). In contrast, 78.1% of the general population and 85.4% of adults with diabetes knew the term fatty liver disease, with healthcare providers as the main information source. MASLD awareness was significantly associated with higher education and healthcare use, with ethnic minorities less aware. People with diabetes were most aware of alcohol use as a risk factor, and least aware of high-calorie diet and sedentary lifestyle. Risk factor awareness increased significantly with higher education (OR 1.50, CI 1.4-1.6, p<0.001) and age (OR 1.07, CI 1.01-1.14, p=0.026).Conclusion: Awareness of MASLD was relatively low among adults with diabetes in this study compared to the burden of disease, but linked to higher education, healthcare use, and age. These findings highlight the need for targeted health communication, especially for ethnic minorities and those with T2DM, to improve understanding of MASLD and its risk factors.DisclosureM.I. Manolas: None. N. Alkhouri: Research Support; Novo Nordisk. Speaker's Bureau; Madrigal Pharmaceuticals, Inc. Research Support; Madrigal Pharmaceuticals, Inc, Eli Lilly and Company, Inventiva Pharma, 89bio, Inc, Akero Therapeutics, Inc. A. Allen: Research Support; Novo Nordisk. Advisory Panel; Novo Nordisk, Boehringer-Ingelheim, Madrigal Pharmaceuticals, Inc, GlaxoSmithKline plc. Research Support; TARGET PharmaSolutions, Inc, Pfizer Inc. M. Bansal: Advisory Panel; Novo Nordisk, Merck & Co., Inc, GlaxoSmithKline plc, Madrigal Pharmaceuticals, Inc, Fibronostics, Boehringer-Ingelheim. Research Support; Pfizer Inc. Advisory Panel; Boston Pharma, Curve Bio. Research Support; The Kinetix Group. B.E. Fortune: Consultant; WL Gore and Associates, Gilead Sciences, Madrigal Pharmaceuticals, Inc. Other Relationship; BD Medical. Y. Handelsman: Research Support; Amgen Inc. Consultant; Amgen Inc. Research Support; Applied Therapeutics. Consultant; Applied Therapeutics. Research Support; Corcept Therapeutics. Consultant; Corcept Therapeutics. Research Support; Ionis Pharmaceuticals, Lilly Diabetes, Merck Sharp & Dohme Corp, Regeneron Pharmaceuticals. S. Isaacs: None. S. Kumar: Speaker's Bureau; Madrigal Pharmaceuticals, Inc. Consultant; Madrigal Pharmaceuticals, Inc. Speaker's Bureau; Novo Nordisk. Consultant; Novo Nordisk. S. Pannain: None. J.V. Lazarus: Consultant; GlaxoSmithKline plc. Research Support; Madrigal Pharmaceuticals, Inc, Boehringer-Ingelheim, Novo Nordisk A/S. Advisory Panel; Novo Nordisk A/S. Consultant; Echosens. Research Support; Pfizer Inc.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-528-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 529-P: Structured Treatment and Education Program (STEP) in Improving
Metabolic Control and Psychological Outcomes—Research of Type 2 Diabetes
(T2DM) Patients in Yunnan Rural Community-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 529-P
Abstract: Introduction and Objective: Diabetes mellitus (DM) is a serious global public health issue, and China has the highest number of diabetes patients in the world. Diabetes education is key to the treatment of diabetes. Internationally and in guidelines from other countries, it is often recommended to provide diabetes education to patients through structured treatment and education program (STEP). The aim was to evaluate the advantages of STEP for T2DM patients in Yunnan rural community, with or without insulin use, over a six-month follow-up period.Methods: Data concerning physical measurements, metabolic states, psychological conditions, and nutritional situations were gathered from 41 T2DM patients. They received the STEP intervention for T2DM. Subsequently, the identical indicators were recollected at 3- and 6-months post-intervention. SPSS 26.0 was utilized for data analysis, applying one-way ANOVA and paired t-tests.Results: Post-STEP intervention for T2DM, hemoglobin A1c notably declined at 6 months (8.64% vs. 8.03%, P < 0.027). The Mini Nutritional Assessment score remarkably rose at 3 and 6 months (23.057, 23.857, 24.22; P < 0.01). The Diabetes Distress Scale score significantly dropped at 3 and 6 months (61.1, 57.46, 39.15; P < 0.01). The Diabetes Self-Efficacy Scale and Diabetes Self-Management Scale scores also markedly increased. The hypoglycemic episode count at 6 months was significantly fewer than at baseline (P < 0.01). Although BMI, waist-to-hip ratio, diastolic blood pressure, and blood lipid levels were lower than baseline, the differences lacked statistical significance (P > 0.05).Conclusion: The STEP intervention can enhance metabolic parameters like HbA1c, waist-to-hip ratio, and blood lipids in T2DM patients.DisclosureR. Li: None. J. Liu: None. J. Zhang: None. S. Quan: None. L. Zhang: None.FundingHealth Science and Technology Program of Yunnan Province (202301AY070001-092), Yunnan health training project of high level talents(L-2024011) (YWLCYXZXXYS20221005)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-529-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 530-P: Evaluating the Role of a Digital Health Platform in Supporting
GLP-1 Adherence and Sustained Outcomes Post-discontinuation-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 530-P
Abstract: Introduction and Objective: GLP-1 agonists improve blood glucose (BG) and weight in adults with T2D or obesity alongside diet and exercise. Dario Health, a digital health platform, may help identify users likely to adhere to GLP-1 treatment and advance lifestyle interventions to facilitate smooth discontinuation of GLP-1 maintaining positive clinical outcomes. The study aimed to investigate survey outcomes conducted on Dario users who have ever taken GLP-1.Methods: This study utilized a survey conducted among Dario users in November 2024 to gather insights into their GLP-1 usage, identify users who had used GLP-1 and evaluate their clinical outcomes, engagement and behavioral change. Chi-square, t-tests, linear mixed-effects models, and simple slope analysis were employed to assess group differences and clinical outcomes over time.Results: A group of 715 users reported having used GLP-1; 15% (108/715) reported discontinuation while 85% (607/715) continued and are currently taking GLP-1. A significantly higher proportion in the continued cohort reported taking GLP-1 for >6 months than in the discontinued group (χ²(3)=56.3;p<.001). In the continued cohort, lifestyle digital activities (meal and physical activity logging) significantly moderated the reduction in monthly average BG over time (p<.01); Monthly weight measurements and engagement with educational content moderated the reduction in monthly average weight (p=.02 and p<.001). In the discontinued cohort, monthly average BG and weight remained stable over the past 6 months [BG p=.11; Weight p=.65], statistically equivalent to the continued during the same period [BG p=.35; Weight p=.30].Conclusion: The results demonstrate the potential of a digital health platform to navigate users to continue their GLP-1 treatment, drive behavioral change and sustain weight loss and BG levels following discontinuation of GLP-1 therapy.Disclosure Y. Fundoiano-Hershcovitz: Employee; DarioHealth Corp. I. Breuer Asher: None. O. Manejwala: Employee; DarioHealth Corp. Stock/Shareholder; DarioHealth Corp.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-530-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 531-P: Interactive, Online, Case-Based Education Effective at Improving
Clinical Competence Related to Screening and Diagnosing Hypercortisolism
in People with Difficult-to-Control T2D-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 531-P
Abstract: Introduction and Objective: We sought to determine if interactive, case-based, online continuing medical education (CME) could improve the competence and confidence of primary care physicians (PCPs) and diabetologists/endocrinologists (D/Es) related to screening and diagnosing hypercortisolism in people with difficult-to-control T2D.Methods: Educational design included a “test then teach” approach with evidence-based feedback following each clinical decision. A repeated pairs pre-/post-assessment study design and a McNemar’s test (P <.05 is considered significant) assessed educational effect, with Cohen’s d being used to assess educational impact (<0.2 modest effect, 0.2-0.49 small effect, 0.5-0.79 moderate effect and >0.8 extensive effect). The activity launched July 19, 2024 and data were collected through September 30, 2024.Results: 577 PCPs and 67 D/Es were included in the analysis, of which 73% of PCPs and 57% of D/Es improved competence (P<.001 for both groups with extensive overall impact of 1.11 for PCPs and 0.85 for D/Es). On a question-level: 34% of PCPs (P<.001) and 19% of D/Es (P<.05) improved at screening for hypercortisolism. 47% of PCPs (P<.001) and 25% of D/Es (P<.01) improved at interpreting lab data related to hypercortisolism. 24% of PCPs (P<.001) and 28% of D/Es (P<.001) improved at screening to identify hypercortisolism source. 42% of both PCPs and D/Es reported increased confidence.Conclusion: This study demonstrates the success of interactive, case-based, online CME on improving competence and confidence of both PCPs and D/Es related to screening and diagnosing hypercortisolism in patients with difficult-to-control T2D. Case-based education with interactive polling questions and detailed explanations related to best choices should be employed more often to help clinicians apply guidelines into practice to improve patient care.DisclosureA. Larkin: None. A. Le: None.FundingIndependent educational grant from Corcept Therapeutics
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-531-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 532-P: Assessment of Impact of Online CE Activity within a Curriculum at
Improving Primary Care Provider Knowledge, Competence, and Confidence
regarding T2D Treatment Intensification-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 532-P
Abstract: Introduction and Objective: We sought to determine if an online continuing medical education (CME) activity within a curriculum could improve the clinical knowledge, competence and confidence of PCPs related to treatment intensification.Methods: The CME intervention was a 30-min online, active learning discussion with point-of-care tools. The effect was assessed using a linked, matched pre-/post-assessment design. A paired samples t-test was conducted for significance testing and a McNemar test was conducted at the question level (5% significance level, P <.05). Confidence was assessed using a Likert scale. The activity posted December 20, 2023, and data were collected through August 2024.Results: 128 PCPs answered all questions and were included. Overall baselines were similar to results from a previously reported assessment (ADA 2024). Within this activity, these gaps were addressed, resulting in significant knowledge/competence improvements. Treatment goals: 68% (P<.001) improved at identifying weight management for people with T2D and 43% (P<.001) improved at identifying a glycemic goal for a given patient. T2D guidelines: 48% (P<.001) improved at identifying weight loss goal for person with T2D and 42% (P<.001) improved at recognizing T2D agents with very high glucose and weight efficacy according to guidelines. 46% (P<.001) demonstrated improvement related to competence in applying strategies for shared decision-making in T2D management. 28% measurable improvement in learners who were confident after the activity (P<.001).Conclusion: This study demonstrates the success of an online, active learning CME activity with point-of-care tools on improving knowledge, competence and confidence of PCPs related to T2D treatment intensification. Impact of these knowledge/competence/confidence improvements will be measured in a real world outcomes assessment in 2025.DisclosureA. Larkin: None. A. Le: None.FundingIndependent educational grant from Lilly
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-532-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 533-P: Impact of Online CME on Clinical Knowledge of Emerging Strategies
for Continuous Ketone Monitoring-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 533-P
Abstract: Introduction and Objective: We sought to determine if online continuing medical education (CME) could improve the clinical knowledge of primary care physicians (PCPs) and diabetologists/endocrinologists (D/Es) related to emerging strategies for continuous ketone monitoring (CKM).Methods: Intervention was a 15-min online video discussion with downloadable slides. Education effect assessed with matched pre-/post-study design. A paired samples t-test was conducted for significance testing and a McNemar test was conducted at the question level (5% significance level, P <.05). Confidence was assessed using a Likert scale. Data collection was August 27, 2024 to October 8, 2024.Results: 139 PCPs and 44 D/Es were included in the study, of which 40% of PCPs and 16% of D/Es improved their knowledge. On a question-level: 12% of PCPs and 9% of D/Es demonstrated improvements at recognizing benefit of CKM (P<.05 for both PCPs and D/Es). 22% of PCPs and 2% of D/Es demonstrated improvements at identifying diabetic ketoacidosis (DKA) risk (P<.01 for PCPs and P=NS for D/Es). 11% of PCPs and 5% of D/Es demonstrated improvements at recognizing benefit of earlier DKA detection (P<.05 for PCPs and P=NS D/Es). 47% of PCPs and 32% of D/Es had a measurable improvement in confidence (P<.01 for both PCPs and D/Es). Continued educational gaps include 71% of PCPs and 66% of D/Es need additional education on knowledge of benefit of CKM and 41% of PCPs need additional education on association of SGLT2 inhibitors with DKA.Conclusion: This study demonstrates the success of online CME consisting of discussions between 2 faculty experts on improving clinical knowledge of future implications of CKM in both PCPs and D/Es. Baseline knowledge was much lower in PCPs, which led to more significant knowledge gains after education. Continued knowledge gaps were identified in both groups.DisclosureA. Larkin: None. M. LaCouture: None. A. Le: None.FundingIndependent educational grant from Abbott Diabetes Care
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-533-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 534-P: Evaluating the Impact of Multichannel Diabetes Care Coaching and
Education in Patients New to Continuous Glucose Monitoring-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 534-P
Abstract: Introduction and Objective: The purpose of this study was to evaluate whether individuals with diabetes (Type 1 and Type 2) newly prescribed a continuous glucose monitor (CGM) with coaching and education from a certified diabetes care and education specialist (CDCES) achieve better outcomes than those using CGM alone.Methods: Adults aged 18+ newly prescribed a CGM provisioned through a durable medical equipment (DME) supplier were randomized into two groups: CGM plus coaching (CGM-LC) or CGM only (CGM-O). The CGM-LC group accessed a care management solution integrating education, coaching, and monitoring. Clinical outcomes included average blood glucose, glucose management indicator (GMI), and time in range (TIR) at baseline and 3 months.Results: Analysis included 118 participants with a mean age of 67.1 years. Results showed a significant improvement in TIR for the CGM-LC group, with a notable increase in TIR at 3 months compared to baseline, while the CGM-O group showed no improvement. For GMI, the TIR interaction was influenced by age and gender, with individuals under 65 years and males in the CGM-LC group demonstrating significant improvement. Similar trends occurred for average blood glucose levels but did not reach statistical significance.Conclusion: Results suggest providing coaching and education alongside DME-provisioned CGM supplies improves clinical outcomes for individuals newly prescribed CGMs compared to CGM use alone.DisclosureA. Masturzo: None. J. Allaire: Consultant; CCS Medical.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-534-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 535-P: Objectively and Subjectively Measured Physical Activity in Chinese
Immigrants with Type 2 Diabetes in New York City-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 535-P
Abstract: Introduction and Objective: There is a paucity of objectively measured physical activity (PA) data in underserved populations. We examined objectively measured and self-reported PA among Chinese immigrants with type 2 diabetes (T2D) in NYC.Methods: We analyzed baseline data from 60 participants. PA was measured by a wrist-worn ActiGraph GT9X accelerometer and the International Physical Activity Questionnaire-Short Form (IPAQ-SF). Weekly PA and adherence to moderate-to-vigorous PA (MVPA) guidelines (≥150 min/week) were compared.Results: Of the 60 participants (mean age 54.3 ± 11.5, 61.7% male, 70% ≤high school, 51.7% household income ≤$25,000), 52 (87%) provided accelerometer data, with a mean wear time of 22.2 hrs/day for 8.5 days. While over 91.7% engaged in moderate PA, a few engaged in vigorous or strength training. The median MVPA was 844.3(531.4, 1133.5) min/week and 280(120, 420) min/week for accelerometer and IPAQ data, respectively. Accelerometer data showed that 96.2% met PA guidelines, compared to 66.7% via IPAQ, which reported lower moderate PA levels but slightly overestimated vigorous PA (Table 1).Conclusion: The objective PA data suggested Chinese immigrants with T2D had relatively high PA levels, likely underestimated by self-reports. Low engagement in strength training suggests a need to explore barriers and design interventions to promote it in this population.DisclosureY. Shi: None. S. Cheng: None. J. Liu: None. H. Song: None. O.Z. Friedman: None. X. Yang: None. S. Huang: None. K. Tamura: None. L. Hu: None.FundingNational Institutes of Health (K99MD012811), National Institutes of Health (R00MD012811)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-535-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 536-P: Food Insecurity, Body Weight, and Healthy Eating among Overweight
Chinese Americans at High Risk for Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 536-P
Abstract: Introduction and Objective: This study assessed the prevalence of food insecurity and examined its associations with body mass index (BMI), body weight, and healthy eating among overweight Chinese Americans at high risk for diabetes.Methods: We analyzed baseline data from a randomized controlled trial of 150 overweight Chinese Americans at risk for diabetes in New York City. Food insecurity was measured using the San Francisco Chinese Food Security Module, and higher scores indicated higher food insecurity. Healthy eating was measured by the Starting the Conversation scale. Weight and height were measured during the in-person baseline visit. Regression analyses were conducted to examine whether food insecurity (independent variable) was associated with three dependent variables: BMI, weight, and healthy eating, respectively while adjusting for age and gender.Results: Our sample (n = 150) had a median age of 49 years [IQR 39-62] and a mean BMI of 27 (SD 3.69). The majority were female (82.7%), had ≤ high school education (54%), and reported annual household incomes of ≤ $25,000 (37.3%). Approximately a quarter (25.4%) of participants reported varying levels of food insecurity (12.7% marginal, 8.7% low, 4.0% very low food security). After adjusting for age and gender, food insecurity was negatively associated, but not statistically significant, with BMI (β = -0.18, p = 0.22) and weight (β = -1.1, p = 0.23) and showed no association with healthy eating (β = -0.013, p = 0.87).Conclusion: Nearly 25% of Chinese Americans at high risk for diabetes face food insecurity, underscoring the need for targeted strategies to address this issue within the community. We observed a trend of negative association between food insecurity and weight, indicating that a large-scale study may be needed to confirm the result.DisclosureX. Yang: None. J. Liu: None. Y. Shi: None. Y. Zhao: None. O.Z. Friedman: None. H. Song: None. H. Li: None. Y. Jiang: None. I.H. Ong: None. Y. Xiao: None. Y. Cheung: None. H. Wang: None. Y. Bai: None. R. Zhao: None. L. Hu: None.FundingAmerican Diabetes Association (7-22-ICTSN-08)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-536-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 537-P: Pilot Randomized Controlled Trial Outcomes from Examining What Can
I Eat' Diabetes Nutrition Education and a Food Security Resource for
American Indians with Type 2 Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 537-P
Abstract: Introduction and Objective: American Indians experience high rates of type 2 diabetes (T2D). Limited access to quality healthcare and healthy food can impact American Indians’ ability to manage T2D. We developed a classroom-based, culturally-tailored, ADA-sponsored diabetes nutrition education curriculum, entitled “What Can I Eat'” Healthy Choices for American Indians and Alaska Natives with T2D (WCIE). We evaluated the impact of engaging in WCIE classes augmented by a food security resource (FSR) which was a weekly $30 grocery gift-card for 12 weeks.Methods: We conducted a pilot 3-arm randomized controlled trial for American Indian adults with T2D (n=67) at one urban Indian clinic. Treatment arms for the 3-month intervention included: WCIE+FSR; WCIE alone; FSR alone. Clinical measures, surveys, and 24-hour diet recalls were collected at baseline and 3 months. We evaluated outcomes at 3 months using Chi squared and Kruskal Wallis tests and linear mixed models.Results: WCIE class attendance (90%) and retention at 3-month assessments (93%) was high. No changes were seen in clinical outcomes or food security however self-efficacy for healthy eating (mean changes= 0.3-0.6, p<0.05), and use of the ADA diabetes plate method (mean changes= 0.7-1.0, p<0.05) improved in all groups. Though all 3 groups improved in dietary behavior, the WCIE+FSR group experienced the greatest improvement on the Healthy Eating Index (50.4 from 47.2) compared to the WCIE alone (53.0 from 50.4) and FSR alone (56.0 from 55.1), though results were not significant.Conclusion: WCIE can improve healthful eating behavior and self-efficacy and could augment comprehensive diabetes self-management education and support.DisclosureS.A. Stotz: None. L.E. Hebert: None. K.R. Begay: None. M. Dennison: None. J.L. LaFromboise: None. N. Begick: None. B. Cunningham: None. A. Trice: None. D. Duran: None. C. Byker-Shanks: None. S.A. Berkowitz: None. L. Jiang: None. S.M. Manson: None.FundingAmerican Diabetes Association (11-22ICTSN-10); National Institutes of Health - National Institute of Diabetes and Digestive and Kidney Disease (K01DK128023) PI: Stotz
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-537-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 538-P: Leadership and Change Management in Diabetes Education—Addressing
Health Literacy and Health Disparities in the Diabetes Belt-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 538-P
Abstract: Introduction and Objective: The Diabetes Belt, spanning 644 counties across 15 southern states, faces disproportionately high rates of type 2 diabetes, compounded by limited health literacy and systemic inequities. This study investigates how health educators employ leadership and behavior change theories—transformational leadership, transactional leadership, the transtheoretical model, and diffusion of innovation—to design effective interventions. The objective is to explore strategies that enhance patient engagement, address literacy barriers, and improve self-management outcomes.Methods: A qualitative phenomenological approach analyzed data from semi-structured interviews with 12 diabetes health educators. The study examined how theoretical frameworks guided tailored, culturally relevant, and patient-centered interventions for underserved populations.Results: Key themes included personalized care, building trust, fostering self-efficacy, and clear expectations for diabetes management. Educators used visual aids, simplified information, and culturally relevant examples to enhance comprehension and engagement. Transformational leadership principles, such as individualized consideration, and adult learning strategies, like the teach-back method, were pivotal in building patient confidence and sustainable behavior change. Despite systemic challenges, tailored interventions improved glycemic control, medication adherence, and quality of life.Conclusion: This study underscores the role of health educators in addressing disparities through leadership-driven, patient-centered approaches. Findings highlight the importance of integrating leadership and behavior change theories to overcome literacy barriers and foster health equity. These insights offer practical recommendations for enhancing diabetes education and self-management in underserved communities.DisclosureM. Campos-Marquetti: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-538-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 539-P: Do Distance-Learning National Diabetes Prevention Program
Participants Have Similar Biometric Outcomes Compared with In-Person
Participants'-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 539-P
Abstract: Introduction and Objective: In Montana, the National Diabetes Prevention Program (NDPP) is available either in-person or via distance learning (DL) delivery. This study compares these modalities to measure differences in enrollment, retention, physical activity, weight, and biometric values (blood pressure, blood glucose, lipids, triglycerides, and cholesterol).Methods: Participant data were collected in Montana’s Prevention Access Web-based System, including intake interviews and metrics, biometrics for months six and twelve, and session data up to 30 sessions. To ensure data comparability between cohorts, observed sessions were capped at 22, the minimum required sessions. Analysis was limited to participants whose first session occurred between January 1, 2022 - June 30, 2024, and includes session data up to December 31, 2024. Participants presented met all eligibility requirements for the NDPP. Participants with make-up sessions outside their regular modality were excluded from analysis.Results: There were 1,127 in-person and 161 DL participants who met all criteria. DL cohorts tended to have more people in younger age groups than in-person cohorts, with no other notable demographic differences. In-person participants were engaged in the program longer than DL participants. DL participants had a higher initial number of physical activity minutes, a higher average number of active minutes per week, and achieved 150 minutes per week more times. DL participants achieved lower diastolic blood pressure by the end of the program. No other differences were observed in either intake or at the end of the program.Conclusion: DL is offered as a solution for the rural spread of Montana. DL participants tended to be younger, engaged in more physical activity and achieved lower diastolic blood pressure compared to in-person participants. These data are limited by the rurality of Montana, further research may provide more findings.DisclosureW. Gardner: None. J. Fernandes: None. M. House: None. A. Lanes: None. C. Gale: None. M. Butcher: None. T. Filan: None.FundingCenters for Disease Control and Prevention (DP-23-0020)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-539-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 540-P: Baseline Findings from an Adapted DSMES for Filipinos with Type 2
Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 540-P
Abstract: Introduction and Objective: Type 2 diabetes (T2D) prevalence is high in Filipinos, yet they remain an understudied ethnic minority group with limited tailored programs to meet their specific health needs. This study describes baseline (BL) findings in an in-progress pilot trial that examines the effectiveness of an adapted diabetes self-management education and support (DSMES) program in improving glycemic outcomes of Filipino adults (N = 48) with T2D and BL A1C ≥ 7.5%.Methods: Descriptives statistics; Pearson correlations.Results: Of the 463 patients identified via electronic health record review, 379 (82%) were approached, 56 (12%) were eligible/interested, and 23 (6%) were enrolled. The average age was 60 ± 9.7 years old. More than half were men (52%), had an annual income of ≥ $96K (57%), a college degree (61%), and were employed full-time (65%). The average diagnosis length was 10 years ± 10.0 and BL A1C was 8.5% ± 1.3, yet only 26% had a DSMES referral. Mean BL scores for the Summary of Diabetes Self-Care Activities subscales were: general diet = 4.3 ± 2.0, specific diet = 3.1 ± 1.5, exercise = 3.6 ± 2.1, blood glucose monitoring = 3.8 ± 2.7, and foot care = 2.9 ± 2.5; range: 0-7. Mean score for the Diabetes Knowledge Test was 16.8 ± 4.1; range: 9-22. Although correlations were weak, age is inversely correlated with diabetes knowledge (r = -.50) and specific diet (r = -.51), ps <.05; employment is positively correlated with general diet (r =.54) and foot care (r =.49), ps <.01; and diagnosis length is inversely correlated with specific diet (r = -.51, p <.05). A1C was not significantly correlated with diabetes knowledge, self-care behaviors, or sociodemographic factors.Conclusion: Mean BL A1C was elevated with few referrals to DSMES. Mean BL scores for self-care behaviors and diabetes knowledge were moderate. Multilevel approaches and sociodemographic considerations (e.g., collaborating with providers to improve DSMES referrals; tailoring curricula) are needed to enhance reach to this understudied group.DisclosureE.N. San Diego: None. G.G. Ramon: None. M. Handojo: None. M. Ruiz: None. K. Brown: None. S. Subramanian: None. N. Orendain: None. S.R. Spierling Bagsic: None. A. Philis-Tsimikas: Advisory Panel; Dexcom, Inc. Research Support; Dexcom, Inc. Advisory Panel; Lilly Diabetes. Research Support; Lilly Diabetes. Advisory Panel; Novo Nordisk. Research Support; Novo Nordisk. Advisory Panel; Medtronic, Sanofi.FundingNational Institutes of Health (K12 TR004410); National Institutes of Health (KL2 TR001112)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-540-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 541-P: Intensive Diabetes Self-Management Education and Support for the
Underserved Population in Galveston, Texas—A Community Experience-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 541-P
Abstract: Introduction and Objective: The prevalence of diagnosed diabetes in Texas is higher than the national rate (12.3% vs. 11.3%). The Texas Diabetes Council recommends expanding access to diabetes care in populations faced with socioeconomic challenges. This study aims to assess the impact of a 12-month intensive Diabetes Self-Management Education and Support (iDSMES) program on the glycemic control of patients with type 2 diabetes in an underserved population in Galveston, Texas.Methods: People living with type 2 diabetes (aged 18-84, BMI>25, HbA1c ≥7%) were recruited from St. Vincent’s House, an organization providing healthcare services to the underserved and underinsured in Galveston. Participants were enrolled in the iDSMES program presented in English or Spanish, online or in-person. Point of Care HbA1c and blood pressure were measured at baseline (before iDSMES), 6 months, and 12 months into the iDSMES intervention. A two-tailed independent t-test was used to assess changes.Results: Of the 61 enrolled participants, 13 completed the year-long iDSMES intervention (6 male, 7 female - Age 34-75), with two to three assessments and a mean attrition rate of 79%. Over half of the participants (53.8%) achieved HbA1c reduction by ≥1% at 6 and 12 months. Over a third (38.5%) normalized their blood pressure at 12 months.Conclusion: Despite favorable outcomes and better glycemic control, the preliminary results suggest that retention is a primary obstacle in implementing a year-long diabetes education program. A qualitative assessment of factors affecting the attrition rate is warranted to tailor diabetes educational programs to better serve underserved communities.DisclosureJ. Li: None. H. Sallam: None. W. Lee: None. A.G. Mark: None. H. Serag: None.FundingTexas Department of State Health Services (HHS000740800001, HHS000384500001)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-541-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 542-P: Development and Baseline Characteristics of a Novel Community-Based
Nutrition-Lifestyle Therapy for Pregnant Women with Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 542-P
Abstract: Introduction and Objective: Socioeconomically disadvantaged (SED) pregnant Latina women are disproportionately burdened by type 2 and gestational diabetes. While diet and lifestyle therapy can help maintain glycemic control in pregnancy and plant-forward interventions have been successful in Latino populations, there is little data in pregnancy. This study evaluates a culturally tailored, plant-forward, dietary-lifestyle intervention delivered by community health workers (CHWs). We hypothesize that it will improve glycemic control in pregnant Latina women with diabetes, including time in continuous glucose monitoring (CGM) pregnancy range (TIR) 63-140 mg/dL, average glucose and glycemic variability.Methods: We performed a baseline analysis in the 12 out of target 30 participants currently enrolled. Participants are randomized to either plant-forward dietary-lifestyle intervention or to standard of care. The intervention arm receives 12 CHW-led classes. Standard of care group receives their regular pregnancy care visits. Both groups wear CGM unblinded as best practice for diabetes in pregnancy.Results: Of the 12 participants mean age was 33.17 ± 6.27 years and mean gestational age at enrollment was 22.05 ± 5.73 weeks. 41.67% have food insecurity and 8.13% have housing insecurity. 50% are primarily Spanish speaking and 67.77% have a high school education or less. Average baseline A1c was 5.78 ± 1.25%, range 4.5-9.3%. Mean CGM TIR 63-140 mg/dL was 78.39 ± 24.28%.Conclusion: This baseline data suggests a need for an effective, culturally and linguistically tailored dietary-lifestyle intervention in SED pregnant Latina women with diabetes. While on average goal pregnancy TIR of >70% was met, there is significant variation and several participants are not meeting this goal. Overall, results of this pilot study will increase understanding of the effect of high-quality CHW-led education interventions on glycemic profiles, and maternal and fetal pregnancy outcomes of this vulnerable population.DisclosureR. Pines: None. C. Axelrod: None. S. Bell: None. K. Nelson: None. E. Romero Gutierrez: None. K. Victoria: None. K.N. Castorino: Research Support; Abbott, Medtronic, Dexcom, Inc., Lilly Diabetes, MannKind Corporation, Eli Lilly and Company, Insulet Corporation. Speaker's Bureau; Dexcom, Inc. Advisory Panel; MannKind Corporation. Speaker's Bureau; Insulet Corporation.FundingNational Institutes of Health NIMHD (P50MD017344 subaward SCON-00003510)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-542-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 543-P: From the Clinic to the Community—Exploring Hair Salons for
Diabetes Risk Screening and Education among Black Women-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 543-P
Abstract: Introduction and Objective: Black women in the U.S. women are disproportionately affected by type 2 diabetes. This disparity partly stems from gaps in clinical diabetes risk screening and education. Hair salons are community settings that are frequented by Black women and could offer unique opportunities to implement diabetes education and prediabetes screening in a trusted environment. The objective of this study was to explore diabetes risk screening and education intervention in hair salons.Methods: A qualitative descriptive study was conducted with hairstylists and salon clients. Participants provided informed consent and were compensated for their time. Focus group discussions and semi-structured interviews were audio-recorded via Zoom and transcribed verbatim by Rev.com. Transcripts were coded and thematically analyzed using Dedoose software.Results: Salon clients (n=50) and hairstylists (n=10) identified as Black women. On average, stylists were licensed for 12 years and >50% were salon owners. Participants described experiences with clinic-based diabetes risk screening noting challenges in accessing healthcare services and unsatisfactory communication from healthcare providers. Themes centering salon-based diabetes risk screening and education included trusted relationships between stylists and clients, accessibility of salons, and the cultural significance of the salon for Black women. Participants discussed a need for culturally tailored diabetes education and ensuring privacy, logistical, and liability issues are addressed for salon-based interventions.Conclusion: Hair salons are culturally relevant, highly accessible community settings that can be engaged to implement diabetes risk screening and education for Black women. By leveraging stylist-client relationships, and tailoring education materials, salon-based prediabetes risk screening interventions can mitigate barriers to healthcare, aid in early detection and intervention, and enhance health equity.DisclosureK.N.B. Palmer: None. R. Yurika: None. A. Suero-Davis: None. K. Pryor: None.FundingAmerican Diabetes Association (11-22-JDFHD-04)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-543-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 544-P: Developing a Program to Improve Type 1 Diabetes Management in
Ugandan Schools-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 544-P
Abstract: Introduction and Objective: It is considered a legal expectation in resource-rich nations that children with diabetes (T1D) receive support at school, but this is largely unavailable in low resource settings. In Uganda, we identified lack of diabetes support during the school day as a major impediment to safe metabolic control. We worked with families and teachers in Kampala to develop a program for school staff to impart essential diabetes knowledge and address myths and fears that contribute to social stigma.Methods: Youth with T1D, their caretakers and their teachers were enrolled in a pilot program development initiative that included didactic training and qualitative focus group discussions. Educational content was adapted from international resources and tailored to the local context. Discussions were recorded and transcribed. Data were analyzed using a content thematic approach. Youth/caretakers assessed school support before and after.Results: Seven youth with T1D (13.3±2.4 yrs, 6 girls) were enrolled from 3 public and 4 private day schools. Pre-program, they reported frequent hypoglycemia at school but no treatment supplies, no space for glucose monitoring or administering insulin, stigmatization by students and teachers, and non-disclosure of diabetes diagnosis to school authorities. Pre-program, patients’ teachers demonstrated poor basic diabetes knowledge. Post-program testing revealed improvement and identified areas where further educational emphasis is needed. As a result of the initiative, supervised insulin administration areas and protocols for hypoglycemia assessment/management were created. One teacher diagnosed a child with T1D. School staff requested continued training/support. Youth and their families reported improved conditions at school.Conclusion: Developing and implementing a school staff diabetes education and support program improved the school environment to provide better care for children with T1D. This is our first step towards creating and implementing a Ugandan national T1D school program.DisclosureC. Nyangabyaki: None. T.W. Piloya: Research Support; Abbott. Other Relationship; Novo Nordisk. J. Rujumba: None. D. Malinga: None. M. Nakitto: None. N. Jemima: None. E. Pappenfus: None. B.M. Nathan: None. S. Beasley: None. A. Moran: Research Support; Abbott. Consultant; Abata Therapeutics. Other Relationship; Novo Nordisk.FundingNIH (R01DK126726)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-544-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 545-P: Pediatric Endocrinology Fellows’ Education and Knowledge about
Automated Insulin Delivery Systems (AID)-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 545-P
Abstract: Introduction and Objective: The ACGME requires pediatric endocrinology fellows to master diabetes management, including AID. Despite the demonstrated benefits of AID, many youth are unable to attain glycemic targets. Insufficient clinician understanding of AID may contribute to suboptimal clinical outcomes.Methods: We evaluated pediatric endocrinology fellows' AID knowledge using a 42-item survey distributed to Pediatric Endocrine Society members. Responses to 5 point Likert scale questions were grouped into agree and disagree (4,5 v 1,2,3). Pearson’s chi-squared assessed for differences in knowledge of specific AID systems.Results: Pediatric endocrinology fellows (n=54) and attending physicians (n=52) participated. Because responses did not differ between groups, data are presented in aggregate. The majority (98%) agreed about the importance of endocrinologists understanding AID, and 37% reported fellowship was the most common source of AID knowledge. Although 91% agreed that a formal AID curriculum for trainees would improve patient care, only 35% had a curriculum at their institution. For the most commonly (Omnipod 5) versus least commonly used systems (iLet) there were significant differences (all p<0.01) in perceived comfort in counseling about AID system features (86% v 39%), managing AID users (86% v 40%), changing settings (79% v 30%), analyzing reports (82% v 29%), ketone management (89% v 42%), and exercise management (83% v 31%). Regardless of system, fellows were uncomfortable (47%) counseling youth with low total daily insulin needs in choosing an AID system.Conclusion: Despite near universal agreement about the importance of trainees understanding AID, current education is perceived as inadequate. With limited access to formal curricula trainees are primarily learning about AID experientially, creating challenges for mastering less commonly used systems. Formal AID curricula are needed to support fellows in attaining ACGME requirements.DisclosureJ. Iyer: None. S. Meighan: None. B.E. Marks: Consultant; Insulet Corporation. Board Member; International Society for Pediatric and Adolescent Diabetes. Research Support; Tandem Diabetes Care, Inc, Dexcom, Inc., Medtronic. Advisory Panel; T1D Exchange.FundingNIH T32 Grant (GRT-00004137)Children's Hospital of Philadelphia, Center for Leadership and Innovation in Medical Education (CLIME) Educator Development Grant
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-545-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 546-P: Comparing Diabetes Risk Perception between Latina and White Women
with T2D Risk Factors-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 546-P
Abstract: Introduction and Objective: Latinas have the highest lifetime risk of developing T2D compared to other racial/ethnic groups. An individual's perception of T2D risk can influence their behavior to engage in a healthy lifestyle. We compared Latina and White women’s perceived T2D risk and explored Latinas’ risk perceptions.Methods: Using an explanatory sequential mixed methods design, we identified women with T2D risk factors via the EHR (i.e., ICD 10 codes) of an academic medical center. Participants from 4 high-risk groups (GDM, BMI ≥24.9, hypertensive disorders of pregnancy, prediabetes) completed an online survey assessing diabetes risk then accessed an infographic which illustrated their T2D risk to the average US woman. Two subscales from the RPS-DD measured personal control and optimistic bias. Differences in means were compared using Two-sample t- tests. A random sample of survey respondents participated in a semi-structured interview. We used deductive and inductive coding, and thematic analysis.Results: A total of 397 participants, aged 19-46 (M=34.7, SD=5.8) complete the survey. Most were White (84.0%), and 15% identified as Latina. Both groups had similar rates of GDM and prediabetes. Latinas were significantly more likely to have a first-degree relative with T2D (p<0.001). T-tests revealed a statistically significant lower score in mean personal control (p=0.002) among Latinas and no significant difference in optimistic bias. Qualitative exploration revealed Latinas were aware of their strong family history, and perceived developing T2D as “inevitable” but were interested in lifestyle changeConclusion: Latinas have a lower perception of personal control in developing T2D compared to White women. Due to Latina participants’ family history of T2D, they desired to make lifestyle changes and reported a sense of urgency in educating their family and community.DisclosureC. Medina Poeliniz: None. J.M. Kent-Marvick: None. T.B. Aderibigbe: None. C.P. Poynot: None. S. Lee: Research Support; Clairvoyant Networks, Olera. B.D. Landrum: None. S.E. Simonsen: None.FundingThe Healthy4Life study was funded by the University of Utah Emma Eccles Jones Nursing Research Center Pilot Grant.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-546-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 547-P: Harnessing Continuing Education to Identify Drivers of Obesity
Medication Use among Primary Care Providers-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 547-P
Abstract: Introduction and Objective: Obesity is a risk factor for type 2 diabetes (T2D), with weight loss linked to improved glycemic control and reduced disease burden. Obesity medications (OMs) are available to reduce weight and risk associated with T2D, yet misinformation and lack of confidence hinder their use.Methods: In September 2024, Vindico provided the 12th Annual Obesity Forum®, a 2-day continuing education (CE) webinar series for primary care providers (PCPs) managing patients with overweight or obesity. Knowledge, attitudes, perceptions, practice patterns, and impact were assessed pre- and post-education, with behavior changes measured at 30-day follow-up.Results: At baseline, among the 223 PCPs who completed the education, only 20% were aware of long-term data for OMs like semaglutide and tirzepatide. Encouragingly, compared to 2023, PCPs are 10% more likely to recognize the need for long-term use of OMs, and 82% were prepared to do so post-education. Only 30% of PCPs were familiar with guidelines for use of OMs in adolescents, yet 60% would recommend OMs for an eligible adolescent. Importantly, PCPs who are comfortable in using OMs are 7 times more likely to do so. Sources of discomfort include lack of familiarity with safety data, evolving guidelines, and counseling patients who have been influenced by misinformation on social media. At 30-day follow-up, 75% of PCPs were more aware of and using the latest safety and efficacy data when making management decisions, and 50% felt more empowered to discuss, and were discussing social media facts and misconceptions, with patients.Conclusion: Comfort in using OMs among PCPs has increased since 2022, which is driving increased usage. While PCPs continue to face practice challenges regarding rapidly evolving evidence and guidelines as well as combating misinformation on social media about obesity and its management, continuing education remains an effective tool to promote utilization of the latest evidence-based care.DisclosureB. Hegde: None. H. Collier: None. J. Frederick: None. S. Johnson: None. K. Robinson: None.FundingThis activity was supported by an educational grant from Lilly.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-547-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 548-P: Evaluating the Effectiveness of a Train-the-Trainer
Model—Training Researchers to Implement a Clinical Culinary Medicine
Intervention for At-Risk Youth with Type 1 Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 548-P
Abstract: Introduction and Objective: Chronic disease behavioral interventions have become widespread across healthcare sectors. While success of these interventions is largely dependent on their implementation, there is an absence of train-the-trainer (TTT) protocols and evaluations to serve as frameworks for behavioral interventions. Therefore, the objective of this study was to develop and evaluate the effectiveness of a theory-based TTT protocol at training researchers to deliver a clinical culinary medicine intervention for at-risk youth with T1D in a public health setting utilizing a mixed methods approach.Methods: A multi-component TTT protocol was developed and implemented to research assistants (RAs) of the intervention. A 24-item survey assessing key TTT constructs (T1D knowledge, disparities; health literacy, cultural sensitivity; research ethics, study design) was completed by RAs at baseline and post-test. Six additional qualitative questions gathered RA feedback on the TTT protocol at post-test.Results: Eighteen RAs completed the baseline and post-test surveys (100%), with significant improvements from baseline to post-test across all key TTT constructs (T1D knowledge (p<0.001); T1D disparities (p<0.001); health literacy, cultural sensitivity (p= 0.02); research ethics, study design (p<0.001)). Post-training feedback indicated strong preference (94.4%) for the multi-component approach but the in-person training day 2 (knowledge application with role play, demonstrations) best prepared RAs for their role.Conclusion: The TTT framework is an effective training model for clinical and public health diabetes interventions. Utilizing a multi-component approach with in-person knowledge application appears to resonate best with trainees and can serve as a model to integrate into chronic disease behavioral interventions in the clinical and public health sector to enhance chronic disease intervention efficacy and patient outcomes.DisclosureC.R. McManus: None.FundingAmerican Diabetes Association (11-21-JDFHD-13)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-548-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 549-P: Visual Food Portion Guide for Diabetes Self-Management Education in
Nigeria—Development and Validation-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 549-P
Abstract: Introduction and Objective: Dietary management through food portion control remains a key component of any diabetes care. This study aimed at developing and validating a visual food portion guide (VFPG) for diabetes self-management in NigeriaMethods: The VFPG was developed following standard method for portion control in diabetes management. Through a mixed-method design, 12 healthcare providers (HCPs) and 31 individuals with diabetes were engaged in the validation process.Results: The findings revealed strong support for the VFPG among HCPs and individuals with diabetes. Among HCPs, 75% rated it as highly relevant for text clarity, illustration suitability, and promoting behavioral change, while 66.7% found the visuals effective for understanding portion control. Similarly, 75% of HCPs rated its diabetes management content of the guide as very relevant. Diabetes individuals responded positively, with 83.9% affirming the clarity of the message, and 80.6% approving the final visual design. Additionally, 80.6% noted its usefulness for portion control and food choices, and 87.1% reported improved understanding of diabetes management. Qualitative findings indicated that HCPs recommend more emphasis on vegetables, reduced salt and bouillon cubes usage, and household measures for portioning. Participants requested more visual examples of traditional foods, diabetic-friendly snacks, and clearer portion size demonstrations. The VFPG achieved high content validity, with a mean item-level index (I-CVI) of 0.91 and scale-level index (S-CVI) of 0.96, affirming its relevance as a portion control tool.Conclusion: The VFPG is a well-received tool for portion control and diabetes management. It shows great potential as a valuable resource for diabetes education and self-management in Nigeria.DisclosureO. Folasire: None. O. Adetula: None. O. Leshi: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-549-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 550-P: Interest in Lifestyle Change Programs among Reproductive-Aged Women
at Risk for T2D-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 550-P
Abstract: Introduction and Objective: The reproductive years provide a unique opportunity to identify women at risk for T2D and intervene earlier in the life course to prevent T2D. The objective of this study is to describe factors associated with interest in learning about lifestyle change programs (LCPs) among reproductive-aged women with T2D-related risk factors.Methods: Participants identified through the EHRs of a large health system included English and Spanish-speaking women with T2D-related risk factors (ICD-10 codes indicating: 1) gestational diabetes, 2) hypertensive disorders of pregnancy, 3) pre-diabetes, or 4) BMI>24.9). Participants completed an online survey about perceived diabetes risk and healthcare provider recommendations, were shown infographics about their T2D risk compared to the average US woman and were asked if interested in learning about available LCPs. Multivariable logistic regression was used to identify factors associated with interest in learning about LCPs.Results: Participants (n=403, mean age of 35 years) had a mean BMI of 33.3; 84% were white and 15% were Latina. The majority (65%) had received some provider counseling about healthy lifestyle. There were high levels of interest in learning about available LCPs (73%). Factors associated with interest in learning about LCPs included non-Latina ethnicity (OR=4.10, 95% CI 1.35-12.43), perceived probability of developing T2D (OR=1.02, 95% CI 1.01-1.03), and healthcare provider recommendations about exercise or healthy eating (OR=1.87, 95% CI 1.06-3.28).Conclusion: Reproductive-aged women at risk for T2D are interested in learning about LCPs and are more likely to request information if they are non-Latina, have received healthcare provider recommendations about lifestyle change, and have higher perceived probability of developing T2D. Providing guidance about T2D risks and the importance of healthy lifestyle during the reproductive years is critical to slowing the T2D epidemic.DisclosureS.E. Simonsen: None. J.M. Kent-Marvick: None. T.B. Aderibigbe: None. C.P. Poynot: None. C. Medina Poeliniz: None. S. Lee: Research Support; Clairvoyant Networks, Olera.FundingUniversity of Utah Emma Eccles Jones Nursing Research Center Pilot Grant
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-550-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 551-P: Impact and Acceptability of a Virtual Nutrition, Exercise, and
Diabetes Coaching and Education Program in Individuals Living with
Diabetes Mellitus-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 551-P
Abstract: Introduction and Objective: Telehealth has grown over the past decade, especially since the Covid-19 pandemic, and has demonstrated positive outcomes for patients’ health outcomes and quality of life. Our objective was to determine both the acceptability and impact of an online-based diabetes education and coaching program in patients wishing to improve their glycemic control.Methods: We conducted 15 patient interviews with participants who had completed at least 6 months of intervention with the Your Diabetes Insider registered dietitians, focusing on initial expectations of participating in an intervention like this, changes in quality of life, changes in confidence of diabetes management, and changes in glycemic control.Results: Participants had an average age of 44 years, lived with diabetes for a mean length of 19.3 years, and joined the program to improve glycemic control and improve quality of life with advanced support. All completed at least 6 months (mean=15.6 mo, range=6-29 mo), all reported substantial drops in HbA1c (starting mean HbA1c 7.48%, ending mean HbA1c 6.07%), as well as improvements in glucose time in range by 15-20%. Participants also reported an increase in quality of life, increased confidence in handling day-to-day diabetes decision making, and improved ability to engage in intensive physical activities while avoiding hypoglycemia. Participants emphasized greater understanding of nutrition as it fits into their diabetes management, more freedom in food choices, and decreased fear and stress surrounding food and glucose variability.Conclusion: A virtual nutrition, exercise, and diabetes coaching and education intervention can improve both glycemic control and quality of life in patients with diabetes.Disclosure B. Tzeel: Other Relationship; Zucara Therapeutics, T1D Exchange.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-551-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 552-P: Increasing Access to Diabetes Self-Management Support (DSMS)
Programs via Electronic Health Record (EHR)–Based Clinical- (CDST) and
Patient-Decision Support Tools (PDST)-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 552-P
Abstract: Introduction and Objective: Approximately 556,000 adults in the state of South Carolina live with diabetes and only 50% have participated in a diabetes self-management/support class. Community-based DSMS programs improve participant's A1C values, nutrition and physical activity behaviors, and diabetes knowledge. With ADA funding, Clemson University partnered with Prisma Health, the largest health system in the state, to create CDST/PDST to increase awareness and referrals to Health Extension for Diabetes (HED), a DSMS program.Methods: Two CDSTs were created: an EPIC SmartPhrase (.HEDREF) and a DSMES (Diabetes Self-Management Education and Support) referral order set which was modified to include HED. Inclusion criteria given to providers included: a diagnosis of Type 1 or Type 2 diabetes and being 18 years of age or older. Exclusion criteria included: pregnancy, end-stage renal disease, or patient not overseeing their own care plan. Healthfeed, the PDST created, displayed a banner with a program summary and sign-up link in the EHR MyChart of adults with Type 1 or 2 diabetes.Results: Since its creation in June of 2022, HEDREF has resulted in 1,888 referrals to the HED program. Since January 2024, the referral order set has resulted in 120 referrals. Healthfeed was activated in English from January to March 2024 and resulted in 2,325 patient interaction interest “clicks”. From September through December 2024, the Spanish Healthfeed banner resulted in 44 “clicks”.Conclusion: The EHR SmartPhrase tool was the most successful at increasing referrals to the diabetes management and support program. Nevertheless, adults with diabetes in the health system are largely unengaged by these decision support tools. Future efforts should focus on identifying more effective referral mechanisms and increasing the participation of underserved populations.DisclosureM.D. Stancil: None. W.W. Sherrill: None. A. Diblin: None. A. Pulido: None. J.H. Evatt: None.FundingAmerican Diabetes Association (11-22ICTSN-04)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-552-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 553-P: Acceptability of a Complex Behavioral Intervention to Prevent
Recurrent Diabetic Foot Ulcers among Veterans-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 553-P
Abstract: Introduction and Objective: In patients with a previously healed diabetic foot ulcer (DFU), recurrence is a major problem. Despite the seriousness of DFU, foot self-care and self-monitoring remains suboptimal. We developed and tested a comprehensive tailored intervention (TI) to lower ulcer recurrence among Veterans with a previous DFU. Since it is critical to understand patient acceptability of new technology that is coupled with counseling calls, this abstract reports on patients’ acceptability of this novel TI.Methods: We evaluated the acceptability of the TI in comparison to a current practice (CP) control group during a randomized clinical trial (RCT) to evaluate the TI. The TI focused on plantar thermometry and foot self-care while the CP focused on non-diabetes specific health care. Upon completion of the 18-month study period, we administered the validated 8-item Treatment Acceptability Questionnaire (TAQ) to both groups. We examined both individual items and the total score (minimum 8; maximum 48), which were compared using t-tests and reported as means (SD).Results: We surveyed 84 out of the 91 eligible participants (92% response rate) who completed the 18-month study visit or the close-out study visit; 47 of the CP and 37 of the TI. At baseline, there were no significant differences by arm. For the overall sample, mean (SD) of age in years was 67.2 (7.7); 98.8% were men, 52% black and 51% lived alone. For each of the 8 TAQ items, the TI mean was greater than the CP mean; with the CP mean for the 8 items ranging from 4.6 to 5 and the corresponding TI means ranging from 5.1 to 5.6. Overall, the TI acceptability score was 43.1 (4.7) and the CP total was 39.2 (5.7) (p < 0.001).Conclusion: The TI had a higher degree of acceptance than the CP control even in this study population with advanced diabetes. Treatment acceptability can predict patients’ usage of the program in usual care. Healthcare systems can use acceptability outcomes to further refine the TI and successfully implement it in clinical practice.DisclosureL. Haley: None. Y. Magar: None. K. Liu: None. P.M. Kumar: None. A. Nicholson: None. N. Illenberger: None. S. Natarajan: None.FundingVA Rehabilitation Research and Development (IO1RX001858)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-553-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 554-P: Factors Associated with Participation in Diabetes Self-Management
Education and Support in Arkansas—Analysis of Behavioral Risk Factor
Surveillance System Data-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 554-P
Abstract: Introduction and Objective: In Arkansas, about 12% of adults have been diagnosed with diabetes. While DSMES improves diabetes management, little is known about the factors associated with its utilization in Arkansas. This study aims to determine the associations of demographics, health behaviors, and healthcare access with DSMES.Methods: Using BRFSS data, we assessed the participation of individuals with diabetes in DSMES. Weighted multivariate logistic regression models were used to evaluate the associations between DSMES and factors including demographics (age, race, gender), socioeconomics (education, annual household income), healthcare access (medical cost, healthcare providers availability, insurance status), self-management behaviors (physical activity, foot examination, blood glucose testing), and comorbidities (high blood pressure, heart disease).Results: There were 977 (2019) and 924 (2021) respondents with diabetes. DSMES was 15% higher in 2019 (n= 610; 61% [weighted]) than in 2021 (n= 470; [46%]). In 2019, respondents with a college education or higher [OR = 3; 95% CI, 1.3 - 6.9] or obesity [OR = 2; 95% CI, 1.1 - 3.4] had higher odds of DSMES participation. In 2021, respondents who did not perform foot self-exams [OR = 0.4; 95% CI, 0.2 - 0.7] or did not test blood sugar at least once monthly [OR = 0.4; 95% CI, 0.2 - 0.8] or yearly [OR = 0.3; 95% CI, 0.1 - 0.8] had lower odds of DSMES participation. Using merged datasets for both years, respondents more likely to utilize DSMES had some college or higher education [OR = 2; 95% CI, 1.3- 4.7] or lived in counties with non-federal primary care physicians greater than 60 per 100,000 population [OR = 2; 95% CI, 1.02 - 3.5].Conclusion: Our findings highlight the association between diabetes self-care behaviors and DSMES participation. Additionally, it shows that a higher level of availability of non-federal primary care physicians will likely increase access to DSMES.DisclosureN.D. Boateng-Antwi: None. J. Henske: None. M. Rezaeiahari: None.FundingMR was supported by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health (1K25DK136966)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-554-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 555-P: Understanding Information Needs and Digital Support Preferences for
Type 2 Diabetes Management from People with Diabetes and Their Carers in
Australia-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 555-P
Abstract: Introduction and Objective: Tailored support and information are critical for the effective management of type 2 diabetes (T2D), yet the specific needs of people living with diabetes (PWD) and their carers, particularly in the context of digital health tools, remain underexplored in Australia. This study examines these needs, preferences, and barriers to enhancing patient-centred care.Methods: We conducted a survey with 27 PWD and 11 carers. Participants provided insights into their learning needs, enablers and barriers to care, and preferred methods for accessing support, including using digital health applications.Results: Most PWD (48%) and carers (55%) had been managing diabetes for over 10 years. Both groups identified nutrition and healthy eating as the most critical information need (82% PWD, 82% carers), followed by physical activity (70% PWD, 64% carers), medications (70% PWD, 55% carers) and stress and anxiety support (56% PWD, 82% carers). Enablers included motivation and confidence in managing diabetes, health goal plans and monitoring tools (95%). Barriers included program costs (74%) and unawareness of suitable evidence-based programs (71%). Face-to-face sessions (76%) and digital applications (66%) were the most preferred. While most respondents were comfortable using digital health (92%), privacy, data security (53%), and cost (58%) were major concerns.Conclusion: This study highlights the shared and unique need of PWD and their carers in managing T2D, emphasising the importance of supporting self-management and providing practical strategies to achieve health goals. Despite ongoing privacy, security, and cost challenges, it also underscores the growing acceptance of digital applications as valuable support tools. These findings may provide key insights for developing patient-centred digital solutions to enhance diabetes care and self-management.DisclosureK. Nguyen: None. D. Gargya: None. V. Chan: None. T. Thrimawithana: None. C. Lim: None. B. de Courten: None.FundingAustralian Government Research Training Program Scholarship
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-555-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 556-P: NextGen Fellowship—Strengthening Career Pathways in Diabetes
-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 556-P
Abstract: Introduction and Objective: Current trends in the decreasing number of endocrinologists, the consistency in diabetes funding from the NIH, and the rising prevalence and costs of diabetes elucidate the importance of expanding the pipeline for future leaders in diabetes, encouraging them to consider diabetes care, research, and advocacy as career options. The Diabetes Link, a non-profit committed to supporting young adults with diabetes, offers the NextGen Fellowship (“NextGen”) to provide mentorship, educational sessions, conference attendance, and a network of peers to cultivate the “next-generation” of diabetes leaders. Aim: To assess the effectiveness in educating and proving a clear career pathway of the 2024 NextGen Cohort.Methods: Fellows completed surveys before and after the fellowship which included likert-style questions, ranking activities, and qualitative feedback. These questions polled demographic information; diabetes care, research, and advocacy knowledge; main takeaways of the fellowship; and knowledge of diabetes organizations. T-tests to explore significance before and after the fellowship and among different demographics were used as statistical tests.Results: Fifteen fellows were surveyed across different ages, backgrounds, and career paths, and analyses of their surveys revealed significant increases in diabetes research knowledge (p <.05), advocacy knowledge (p <.001), and familiarity with diabetes organizations (p <.05). Improvements in career confidence, cultural care understanding, and education knowledge were observed, but did not reach statistical significance. Meeting peers along a similar career pathway also positively contributed to fellows’ experience.Conclusion: NextGen provides a strong foundation for young adults interested in pursuing a career in diabetes. This illuminates the importance of providing early career professionals interested in diabetes with experience, equipping them for success in the field and effectively expanding the pipeline of young talent entering the diabetes workforce.DisclosureP. Bischoff: None. M. Roche: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-556-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 557-P: Diabetes Conditional Cash Transfer (DM-CCT) Intervention to Improve
Glycemic Control—A Pilot Randomized Controlled Trial-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 557-P
Abstract: Introduction and Objective: A pilot randomized controlled trial among inner-city African Americans with poorly controlled type 2 diabetes (HbA1c >=8%) tested the feasibility and preliminary efficacy of conditional and unconditional cash transfers.Methods: 100 participants were randomized to receive: 1) unconditional cash transfers (UCT) of $500 per month for 6 months and mailed diabetes education every two weeks, or 2) conditional cash transfers (CCT) of $500 per month for 6 months, conditional on attending a 1 hour diabetes education/skills training session every 2 weeks. Longitudinal mixed models with treatment, time, and treatment x time interactions were used to measure change in HbA1c from baseline.Results: Mean age of participants was 54 years, with the sample consisting mostly of women (66%). Approximately 53% were never married, and 65% had a household income less than $20,000 annually. Statistically significant differences within both groups were found: UCT at 3-months (-0.51 (-0.93, -0.09), p=0.02); UCT at 6-month not significant; CCT at 3-months (-0.55 (-1.10, 0.002), p=0.05) and 6-months (-0.61 (-1.18, -0.04), p=0.04), see Figure 1.Conclusion: These findings show clinically meaningful change from baseline to 3-months for each of the intervention arms and to 6-months for the CCT arm. These preliminary data provide evidence that conditional cash transfers can significantly improve HbA1c.DisclosureJ.A. Campbell: None. R.J. Walker: None. L.E. Egede: None.FundingK01DK131319
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-557-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 558-P: Development of Noninvasive Diabetes Management Method Using
Glycated Albumin in Tears-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 558-P
Abstract: Introduction and Objective: Several clinical trials have demonstrated the importance of strict glycemic control in minimizing the risk of diabetic complications. Although frequent blood glucose measurement using the invasive finger-prick method is effective for achieving strict glycemic control, it is burdensome and uncomfortable for patients. Glycated albumin (GA) is a biomarker that reflects glycemic control over the preceding two weeks. Previously, we demonstrated that GA levels in tears correlate with those in blood. We hypothesized that regular GA testing in tears could promote behavior changes and improve glycemic control.Methods: Participants with type 2 diabetes were recruited and randomly divided into two groups. The intervention group underwent tear GA testing every two weeks and reported the results online, while the control group did not receive this intervention. After an 8-week intervention period, outcomes were compared between the two groups. GA levels in tears were measured using liquid chromatography-mass spectrometry.Results: A total of 56 participants were enrolled in the study. The intervention group showed significant improvements in fasting blood glucose, HbA1c, GA, and non-HDL cholesterol levels compared with the control group.Conclusion: GA levels in tears, a diabetes-related biomarker, can be measured noninvasively. Regular measurement of tear GA levels has the potential to enhance digital health education and telehealth practices, providing a noninvasive approach to improving glycemic control.DisclosureM. Aihara: None. N. Kubota: None. T. Yamauchi: Research Support; Asahi Mutual Life Insurance Company. Other Relationship; Astellas Pharma Inc, AstraZeneca, Abbott Japan Co., Ltd, ARKRAY Marketing, Inc., Amgen Inc. Research Support; Boehringer-Ingelheim. Other Relationship; Boehringer-Ingelheim, Bayer Pharmaceuticals, Inc, Covidien Japan Inc., Daiichi Sankyo, Eli Lilly and Company. Research Support; EA Pharma Co.,Ltd. Other Relationship; GlaxoSmithKline K.K. Research Support; Kowa Company, Ltd. Other Relationship; Kowa Company, Ltd, Kyowa Kirin Co., Ltd, Medtronic, Merck Sharp & Dohme Corp, Mitsubishi Tanabe Pharma Corporation. Research Support; Novo Nordisk. Other Relationship; Novo Nordisk, Ono Pharmaceutical Co., Ltd, Sumitomo Pharma Co., Sanofi K.K., SANWA KAGAKU KENKYUSHO CO.,LTD., Taiho Pharmaceutical Co. Ltd, Teijin Pharma Limited, Nipro Corporation. Research Support; NITTO BOSEKI CO.,LTD. Other Relationship; ViewSendICT Inc.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-558-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 559-P: Use of Gamification in Diabetes Education and Its Impact on Quality
of Life in Children and Adolescents with Type 1 Diabetes in Argentina-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 559-P
Abstract: Introduction and Objective: Therapeutic education for the self-management of type 1 diabetes (T1D) in pediatrics is essential to improve decision-making. However, it is often taught in a boring manner, with few benefits on quality of life (QL).1) To evaluate the impact of a gamified educational intervention program on QL, in pediatrics with T1D. 2) To compare glycemic metrics obtained through CGM, before and after the intervention.Methods:"Diabetes Explorers Program" consisted on an educational meeting that took place in Corrientes, Argentina. All participants received prior to the meeting a “Diabetes Explorer's Manual” prepared by the health team, that incorporated gamified educational tools (storytelling, games and interactive activities) to be used in the meeting, to teach participants about topics related to T1D.We used the PedsQL Diabetes Module questionnaire (version 3.0), before and 60 days after the intervention program to measure QL. Glucose metrics were analyzed by data download.Results: N=35 participants. 60% female, average age of 12.1 years, T1D median duration: 3.7 years.The global scores of the PedsQL questionnaire showed improvements in areas related to daily diabetes management and confidence in decision-making, although these differences were not statistically significant.There were improvements between CGM glucose metrics PRE vs POST intervention: TIR (33 vs 40%), TAR (66 vs 58%), average glucose (227 vs 202 mg% ), number of scans (7 vs 10) and GMI (8.7 vs 8.2), all p < 0.05.Conclusion: The gamified project achieved significant improvements in glycemic control metrics and provided indications of perceived quality-of-life enhancement among participants. While these improvements were not statistically significant, qualitative results underscore the subjective value of the intervention. Longitudinal studies are recommended to evaluate medium and long-term impact on QL, using gamified tools for diabetes education.DisclosureM.L. Pomares: None. C. Gomez Martin: None. A. Benitez: None. J. Zappa: None. S. Insaurralde: None. D. Pomares: None. C.E. Lopez: None. G. Cuzziol: None. E. Piasentini: None. S. Kremer Sendros: None. V.M. De la Vega: None. M. Villagra: None. I. Vera: None. S. Gorban de Lapertosa: Speaker's Bureau; Boehringer-Ingelheim, Merck Sharp & Dohme Corp.FundingGrant of the Argentinian Diabetes Society
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-559-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 560-P: Mapping Barriers and Interventions to Diabetes Self-Management in
Latino Youth—A Scoping Review-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 560-P
Abstract: Introduction and Objective: Effective diabetes self-management is critical for glycemic management and overall well-being, yet Latino youth face unique cultural and socioeconomic barriers that are insufficiently explored in the literature. This scoping review aimed to map the evidence on diabetes self-management for Latino youth with diabetes.Methods: A systematic search was conducted in PubMed, CINAHL, SCOPUS, Web of Science, LILACS, ERIC, and The Cochrane Library, adhering to the Joanna Briggs Institute guidelines. Studies included qualitative, quantitative, mixed-methods, or reviews focusing on Latino with type 1 or type 2 diabetes. Two reviewers independently extracted data and appraised study quality using the Joanna Briggs Institute Critical Appraisal Tools. Results were analyzed according to the ADCES7 self-care behaviors: healthy eating, being active, monitoring, taking medication, problem-solving, reducing risks, and healthy coping.Results: Forty-two studies were included from 857 citations retrieved. Findings highlighted challenges in adopting diabetes-friendly diets, including cultural preferences, food insecurity, and limited resources. Physical activity improved glycemic control but was hindered by family and school obligations. Continuous glucose monitoring (CGM) enhanced outcomes, though economic barriers limited access. Family-centered education improved medication adherence, while family support strengthened problem-solving skills. CGMs and insulin pumps reduced complications, and culturally adapted psychological support enhanced emotional well-being and glycemic management.Conclusion: This review underscores substantial disparities in diabetes self-management among Latino youth, emphasizing the importance of culturally tailored interventions that address structural barriers.DisclosureM. de Lucca: None. S.M. Namoc Leturia: None. T. Andre: None. M. Visser: None. L.C. Nascimento: None. R.O. Barber: None.FundingCoordination for the Improvement of Higher Education Personnel - Brazil (CAPES)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-560-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 561-P: A Qualitative Evaluation of Clinicians’ Practices in Diagnosis
and Management of Women with Gestational Diabetes (GDM) in Pune, India-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 561-P
Abstract: Introduction and Objective: Despite India’s growing prevalence of gestational diabetes (GDM), ambiguity exists around GDM diagnosis and management guidelines. This study sought to understand the experiences and practices of clinicians regarding the diagnosis and management of GDM in order to identify areas in which guideline standardization or targeted training is needed.Methods: We conducted a single qualitative interview with purposively sampled clinicians in public and private hospitals in Pune, India. Clinicians were included if they were ≥ 18 years, provided care to pregnant women in the area, completed an allopathic medical degree, and were in a patient-facing position for over 1 year. Interviews were conducted in Marathi by a trained interviewer, recorded, transcribed, translated into English, and analyzed using a thematic analysis approach.Results: Twenty clinicians were interviewed. Four key themes emerged from the data: 1) Two forms of GDM screening were most common: the 75g non-fasting oral glucose challenge test (OGCT) and the 75g fasting oral glucose tolerance test (OGTT), with OGCT being preferred because it is a non-fasting test that is easier to administer; 2) Among clinicians, obstetricians commonly consider GDM management outside of their scope of practice and refer women to physicians specializing in general medicine or endocrinology; 3) Availability of hospital resources (i.e. laboratory equipment, technicians, specialist clinicians) is a major driver of GDM screening, diagnosis, and treatment; and 4) Screening for postpartum diabetes among women diagnosed with GDM is rare due to lack of tracking systems and dedicated workforce for this process.Conclusion: Our data highlights variability in GDM care practices among clinicians in one urban area of India. Standardized guidelines for obstetricians on diagnosis, treatment options, and postpartum follow-up may help manage the growing burden of GDM and post-partum diabetes in IndiaDisclosureG. Maines: None. S. Gogineni: None. S. Satkar: None. A. Onawale: None. P. Chebrolu: None. J.S. Mathad: None. R. Sundararajan: None.FundingNational Institutes of Health (5R01HD112141)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-561-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 562-P: Navigating Regulatory Challenges for Diabetes Devices—A
Comparative Analysis of EU and U.S. Frameworks-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 562-P
Abstract: Introduction and Objective: The growing prevalence of diabetes presents major public health and economic challenges, driving the need for innovative medical devices. However, navigating the regulatory frameworks of the European Union (EU) and the United States (US) is complex, requiring substantial resources and expertise.Methods: Using qualitative research methods, including case studies and semi-structured interviews, we identified differences and similarities between the EU and US risk classifications. The findings were used to design flowcharts that guide the classification of diabetes-related medical devices.Results: Our research revealed that while both the EU and the US classify medical devices based on risk, their approaches differ: the EU employs a rule-based system, whereas the US uses a code-based system. We compared specific cases (Fig.) and developed flowcharts illustrating similarities and discrepancies between the two jurisdictions, offering insights into strategic regulatory compliance and identifying potential synergies to manufacturers.Conclusion: The significant differences in US and EU medical device risk classifications reflect their distinct regulatory approaches, highlighting the need for early strategy clarification and comprehensive classification tools. A streamlined strategy across jurisdictions can better facilitate innovation in diabetes care, improving outcomes for those living with diabetes.DisclosureS. Hossmann: None. C. Malonzo Marty: Other Relationship; Siemens Healthcare Diagnostics, Eli Lilly and Company. Employee; Hylomorph AG. Consultant; Evido Denmark, FlenHealth Belgium. D. Brandt: None. L. Heinemann: Consultant; Dexcom, Inc., Roche Diabetes Care. Board Member; Lifecare. Stock/Shareholder; Science Consulting in Diabetes GmbH, Profil Institut für Stoffwechselforschung GmbH, diateam GmbH. Consultant; Indigo. M. Rothenbühler: None.FundingThe work is supported by the Diabetes Center Berne.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-562-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 564-P: Improving Identification of Disease Management Concerns—Using the
Diabetes Distress Scale to Guide Patient Visits and Improve Outcomes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 564-P
Abstract: Introduction and Objective: The purpose of this project was to design a workflow utilizing the Diabetes Distress Scale (DDS) to implement changes in treatment regimen to improve glycemic control in a diabetes transitional care clinic.Methods: This project used a pre- and post-implementation design. The project consisted of administering the DDS at the patients’ first post-hospitalization visit as well as collecting an A1C and using these results to guide their care. DDS scores and A1C were then collected again 3 months later. Workflow adherence and staff satisfaction were also measured.Results: The sample consisted of 54 adults with type 2 diabetes completing all parts of the protocol. Mean A1C at baseline was 9.4% and decreased to 6.72 post-implementation. DDS scores had statistically significant reductions in the DDS CORE, long-term complications, and healthcare access categories. Workflow adherence and staff satisfaction with the workflow were high.Conclusion: This project demonstrated that a nurse practitioner-led clinic can be effective at improving glycemic control in high-risk patients as well as assist in reducing diabetes distress. Staff found the survey easy to administer and found it informed the care they provided to patients and did not add unnecessary burden to clinic visits.Disclosure J. Beaulieu: Speaker's Bureau; Insulet Corporation. A. Kreke: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-564-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 565-P: From Knowledge to Practice—Evaluating Diabetes Training for U.S.
Physical Therapy Residents-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 565-P
Abstract: Introduction and Objective: Exercise is key in diabetes management, yet patients’ knowledge and absence of exercise specialists may be limiting factors. Physical therapists (PTs), as exercise specialists, should be part of diabetes care. Yet PTs knowledge of diabetes in the US and abroad is limited. The aim of this study was to 1) compare baseline knowledge of US PTs in a residency program to PTs in Canada (CA) and Saudi Arabia (SA), and 2) assess the effect of an education module for US PTs.Methods: Eight participants enrolled in PT residency programs, at two universities, completed pre- and post-training surveys. The surveys have been used to describe PTs knowledge of diabetes in CA and SA. The module was a 2-hour lecture about foundational diabetes and pathophysiology knowledge, the role of PTs, and clinical decision making. Correct responses to knowledge questions were compared across studies, and over time for US PTs.Results: US trained PTs baseline diabetes knowledge varied but was comparable to CA and SA. (Table) Current clinical practice standards were poorer for US PTs compared to CA and SA. (Table) However, after the module, all US diabetes scores improved and were higher than CA and SA scoresConclusion: US PTs diabetes knowledge is comparable to those in CA and SA. However, PTs current clinical practice approach was worse. US PTs knowledge improved after an education module about diabetes. Follow-up is needed to determine if the education module impacted clinical practice.DisclosureK. Cummer: None. M.D. Ferguson: None. D. Quach: None. M. Hastings: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-565-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 566-P: Engagement Moderates mHealth Outcomes in Latine Adults with Type 2
Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 566-P
Abstract: Introduction and Objective: One static and two adaptive, personalized type 2 diabetes (T2D) education and support mHealth interventions recently showed comparable effectiveness in reducing A1c among low-income Latine adults with T2D. However, as the delivery of adaptive components was contingent on engagement [i.e., participants’ completion of ecological momentary assessments (EMA)], those who responded to fewer EMAs received less personalized feedback. This secondary analysis evaluates whether mHealth engagement moderates A1c outcomes.Methods: N = 310 Latine T2D adults with A1c ≥ 8% in a Federally Qualified Health Center were randomized to Dulce Digital (DD; static education and support messaging), DD-Me-Auto (DD + algorithm driven text based feedback), or DD-Me-Tel (DD + coach delivered feedback). To test moderation of 6-month A1c by engagement, its main effect and interactions with DD-Me-Auto and DD-Me-Tel (vs. DD) were added to the published outcome model, controlling for age, gender, language, employment.Results: Participants were 52 (±10) years old, 70% female, M baseline A1c = 9.3% (±1.6). Engagement moderated the effect of DD-Me-Auto, b = -0.5, 95% CI [-1.0,-0.1], p =.02, with more engagement linked to greater A1c improvements in DD-Me-Auto vs. DD (Fig. 1).Conclusion: Adding personalized, automated feedback to static education and support interventions may enhance outcomes for highly engaged Latine adults.DisclosureE.C. Soriano: None. S.R. Spierling Bagsic: None. A. Philis-Tsimikas: Advisory Panel; Dexcom, Inc. Research Support; Dexcom, Inc. Advisory Panel; Lilly Diabetes. Research Support; Lilly Diabetes. Advisory Panel; Novo Nordisk. Research Support; Novo Nordisk. Advisory Panel; Medtronic, Sanofi. A.L. Fortmann: None. T. Clark: None. E. Farcas: None. S. Roesch: None. J.H. Schultz: None. L. Gallo: None.FundingNational Institute of Diabetes and Digestive and KidneyDiseases of the National Institutes of Health (R01DK112322), National Center for AdvancingTranslational Sciences (UL1TR002550), the New YorkCenter for Diabetes Translational Research (P30 DK111022)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-566-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 567-P: “It made me take pause. I didn’t realize that.”—Use of
Infographics for T2D Risk Communication following Gestational Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 567-P
Abstract: Introduction and Objective: Gestational diabetes (GDM) increases T2D risk seven- to 10-fold and doubles the risk of cardiovascular disease; however, people with a history of GDM may be unaware of these elevated risks. Our objectives were to 1) assess risk perception for T2D development among reproductive-aged people with a history of GDM (n=95) versus a comparison group [no GDM history & BMI<25, (n=91)]; and 2) describe how a T2D risk-communication infographic was perceived by participants with GDM.Methods: For our cross-sectional mixed-methods study, we worked with a community advisory board and graphic designer to develop a T2D risk-communication infographic comparing the average US woman’s risk with that of women with a history of GDM. We assessed risk perception and piloted the infographic in an online survey; six participants with a history of GDM were interviewed. We used t-tests to assess the difference in mean TRIRISK risk-perception scores (dependent variable) between participants with and without a history of GDM (independent variable). We used deductive and inductive coding and thematic analysis.Results: Participants’ ages ranged from 18-46 (M=34.4, SD=6.5). Most were white (90.4%) and non-Hispanic/Latino (88.4%). We found a statistically significant difference in mean risk-perception scores (assessed before seeing infographics) between the GDM (M=12.9, SD=0.32) and comparison (M=11.4, SD=0.34) groups, p=0.002. Interviewees who were not previously aware of their risk agreed the infographic was “shocking” in a good way—that it cued them to make lifestyle changes to prevent T2D; they shared that this risk information should be available to those with a history of GDM.Conclusion: Despite greater T2D risk perception among women with a history of GDM, triangulation of data supports the use of a T2D risk-communication infographic to promote risk awareness and motivation for T2D-prevention lifestyle change in this population.DisclosureJ.M. Kent-Marvick: None. T.B. Aderibigbe: None. C.P. Poynot: None. C. Medina Poeliniz: None. B.D. Landrum: None. S. Lee: Research Support; Clairvoyant Networks, Olera. S.E. Simonsen: None.FundingUniversity of Utah Emma Eccles Jones Nursing Research Center Pilot GrantNational Institute of Nursing Research (F31NR020431)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-567-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 568-P: Prevention of Diabetes Distress in Adults with Type 2
Diabetes—Systematic Integration of Dialogue Tools Addressing the
Psychosocial Aspects of Diabetes in Group-Based Patient Education in
Community Rehabilitation Service-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 568-P
Abstract: Introduction and Objective: The prevalence of diabetes distress in adults with type 2 diabetes (T2D) is high yet interventions aiming to prevent diabetes distress are lacking. Our study aimed to evaluate the feasibility and acceptability of an intervention to facilitate conversations about diabetes distress in group-based patient education.Methods: Four visual dialogue tools aiming to increase awareness of and encourage peer-conversations about psychosocial aspects of living with diabetes and diabetes distress were used in 13 group-based patient education sessions for adults with T2D. Participants (n=159) and health professionals (HPs) (n=30) evaluated the tools via a questionnaire with space for free text responses. Free text responses were analysed thematically, other data descriptively.Results: Most adults with T2D (87%) and HPs (85%) found that the dialogue tools were helpful or very helpful in exploring and expressing psychosocial aspects of diabetes. Adults with T2D highlighted their ability to support sharing among peers that normalized common experiences and challenges. HPs found that the tools provided invaluable support to the peer conversations by enabling participants to articulate their thoughts and experiences. Some HPs found it challenging to introduce the tools to participants and emphasized the need for training and support during implementation.Conclusion: Systematic integration of visual dialogue tools is feasible and acceptable and can support adults with T2D to have conversations about psychosocial aspects of living with diabetes and diabetes distress in group-based patient education provided by rehabilitation services. HPs need training and support in facilitating the tools. Further research is needed to assess the long-term effects of the tools in terms of their ability to prevent diabetes distress in a larger study.Disclosure M. Due-Christensen: Stock/Shareholder; Novo Nordisk. R. Pals: None. M. Madsen: None. M. Bejerholm: None. H.N. Grønbæk: Stock/Shareholder; Novo Nordisk. Speaker's Bureau; Novo Nordisk. V. Stenov: None. B. Cleal: None. C. Glümer: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-568-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 569-P: Sociodemographic Factors and Diabetes Status Associated with
Physical Activity Sources from NHANES-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 569-P
Abstract: Introduction and Objective: Insufficient physical activity (PA) is a significant risk factor of the development of diabetes and negatively impacts diabetes management and overall health. PA is derived from various sources, including work-related, transportation, and recreational activities. This study investigates sociodemographic factors associated with these different PA sources and diabetes status.Methods: Self-reported PA data from the 2017-2020 National Health and Nutrition Examination Survey (NHANES) (n=1,420) were analyzed using the Physical Activity Questionnaire (PAQ). Weighted logistic regression models were used to assess associations between moderate-to-high PA levels in various PA sources and participants’ sociodemographic and diabetes status.Results: Overall, 40.8% achieved moderate or high PA levels. Men were significantly more likely than women to engage in PA (OR, 0.49, 95% CI 0.44-0.54, P<0.001). About 29% reported moderate or high levels of work-related PA, 13.4% reported recreational PA, and 4.7% reported transportation PA. College graduates had higher odds of engaging in overall PA (OR, 1.60, 95% CI 1.35-1.90, P<0.001) and recreational PA (OR, 3.49, 95% CI, 2.82-4.31, P<0.001), but lower odds of work-related PA (OR, 0.68, 95% CI, 0.57-0.81, P<0.001). High income levels (>1.85 times the poverty level) were associated with increased PA (OR, 1.29, 95% CI 1.13-1.46, P<0.001). Participants with diabetes were less likely to engage in PA compared to those without diabetes (OR, 0.77, 95% CI 0.67-0.89, P<0.001).Conclusion: Sociodemographic characteristics associated with a lack of PA included being women, having a low-income level, and having diabetes. Education levels were particularly linked to PA sources, with college graduates more likely to engage in recreational PA and less likely to engage in work-related PA. These findings highlight the need for tailored interventions targeting different sociodemographic groups to improve PA levels.DisclosureM. Lee: None. S. Nam: None.FundingNational Institutes of Health (R01DK132069)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-569-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 570-P: Exercise Determinants Influence Quality of Life and Fear of
Hypoglycemia in Well-Controlled Youth with Type 1 Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 570-P
Abstract: Introduction and Objective: Despite the well-documented benefits of physical activity (PA) for health and diabetes management, individuals with type 1 diabetes (T1D) face significant barriers to exercise.Methods: This cross-sectional study investigated PA determinants and psychometric outcomes in ninety well-controlled individuals with T1D from Northwest Italy (55% female; age: 16 ± 6 years; HbA1c: 6.8 ± 1%). PA timing, type, duration, intensity, and volume were recorded through a 7-day training log, and participants were grouped by exercise timing: morning (6 am-12 pm), afternoon (12 pm-6 pm), and evening (6 pm-12 am).Results: Higher PA volume was associated with improved quality of life (Pearson r = -0.25, P = 0.02) and reduced fear of hypoglycemia (Spearman Rho = -0.23, P = 0.03). Mixed-model analysis revealed that quality of life was significantly influenced by PA type (P = 0.03) and intensity (P = 0.04), with low-intensity aerobic activity yielding better scores than mixed activity (P = 0.009). Fear of hypoglycemia was significantly affected by PA type (P = 0.007) and timing (P = 0.03), with greater anxiety reported for evening (P = 0.01) and anaerobic activities (P = 0.018) compared to afternoon and mixed activities, respectively. Gender had no significant effect on these outcomes.Conclusion: These findings highlight the importance of tailoring exercise recommendations for youth with T1D, emphasizing consistent routines and careful selection of activity types and intensities to enhance quality of life while minimizing fear of hypoglycemia. Promoting adherence to such strategies could optimize both physical and psychological well-being in this population.DisclosureR. Codella: None. A. Bisio: None. D. Gotti: None. M. Bassi: None. N. Minuto: Consultant; Novo Nordisk. P. Ruggeri: None. L. Luzi: Speaker's Bureau; A. Menarini Diagnostics, Amgen Inc. Research Support; Boehringer-Ingelheim. Advisory Panel; Eli Lilly and Company. Speaker's Bureau; Eli Lilly and Company. Research Support; Medtronic. Speaker's Bureau; Novartis AG, Novo Nordisk. D. Maggi: None. E. Faelli: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-570-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 571-P: Association of Physical Activity with Hospitalizations by Glycemic
Status and Peripheral Artery Disease—The Hispanic Community Health
Study/Study of Latinos (HCHS/SOL)-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 571-P
Abstract: Introduction and Objective: Altered glycemic status and peripheral artery disease/claudication (PADC) may co-occur and increase hospitalization risk. Sedentary behavior (SB) and physical activity (PA) also relate to hospitalization risk, but whether this applies equally to those with normoglycemia (NG), prediabetes (PDM), diabetes (DM), and PADC is unclear.Methods: In 12,517 HCHS/SOL participants, survey-weighted mean (SE) age 41.2 (0.3) years, 52.6% female, we studied the association between accelerometer-measured activity (SB; light/LPA; moderate/MPA; vigorous/VPA) and hospitalization, using Anderson & Gill recurrent event models. We tested whether the association differed by baseline glycemic/PADC status: NG/no PADC, n=4497; NG+PADC, n=494; PDM/no PADC, n=3920; PDM+PADC, n=937; DM/no PADC, n=1796; DM+PADC, n=873. We modeled PA/SB continuously and categorically, adjusting for demographic, lifestyle, and clinical factors. Over 11 years of follow-up, participants self-reported 7911 hospitalizations, excluding emergency room only and pregnancy.Results: SB was associated with greater and LPA with lower hospitalization risk in all glycemic/PADC groups, with HR (95% CI) of 1.02 (1.01, 1.03) per 30 min/day SB, and 0.98 (0.96, 0.99) per 30 min/d LPA. Categorical SB and LPA results were similar, but the binary SB-hospitalization association was not significant after adjusting for BMI. MPA was not associated with hospitalization. The VPA-hospitalization association differed by glycemic/PADC status. Within the PADC groups, performing any VPA (vs none) was inversely associated with hospitalization in those with NG, HR 0.48 (0.30, 0.79), and directly associated in those with PDM, HR 1.34 (1.06, 1.71).Conclusion: Less SB and greater LPA are associated with lower hospitalization risk. Ability to perform VPA may be a marker of health among those with vascular and metabolic comorbidities.DisclosureS.K. Alver: None. Y. Mossavar-Rahmani: None. K.R. Evenson: None. C. Cuthbertson: None. K. Matsushita: Other Relationship; Fukuda Denshi. Consultant; RhythmX AI. J. Schrack: Consultant; Edwards Lifesciences, The Villages, Inc. Advisory Panel; BellSant, Inc. D. Sotres-Alvarez: None. L. Gallo: None. J. Carlson: None. J. Cai: None. X. Xue: None. R. Kaplan: None.FundingNational Institutes of Health (HHSN268201300001I, N01-HC-65233HHSN268201300004I, N01-HC-65234HHSN268201300002I, N01-HC-65235HHSN268201300003I, N01-HC-65236 HHSN268201300005I, N01-HC-65237R01HL146132T32CA094880)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-571-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 572-P: Identifying Insulin and Non–Insulin-Mediated Mechanisms during
Physical Activity from Real-World T1D Data-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 572-P
Abstract: Introduction and Objective: Developing a data-driven mathematical model to predict the impact of physical activity (PA) on glucose levels in individuals with T1D is non-trivial due to the concurrent insulin and non-insulin-mediated mechanisms. To understand how each mechanism affects the glucose, we performed a sensitivity analysis using the 4 most common PAs from the T1DEXI dataset.Methods: Net insulin on board (netIOB) is the change in insulin delivery relative to the basal rate in the past 4 hours. The dataset was divided into 1) positive (netIOB>0) and 2) negative (netIOB<0) netIOB at the onset of PA. For each PA, we identified a 1st-order linear time series model that predicts the glucose from the heart rate (non-insulin-mediated). Then, we analyzed how parameters change when netIOB varies.Results: We used 65 and 327 sessions of strength training for netIOB>0 and netIOB<0, 70 and 416 biking, 90 and 313 jogging, and 256 and 1072 walking, respectively. The netIOB ranged from -10 U to 10 U. Fig. 1 shows the cutoff between insulin and non-insulin-mediated effects. The parameters remain stable for netIOB<0. The model gain increases with netIOB for netIOB>0.Conclusion: Data with netIOB<0 at PA onset are representative of the non-insulin-mediated glucose uptake due to the muscle contraction based on Fig.1, while data with netIOB>0 are fundamental to identifying insulin-mediated glucose disposal.Disclosure E. Aiello: Research Support; Hemsley Charitable Trust. K. Tang: Research Support; Hemsley Charitable Trust. M.P. Dhaliwal: Research Support; Hemsley Charitable Trust. R. Lal: Consultant; Abbott, Biolinq, Capillary Biomedical, Inc, Gluroo, PhysioLogic Devices, Portal Insulin, Sanofi, Tidepool. Advisory Panel; Provention Bio, Inc, Provention Bio, Inc, Microbion, Microbion, Lilly Diabetes. Research Support; Insulet Corporation, Medtronic, Tandem Diabetes Care, Inc, Sinocare Inc. C. Summers: Consultant; Tidepool. M. Connolly: Employee; Tidepool. D.P. Zaharieva: Research Support; Hemsley Charitable Trust. Speaker's Bureau; Dexcom, Inc. Research Support; Insulet Corporation, International Society for Pediatric and Adolescent Diabetes. B. Arbiter: Stock/Shareholder; Eli Lilly and Company, Dexcom, Inc. Employee; Tidepool. K. Watson: Employee; Tidepool. M. Friedman: None. L. Figg: None. A.L. Cortes-Navarro: None. I. Balistreri: None. R.S. Kingman: None. B. Suh: None. M.C. Riddell: Advisory Panel; Zucara Therapeutics, embecta. Consultant; Dexcom, Inc., Insulet Corporation, Eli Lilly and Company, Novo Nordisk. Speaker's Bureau; Novo Nordisk, Dexcom, Inc., Sanofi, Eli Lilly and Company. Stock/Shareholder; Zucara Therapeutics. Research Support; Dexcom, Inc., Insulet Corporation, Eli Lilly and Company. Y. Qin: None.FundingThe Leona M. & Harry B. Helmsley Charitable Trust Grant (2404-06905).
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-572-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 573-P: Pre-exercise Whey Protein Ingestion to Mitigate Exercise-Induced
Hypoglycemia in Adults with Type 1 Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 573-P
Abstract: Introduction and Objective: Exercise increases hypoglycemia risk in people with T1D. Pre exercise whey protein ingestion, which stimulates glucagon secretion and endogenous glucose production, may be a novel strategy to mitigate hypoglycemia with exercise in T1D.Methods: Three adults with T1D (mean ± SD HbA1c 6.6 ± 0.3%) using MiniMed 780G underwent two bouts of moderate intensity continuous cycling in the afternoon (60min at 50% VO2max). A standard meal was ingested 4 hours prior and a temporary target set 2 hours pre-exercise. In random order water (control) or whey protein (0.5g/kg) was ingested 30min pre-exercise.Results: Protein ingestion resulted in a diminished exercise associated fall in glucose from exercise onset to end of exercise (-9.6 ± 7.5 vs -55.2 ± 31.6 mg/dL, mean ± SD). From exercise onset to 2 hours post exercise, protein vs control resulted in higher mean glucose (118.7 ± 24.5 vs 168.5 ± 34.4 mg/dL, mean ± SD), and more time >180mg/dL (24.3 ± 29.2 vs 1.8 ± 3.1 %, mean ± SD). There were no instances of hypoglycemia.Conclusion: Pre exercise whey protein ingestion mitigates the drop in glucose during exercise in people with T1D, although the optimal timing and dose of protein ingestion pre-exercise may need to be optimized.DisclosureD. Morrison: None. L. Agnoletto: None. C. Schofield: None. D.T. Hennessy: None. D.P. Zaharieva: Research Support; Hemsley Charitable Trust. Speaker's Bureau; Dexcom, Inc. Research Support; Insulet Corporation, International Society for Pediatric and Adolescent Diabetes. Y.W. Kong: None. J. Apostolopoulos: None. J. Ngan: None. C.E. Smart: None. C. Bruce: None. G.M. Kowalski: None. D.N. O'Neal: None.FundingThe Leona M. & Harry B. Helmsley Charitable Trust Grant (2311-06395)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-573-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 574-P: A Comparison of the Effects of Morning and Afternoon Exercise on
Glucose Control in People with Type 1 Diabetes—A Randomized Crossover
Trial-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 574-P
Abstract: Introduction and Objective: Data indicate that the time of day at which exercise is performed may modulate glucose responses to resistance exercise, although limitations mean certainty of evidence is low. The objective of the current study, therefore, is to compare glucose responses to a bout of resistance exercise performed in the morning or in the afternoon in people with type 1 diabetes.Methods: In a randomized cross over trial people with type 1 diabetes performed three acute bouts of resistance exercise in the 1) morning (6am-10am) in a fed state, 2) morning in a fasted state and 3) afternoon (3pm-8pm) in a fed state, with interstitial glucose responses measured, via continuous glucose monitoring (CGM) for 6-h post exercise and in the nocturnal period (11pm-6am). A repeated measures ANOVA and post-hoc paired t-tests was conducted to compare the effect of the three exercise sessions on CGM data.Results: We recruited 59 people with type 1 diabetes to the study (aged 21-64 years). In multiple daily injections (MDI) users (n=42), but not insulin pump users (n=17), mean glucose levels were higher in the 6-h period after morning fasted and fed sessions (fasted: 9.48 ±2.63 mmol/L, fed: 9.27 ±2.31 mmol/L) compared to afternoon fed session (8.34 ±1.98 mmol/L). In MDI, but not insulin pump, users time in range was lower (52.1% vs 66.6%, p = 0.026) and time above range (43.8% vs 29.4%, p = 0.036) was higher in morning fasted vs afternoon fed sessions. In the nocturnal hours, time in range was higher in insulin pump, but not MDI, users after the morning fasted compared to afternoon fed sessions (72.4% vs 43.9%, p = 0.03). No other differences between the sessions were noted.Conclusion: The time at which resistance exercise was performed results in differential glucose responses in people with type 1 diabetes. This may allow optimization of exercise prescription, based on the time of day, in this population.DisclosureY. Hamdan: None. N. AlOtaibi: None. J. AlKandari: None. D. Taliping: None. E. Taghadom: None. A. AlAwadhi: None. S.R. Gray: None. E. Al-Ozairi: None.FundingKuwait Foundation for the Advancement of Sciences (KFAS), Kuwait
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-574-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 575-P: Development of a Complex Intervention to Improve Physical Activity
Levels in People with Young-Onset Type 2 Diabetes (18–40
Years)—Evidence- and Theory-Based Codesign Approach-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 575-P
Abstract: Introduction and Objective: The incidence of type 2 diabetes (T2D) in younger adults is increasing, yet physical activity engagement in this population is underexplored. This study used co-design to develop a complex intervention to improve physical activity levels in people with young-onset T2D (18-40 years).Methods: Development involved three stages. Stage 1 extracted evidence from a systematic review and a qualitative study, yielding candidate intervention elements and behavior change techniques. In stage 2, animated trigger films were created based on findings from stage 1, depicting the physical activity experiences of people with young-onset T2D. Stage 3 integrated the evidence, the Design Thinking Approach, and outputs from the first two stages to inform four co-design workshops where the animations were screened. Data were analyzed using reflexive thematic analysis.Results: A total of 25 participants (12 individuals with T2D, 11 health care providers, one family member, and one physiotherapist) attended the stage 3 workshops. About half (n=13) were female. In line with the Design Thinking Approach, the workshops prioritized a list of five intervention elements and 23 behavior change techniques identified in Stage 1. The resulting prototype intervention, the multimodal IPAYD (Improving Physical Activity in people with Young-onset type 2 Diabetes), was designed to provide tailored support. It focuses on individualized goal setting, planning, monitoring, professional knowledge, and social support, integrated with behavior change techniques. It will be delivered through the IPAYD website, activity trackers, one-to-one consultations, and optional group sessions.Conclusion: This study outlines the process of using an evidence- and theory-based approach to co-design a multimodal intervention to improve physical activity levels in people with young-onset T2D.DisclosureX. Zhao: None. A. Forbes: None. H. Abu Ghazaleh: None. M. Duaso: None.FundingKing's-China Scholarship Council PhD Scholarship (202108440151)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-575-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 576-P: Culturally Tailored Exercise Intervention for Sustained Weight Loss
and Increased Functional Mobility in Obese African-American Women-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 576-P
Abstract: Introduction and Objective: Physical activity (PA) is a well-known intervention resulting in weight loss, improved physical fitness and metabolic parameters, thereby contributing to reduced risk of conditions such as type 2 diabetes, cardiovascular disease, hypertension, and hyperlipidemia. Interventions promoting healthy lifestyle are more likely to succeed if they are culturally tailored. The goal of this study is to assess the impact of a 48 week tiered, supervised, and culturally tailored PA intervention in obese AA women.Methods: This is a pilot, single arm study in obese AA females at risk for diabetes. The 48 week tiered exercise intervention included both in-person and virtual exercise sessions occurring 3 times/week with independent sessions starting at week 24. Outcome measures were assessed at baseline, 24- and 48 weeks. The supervised intervention included cardiovascular, resistance, balance, and flexibility exercises.Results: A total of 60 sedentary, obese AA females were enrolled in the study (mean age 51, weight 219 lbs, BMI 37, 31% hypertensive, 18% dyslipidemic, and 34% pre-diabetic. A total of 32 and 28 participants completed 24- and 48 weeks of exercise, respectively. Compared to baseline, significant improvements were seen as follows: 1) weight, body mass index, waist and hip circumference, and blood pressure at week 48; 2) functional mobility (timed up & go, 6-minute walk distance tests, and length walked) in both weeks 24 and 48; 3) total body fat (including arms, legs, trunk, and waist), percentage of lean tissue, and Norfolk Quality of Life-Fatigue Survey scores in both weeks 24 and 48; 4) HemoglobinA1c at week 24. There were no changes in fasting blood glucose, insulin, triglycerides, and cholesterol.Conclusion: These results indicate that a culturally sensitive, supervised exercise intervention for obese AA women can lead to sustained weight loss, increased functional mobility, reduced levels of fatigue and improvements in body composition as well as metabolic parameters.DisclosureH. Parson: None. K.S. Thomas: None. D. Wolf: None. C.M. Casellini: Employee; Eli Lilly and Company. J. Patel: None. T. Sears: None. M. Karpov: None. E.S. Siraj: Consultant; Novo Nordisk. Research Support; Novo Nordisk. Consultant; Boehringer-Ingelheim. Research Support; Boehringer-Ingelheim.FundingEastern Virginia Medical School
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-576-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 577-P: Association of Prolonged Sedentary Behavior with Glycemic Profiles
in Individuals with Type 1 Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 577-P
Abstract: Introduction and Objective: The association between sedentary behavior (SB) and glycemic profiles in individuals with type 1 diabetes (T1D) is unclear. This study aimed to examine this relationship cross-sectionally.Methods: Ninety-three Japanese adults with T1D participated in this study (75 women; age: 45.0 [36.0-55.0] years, HbA1c: 7.3 [6.8-8.1] %, median [25%-75% quartiles]). Physical activity (PA) was measured using a triaxial accelerometer and classified according to intensity: SB (≤1.5 metabolic equivalents [METs]), light-intensity PA (1.6-2.9 METs), and moderate-to-vigorous-intensity PA (≥3.0 METs).Results: Participants spent a median of 543.6 minutes per day in SB. Longer SB was associated with lower time in range (TIR). Longer periods of prolonged SB (≥30 min) were associated with higher mean 24-hour sensor glucose values (SG), time above range (TAR), HbA1c, and lower TIR (Figure). Furthermore, multiple regression analysis revealed that prolonged SB was the only PA type significantly associated with SG, TAR, TIR, and HbA1c (β = 0.546, 0.565, −0.567, and 0.468, respectively).Conclusion: These results suggest that increased time spent in prolonged SB may contribute to the deterioration of glycemic profiles in individuals with T1D. Therefore, these factors should be considered when managing T1D.DisclosureH. Honda: None. N. Hashimoto: None. M. Zenibayashi: None. T. Takeuchi: None. A. Yamamoto: None. Y. Hirota: Speaker's Bureau; Novo Nordisk, Sanofi, Eli Lilly and Company, Terumo Corporation, Sumitomo Dainippon Pharma Co., Ltd. Research Support; Medtronic, Kyowa Kirin Co., Ltd, Abbott Japan Co., Ltd.FundingJapan Association for Diabetes Education and Care (2017)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-577-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 578-P: Resistance Training Prevents the Progression of Diabetec
Nephropathy in Patients with 2 Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 578-P
Abstract: Introduction and Objective: Diabetic nephropathy is one of the most important complications of diabetes mellitus. In recent years, exercise has been reported to be potentially effective in preventing nephropathy. However, the relationship with resistance training(RT) is not clear. In this study, we researched the effect of resistance RT on the progression of nephropathy in patients with type 2 diabetesMethods: We analyzed retrospectively the cohort study of type 2 diabetic patients (T2DM) with urinary albumin-to-creatinine ratio (UACR) under 30 mg/gCr who visited Ayabe City Hospital from April 2020 to March 2022 and were observed until May 2024. The progression of nephropathy was defined as UACR of 30 mg/gCr or higher during observation period. Participants were asked how many times per week they engaged in RT and the average duration per session. Individuals who performed RT at least once per week were classified as RT participants. Hazard ratio of RT for the progression of nephropathy was calculated by Cox hazard model after adjusting by age, gender, BMI, hemoglobin A1c(HbA1c), smoking states, alcohol consumption, physical activity, sitting time, sarcopenia, use of RAS inhibitor and use of SGTL2 inhibitors at baseline.Results: 266 patients (173 men), mean age, body mass index, HbA1c, UACR, RT and median observation period were 72.0 ± 13.2 years, 23.7 ± 3.5 kg/m2, 7.2 ± 0.7 %, 56.8 ± 137.4 mg/gCr, 44 participant(16.5%) and 981 (260-1269) days. Participants who engaged in RT performed it an average of 4.6 times per week, with a mean duration of 13.8 minutes per session. During follow-up, progression of nephropathy was observed in 39.1 % (104/266). The adjusted hazard ratio of RT of progression of nephropathy was 0.55 (95% confidence interval 0.30-0.98, P = 0.033).Conclusion: Patients with T2DM with RT were shown to be at lower risk of developing diabetic nephropathy. This suggests that RT is important in terms of preventing diabetic nephropathy.DisclosureT. Osaka: None. M. Fukui: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-578-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 580-P: Engagement across DiabetesWise—A Platform for Support around
Diabetes Technology and Exercise-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 580-P
Abstract: Introduction and Objective: To gain feedback from users and assess engagement with the DiabetesWISER (DWer) community forum and DiabetesWise (DW) website - a neutral and unbiased platform for diabetes technology and exercise resources.Methods: User testing was conducted to understand needs and utilization patterns of people with diabetes and healthcare providers (HCPs) using these platforms.Results: During 2024, DW had 43,000 active users. The top searches were 1) Device finder: Comparison tool; 2) Exercise; and 3) Checkup tool. DWer was released in Nov 2024 so data are not available yet. Fifteen adults were interviewed (Table 1), and they found the main DW page helpful for its images (n=8) and materials for new-onset diabetes (n=5). While feedback on the exercise page was positive, users (n=6) requested more inclusive content for older adults. We shared content in development (i.e. activity tracker table comparing various devices). Most users (n=11) wanted to see the full table published. Some users (n=3) would utilize DW more if they could upload their CGM data for glycemia optimization advice around exercise. Those who used DWer regularly (n=9) valued the “Ask the Expert" series and its association with Stanford.Conclusion: Feedback from users about the content and community was very positive. Next steps include adding more content and making it easier for people with diabetes and HCPs to access and utilize vetted resources around diabetes technology and exercise.DisclosureA.L. Cortes-Navarro: None. I. Balistreri: None. A.K. Schneider-Utaka: None. L. Figg: None. S.A. Alamarie: None. S. Hanes: None. K.K. Hood: Consultant; Sanofi. Advisory Panel; MannKind Corporation. Consultant; Havas Health. Research Support; embecta. D.P. Zaharieva: Research Support; Hemsley Charitable Trust. Speaker's Bureau; Dexcom, Inc. Research Support; Insulet Corporation, International Society for Pediatric and Adolescent Diabetes.FundingLeona M. and Harry B. Helmsley Charitable Trust
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-580-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 581-P: Targeting REV-ERBα to Enhance Glucose Regulation and Address
Aging-Related Muscle Dysfunction-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 581-P
Abstract: Introduction and Objective: Skeletal muscle is pivotal for glucose uptake, accounting for over 80% of postprandial glucose clearance. Insulin resistance (IR), a precursor to type 2 diabetes (T2D), impairs this process, resulting in hyperglycemia. Aging exacerbates declines in muscle function and mass, as well as mitochondrial efficiency, with these effects further aggravated by T2D. Rev-erbα, a critical regulator of mitochondrial dynamics and muscle integrity, has emerged as a potential therapeutic target for mitigating aging-associated dysfunctions. This study explored: 1) whether activating Rev-erbα using the agonist SR9009 could improve glucose uptake in aging mice; 2) the relationship between aging and mRNA levels of clock genes in skeletal muscle; 3) the effects of physical exercise on the mRNA expression levels of skeletal muscle clock genes.Methods: Aging-resistant mice (SAMR1) and accelerated aging mice (SAMP8) were used. SAMP8 mice underwent treatment with either vehicle or SR9009 for three days and participated in a 3-week combined exercise protocol.Results: Glucose tolerance test results revealed that SR9009 treatment improved glucose regulation in SAMP8 mice, with significantly lower blood glucose levels compared to the vehicle-treated group. Moreover, aging reduced Nr1d1 and Bmal1 expression in the gastrocnemius, but not in the soleus muscle, suggesting differential effects of aging on muscle tissues. Body weight was lower in the SAMP8 group compared to the SAMR1 group. The combined physical exercise protocol improved balance, bradykinesia, maximal strength, and motor coordination, as well as mitigated the Nr1d1 reduction in the gastrocnemius of SAMP8 mice.Conclusion: Overall, Rev-erbα activation can influence glucose metabolism in aging and highlight the complex relationship between Rev-erbα signaling and muscle health.DisclosureA.S. Pinto: None. V.R. Muñoz: None. D.E. Cintra: None. E.R. Ropelle: None. J.R. Pauli: None. E.C. Freitas: None. A.S.R. da Silva: None.FundingThis study was financed, in part, by the S'o Paulo Research Foundation (FAPESP; process numbers 19/11820-5, 21/08693-1, and 21/08692-5) and by the National Council for Scientific and Technological Development (CNPq; process number 308999/2022-3).This study was financed, in part, by the Sao Paulo Research Foundation (FAPESP; process numbers 19/11820-5, 21/08693-1, and 21/08692-5) and by the National Council for Scientific and Technological Development (CNPq; process number 308999/2022-3).
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-581-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 582-P: Enhancing ABC Target Achievement in Type 2 Diabetes through
Integrated Intensive Lifestyle Interventions—A One-Year Study in an
Indian Population-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 582-P
Abstract: Introduction and Objective: Achieving ABC targets (A1c<7%, blood pressure<140/90 mmHg, LDL cholesterol <100 mg/dL) is vital for managing type 2 diabetes (T2D) and reducing cardiovascular risks, yet only 7.7% in India meet these targets. This study evaluated the efficacy of an intensive lifestyle intervention (ILI) and the roles of BMI, weight loss, and insulin sensitivity in achieving ABC targets.Methods: Data from 1857 adult T2D patients (not on insulin) enrolled in a one-year online lifestyle program at Freedom from Diabetes Clinic, India, were analyzed. The program included a personalized plant-based diet, physical activity, stress management, and medical support. Outcomes included ABC target achievement and biochemical improvements. Logistic regression identified predictors of ABC target achievement.Results: The mean age and median diabetes duration were 52.5±9.4 years and 9.0(4.4-14.2) years, respectively; 65% were males. Post-intervention, the percentage of individuals achieving all three ABC targets rose from 16% to 26%, while those meeting at least two targets increased from 38% to 48% (p<0.05). Significant post-intervention improvements (%) were noted in weight [-5.0], BMI [-5.0], HbA1c [-11.0], blood pressure (systolic [-2.0], diastolic [-1.0]), LDL-C [-2.4], and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) [-20.4] (p<0.05). Factors associated with achieving all three targets included male gender [OR 1.8, 95% CI:1.1-3.1], weight loss>10% [OR 5.9, 95%CI: 2.4-14.3], BMI<25 kg/m2 [OR 2.2, 95% CI: 1.2-4.2], and HOMA-IR<2.5 [OR 2.1, 95% CI: 1.2-3.9] (p<0.05).Conclusion: Structured ILI significantly improved ABC target achievement in T2D, with key predictors including weight loss, BMI, and insulin sensitivity. Broader implementation of such programs may help enhance diabetes care outcomes.DisclosureP. Tripathi: None. D. Tiwari: None. N.S. Kadam: None. T. Kathrikolly: None. B. Sharma: None. A.R. Vyawahare: None. M.H. Ganla: None. B.D. Saboo: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-582-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 583-P: Impact of Online Supervised Nine-Day Progressive Fasting Program on
Anthropometric and Glycemic Outcome in Patients with Type 2 Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 583-P
Abstract: Introduction and Objective: The rising prevalence of Type 2 Diabetes (T2D) necessitates effective, accessible, and scalable interventions for glycemic control and weight management. This study evaluated the efficacy of an online supervised 9-day Progressive Fasting (PF) program on anthropometric and glycemic parameters in patients with T2D.Methods: This study included 608 patients with T2D (142 with pre-diabetes) who participated in the PF program conducted in November 2024. The program had three phases: preparatory (days 1-2), fasting (days 3-7), and refeeding (days 8-9), with fasting protocols tailored to the patient’s preferences and health conditions. Protocol included SSS (Smoothie, Shahi Pani [1 tsp basil seed, saffron, rock salt, and lemon juice in 1-liter water], Soups), SNS (Smoothie, Nuts, Soups), SSSN (Smoothie, Shahi Pani, Soups, Nuts), and water fasting. Patients were monitored by a team of physicians and dietitians via a WhatsApp group. Fasting blood glucose (FBG), blood pressure, and anthropometric measurements were self-reported at baseline and 9th day.Results: The mean age, diabetes duration, and HbA1c were 52.6±8.04 years, 9.1±7.5 years, and 7.6±1.7%, respectively. Most participants followed SSS (73.4%) or SNS (13.3%), with SSS showing better outcomes. Post-fasting, significant improvements were observed, including mean weight reduction (73.4 kg to 70.6 kg), decreased BMI (27.6 to 26.5 kg/m²), and improved FBG (133.6 to 101 mg/dl) (p = 0.000). Benefits reported included ‘weight loss’ (75.5%), ‘reduced blood sugar levels’ (64.6%), and ‘a sense of physical and mental lightness’ (59.9%).Conclusion: The 9-day online supervised PF program significantly improved weight, BMI, and glycemic indicators while promoting positive participant experiences. These findings underscore the potential of structured online fasting protocols in diabetes and weight management, warranting further exploration in long-term studies.DisclosureP. Tripathi: None. B. Sharma: None. N.S. Kadam: None. D. Tiwari: None. A.R. Vyawahare: None. T. Kathrikolly: None. M.H. Ganla: None. B.D. Saboo: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-583-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 584-P: Impact of Diet on Gingival Crevicular Fluid Microbiome and
Metabolome in People with Type 1 Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 584-P
Abstract: Introduction and Objective: People with type 1 diabetes (PwT1D) are at higher risk of developing periodontal diseases (PD). We aimed to investigate the impact of dietary habits on the gingival crevicular fluid (GCF) microbiome and metabolome in people with T1D.Methods: PwT1D were recruited and matched with non-diabetic controls. The periodontal examination was performed and GCF was sampled. Genomic DNA was extracted, bacterial 16S rRNA sequenced and concentrations of short-chain fatty acids and trimethylamine derivatives determined. Pro-healthy (pHDI) and non-healthy diet indices (nHDI) were calculated using the validated Questionnaire of Eating Behaviours.Results: In total, 110 participants were included (mean age 27.1 ± 5.9 years, 60.0% male). In 65 PwT1D, the mean duration of diabetes was 15.5±8.4 years and mean Hba1c% 6.97 ± 0.95% (53±2.2 mmol/mmol). 22 cases of mild gingivitis (G) were identified, all in the T1D group. There were no significant differences in the frequencies of pHDI categories between study groups (T1D with G, low 19 [86.4%] and moderate 3 [13.6%]; T1D without G, low 28 [66.7%] and moderate 14 [45.2%]; control, low 30 [68.2%], moderate 14 [31.8%]; p=0.213). All participants scored low on the nHDI. GCF community composition did not differ between pHDI categories. In PwT1D and G caproic acid was higher in low vs. moderate pHDI category (3.5 [0.9-4.9] vs. 0.64 [0.49-NA] umol/l, p=0.04). In PwT1D without G, isocaproic acid and glycerophosphorylcholine were lower in low vs. moderate pHDI category (0.14 [0.13-0.46] vs. 0.45 [0.18-1.24] umol/l, p=0.032, and 71.23 [32.83-120.40] vs. 129.8 [70.5-228.1] ng/ml, p=0.013).Conclusion: This is the first study to report on the impact of diet on GCF in PwT1D. G was observed only in PwT1D, who were more likely to eat less healthy as compared to the remaining participants. Concentrations of few metabolites showed differences depending on the pHDI category. Other factors than diet impact the GCF microbiome and metabolome in PwT1D.Disclosure M. Kania: Consultant; Novo Nordisk A/S. Other Relationship; Takeda Pharmaceutical Company. Consultant; PTC. M. Dabrowska: None. E. Samborowska: None. N. Zeber-Lubecka: None. M. Kulecka: None. T. Klupa: Speaker's Bureau; Lilly Diabetes, Novo Nordisk, AstraZeneca, Boehringer-Ingelheim, Sanofi. Research Support; Medtronic. Speaker's Bureau; Medtronic, Abbott, Dexcom, Inc. I. Gregorczyk-Maga: None.FundingThis study was supported by the Polish Ministry of Science and Higher Education grant (NdS/545131/2022/2022).
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-584-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 585-P: Pilot Study on AI-Based Automatic Carbohydrate Counting for Chinese
Americans with Type 2 Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 585-P
Abstract: Introduction and Objective: Chinese Americans face prominent disparities in prevalence and managing type 2 diabetes (T2D). Their traditional food patterns, such as high intakes of carbohydrate (carb)-rich foods (e.g., rice and wheat), significantly contribute to elevated postprandial hyperglycemia and glucose variability. Developing accurate methods for carb counting is critical to reducing carb-rich food intake. Artificial intelligence (AI)-based automatic estimation is promising, but its application to carb counting remains unexplored. Thus, we aimed to evaluate the accuracy of AI-based automatic estimation of carbs compared with food diary (common clinical method) relative to food weighing (standard method) among Chinese Americans with T2D.Methods: This was a one-group prospective study. Chinese Americans with T2D (N=11) wore a wearable device eButton that automatically captured food images for 10-day meals, which were then analyzed using the large language models (an advanced form of AI), to automatically identify food types, estimate portion size, and estimate carbs. We analyzed 3 participants’ food data as a preliminary analysis.Results: Chinese Americans aged 42-77 years, with 72.7% female. The number of meals of 3 participants was 28, 28, and 33. Compared with food weighing, AI-based automatic estimation slightly underestimated carb grams across 3 participants (mean ±SE: -5.6 ± 4.4, -9.6± 7.2, and -8.1±5.4), while food diary mixed with under- and over-estimation (-0.43± 5.8, -20.3±6.7, and 13.1±7.3). Additionally, AI-based automatic estimation had a higher % of meals’ absolute error within 10g of carb estimation than food diary across these participants’ meals (44.8%, 28.6%, and 39.4% vs. 44.8%, 22.6%, and 27.3%).Conclusion: Although AI-based carb estimation may produce some errors, it demonstrates greater accuracy than the traditional method. This innovative approach holds promise for reducing T2D management disparities among Chinese Americans.DisclosureY. Zheng: None. W. Jia: None. B. Wu: None. B. Li: None. K. Chen: None. S. Zweig: None. M. Sun: None.FundingNIH/NCATS UL1TR001445; CTSI Collaborative Translational Pilot Award; CTSI Clinical Research Center
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-585-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 586-P: Effects of Replacing Diet Beverages with Water on Sustained Weight
Loss and Type 2 Diabetes Remission—An 18-Month Randomized Clinical Trial
-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 586-P
Abstract: Introduction and Objective: To evaluate the effects of replacing diet beverages (DBs) with water on the durability of weight loss and Type 2 Diabetes (T2D) remission over an 18-month weight management follow-up, which included a 6-month weight loss intervention and a subsequent 12-month weight maintenance program.Methods: 81 adult women with obesity or overweight and T2D, who usually consumed DBs in their diet, were randomly assigned to either substitute with water or continue drinking DBs 5 times/week after their lunch for the 18-month follow-up.Results: The participants who were randomly assigned were included in the study by using an intention-to-treat analysis. After the 18-month follow-up period, significant weight change (mean ± SD) in the water group was observed compared with the DBs group (-6.82 ± 2.73 kg vs. -4.85 ± 2.07kg) (P<0.001). Diabetes remission was achieved in 37/41 (90%) participants of the water group vs. 18/40 (45%) in the DBs group (P<0·0001). There were also significant changes in BMI, fasting plasma glucose, insulin levels, the homeostasis model assessment of insulin resistance, 2h postprandial glucose and serum triglyceride in the water group compared with DBs over the 18 months.Conclusion: Sustained replacement of DBs with water after the main meals in women with T2D may promote further weight reduction during an 18-month weight management program. It may also offer benefits in glycemic control and diabetes remission during the long-term diet plan.DisclosureM. Farshchi Nasr: None. A. Madjd: None. H.R. Farshchi: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-586-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 587-P: Impaired Arginine, Citrulline, and Glutamine Metabolism in Type 2
Diabetes (T2D)—Insights from a Stable Isotope Study-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 587-P
Abstract: Introduction and Objective: Arginine (ARG) is an important amino acid in T2D as a potent insulin secretagogue and precursor for nitric oxide (NO). Citrulline (CIT), the substrate for de novo ARG synthesis, is mostly produced from glutamine (GLN). Here, we aimed to investigate their metabolism in T2D using a novel stable isotope tracer approach.Methods: We studied 42 individuals (21 with T2D, 21 controls). After an overnight fast, we collected blood samples following pulse administration of ARG, CIT, and GLN stable amino acid tracers. Plasma concentrations and isotopic enrichments were measured by LC-MS/MS and lean soft tissue (LST) by DXA. Compartmental analysis was performed to calculate their WBP. Data are mean (SD) or [95% CI] (t-test and ANCOVA by JASP).Results: The cohort was 60% female, mean age 64.4 (7.5) years, and BMI 33.0 (4.3) kg/m2 (all p>0.05). After adjusting for sex and age, T2D group had lower plasma concentrations of ARG (57.7 [48.9, 66.4] vs. 75.8 [66.9, 84.5] µM, p=0.005), CIT (23.4 [18.9, 27.9] vs. 34.4 [29.9, 38.9] µM, p=0.001), and GLN (463.5 [421.1, 506] vs. 561.7 [519, 604.3] µM, p=0.002). In T2D, WBP was lower for CIT (11.8 [10.1, 13.6] vs. 15.5 [13.8, 17.2] µmol/min, p=0.004) but higher for GLN (537 [503, 571] vs. 481.9 [448.3, 515.5] µmol/min, p=0.004) after controlling for age, sex and LST. T2D group also had lower CIT intracellular production (p=0.003), but higher GLN clearance (p=0.001) and intracellular pool size (p=0.007), and a trend towards higher ARG clearance (p=0.06).Conclusion: In T2D, significant dysregulation exists in ARG, CIT and GLN metabolism. We hypothesize that increased muscle GLN synthesis stimulates gluconeogenesis, increases GLN consumption, and contributes to T2D pathogenesis via blunted insulin secretion, sensitivity and incretin response by having less GLN available for CIT production that may affect ARG (and NO) metabolism. Interventions aiming to reduce GLN production but increase CIT availability may be useful in T2D.DisclosureM. Tosur: None. R. Wierzchowska-McNew: None. M.P. Engelen: None. N.E. Deutz: None.FundingNational Institutes of Health (K23-DK129821)(MT)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-587-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 588-P: Nutrient Intake Order on Metabolic Outcomes in Type 2 Diabetes—A
Systematic Review and Meta-analysis-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 588-P
Abstract: Introduction and Objective: Non-pharmacological therapies for type 2 diabetes (T2D) require simpler, adaptable recommendations that align with diverse contexts, preferences, and long-term goals. This study aims to evaluate the impact of a carbohydrate-last (CL) strategy compared to carbohydrate-first or unordered (CF) nutrient intake on metabolic parameters in T2D.Methods: PubMed, EMBASE, and Cochrane Central were systematically searched for randomized controlled trials (RCTs) evaluating nutrient intake order in T2D. Mean difference (MD) with 95% confidence intervals (CI) was used for all outcomes. Heterogeneity was assessed with I² statistics. Statistical analyses were performed using R version 4.2.3.Results: Seventeen studies involving 389 participants were included, with 114 (29%) in a parallel design and 192 (49%) in a crossover design receiving CL. In the pooled analysis, the CL group had significantly lower postprandial glucose at 120 minutes (MD: -13.00 mg/dL; 95% CI: -21.07, -4.93; p<0.01). Insulin levels at 120 minutes postprandial (MD: -3.90 uIU/mL; 95% CI: -16.85, 9.04; p=0.55) showed no significant differences. The CL group had significantly higher postprandial GLP-1 levels at 120 minutes (MD: 8.21 pmol/L; 95% CI: 2.33, 14.09; p<0.01), while GIP levels at the same time point (MD: 5.79 pmol/L; 95% CI: -6.33, 17.90; p=0.35) showed no significant differences. Gastric emptying half-time in the CL group (MD: 28.14 min; 95% CI: 16.06, 40.23; p<0.01) was significantly delayed. Glycated hemoglobin (HbA1C) levels at the end of the follow-up (MD: -0.16%; 95% CI: -0.31, -0.01; p=0.04) were significantly lower in the CL group.Conclusion: Carbohydrate-last nutrient intake is associated with improved postprandial glucose profile and HbA1C levels in individuals with T2D. Further research is needed to confirm its sustainability and applicability across diverse populations.DisclosureL. Saldarriaga: None. A.D. Andrade: None. P. Ratan: None. S. Kodalak: None. E. Pasqualotto: None. T.G. Bovi: None. T. Trevisan: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-588-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 589-P: Using One-Shot Prompting of Fine-Tuned Commercial Artificial
Intelligence Models to Assess Nutrients from Photographs of Japanese Meals
-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 589-P
Abstract: Introduction and Objective: Diet interventions to treat diabetes have poor adherence due in part to burdensome food logging. Assessing photos of meals may make food logging easier, and we investigated the accuracy of AI for this task.Methods: We assessed 1363 Japanese meals with photographs and nutritional data: 364 real world with weighed food records (WFR), 470 laboratory with WFR, and 529 real world with dietician estimates. Using one shot prompting implementing chain-of-thought logic, we used 988/247/128 train/validate/evaluate splits to fine-tune gpt-4o-2024-08-06, assessing nutrient estimates against estimates from non-fine-tuned baseline models.Results: Performance against the evaluation set was good for the baseline models. The finetuned GPT-4o model had mixed improvement results, with comparable performance or small improvements in most factors but a decrease in performance against protein. The finetuned model was comparable to or better than the performance of human dieticians in a previous study, with particular strengths (mean ICC, [95% CI]) in fat (0.57 [0.55-0.58]), energy (0.79 [0.78-0.79]), and fiber (0.67 [0.65-0.68]).Conclusion: For our data, fine tuning improved some measures but degraded others. Overall, current AI provides useful levels of accuracy for nutritional estimates based on photos of meals, with or without fine tuning.DisclosureY. Ji: None. K. Waki: Consultant; Astellas Pharma Inc. Other Relationship; Astellas Pharma Inc, Sumitomo Dainippon Pharma Co., Ltd. Consultant; Terumo Corporation. Other Relationship; Terumo Corporation. Speaker's Bureau; Sanofi. D. Lane: None. T. Yamauchi: Research Support; Asahi Mutual Life Insurance Company. Other Relationship; Astellas Pharma Inc, AstraZeneca, Abbott Japan Co., Ltd, ARKRAY Marketing, Inc., Amgen Inc. Research Support; Boehringer-Ingelheim. Other Relationship; Boehringer-Ingelheim, Bayer Pharmaceuticals, Inc, Covidien Japan Inc., Daiichi Sankyo, Eli Lilly and Company. Research Support; EA Pharma Co.,Ltd. Other Relationship; GlaxoSmithKline K.K. Research Support; Kowa Company, Ltd. Other Relationship; Kowa Company, Ltd, Kyowa Kirin Co., Ltd, Medtronic, Merck Sharp & Dohme Corp, Mitsubishi Tanabe Pharma Corporation. Research Support; Novo Nordisk. Other Relationship; Novo Nordisk, Ono Pharmaceutical Co., Ltd, Sumitomo Pharma Co., Sanofi K.K., SANWA KAGAKU KENKYUSHO CO.,LTD., Taiho Pharmaceutical Co. Ltd, Teijin Pharma Limited, Nipro Corporation. Research Support; NITTO BOSEKI CO.,LTD. Other Relationship; ViewSendICT Inc. M. Nangaku: Other Relationship; Astellas Pharma Inc, AstraZeneca, Daiichi Sankyo, GlaxoSmithKline plc, Daiichi Sankyo, Kyowa Kirin Co., Ltd, Boehringer-Ingelheim. Consultant; Novo Nordisk. Research Support; Bayer Pharmaceuticals, Inc. Other Relationship; Mitsubishi Tanabe Pharma Corporation. K. Ohe: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-589-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 590-P: Improved Carbohydrate Quality Associated with Better Glycemic
Control in Individuals with Type 1 Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 590-P
Abstract: Introduction and Objective: The aim of this study is to investigate the association between the quality of carbohydrates in the diet and the attainment of long-term blood glucose control as well as short-term blood glucose fluctuations in patients with type 1 diabetes (T1D).Methods: A dietary survey involving 155 patients with T1D used a food frequency questionnaire (FFQ) and 3-day dietary records from 65 patients to analyze 538 meals. The relationship between short-term dietary factors and postprandial glycemic fluctuations was evaluated by a mixed-effects model. The LightGBM model and SHAP analysis method were established to predict the key factors influencing postprandial blood glucose, helping patients with T1D to better understand the factors affecting postprandial blood glucose and thus adjust their diet and insulin regimens.Results: The FFQ survey indicated that a higher intake of dietary fiber was associated with better long-term blood sugar control (HbA1c≤6.5) in T1D patients (OR 1.101; 95%CI [1.009 - 1.201]). Data from 3-day diet records and CGM demonstrated that a greater proportion of whole grains in carbohydrate sources was negatively correlated with post-meal blood glucose fluctuations (SD, LAGE, MAGE) (Est = -0.83, p < 0.01; Est = -2.4, p < 0.01; Est = -1.47, p = 0.04). Specifically, blood glucose fluctuations were more significant after lunch (1.53(0.85), p < 0.05; 5.44 (2.68), p < 0.05; 3.49(1.81), p < 0.05), and these fluctuations were significantly and negatively related to the intake of whole grains (Est= -0.45, p=0.02; Est= -1.52, p=0.01; Est= -1.39, p<0.01).Conclusion: Increasing the consumption of dietary fiber is beneficial for achieving long-term glycemic control. Additionally, increasing the intake of whole grains, especially at lunch, as a source of high-quality carbohydrates, is helpful in reducing post-meal glycemic fluctuations, which is of crucial significance for reducing the risk of long-term complications in T1D patients.DisclosureH. Liu: None. L. Bian: None. C. Yang: None. Y. Jin: None. H. Wang: None. M. Zhu: None. J. Xu: None. M. Zhang: None. Y. Gu: None. T. Yang: None. J. Bai: None.FundingThis research was funded by the Noncommunicable Chronic Diseases-National Science and Technology Major Project (NO. 2023ZD0507400, 2023ZD0507401, 2023ZD0507403), National Natural Science Foundation of Jiangsu Province (NO. BK20220708) and National Natural Science Foundation of China (NO. 82170837, 82230028, 82404271)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-590-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 591-P: Assessment of Diabetes Medical Provider Perceptions and Practices
Regarding Medical Nutrition Therapy in Pediatric Type 1 Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 591-P
Abstract: Introduction and Objective: In addition to registered dietitians (RDs), diabetes medical providers (DMPs = physicians and diabetes educators) play a role in providing medical nutrition therapy (MNT) to children with T1D. However, there are limited data on DMP perceptions and practices regarding MNT in pediatric T1D - the focus of this study.Methods: Surveys were fielded across the US in 2024 to DMPs who had cared for ≥5 outpatient pediatric patients with T1D in the prior year. Surveys included questions evaluating DMP perceptions of MNT in pediatric T1D with Likert scales to compute MNT importance rating and assessment of DMP MNT practices. DMPs were also asked to assign importance and comfort ratings to incorporating MNT into various clinical scenarios. Logistic regression analyses, controlling for provider type, years of clinical experience, and number of patients with T1D under provider care, assessed the relationship between MNT importance rating and likelihood of (1) perceived enough time spent on MNT and (2) encouraging patients to see an RD annually.Results: Among 144 completed surveys, DMPs assigned a high importance rating to MNT (82±5.3; scale 0-100), with no difference by provider type (P=0.411). Higher MNT importance rating was associated with greater likelihood of perceived enough time spent discussing MNT (P=0.009) and encouraging patients to see an RD annually (P=0.006). There was a >10% difference in the percentage of DMPs recognizing the importance of and expressing comfort in incorporating MNT in the counseling of bolus strategies for protein- and fat-rich foods, low carbohydrate diets, weight management, abnormal lipids, and disordered eating.Conclusion: Greater DMP perception of the importance of MNT in pediatric T1D is associated with focus on MNT-based practices. There was a mismatch between perception of importance of certain MNT topics and DMP comfort addressing these, endorsing a need for additional MNT support and education.DisclosureS. Azova: None. B.S. Lennerz: None. C. Petty: None. H.B. Wilson: None. E. Rhodes: Other Relationship; National Institutes of Health. K. Garvey: Consultant; Sanofi. Speaker's Bureau; Tandem Diabetes Care, Inc.FundingNational Institutes of Health (K12DK133995)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-591-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 592-P: Metabolic Effects of Time-Restricted Eating and Exercise
-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 592-P
Abstract: Introduction and Objective: Aging leads to increased fat mass, decreased lean mass, and insulin resistance, heightening the risk of prediabetes and diabetes. Time-restricted eating (TRE), combined with exercise, has shown promise in younger active adults for weight loss and metabolic health. This pilot study aims to explore the effects of 8-hour TRE paired with resistance training (RT) or aerobic training (AT) on glucoregulatory markers in older adults with prediabetes and obesity.Methods: In a 12-week randomized trial, participants performed 4 days per week of either RT or AT alongside 8-hour TRE, selecting one of three eating windows (10 AM-6 PM, 11 AM-7 PM, or 12 PM-8 PM). Anthropometric measurements and fasting glucoregulatory markers were collected at baseline and week 12.Results: A total of 26 female participants completed the trial, 14 in the aerobic training group and 12 in the resistance training group. Both groups experienced decreases in insulin and HOMA-IR, as well as increases in glucose, QUICKI, and HbA1c; however, none of these changes reached statistical significance.Conclusion: While this study was not powered to detect statistically significant effects, both groups exhibited modest metabolic improvements, including reductions in fasting insulin and insulin resistance and improvements in insulin sensitivity. These results are promising and support future work in this area. Future research with larger cohorts and longer durations is necessary to better understand the effects of TRE combined with exercise in older adults with prediabetes and obesity.DisclosureJ. Sanchez Perez: None. K. Gabel: None.FundingT32DK128782
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-592-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 593-P: Preoperative Carbohydrate Loading Supports Blood Glucose in
Patients with Diabetes Undergoing Cardiac Surgery-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 593-P
Abstract: Introduction and Objective: Preoperative carbohydrate loading is recommended in many surgery protocols. However, concerns remain about the impact carbohydrate loading may have on patients with diabetes. This study examines the impact of carbohydrate loading on outcomes of cardiac surgery patients with and without diabetes.Methods: This retrospective analysis included 125 cardiac surgery patients at a major Midwest hospital utilizing a maltodextrin-based carbohydrate drink as part of a quality improvement project. The protocol included consuming a drink containing 50g of a carbohydrate 2-4 hours prior to surgery. Patients’ blood glucose was measured preoperatively and at intervals of 45-120 minutes postoperatively. Blood glucose, 30-day readmissions, intensive care unit (ICU) and hospital length of stay were compared between patients with and without diabetes.Results: Patients had median age of 65 (IQR 56-72) years, 79% (n=99) were male, and 30.4% (n=38) had a diagnosis of diabetes. Median (IQR) preoperative glucose levels were 143 (112-159) mg/dL and 97 (90-160) mg/dL for patients with and without diabetes, respectively. The peak post-operative median glucose was 153 mg/dL and 137 mg/dL for patients with and without diabetes, respectively. Readmission rates were 7.9% in those with diabetes and 4.6% in those without diabetes (p=0.4). Total length of stay for ICU (in hours) and postoperative hospital stay (in days) was comparable between groups (65 vs. 64 hours, p=0.6; 5.1 vs. 6 days, p=0.4, respectively).Conclusion: Cardiac surgery patients with diabetes given maltodextrin-based carbohydrate loading drinks before surgery were able to maintain blood glucose within acceptable ranges and did not demonstrate a higher risk for 30-day readmissions or longer length of stay when compared to those without diabetes. These data add to the growing body of literature supporting the use of carbohydrate loading for cardiac surgical patients with diabetes.Disclosure K.W. Kerr: Employee; Abbott Nutrition. Stock/Shareholder; Abbott. B. Cassady: Employee; Abbott Nutrition. Stock/Shareholder; Abbott. K. Robinson: Employee; Abbott Nutrition. C. Johns: None.FundingThis research was funded in part by Abbott.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-593-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 594-P: Non-nutritive Sweetener Consumption in Youth with Type 1 Diabetes
-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 594-P
Abstract: Introduction and Objective: Diabetes guidelines advise non-nutritive sweeteners (NNS) can be consumed in moderation, within FDA acceptable dietary intake. Little has been reported about typical NNS use in youth with T1D. Here, we aimed to determine the prevalence and frequency of NNS-containing product use in youth with and without T1D.Methods: A cross-sectional electronic survey of youth aged 7-17 years with T1D of ≥ 6 months duration and age-and sex-matched healthy controls was performed. The survey assessed the frequency at which NNS- and sugar-containing products (soda, sports drinks, energy drinks, juice, tea, coffee, packets, snack foods, ice cream) were consumed. Differences between cohorts in ≥ 1/wk consumption of a given product were analyzed by Fisher’s Exact Test.Results: Sixty respondents with T1D and 60 controls were surveyed. Cohorts were 50% male, 50% aged 7-12, and 50% aged 13-17. Cohorts were similar for race/ethnicity, insurance type, and parental education. T1D youth were 3.5x more likely (95%CI: 1.5, 8.1) than controls (85% vs 62%) to consume any NNS-containing product and 6x more likely (95%CI: 2.78, 13.3) than controls (67% vs 25%) to drink NNS-soda ≥ 1/wk. Of consumers, 17% vs 2% drink NNS soda ≥ 1/day. T1D youth were 2.5x more likely (95% CI: 1.2, 5.2) and 3x more likely (95%CI: 1.1, 7.5) than controls to consume an NNS-electrolyte sports drink (45% vs 25%) or NNS snack food (yogurt, pudding; 28% vs 12%) ≥ 1/wk. Prevalence and frequency of other NNS-containing products were similar between cohorts. Conversely, controls were 4x (95%CI: 1.8,8.2) and 2.8x (95%CI: 1.3, 6.2) more likely to drink sugar-sweetened soda and sports drinks than T1D youth.Conclusion: There is high overall prevalence of NNS consumption in youth aged ≥ 7 yrs, but T1D youth were more likely to consume NNS-containing soda, sports drinks, and snack foods than healthy peers. Limitations include potential for inaccurate recall and difficulty assessing all NNS products. Studies are needed to quantify NNS and correlate to health outcomes.DisclosureA. Gladding: None. M. Edwards: None. S.M. Cabrera: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-594-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 595-P: Hypertension Management in Individuals Participating in
Carbohydrate-Restricted Nutrition Therapy-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 595-P
Abstract: Introduction and Objective: Blood pressure (BP) control is essential for individuals with type 2 diabetes, prediabetes, and obesity, especially those with hypertension (HTN), due to the increased risk of cardiovascular complications.Methods: Virta’s telemedicine clinic, using carbohydrate-restricted nutrition therapy with continuous remote care (CRNT-CRC), has shown effectiveness in improving glycemia and weight loss. This retrospective cohort study evaluates its impact on BP control over 6 months (6m) in individuals with hypertension (HTN) on BP medications at enrollment (E). Changes in systolic (SBP) and diastolic BP (DBP) from E to 6m were analyzed using linear mixed effects models. Random samples of 800 individuals, stratified by SBP at E (T-NBP, EBP, HTN1, HTN2), were included (Table 1).Results: Significant reductions were seen in SBP (-5.8 mmHg) and DBP (-3.3 mmHg) across the entire cohort (n=3200), with improvements in EBP, HTN1, and HTN2 groups (Table 1). The average number of BP medications prescribed also significantly decreased in the entire cohort and across all SBP categories. In the HTN1 group, 66.4% reduced BP, with 30.7% reverting to T-NBP, while in the HTN2 group, 71.5% lowered BP, and 16.9% transitioned to T-NBP.Conclusion: This study highlights CRNT-CRC as a promising approach for managing blood pressure, with significant reductions in SBP and DBP, particularly in HTN1 and HTN2.Disclosure S.J. Athinarayanan: Employee; Virta Health Corp. C.G.P. Roberts: Employee; Virta Health Corp. Stock/Shareholder; Virta Health Corp. G.K. Shetty: Employee; Virta Health Corp.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-595-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 596-P: Effects of a Very-Low-Calories Ketogenic Diet on Visceral Adipose
and Muscular Tissues in Comparison with a Mediterranean Dietary
Intervention-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 596-P
Abstract: Introduction and Objective: Compared to a low caloric Mediterranean diet (LC-med), Very Low Calories Ketogenic Diet (VLCKD) obtains weight loss with a greater caloric deficit and an almost complete carbohydrates restriction that markedly reduces insulin secretion. We compared the impact of VLCKD and LC-med on visceral fat (VAT) and muscle loss.Methods: We studied prospectively 116 subjects who underwent LC-med, and 53 who underwent VLCKD. VAT was measured by ultrasound, Arm Muscle Area (AMA) by anthropometry. HOMA index was derived from fasting insulin and glucose concentrations. LC-med and VLCKD groups were, respectively, 70% vs 72% females, median (IQR) age 55 (44-65) vs 51 (46, 57) yrs, BMI 32 (28.8-35.2) vs 35 (31.5-39.2) kg/m², waist circumference 104 cm (98-113) vs 112 cm (101-122) cm, VAT 5.4 (3.38-6.88) vs 5.64 (3.53-7.32) cm and AMA 56 (47,68) vs 62 (51-76) cm².Results: The duration of intervention was similar but VLCKD reached more rapidly the -5% and the -10% weight loss targets. Nonetheless, at - 5% and -10% wt loss, VLCKD and LC-med lost similar amounts of VAT (-28% vs -41% and -69 vs - 64%) and of AMA (-3% vs -8% and -11% and -7%) from basal. VLCKD showed greater reductions in insulin at -5% wt loss (-23% vs -0%, p<0,001), in glucose concentration at -10% wt loss (-16 vs -3% p=0,045) and in HOMA at -10% wt loss (p=0.025).Conclusion: VLCKD is associated with a more rapid body weight reduction and to lower insulin concentrations compared to LC-med. Nonetheless, both treatments are equally effective in reducing visceral adipose tissue and in preserving muscle mass.DisclosureG. Pozzi: None. A. Foppiani: None. F. Sileo: None. S. Bertoli: None. A. Battezzati: None.FundingNational Recovery and Resilience Plan (NRRP), Mission 4 Component 2 Investment 1.3 - Call for proposals No. 341 of 15 March 2022 of Italian Ministry of University and Research funded by the European Union NextGenerationEU; Award Number: Project code PE00000003, Concession Decree No. 1550 of 11 October 2022 adopted by the Italian Ministry of University and Research, CUP D93C22000890001, Project title ON Foods - Research and innovation network on food and nutrition Sustainability, Safety and Security Working ON Foods.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-596-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 597-P: Vegan Diet and Processed Foods—A Secondary Analysis of a
Randomized Clinical Trial-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 597-P
Abstract: Introduction and Objective: The consumption of some ultra-processed foods has been suggested to contribute to weight gain and a higher risk of type 2 diabetes. This secondary analysis assessed the associations between changes in processed food intake and weight loss in overweight adults.Methods: Participants (n=244) were randomly assigned to a vegan (n=122) or control group (n=122) for 16 weeks. Three-day dietary records were analyzed using the NOVA system, which categorizes foods from 1 to 4, based on degree of processing. A repeated measure ANOVA was used for statistical analysis.Results: The consumption of animal foods in categories 1-3 decreased in the vegan group, compared with the control group; effect sizes: -141 g/day (95% CI -173 to -109); p<0.001 for category 1; -3 g/day (95% CI -5 to -1); p=0.002 for category 2; and -23 g/day (95% CI -33 to -14); p<0.001 for category 3. Changes in foods of animal origin in categories 1-3 were positively associated with changes in body weight: r=+0.34; p<0.001 for category 1; r=+0.18; p=0.008 for category 2; and r=+0.17; p=0.01 for category 3.Conclusion: These findings suggest that minimizing the consumption of animal foods, regardless of their processing level, may be an effective weight-loss strategy in overweight adults.DisclosureH. Kahleova: None. T. Znayenko-Miller: None. N. Barnard: None.FundingThe Physicians Committee for Responsible Medicine
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-597-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 598-P: The Glycemic Impact of Whey Protein Ingestion in Adults with Type 1
Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 598-P
Abstract: Introduction and Objective: In people with T1D, ingestion of fast-absorbing protein potently stimulates glucagon secretion and can effectively increase endogenous glucose production. The study characterizes the glucose responses to whey protein ingestion in adults with T1D, which will inform future research into using whey protein to manage hypoglycemia.Methods: Nine adults (5F/4M) with T1D (Age: 50.22±16.9y; BMI: 26.2±4.1kg/cm2) on insulin pumps received 3 interventions in random order after an overnight fast: i) water (CON), ii) low-dose protein (LP; 0.25g/kg), iii) medium-dose protein (MP; 0.5g/kg); 3 participants received a 4th intervention iv) high-dose protein (HP; 0.75g/kg). On test days, insulin pumps were replaced with IV insulin. After 4h for subcutaneous insulin wash-out, insulin infusion rate was fixed, the test drink was given, and blood was sampled every 10min for 3h.Results: Peak increase in glucose and glucose AUC were similar for HP and MP, and were lowest for LP (Fig. 1A). Blood glucose decreased steadily for CON (Fig. 1A). Postprandial plasma glucagon was higher with increasing protein amount, while glucagon remained unchanged from baseline for CON (Fig. 1B).Conclusion: Whey protein ingestion stimulates glucagon secretion and raises blood glucose in a dose-dependent manner in people with T1D, suggesting a potential use of whey protein to manage hypoglycemia in this population.DisclosureG. Dao: None. S. Zhao: None. G.M. Kowalski: None. C. Bruce: None. C.E. Smart: None. D.P. Zaharieva: Research Support; Hemsley Charitable Trust. Speaker's Bureau; Dexcom, Inc. Research Support; Insulet Corporation, International Society for Pediatric and Adolescent Diabetes. J. Ngan: None. J. Apostolopoulos: None. Y.W. Kong: None. D.N. O'Neal: None. D. Morrison: None.FundingLeona M, and Harry B. Helmsley Charitable Trust (grant #2311-06395)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-598-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 599-P: Effects of Vitamin D Supplementation on Inflammatory and Metabolic
Biomarkers in Patients with Type 2 Diabetes—A Systematic Review-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 599-P
Abstract: Introduction and Objective: Recent studies indicate that vitamin D may exhibit significant anti-inflammatory and metabolic properties. Despite this potential, individuals with type 2 diabetes mellitus (T2DM) frequently present with low vitamin D levels, which are associated with increased inflammatory markers and impaired metabolic regulation. This work evaluates the impact of vitamin D supplementation compared to placebo/no supplementation on inflammatory biomarkers, glycemic parameters, and lipid profiles in adults with T2DM. This review aims to identify dose-response relationships and optimal supplementation regimens to improve clinical outcomes in this population.Methods: Following PRISMA guidelines, this systematic review analyzed 24 randomized controlled trials and clinical studies articles sourced from PUBMED. Studies included adults with T2DM who received vitamin D supplementation, assessing changes in inflammatory biomarkers, glycemic parameters, and lipid profiles. Exclusion criteria included studies on type 1 or gestational diabetes, or observational designs.Results: Vitamin D supplementation significantly reduced IL-6 and TNF-α levels, particularly at doses ≥4000 IU/day or with prolonged use (≥6 months). Modest improvements in HbA1c and HOMA-IR were more evident in those with severe deficiency or combined with lifestyle interventions. Effects on lipid profiles were inconsistent, with slight increases in HDL, reductions in triglycerides, and no changes in LDL or total cholesterol. High-dose supplementation (≥40,000 IU/week) improved neuropathy severity and microcirculation.Conclusion: Vitamin D supplementation shows promise in reducing inflammation and modestly improving glycemic control in T2DM, particularly with higher doses and longer durations. Effects on lipid profiles and microvascular complications remain inconsistent, highlighting the need for further research.DisclosureA. Reis Melo da Costa: None. R.R. Freitas: None. J.G. Lima da Silva: None.
PubDate: Fri, 13 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-599-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 600-P: The Healthy Gut Diet for Preventing Gestational Diabetes Improves
Dietary Intake and Diet Quality-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 600-P
Abstract: Introduction and Objective: Emerging evidence suggests that gut microbiota influences gestational diabetes mellitus (GDM) development. Dietary interventions to modulate gut microbiota may help prevent GDM. The Healthy Gut Diet for preventing GDM Study aimed to achieve this in pregnant women with one or more risk factors. Here, we share dietary intake and diet quality results.Methods: This pilot single-blind, two-arm randomised control trial in Queensland, Australia, compared dietary intervention with usual care. Women in the intervention group received dietetic education to increase intake of foods improving gut microbiota health. Baseline and 36-week dietary intakes were assessed using the Australian Eating Survey and a Modified Short Dietary Questionnaire.Results: We randomised 129 women between 9- and 18-weeks’ gestation. Baseline characteristics and dietary intakes showed no significant differences between groups (Table 1). However, dietary quality significantly improved in the intervention group, with higher vegetable, meat alternatives, fermented, and prebiotic food intake than controls.Conclusion: The HGD study successfully improved diet quality, diversity of plant-based foods and fermented and prebiotic food intakes in the intervention group compared with the control group at thirty-six-week gestation.DisclosureH.M. O'Connor: None. S.J. de Jersey: None. S. Wilkinson: None. N.J. Meloncelli: None.FundingOffice of Research and Innovation
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-600-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 601-P: Diabetes Self-Efficacy—Longitudinal Relationships with Diabetes
Overall Self-Management, Medication Adherence, Diabetes Distress, and
Glycemic Control in Adults with Type 2 Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 601-P
Abstract: Introduction and Objective: Self-efficacy and diabetes distress are inextricably linked to coping with diabetes. The role of diabetes distress in the relationship between diabetes self-efficacy and glycemic control in T2DM over time is understudied. The objective of this study was to evaluate the longitudinal associations of self-efficacy with overall diabetes self-management, medication adherence, diabetes distress, and glycemic control.Methods: Within the context of a randomized controlled trial comparing telephonic self-management support to enhanced standard of care among 812 predominantly socioeconomically disadvantaged ethnic minority adults with suboptimal control of T2DM (HbA1c >7.5%), we investigated between-group differences in self-efficacy and examined self-management, medication adherence, and diabetes distress, self-reported on validated scales at 6-months, as potential mediators between baseline diabetes self-efficacy and HbA1c at 12-months using multiple-linear regression.Results: Participants (M[SD] age = 59.2 [10.8], M[SD] HbA1c = 9.3 [1.8], 57% females, and 86% Hispanic/Latino) were mostly less educated (75% less than grade 12 or GED ). An increase of 4.19 points for self-efficacy relative to the baseline in the intervention group was significant (95% CI = -6.08, -2.30; p <.001 ) at 12-month follow-up. There was a significant indirect effect of baseline self-efficacy on lowered 12-month HbA1c through increased medication adherence at 6-month follow-up (ab = -0.005, 95% CI = -0.007, -0.003; p <.001). Results did not support overall self-management or diabetes distress as mediators of self-efficacy.Conclusion: These associations are consistent with Bandura’s self-efficacy theory and suggest that diabetes self-efficacy is responsive to intervention and predictive of glycemic outcomes among disadvantaged adults with suboptimal control of T2DM.DisclosureR. Fang: None. C. Schechter: None. E.A. Walker: None. J.S. Gonzalez: None.FundingThis study was supported by grant R 18 DK098742 from the National Institutes of Health. This study was also partially supported by the Einstein Mount Sinai Diabetes Research Center (P30 DK020541) and the New York Regional Center for Diabetes Translation Research (P30 DK111022). Dr. Gonzalez is supported by grants R01 DK104845, R01 DK121298, R01 DK121896 and R18 DK098742 from the National Institutes of Health.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-601-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 602-P: Extent and Impact of Provider Engagement with EHR-Based Diabetes
Distress (DD) Screening-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 602-P
Abstract: Introduction and Objective: ADA Standards of Care recommend screening for and addressing elevated DD, yet implementation is challenging. We built a validated, 8-item screener (T1-DDAS) into EPIC in the online e-CheckIn process for adults with T1D. A positive screen for DD (>= 2.0) generates a Best Practice Advisory (BPA) notification during the clinical encounter with suggested language to discuss elevated DD and refer to a research study for evidence-based treatment. Our objective was to evaluate the extent and impact of provider engagement with the BPA.Methods: We measured provider BPA engagement for 8 weeks (10/28-12/20/24; goal = 50% engagement across all patients with DD) and subsequent patient interest in the study. Patients were contacted up to three times by research staff to enroll in the study for treatment; failure to contact was classified as ‘No response’. Those contacted were coded as ‘Interested’ vs ‘Not interested’.Results: Of N=84 encounters, 48% (n=40) of BPAs were addressed to discuss elevated DD. Provider discussion about elevated DD resulted in 69% increased interest in the study and decreased the no-response rate in recruitment efforts (Figure).Conclusion: Provider engagement with the BPA (signaling DD and its treatment was discussed in the clinic setting) increased responsiveness to subsequent contact by the research team and study enrollment among adults with T1D and elevated DD.DisclosureA. Kahkoska: None. G. Ercolino: None. L.A. Young: Research Support; Novo Nordisk, Rhythm Pharmaceuticals, Inc, Lilly Diabetes, vTv Therapeutics, Carmot Therapeutics, Inc, Insulet Corporation, Corcept Therapeutics, Diasome Pharmaceuticals, MannKind Corporation, Fractyl Health, Inc. A. Fruik: None.FundingAmerican Diabetes Association (12-22-ACE-18)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-602-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 603-P: Diabetes Distress Is Associated with Poor Glycemic Control after
Islet Autotransplantation-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 603-P
Abstract: Introduction and Objective: Diabetes distress (DD), characterized by the emotional and psychological challenge of managing diabetes, has been studied in type 1 and 2 diabetes, but data are limited following total pancreatectomy with islet autotransplantation (TPIAT). This study evaluated DDS after TPIAT, and its association with diabetes outcomes.Methods: DD scale (DDS) was assessed in 124 patients >5 years post-TPIAT (median 9.5 years post-TPIAT, 73% female, mean age 47 years). Association of DDS with time in range (TIR) by CGM, insulin use, islet graft function (defined by mixed meal tolerance testing), and acute diabetes complications was evaluated using univariable and adjusted models, accounting for age, sex, race/ethnicity, socioeconomic status, and time since TPIAT.Results: Ninety-two percent of participants had graft function, 31% were insulin-independent, mean A1C was 6.6%, 57% had CGM TIR>70%, and 19% had TIR<50%. Moderate distress (DDS≥2) was observed in 27%, with the highest subscale scores in emotional burden and regimen distress. Insulin dependence was associated with higher DDS (1.78 vs1.52, p=0.043) with greater emotional burden score (2.01vs1.52, p=0.008). TIR<50% was linked to higher DDS (2.00 vs1.35, p=0.021). A history of DKA and/or severe hypoglycemia was significantly associated with higher DDS. All associations persisted after adjusting for confounders. Graft function showed a non-significant trend towards reduced DDS.Conclusion: Insulin dependence, inadequate glycemic control, and acute diabetes complications may contribute to DD after TPIAT. Addressing these factors is essential for improving outcomes in this unique population. Future studies could also assess whether DD promotes diabetes complications.DisclosureA.A. Ishola: None. A. Eaton: None. S. Kim: None. M. Basina: None. G. Beilman: None. M. Bellin: Advisory Panel; Vertex Pharmaceuticals Incorporated. Research Support; ViaCyte, Inc. Advisory Panel; Novo Nordisk. Consultant; Soleno. Research Support; Dexcom, Inc. Advisory Panel; bridgebio.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-603-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 604-P: Parent Sleep Quality and Diabetes Distress in Families of Youth
with Type 1 Diabetes (T1D)-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 604-P
Abstract: Introduction and Objective: Many parents of youth with T1D report poor sleep quality due to increased nighttime awakenings, and some also experience increased diabetes distress related to nighttime caregiving. Research has previously examined associations between parent sleep quality, diabetes distress, and youth HbA1c. Here, we used continuous glucose monitoring (CGM) data to examine associations between youth’s nighttime glucose levels and their parents’ sleep quality and diabetes distress.Methods: In 123 parents, we measured sleep quality using the Pittsburg Sleep Quality Scale (PSQS) and diabetes distress using the Parent Problem Areas in Diabetes (PAID-PR). Youth provided 14 days of personal CGM data. We conducted regression models and mean comparisons.Results: Most parents were mothers (89%) with a mean age of 41.8 + 6.5 yrs. Youth were 49% female with a mean age of 13.4 + 2.6 yrs and a mean HbA1c of 7.8 + 1.4. Parents’ mean PSQS global score was 7.6 + 4.0, with 67% scoring above the cut-off for elevated sleep disturbances. Their mean PAID-PR total score was 31.9 + 16.3. Model results revealed that youth’s nighttime glucose SD was a significant predictor of greater parent diabetes distress (β= 0.22, p< 0.05) and lower sleep quality (β= 0.20, p< 0.05). Further, parents above the cut-off for elevated sleep disturbances reported greater diabetes distress (M= 37.5) than parents below the cut-off (M= 22.3), p<.05. There were no differences between PSQS and PAID-PR scores for parents of children on an insulin pump versus injections.Conclusion: Parents of youth with T1D may report poorer sleep quality and higher diabetes distress if their child experiences wide fluctuations in their nighttime glucose levels. Future research should examine how nighttime caregiving (e.g., glucose monitoring and treating out-of-range glucose) interact with parent sleep disturbances and diabetes distress to determine the appropriate treatment options for families (i.e., diabetes education or stress management).DisclosureA. Monzon: None. M. Campbell: None. R. McDonough: Speaker's Bureau; Sanofi-Aventis U.S. S.R. Patton: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-604-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 605-P: Diabetes Distress Is Associated with Higher Risk of Hypoglycemia in
Older Adults with Type 1 Diabetes in the AIDE Trial-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 605-P
Abstract: Introduction and Objective: The prevalence of type 1 diabetes (T1D) in older adults has increased over the last few decades. Many aspects of self-care may be impacted by age related changes, comorbidities, and risk of hypoglycemia. Yet, few studies have characterized the emotional burden of diabetes distress (DD) in this age group and its clinical impacts, including association with glycemic control.Methods: We conducted a post-hoc analysis of baseline data from a randomized, multicenter trial of 82 older adults (≥65 yrs). DD was measured by T1-DDS questionnaires that includes overall score and 7 subscales. Scores were dichotomized into mild or no DD (0-1.9) vs. moderate to severe DD (≥2). All participants used study continuous glucose monitor.Results: The baseline characteristics of 82 participants are demonstrated in table. A total of 23 participants (28%) had moderate to severe overall DD; 30 (36.5%) had moderate to severe hypoglycemia distress (subscale). Older adults with elevated DD spent more time <70 mg/dL as compared to those with mild or no DD.Conclusion: The prevalence of moderate to severe DD in older adults was lower than what has been reported for younger adults with T1D (42%). Though association between DD and hyperglycemia (specifically HbA1c) has been observed in younger population, these data suggest that DD may be associated with increased hypoglycemia and glycemic variability in older adults.DisclosureS. Rizvi: None. R.J. Henderson: None. L. Kanapka: None. A. Kahkoska: None. C. Reid: None. D. Desjardins: None. N. Chaytor: None. R.S. Weinstock: Research Support; Amgen Inc, Eli Lilly and Company, Tandem Diabetes Care, Inc, Diasome Pharmaceuticals, Insulet Corporation, MannKind Corporation, Dexcom, Inc. M.R. Rickels: Consultant; Vertex Pharmaceuticals Incorporated, Sernova, Corp. Research Support; Dompé, Tandem Diabetes Care, Inc. Consultant; Novo Nordisk. R.E. Pratley: Consultant; AbbVie Inc. Stock/Shareholder; Altanine, Inc. Consultant; Amgen Inc, AstraZeneca. Other Relationship; Bayer AG, Bayer Pharmaceuticals, Inc, Biomea Fusion. Consultant; Boehringer-Ingelheim. Other Relationship; Carmot Therapeutics, Inc, Corcept Therapeutics, Dompé, Eli Lilly and Company, Endogenex. Consultant; Endogenex. Other Relationship; Fractyl Health, Inc., Gasherbrum Bio, Inc. Consultant; Genprex, Getz Pharma, Hanmi Pharm. Co., Ltd, Intas Pharmaceuticals Ltd, Lexicon Pharmaceuticals, Inc, Lilly USA LLC. Speaker's Bureau; Lilly USA LLC. Other Relationship; Metavention, Novo Nordisk, Novo Nordisk. Speaker's Bureau; Novo Nordisk. Other Relationship; Pfizer Inc, Poxel SA. Consultant; Regeneron Pharmaceuticals. Other Relationship; Sanofi. Consultant; Scholar Rock. Other Relationship; Sun Pharmaceutical Industries Ltd. Y.C. Kudva: Advisory Panel; Novo Nordisk, Vertex Pharmaceuticals Incorporated, Tandem Diabetes Care, Inc. Research Support; Dexcom, Inc., Insulet Corporation.FundingR01DK122603
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-605-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 606-P: Addressing Diabetes Distress in Clinical Practice—Provider
Feedback and Resource Gaps following Screening Implementation-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 606-P
Abstract: Introduction and Objective: While diabetes-related distress is common, healthcare systems may lack resources for adequately addressing this aspect of diabetes care. As part of a quality improvement initiative, we surveyed providers after implementation of annual diabetes distress (DD) screening for persons with Type 1 diabetes (PwT1D) in an academic center with the goal of better understanding how to best address DD in clinical practice.Methods: PwT1D were assigned the Type 1 Diabetes Distress Assessment System (T1DDAS) core scale prior to their adult endocrinology visits with results visible to providers in the electronic medical record during the clinical encounter. Providers were surveyed 1-year after screening implementation.Results: Between December 2023-2024, 2,081 T1DDAS questionnaires were completed by 1,852 unique patients out of 2,452 eligible patients (75.5%). The average score was 1.84±0.88 with 22.9% (n=477) reporting moderate (2.0-2.9) and 12.9% (n=268) reporting high (>3.0) distress. Sixteen of 42 providers responded (38%) to the post-implementation survey. While 15 (94%) agreed that DD is an important to address, only 11 (69%) felt confident in their ability to identify DD, and 3 (19%) were satisfied with the resources currently available to address DD. The most common barriers were limited clinic time (56%), inadequate resources (56%), and insufficient training (31%). Providers identified social work referrals, an embedded psychologist, and handouts with local mental health resources as the most helpful supports for patients with DD.Conclusion: Over one-third of PwT1D in our clinic reported moderate to high diabetes distress (DD), emphasizing the need for strategies to address elevated DD scores. Providers recognize the importance of addressing DD but express dissatisfaction with available resources. These findings will guide future Plan-Do-Check-Act cycles to improve support for PwT1D experiencing DD.DisclosureJ.J. Iyengar: None. H. Centola: None. D. Broome: Research Support; Fractyl Health, Inc., Sanofi, T1D Exchange, Rhythm Pharmaceuticals, Inc, Novo Nordisk. K.R. Mizokami-Stout: None. L. Ang: None. J. Lee: None. J. Wyckoff: None. B. Mezuk: None. S. Soleimanpour: Research Support; Ono Pharmaceutical Co., Ltd. J.M. Lee: Advisory Panel; GoodRx.FundingMichigan Nutrition Obesity Research Center (P30DK089503), Michigan Diabetes Research Center (P30DK020572), Michigan Center for Diabetes Translational Research (P30DK092926), the Elizabeth Weiser Caswell Diabetes Institute, and the Breakthrough T1D Center of Excellence at the University of Michigan.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-606-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 607-P: The Effect of a Cognitive Behavioral Therapy Intervention on
Quality of Life in Young Adults with Type 1 Diabetes—A Secondary
Analysis-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 607-P
Abstract: Introduction and Objective: Despite advancements in diabetes technology, such as continuous glucose monitoring (CGM) and automated insulin pumps, hypoglycemia remains a limiting factor for individuals with type 1 diabetes (T1D), often leading to fear of hypoglycemia (FOH) and reduced quality of life (QoL). This secondary analysis examined the effect of a cognitive behavioral therapy (CBT) intervention, designed to reduce FOH, on QoL in young adults with T1D.Methods: Fifty young adults (18 to 35 years) with T1D ≥1 year, in endocrinology care, who screened positive for FOH, and had previously attended a basic diabetes education program were recruited to the study. Participants were randomized to an 8-week CBT intervention or an attention control (diabetes education). Exclusion criteria included pregnancy, breastfeeding, and any chronic condition or medications (excluding insulin) that could affect diabetes self-management or glucose control. All participants wore unblinded CGM devices. QoL was measured with the 46-item, 5-point Likert scale (1=best QoL, 5=worst), encompassing satisfaction (general satisfaction with diabetes management), impact (effects on daily life and functioning), and worry (fear of complications and health outcomes). Descriptive statistics and generalized estimation equation were used to assess CBT’s impact on QoL.Results: Participants receiving the CBT intervention experienced a statistically significant improvement in overall QoL (β = -14.048, p = 0.020), compared to controls. Specifically, the CBT intervention demonstrated a significant improvement in QoL satisfaction and impact subscales β = -7.122, p = 0.018 and β = -5.568, p = 0.015 respectively.Conclusion: The CBT intervention resulted in improvement in overall QoL. The most substantial gains were observed in satisfaction and impact, highlighting immediate and tangible experiences.DisclosureE. Peprah Osei: None. A.H. Saleh: None. C.G. Park: None. P. Martyn-Nemeth: Stock/Shareholder; Pfizer Inc.FundingNIH (R21DK116146)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-607-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 608-P: The Association of Perceived Discrimination with Diabetes
Management in Youth and Young Adults with Youth-Onset Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 608-P
Abstract: Introduction and Objective: Discrimination can lower self-esteem and undermine self-care and health seeking behaviors, but its impact on young people with diabetes is poorly studied. We assessed if perceived discrimination was associated with diabetes management among youth and young adults (YYA) with youth-onset type 1 (T1D) and type 2 diabetes (T2D).Methods: We conducted a cross-sectional analysis of the multicenter SEARCH Food Security Cohort (2018-2023) among 782 YYA with youth-onset T1D and 110 with T2D (age range 11-37 years). The 10-item Everyday Discrimination Scale, hemoglobin A1c (HbA1c), and self-reported diabetes management were analyzed using logistic regression models adjusted for age, sex, race/ethnicity, study site, education, income, health insurance, food insecurity, diabetes duration, insulin regimen, and continuous glucose monitor use.Results: Overall, 57.7% of YYA (T1D 59.0%, T2D 49.1%) reported experiencing discrimination. Of YYA who reported discrimination, 41.8% (T1D 40.6%, T2D 51.9%) experienced it a few times a year or more. Among YYA with T1D who reported discrimination, the most mentioned reasons were gender (36%), age (33%), weight (24%) and race/ethnicity (21%); among YYA with T2D they were race/ethnicity (59%), weight (54%), and education or income (33%). Each one-point increase in the mean discrimination summary score was associated with greater odds of elevated HbA1c ≥ 7% (OR=1.9, 95% CI = 1.3-2.8), missing diabetes medication(s) (OR=1.6, 95% CI = 1.2-2.0) and severe hypoglycemia (OR=1.5, 95% CI = 1.1-1.9) in YYA with T1D. No associations were found in YYA with T2D.Conclusion: Most YYA with diabetes reported experiencing some form of discrimination but the reasons differed by diabetes type. Among participants with T1D, experiencing more discrimination was associated with poorer diabetes management and higher HbA1c levels. The reasons for the differences between diabetes types need to be further explored.DisclosureE.F. Julceus: None. A.D. Brown: None. J.A. Mendoza: None. F. Malik: None. D.M. Krobath: None. A. Bellatorre: None. T.A. Bekelman: None. L. Knight: None. C. Pihoker: None. A.D. Liese: None.FundingNational Institute of Diabetes and Digestive and Kidney Diseases (R01DK117461); National Institute of General Medical Sciences (T32-GM081740)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-608-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 609-P: Does Patient Activation Correlate with Lifestyle Change Program
Study Completion in Patients with a History of Gestational Diabetes
Mellitus'-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 609-P
Abstract: Introduction and Objective: Women with a history of gestational diabetes mellitus (GDM) face a high risk of type 2 diabetes, making lifestyle change for prevention essential. Cost and accessibility are barriers to lifestyle change programs. This study evaluated the relationship between patient activation and engagement with diabetes prevention strategies in women with a history of GDM.Methods: Women with a history of GDM were offered free participation in one of seven evidence-based lifestyle change programs. Programs varied in delivery mode, duration, time of day, and childcare availability. Demographic data, BMI, HbA1c, and patient activation (PAM survey) scores were collected at baseline and 12 months. Study completion was defined as attending study visits through the 12-month visit. Non-parametric tests assessed correlations between PAM scores, study completion and changes in BMI and HbA1c.Results: Ninety-two women enrolled, with a median age of 35 years and median BMI of 32.6 kg/m². Most were White (55.4%) and had high patient activation levels (80.4%) at baseline. By 12 months, the dropout rate was 26.1%. Study discontinuation did not vary by baseline PAM score (p=0.290). Among completers, 76.1% retained high activation levels. Median changes in BMI (0%; IQR: -3.1 to 4.0) and HbA1c (1.9%; IQR: -1.9 to 4.7) were not associated with baseline activation level (BMI p=0.707; HbA1c p=0.601).Conclusion: Women with history of GDM may have high activation levels for diabetes prevention. However, support for continued lifestyle change is needed, as patient activation scores alone are not sufficient for predicting program engagement. Future interventions may require additional strategies, such as targeted incentives or enhanced support, to sustain participation in lifestyle programs.DisclosureN. El Yaman: None. J.M. Pike: None. K. Haberlin-Pittz: None. L.A. Machuca: None. B.M. McKinney: None. T.S. Hannon: Research Support; Eli Lilly and Company, Novo Nordisk.FundingIndiana University Precision Health Initiative
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-609-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 610-P: Prevalence of Loneliness and Lack of Social and Emotional Support
among U.S. Adults with Diabetes, 2023-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 610-P
Abstract: Introduction and Objective: Reducing loneliness and lack of social and emotional support (LSES) among adults with diabetes (DM) can improve diabetes management and health outcomes. Considering the distinct pathophysiology and risk factor profile of each diabetes type, we explored the prevalence of loneliness and LSES among adults with type 1 or type 2 DM using 2023 Behavioral Risk Factor Surveillance System.Methods: Our study included 17,054 respondents with DM aged ≥18 years from 20 US states providing loneliness and LSES data. Loneliness was defined as always/usually/sometimes feeling lonely. LSES was defined as sometimes/rarely/never getting needed social and emotional support. Type 1 DM was defined as physician-diagnosed type 1 DM and currently using insulin; others were considered having type 2 DM. All data were self-reported. Crude prevalence and age-, sex-, and race and ethnicity-adjusted prevalence ratio (aPR) were estimated using logistic regression.Results: The prevalence of loneliness and LSES (%, 95% CI) were 39.0 (34.2-43.7) and 28.8 (24.3-33.3) for type 1 DM and 32.3 (30.7-33.9) and 24.9 (23.3-26.6) for type 2 DM, respectively. Compared to adults without DM, the aPR (95% CI) of loneliness and LSES were 1.32 (1.17-1.49) and 1.33 (1.14-1.56) for adults with type 1 DM and 1.22 (1.16-1.28) and 1.25 (1.16-1.34) for adults with type 2 DM, respectively. We found no significant difference in the prevalence of loneliness and LSES by diabetes type (all P values >0.05). Among adults with either type 1 or type 2 DM, those aged <65 years, Hispanic or Latino ethnicity, and those who had never participated in diabetes self-management education and support (DSMES) services had a higher prevalence of loneliness and LSES (all P values <0.05.Conclusion: More than a third of adults with type 1 or type 2 diabetes report loneliness and a quarter report LSES. Addressing loneliness and LSES among people with diabetes may improve diabetes self-management skills and enhance social connectedness.DisclosureY.J. Cheng: None. G. Zhao: None. R. Li: None. C.S. Holliday: None. R. Montierth: None. B. Rodriguez: None. K.M. Bullard: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-610-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 611-P: Prevalence of Substance Use, Substance Use Disorders, and Substance
Use Treatment among U.S. Adults with Diagnosed Diabetes, 2021–2022-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 611-P
Abstract: Introduction and Objective: Substance use (SU) and SU disorders (SUDs) adversely affect diabetes management and increase the risk of diagnosed diabetes (DM) complications. We estimated disparities in the prevalence of SU, SUDs, and SUD treatment among those with SUDs (SUDT) among US adults with DM by sociodemographic characteristics.Methods: We used 2021-2022 National Survey on Drug Use and Health self-reported data from 6,816 adults aged ≥18 years with DM. SU was defined as heavy alcohol use or binge drinking in the last 30 days or, in the past year, using any cannabis, cocaine in any form, heroin, hallucinogens, inhalants, or methamphetamine, or misusing prescription medications. A diagnosis of SUD was based on meeting criteria for use or misuse of any of these substances. Receipt of any SUDT (2022 only) was assessed among adults with any SUDs. We estimated crude prevalence (cPrev) for each outcome and adjusted prevalence ratios (aPR) using logistic regression adjusted for age, sex, race and ethnicity, education, self-rated health, family income, insurance coverage, and rurality.Results: Among those with DM, cPrev estimates (%, 95% CI) were 24.6 (23.1-26.2) for SU and 8.7 (7.8-9.8) for SUDs. Among those aged ≥65 years, cPrev estimates (%) were 14.6 (12.3-17.4) for SU, 23.3 (15.6-34.8) for SUDs, and 4.2 (1.3-13.0) for SUDT. Compared with those aged ≥65 years, aPRs (95% CI) of SU, SUDs, and SUDT were 3.4 (2.7-4.3), 2.0 (1.3-3.1), and 10.2 (2.3-46.0) for adults aged 18-34 years, and 3.0 (2.4-3.6), 1.6 (1.0-2.4), and 7.3 (1.5-36.3) for adults aged 35-49 years. Men, non-Hispanic (NH) White adults (vs. NH Asian adults), those in fair/poor health (vs. good), and those living in large metro areas (vs. nonmetro) had higher prevalence of SU.Conclusion: Among adults with DM, SU and SUDs, are common. SUDT among those with SUDs was low, especially among older adults. Addressing availability and accessibility of SUDT may improve health outcomes in adults with DM.DisclosureY.J. Cheng: None. I. Zaganjor: None. J. Ko: None. R. Li: None. C.S. Holliday: None. K.M. Bullard: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-611-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 612-P: Strategies to Increase Inclusion in Pediatric Type 1 Diabetes
Psychosocial Intervention Studies-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 612-P
Abstract: Introduction and Objective: Evidence-based pediatric psychosocial type 1 diabetes (T1D) care improves child (glycemic levels, diabetes distress) and family (conflict) health outcomes. However, few intervention studies have included substantial proportions of African American or low income families of any race. This community-engaged study aimed to identify strategies to increase engagement of these families in T1D psychosocial intervention research.Methods: Adolescents with T1D (n=10; MAge=14.8±1.6 years, Female=60%, African American=60%, White=30%, >1 race=10%, LatinX=0%, public/no insurance=70%) and their caregivers (n=10; MAge=44.8±6.2 years, Female=90%, African American=60%, White=30%, Asian=10%, LatinX=0%) were recruited from one mid-Atlantic children’s hospital. Four cohorts of adolescent-caregiver dyads completed a series of two focus groups (2 to 3 dyads per cohort) guided by semi-structured interview guides. Each focus group was recorded and analyzed using a rapid analysis approach.Results: Most teens and caregivers expressed interest in participating in T1D psychosocial intervention research and also identified similar multi-level strategies to increase participation, such as those related to logistics (evening, virtual visits), those specific to the intervention (length, target), who should invite participation (T1D providers if nonjudgemental), when/where should families be invited (in-clinic, evening phone call or text), and level of trust in researcher(s). Ways to improve researcher trustworthiness were noteworthy (share own expertise/reason to do research/reason for eligibility criteria, honest, genuine, personable).Conclusion: This foundational knowledge is critical to advancing inclusive T1D research and has potential to improve equity in the psychosocial intervention evidence base.DisclosureJ. Price: None. C. Yang: None. J.A. Deatrick: None. C. Thomas: None. I. Rogers: None. M. Rogers: None. L. Rogers: None. A. Byrne: None. O. Byrne: None. M. DeEmedio: None. A. Gannon: None. C.M. Cammarata: None. A. Butler: None. K. Shoe: None. A. Kazak: None.FundingNational Institute of General Medical Sciences (P20GM144270)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-612-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 613-P: Development of Implementation Strategies for a Pediatric Type 1
Diabetes Behavioral Intervention-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 613-P
Abstract: Introduction and Objective: Behavioral Family Systems Therapy for Diabetes (BFST-D), a family-based pediatric psychosocial type 1 diabetes (T1D) intervention, improves glycemic levels and family conflict. A brief group-based version of bBFST-D has evidence of effectiveness. However, few families receive this care. Using evidence-based quality improvement (EBQI), the current study aimed to develop and tailor a toolkit of implementation strategies for bBFST-D.Methods: Following steps of EBQI, a Family Advisory Board (FAB) and Healthcare Professionals Advisory Board (HPAB) from one free-standing children’s hospital provided iterative feedback to (1) prioritize barriers, (2) select, specify, and tailor implementation strategies, and (3) create a toolkit. The FAB included 4 adolescents with T1D (3 males, Mag e= 14.00 ± 0.82, 75% African American, 100% Non-Hispanic, MHbA1c = 11.00 ± 2.25, 50% Medicaid) and their caregivers (3 mothers, 1 father, Mage = 43.75 ± 2.22, 75% African American, 100% Non-Hispanic). The HPAB included 5 T1D professionals (Mage = 47.20 ± 11.78; 3 females, 100% White, Non-Hispanic). Three FAB and five HPAB virtual meetings were held.Results: The FAB selected and tailored strategies to address key barriers to engaging in bBFST-D, such as timing (evening), format (telehealth), and medical provider education (communication with families). The HPAB identified key malleable barriers to bBFST-D implementation (medical provider efficacy in how to refer, psychosocial provider knowledge of bBFST-D), provided feedback on the acceptability, feasibility, and effectiveness of implementation strategies (education, champions, facilitation, audit and feedback), and then on an implementation toolkit.Conclusion: The process of using EBQI to engage diverse community partners for tailoring implementation strategies optimized the likelihood that the toolkit will effectively increase the reach of bBFST-D and improve the health of youth with T1D and their families.DisclosureJ. Price: None. C. Yang: None. J.A. Deatrick: None. C. Thomas: None. G. Curran: None. A. Kazak: None.FundingNational Institute of Diabetes and Digestive and Kidney Diseases (5K23DK125666)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-613-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 614-P: Hyperglycemia and Glucose Fluctuations Predict Worse Sleep Quality
Which Then Predicts Elevated Depressive Symptoms and Diabetes Distress in
People with Type 1 and Type 2 Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 614-P
Abstract: Introduction and Objective: The aim was to analyze which glycemic parameters predict sleep quality and whether sleep quality predicts psychosocial well-being.Methods: People with type 1 and type 2 diabetes rated their sleep quality daily for 17 days (range: 0-10) on a ecological momentary assessment (EMA) app. CGM was used to calculate %<70 mg/dl (TBR), %>180 mg/dl (TAR) and coefficient of variation (CV). At the 3-month follow-up, elevated depressive symptoms were assessed via the Center for Epidemiology Studies - Depression (CES-D; Cut-off: 22), and elevated distress via the Problem Areas in Diabetes (PAID) scale (Cut-off: 40). Glycemic predictors of next-night sleep quality were analyzed with multilevel regression, controlled for age, sex, diabetes type, BMI. Logistic regression analyses were calculated with elevated CES-D and PAID as dependent variables, respectively, and sleep quality as independent variable, controlled for age, sex, BMI, diabetes type and respective baseline value.Results: Data from 390 participants were analyzed (50.6% type 1 diabetes). During the EMA phase, higher TAR (-0.35; p=0.03) and higher glucose CV (-0.84; p=0.04) on the previous day significantly predicted worse sleep quality. Each point increase in mean sleep quality was associated with a 35% reduced risk of having elevated depressive symptoms at follow-up (OR=0.65, p<.001) and a 31% reduced risk of having elevated diabetes distress (OR=0.69, p<.001). Increased fluctuations in sleep quality were also predictive of elevated depressive symptoms (10% increase: OR=1.23, p=.004) and distress (OR=1.21, p=.009).Conclusion: Hyperglycemic values and fluctuations were predictive of sleep quality. Mean sleep quality and fluctuations of sleep quality were indicative of an elevated risk for worse psychosocial well-being. This highlights the importance of sleep quality for people with type 1 and type 2 diabetes.Disclosure D. Ehrmann: Advisory Panel; Dexcom, Inc. Speaker's Bureau; Dexcom, Inc. Consultant; Roche Diabetes Care. Speaker's Bureau; Roche Diabetes Care, Sanofi, Eli Lilly and Company, Boehringer-Ingelheim. A.J. Schmitt: None. L.Y. Klinker: None. B. Kulzer: Advisory Panel; Abbott, Dexcom, Inc. Consultant; Becton, Dickinson and Company. Other Relationship; Insulet Corporation, AstraZeneca. Board Member; Sanofi-Aventis Deutschland GmbH. Advisory Panel; Roche Diabetes Care, Novo Nordisk. N. Hermanns: Advisory Panel; Dexcom, Inc., Abbott Diagnostics. Speaker's Bureau; Abbott Diagnostics. Advisory Panel; Roche Diabetes Care.FundingGerman Center for Diabetes Research (DZD) (FKZ 82DZD01102, FKZ 82DZD11E03)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-614-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 615-P: Bias in Medical Students’ Perceived Understanding of Type 1 and
Type 2 Diabetes—A Cross-Sectional Survey Study-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 615-P
Abstract: Introduction and Objective: The causes and management of diabetes are widely misunderstood. The prevailing narrative misrepresents diabetes as a self-inflicted condition, attributed to laziness, gluttony, and irresponsibility. While many health care professionals are supportive, evidence suggests biases exist in diabetes care. The purpose of this study was to examine if these biases develop early in medical training.Methods: We conducted an anonymous cross-sectional survey comparing medical students’ knowledge and attitudes toward type 1 and type 2 diabetes, using Wilcoxon signed rank tests and Chi-Square Tests to assess differences by year in medical school. We analyzed short answer responses via content and thematic analyses.Results: A total of 267 medical students (mean age=25.4±2.7, 71.9% women, 32.6% 2nd-year) completed the survey. Qualitatively, participants understood that type 1 diabetes is caused by autoimmune destruction of beta cells resulting in insufficient insulin production, whereas type 2 diabetes results from a complex interplay of genetic, environmental, and lifestyle factors. Despite understanding the causes of type 1 and type 2 diabetes, participants differed in their attitudes towards the conditions. Participants were more likely to agree that people with type 1 diabetes would follow medical advice (Z= -7.349, p<.001), be truthful during medical visits (Z= -7.155, p<.001), and commit to bettering their condition (Z= -6.295, p<.001) compared to people with type 2 diabetes. When comparing these responses by year in medical school, only one question differed, with 3rd and 4th year participants more likely to agree that people with type 2 diabetes would follow medical advice (χ2=23.774, p=.022).Conclusion: Findings suggest medical students’ held biases toward type 2 diabetes, despite understanding the causes. Targeted educational interventions in the early stages of medical training may correct biases towards type 2 diabetes.DisclosureR. Taylor: None. E.A. Beverly: None.FundingOsteopathic Heritage Foundation
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-615-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 616-P: Navigating a New Reality—Exploring Unmet Psychosocial Needs in
Adults Newly Diagnosed with Type 2 Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 616-P
Abstract: Introduction and Objective: Few studies have explored the experiences of people newly diagnosed with type 2 diabetes (T2D). This study aimed to understand these experiences through in-depth interviews to identify unmet psychosocial needs.Methods: Thirty adults with T2D diagnosed within the past six to nine months were interviewed using a semi-structured guide to capture their experiences and perceived challenges in navigating this new diagnosis. Questions addressed the adequacy of diabetes education at the time of diagnosis, barriers to managing T2D, and the condition's psychosocial impacts. Three researchers coded the transcribed interviews, met to resolve discrepancies, and agreed on common themes.Results: Qualitative analysis revealed four themes: 1) Perceived Gaps in Information Adequacy and Understanding of Diagnosis: Participants expressed concerns about the lack of diabetes education specific to their needs and felt compelled to seek additional information. 2) The Emotional Impact of the Diagnosis: Participants expressed that the diagnosis created a significant negative emotional impact and reported difficulty accepting the diagnosis. 3) Barriers with Lifestyle Adjustments: Participants described challenges with taking medications consistently, accessing fresh and healthy foods, and problem-solving skills to manage diabetes. 4) Future Worries: Participants expressed fears of developing complications (e.g., amputation, weight gain) and medication-specific fears such as going on insulin.Conclusion: Findings show a gap in primary care. People with newly diagnosed T2D need support to integrate this diagnosis into their everyday lives. Addressing these barriers through enhanced diabetes education, emotional support, and accessible resources may empower them in T2D management.DisclosureE.J. Unni: None. C. Young: Consultant; Sanofi. T.J. Rath: None. E.A. Beverly: None.FundingTouro University Seed Grant
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-616-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 617-P: College Education May Influence Preference for Normal Weight
Silhouettes in African Immigrant and African American Women-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 617-P
Abstract: Introduction and Objective: Body size preference is influenced by both globalization and education and affects health behavior. Recent data on body size preferences of African Immigrant (Afr-Im) and African American (AA) women are lacking. Hence, in a pilot study of 23 Afr-Im and 23 AA women matched for age (40±16, (mean±SD) range 20 - 68y) and BMI (29.9+5.7, 20.2 - 42.4 kg/m2), we compared wish body size, body size dissatisfaction and basic demographics.Methods: The Stunkard Figure Rating Scale has 9 silhouettes with each corresponding to a BMI category: underweight (Silhouettes 1 & 2), normal weight (Silhouettes 3 & 4), overweight (Silhouettes 5 & 6 & 7) and obese (Silhouettes 8 & 9). Each woman chose 2 silhouettes, 1 for wish body size and 1 for perceived body size. Body size dissatisfaction was determined by the difference in silhouette number between wish and perceived body size.Results: The African regions of birth of the Afr-Im were: West 44% (10/23), East 44% (10/23), Central 13% (3/23). BMI distribution of the participants was: obese 37% (17/46); overweight 37% (17/46); normal weight 26% (12/46), and underweight 0% (0/46). Wish body size did not differ by ethnicity (P=0.737). Wish body size for Afr-Im women were: obese 0% (0/23), overweight 22% (5/23), normal weight 74% (17/23), and underweight 4% (1/23). Wish body size for AA women were: 0% (0/23), 13% (3/23), 83% (19/23) and 4% (1/23), respectively. Dissatisfaction due to feeling too large in Afr-Im and AA women occurred in 70% (16/23) vs 57% (13/23), (P=0.606). College graduation rates in Afr-Im and AA women were: 74% (17/23) vs 70% (16/23), P=0.743).Conclusion: In this cohort of highly educated Afr-Im and AA women, attitudes toward body size preference did not vary by ethnicity and the most favored BMI was normal weight.DisclosureG.G. Smith: None. E.A. Huefner: None. M. Sayed: None. C. DuBose: None. M.F. Horlyck-Romanovsky: None. A.E. Sumner: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-617-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 618-P: Obtrusiveness of Diabetes—How Many Minutes Are People with
Diabetes Thinking about Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 618-P
Abstract: Introduction and Objective: Diabetes imposes a significant mental load on individuals with diabetes and their caregivers. This study aimed to quantify the mental load by assessing the time spent thinking about diabetes-related aspects among adults with type 1 diabetes (PWT1D), type 2 diabetes (PWT2D), and parents of children with diabetes.Methods: Daily time (in minutes) spent thinking about diabetes-related topics, including hypoglycemia, glucose variability, and self-management, was reported by 555 participants. Group differences in mental load were analyzed.Results: Participants reported a mean of 65.7 ± 66.5 minutes per day thinking about diabetes, highlighting the obtrusiveness of the condition. Self-management accounted for the longest duration (27.0 ±32.0 minutes), followed by glucose fluctuations (15.8 ±19.7 minutes) followed by Hypoglycemia (9.3 ±13.9 minutes) whereas positive or negative thoughts about diabetes were less burdensome. Parents of children with type 1 diabetes reported the highest mental load, followed by PWT1D and PWT2D.Conclusion: Self-management problems, glucose fluctuations and hypoglycemia related concerns are key contributors to mental load of diabetes. Tailored psychological support and improved insulin delivery and sensor systems that minimize self-management effort and glucose fluctuations could reduce this burden and enhance quality of life.Disclosure N. Hermanns: Advisory Panel; Dexcom, Inc., Abbott Diagnostics. Speaker's Bureau; Abbott Diagnostics. Advisory Panel; Roche Diabetes Care. D. Ehrmann: Advisory Panel; Dexcom, Inc. Speaker's Bureau; Dexcom, Inc. Consultant; Roche Diabetes Care. Speaker's Bureau; Roche Diabetes Care, Sanofi, Eli Lilly and Company, Boehringer-Ingelheim. B. Kulzer: Advisory Panel; Abbott, Dexcom, Inc. Consultant; Becton, Dickinson and Company. Other Relationship; Insulet Corporation, AstraZeneca. Board Member; Sanofi-Aventis Deutschland GmbH. Advisory Panel; Roche Diabetes Care, Novo Nordisk.FundingMuSiC4Diabetes has received funding from the European Innovation Council (EIC) under grant agreement No. 101115233. The EIC receives support from the European Unions Horizon Europe research and innovation programme.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-618-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 619-P: Implementation of Depression Screening in Newly Diagnosed Pediatric
Type 1 Diabetes Patients-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 619-P
Abstract: Introduction and Objective: Mental health can have a significant impact on one’s ability to manage chronic illnesses such as type 1 diabetes. Conversely, diagnosis of a chronic illness is associated with negative impacts on mental health. Depression screens were implemented at new onset of T1D and characteristics of those screened were assessed.Methods: A large academic center launched a standardized PHQ-2 depression screen at the time of diabetes diagnosis. The screen consists of 2 questions, with scores ranging from 0-6 with higher scores indicating more depressive symptoms. Patients who score a 4 or higher are referred to psychology for additional support. Comparisons among new onset T1D patients (NODPs) were made to assess patterns between race, ethnicity, and insurance.Results: Thirty-two PHQ-2s (31% non-Hispanic Black (NHB), 22% non-Black Hispanic (NBH), 28% White, 13% Other, 6% declined/unknown) were completed by T1 NODPs. NBH patients scored the highest (mean=1.86), with NHB patients scoring the second highest (mean=1.30), followed by White patients (mean=0.44). For the 6 identified as "Other" or "declined/unknown," all but one individual scored 0. Patients with public insurance (mean=1.38) scored higher than those with private insurance (mean 0.77).Conclusion: Average depressive screening scores were below positive screening cut-offs, but scores were notably higher in minoritized youth. These results emphasize the importance of early mental health screening, especially in diverse patient populations, so appropriate support can be incorporated starting at diagnosis. Future steps include expanding depression screening further in NODPs and assessing mental health follow-up in those with positive depressive symptoms.DisclosureJ. Roberts: None. S.L. Holly: None. L. DeAnna: None. D. Patrick: None. S. Majidi: Speaker's Bureau; Sanofi.FundingCareFirst BlueCross BlueShield
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-619-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 620-P: The Moderating Role of Diabetes Resilience in the Relation between
Diabetes Distress and HbA1c in School-Sge Children-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 620-P
Abstract: Introduction and Objective: Diabetes distress (DD) is a multi-symptom emotional condition related to living with type 1 diabetes (T1D). In school-age children, research suggests a positive association between DD and HbA1c, while diabetes resilience appears to have negative associations with DD and HbA1c. We examined whether diabetes resilience may buffer the relationship between DD and HbA1c in children.Methods: At one time point, we measured DD with the Problem Areas in Diabetes-Child (PAID-C) and diabetes resilience with the Diabetes Strengths and Resilience (DSTAR). For the PAID-C, higher scores reflect more DD and for the DSTAR, higher scores reflect greater resilience.Results: 155 children participated. They were 50% male and 82% White [(M±SD) age= 10.2±1.5 years, T1D duration= 3.8±2.4 years, HbA1c= 7.97±1.87%]. Mean scores were 31.5±12.3 (range: 11-66) and 47.7±6.3 (range: 12-60) for the PAID-C and DSTAR, respectively. Moderation analyses revealed a significant interaction between PAID-C and DSTAR scores on child HbA1c (β=.004, t(151)=2.84, p=0.005). Specifically, the conditional effects suggest there may only be a significant positive association between PAID-C and HbA1c for children with DSTAR scores >45.55.Conclusion: Our results suggest interventions to reduce child HbA1c by targeting DD may also need to include strategies to promote child diabetes resilience.DisclosureS.R. Patton: None. J.S. Pierce: None. N. Kahhan: None. R. McDonough: Speaker's Bureau; Sanofi-Aventis U.S. M.R. Benson: Research Support; Novo Nordisk, Enable Biosciences, Calcilytix. Speaker's Bureau; Beta Bionics, Inc. Research Support; Diurnal Chronocort. Stock/Shareholder; Kihealth. L.A. Fox: Advisory Panel; KiHealth. Research Support; Dexcom, Inc. M.A. Clements: Consultant; Glooko, Inc. Research Support; Dexcom, Inc., Abbott.FundingNational Institutes of Health (DKR01127493)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-620-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 621-P: Longitudinal Phenotypes of Parent-Reported Diabetes Distress in
School-Age Families-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 621-P
Abstract: Introduction and Objective: Diabetes distress (DD), a multi-symptom emotional condition related to living with type 1 diabetes (T1D), affects both children and parents. Our clinic has been routinely screening for DD in school-age families using the Parent Problem Areas in Diabetes-Child (PPAID-C) and the Problem Areas in Diabetes-Child (PAID-C) since 2022. Using these clinical data, we aimed to explore whether there may be “DD phenotypes” for parents that relate to other demographic or clinical data.Methods: We collected demographic (youth age, sex, race, ethnicity) and T1D clinical (youth HbA1c%], PAID-C scores) data for clinic visits with a corresponding PPAID-C score. We focused on parents with consistently high (≥75th percentile; Q4) or low (≤25th percentile; Q1) PPAID-C scores across ≥2 and <7 unique clinic visits. We compared these groups using Pearson chi-square or two-sample Wilcoxon rank-sum (Mann-Whitney) tests.Results: We had 686 parents (n=2529 observations) in total. Of these, 65 parents (n=230 observations) consistently reported PPAID-C scores in Q1 (range: 16-24) and 73 parents (n=232 observations) consistently reported PPAID-C scores in Q4 (range: 46-96). There were no differences for groups based on youth age, sex, or race. However, parents with PPAID-C scores consistently within Q1 had youth with lower HbA1c levels [median, (IQR), 7.5% (6.9,8.3)] and lower PAID-C scores 12.5 (11,17) than parents with PPAID-C scores consistently within Q4 [HbA1c: 8.2% (7.0,10.1), PAID-C: 34 (27,42.5)], p<0.01. There was also a greater proportion of families who self-identified as Hispanic/Latino in the PPAID-C Q4 versus Q1 group (12.8% versus 5.2%, p<0.01).Conclusion: Among parents reporting consistently high levels of DD, youth report higher DD levels and higher HbA1c levels. Families who self-identify as Hispanic/Latino may be most vulnerable to high DD levels. Findings may help inform the design and testing of routine screen-to-treat programs to address DD in parents and school-age children.DisclosureS.R. Patton: None. D.D. Williams: None. M.A. Clements: Consultant; Glooko, Inc. Research Support; Dexcom, Inc., Abbott.FundingNational Institutes of Health (DKR01 127493)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-621-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 622-P: Role of Mindfulness in the Quality of Life and Promotion of
Well-Being in Type 1 Diabetic Patients-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 622-P
Abstract: Introduction and Objective: Mindfulness is a meditation focused on awareness of present moment, encouraging open, curious, and non-judgmental observation of one's personal experience. The Mindfulness-Based Stress Reduction (MBSR) program is used in hospital settings. Primary objective was to evaluate the impact of the MBSR program on quality of life in type 1 diabetic patients. Secondary objectives: to evaluate the impact on diabetes related stress, depression, satisfaction with diabetes therapy and psychopathological symptoms.Methods: Retrospective observational study of 33 type 1 diabetic patients (13 with traditional pumps, 20 with MDI). Psychological aspects were assessed at beginning of the program (T0) and at the end (T1), with: Audit of Diabetes-Dependent Quality of Life(ADDQoL); Problem Areas In Diabetes(PAID-5); Beck depression inventory(BDI); Diabetes Treatment Satisfaction Questionnaire(DTSQ); Symptom CheckList 90(SCL-90). The protocol was approved by local ethics committee. Wilcoxon signed-rank test was used for paired data, and linear regression models assessed associations between pre/post.Results: Regarding quality of life, significant improvements were observed in items related to family life and physical appearance (p=0.007 and p=0.02). Diabetes-related stress, measured with PAID-5, showed reductions in both total scores and subitems (p=0.003, p<0.01). Total scores and subitems of BDI and SCL-90 also decreased (p<0.001). HbA1c levels improved in patients using traditional pumps (p<0.03), in those with high school diploma (p=0.02), in those with increased importance of physical appearance (p<0.001) and in those with a reduction in diabetic related stress (p=0.02).Conclusion: Mindfulness might improve quality of life, reduce depression, stress, and psychopathology, supporting well-being in type 1 diabetic patients.DisclosureE. Resmini: None. V. Turra: None. Y. Jin: None. A.V. Cornaghi: None. M. Sandri: None. E. Cimino: Speaker's Bureau; roche, Abbott. E. Zarra: None. C. Mascadri: None. G. Massari: None. S. Madaschi: None. B. Pasquino: None. M. Migazzi: None. A. Girelli: Consultant; Abbott Diagnostics, Sanofi, Roche Diabetes Care.
PubDate: Fri, 13 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-622-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 623-P: Use of Social Media to Support Gestational Diabetes Risk Reduction
for American Indian and Alaska Native Females—Perspectives from Native
Youth, Mothers, and Content Experts-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 623-P
Abstract: Introduction and Objective: American Indian and Alaska Native (AI/AN) women experience a higher rate of GDM than most non AI/AN women. The Stopping Gestational Diabetes in Daughters and Mothers (SGDM) program is the only known preconception counseling intervention designed to reduce GDM risk for AI/AN females. Our team is developing a social media toolkit by which SGDM content can be widely shared in AI/AN communities.Methods: Participants were recruited through the social networks of 3 Native community-based recruiters and the research team’s professional networks. Individual interviews with content experts (n=20) and focus group interviews with female AI/AN youth (n=20) and AI/AN mothers of female youth (n=20) were conducted via Zoom by a trained Native moderator. Interviews were recorded, transcribed verbatim, and analyzed using thematic analysis. After each interview/focus group, participants completed a short demographic survey using Qualtrics.Results: All youth (100%) and most mothers (95%) identified as AI/AN; 40% of content experts identified as AI/AN. The mean age for youth participants was 17.6 years (SD=2.82). All youth and mothers (100%) reported using social media daily; 60% of content experts reported daily social media use. Three salient themes emerged: 1) there are negative aspects of social media use that need to be considered for health-promotion messaging (e.g., promotion of unrealistic body image); 2) female AI/AN youth need positive AI/AN female role models and support to be healthy; 3) key recommendations to engage female AI/AN youth on social media include: videos, humor, and co-development of content (e.g., youth + experts).Conclusion: Understanding the perspectives on social media for GDM risk reduction of experts and members of the priority audience is a key first step in developing an AI/AN culturally relevant and community-engaged social media toolkit.DisclosureS.A. Stotz: None. S.R. McCage: None. S.J. Mumby: None. N.D. Reed: None. H. Garrow: None. D. Charron-Prochownik: None. M.L. Aspaas: None. M. Charley: None. S. Palmer: None. J. Leon: None. K. Gonzales: None. K.R. Begay: None. A.G. Brega: None.FundingAmerican Diabetes Association (7-23-ICTSHW-08)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-623-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 624-P: Bridging Psychiatric Interventions and Glycemic Control in Children
with Type 2 Diabetes Mellitus Based on Machine Learning-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 624-P
Abstract: Introduction and Objective: The impact of psychiatric interventions on glycemic control in pediatric and adolescent patients with type 2 diabetes mellitus (T2DM) has not been assessed using machine learning methods. We investigated the integration of psychiatric interventions in the management of T2DM, emphasizing the need for psychosocial support, as recommended by the 2024 American Diabetes Association and 2022 International Society for Pediatric and Adolescent Diabetes guidelines.Methods: We applied machine learning on a dataset from Inha University Hospital, Korea, involving 111 pediatric patients with T2DM to predict the optimal timing for psychiatric intervention to enhance glycemic control.Results: The analysis revealed that early psychiatric interventions contributed to more stable glycemic control with a slight improvement in HbA1c levels, indicating the effectiveness of these interventions. Advanced analytical techniques identified patient subgroups that benefited from early intervention, although age did not significantly affect the outcomes.Conclusion: This study serves as a foundation for future research utilizing datasets in the field of medicine, emphasizing the role of machine learning in predicting disease prognosis and adopting a multifaceted approach to analyze factors influencing disease outcomes. It advocates a shift towards leveraging comprehensive data analysis to enhance our understanding of diseases, thereby fostering more informed, predictive, and personalized disease management strategies. This aspiration pioneered the application of machine learning to explore the breadth of data to advance patient care.DisclosureJ. Park: None. S. Kim: None. J. Lee: None. S. Kim: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-624-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 625-P: Evaluating the Spectrum of Emotional Distress in Diabetes—A
Study on Its Impact on A1C-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 625-P
Abstract: Introduction and Objective: Diabetes distress (DD) significantly influences glycemic control in T2D. This study assessed DDS levels and their sub-domains [physician distress (PD), emotional distress (ED), regimen distress (RD), and interpersonal distress (IPD)] to analyze their impact on glycemic status using the diabetes distress scale (DDS).Methods: T2D participants (1062) were categorized into 250 high (G1), 352 moderate (G2), and 460 low-distress groups (G3) based on DDS-17 scores, with glycemic status assessed. G1 received psychologist consultations, health coach (HC), and physician support (PS); G2 received focused HC advice and PS; and G3 followed general wellness advice with HC and PS.Results: Over 90 days, DDS and HbA1c significantly improved (p<0.001) in all groups, except low-distress DDS reduction (p<0.5). G1 experienced a significant reduction in DDS (ED, RD, PD, and IPD) of 3.65±0.58 (4.1±0.94, 3.98±0.9, 2.98±1.2 and 2.9±1.4) to 2.69±1.0 (3.06±1.28, 2.91±1.31, 2.06±1.26 and 2.2±1.4), and HbA1c from 8.85±1.67% to 7.51±1.26%, respectively. G2 experienced a decline in DDS (ED, RD, PD, and IPD) from 2.4±0.3 (2.8±0.8, 2.8±0.7, 1.9±0.9 and 1.6±1.0) to 2.0±0.7 (2.4±0.9, 2.3±1.0, 1.5±0.8 and 1.6±0.7), and HbA1c from 8.8±1.7% to 7.3±1.2%, respectively. G3 exhibited a reduction in DDS (ED, RD, PD, and IPD), to 1.5±0.6 (1.62±0.7, 1.64±0.8, 1.3±0.6 and 1.3±0.6), to 1.5±0.3 (1.60±0.5, 1.68±0.5, 1.2±0.4 and 1.1±0.3), and HbA1c from 8.4±1.6%, to 7.0±1.1%, respectively.Conclusion: Tailored interventions for high and moderate distress significantly reduced DDS and improved glycemic outcomes over 90 days, highlighting their efficacy and need for long-term research.DisclosureC. Goyal Mehra: None. A.M. Raymond: None. J.J. J: None. A. Sequeira: None. S. Kumar: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-625-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 626-P: Diab@ease—A Pilot Study on Holistic Mental Health Integration for
Diabetes, Cognitive Function, and Physical Frailty-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 626-P
Abstract: Introduction and Objective: Diabetes is a chronic condition closely linked to cognitive decline, physical frailty, and mental health issues. This pilot study evaluated the feasibility and preliminary outcomes of a multidisciplinary, patient-centered intervention, providing insights for scaling to a larger study.Methods: Enrolled 53 subjects with type 2 diabetes, aged ≥ 60 years, with duration > 5 years. Each subject was provided with personalized dietary interventions focused on low-glycemic, nutrient-dense foods, tailored physical activity programs and mindfulness-based stress reduction techniques. Baseline assessments included Mini-Mental State Examination [MMSE], Montreal Cognitive Assessment [MoCA]), frailty evaluation (Fried Frailty Index), mental health assessments (PHQ-9, GAD-7) and HbA1c and repeated after 6 months. Feasibility metrics included retention, adherence, and implementation challenges.Results: Of the 53 enrolled, 39 participants (74%) completed the study. Attrition included 9 losses (17%) due to age-related complications and 5 withdrawals (9%) due to mobility constraints, underscoring the need for adaptive strategies in geriatric populations. Cognitive scores improved significantly (MMSE: +2.5, 95% CI: 1.1-3.9; MoCA: +3.1, 95% CI: 2.0-4.2), Frailty scores showed marked reductions (Fried Frailty Index: -1.2, 95% CI: -1.7 to -0.7), Depression (PHQ-9: -4.3, 95% CI: -5.6 to -3.0) and anxiety (GAD-7: -3.7, 95% CI: -4.9 to -2.5) symptoms improved significantly, Glycemic control also improved (HbA1c: -0.7%, 95% CI: -1.1% to -0.3%).Conclusion: This pilot study demonstrated the feasibility of integrating cognitive, physical, and mental health interventions into diabetes care, yielding promising preliminary outcomes. The Diab@ease pilot study underscores the importance of a multidisciplinary approach in diabetes care.DisclosureS. Shaji: None. C. Radhakrishnan: None. S.S. K p: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-626-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 627-P: Learnings from Equitably Developing and Administering a Survey for
the National Center for Engagement in Diabetes Equity Research (CEDER)-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 627-P
Abstract: Introduction and Objective: The National Center for Engagement in Diabetes Equity Research (CEDER) fosters nationwide collaborations to increase engagement and equity in type 2 diabetes research. Co-led by community and academic partners, CEDER utilizes a partnership hub (PH) and steering committee (SC), comprising diverse members, to provide input on CEDER’s model. We describe lessons learned on how to advance equity in co-developing and co-administering CEDER’s national needs & asset assessment.Methods: CEDER staff and faculty trained in community-based participatory methods developed a survey and outreach plan from March-June 2024. Materials were shared in advance of and during 5 PH and SC meetings; two 1.5 hour listening sessions with 12 community-based and academic partners from varied geographical locations and experience with diverse populations; and were disseminated through partner networks to broaden reach/input. To increase accessibility, partners could share written or oral feedback. Feedback was iteratively synthesized and applied to improve relevance and acceptability of the materials and strategies.Results: Lessons learned were: 1) Include community members earlier in the development phase; 2) Include more iterations to incorporate feedback adequately; 3) Leverage non-traditional engagement methods, including informational videos and use of existing networks to boost participation from community-based organizations; and 4) Ensure materials language, tone, and content resonate with different audiences, which may require cultural and linguistic tailoring.Conclusion: Coordinating national efforts to assess diabetes equity research across diverse partners and underrepresented communities highlights challenges in community-partnered research. When developing materials, centers may benefit from implementing processes to better integrate and balance community participation and perspectives.DisclosureC. Cooper: None. T. Akintobi: None. S.L. Albert: None. S. Albrecht: None. M. AuYoung: None. D. Buchwald: Advisory Panel; Novo Nordisk. C.K. Townsend: None. G. Kim: None. D.W. Lounsbury: None. A. Luitel: None. K.D. Ramirez: None. E. Rodgers: None. S.A. Stotz: None. R.C. Quarells: Consultant; UCB Pharmaceutical Company. C. Trinh-Shevrin: None. J.A. Wong: None. L. Wyatt: None. J. Zanowiak: None. A. Brown: None. E. Chambers: None. N. Islam: None.FundingU2CDK137135
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-627-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 628-P: Assessing Needs and Expertise for the National Center for
Engagement in Diabetes Equity Research (CEDER)-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 628-P
Abstract: Introduction and Objective: CEDER aims to enhance community engagement and equity in type 2 diabetes (T2D) research through a research consultation and community engagement studio model. Phase 1 included a needs and assets assessment (NAA) of potential CEDER clients and experts engaged in T2D research. Results on identified needs and expertise are presented.Methods: The 20-minute NAA was administered to a purposive sample of individuals engaged in T2D programs or research, including CEDER members, nominated individuals, and NIDDK-funded researchers from June-November 2024; respondents received a gift card. The NAA covered 11 aspects of conducting research (e.g., funding, data collection, dissemination); question phrasing differed based on respondent type (researcher, service provider, both). Participants rated challenges (not at all to extremely challenging) and experience (leading/participating in 0 to 10+ projects) for each aspect. Aspects were considered needs when ≥25% selected “Very or Extremely challenging.” Experience on 3+ projects identified expertise. Descriptive analyses were run overall and stratified by respondent type.Results: The NAA was completed by individuals from various sectors, geographies, and populations of interest, and consisted of researchers (n=94), service providers (n=29), and both (n=67). Most were women (70%) and identified as an ethnic minority (57%); 21 US states were represented. Needs included: 1) finding/securing funding (44%); 2) sustaining programs/partnerships (32%); and 3) recruiting/retaining participants (27%). Expertise included: 1) data collection/management (80%); 2) collaboration with partners (74%); and 3) data analysis (74%).Conclusion: The NAA identified needs, as well as availability of diverse expertise, across the US. This can be leveraged to support T2D equity research through CEDER activities/resources. Variability was identified by respondent type and will be presented in final analyses.DisclosureL. Wyatt: None. S.L. Albert: None. M. AuYoung: None. C. Cooper: None. D.W. Lounsbury: None. A. Luitel: None. K.D. Ramirez: None. E. Rodgers: None. J. Zanowiak: None. S. Albrecht: None. C. Trinh-Shevrin: None. A. Brown: None. E. Chambers: None. N. Islam: None.FundingU2CDK137135
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-628-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 629-P: National CEDER Lessons Learned from Piloting T2D Community
Engagement and Research Support Services-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 629-P
Abstract: Introduction and Objective: The NIDDK-funded National Center for Engagement in Diabetes Equity Research (CEDER) fosters nationwide community-academic collaborations to increase community engagement and equity in type 2 diabetes (T2D) research and projects. We describe lessons learned from piloting services, including research consultations consisting of expert discussions and community engagement studios with community-partnered structured expert discussions.Methods: The pilot phase (Jul-Dec 2024) included development of a triage process and matching clients with appropriate services and expertise (i.e., community partners, lived experience, T2D intervention expertise).Results: To date, CEDER’s community-academic partners have responded to 29 requests from six states for support with grant applications, study design, community partnerships, health equity, and funding source identification. Process lessons learned include triaging and prioritizing needs for matching community-academic expertise, promoting community-academic discussion, and supporting community-engaged research methods. Project recommendations from community-academic experts included strategies for identifying community-based partnerships, improving accessibility and community-relevant messaging, recruitment and retention, and guidance for NIDDK funding priorities.Conclusion: Community-partnered services supported community and research projects focused on T2D, catalyzing innovative, community-relevant, health-equity-focused research projects, providing early community-engaged feedback for grant applications, and promoting community-academic partnerships and relationship-building. Future goals include geographic expansion, promoting services within public entities and community organizations, and tracking national priorities within T2D projects.DisclosureA. Luitel: None. K.D. Ramirez: None. S.L. Albert: None. S. Albrecht: None. M. AuYoung: None. S.L. Carson: None. Y.M. Castellon-Lopez: None. C. Cooper: None. E.M. Everett: None. M. Hernandez: None. G. Kim: None. T. Moin: None. S. Nicholas: Consultant; Boehringer-Ingelheim, AstraZeneca, Bayer Pharmaceuticals, Inc. Speaker's Bureau; Boehringer-Ingelheim. Consultant; Novo Nordisk, Vertex Pharmaceuticals Incorporated. E. Rodgers: None. C. Trinh-Shevrin: None. J. Zanowiak: None. A. Brown: None. E. Chambers: None. N. Islam: None.FundingU2CDK137135
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-629-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 630-P: Strategies for Building Equitable Partnerships to Advance Diabetes
Equity Research—Reflections from Community and Academic Leaders across
the United States-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 630-P
Abstract: Introduction and Objective: The National Center for Engagement in Diabetes Equity Research (CEDER) is a partnership of academic institutions and community-based organizations that seeks to strengthen involvement of investigators, community organizations, health systems, and other partners in type II diabetes-related research.Methods: Identify and share strategies for building equitable partnerships in diabetes research as described by 8 community and academic leaders and synthesized into key themes.Results: Four strategies emerged as contributing to successful partnerships: 1) Engage communities from the outset of research, beginning with research conceptualization and prioritization through a continuous presence in community spaces and by embracing shared values as well as cultural safety; 2) Maintain successful research partnerships by committing to equalized power, co-learning, co-sharing and co-creation of knowledge, as well as candid, respectful discussions and equitable distribution of resources; 3) Develop local capacity to ensure studies create pathways towards community research leadership and community-led research; 4) Build research teams and staff that meaningfully include community members and thus promote the science, application of findings, and benefit to all participants.Conclusion: We will discuss how lessons learned are applied to CEDER’s efforts to support and strengthen future community and academic partnerships.DisclosureN. Islam: None. T. Ashford: None. F. Barrow: None. O. Carrasquillo: None. A.Y. Dillard: None. L.M. Hoffman: None. S.M. Manson: None. R. O'Leary: None. R.C. Quarells: Consultant; UCB Pharmaceutical Company. S.L. Albert: None. S. Albrecht: None. S. Artis Dickerson: None. J. Brown: None. C. Cooper: None. E. Rodgers: None. C. Trinh-Shevrin: None. J. Zanowiak: None. A. Brown: None. E. Chambers: None.FundingU2CDK137135
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-630-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 631-P: Increasing Sleep Duration among Short-Sleeping Type 2 Diabetes
Patients via mHealth—A Pilot Randomized Controlled Trial-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 631-P
Abstract: Introduction and Objective: Sleep duration is associated with glycemic control, but causality is unclear. Our mHealth intervention promoted earlier bedtime to assess impact on sleep duration and glycemic control.Methods: We conducted a 12 week single-blind, two-arm RCT with 70 short-sleeping T2D patients in Japan using actigraphs and sleep diaries. The key eligible criteria included short sleep duration (≤ 6 h), elevated HbA1c levels (≥ 7.5 %), and no sleep disorders. The Intervention group received Theory of Planned Behavior-based interventions targeting earlier bedtimes using achievable bedtime goal setting and feedback.Results: The arms were well matched, except for BMI (Intervention 24.7 vs. Control 26.6 kg/m2). The Intervention demonstrated a significant 32.8 minute improvement in mean sleep duration (p = 0.004) and suggestive but not significant improvements in BMI (0.24, p = 0.17]) and HbA1c (0.11, p = 0.51). The pooled SD of HbA1c change, at 0.70, exceeded our prior estimate of 0.41.Conclusion: The intervention improved sleep duration, piloting effective methods. The improvements in BMI and HbA1c, while not statistically significant, are suggestive of a causal link. High pooled SD of change in BMI and HbA1c suggests the need for follow up with larger sample sizes.DisclosureR. Nakada: None. K. Waki: Consultant; Astellas Pharma Inc. Other Relationship; Astellas Pharma Inc, Sumitomo Dainippon Pharma Co., Ltd. Consultant; Terumo Corporation. Other Relationship; Terumo Corporation. Speaker's Bureau; Sanofi. D. Lane: None. S. Iwata: None. A. Isogawa: None. K. Miyoshi: Research Support; The Descente and Ishimoto Memorial Foundation for the Promotion of Sports Science. H. Waki: Speaker's Bureau; LifeScan Diabetes Institute, MSD Life Science Foundation, Astellas Pharma Inc, AstraZeneca, Abbott, Eisai, Sanofi, Novartis AG, Novo Nordisk, Bayer Pharmaceuticals, Inc, Kyowa Kirin Co., Ltd, Kowa Company, Ltd. Research Support; Kowa Company, Ltd. Speaker's Bureau; Sumitomo Dainippon Pharma Co., Ltd, Ono Pharmaceutical Co., Ltd, Taiho Pharmaceutical Co. Ltd, Daiichi Sankyo, Mitsubishi Tanabe Pharma Corporation, Eli Lilly and Company, Boehringer-Ingelheim. S. Kato: None. H. Sawaki: None. T. Murata: Research Support; Medtronic. Speaker's Bureau; Abbott Japan Co., Ltd, Dexcom, Inc. Y. Hirota: Speaker's Bureau; Novo Nordisk, Sanofi, Eli Lilly and Company, Terumo Corporation, Sumitomo Dainippon Pharma Co., Ltd. Research Support; Medtronic, Kyowa Kirin Co., Ltd, Abbott Japan Co., Ltd. S. Saito: None. S. Nishikage: None. A. Tone: Speaker's Bureau; Johnson & Johnson Medical Devices Companies, Medtronic, Eli Lilly and Company, Sanofi, Kowa Company, Ltd, Mitsubishi Tanabe Pharma Corporation, Novo Nordisk, Sanwa Kagaku Kenkyusho Co., Ltd, Sumitomo Dainippon Pharma Co., Ltd, Novartis Pharmaceuticals Corporation, Taiho Pharmaceutical Co. Ltd, Kyowa Kirin Co., Ltd, Abbott Japan Co., Ltd, Boehringer-Ingelheim, Terumo Corporation, Roche Diagnostics, ARKRAY, Inc., Dexcom, Inc. M. Toyoda: None. S. Kajino: None. K. Yokota: None. Y. Tsurutani: None. T. Yamauchi: Research Support; Asahi Mutual Life Insurance Company. Other Relationship; Astellas Pharma Inc, AstraZeneca, Abbott Japan Co., Ltd, ARKRAY Marketing, Inc., Amgen Inc. Research Support; Boehringer-Ingelheim. Other Relationship; Boehringer-Ingelheim, Bayer Pharmaceuticals, Inc, Covidien Japan Inc., Daiichi Sankyo, Eli Lilly and Company. Research Support; EA Pharma Co.,Ltd. Other Relationship; GlaxoSmithKline K.K. Research Support; Kowa Company, Ltd. Other Relationship; Kowa Company, Ltd, Kyowa Kirin Co., Ltd, Medtronic, Merck Sharp & Dohme Corp, Mitsubishi Tanabe Pharma Corporation. Research Support; Novo Nordisk. Other Relationship; Novo Nordisk, Ono Pharmaceutical Co., Ltd, Sumitomo Pharma Co., Sanofi K.K., SANWA KAGAKU KENKYUSHO CO.,LTD., Taiho Pharmaceutical Co. Ltd, Teijin Pharma Limited, Nipro Corporation. Research Support; NITTO BOSEKI CO.,LTD. Other Relationship; ViewSendICT Inc. M. Nangaku: Other Relationship; Astellas Pharma Inc, AstraZeneca, Daiichi Sankyo, GlaxoSmithKline plc, Daiichi Sankyo, Kyowa Kirin Co., Ltd, Boehringer-Ingelheim. Consultant; Novo Nordisk. Research Support; Bayer Pharmaceuticals, Inc. Other Relationship; Mitsubishi Tanabe Pharma Corporation. K. Ohe: None. T. Kawaguchi: Other Relationship; Nitto Boseki Co., Ltd.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-631-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 632-P: Engaging Hispanic Men in the National Diabetes Prevention Program
(NDPP)—A Comparative Qualitative Study Examining Influences on Low
Engagement-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 632-P
Abstract: Introduction and Objective: Hispanic men have a relatively high prevalence of diabetes but relatively low rates of enrollment and engagement in preventive interventions like the NDPP. This qualitative study aimed to comprehensively explore influences unique to Hispanic men with low engagement in the NDPP, compared to those with high engagement, with the goal of informing strategies to improve their engagement in the program.Methods: Participants were self-identified Hispanic men, aged ≥18 years, at risk for diabetes per electronic medical records at an urban outpatient network, and invited to the NDPP. They completed individual audio-recorded interviews in English and Spanish. Using Nvivo, transcripts were analyzed deductively, informed by the Theoretical Domains Framework, to identify influences on engagement in the NDPP. Codes emerging uniquely among those with low engagement (attendance at <4 NDPP sessions) were identified through consensus.Results: Of 32 Hispanic men interviewed, 15 had low engagement in the NDPP. More of those with low engagement had limited English proficiency and did not complete high school. Three major themes delineated their Capacity, Motivations, and Opportunities for engaging with the NDPP. They expressed limited awareness of their prediabetes diagnosis, felt self-sufficient about enacting lifestyle change, and were skeptical about their diabetes risk and the utility of the NDPP. They also mentioned financial barriers and limited access to the program.Conclusion: Addressing the unique barriers faced by Hispanic men in engaging with the NDPP is critical to reducing diabetes-related inequities and may require tackling knowledge gaps, financial barriers, and perceptions of program relevance before, during, and after enrollment. Future research should explore how to tailor recruitment strategies and program content to Hispanic men’s specific identities, motivations, and challenges.DisclosureC.J. Gonzalez: None. C.N. Perez-Mejia: None. N. Hernandez: None. H. Flaxman: None. C. Stephenson-Hunter: None. E.N. Gil: None. T. Formagini: None. E. Chambers: None. J.S. Gonzalez: None.FundingRobert Wood Johnson Foundation (234326-01); UCSF Research in Implementation Science for Equity Subaward (R25HL126146 Subaward No 13969sc); National Heart, Lung, and Blood Institute (T32HL079891); National Institute of Diabetes and Digestive and Kidney Diseases (3R01DK121896); National Institute of Diabetes and Digestive and Kidney Diseases (3P30DK111022)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-632-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 633-P: Factors Associated with Diabetes Distress in a Spanish-Speaking
Hispanic/Latino Population Living with Type 2 Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 633-P
Abstract: Introduction and Objective: Despite the dire consequences of diabetes distress, current literature is sparse on factors that aggravate/alleviate diabetes distress in Hispanic/Latino (H/L) patients, a group at high risk for negative diabetes outcomes. Thus, our study aimed to identify predictors of diabetes distress in a Spanish-speaking H/L sample.Methods: Data were collected from 152 Spanish-speaking H/L participants (77% female) with type 2 diabetes (T2D) at a clinic serving largely uninsured patients in South Texas (2020-2022). Distress was measured using the Diabetes Distress Scale (DDS-17). HbA1c, sociodemographics, depression and anxiety symptoms (PROMIS-4), health-related quality of life (HRQOL), and diabetes self-care (Summary of Diabetes Self-Care Activities Scale; SDSCA) were also assessed. Univariate (UV) and multivariate (MV) linear regression models evaluated relationships between factors and diabetes distress.Results: In the UV analysis, total DDS was associated with being single (β=0.24), HRQOL-general health (β=0.35), anxiety (β=0.6), and depression (β=0.62), all ps < 0.01. Also, total DDS was associated with higher A1C (β=0.16), lower education (β=0.19), SDSCA (β=-0.19), and HRQOL-activity limitation days (β=0.2), all ps < 0.05. Results were similar for DDS subscales. In MV models, SDSCA (β=-0.18), depression (β=0.56) and HRQOL-general health (β=0.20) were unique predictors of total DDS (all ps <0.05). DDS subscales revealed similar unique associations.Conclusion: In this H/L Spanish-speaking cohort, high depression, poor self-reported diabetes management, and perceived poor health were significantly related to diabetes distress, even in the presence of other strong correlates. Culturally appropriate interventions to address these factors as part of integrated diabetes care may alleviate distress and improve outcomes for affected patients.DisclosureO. Asemota: None. A. Amspoker: None. C. Igweike: None. O. Morris: None. Y. Johnson-Esparza: None. R.L. Romero: None. K.E. Kanzler: None.FundingNational Institutes of Health (K23DK123398)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-633-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 634-P: Childhood Exposure to Parental Substance Abuse and Adult-Onset
Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 634-P
Abstract: Introduction and Objective: Childhood adversity has been linked to long-term metabolic health risks. However, the relationship between parental substance abuse during childhood and adult-onset type 2 diabetes remains underexplored. This study aimed to examine the association between childhood exposure to parental substance abuse and the subsequent risk of developing adult-onset diabetes.Methods: This population-based cohort study utilized data from the China Health and Retirement Longitudinal Study (CHARLS) collected between 2011 and 2020, with a 9-year follow-up period. Early-life exposure to parental substance abuse (alcoholism and drug use) was assessed through questionnaires. The primary outcome was self-reported, physician-diagnosed diabetes. Cox proportional hazards models with age as the time scale were used to estimate hazard ratios (HRs) for diabetes risk, adjusting for demographic, lifestyle, and psychosocial factors.Results: Among 12,953 participants (mean age: 59±10 years; 51.6% female), 880 (6.8%) reported exposure to parental substance abuse during childhood. These individuals were more likely to be current smokers (37% vs. 30%) and alcohol consumers (47% vs. 33%) compared to those without such exposure. Childhood exposure to parental substance abuse was significantly associated with an increased risk of adult-onset diabetes (n = 1,670 cases; HR: 1.27, 95% CI: 1.06-1.51) after adjustment for confounders, including childhood physical health, financial status, relationships with parents, adult obesity, and depression. The association was stronger among men (HR: 1.47, 95% CI: 1.16-1.87) compared to women (HR: 1.11, 95% CI: 0.85-1.45).Conclusion: Childhood exposure to parental substance abuse was associated with a significantly higher risk of adult-onset diabetes, particularly among men. These findings highlight the importance of addressing social determinants of health, supporting households affected by substance abuse, and implementing early interventions to mitigate long-term health consequences.DisclosureZ. Wu: None. Z. Guo: None. C. Sheng: None.
PubDate: Fri, 13 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-634-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 635-P: Differential Associations of Diabetes Distress with
Diabetes-Dependent QoL in Young Adults with Type 1 Diabetes—The
Buffering Role of Social Media-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 635-P
Abstract: Introduction and Objective: Diabetes distress (DD) has a major impact on diabetes-dependent QoL (DDQoL), but the subtypes and mechanisms by which DD impacts DDQoL are poorly understood. The study explored how DD subtypes (emotional, physician, regimen, interpersonal) are related to DDQoL and how social media (SM) as social support impacts these associations in young adults (YAs) with T1D.Methods: Baseline data from the Resilient, Empowered, Active Living-Telehealth Study, including participants aged 18-30 with T1D >1 yr and A1c ≥ 7.5%, were analyzed. Diabetes Distress Scale (DDS) and Audit of Diabetes-Dependent Quality of Life (ADDQOL) measured DD and DDQoL, respectively. Social support was categorized into SM or non-SM. Univariate regressions examined associations between DD subtypes with DDQoL, while multivariate regression tested combined impacts of DD subtypes. Interaction terms tested SM’s moderating role, and models were adjusted for demographics.Results: Among 209 YAs (66% female, age 24.5 yr, 42.6% Hispanic), 129 (61.7%) participants used SM for support. All DDS subscales were significantly associated with DDQoL (p <.001). Emotional DD had the strongest negative association in univariate models (β =-.79, CI =-.93 ~ -.64) and was the only significant predictor in multivariate model (β =-.86, CI =-1.08 ~ -.63). SM buffered interpersonal DD’s negative impact on DDQoL (interaction: β =.46, CI =.11 ~.82). The final model showed emotional DD (β =-.76, CI =-.94 ~ -.58), interpersonal DD (β =-.31, CI =-.59 ~ -.03), and SM (β =-1.66, CI =-2.54 ~ -.79) significantly affected DDQoL, with SM reducing interpersonal DD’s adverse effects on DDQoL, demographics adjusted and female correlated with better DDQoL (β =.60, CI =.15 ~ 1.05).Conclusion: Emotional DD significantly reduces DDQoL, while SM buffers the negative impact of interpersonal DD. The findings necessitate targeted emotional support and effective use of SM in T1D care.DisclosureY. Mo: None. J. Sideris: None. P. Lee: None. J. Blanchard: None. G. Granados: None. J. Raymond: None. D. Fox: None. N.D. Nnoli: None. J.D. Leite Junior: None. E. Pyatak: None.FundingNIH / National Institute of Diabetes and Digestive and Kidney Diseases (R01DK116719-01A1)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-635-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 636-P: Diabetes and Driving—Current Legal Issues in Switzerland
-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 636-P
Abstract: Introduction and Objective: According to the current Swiss legal issues, drivers who suffer from diabetes are placed in a certain risk category depending on the form of treatment and the concomitant risk of hypoglycaemia (no risk, low risk, increased risk or high risk). Stricter requirements apply to professional drivers of goods and passenger transport vehicles. The objective of this study was to investigate de degree of knowledge by general practitioners of the guidelines of the Swiss Society of Diabetology concerning the requirement of drivers suffering from diabetes.Methods: A questionnaire was sent to 100 general practitioners in order to evaluate their knowledge of the current guidelines of the Swiss Society of Diabetology concerning the requirement of drivers suffering from diabetes, particularly pertaining to the current risk category according to the prescribed treatment (no risk of hypoglycaemia, low risk, increased risk or high risk) as well as information transmitted to patients concerning risk of hypoglycaemia and precautionary measures for drivers of private vehicles.Results: The return rate of the sent questionnaires was 88 % and revealed that general knowledge pertaining to hypoglycaemia risk according to the prescribed treatment was overall high. Greater difficulties were observed regarding the assessment of the risk of hypoglycaemia (and the possible risks for road traffic) for treatment with multiple oral antidiabetic drugs, as well as regarding the specific situation of drivers of professional vehicles or vehicles used to transport of people.Conclusion: As already highlighted by former studies on this topic, preliminary results from this study seem to confirm that education in problems associated with diabetes and driving should be improved among general practitioners to ensure quality counseling for their patients.DisclosureC. Palmiere: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-636-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 637-P: Sleep Screening in Adolescents with Type 1 Diabetes (T1D) Using the
PROMIS Four-Item Sleep Surveys-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 637-P
Abstract: Introduction and Objective: Most adolescents do not achieve sleep recommendations and T1D causes unique nocturnal disruptions which may contribute to poor sleep. Yet, screening for sleep health is not regularly part of diabetes visits. The purpose of this study was to evaluate the feasibility of sleep screening in adolescents with T1D.Methods: Adolescents (11-17yo) with T1D completed sleep screening consisting of PROMIS Sleep Disturbance (SD) and Sleep-Related Impairment (SRI) surveys (4-items each, t-scores >50 indicate more problems than the population mean). For this study, a score of >55 was considered clinically significant, indicating need for further assessment. Participants were categorized by gender and age (11-13yo and 14-17yo).Results: 50 adolescents (age 14.7±2.2yrs, T1D duration 6.4±4.5yrs, 50% Female, 66% NHW) participated. PROMIS SD and SRI mean (SE) t-scores were 55.1 (3.2) and 53.6 (3.1), respectively, and took 5.5 minutes to complete. 31 (62%) scored above 55 on at least one survey. Females had significantly higher t-scores for both SD and SRI (Table). There were no differences by age.Conclusion: PROMIS sleep surveys identified a high proportion of adolescents with T1D with sleep concerns. Females reported higher levels. Routine screening for sleep health in adolescents using the PROMIS SD and SRI surveys is feasible during routine diabetes visits and can be an important part of T1D care.Disclosure E.C. Cobry: Advisory Panel; Dexcom, Inc. E. Fivekiller: None. S.S. Jaser: None. L.J. Meltzer: Consultant; Harmony Biosciences, Egetis Therapeutics, Zepp Health. R. Wadwa: Consultant; Dexcom, Inc., Tandem Diabetes Care, Inc. Advisory Panel; Provention Bio, Inc, Provention Bio, Inc, Microbion, Microbion, Sequel Med Tech. Research Support; Dexcom, Inc., Eli Lilly and Company, Tandem Diabetes Care, Inc.FundingBreakthrough T1D (5-ECR-2022-1179-A-N)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-637-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 638-P: An Analysis of Early Engagement in a Smart-Technology–Based
Weight Loss Intervention and Predictive Capability of Weight Loss-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 638-P
Abstract: Introduction and Objective: We previously reported that a smartphone app-based lifestyle intervention in overweight or obese subjects produced statistically significant weight loss in kg at 6 months over standard-of-care in a randomized controlled clinical trial (RCT; prespecified primary outcome) (1). The intervention included challenges during which a remote coach encouraged participants to increase step counts within a specific timeframe. We now sought to determine if the individual performances of participants in the intervention group during a single step challenge early in the 6-month RCT could predict who would successfully lose weight by the end of the trial.Methods: Methods of the RCT follow those previously published (1). We focused on the first 2-day step challenge that was unencumbered, meaning that no other challenge occurred within 7 days beforehand, nor the 7 days afterwards. For each participant, the first 2-day unencumbered challenge period was compared with a similar 2-day window 7 days earlier (pre-challenge). To assess individual engagement, objectively determined average step counts from wrist-worn accelerometers were compared between the challenge vs the pre-challenge.Results: Participants who achieved weight loss ≥5% body weight at 6 months increased their daily step counts during the first unencumbered step challenge period by 5992.6 ± 5819.9 (mean ± SE). In contrast, participants who did not achieve this degree of weight loss at 6 months decreased their daily step counts during the first challenge period by 2943.1 ± 5438.1 (t-test p=0.019).Conclusion: Successful engagement in a single step-challenge early in the trial is associated with clinically meaningful and statistically significant weight loss at 6 months. This finding can be used to better predict outcomes for participants in our technology-based remote weight loss intervention and could be used to adjust the coaching intervention to benefit early low-responders.DisclosureB. Sheridan: None. C. Deutsch: None. H. Zhao: None. K. Williams: Stock/Shareholder; Hygieia. C. Vaz: Consultant; Novo Nordisk.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-638-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 639-P: Assessing the Role of Diabetes-Specific Social Connection in
Adolescents and Young Adults with Type 1 Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 639-P
Abstract: Introduction and Objective: The importance of social support in adolescents and young adults (AYA) is well-established, although research pertaining to its role for person(s) living with type 1 diabetes (PWT1D) is limited. We explored factors associated with improved outcomes in AYA with type 1 diabetes (T1D), particularly specific to the potential role of social connections (SC) and relationships between PWT1D.Methods: AYA with T1D who were patients at Loyola Medicine endocrinology clinics in Illinois were included. We utilized chart review and a survey with novel T1D SC questions and the Diabetes Empowerment Scale-Short Form completed during a clinic appointment.Results: Seventeen AYA were recruited [M age = 15.9±2, M DM duration = 5.6 ± 3.6 years, M HbA1c = 7.5 ±1%]. Most AYA had met a PWT1D in their lifetime (94%), at least annual contact with a PWTID (59%), and a DM mentor (71%). A minority of AYA reported “regular connection” with a PWT1D (24%), having a DM community (18%), and attendance at a DM camp or event (35%). Nine AYA (53%) thought they would benefit from talking to a PWT1D.Conclusion: This study serves as a feasible model for assessing the impact of T1D SC in AYA. Our data is not powered to detect differences between groups, however such data would better inform patient care, advocacy, funding, and policy changes.DisclosureH. Carey: None. S. Bansal: None. R. O'Meara: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-639-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 640-P: Exploring Self-Management Practices and Education Needs among
Low-Income Adults with Type 2 Diabetes Using the Information, Motivation,
and Behavioral Skills Model-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 640-P
Abstract: Introduction and Objective: Individuals with low income face a disproportionate burden of type 2 diabetes (T2D). Engaging in diabetes self-management behaviors (SMB) is essential for optimal health outcomes. Guided by the Information, Motivation, and Behavioral Skills (IMB) model, we explored the SMB, motivations, challenges, and information needs of low-income adults living with T2D.Methods: We conducted semi-structured interviews with 17 adults recruited from the community and online. Data were analyzed using deductive and inductive thematic approaches guided by the IMB model.Results: Participants (11 females, 7 males) ages ranged from 24 to 73 years (mean: 44±18), and 100% earned <$50,000/year. T2D diagnosis duration ranged from 1-20 years. Three main themes related to SMB emerged: 1) self-directed behavioral changes amid challenges, 2) fear, support, and health aspirations drive SMB engagement, and 3) the need for tailored education and skill development for proficient self-management. Participants reported engaging in four common SMBs: dietary modifications, physical activity, medication use, and glucose monitoring using information from family, friends, the internet, and some healthcare professionals. These practices were carried out despite highlighted cultural, psychosocial, financial, and systemic barriers, including limited diabetes education and lack of insurance. Motivators included social support, a desire to improve their health, and the fear of complications, often influenced by observing severe diabetes-related complications in family and friends. Participants expressed the need to better understand T2D and more personalized, comprehensive self-management education.Conclusion: Interventions that increase access to health insurance and personalized diabetes education and strengthen social support networks may reduce disparities in low-income adults with T2D.DisclosureE.O. Owolabi: None. M. Boakye: None. A.R. Rajan: None. G.Q. Shaibi: None.FundingArizona State University Institute of Social Science Research
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-640-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 641-P: “Feeling secure is important to me, but I just don't… most of
the time”—Patient Definitions of Success in Diabetes Management-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 641-P
Abstract: Introduction and Objective: Healthcare systems focus diabetes management on clinical metrics (e.g., A1c). However, people with diabetes (PWD) may evaluate diabetes care in more complex ways. This mixed methods study explores patient definitions of success in diabetes management within a diverse sample of PWD.Methods: Forty adults with type 1, type 2 or gestational diabetes were selected using maximum variation sampling based on their responses to a larger (n=573) quantitative study of PWD. Semi-structured 1:1 interviews assessed beliefs and experiences regarding psychosocial aspects of diabetes care. Thematic analysis was used to explore patient definitions of success in diabetes management.Results: Participant characteristics (mean age: 49 (SD: 16), 60% female, 58% non-hispanic white; A1c range: 4.7%-12.0%, PAID-11 range: 0-39). Preliminarily, emerging success-related themes included: (1) blood sugar (“I get up in the morning and the first thing I do is I check with my CGM, my blood sugar, kind of see what's going on.”); (2) feeling secure (“Feeling secure is important to me, which I don't.... around diabetes, so I can live semi-normally, but I just don't feel secure most of the time.”); (3) mental health (“I think it's important to have good counseling to keep you focused. Seeing an actual therapist about it.”); (4) and supportive relationships with providers ( “The most important to me is the communication between me and my diabetes team⋯ I've gone through so many doctors that don't actually care about the patient.”)Conclusion: While participants valued clinical measures, they defined success more broadly. Addressing these aspects when setting goals can enhance patient-centered diabetes care.DisclosureC.A. Okine: None. A.A. Rodriguez-Putnam: None. K.M. Mannor: None. D. LaQueen: None. B. Mezuk: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-641-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 642-P: Correlates of Device Use as Young Adults (YA) with Type 1 Diabetes
(T1D) Leave Pediatric Care-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 642-P
Abstract: Introduction and Objective: Continuous glucose monitors (CGMs) and insulin pumps can optimize diabetes outcomes, yet their use in YA has been under-investigated, especially during the transition from pediatric to adult care. We explored patterns of diabetes device use at the start of this transition period.Methods: At baseline of a behavioral trial, 100 YA (age 17-25) with T1D reported on demographics, clinical variables, and measures of T1D self-management, diabetes distress, and quality of life. HbA1c was obtained from medical records or home kits. Device use was categorized as (1) CGM or pump or neither vs. (2) CGM and pump. T-tests and X-square tests compared device use groups.Results: As noted in Table, YA using more advanced technologies were more likely to live away from parents, attend post-high school, have private insurance, and have lower social vulnerability. They had lower HbA1c and reported less diabetes distress.Conclusion: At the cusp of transition to adult care, socioeconomic disparities in advanced device use across demographically diverse YA with T1D may be associated with differences in glycemic and psychosocial outcomes. Pediatric and adult clinicians should support sustained device use throughout transition. Policy change is needed to facilitate access to advanced devices.DisclosureS.S. Eshtehardi: None. C.G. Minard: None. S.A. Carreon: None. S. Camey: None. W. Levy: None. S. Lyons: None. S. Mckay: None. S. Devaraj: None. R. Streisand: None. T.S. Tang: None. B.J. Anderson-Thomas: None. M.E. Hilliard: None.FundingNational Institute of Health (1R01DK119246)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-642-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 643-P: Healthy Eating among Postpartum Women with Gestational Diabetes—A
Preliminary Analysis of Barriers and Facilitators Using Patient Journey
Maps-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 643-P
Abstract: Introduction and Objective: A healthy diet is crucial for preventing type 2 diabetes (T2D) after gestational diabetes mellitus (GDM). Black, Hispanic, Southeast Asian women face higher rates of GDM and progression to T2D. This study explored barriers and facilitators of healthy eating in postpartum women of color with GDM.Methods: We used patient journey mapping, a qualitative research method, to study factors influencing T2D development after GDM. Participants were Black, Latina, or South Asian women who gave birth in New York City and were 1 to 15 years postpartum. Twelve interviews were conducted between July and December 2024. Journey maps were created for each participant within a week of the interview. A matrix identified individual-level and structural pain points and bright spots affecting dietary behaviors during pregnancy through postpartum.Results: Nine of 12 participants were married and 8 were college educated. Seven had private insurance; the rest had public or no insurance. Half had progressed to T2D. During pregnancy, participants described being motivated to eat healthier for the baby’s sake. Access to a nutritionist and support from family and co-workers also facilitated healthy eating. Postpartum, participants described a loss of motivation and time for self-care, exacerbated by stress and poor mental health. Returning to work in-person was challenging for some, as cooking at home made it easier to eat healthier. At a structural level, there was minimal support from the healthcare system to sustain lifestyle changes. During both pregnancy and postpartum, poor physical or financial access to healthy food near home or work were often identified as structural pain points, though some overcame this by driving farther or ordering groceries online.Conclusion: This study identified preliminary barriers and facilitators of healthy eating as a means to prevent T2D in women with GDM.DisclosureS. Albrecht: None. F.M. Howell: None. A. Balbierz: None. E. Lopez: None. T. Janevic: None.FundingNIH/NIDDK (R01 DK34725-02)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-643-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 644-P: Eating Disorders among Adults with Diabetes
-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 644-P
Abstract: Introduction and Objective: Individuals with diabetes have higher incidence of eating disorders (ED). This chart review of all patients with diabetes receiving care in a large, Southern California health system aimed to investigate the rates of diagnosed EDs in this population, and the demographic and clinical characteristics of the individuals with both diabetes and an ED.Methods: A retrospective analysis was conducted on N = 75,957 adults with any ICD-10 coded diagnosis of diabetes who had an encounter at the Scripps Heath system between 2017 - 2024. Coded diagnoses of an ED (F50 family) in a patient’s record were used to define an individual with a diagnosed ED. Propensity matching based on demographics that differed between those who did and did not have an ED was employed prior to examining clinical differences.Results: Approximately 4% (n= 334) of patients with diabetes had an ED. Among those, binge eating (28%), anorexia (13%), and bulimia nervosa (10%) accounted for about half of the EDs, while the rest were unspecified. Patients with an ED were more likely to be female (75% vs. 49%), white (74% vs 67%), and younger (61±19 vs 69±15) than those without (ps <.001). While 8% of the patients who did not have an ED had T1D, 18% of those who did have an ED had T1D (p <.001). After matching on race, sex, age, and diabetes type, patients with an ED had higher rates of cardiovascular, liver, and renal disease, anemia, hypertension, substance use disorders, and depression comorbidities (ps <.05). Rates of diabetes medication orders for insulin, metformin, or SGLT-2 inhibitors did not differ between those who did and did not have an ED; however, higher rates of GLP-1 receptor antagonists (44% vs 28%) were observed in those with an ED (p <.001).Conclusion: Comorbidity burden and T1D diagnosis was higher in individuals with EDs, while diabetes medications use rates were similar besides GLP-1s. Research to increase ED screening in individuals with diabetes and understanding the impact of ED management on diabetes outcomes is ongoing.DisclosureS.R. Spierling Bagsic: None. E.C. Soriano: None. A.L. Fortmann: None. A. Philis-Tsimikas: Advisory Panel; Dexcom, Inc. Research Support; Dexcom, Inc. Advisory Panel; Lilly Diabetes. Research Support; Lilly Diabetes. Advisory Panel; Novo Nordisk. Research Support; Novo Nordisk. Advisory Panel; Medtronic, Sanofi.FundingScripps Collaborative for Health Equity Pilot Award
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-644-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 645-P: Perspectives on Two Low-Carbohydrate and Lifestyle Programs for
Adults with Prediabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 645-P
Abstract: Introduction and Objective: The National Diabetes Prevention Program (NDPP) can reduce risk of type 2 diabetes (T2D), yet many people face barriers. Alternative diets to the NDPP low fat diet, such as a very low carbohydrate diet (VLCD), may improve engagement and outcomes. Thus, we are conducting a 12-month randomized controlled comparative effectiveness trial of the NDPP and a VLCD version for adults with overweight/obesity and prediabetes. The objective of this study was to compare experiences during the programs to understand acceptability and influences on outcomes.Methods: Interviews were conducted with a subsample of trial participants after 4 months. We invited participants with high and low relative weight loss from both programs to ensure representation in study outcomes. Data were analyzed using thematic analysis, including line-by-line coding, participant summaries, and discussion to develop themes within and between the NDPP and VLCD programs.Results: We have interviewed 31 participants to date (13 NDPP, 18 VLCD). Mean age was 58, 52% were female and 42% were White, 26% Asian, 13% Black, and 13% Hispanic. Themes were: 1) Motivated to lose weight, avoid T2D; 2) Social support promoted accountability, social pressure limited adherence; 3) Growth mindsets helped face challenges; 4) Health improvements increased commitment; 5) Desired more nutrition and T2D risk information. Differences between programs included what type of information was desired, perceived flexibility of the diet, and acceptability among family, friends, and providers.Conclusion: NDPP and VLCD programs were viewed positively, and engagement was supported by program structure. Future interventions may benefit from group interaction to emphasize support and accountability. Understanding the link between diet and T2D could increase motivation and may similarly support patient counseling in clinical settings. VLCD participants may need additional resources to support flexibility in social settings.DisclosureM. DeJonckheere: None. D. Dikeman: None. A.M. Fritz: None. S. Greenwell: None. M. Munawar: None. J. Krinock: None. W.S. Yancy: Consultant; FoodMinds. D.H. Griauzde: None. L. Saslow: None.FundingNational Institutes of Health (R01DK125792)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-645-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 646-P: Maternal Quality of Life during the Transition to Adulthood—A
Mixed Methods Approach-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 646-P
Abstract: Introduction and Objective: The transition to adulthood for adolescents and young adults with type 1 diabetes (T1D) presents unique challenges for mothers who must balance their child’s growing independence with their own quality of life (QoL) and the demands of diabetes management. This study aimed to explore the influence of social support and T1D-related distress on maternal QoL during their child’s transition to adulthood.Methods: This convergent parallel mixed methods study explored maternal experiences during the transition to adulthood. In addition to demographic and clinical data, quantitative data were collected from 72 mothers of adolescents and young adults with T1D (ages 15-25) using validated measures, including the Type 1 Diabetes and Life Measure, the Parent Diabetes Distress Scale, and the Multidimensional Scale of Perceived Social Support. In-depth, semi-structured interviews were conducted with a subset of 12 mothers to capture qualitative insights into challenges and role transitions. Quantitative and qualitative data were analyzed independently and merged during interpretation to identify converging and diverging themes.Results: Quantitative findings revealed significant negative associations between maternal diabetes-related distress and QoL, particularly in emotional experiences and parent-young adult relationships. Perceived social support from family and friends showed small but positive correlations with QoL. Qualitative analysis highlighted themes of disrupted sleep, persistent anxiety, and loss of control as primary contributors to distress. Mothers expressed concerns about their child’s readiness for self-management and difficulties relinquishing management responsibilities.Conclusion: This study underscores the impact of diabetes-related distress on maternal QoL during the transition to adulthood. The findings highlight the need for targeted interventions to reduce maternal distress, enhance support systems, and facilitate healthier transitions for both mothers and their children.DisclosureM. Ness: None. J. Saylor: None.FundingTowson University: OSPR Seed Funding for Grantseekers
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-646-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 647-P: Diabetes Management among Young Adults during Hurricane Helene in
South Carolina—Experiences and Coping Strategies-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 647-P
Abstract: Introduction and Objective: Natural disasters can disrupt critical health-related resources for individuals with chronic conditions like diabetes. This study examines the experiences of young adults with youth-onset diabetes during and immediately after Hurricane Helene.Methods: Thematic analyses were conducted on data obtained from interviews with 9 participants in the ongoing SEARCH Food Security 2 Cohort study (7 participants with type 1 diabetes, 2 with type 2 diabetes, 7 classified as food insecure) from September to December 2024.Results: Some of the participants shared that they were unprepared for the storm's severity. The resulting power outages, property damage, limited access to food and closed pharmacies challenged their diabetes self-management. One challenge mentioned by participants was a decreased importance of a nutritious diet since they were in “survival mode,” which led to unregulated blood sugar levels from limited eating or eating processed, unhealthy foods. Another challenge identified was difficulty monitoring their blood sugar levels and adjusting insulin since some participants did not have means to charge the technology they relied on for regular management. This challenge resulted in more “roller-coastery” levels since they were relying on bodily symptoms to identify blood sugar abnormalities. The final key challenge mentioned by participants was the ability to access and store medication since power was out and there was not cold storage easily available. This limited the amount of insulin participants were willing to administer, and one of the participants ran out of insulin and was unable to access more since pharmacies were closed.Conclusion: This study highlights the vulnerabilities of people with diabetes during a hurricane. Emergency preparedness planning involving patients, clinicians, and the healthcare system may enhance diabetes management during crisis situations.DisclosureS. Sultana: None. M.E. Austin: None. R.E. Davis: None. T.A. Bekelman: None. J.A. Mendoza: None. M.T. Pruitt: None. M. Parker: None. A.D. Liese: None.FundingNational Institute of Diabetes and Digestive and Kidney Diseases (R01DK117461)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-647-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 648-P: Qualitative Evaluation of an Evidence-Based Diabetes Prevention
Program for Adolescents and Young Adults Using the RE-AIM Framework-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 648-P
Abstract: Introduction and Objective: Despite rapidly increasing rates of Type 2 diabetes among adolescents/young adults (AYA), this population is underserved by current diabetes prevention efforts. The Targeted Upstream Prevention (T-UP) study was designed to address gaps in knowledge about the implementation of a developmentally tailored version of the National Diabetes Prevention Program (DPP) among undergraduate student participants.Methods: We conducted qualitative interviews with T-UP participants to examine perceptions of reach, effectiveness, adoption, implementation, and maintenance (RE-AIM) of the T-UP program after a pilot administration in the 2023-24 academic year. Interviews were recorded, professionally transcribed, and analyzed using rapid qualitative analysis (RQA). Emergent themes were organized using RE-AIM dimensions. Participants provided informed consent and the study was IRB approved.Results: Ten participants completed interviews between August and September 2024. Students discussed their perceptions of the program; examples include reach (i.e., motivation to participate, including desire for health education, diabetes prevention, and family history of diabetes); effectiveness (e.g., high degree of satisfaction with program, coaches, and experiential components (e.g., teaching kitchen, exercise and grocery shopping sessions)); adoption (e.g., learning about setting goals, healthy food choices and options, and impact on mental health); implementation (e.g., appreciated program materials and weekly, in-person format but experienced scheduling conflicts due to heavy and/or changing academic and work commitments); maintenance (e.g., perceived the program to facilitate positive lifestyle changes and would recommend to others).Conclusion: These findings provided critical evidence that was used to further optimize and expand the program for a second administration in the current academic year.DisclosureA. Michel: None. T.B. Loeb: None. K. Diaz Roldan: None. S. Soetenga: None. T. Moin: None. L.E. Wisk: None.FundingAmerican Diabetes Association (7-23-ICTST2DY-11)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-648-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 649-P: Sex Differences in Predictors of Food Craving, Eating Behavior, and
Weight Changes Assessed Longitudinally over a 24-Month Period-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 649-P
Abstract: Introduction and Objective: The COVID-19 pandemic produced significant lifestyle changes and restrictions, and recent research indicates that sex differences in stress and eating behaviors may contribute to elevated weight gain in women. However, the understanding of interactions between stress and resilience on weight gain and eating behavior remains limited. Thus, we examined how sex differences in emotion regulation, coping, and stress impacts eating behavior and BMI in a longitudinal cohort.Methods: In 157 individuals (79 female), we measured BMI, eating behavior, food craving, and stress every 6 months over a 24-month period, as well as baseline resilience factors. Eating behavior was measured by the Dutch Eating Behavior Questionnaire and the Food Craving Inventory. Stress and resilience were measured by the Perceived Stress Scale, the Difficulties in Emotion Regulation Scale, and the Coping Orientation to Problems Experienced Questionnaire. Linear mixed-effects models included individual random effects and were either sex-stratified or included gender as a covariate.Results: Higher stress significantly predicted higher overeating behavior (p<0.001) and cravings (p<0.05). Worse baseline emotion regulation also predicted more overeating behavior (p<0.01) over the study. Higher stress predicted higher BMI and change in BMI overall (p<0.05) and specifically in women (p<0.05).Conclusion: These analyses provide insight into resilience factors and eating behavior as they relate to stress and obesity risk, suggesting that stress and deficits in emotion regulation may result in overeating, craving, and ultimately weight gain. This suggests that specific interventions that target stress and emotion regulation could be of benefit, especially among women to reduce obesity risk.DisclosureE. Dauginikas: None. C. Horvath-Diano: None. E.A. Heilner: None. E. Sakmar: None. R. Sinha: Research Support; Tenacia Biotechnologies, AELIS FARMA. Board Member; Menda Health. Research Support; Connecticut Pharmaceuticals Research Solutions. Z.M. Harvanek: None.FundingNational Institutes of Health (RO1DK099039-01A1); National Institutes of Health (K23DK136932)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-649-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 650-P: Longitudinal Associations of Peer Support with Self-Efficacy,
Depression, and Diabetes Management in Early Emerging Adults with Type 1
Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 650-P
Abstract: Introduction and Objective: Social support is important for optimal type 1 diabetes (T1D) management, but data on support from peers during emerging adulthood have been inconsistent. This may be because prior research has largely focused on instrumental or informational support that can threaten needs for competence. We developed a measure of peer support that may facilitate T1D management without undermining competence needs and examined its longitudinal associations with self-efficacy (i.e., perceived competence), depression, and T1D management from late adolescence into emerging adulthood.Methods: As part of a larger study, emerging adults (N=186; 62% female; 14% Latinx; 83% non-Latinx White) completed surveys annually for four years beginning their last year of high school. Surveys assessed peer support, self-efficacy, depression, and self-management behaviors at each time point. HbA1c was measured with mail-in test kits. Peer support consisted of having friends who provided T1D-specific emotional support, were knowledgeable about T1D and how to handle emergencies, and were perceived as generally helpful.Results: Multilevel modeling was conducted controlling for gender, illness duration, pump status, and household income. Emerging adults with higher average levels of peer support had higher self-efficacy (p<.001), higher self-management behaviors (p<.001), and lower depression (p=.02) on average, but did not differ from those with low support on average levels of HbA1c (p=.828). Further, on years when emerging adults had higher than their average level of peer support, they also had higher self-efficacy (p<.004) and higher self-management behaviors (p<.001), but not lower depression (p=.114) or HbA1c (p=.784).Conclusion: Peer support can be provided in ways that do not undermine competence and can benefit self-efficacy, depression, and self-management behaviors among emerging adults with T1D.DisclosureE. Ellis: None. D. Wiebe: None. C. Berg: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-650-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 651-P: Enhancing Diabetes Self-Management—Feasibility and Impact of a
Culturally Tailored Program for Black Adults Using an Embedded Mixed
Methods Pilot Implementation Trial-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 651-P
Abstract: Introduction and Objective: Low participation in Diabetes Self-Management Education and Support Programs (DSMES) among Black adults is attributed to unique barriers. To enhance DSMES reach and adoption, we co-designed a culturally tailored program and evaluated its feasibility, implementation and preliminary effectiveness.Methods: Two 6-week culturally tailored DSMES were delivered by trained Black facilitators. Using an embedded mixed methods design guided by RE-AIM, and Proctor Outcomes, we assessed implementation feasibility and effectiveness. Outcomes were measured at baseline and 6 months using Wilcoxon Signed-Rank tests. Qualitative content analysis of semi-structured interviews and focus groups explored participant and facilitator perceptions, and program adoptionResults: Thirty-two Black adults participated, primarily female (87%) with a mean age of 57 (SD = 12). At 6 months, significant improvements (p <.05) were observed in self-reported health (12%), health engagement (83%), and diabetes empowerment (20%). Participants reported increased adherence to healthy eating (30%), glucose monitoring (17%), and foot care (54%) compared to baseline. Qualitative findings highlighted the importance of culturally relevant recommendations in diet, stress management, and provider communication for fostering engagement and adherence. High program satisfaction (4.2/5.0) rated by participants was related to an empowering facilitation and safe space. Facilitators found the tailored training to be feasible and acceptable (4.7/5.0). However, program providers noted that funding and leadership support posed barriers to broader implementationConclusion: The culturally tailored DSMES program demonstrated feasibility and significant improvements in health engagement and self-care behaviors among Black adults, with participants and facilitators valuing the culturally relevant approaches to implementationDisclosureO. Shiyanbola: None. M. Wen: None. M.A. Maurer: None.FundingUW School of Medicine and Public Health from the Wisconsin Partnership Program, and NIH-NCATS Clinical and Translational Science Award (WPP 5129 and UL1TR002373)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-651-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 652-P: Effectiveness of a Digital Lifestyle Intervention for Glycemic
Control in People with Type 2 Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 652-P
Abstract: Introduction and Objective: This study aims to evaluate the effectiveness of a digital lifestyle-based interventional program, developed by us, [D-LITE (Diabetes- Lifestyle Intervention for Therapeutic Enhancement)], on metabolic control in individuals with diabetes.Methods: An online diabetes management program utilizing a WhatsApp-based model facilitated continuous and collaborative care among patient, a dietitian, and physicians. The program emphasized real-time engagement, with patients sharing daily photos of their meals and glucose readings in a group setting. This data-driven approach enabled us to deliver personalized recommendations on diet, exercise, pharmacotherapy and sleep, facilitating immediate behavioral modifications. Data was analyzed for 39 patients enrolled in the program between Jan 2023 and Nov 2024.Results: Significant improvements in glycemic parameters were observed even at the end of the first month of the program, as demonstrated in the data presented in the table.Conclusion:Conclusion: This WhatsApp-based diabetes management program helped with significant improvements in glycemic control while empowering patients through real-time feedback and behavioral coaching. The scalability and low-cost nature of the intervention make it a promising model for widespread adoption, particularly in resource-limited settings.DisclosureJ. Gopal: None. M.M. Selvaraj: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-652-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 653-P: Psychosocial Factors and Technology Perceptions Are Associated with
Glycemic Outcomes in Fully Closed Loop Systems (FCL)-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 653-P
Abstract: Introduction and Objective: To evaluate the impact of psychosocial factors, as assessed by the INSPIRE Questionnaire, and perceptions of technology efficacy (TES metrics) on glycemic outcomes and user acceptance of FCL systems in adults with type 1 diabetes.Methods: Data were analyzed from a cohort of 12 adults with T1D who participated in a 1-week at home study of FCL (NCT06041971). Key psychosocial variables, including INSPIRE baseline, TES Benefit, TES Burden, and TES efficacy, were assessed post FCL intervention and examined in relation to its glycemic outcomes, including Time<54, Time Below Range (TBR), Time in Range (TIR), Time Above Range (TAR), and Time>250 in FCL. Pearson correlations identified significant relationships, and insights were drawn regarding the influence of psychosocial factors and perceived efficacy on glycemic control and satisfaction with the FCL system.Results: Higher INSPIRE scores were significantly associated with lower perceived burden (r = -0.587, p < 0.01), better time-in-range (TIR; r = 0.575, p < 0.05) with reduced hypoglycemic exposure (r = -0.716, p < 0.01). TES Benefit strongly correlated with increased TIR (r = 0.805, p < 0.01) and lower hypoglycemic exposure (r = 0.707, p < 0.01), while higher TES Burden was linked to poorer TIR (r = -0.562, p < 0.05) and more hypoglycemic episodes (r = -0.716, p < 0.01). TES benefit strongly associates with overall system acceptance (r = 0.982, p < 0.01). TES efficacy did not correlate significantly with glycemic outcomes.Conclusion: Higher psychosocial engagement, as reflected by INSPIRE scores, and positive perceptions of system benefit are significantly associated with better glycemic outcomes and acceptance of FCL systems. These findings highlight the need for strategies that reduce burden and enhance benefit perception to optimize FCL system adoption, user satisfaction, and clinical outcomes.DisclosureA. Fernandes Moura B Batista: None. M. Moscoso-Vasquez: Other Relationship; Dexcom, Inc. Research Support; Tandem Diabetes Care, Inc, National Institute of Diabetes and Digestive and Kidney Diseases. S.A. Brown: Research Support; Dexcom, Inc., Insulet Corporation, Tandem Diabetes Care, Inc, Tolerion, Roche Diabetes Care. Other Relationship; MannKind Corporation. M.D. DeBoer: Research Support; Dexcom, Inc., Tandem Diabetes Care, Inc, Medtronic. L. Gonder-Frederick: Other Relationship; HFS-Global LLC. M.D. Breton: Speaker's Bureau; Sinocare Inc, Tandem Diabetes Care, Inc. Consultant; Roche Diabetes Care, Boydsense.FundingNational Institutes of Health (NCT06041971)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-653-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 654-P: How Is Diabetes Distress Associated with Glycemic Metrics in Older
Adults with Type 1 Diabetes'-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 654-P
Abstract: Introduction and Objective: Diabetes distress (DD) is associated with sub-optimal glycemic control, impaired awareness of hypoglycemia and overall fear of hypoglycemia. However, the relationship between DD and the rates of hypo- and hyperglycemia using continuous glucose monitoring (CGM) is not well characterized. We looked at the association between DD and CGM metrics in older adults with type 1 diabetes (T1D).Methods: We evaluated a cohort of older adults (age≥ 65 years) with T1D. Data from 2 weeks of CGM, along with the T1D Distress Scale, were analyzed. Statistical analysis using computed linear and multi-regression analysis was performed.Results: We evaluated 162 older adults, mean age 71 ± 5 years, duration of diabetes 39 ± 16 years, 64% female, 44% CGM naïve and 29% with depression. DD was positively correlated with time above range (>180 mg/dL) (r = 0.23, p = 0.01) and negatively correlated with time below range (<70 mg/dL) (r = -0.24, p = 0.01). The correlation between higher levels of DD with lower time spent in hypoglycemia was independent of age, gender, living situation, and presence of depression (beta: -1.7 (95% CI: -3.5 to -0.2, p = 0.03).Conclusion: In older adults with T1D, higher levels of DD are associated with reduced time spent in hypoglycemia and increased time spent in hyperglycemia measured by CGM. The relationship between DD and hypoglycemia is independent of age, gender, living status and presence of depression. This finding suggests that the presence of DD may impact emotional and cognitive factors influencing diabetes self-management. Further research is needed into this relationship.DisclosureC. Johnson: None. C. Slyne: None. M. Munshi: Advisory Panel; Abbott, Medtronic. Research Support; Dexcom, Inc. Advisory Panel; Sanofi. E. Toschi: Consultant; Vertex Pharmaceuticals Incorporated, Sequel Med Tech. Research Support; Dexcom, Inc.FundingThis study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health (grant DP3DK112214 to M.N.M. and E.T.). CGM materials were partially supplied by Dexcom.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-654-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 655-P: Characteristics of Emerging Adults with Type 1 Diabetes Who No-Show
or Cancel Clinic Visits-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 655-P
Abstract: Introduction and Objective: Higher A1c and increased complications are seen in people with T1D who miss clinic visits. No-shows, while problematic, are visible to providers. Last-minute cancelations may go unnoticed, which can lead to longer care gaps. We explored differences between no-shows, last-minute cancelations, and completed visits.Methods: Schedules of 3 endocrinology clinics (2 pediatric, 1 adult) were reviewed for patients with T1D (>1 year) ages 15-35 who had visits scheduled in a 2-month period. Demographics, visit completion, A1c, and use of emergency (ED)/inpatient care over the last year were recorded. We compared these factors by visit completion status (completed, canceled within 1 week, no-show) with ANOVA, chi-square, and Fisher’s exact tests.Results: Of 282 visits, 9% were no-shows and 21% were last-minute cancelations. Visit cancelations/no-shows were more common in people with public than private insurance (24% vs 18%, 13% vs 6% respectively, p=0.002). No-shows were similar in pediatric and adult clinics (9% for both), but cancelations were more common in the adult clinic (26% vs 11%, p=0.011). A1c was higher in people who no-showed (9.5%) than those who canceled (8.3%) or completed visits (8.0%, p=0.002). There were differences in number of cancelations/no-shows in the last year between those who no-showed (2.4), canceled (1.9), and completed visits (1.3, p<0.001). Those who received ED/inpatient care in the last year were more likely to have no-showed (17% vs 7%) or canceled (26% vs 19%) than those who did not. There were no differences by visit completion status in age, gender, number of completed visits, or days since last completed visit.Conclusion: Among 15-35-year-olds with T1D, 9% of visits were no-showed and 21% canceled last-minute. Those who canceled had similar A1c to those who completed visits but were more likely to have used ED/inpatient care. Mechanisms to ensure appropriate follow-up among patients with T1D who have last-minute cancelations should be explored.Disclosure I. Patterson: Stock/Shareholder; CRISPR Therapeutics. H. Ruggles: None. D.A. DeWalt: Research Support; Blue Cross Blue Shield of North Carolina. R.J. Vitale: None.FundingNIH (U24DK132715, K12DK133995)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-655-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 656-P: Psychological Assessment at Type 1 Diabetes Diagnosis—Assessing
-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 656-P
Abstract: Introduction and Objective: Anxiety, depression, ADHD, and diabetes distress are all associated with adherence issues and risk for poor health outcomes in people with type 1 diabetes (T1D). However, there is limited research assessing youth at time of T1D diagnosis for psychological factors that increase risk for low treatment adherence. Our objective is to assess baseline history of anxiety, depression, and ADHD, as well as anxiety related to the onset of T1D diagnosis.Methods: An automatic psychology inpatient consult was added for all youth admitted with new onset of T1D at a large pediatric hospital. Psychologists assessed all patients admitted on weekdays using clinical interview with patients and parents. Parent interview assessed symptoms for infants and young children. Interventions included psychoeducation about the adjustment period, coping strategies to manage anxiety, and providing anticipatory guidance on how ADHD can affect diabetes management.Results: Psychologists screened 119 patients (range 9 months to 18 yrs; M = 9.05 years). Screening showed that 38 patients (32%) had a history of mental health concerns (25 with anxiety; 11 with depression; 21 with ADHD) and 64 patients (54%) endorsed anxiety related to diabetes diagnosis. Some patients had injection anxiety, general diabetes distress, worries about peer reactions to diabetes diagnosis, worries about managing diabetes at school, and worries about complications. Of note, 11 patients had mental health comorbidities such as both anxiety and depression.Conclusion: At T1D diagnosis, 32% of our pediatric cohort had a history of baseline anxiety, depression, and/or ADHD and 54% of patients had anxiety related to diabetes diagnosis. Since anxiety, depression, and ADHD can increase risk for hospitalizations and diabetes related complications, early identification of psychological concerns at T1D diagnosis can help promote earlier therapeutic interventions.DisclosureK. Semenkovich: None. M.K. Kamboj: None. M.M. Perry: None. M. Abdelhadi: None. D.A. Buckingham: None. K. Hong: None. J.A. Indyk: None. H. Yardley: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-656-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 657-P: “If I'm not hard on myself, I'm not gonna do a good
job”—Self-Criticism vs. Self-Compassion in Type 1 Diabetes (T1D)-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 657-P
Abstract: Introduction and Objective: T1D requires a burdensome self-management regimen to prevent short- and long-term complications, and creates opportunities for self-criticism. Compassion-based approaches offer alternative ways of responding to challenges of living with T1D. Less is known about acceptability of these approaches for people living with T1D.Methods: This qualitative study explored experiences with and attitudes toward self-criticism vs self-compassion among adults who attended a T1D self-compassion workshop series. Focus groups were audio-recorded, transcribed and coded using content analysis.Results: Twenty-three adults (age 43±15 years; T1D duration 28±13 years; 65% female; 61% White, 22% Asian, 4% Hispanic, 4% Black; 78% closed loop users) participated. Many described self-critical tendencies when facing T1D challenges (see Table 1). Self-criticism was viewed by some as necessary to motivate T1D management. Participants described experiences with clinicians who were compassionate vs less compassionate and expressed a preference for incorporating compassion strategies and attention to emotional well-being into clinical care. Conclusion: More research is needed on the role of self-criticism vs self-compassion in T1D management which could inform development of acceptable, feasible compassion-based programs with people living with T1D. DisclosureM.B. Pasmooij: None. B. Cassoff: None. C.J. Kaelberer: None. K.E. Judge: None. M. Basina: None. M.L. Tanenbaum: None.FundingPilot funding from the Stanford Diabetes Research Center (P30DK116074)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-657-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 658-P: Acceptability of an Intervention to Reduce the Use of
Diabetes-Stigmatizing Language in the Primary Care Environment-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 658-P
Abstract: Introduction and Objective: Adults with type 2 diabetes experience stigmatizing language within healthcare environments. The American Diabetes Association and the Association for Diabetes Care & Education Specialists issued guidelines aimed at reducing the use of such language. We developed an intervention aimed at healthcare providers (HCPs) to enhance their awareness and encourage the adoption of these guidelines within primary care settings. The intervention comprises a simulated clinical encounter with a standardized patient, an educational video, and a self-reflective exercise centered on the language used in the interaction with the standardized patient. The objective was to pilot the intervention.Methods: A sequential mixed methods randomized controlled pilot design was used. This presentation focuses on the data derived from the debriefing interviews. For the analysis, a qualitative descriptive approach was used, with the assistance of Atlas.ti.Results: Qualitative analysis of the participant data (N=21; mean age=38±12 years, 76% female, 57% non-Hispanic white, 62% physicians) resulted in four main themes: (1) the impact of language on patient engagement, (2) the reinforcement of professional values through language, (3) the identification of communication barriers, and (4) the recognition of benefits associated with language training. Participants emphasized the critical role of language in enhancing patient engagement. While many HCPs acknowledged that the use of appropriate language aligns with professional values, some questioned its significance relative to clinical expertise. Barriers to reducing the use of diabetes-stigmatizing language included constraints such as time limitations and inadequate training.Conclusion: The findings of this pilot study provide insights into addressing identified barriers and leveraging recognized benefits to optimize the effectiveness and implementation of such interventions.DisclosureA. Agapiou: None. S. Lin: None. A.G. Carmichael: None. B.P. Labbree: None. R. Gonzalez: None. K. Joiner: None.FundingAmerican Diabetes Association (CDTR-03)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-658-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 659-P: Barriers and Facilitators to Attending Postpartum Diabetes
Screening among Women with Gestational Diabetes (GDM) in
China—Qualitative Insights from Women with GDM and Health Care
Professionals-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 659-P
Abstract: Introduction and Objective: Women who experience gestational diabetes mellitus (GDM) have an increased risk of future type 2 diabetes. Postpartum diabetes screening is recommended to identify impaired glucose regulation and to deliver diabetes prevention care. However, screening uptake is suboptimal in many countries, particularly in China, where GDM is prevalent. This study explored mediating factors for the uptake of postpartum diabetes screening from the perspectives of women with GDM and healthcare providers (HCPs).Methods: Semi-structured interviews were conducted virtually with women with GDM and HCPs involved in GDM care. The sample was purposively recruited, and informational power was used to determine the sample size. Data from both groups were analyzed separately using Framework analysis and synthesized to identify areas of convergence.Results: Twenty-four women with GDM and 18 HCPs participated. Both groups identified individual mediating factors, including GDM risk perceptions, competing priorities, childcare responsibilities, and postpartum health motivation, alongside organizational barriers such as screening acceptability and accessibility. Women noted a lack of prioritization of GDM from HCPs, dismissal of their concerns, and insufficient follow-up support. HCPs emphasized their own focus on short-term birth outcomes, and that postnatal care was beyond their remit. HCPs also reported challenges with diabetes education, communication, managing heavy workloads, and a healthcare system not effectively orientated toward GDM follow-up care.Conclusion: The findings reveal multifaceted barriers and facilitators to postpartum diabetes screening. Improved communication between women and HCPs and systemic changes are required to enhance postpartum GDM care, screening uptake and engagement with diabetes prevention strategies.DisclosureJ. Huang: None. A. Forbes: None. R. Forde: None. J. Parsons: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-659-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 660-P: Understanding the Association between Health-Related Social Needs
and Digital Health Use among People with Type 2 Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 660-P
Abstract: Introduction and Objective: Digital health can improve outcomes for people with type 2 diabetes (T2D). Use of digital health tools, however, vary across patient populations. How health related social needs (HRSN) impact digital health use is largely unknown.Methods: Data from the 2022 Health Information National Trends Survey were analyzed to investigate the association between HRSN and digital health use among people with T2D. HRSN variables of interest included self-report of 1) food insecurity, 2) housing instability, and 3) transportation challenges. Primary outcomes of digital health use included self-reported use of 1) telehealth and 2) patient portals in the previous 12 months. Logistic regressions, adjusted for age, gender, and race, produced Odds Ratios (OR) and 95% Confidence Intervals (CI) to estimate the association between HRSN and digital health use.Results: Among 1304 adults with T2D and mean age of 62.4 years, 18.2% reported food insecurity, 12.6% housing instability, and 15.4% transportation challenges. Among this group, 47.8% reported telehealth use and 56.1% patient portal use. Food insecurity was associated with increased telehealth use (OR 1.4, 95% CI 1.0-2.0) and decreased patient portal use (OR 0.7, 95% CI 0.5-0.9). Housing instability was associated with increased telehealth use (OR 1.6, 95% CI 1.1-2.3). Transportation challenges was associated with decreased patient portal use (OR 0.6, 95% CI 0.4-0.9). Non-significant associations were seen between transportation challenges and increased telehealth use (OR 1.4, 95% CI 1.0-1.9) and between housing instability and decreased patient portal use (OR 0.7, 95% CI 0.5-1.1).Conclusion: In this analysis of adults with T2D, differential relationships between HRSN and digital health use were observed with HRSN associated with increased telehealth use and decreased patient portal use. The observed increase in telehealth use may suggest that it is more of an essential digital health tool than the patient portal is for people who experience HRSN.DisclosureD. Elagi: None. J. Lee: None. D.J. Amante: None.FundingNational Institutes of Health (K01DK131318)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-660-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 661-P: Comparative Analysis of Physical Activity and Dietary Behavior
between Prediabetes and Normoglycemic Population-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 661-P
Abstract: Introduction and Objective: Prediabetes (preDM) among adults is on the rise, physical activity (PA) and healthy diet as modifiable lifestyle influencing factors can help prevent or delay progression to type 2 diabetes in adults with preDM, but it is unclear whether these factors vary by prediabetic status.Methods: Cross-sectional study of Chines adults without DM who attended at a tertiary A hospital in Guangzhou from December 2023 to August 2024, we classified the participants into PreDM group (n=151), Non-preDM group (n=302). We calculated means or medians for PA (from one week of recall data), Planetary Health Diet Score (PHD-S) (from one month of recall data, higher score indicates healthier diet). After controlling for confounders using propensity score matching, independent samples t-tests, rank-sum tests, chi-square tests, or Fisher’s exact probability methods were used to compare PA and dietary differences between the preDM and non-preDM groups. Using R software for statistical analysis.Results: Compared with non-preDM group, the preDM group had more metablic equivalent (MET) for light physical activity (p<0.001), but fewer the number of days per week involving moderate (p<0.001) and vigorous physical activity (p=0.032). PA levels did not significantly vary across the 2 groups (p=0.315). The PHD-S of saturated oils (p=0.007) and added sugars (p=0.011) were higher in the preDM group, but the PHD-S of fish (p=0.021), soy foods (p=0.002) and nuts (p<0.001) were lower. Mediation analysis revealed that in preDM group BMI significantly mediated the relationship of diet to uric acid with mediation proportions of 29.3%.Conclusion: There were differences in PA and diet between the preDM and non-preDM groups. Among adults with preDM, their status of light physical activity, intake of saturated oils and added sugars were better, but they still did not meet the guidelines, and more standardized individualized health interventions should be given to them in the future.DisclosureJ. Lin: None. X. Hu: None.FundingNational natural science foundation of China (72204277); Nursing innovation development research project (YJYZ202304); 3rd Affiliated Hospital of Sun Yat-sen University, Clinical Research Program (YHJH202404)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-661-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 662-P: Diabetes Distress, Management, and Psychosocial Needs among Black
Young Adults with Type 1 Diabetes from Two Health Care Systems—An
Integrated Care System and Public Safety-Net Hospital'-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 662-P
Abstract: Introduction and Objective: Private integrated healthcare and public safety-net care systems address the medical needs of different socioeconomic (SES) status groups. Irrespective of SES, many young adults with T1D struggle with diabetes management. The study evaluated survey data of Black young adults with T1D in two different healthcare systems to understand psychosocial factors, diabetes care behaviors and health outcomes. Methods: Participants were Black young adults with T1D (18-30 years) from a private, integrated healthcare system and a public safety-net hospital-based system with HbA1c > 7.5%. Data were from baseline assessment of an ongoing randomized trial measuring social determinants of health, Diabetes Distress (DDS), Diabetes Self-Management (DSMQ), and HbA1c. T- and Chi-Square Tests assessed differences by recruitment site.Results: Data were collected from 52 Black young adults with T1D (25 private care, 27 public care). Mean age=23.8 years and 38% were male. Mean diabetes distress and self-management scores in private care and public care were 3.4 (SD=1.0) and 2.8 (SD=1.1) (p=.03) and 5.0 (SD=1.8) and 5.6 (SD=1.9) (p=.20), respectively, indicating high and moderate distress and suboptimal self-management. Overall, participants self-reported high financial insecurity (60%). Public care participants reported higher food insecurity (55.6% vs. 28.0%, p=.04) and higher HbA1cs (11.2% vs. 9.3%., p=.0003). Conclusion: Despite better glycemic control in private care, HbA1cs were high across both healthcare systems. Attention should be given to Black young adults with T1D to alleviate diabetes distress, financial challenges, and barriers to self-management regardless of healthcare system. For patients in public care, additional screening and intervention for food insecurity should be considered.DisclosureR. Wolf: None. J. Haw: None. P. Vellanki: Advisory Panel; Eli Lilly and Company. A.F. Hudgins: None. J.I. Barzilay: Stock/Shareholder; Eli Lilly and Company, Medtronic, AbbVie Inc. Other Relationship; Bayer Pharmaceuticals, Inc. Stock/Shareholder; Gilead Sciences, Inc, Merck & Co., Inc. Research Support; National Institutes of Health. Stock/Shareholder; Vertex Pharmaceuticals Incorporated. M. Crawford: None. L. Fisher: None. L.M. Gonzalez Paz: None. I. Graetz: Research Support; Pfizer Inc, PRIME Education, LLC. C. McCracken: None. T.L. Davis: None.FundingNational Institute of Health, National Institute of Diabetes and Digestive and Kidney Diseases (5R01DK128236); Helmsley Charitable Trust (2310-06383)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-662-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 663-P: Associations between Relationship Status and Parenting on Glycemic
and Emotional Outcomes in Adults with Type 1 Diabetes (T1D) Enrolled in
the GluCog Study-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 663-P
Abstract: Introduction and Objective: Prior research has shown a link between marital quality and HbA1c in adults with T1D, however, little is known about how parenting impacts glycemic control, including CGM metrics. The aim of the current study was to investigate whether relationship and parenting status impact glycemic outcomes in adults with T1D. Emotional distress was investigated as a secondary outcome.Methods: A total of 208 participants with T1D (mean [range] age = 45.60 [18-84] years, 53.40% female, 74.5% married or partnered, 30.8% with children ≤18) were recruited from four diabetes centers. Glycemic (HbA1c, CGM time in range [TIR], percent time <70 mg/dL) and emotional (Generalized Anxiety Disorder-7, Patient Health Questionnaire-8, Perceived Stress Survey) outcomes were assessed. Analysis of covariance (ANCOVA) was used to examine the impact of relationship and parenting status on glycemic and emotional outcomes while controlling for age and gender.Results: Single participants (N=53) spent more time in hypoglycemia compared to married/partnered participants (N=155) after controlling for age, gender, and parenting, F (1, 191) = 5.38, p =.02. While there was no main effect of parenting on any outcome, there was a significant interaction between relationship status and parenting on HbA1c, F (1, 196) = 5.29, p =.02, and TIR, F (1, 191) = 6.45, p =.01. Single parents (N=16) had higher HbA1c and lower TIR than single adults without children and married/partnered participants with/without children. Neither relationship status nor parenting was associated with emotional distress.Conclusion: These findings suggest that adults with T1D who are single, and particularly those who are single parents, have poorer glycemic control than those in a relationship. Emotional distress did not differ by relationship or parenting status. Further research is needed to confirm these findings and suggest possible mechanisms.DisclosureM.S. Zuniga-Kennedy: None. L.M. Fonseca: None. Y.C. Kudva: Advisory Panel; Novo Nordisk, Vertex Pharmaceuticals Incorporated, Tandem Diabetes Care, Inc. Research Support; Dexcom, Inc., Insulet Corporation. S. Rizvi: None. R.S. Weinstock: Research Support; Amgen Inc, Eli Lilly and Company, Tandem Diabetes Care, Inc, Diasome Pharmaceuticals, Insulet Corporation, MannKind Corporation, Dexcom, Inc. J.D. Bulger: None. R.E. Pratley: Consultant; AbbVie Inc. Stock/Shareholder; Altanine, Inc. Consultant; Amgen Inc, AstraZeneca. Other Relationship; Bayer AG, Bayer Pharmaceuticals, Inc, Biomea Fusion. Consultant; Boehringer-Ingelheim. Other Relationship; Carmot Therapeutics, Inc, Corcept Therapeutics, Dompé, Eli Lilly and Company, Endogenex. Consultant; Endogenex. Other Relationship; Fractyl Health, Inc., Gasherbrum Bio, Inc. Consultant; Genprex, Getz Pharma, Hanmi Pharm. Co., Ltd, Intas Pharmaceuticals Ltd, Lexicon Pharmaceuticals, Inc, Lilly USA LLC. Speaker's Bureau; Lilly USA LLC. Other Relationship; Metavention, Novo Nordisk, Novo Nordisk. Speaker's Bureau; Novo Nordisk. Other Relationship; Pfizer Inc, Poxel SA. Consultant; Regeneron Pharmaceuticals. Other Relationship; Sanofi. Consultant; Scholar Rock. Other Relationship; Sun Pharmaceutical Industries Ltd. M.R. Rickels: Consultant; Vertex Pharmaceuticals Incorporated, Sernova, Corp. Research Support; Dompé, Tandem Diabetes Care, Inc. Consultant; Novo Nordisk. L. Germine: Stock/Shareholder; Intelerad Medical Systems. N. Chaytor: None.FundingNational Institute of Health - National Institute of Diabetes, Digestive and Kidney Diseases, NIH- NIDDK (R01-DK121240-01)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-663-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 664-P: Identifying Diabetes Distress across Adult Age
Groups—Insights from the ReDUCe Study-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 664-P
Abstract: Introduction and Objective: Diabetes distress, the emotional and behavioral challenges of living with type 1 diabetes (T1D), is common over the lifespan and can lead to adverse medical and psychological outcomes. Interventions that incorporate stakeholder input on diabetes distress across the lifespan remain limited. The ReDUCe Study aims to reduce diabetes distress in adults with T1D by incorporating stakeholder input into its cognitive behavioral therapy protocol.Methods: We used user-centered design to obtain input from younger (18-35) and middle-age (35-64) adults with T1D. We completed remote group sessions to discuss diabetes distress, review the study protocol and receive feedback. Participants were recruited from Montefiore Medical Center and Breakthrough T1D's Patient Advisory Council. A modified inductive coding approach with two independent coders was conducted. Workshops were recorded, transcribed, and analyzed using deductive coding until thematic saturation.Results: We conducted a total of 4 young adult and 2 middle-age adult user-centered design sessions. Young adults: n=12, mean age 27 (Range: 23-33) years; 50% female. Middle-age adults: n=5, mean age 45 (Range: 35-58) years; 100% female. Common themes included: competing priorities with lifestyle management, financial barriers, and system-level issues (e.g., insurance). Both groups viewed financial and insurance issues as major stressors, feeling overwhelmed by the high costs of treatment and medication, which hindered effective diabetes management. Middle-age adults worried about co-existing conditions and costs associated with managing diabetes, while younger adults were concerned with immediate challenges, such as how diabetes disrupted their lifestyle and daily routine.Conclusion: Both young adults and middle-age adults with T1D experience diabetes distress, but differences exist. Adapting interventions to the context for diabetes distress across the life course may enhance engagement.DisclosureM. Finnan: None. R. Rayden: None. G. Crespo-Ramos: None. C.J. Hoogendoorn: None. T. Farchione: Research Support; National Institutes of Health. S. Agarwal: Research Support; Dexcom, Inc. J.S. Gonzalez: None.FundingBreakthrough T1D (4-SRA-2021-1071-M-B)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-664-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 665-P: Association between Housing Insecurity and Hemoglobin A1c among
Adults with Type 2 Diabetes—A Cross-Sectional Analysis of the All of Us
Research Program-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 665-P
Abstract: Introduction and Objective: Housing insecurity is an upstream social determinant of the health factors associated with poor health outcomes. Among adults with diabetes, there is little evidence of an association between housing insecurity and glycemic control. Therefore, a secondary data analysis was conducted to assess the association between housing insecurity and hemoglobin A1C (HbA1C) among 695 adults with type 2 diabetes (T2D) in the United States.Methods: Data was obtained from the “All of Us research program” and analyzed using R programming. A multiple linear regression model was used to assess the association between housing insecurity and HbA1C while adjusting for all covariates.Results: It was found that compared with participants with stable housing, adults with T2D who experienced housing insecurity had a clinically and statistically significant higher HbA1C (Adjusted β = 0.50, 95% CI: 0.07 to 0.93, p = 0.0239) (Figure 1). Additionally, non-Hispanic Blacks had higher HbA1C compared to their non-Hispanic White counterparts (Adjusted β= 0.33, 95% CI: 0.08 to 0.57, p = 0.009). Lastly, men had significantly higher HbA1C than women (Adjusted β=0.32, 95% CI: 0.12 to 0.52, p =0.002).Conclusion: There is a need to incorporate screening for housing instability into patient assessments and facilitate connections with appropriate resources and support services to improve health outcomes.DisclosureE.A. Adawudu: None. E. Ekpor: None.FundingThe All of Us Research Program is supported by the National Institutes of Health, Office of the Director: Regional Medical Centers: 1 OT2 OD026549; 1 OT2 OD026554; 1 OT2 OD026557; 1 OT2 OD026556; 1 OT2 OD026550; 1 OT2 OD 026552; 1 OT2 OD026553; 1 OT2 OD026548; 1 OT2 OD026551; 1 OT2 OD026555; IAA #: AOD 16037; Federally Qualified Health Centers: HHSN 263201600085U; Data and Research Center: 5 U2C OD023196; Biobank: 1 U24 OD023121; The Participant Center: U24 OD023176; Participant Technology Systems Center: 1 U24 OD023163; Communications and Engagement: 3 OT2 OD023205; 3 OT2 OD023206; and Community Partners: 1 OT2 OD025277; 3 OT2 OD025315; 1 OT2 OD025337; 1 OT2 OD025276. In addition, the All of Us Research Program would not be possible without the partnership of its participants.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-665-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 666-P: Diabetes Distress after Participation in Blue Circle Health—An
Innovative Diabetes Care Delivery Program-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 666-P
Abstract: Introduction and Objective: Fee-for-service healthcare makes it difficult for people with T1D to access the care, education, and support that they need. Blue Circle Health (BCH) is a program that closes this gap. BCH is delivered remotely, is 6 months long, and includes coordinated services of endocrinology, peer support, diabetes counseling, case management, insurance navigation, and education. This study aimed to measure the change in patient-reported diabetes-related distress prior to and post completion of their participation in BCH.Methods: Participants completed the T1-Diabetes Distress Assessment System (T1-DDAS) on enrollment and completion of the program. We analyzed pre- and post-intervention Source scale data of the participants that completed the program between June and Dec 2024 (n=47).Results: Mean age at enrollment was 43 yrs; 64% identified as female, 43% were caucasian, 30% hispanic, 20% black. Additionally, 9% were uninsured, 30% had government insurance, and 43% were unemployed or on disability. Post-intervention, there were reductions in distress in 9 of the 10 categories (p<.05).Conclusion: The findings from this study demonstrate important reductions in diabetes distress after 6 months of receiving BCH services. Future data will examine other diabetes-related outcomes of this one-of-a-kind service.DisclosureM.A. Gomberg: None. C. Mullaney: None. M.E. Buhler: None. K. Chaney: Employee; Biofourmis. K.Y. Ward: None. S. Westen: None. L.W. D'Avolio: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-666-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 667-P: A Guided Self-Determination Intervention vs. an Attention Control
Group of People with Type 2 Diabetes in an Outpatient Clinic Setting—A
Randomised Clinical Trial-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 667-P
Abstract: Introduction and Objective: Evidence suggests that the autonomy supportive intervention, the guided self-determination method (GSD), may reduce diabetes distress in people with type 1 diabetes. The objective was to determine the benefits and harms of a GSD intervention versus an attention control group in adults with type 2 diabetes.Methods: The design was a pragmatic, dual-centre, randomised, assessor-blinded, superiority clinical trial of adults (≥18 years) with type 2 diabetes. The participants were randomly assigned to GSD versus attention control group, both groups provided face-to-face or over video. The primary outcome was diabetes distress assessed with the Problem Areas in Diabetes questionnaire. The secondary outcomes were depressive symptoms assessed with Hospital Anxiety and Depression scale; quality of life assessed with SF-36; and non-serious adverse events assessed with the Negative Effects Questionnaire at baseline and 5- and 12-months follow-up.Results: The trial included 150 participants (GSD n=76 versus attention control n=74). This was below our predefined sample size and thresholds for statistical significance were adjusted accordingly. Linear regression showed evidence of beneficial effects of GSD on diabetes distress (MD -5.83; 98.75% CI -11.26;-0.41, p=0.007) and depression (MD -2.77; 98.75% CI -5.24;-0.30, p=0.005). Linear regression showed evidence of a beneficial effect of attention control on quality of life (mental component) (MD 8.10; 98.75% CI 0.94;15.27, p=0.005) but no difference on the physical component (MD 1.79; 98.75% CI -5.72;9.31) or adverse events (MD 0.00; 98.75% Hodges-Lehmann CI 0.00;0.00).Conclusion: The GSD intervention versus attention control seems to reduce diabetes distress and depression. Attention control may improve quality of life.DisclosureA.S. Mathiesen: None. V. Zoffmann: None. M. Olsen: None. J.C. Jakobsen: None. E.H.S. Marqvorsen: None. J. Lindschou: None. B. Rasmussen: None. C. Gluud: None. M.D. Rothmann: None.FundingThe Novo Nordisk Foundation, Steno Collaborative Grant (NNF10OC0057720)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-667-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 668-P: Clustering Technological Attitudes and Experiences of Adolescents
and Adults with Type 1 Diabetes, Family Members, and Health Care Providers
-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 668-P
Abstract: Introduction and Objective: The uptake and continued use of insulin pumps and glucose sensors may be influenced by individual factors. Despite quick developments of technologies, studies informing tailored support related to (perceived or experienced) device disadvantages date back at least five years. We studied how different attitudes, experiences and expectations about diabetes technology cluster together in people with type 1 diabetes (PWD), parents/partners (P/P), and healthcare providers (HCPs) in the era of automated insulin delivery.Methods: Dutch PWD (12+ years), P/P (18+ years), and HCPs completed a cross-sectional online survey. Per sample, K-means (3-)cluster analysis was based on attitudes towards general and diabetes technology, and reasons for device non-uptake (PWD, P/P) or technology readiness (HCPs). Cluster validation compared demographic and clinical variables across the clusters using ANOVAs and X2 tests.Results: In total 219 PWD (mean age 36 years ± 15), 55 P/P and 120 HCPs participated. Across samples, 56-67% reported positive attitudes and less negative expectations/experiences. Among those, PWD and P/P had the lowest diabetes distress and HCPs the most weekly T1D consultations. PWD and P/P with the most negative attitudes (9-31%) also had the most negative expectations/experiences, especially nervousness to rely on a device, and were less likely to use technological devices. A group of PWD (31%) scored average on attitudes, but experienced high burden of device wear. For HCPs with negative attitudes, one group felt less ready than the other and was more likely from a general hospital.Conclusion: When present, negative technology attitudes either span multiple domains or are specifically focused on the burden of wear. This advocates for general as well as wear-specific support. Regarding HCPs, (more) support related to readiness might be beneficial in general hospitals.DisclosureM. Horsselenberg: None. G. Nefs: Other Relationship; Dexcom, Inc., Dexcom, Inc. H. Aanstoot: Consultant; Metronics. Advisory Panel; Sanofi, Dexcom, Inc., Eli Lilly and Company, Kaleideo/ ViCentra. M. Boenink: None. J. Prins: None.FundingDutch Diabetes Research Foundation (2021.82.013)
PubDate: Fri, 13 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-668-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 669-P: Sleep Companions Improve Sleep Quality and Depression in Older
Adults with Type 1 Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 669-P
Abstract: Introduction and Objective: Compared to people without type 1 diabetes (T1D), those with T1D are at increased risk of mood disorders and sleep difficulties. Partner support is overlooked when assessing these factors in older adults with T1D. We aimed to evaluate whether a sleep companion (SC) influences depression, anxiety, and sleep in the Joslin Medalists (T1D ≥50 years, mean age 67).Methods: Depression, anxiety, and sleep were surveyed in Medalists (n=324) using the Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), and Pittsburgh Sleep Quality Index (PSQI), respectively. Associations between scores and self-reports of sleeping alone or with a partner were assessed cross-sectionally with linear regression models adjusted for age, sex, and HbA1c.Results: Mean (±SD) scores for PHQ-9, GAD-7, and PSQI were 3.3 (±3.9), 2.1 (±3.4), and 5.3 (±3.6), respectively. 8% of Medalists met the clinical threshold for moderate-severe depression, 6% for anxiety, and 38% for poor sleep quality. Female Medalists showed more depression symptoms (β=0.95, p=0.03) and worse sleep (β=0.97, p=0.02) than males. Age did not affect scores. Mean HbA1c in Medalists was 6.9 (±0.8). HbA1c positively correlated with depression (β=0.54, p=0.04) but did not correlate with anxiety or sleep. 75% of Medalists had an SC, and HbA1c did not differ between those with and without an SC. Medalists with an SC showed fewer depressive symptoms (β=-1.12, p=0.03) and improved sleep quality (β=-1.10, p=0.03) compared to those without. There was no association with anxiety.Conclusion: Higher HbA1c and female sex increased risk of depression in older adults with T1D, while anxiety remained unaffected. Although women had worse sleep quality than men, having sleep companions improved mood and sleep quality, independent of age, sex, and glycemic control. This could be due to a shared responsibility of diabetes management. Further studies are needed to understand the mediating factors of these relationships.DisclosureE.R. Viebranz: None. S. Jangolla: None. M. Yu: None. N.A. Ziemniak: None. J. Gauthier: None. A. Adam: None. G.L. King: None. H. Shah: None.FundingBeatson Foundation (2791-20005-2500103)NIH (P30DK036836)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-669-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 670-P: Associations between Social Needs and Diabetes-Related Health
Outcomes among Latino Farmworkers-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 670-P
Abstract: Introduction and Objective: Adverse social determinants, or social needs, are increasingly being recognized as contributors to diabetes-related disparities, in particular among high marginalized populations, such as Latino farmworkers. In this stud we aimed to assess the association between social needs (housing, food insecurity, transportation, financial hardship) and diabetes related outcomes (HbA1c, total cholesterol, HDL, LDL, triglycerides, BMI) among Latino farmworkers (n=100).Methods: We leveraged the PRAPARE tool to assess social needs and used various point-of-care tools to assess diabetes related outcomes (A1c+ Now, CardioChek-PTS Diagnostic) in collaboration with community partners, and additionally various sociodemographic were collected. Descriptive statistics were used to assess the sample. Linear regression models were used to assess association between independent and dependent variables.Results: Overall 74% of participants were born outside of the US (Mexico and El Salvador), the average age was 46, in total 71% identified as female. In total 100% had a Spanish-language preference, and 79% reported at least one social need. Higher HbA1c value was found to be associated with higher social needs, and found to be statistically significant. All other diabetes-related outcomes did not have statistically significant association with social needs.Conclusion: This study demonstrates Latino farmworkers face a number of social needs, which need to be addressed in the context of diabetes prevention and self-management. Those living with diabetes should be provided additional support in the form of social and clinical care navigation, community-clinical linkages and referrals, and provided additional resources for maintenance.DisclosureB. Aceves: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-670-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 671-P: Examination of Transition Readiness (TR) and HbA1c in the Year
after Discharge from Pediatric Type 1 Diabetes (T1D) Care-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 671-P
Abstract: Introduction and Objective: Assessment of young adults’ (YA) TR levels can provide insight into their ability to successfully transition to adult T1D healthcare. We assessed TR and HbA1c over the year after discharge from pediatric T1D care in a pilot observation study. We hypothesized that TR levels would increase as YA transitioned and that higher TR levels would relate to lower A1c.Methods: We used the READDY (Readiness of Emerging Adults with Diabetes Diagnosed in Youth) survey to measure TR at 3 timepoints: baseline (discharge from pediatric T1D care), 6-, and 12-months-post-discharge. READDY items are divided into four domains: Diabetes Knowledge, Health System Navigation, Insulin Self-Management, and Health Behaviors, and are scored on a 5-point Likert scale (1=Haven’t thought about it; 5=Yes, I can do this). Domain mean scores of 1-3 are considered low TR; scores 4-5 are high TR. We ran paired sample t-tests for READDY domains between baseline and 6-mos, 6- and 12-mos, and baseline and 12-mos. We ran Pearson correlations between READDY domains at all 3 timepoints and A1c at 12-mos.Results: 24 YA identified as 58% female, 50% NHW, 29% Medicaid, 63% on pumps, 71% on CGM; baseline M±SD age=18.5±1.0 yrs, A1c=9.3±2.0%. Mean READDY domain scores range was 1-1.5. The only significant change was on the Diabetes Knowledge domain, which decreased between baseline and 12-mos. (t=3.11, p=0.01). The correlation between the Health Systems Navigation domain at baseline and A1c at 12-mos approached significance (r=-0.62, p=0.06).Conclusion: Most TR scores were low and remained relatively stable during transition from pediatric T1D care, indicating that interventions are needed to increase TR. Results also suggest that 1) YA may need refresher education courses to improve diabetes knowledge during the transition, 2) YA ability to navigate the health system may have the greatest impact on glycemic outcomes, and 3) Larger, fully powered longitudinal studies are needed to identify additional modifiable targets for TR interventions.DisclosureJ.S. Pierce: None. A. Milkes: None. S. Gurnurkar: None. S.R. Patton: None.FundingDK020593, Vanderbilt Diabetes and Research Training Center Pilot & Feasibility Program
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-671-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 672-P: Association of Different Antidiabetic Medications with Depression
Scores in Veterans-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 672-P
Abstract: Introduction and Objective: There is a bi-directional association between depression and Type-2 Diabetes Mellitus (T2DM), with higher scores being associated with increased prevalence of cardiometabolic disease risk. Current T2DM meds of interest include Glucagon-like-peptide-1 receptor agonists (GLP1A +/- insulin or metformin), Sodium-glucose cotransporter-2 inhibitors (SGLT2i +/- ins or met), Metformin and/or Insulin. We wanted to study whether there are differences in depression scores (PHQ-9 scores) amongst these groups. We hypothesized that centrally acting agent such as GLP1A may have lower scores compared to other regimens.Methods: We conducted a cross-sectional single-timepoint study patient-visits from the DM Clinic at VA Med Center over 16 months. Of 318 patient visits we analyzed 159 patient visits that had a PHQ9 score of at least 5 or above to indicate mild, moderate, or severe depression as per PHQ9 scoring system.Results: Across the patient visits we had a mean age of 65.86±0.83 years old. The mean BMI was 32.46±0.56 across groups with SGLT2i (+/- ins or met) having a slightly lower BMI of 29.76±0.98. The mean A1C was 8.0±0.12 which was again similar across groups. GLP1A (+/- ins or met) (n=40) had a slightly lower mean PHQ9 score of 9.675±0.54 compared to other groups such as SGLT2i (+/- ins or met) (n=41) with an 11.51±0.81 and met and/or ins (n=78) with a 10.73±0.57 score, though there was no statistically significant PHQ-9 score difference across the groups.Conclusion: In a real-life setting of diabetes clinic with veterans, depression scores were lower in patients taking GLPA group, independent of differences in BMI or A1C metrics between the groups. Only about 50% of veterans with T2DM were prescribed either insulin or metformin indicating under-utilization of SGLT2i and GLP-1RA. Our ongoing study may provide insight into choice of appropriate T2DM medications that may help both concomitant T2DM and depression.DisclosureS. Ubalde: None. K. Meyer: None. J. Powell: None. S. Sen: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-672-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 673-P: Is Loneliness a Mediator of the Relationship between Discrimination
and Dementia in Older Adults with Diabetes in High- and Middle-Income
Countries'-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 673-P
Abstract: Introduction and Objective: While it is known that adults with diabetes mellitus (DM) have twice the risk of developing dementia, and discrimination has been shown to be associated with dementia in some older adult populations, it is unknown whether this association is mediated by loneliness. Therefore, the aims of this analysis were to: 1) understand whether there is a differential association between discrimination and dementia in older adults with DM in high- and middle-income countries; and 2) understand whether loneliness is a mediator of this relationship.Methods: Data for adults with DM aged 50+ in Europe (n=10622, 2017-Survey of Health, Aging and Retirement), 45+ in India (n=8857, 2017-2019-Longitudinal Aging Study), and 50+ in Brazil (n=1780, 2019-2021-The Longitudinal Study of Aging) were analyzed. Logistic regression models were used to investigate the relationship between discrimination and loneliness, loneliness and self-reported dementia, and discrimination and dementia. A final mediation model with discrimination and loneliness as independent variables and dementia as the dependent variable was run.Results: The prevalence of dementia was 0.85%, 3.8%, and 5.2% in India, Europe, and Brazil respectively. The prevalence of discrimination was 6.7% in Europe, up to 5.4% in Brazil, and up to 7.4% in India. There was no association between discrimination and dementia in older adults with DM in Europe and Israel (OR:1.04; 95%CI:0.66,1.66), nor was there an association between loneliness and dementia in India (OR:1.73; 95%CI: 0.89,3.35). However, amongst older adults in Brazil with DM, loneliness was found to fully mediate the relationship between medical care discrimination and dementia.Conclusion: There was a differential relationship between discrimination and dementia in high- and middle-income countries; and loneliness was found to fully mediate this relationship only for older adults with DM in Brazil.DisclosureA.Z. Dawson: None. J. Price: None. J.S. Williams: None. M.N. Ozieh: None.FundingAmerican Diabetes Association (11-22-JDFHD-01); National Institutes of Health (1R21DK135965-01)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-673-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 674-P: Alcohol, Vaping, and Marijuana Use among Young Adults with Type 1
Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 674-P
Abstract: Introduction and Objective: Despite health risks, some young adults with type 1 diabetes (YA-T1D) use substances, e.g., alcohol, marijuana. We examined individual, social, and diabetes-related factors associated with substance use in YA-T1D.Methods: We surveyed 203 YA-T1D (age 18-25; 54% Female, 1.5% Transgender, 82% Non-Hispanic White, 9% Hispanic/Latino, 11% Non-Hispanic Black, 46% in college, 63% pump-users, and mean HbA1c = 7.7 ± 1.6%.) in an online, cross-sectional design. The survey assessed engagement in diabetes management and frequency of substance use over the past year. Participants provided HbA1c and blood glucose (BG) data to calculate Average Daily Risk Range (ADRR)- higher score indicates greater risk for out-of-range BG over the next month.Results: At least once within the previous year, 79% of YA-T1D used alcohol, 46% binge drank, 30% vaped (non-marijuana), 30% used marijuana or other drugs, and 12% used cigarettes. Weekly alcohol use was associated with binge drinking, cigarette use, vaping, and marijuana use (χ2=6.3-31.5). Older YAs reported weekly alcohol use and binge drinking (ß=.22-.26) more often, while males reported weekly marijuana use (χ2=7.7) more often. Those who reported weekly alcohol or marijuana use, or binge drinking also reported lower engagement in diabetes self-management tasks (t=-2.8 to -2.0). Vaping was associated with higher ADRR score (t=2.0; all p<.05). Substance use was not associated with race/ethnicity, diabetes technology, marital status, education, living status, insurance, or HbA1c.Conclusion: Rates of alcohol, marijuana, and cigarette use were similar to other studies, binge drinking and vaping rates were higher than other studies with YA-T1D and US population data. Vaping was associated with more frequent glycemic extremes, and frequent alcohol and marijuana use were associated with lower engagement in T1D management. Vaping rates are increasing, including among YA-T1D, and may be associated with greater risk for out-of-range BGs.DisclosureR.M. Wasserman: None. B. Ergun-Longmire: None. P. Vining Maravolo: None. A. Monzon: None.FundingSPP Targeted Research Award
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-674-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 675-P: Impact of Smoking Status on Suicide Risk in Patients with Type 2
Diabetes—A Nationwide Population-Based Cohort Study-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 675-P
Abstract: Introduction and Objective: Suicide is a major global concern, and people with type 2 diabetes (T2D) are particularly at risk due to the stress and difficulties of managing their disease. Smoking adds to this burden, but the impact of smoking on suicide risk in people with T2D is not well understood. This study aimed to investigate the association between smoking and suicide in people with T2D to help inform preventive measures.Methods: This longitudinal cohort study utilized data from the Korean National Health Insurance Service (NHIS) database. A total of 2,524,769 patients with T2D aged 20 years or older who underwent a national health examination in 2015-2016 were included in the study. Participants were followed up until suicide or the end of the study.Results: During a mean follow-up of 5.8 years, 5,578 people (0.22%) died by suicide. Current smokers had a significantly higher risk of suicide compared to never-smokers (adjusted hazard ratio [HR]: 1.55). Ex-smokers did not have a significantly increased risk after adjustment, except for those with a smoking history of 30 years or more (HR: 1.12). Subgroup analysis showed that women who were current smokers had a significantly higher risk (HR: 2.71) compared to men (HR: 1.47). For participants aged 65 and older, current smoking did not significantly increase the risk of suicide (HR: 1.13, 95% CI: 0.99-1.28), unlike those under 65 (HR: 1.78, 95% CI: 1.61-1.92).Conclusion: Current smoking significantly increases the risk of suicide in people with T2D, especially among women and younger people. A long-term smoking history further increases the risk, emphasizing the need to quit smoking in this high-risk population.DisclosureH. Kwon: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-675-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 676-P: Stability and Impact of Diabetes Distress among Adults with Type 1
Diabetes over Time-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 676-P
Abstract: Introduction and Objective: Diabetes distress (DD) refers to the fears, worries, and burdens associated with living with and managing diabetes. The Type 1 Diabetes Distress Assessment System (T1-DDAS) was developed to provide a valid and comprehensive measure of DD that addresses the contemporary concerns and worries of adults with T1D. We previously reported strong initial support for its validity through cross sectional associations with psychosocial, self-management and glycemic measures. In this report we expand our exploration of the scale's utility by examining the stability and change of T1-DDAS scores over time, define a minimal clinically important difference (MCID), and examine the predictive validity of the new T1-DDAS.Methods: Adults with type 1 diabetes recruited through national registries and previous studies completed the T1-DDAS Core and Source scales alongside a report of insulin taking and glycemic measures at baseline and 6 months later.Results: 574 individuals completed both assessments. T1-DDAS scores were highly stable over 6 months:88% of individuals with elevated Core Diabetes Distress (DD) in the study continued to report elevated DD at or above the 2.0 threshold 6 months later. 57% reported no improvement or a worsening in Core DD based on a MCID of ±0.27. Elevated DD on the Core and majority of Source scales at baseline was linked to worsening in reported missed insulin bolus taking and HbA1c at 6 months.Conclusion: Findings add to our understanding of DD and the utility of the T1-DDAS by demonstrating the stability and predictive validity of the T1-DDAS Core and Source scales to assess DD. The overall stability in DD over a 6-month period points to the striking chronicity of DD and the need for active, comprehensive intervention to address elevated DD as part of regular clinical care. The predictive findings reinforce that, if left unaddressed, DD can lead to cumulative negative impacts on medication taking and subsequent glycemic management over time.DisclosureD.M. Hessler: None. W.H. Polonsky: Consultant; Abbott. Research Support; Abbott. Consultant; Dexcom, Inc. Research Support; Dexcom, Inc. Other Relationship; Ascensia Diabetes Care. L.A. Strycker: None. D. Naranjo: Consultant; Sanofi. K. Greenberg: None. L. Fisher: None.FundingThe Leona M. and Harry B. Helmsley Charitable Trust.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-676-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 677-P: Health-Related Quality of Life (HRQOL) in Youth with Type 1
Diabetes (T1D)—Comparisons with Other Chronic Health Conditions-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 677-P
Abstract: Introduction and Objective: Given the demands of T1D, youth with T1D can experience challenges to HRQOL. This study examines how HRQOL domains of youth with elevated HbA1cs are associated with health outcomes and compare to youth with other chronic conditions.Methods: Youth (N=157) from 5 children’s hospitals were included if 12-17 years old, T1D diagnosis for ≥1 year, and HbA1c ≥10% in past year. Youth completed the PROMIS Pediatric-25. Chart review collected emergency department (ED) visits and HbA1c. Literature review collected PROMIS outcomes for youth with other chronic conditions.Results: Youth mean age was 14.5+1.6 years; 45.9% female; 13% Latinx, 8% Black; HbA1c M=11.1+1.5%. Higher anxiety was associated with more frequent ED visits (r=.179; p<.05), and higher support from peers was related to lower HbA1c (r=-.171; p<.05). Youth reported moderate to severe ratings, respectively, for anxiety (28% and 22%), depression (24% and 23%), and fatigue (25% and 17%). Youth with elevated HbA1c showed greater challenges with HRQOL compared to youth with other health conditions (see Table).Conclusion: Youth with T1D and elevated HbA1c experience greater HRQOL impact compared to youth with other chronic conditions. Key HRQOL domains were associated with worse health outcomes. Given prevalent serious elevations across psychosocial domains, embedded psychosocial screening and treatment should be prioritized for youth with elevated HbA1c.DisclosureR. Delgado-Kiggins: None. K.A. Torres: None. M.A. Clements: Consultant; Glooko, Inc. Research Support; Dexcom, Inc., Abbott. J. Raymond: None. D. Naranjo: Consultant; Sanofi. J.C. Wong: Research Support; Abbott, Dexcom, Inc., Tandem Diabetes Care, Inc. A. Reed: None. M.E. Hilliard: None. J. Flores Garcia: None. L.D. Hicks: None. M.A. Harris: None. D.V. Wagner: None.FundingJDRF
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-677-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 679-P: Behavioral Health Care Utilization amongst Patients with
Insulin-Requiring Diabetes Receiving Care at Federally Qualified Health
Centers-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 679-P
Abstract: Introduction and Objective: Behavioral health comorbidities significantly impact diabetes outcomes. Federally Qualified Health Centers (FQHCs), serving as medical homes for over 30 million underserved individuals, are uniquely positioned to integrate behavioral and physical health care. However, research characterizing behavioral health care utilization in diabetes has not included FQHC populations. This study aimed to describe behavioral health care utilization in a national cohort of FQHC patients with T1D/T2D on MDI/CSII.Methods: A large data platform from 40 FQHCs in 17 states was leveraged to identify and describe documented utilization of behavioral health care for adults with T1D/T2D. Data was analyzed descriptively according to race and ethnicity, Federal Poverty Level (FPL), and insurance type.Results: A cohort of n=16,267 was identified: 2,249 with T1D and 14,018 with T2D; 53.8% below the poverty line (FPL<100); 23.4% Non-Hispanic White (NHW), 28.0% Non-Hispanic Black (NHB), 0.4% American Indian/Alaska Native (AIAN), 2.0%, Native Hawaiian/Pacific Islander (NHPI), 1.2% Non-Hispanic Asian (NHA), 39.0% Hispanic, and 5.9% Other/Multiracial; 47.6% publicly insured, 22.1% uninsured, and 30.3% privately insured. Among T1D, NHPI had the highest utilization rate (28.6%), while NHA had no utilization (0.0%). Among T2D, NHW had the highest utilization rate (24.7%), followed by NHB (22.6%). AIAN consistently showed lower utilization across T1D/T2D. Patients with FPL<100 had lower utilization (19.2% T1D, 23.7% T2D) despite comprising over half the cohort.Conclusion: This is the first known study to describe utilization of and disparities within behavioral health care in diabetes at FQHCs. Given behavioral health comorbidities may compromise treatment engagement and increase risk for complications, descriptive research and future interventions to increase behavioral health equity must include FQHC populations.DisclosureS. Westen: None. B. Churba: None. K.G. Malden: None. T. Long: None. W. Esmond: None. Y. Hong: Consultant; Weight Watchers International. C. Walker: None. N. Marlow: None. M. Gurka: None. K. VanDoren: None. S. Downs: None. S.T. Martinez: None. L. Siman: None. A. Hamilton: None. M.J. Haller: Advisory Panel; SAB Biotherapeutics, Inc, MannKind Corporation. Consultant; Sanofi. A.F. Walker: None.FundingThe Leona M. and Harry B. Helmsley Charitable Trust
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-679-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 680-P: Evolution from the Diabetes Prevention Program Research Trial to
the National Diabetes Prevention Program—Lessons in Type 2 Diabetes
Prevention-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 680-P
Abstract: Introduction and Objective: In 2010, the Centers for Disease Control and Prevention (CDC) established the National Diabetes Prevention Program (National DPP) to address the growing rate of type 2 diabetes (T2D) in the United States and the millions of adults at high risk for the disease. The National DPP supports a structured lifestyle change program (LCP) based on the Diabetes Prevention Program (DPP) research study and subsequent translation studies. Our objective is to compare outcomes from the lifestyle intervention arm of the DPP to that of the National DPP LCP using data from CDC’s Diabetes Prevention Recognition Program.Methods: This study compares participant outcomes from the DPP (n=1,079) to two groups from the National DPP LCP: all participants (n=634,545) and those who more closely matched criteria for DPP inclusion (n=116,330). Outcomes include weight loss at ~6 months and percentage who met the 150 minutes/week of physical activity (PA) goal at ~6 months. Analysis was done using SAS 9.4.Results: Median weight loss was higher for DPP participants (7.2%) than for the two groups of LCP participants: 4.3% (all) and 4.7% (matched). Weight loss in the 5-7% range, the goal of the LCP, was the same or better for those in the LCP, 14% (all) and 16% (matched), compared to the DPP (14%). DPP participants met the PA goal of 150 weekly minutes at a rate of 74%. Among LCP participants, the percentage reporting meeting the goal during the 6-month period was 56% (all) and 62% (matched).Conclusion: The National DPP LCP is offered by various organizations in real-world settings, whereas the DPP was conducted in a controlled environment that included individualized support. Despite this, LCP participants are meeting weight loss goals at similar rates and showing increases in PA. The National DPP shows promise as a model to scale a proven lifestyle intervention from research into widespread practice, helping adults with prediabetes lower their risk for T2D.DisclosureE. Ely: None. M. Bell: None.
PubDate: Fri, 13 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-680-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 681-P: Medication Adherence in the Glycemia Reduction Approaches in
Diabetes—A Comparative Effectiveness (GRADE) Study-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 681-P
Abstract: Introduction and Objective: We examined medication adherence as a predictor of glycemic outcomes and evaluated treatment group differences in the GRADE study.Methods: GRADE participants (T2DM <10 years, HbA1c = 6.8-8.5%, on metformin monotherapy) were randomly assigned to add insulin glargine, glimepiride, liraglutide, or sitagliptin. The Emotional Distress Substudy followed 1,739 participants who self-reported adherence to the assigned medication regimen biannually up to 3 years on a 3-item validated scale (scored 0-100). We examined: a) levels of adherence and differences by treatment group over time; b) adherence as a predictor of primary (HbA1c ≥7.0) and secondary (HbA1c >7.5) glycemic outcomes; and c) treatment group differences in the association between adherence and glycemic outcomes.Results: Across treatment groups, adherence decreased slightly over 3 years (M±SD = -2.0 ± 14.7, p < 0.0001) but was high overall (M±SD = 88.7 ± 10.01). No group differences were observed at 6, 12, or 24 months. However, at 3 years adherence was 5.1% higher for the glimepiride and 3% higher for sitagliptin groups than for liraglutide (both p < 0.05); no other group differences were significant. Across groups, a 10-point decrease in adherence score was associated with 15% and 19% increased risk of reaching primary and secondary glycemic outcomes, respectively (both p < 0.0001). Adherence predicted the primary glycemic outcome conisistently across groups but was somewhat more predictive of reaching the secondary glycemic outcome for those assigned to glargine or liraglutide, as compared to glimepiride or sitagliptin (each p < 0.05). No other group comparisons were significant.Conclusion: Medication adherence was consistently high in GRADE and observed treatment group differences were small, supporting previously reported trial outcomes. Nevertheless, lower adherence robustly predicted worsening glycemic control, highlighting the importance of ongoing assessment.DisclosureJ.S. Gonzalez: None. H. Wen: None. M.R. Gramzinski: None. N.M. Butera: None. D. Uschner: None. D.J. Wexler: Other Relationship; Novo Nordisk. H. Petrovitch: None. B. Fattaleh: None. E.A. Walker: None. C.J. Hoogendoorn: None. C.A. Presley: None. G. Crespo-Ramos: None. V. Lagari: None. H. Krause-Steinrauf: None. A.L. Cherrington: None.FundingNational Institute of Diabetes and Digestive and Kidney Diseases (U01DK098246; U34DK088043; R01DK104845); The National Heart, Lung, and Blood Institute; The Centers for Disease Control and Prevention
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-681-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 682-P: Parental Influences on Diabetes Distress—Distinct Causal
Pathways-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 682-P
Abstract: Introduction and Objective: To examine distinct causal pathways through positive and negative parenting on adolescent and parent diabetes distressMethods: Longitudinal data were collected in an RCT of a family-based 6-week program with 157 adolescents with type 1 diabetes and their parents. Two Structural Equation Models tested paths from intervention through parenting practices at immediate post-intervention (7 weeks post-baseline) to predict youth and parent diabetes distress at 6 months post-baseline. Models adjusted for age, diabetes duration, and baseline parenting, distress, percent time-in-range, and quality of life.Results: Both path models had perfect model fit due to full saturation. The intervention increased parent diabetes warmth/acceptance and decreased diabetes-related conflict, and greater warmth/acceptance predicted less adolescent diabetes distress. The intervention reduced non-supportive parent diabetes involvement, which predicted reduced adolescent and parent diabetes distress. While supportive involvement was not impacted by the intervention, it also uniquely predicted youth and parent distress.Conclusion: The intervention enhanced parental warmth and acceptance and reduced conflict and nonsupportive involvement. While warmth and acceptance, but not conflict, predicted adolescent distress over time, both types of parent involvement predicted changes in youth and parent distress.DisclosureJ.J. Wong: None. S.A. Alamarie: None. H. Flores: None. S. Hanes: None. J. Ngo: None. A.K. Schneider-Utaka: None. K.K. Hood: Consultant; Sanofi. Advisory Panel; MannKind Corporation. Consultant; Havas Health. Research Support; embecta.FundingNational Institutes of Health (K23-DK121771)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-682-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 683-P: Sociodemographic and Behavioral Factors Associated with Diet
Quality in Low-income Adults with Prediabetes and Type 2 Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 683-P
Abstract: Introduction and Objective: Low-income adults face barriers to healthy eating. This study assessed the relative importance of sociodemographic and behavioral factors associated with diet quality in a sample of low-income patients with prediabetes or type 2 diabetes (T2D) to identify modifiable targets for a tailored diabetes self-management education and support (DSMES) program.Methods: Baseline surveys collected demographic (e.g., age, race/ethnicity), social needs (e.g., food and housing security), and behavioral (e.g., mental health, physical activity) factors. Primary outcome was Healthy Eating Index-2020 (HEI) diet quality score (range 0-100, higher=healthier). Random forests were fit and Shapley Additive Explanation values were used to determine relative importance of factors in predicting HEI.Results: Of 278 participants, 42% had prediabetes and 58% had T2D. Median age (IQR) was 52 (43, 57); 58% were Hispanic. Top 6 behavioral factors associated with lower HEI were current smoking, fewer distinct foods eaten per day, longer time sitting per day, lower sleep quality, worse depression symptoms, and cannabis use. The Figure displays radar plots of HEI component scores for the top 4 factors.Conclusion: We identified important behavioral risk factors for lower diet quality which could be targeted in a DSMES program tailored for low-income populations.DisclosureK.D. Gu: None. D. Shinnick: None. T. Thaweethai: None. J. Cheng: None. D.J. Wexler: Other Relationship; Novo Nordisk. A.N. Thorndike: None.FundingNational Institutes of Health F32DK141094
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-683-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 684-P: Community-Based Peer Support for Diabetes Management in Shanghai,
China—Breadth of Benefits and Processes of Change-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 684-P
Abstract: Introduction and Objective: Characterize breadth of benefits, relationships among changes, and processes of change in Community-Based Peer Support (CPS).Methods: CPS was implemented over 24 months in 12 communities (n=1,018) with 4 Comparison Communities (Comp, n=423) in Shanghai, China. CPS participants were = 59.9% female vs 53.5% among Comp, older (mean 66.64 vs 62.94 years), and had longer duration of diabetes (8.04 vs 6.63 years) (ps ≤.004). Accordingly, all subsequent analyses included site, gender, age, and diabetes duration as covariates.Results: At baseline, CPS scored higher on a 4-item measure of diabetes distress (DD) (1.18 vs 1.09) and PHQ8 measure of depressed mood (Dep) (1.85 vs 1.36) but lower on Hemoglobin A1c (A1c) (7.47% vs 7.72%) (ps <.005).To examine intervention effects, analyses of follow-up measures controlled for corresponding baseline measures in addition to covariates noted above. Among all participants, CPS exceeded Comp in beneficial changes in DD (baseline adjusted follow-up = 1.11 in CPS vs 1.17 in Comp, p =.004), Dep (1.32 vs. 1.89, p <.001), and A1c (7.45 vs 7.82%, p <.001).Changes in DD mediated both changes in Dep and A1c as, reciprocally, changes in each of follow-up Dep and A1c mediated effects on DD. Follow-up Dep and A1c, however, were not associated with each other.Participants rated receipt of 5 key functions of CPS: 1) availability/ongoing support; 2) assistance in daily management; 3) social/emotional support; 4) linkage to clinical care/community resources; and 5) “being there.” The mean of key functions was associated with reductions in DD (partial correlation = -.11), Dep (-.16), and A1c (-.12) (ps ≤.002).Conclusion: CPS improved emotional status - DD and Dep, as well as glycemic control - A1c. Reflecting the breadth of benefits, changes in A1c were independent of changes in Dep although DD mediated the effects of CPS on both A1c and Dep. Process evaluation indicated the importance of key functions of CPS as they were associated with improvements in each of DD, Dep, and A1c.DisclosureY. Liu: None. C. Cai: None. P.Y. Tang: None. M.M. Coufal: None. L. Shen: None. E.B. Fisher: None. W. Jia: None.FundingNational Institutes of Health (P30DK092926); Merck Foundation
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-684-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 685-P: Acceptability of Diabetes-Stigmatizing Language Reduction
Intervention for Health Care Providers-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 685-P
Abstract: Introduction and Objective: Evidence suggests that terminology and expressions used in healthcare environments contribute to the stigma associated with diabetes. The American Diabetes Association and the Association of Diabetes Care & Education Specialists published guidance to help healthcare professionals minimize the use of diabetes-stigmatizing language in patient-provider interactions. We developed an intervention designed to reduce the use of diabetes-stigmatizing language among healthcare providers (HCPs) during patient-provider interactions. The intervention has three components: 1) an encounter with a standardized patient, 2) an educational video addressing diabetes-stigmatizing language, and 3) a self-reflection exercise focused on the standardized patient interaction. The objective was to pilot the intervention and assess its acceptability among HCPs.Methods: Participants (N=22) were randomly assigned to the intervention or control groups. Theory of Planned Behavior measures were collected pre- and post-intervention/control. T-tests were utilized to analyze within-group and between-group differences.Results: The intervention group demonstrated greater change in attitude scores, indicating more negative attitudes toward the use of diabetes-stigmatizing language compared to the control group (p<0.001). There was a trend toward greater change in intention scores to avoid the use of diabetes-stigmatizing language in the intervention group compared to the control group (p=0.13). The intervention group reported higher acceptability ratings for clarity (p<0.05), helpfulness (p<0.05), and likelihood of recommending the training (p<0.05), compared to the control group.Conclusion: This pilot study demonstrates the intervention’s acceptability and suggests its potential effectiveness in modifying HCP attitudes toward reducing the use of diabetes-stigmatizing language use in patient-provider interactions.DisclosureK. Joiner: None. A. Agapiou: None. A.G. Carmichael: None. H. Tarraf: None. B.P. Labbree: None. R. Gonzalez: None.FundingAmerican Diabetes Association (CDTR-03)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-685-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 686-P: A Case-Control Study of Mental Health Status of Diabetic Patients
-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 686-P
Abstract: Introduction and Objective: Rising prevalence of diabetes mellitus in developing countries is accompanied by an increase in associated risk factors and multisystem complications, which may negatively impact mental health of affected individuals. Burden of managing DM and its complications often contributes to psychological distress in these patients.This study aimed to assess mental health of DM patients in a developing country setting, with a focus on identifying factors associated with depression.Methods: A case-control study design was employed, with participants recruited consecutively. DM patients (cases) were selected from OPD and IPD departments of PSH, Vadodara, between Jan-22 and Apr-24. Age and sex matched non-diabetic, normotensive controls were chosen from civil servants. Mental health was assessed using validated PHQ-9 instrument, with clinical depression defined as a score greater than 10. Significance threshold was set at p<.05.Results: Study included 100 DM patients and their matched controls, with a male/female ratio of 1.2:0.8. Mean age was 48.9±9 years. Depression was found in 21% of male diabetics and 24% of female diabetics. A significantly higher proportion of diabetic patients had clinical depression compared to controls (p<.05). Among female DM patients, comorbid hypertension, BMI, blood pressure levels, and DM duration were significantly associated with depression (p<.05). Among male DM patients, older age, occasional alcohol consumption, and poor glycemic control were significantly associated with depression (p<.05).Conclusion: There is a high prevalence of depression among DM patients that may adversely impact care outcomes. Study highlights importance of addressing mental health in management of DM, particularly through improved collaboration between diabetologists and mental health professionals. Interdisciplinary approaches to integrate mental health care into DM management could potentially enhance treatment outcomes and quality of life for DM patients.DisclosureV.M. Rathod: None. D. Raval: None. R. Ray: None. N.N. Vora: None. K.R. Rana: None. A. Bhattacharya: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-686-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 687-P: A CGM Behavioral Intervention—Characteristics Associated with
Glycemic Response among Racially Minoritized Youth with T1D-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 687-P
Abstract: Introduction and Objective: Consistent continuous glucose monitor (CGM) use is a challenge for youth with type 1 diabetes (T1D), especially among those affected by racialized health inequities due to centuries of racial oppression. We examined differences in medical/demographic/intervention characteristics between those with and without a glycemic response following a 3-session, diabetes educator-led CGM behavioral intervention.Methods: Participants included 60 youth ages 10-15 years with <75% CGM use, including >90% racially minoritized youth. Glycemic response was dichotomized (n=51 available data): those with ≥0.5% reduction in A1c and/or ≥10% increase in time in range from pre-intervention to post-intervention (n=25), and those without (n=26).Results: For each additional session attended, the odds of experiencing a glycemic response were nearly 4 times greater. Higher pre-intervention A1c was also associated with a glycemic response. All other associations were not significant (see Table 1).Conclusion: Significant results suggest a positive intervention impact. Demographic factors were not significantly associated with glycemic response; evaluation with a larger sample size and more statistical power is needed. Intervention attendance barriers that affect response are also important to further examine.DisclosureE. Straton: None. C.H. Wang: None. A.G. Perkins: Research Support; Tandem Diabetes Care, Inc, Dexcom, Inc. L. Gallant: None. J. Barber: Stock/Shareholder; Boston Scientific Corporation, UnitedHealth Group, AbbVie Inc. S. Majidi: Speaker's Bureau; Sanofi. R. Streisand: None.FundingNational Institutes of Health (R01DK121316)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-687-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 688-P: Personality as a Predictor of Self-Management, Diabetes Distress,
and Glycemic Control in Adults with Type 1 Diabetes (T1D)-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 688-P
Abstract: Introduction and Objective: Personality may influence key glycemic, behavioral, and emotional outcomes in people with T1D. We investigated Five-Factor Model (FFM) personality traits as predictors of self-management (SM), diabetes distress, and continuous glucose monitoring (CGM) metrics among 187 diverse adults with T1D.Methods: Participants wore CGM and rated their SM (each evening on a 0-100 scale) and diabetes distress (5-6 xs/day, 0-100) via smartphone-based prompts over 14 days. Linear regression models tested relationships between baseline FFM traits assessed by a 10-item validated scale and measures of diabetes distress, SM, and glycemic regulation averaged over the monitoring period. Examined CGM indices included % time in range (70-180 mg/dL), % time in hypoglycemia (<70 mg/dL), % time in hyperglycemia (>180 mg/dL), mean glucose level, and glucose coefficient of variation (CV).Results: Greater time-in-range was predicted by higher emotional stability (b=2.49, β=0.14, p=.038) and conscientiousness (b=2.78, β= 0.16, p=.024). Greater conscientiousness also predicted less % time in hypoglycemia (b =-0.16, β =-0.17, p=.045) and lower CV (b=-1.13, β= -0.18, p=.023). Better SM was predicted by higher conscientiousness (b=3.27, β=0.23, p=.002) and emotional stability (b=2.50, β=0.18, p=.020. Lower diabetes distress was predicted by higher emotional stability (b=-3.67, β=-0.22, p=.003) and conscientiousness (b=-2.83, β=-0.17, p=.025). Agreeableness, openness, and extraversion were not related to any outcome.Conclusion: Adults with higher conscientiousness and emotional stability had better self-management and glycemic regulation and less diabetes distress, over time in their daily lives with T1D. These personality traits may serve as protective factors, contributing to more favorable T1D outcomes. Screening for personality may help identify adults with T1D who are at risk of challenges in self-management, diabetes-related distress, and glycemic regulation.DisclosureL.D. Pappalardo: None. C.J. Hoogendoorn: None. S. Schneider: None. E. Pyatak: None. J.S. Gonzalez: None.FundingNational Institute of Diabetes and Digestive and Kidney Diseases at the NIH (1R01DK121298-01); National Institute on Aging at the NIH (NIH/NIA #1U2CAG060408-01); The New York Regional Center for Diabetes Translation Research (NIH/NIDDK #P30DK11022)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-688-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 689-P: What Predicts Intention to Increase Dietary Fiber Intake among
Patients with Type 2 Diabetes' A Survey Based on the Theory of Planned
Behavior (TPB)-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 689-P
Abstract: Introduction and Objective: Despite proven benefits of dietary fiber intake for glycemic control, most T2D patients in Japan fail to meet the recommended daily fiber intake of 20g. This study explored beliefs underlying attitude (ATT), subjective norms (SN), and perceived behavioral control (PBC) towards the intention to increase dietary fiber intake using TPB, as a foundational step toward developing an intervention to address this gap.Methods: We conducted a cross-sectional survey from August to September 2024 at the outpatient clinic of The University of Tokyo Hospital. 120 patients with T2D aged 20 years and above completed a self-administered survey, which consisted of 20 questions on a 7-point Likert-like scale assessing ATT, SN, PBC, and intention to eat 50% more dietary fiber than their usual intake. Four open-ended free-text questions were used to further explore these constructs. Likert-like scale survey responses were analyzed using hierarchical multiple regression, while free-text responses underwent thematic analysis.Results: We recruited 120 participants (63.3% male) with a mean age of 68.3 years. The model's ability to explain variance in intention improved from 17.3% with demographic variables alone (age, gender, BMI, education level, annual income, living alone or with others) to 55.2% with the addition of TPB constructs, with ATT (p < 0.001) and PBC (p=0.001) as the significant predictors of intention. SN was not a significant predictor. Lack of knowledge about fiber, difficulty in estimating fiber amount, and concern about taste of fiber were the prominent themes.Conclusion: ATT and PBC predict intention to increase dietary fiber intake among T2D patients. The findings from this survey informed the development of an AI-powered smartphone app with key features such as fiber estimation for meals, provision of educational information and goal setting. A pilot RCT is underway to evaluate its preliminary efficacy.DisclosureW. Sze: None. K. Waki: Consultant; Astellas Pharma Inc. Other Relationship; Astellas Pharma Inc, Sumitomo Dainippon Pharma Co., Ltd. Consultant; Terumo Corporation. Other Relationship; Terumo Corporation. Speaker's Bureau; Sanofi. D. Lane: None. T. Aoyama: Research Support; Abbott Japan Co., Ltd. K. Miyake: None. Y. Kadowaki: None. T. Kawaguchi: Other Relationship; Nitto Boseki Co., Ltd. Y. Matsuo: None. Y. Sakai: None. T. Yamauchi: Research Support; Asahi Mutual Life Insurance Company. Other Relationship; Astellas Pharma Inc, AstraZeneca, Abbott Japan Co., Ltd, ARKRAY Marketing, Inc., Amgen Inc. Research Support; Boehringer-Ingelheim. Other Relationship; Boehringer-Ingelheim, Bayer Pharmaceuticals, Inc, Covidien Japan Inc., Daiichi Sankyo, Eli Lilly and Company. Research Support; EA Pharma Co.,Ltd. Other Relationship; GlaxoSmithKline K.K. Research Support; Kowa Company, Ltd. Other Relationship; Kowa Company, Ltd, Kyowa Kirin Co., Ltd, Medtronic, Merck Sharp & Dohme Corp, Mitsubishi Tanabe Pharma Corporation. Research Support; Novo Nordisk. Other Relationship; Novo Nordisk, Ono Pharmaceutical Co., Ltd, Sumitomo Pharma Co., Sanofi K.K., SANWA KAGAKU KENKYUSHO CO.,LTD., Taiho Pharmaceutical Co. Ltd, Teijin Pharma Limited, Nipro Corporation. Research Support; NITTO BOSEKI CO.,LTD. Other Relationship; ViewSendICT Inc. M. Nangaku: Other Relationship; Astellas Pharma Inc, AstraZeneca, Daiichi Sankyo, GlaxoSmithKline plc, Daiichi Sankyo, Kyowa Kirin Co., Ltd, Boehringer-Ingelheim. Consultant; Novo Nordisk. Research Support; Bayer Pharmaceuticals, Inc. Other Relationship; Mitsubishi Tanabe Pharma Corporation. K. Ohe: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-689-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 690-P: Participant Characteristics and Engagement in a Young Adult
Diabetes Transition Clinic-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 690-P
Abstract: Introduction and Objective: Young adults with type 1 diabetes (T1D) are vulnerable when transitioning from pediatric to adult care. The Young Adult Diabetes Clinic (YADC) employs a multidisciplinary model to facilitate this transition through a single-session orientation led by a behavioral health specialist. We aim to understand the impact of the YADC, participant characteristics, and patterns of engagement.Methods: The YADC involves a half-day session with orientation, peer-to-peer icebreakers, and discussion of transition-related topics, followed by diabetes education and medical provider visits. YADC participation, demographic and clinical data, including age, zip code (urban vs. rural), insurance status, visit type (virtual vs. in-person), referral source (internal vs. external), technology use (CGM, CGM + pump, or none), T1D Distress Assessment System (T1DDAS) scores, A1c, and visit completion were tracked or manually extracted via chart review. No statistical software or analysis was applied.Results: Of 214 participants (2021-2024, mean age = 20), 27% (N=58) fully participated in YADC, 19% (N=40) partially participated, and 54% (N=116) did not participate. Among 17 full participants (August 2023-June 2024): mean age = 21 years (SD = 1.8); mean A1c = 9% (SD = 2.4); 47% used CGM, 41% CGM + pump, and 11% used neither; 14 were urban residents and 3 were rural residents. Most (70%) had private insurance; 29% had Medicaid. Within 6 months following the YADC session, 9 of 17 completed medical visits, 8 of 17 completed diabetes education, and none accessed additional behavioral health care. Diabetes distress scores were collected for all 10 patients who attended in 2024.Conclusion: Characterizing participants in YADC and non-YADC visits will help highlight patterns of engagement and potential barriers to care. Future research should explore how to enhance program accessibility particularly for underserved groups, address psychosocial barriers, and assess the long-term impact of YADC participation on diabetes management outcomes.DisclosureR. Pandit: None. I. Guttmann-Bauman: None. R. Mullin: None. R.D. Tweet: Other Relationship; Lilly Diabetes. F. Joarder: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-690-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 691-P: Quality of Life and Diabetes Distress among Children and Youth with
Type 1 Diabetes and Their Parents in Kampala, Uganda—Cross-Sectional
Survey-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 691-P
Abstract: Introduction and Objective: Type 1 diabetes (T1D) causes significant stress in affected individuals, which may be worse in those from resource-limited countries. We assessed diabetes distress and quality of life (QOL) among Ugandan children and young adults with T1D and their parents.Methods: Patients aged 4-26yr from two paediatric T1D clinics in Kampala participated. Diabetes distress was assessed using the Problem Areas in Diabetes (PAID) tool for ages 7-12yrs (PAID-C) and their parents (P-PAID-C), and for ages 13-26yrs (PAID T) and their parents for those <18yrs (P- PAID T). Scores ≥40 indicate severe diabetes distress. QOL was assessed using the Diabetes Attitudes Wishes and Needs questionnaire (DAWN) for patients ages 10-26yrs; higher scores indicate worse QOL.Results: We enrolled 104 patients, mean age 16±6yrs, 52% male, diabetes duration 6.5±4.3yrs, Mean A1c 11.1±2.79% and their parents. Mean diabetes distress scores were categorized as severe across all groups, but were higher in both parental groups compared to their children (P-PAID-C: 70.63 vs. PAID-C: 51.39, p<0.001) and young adults (P-PAID-T 62.4 vs PAID-T 48.33, p<0.001). The mean DAWN score was low (25±12.9%), with the greatest negative impacts observed in the areas of parental issues (46%) and health perception (43%). Higher HBA1c ≥7.5% was associated with poorer quality of life, p=0.049.Conclusion: Ugandan children and youth with T1D have poor QOL, particularly regarding health perception and parental issues. Poor QOL is associated with worse glycemic control. Severe diabetes stress is seen in children and young adults and is even greater in their parents, highlighting the need for individual and family psychosocial support in resource-limited settings.Disclosure T.W. Piloya: Research Support; Abbott. Other Relationship; Novo Nordisk. C. Nyangabyaki: None. N. Jemima: None. D. Malinga: None. M. Nakitto: None. B.M. Nathan: None. S. Beasley: None. E. Pappenfus: None. A. Moran: Research Support; Abbott. Consultant; Abata Therapeutics. Other Relationship; Novo Nordisk.FundingNIH (R01DK126726)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-691-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 693-P: Acceptability of Vasoterapia Diabetes—A Novel Tool to Support
Mental Health and Peer Connection among Health Care Providers in Diabetes
Care-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 693-P
Abstract: Introduction and Objective: Healthcare providers (HCPs) working with people with diabetes experience significant burnout. Vasoterapia, a card game tool, was developed with experts in diabetes and psychology to enhance HCPs' peer connections and well-being. This study evaluates the acceptability and usefulness of integrating this intervention into clinical practice.Methods: After a focus group, an online ad hoc Likert survey was completed to evaluate the tool's acceptability and perceived benefits. The survey reflected emotions, physical sensations, and specific benefits experienced during the session and their influence on prioritizing mental health. Descriptive analyses were performed.Results: A total of 68 HCPs participated (83.8% female, 16,2% male), 79.4% Latin, 16.2% Caucasian, and 4.4% others. Professions included 57.4% pediatric endocrinologists, 14.7% dietitians, 10.3% nurses, and 1.5% psychologists. Among participants, 26.9% found the tool "very helpful," 7.5% described it as "extremely helpful," and 28.4% found it "moderately helpful." Only 7.5% indicated "no impact at all." A total of 33% rated their mental health as poor/very poor, and 30% experienced anxiety related to work "almost always or always." Furthermore, 78% reported their professional performance had decreased due to mental health challenges, and 57% stated their work negatively impacted their relationships. Suggestions for improvement included a digital format, offering case study examples, and having follow-up sessions after use in clinical practice.Conclusion: Participants reported that using the tool would enhance their understanding of what to bring to patient visits and potentially impact performance. Modifications can be made to increase its effectiveness. These findings highlight the importance of integrating innovative mental health solutions into clinical practice.DisclosureD. Rojas: None. K. Barnard-Kelly: Speaker's Bureau; Roche Diabetes Care, Sanofi. Stock/Shareholder; Spotlight-AQ Ltd, BHR Ltd.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-693-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 694-P: Which Young Adults (YA) with Type 1 Diabetes (T1D) Return to
Pediatrics during the Transition to Adult Care'-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 694-P
Abstract: Introduction and Objective: Transition from pediatric to adult diabetes care is a complex process for YA with T1D. However, little is known about demographic and clinical characteristics of YA who return to pediatric care after initiating the transfer to adult care. We explored characteristics of YA who did or did not return to pediatric care after their planned final pediatric appointment.Methods: At baseline of a trial, 100 YA with T1D reported demographic and medical information; HbA1c via medical chart or dried blood spot. We tracked pediatric visits over 12 mos and YA reported challenges with transition at follow-up. T-tests and χ2 tests assessed characteristics of YA who did or did not return to pediatric care.Results: As noted in the Table, 34% of YA returned to pediatric care for 59 visits (49 outpatient, 10 emergency care). Only age was significantly associated with return to pediatric care (p=0.015). Common challenges included busy/time constraints, difficulty scheduling, easier to stay in pediatrics.Conclusion: A sizable subset of YA with T1D return to pediatrics after planning to transfer to adult care. While relatively younger YA were more likely to return, we cannot predict who returns to pediatrics. Individualized support is needed in preparation for and during transfer between pediatric and adult care. Thus, the role of pediatric clinicians is not complete until YA establish in adult care.DisclosureS. Camey: None. S.A. Carreon: None. C.G. Minard: None. W. Levy: None. S. Lyons: None. C. Macke: None. R. Streisand: None. T.S. Tang: None. S. Mckay: None. B.J. Anderson-Thomas: None. S. Devaraj: None. M.E. Hilliard: None.FundingNational Institutes of Diabetes and Digestive and Kidney Diseases (1R01DK119246) (PI: M Hilliard); (3R01DK119246-03S1) (PI: M. Hilliard; Mentee: S. Carreon), 1K26DK138332 (PI: M Hilliard)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-694-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 695-P: Exploring Cultural and Immigration-Related Factors Associated with
Type 2 Diabetes among Hispanic/Latino Adults-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 695-P
Abstract: Introduction and Objective: Type 2 diabetes (T2D) prevalence among U.S. Hispanics exceeds the national average, driven by socioeconomic challenges, genetic predispositions, and limited healthcare access. Variations across subgroups suggest cultural and immigration-related factors may play a role. This study evaluates the association of these factors with T2D and prediabetes among rural Hispanic/Latino adults.Methods: This cross-sectional study analyzed self-reported and clinical data from 172 Hispanic/Latino adults in rural Midwest U.S. Diabetes and prediabetes were determined using HbA1c levels (A1CNow). Five cultural/immigration factors (age at immigration, English proficiency, family cohabitation dynamics, length of U.S. stay, and country of origin) were assessed. Univariate and multivariable models adjusted for age, gender, poverty index, and lifestyle factors (e.g., physical activity, diet) were used to evaluate associations.Results: Of participants (62.2% female, mean age 36.7 years), 25% had diabetes or prediabetes. In univariate analysis, language barriers and country of origin were significantly associated with diabetes/prediabetes. Adjusted models revealed no independent associations for cultural/immigration factors (p>0.05). Age and poverty index were the strongest predictors, with older age and higher poverty levels linked to increased risk.Conclusion: Cultural and immigration-related factors were not independently associated with diabetes/prediabetes risk in adjusted models, while age and poverty index emerged as key predictors. Addressing socioeconomic disparities and improving access to preventive healthcare are critical for reducing diabetes burden in Hispanic/Latino populations.DisclosureQ. Ding: None. M.A. Grismer: None. B.S. Wojeck: Consultant; Key Quest Health. D.G. Marrero: None.FundingIndiana Minority Health Coalition
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-695-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 696-P: Teaming Up for T1D through Telehealth (Triple T)—Initial Findings
from an Intervention to Support Families following T1D Diagnosis-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 696-P
Abstract: Introduction and Objective: Few psychosocial interventions exist for families in the first year after a T1D diagnosis. Initial findings from the Triple T pilot, a telehealth intervention designed to support family coping during this first year are reported.Methods: Inclusion criteria: child with a new diagnosis of T1D and fluency in English. Families participated in 6 telehealth visits (1, 2, 3-, 6-, 9-, and 12 months post-diagnosis) focused on supporting healthy coping and had access to a video library addressing common concerns (e.g., diagnosis disclosure, managing activities, school). Descriptive analyses of psychosocial outcomes and qualitative analyses of exit interviews are reported.Results: Thirty-one youth aged 2-17 (M=9.03; SD=4.6) and their caregivers participated. Youth were 54.8% female and identified as White (71%), Hispanic or Latinx (12.9%), Black (9.7%), or multi-racial (6.5%). The majority (77.4%) of caregivers were mothers. One-third (35.5%) of families reported an annual household income of < $100,000. At baseline, many parents reported elevated levels of depression (38.7%) and anxiety (36.7%); however, fewer reported elevated symptoms at 12 months (24%). At 12 months, some youth (21.4%) and parents (13%) reported elevations in diabetes distress and no youth, but some parents (20%), reported elevated family conflict. Participants reported Triple T was helpful, providing emotional support and validation as they adjusted to life with T1D and provided resources to answer difficult questions, helped them not feel alone, built skills to help their children when they were struggling, and reduced distress. Parents and teens reported improved communication and increased understanding of each other’s experiences.Conclusion: Findings from this pilot suggest that families perceived multiple benefits from participating in Triple T. Compared to previous studies, rates of elevation in psychosocial challenges were lower.Disclosure K.R. Howard: Stock/Shareholder; Abbott, AbbVie Inc. Other Relationship; Association of Diabetes Care & Education Specialists. K.P. Garza: None. N.W. Smith: None. M.C. Suhs: None. J.S. Merrick: None. J. Weissberg-Benchell: None. M. Feldman: None.FundingBreakthrough T1D (2-SRA-2020-985-S-B)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-696-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 698-P: Association of Context Type and Context Stability to Insulin Habit
Automaticity and Adherence in Type 1 Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 698-P
Abstract: Introduction and Objective: Habit theory describes context stability as important for the development of habit automaticity, but its role in insulin habit automaticity and adherence is unknown. The objective of the study was to examine the roles of context and context stability on insulin habit automaticity and adherence in adults with T1D.Methods: Adults with T1D (N = 63) completed a 7-day ecological momentary assessment (EMA) protocol using a time-contingent prompt schedule corresponding to approximate mealtimes (morning, afternoon, and evening). Physical, social, and emotional contexts were assessed at each timepoint. Generalized linear mixed-effects models tested associations between specific contexts with momentary insulin habit automaticity and insulin adherence. Spearman correlations were used to assess the strength of associations of context stability with insulin habit automaticity and insulin adherence.Results: The median age of the sample was 49 years, 58.7% were female, 96.8% were using a pump and CGM, and 76.3% were using automated insulin delivery. Feeling fatigued, stressed, and depressed reduced the likelihood of adherence to insulin but were not associated with automaticity. Those who reported feeling stressed were 56% less likely to adhere to insulin compared to those who reported no stress at all. As the extent of feeling fatigued increased, the likelihood of adherence decreased. More stable emotional contexts were associated with higher insulin habit automaticity scores and with greater insulin adherence. Greater stability in emotional context was also associated with less variability in both insulin habit automaticity and insulin adherence. Social context demonstrated a similar pattern of associations to that of emotional context for adherence but not for automaticity.Conclusion: Negative emotional contexts and emotional context stability appear to be important in insulin adherence and insulin habit automaticity.DisclosureJ.Y. Stone: None. M.S. Dietrich: None. L.S. Mayberry: None. K. Clouse: None. S.A. Mulvaney: None.FundingVanderbilt Institute for Clinical and Translational Research (UL1 TR002243)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-698-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 699-P: Associations between Parental T2D and Use of Positive and Negative
Food-Parenting Practices with Adolescents-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 699-P
Abstract: Introduction and Objective: Negative food-related parenting practices, like parental restriction, are associated with higher risk of eating disorders and obesity in their children. Conversely, positive parenting practices, like modeling health eating, may have protective effects. To date, little is known about how parents’ T2D status is related to their use of food-parenting practices. The goal of this study was to determine whether parental T2D is associated with differential use of food-related parenting practices with adolescents.Methods: Surveys were completed by an online convenience sample of adolescents (12-17y), as part of a study investigating adolescents’ eating autonomy. Parents reported health history/demographics and adolescents self-reported on parents comprehensive feeding practices (CFPQ). Independent ANOVAs evaluated whether parental T2D history (IV) was associated with each teen CFPQ subscale (DVs) when controlling for adolescent age, sex, and BMI.Results: Participants (n=146) were 49% female, with mean age 15.1y and BMI 22.9. Two % had T2D, 25%+ parental history, & 40% no family history. We found parental T2D is associated with more modeling of healthy eating (F (1, 138) = 5.4, p=0.02)), monitoring unhealthy eating (F(1,138)=4.1, p=0.045)), & teaching about nutrition (F=1,138)=7.9, p=0.006, but less restriction for weight control (F(1,138)=9.8, p=0.002)). There were no group differences in other negative (parental control, emotional regulation, pressure to eat, restriction for health) or positive (encouragement of balance, healthy environment, involvement) subscales.Conclusion: We found that parental T2D is associated with adolescents experiencing more parental modeling of healthy eating and nutrition, possibly due to effected households need to monitor their own dietary intake to manage T2D. Future research will investigate how to increase the involvement of adolescents in building a healthy home food environment to further support adolescent T2D prevention.DisclosureA. Ziegler: None. L. Hatzinger: None. J.L. Temple: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-699-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 700-P: Quality of Life in Youth and Young Adults (YYA) with Type 1
Diabetes (T1D) That Experience Device-Related Skin Reactions-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 700-P
Abstract: Introduction and Objective: Diabetes device use in T1D is associated with improved clinical outcomes. However, many people experience device-related skin reactions. Our aim was to assess psychosocial outcomes between YYA with T1D that experience device-related skin reactions and those that do not.Methods: YYA (2-25 years) with T1D that use diabetes devices completed an in-house developed survey, and the Problem Area in Diabetes (PAID, measure of diabetes distress, higher scores indicate more distress) and diabetes-specific Pediatric Quality of Life (PedsQL, higher scores indicating better well-being) surveys. Participants were dichotomized based on experiencing skin reactions to devices. T-tests were performed on HbA1c and PAID/PedsQL outcomes.Results: Eighty-eight YYA participated (15.4±6.2 yrs, T1Ddur 6.8±5.4 yrs, HbA1c 7.0±1.0%, 59.1% Female, 88.0% NHW, 98.9% CGM users, 90.9% pump users). Those with device-related skin reactions had significantly higher PAID scores and frequent self-reported negative feelings. No other significant differences were found.Conclusion: Youth and young adults with device-related skin reactions experience diabetes distress and device-related negative feelings, which can impact device use and overall well-being. Future research should focus on mitigating skin reactions and assessing the impact on psychosocial well-being.DisclosureA.J. Karami: None. V.S. Fadhel Hernández: None. C. Sakamoto: None. K. Taylor: None. E. Fivekiller: None. C. Berget: Consultant; Insulet Corporation. Advisory Panel; Tandem Diabetes Care, Inc. Other Relationship; Tandem Diabetes Care, Inc, Insulet Corporation, embecta. S. Lange: Advisory Panel; Medtronic. E.C. Cobry: Advisory Panel; Dexcom, Inc.FundingNational Institute of Diabetes and Digestive and Kidney Diseases (2T32DK063687)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-700-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 701-P: Levels of Diabetes Distress (DD) among Older Adults (OA) with Type
1 Diabetes (T1D)-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 701-P
Abstract: Introduction and Objective: DD- the emotions, stress, and worries associated with diabetes— is associated with glycemic control and severe hypoglycemia in younger individuals with T1D, but little is known about DD in older adults.Methods: We recruited OA (65+) with T1D from the T1D Exchange national registry (08/27/2024-11/05/2024) to complete an electronic survey including the Type 1 Diabetes Distress Assessment System (T1DDAS), which includes a core score and 10 subscores for sources of DD. We assessed univariate linear associations between other self-reported sociodemographic and diabetes-related variables and T1DDAS core scores (clinically significant ≥2.0).Results: Among OA with T1D (n=337; 70.7±4.6 years; 63% female; 96.4% White; median (IQR) T1D duration 45 (25) years; 97% CGM users; 66% HCL users; HbA1c 6.6±0.7%; 36% elevated DD; median (IQR) DD core score 1.75 (1.125), significant positive associations with core scores included sex, HbA1c, and history of 1+ ER visits, while T1D duration and food security status were negatively associated (Figure).Conclusion: Among a self-selected sample of OA with T1D, we corroborated known clinical associations with DD (HbA1c, T1D duration, ER visits). Female sex and food insecurity also emerged as potentially novel risk factors for DD in this age group.DisclosureA. Wisniewski: None. J.B. DeMonte: None. A. Cristello Sarteau: None. A. Fruik: None. A. Kahkoska: None.FundingNIH/NIDDK (P30 DK124723); NCDRC Ignition Award
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-701-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 702-P: Culturally Tailored Educational Materials for Latino Adults Aimed
at Increasing Awareness of Prediabetes and Fostering Enrollment in the
National Diabetes Prevention Program-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 702-P
Abstract: Introduction and Objective: Despite the widespread availability of the Diabetes Prevention Program (DPP) at minimal to no out-of-pocket cost for adults with prediabetes, participation rates remain low, with less than 1 percent of eligible individuals enrolling. There is a lack of research focused on increasing awareness of prediabetes and fostering enrollment in the DPP, particularly within populations experiencing diabetes-related disparities. We developed educational materials in the form of a 16-page graphic novel for Latino adults, with the goal of integrating the materials into an intervention designed to bridge clinical care with community-based DPP providers. The objective was to gather feedback from Latino adults regarding the acceptability of the materials.Methods: Two focus groups were conducted at a community site in Detroit, Michigan, one in English and the other in Spanish. The sessions were recorded and transcribed, and the Spanish-language transcript was translated into English. A qualitative descriptive approach was used for analysis.Results: A total of 17 Latino adults participated in the focus groups, ranging in age from 19 to 75 years, with a mean age of 42 years. All participants self-identified as female and Latino. The majority (n=11) were born in the US, and over half (n=12) reported an educational attainment level of high-school diploma or less. Qualitative analysis identified four main themes: 1) navigating healthcare challenges, 2) promoting awareness and education, 3) cultivating community and connection, and 4) addressing cultural sensitivities.Conclusion: The findings from this formative research highlight considerations for enhancing the educational materials for Latino adults. This research provides valuable insights into developing effective interventions to increase prediabetes awareness and enrollment in the DPP among this underserved population..DisclosureJ.A. Reyes: None. W. Wei: None. K. Joiner: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-702-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 703-P: Addressing Health Disparities—Findings from Community Health
Screenings for Diabetes and Hypertension in Underserved Populations-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 703-P
Abstract: Introduction and Objective: This report summarizes findings from health screening events conducted with grassroots immigrant organizations in Iowa to improve awareness and management of key health indicators like blood pressure and blood sugar. The focus was on underserved populations, particularly Latinos, who face disproportionately high rates of chronic diseases. Diabetes affects 17% of Latinos compared to 8% of non-Hispanic Whites, and hypertension impacts 25%, often due to socioeconomic challenges and limited access to care. This report highlights participant demographics, health conditions, screening outcomes, and recommendations for future interventions.Methods: Between July 1, 2023, and October 19, 2024, 25 health screening events took place in Des Moines, Marshalltown, Perry, and Storm Lake, targeting Spanish-speaking communities. A total of 1,021 participants completed intake surveys gathering demographic and health data. Screenings measured blood pressure and blood sugar levels, with referrals to federally qualified health centers (FQHCs) provided for follow-up as needed. Descriptive statistical analysis identified health trends and gaps in access to care.Results: Of the 1,021 participants, 72% were female, and 56% identified as Mexican. Approximately 64% were uninsured, and 15% had diabetes, with 55% reporting a family history. Hypertension affected 19%, and 47% reported a family history of high blood pressure. Although 71% had prior screenings, 24% had never been tested. Referrals were made for 20 participants with abnormal results.Conclusion: These screenings revealed gaps in healthcare access, especially for diabetes and hypertension. Recommendations include expanding screenings, targeting high-risk groups, improving follow-up care, and increasing education to enhance community health outcomes.DisclosureJ.A. Reyes: None. W. Wei: None. J. O'Hara: None. I. Perez-Rodriguez: None. C. Brandt: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-703-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 704-P: The Impact of an AI-Driven Digital Diabetes Program on Glycemic
Control through Holistic Lifestyle Modification-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 704-P
Abstract: Introduction and Objective: Current diabetes lifestyle management services often fail due to a lack of personalization and scalability. An AI-driven digital platform combined with life coaching can provide tailored solutions to address this gap effectively. This study evaluated its impact on fostering sustainable behavior change and improving glycemic control.Methods: This 3-month, single-arm study enrolled 74 participants with prediabetes or type 2 diabetes, with a mean age of 50.2 years (SD: 10.9 years) and a mean BMI of 35.1 kg/m² (SD: 4.9). The primary outcomes included changes in lifestyle metrics such as physical activity, eating habits, and sleep patterns, which affect glycemic control. Secondary outcomes were changes in HbA1c and body weight.Results: At baseline, 90% of participants had sedentary lifestyles, unhealthy eating habits, and poor sleep. Over three months, 70% engaged in ≥150 minutes of weekly physical activity, while significant reductions in meal skipping, late-night snacking, and sugary food consumption were observed. Sleep patterns also improved significantly. Mean HbA1c decreased by 0.5% (P <.001, 95% CI: -0.3 to -0.7) in prediabetes and by 0.9% (P <.001, 95% CI: -1.3 to -0.5) in diabetes groups. Additionally, 50% of participants achieved >5% weight loss, a key factor in reducing diabetes risk.Conclusion: These findings demonstrate that a holistic, AI-powered digital program integrating life coaching and holistic lifestyle tracking can effectively prevent and manage diabetes by driving sustainable behavioural changes. Further research is needed to confirm its long-term benefits.DisclosureM. Farshchi Nasr: None. A. Madjd: None. D. Taylor: None. H.R. Farshchi: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-704-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 705-P: Enhanced Detection of Efficacy in T1D Prevention Trials Using
Glucose Fractions-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 705-P
Abstract: Introduction and Objective: OGTT-derived AUC glucose (AUCglu) can be separated into fractions, dependent (DEP) or independent (INDEP) from insulin secretion. We hypothesized that removal of INDEP from AUCglu adds specificity for insulin secretion thereby improving the detection of treatment effects in T1D prevention trials.Methods: Index60, a composite measure of glucose and C-peptide, was a surrogate for insulin secretion to separate AUCglu into DEP and INDEP fractions. DEP was defined by the intercept and slope of a simple linear regression equation for AUC glucose vs. Index60 (DEP = 130.74+11.08* Index60). INDEP was calculated by subtracting DEP from AUCglu. Analyses were performed in participants from the positive teplizumab and the negative abatacept Trialnet prevention trials.Results: Changes in AUCglu and glucose fractions from baseline to 1 year in treatment and placebo groups are shown (Table). In the teplizumab trial, the difference between groups for DEP as the endpoint was more significant than for AUCglu. In the abatacept trial, the difference was significant for DEP, but not for AUCglu as the endpoint. The difference for INDEP was of borderline significance in the teplizumab analysis.Conclusion: Removing INDEP from AUCglu can improve specificity for insulin secretion and thus increase the likelihood of detecting a treatment effect using glucose as a metabolic endpoint in T1D prevention trials.DisclosureB.M. Nathan: None. D.D. Cuthbertson: None. H.M. Ismail: Consultant; Rise Therapeutics. L.M. Jacobsen: Advisory Panel; Sanofi. M.J. Redondo: None. E.K. Sims: Consultant; Sanofi. Speaker's Bureau; Med Learning Group. Other Relationship; American Diabetes Association. W.E. Russell: None. K.C. Herold: Consultant; Sanofi, Dompé, Vertex Pharmaceuticals Incorporated, Sonoma, NexImmune. J. Sosenko: None.FundingNational Institutes of Health
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-705-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 706-P: DIRAS2—A Novel Regulator of Glucose Metabolism and Pancreatic
Islet Survival-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 706-P
Abstract: Introduction and Objective: Diras2 is a small Ras-related GTPase, primarily expressed in the brain that is implicated in attention-deficit/hyperactivity disorder (ADHD). Our lab has identified Diras2 in mouse pancreatic islets in response to stress conditions.Methods: To elucidate the novel role of Diras2 in pancreatic islets and its physiological significance, we characterized global Diras2-/- knockout male mice on C57B6N/J background compared to C57B6N/J wildtype (WT) mice with functional Diras2.Results: The glucose tolerance test (GTT) and insulin tolerance test (ITT) under chow and high fat diet revealed enhanced glucose tolerance and insulin sensitivity in Diras2-/- mice, while body weight showed no significant differences compared to WT controls. Functional studies on islets isolated through collagenase digestion showed no significant difference in insulin secretion and content between both studied groups under 11mM and 28mM glucose concentrations over 72 hours, as quantified by ELISA. Stress response studies using beta-cell-specific stressors such as thapsigargin (1цM), rotenone (50nM), and proinflammatory cytokines (IL-1β-5ng/mL, TNF-α 10ng/mL and IFN-ϒ, 100ng/mL) demonstrated that Diras2-/- mice were significantly protected against cytokine-induced apoptosis after overnight treatment when measured through cell death using propidium iodide and annexinV.Conclusion: These findings suggest that improved glucose tolerance and insulin sensitivity in the absence of Diras2 may originate from the alterations in neural signals, given the high expression of Diras2 in the brain. Furthermore, Diras2 may possess a proapoptotic role in islets and reducing Diras2 expression may reduce cytokine-induced damage which further offer insights into its potential contribution to metabolic homeostasis, and its relevance as a therapeutic target for diabetes.DisclosureN. Ajmal: None. K. Corbin: None. N. Cunningham: None. P. Khan: None. M.A. Kalwat: Stock/Shareholder; Eli Lilly and Company, Pfizer Inc. C.S. Nunemaker: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-706-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 707-P: Obesity-Associated Inflammatory Responses Are Significantly
Modified by Insulin Sensitivity-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 707-P
Abstract: Introduction and Objective: Systemic inflammation promotes insulin resistance (IR) and comorbidities like type 2 diabetes. Multiple CD4+ T cell subsets support inflammation in people with excess weight or obesity (herein, obesity). Autophagy is one key mechanism that regulates T cell-generated cytokines and thus inflammation. We tested the hypothesis that obesity-associated changes in T cell autophagy support inflammation and metabolic health declines by analyzing T cells from obese insulin-sensitive (IS) and IR subjects for cytokine production and for indicators of autophagy.Methods: Archived PBMCs from IS (HOMA-IR < 2.2; N=7) or IR (HOMA-IR > 2.5; N=7) subjects (BMI avg. 32.5, avg age 56.3 yrs) were recovered overnight with IL-2. CD4+ T cells were negatively isolated from PBMCs using magnetic beads, then stimulated with phorbol ester and ionomycin for 1.5 hours to induce (1) autophagy, analyzed by confocal microscopic quantification of lipidated LC3, p62, and LAMP1; and (2) inflammation, based on combinatorial cytokine profiles generated by partial least squares discriminant analysis of up to 25 cytokines produced by each cell in a single cell proteomics platform.Results: T cells from IR compared to IS subjects produced a cytokine profile dominated by IL-12 that was similar to a type 2 diabetes T-cell profile. T cells from men compared to women unexpectedly produced a more inflammatory profile. Confocal analysis showed defective autophagy in the IR group compared to IS, as indicated by reduced lipidated LC3B, increased P62 and decreased LC3B/LAMP1 colocalization.Conclusion: Obesity-associated IR is a more inflamed state than IS as expected, with CD4+ T cells from men specifically showing more production of cytokines typical of type 2 diabetes. IR also disrupted CD4+ T cell autophagy, with more severe effects in mens’ cells. These results indicate defective autophagy as a likely mechanistic underpinning of IR-associated T-cell inflammation in obesity.DisclosureA. Javidan: None. L.P. Bharath: None. E. Tevonian: None. B. Marrah: None. A. Konopka: Research Support; Dexcom, Inc. B.F. Miller: None. M.P. Bubak: None. D. Lauffenburger: None. B. Nikolajczyk: None.FundingNational Institute on Aging (R01AG079525-03)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-707-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 708-P: Comparative Effectiveness of Structured Interventions in the Korean
Diabetes Prevention Study (KDPS) vs. the Korean Genome and Epidemiology
Study (KOGES)-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 708-P
Abstract: Introduction and Objective: This study aimed to compare the effectiveness of the Korean Diabetes Prevention Study (KDPS) and the Korean Genome and Epidemiology Study (KoGES) in preventing diabetes among prediabetes populations. The primary focus was to evaluate the outcomes of different intervention strategies and their impact on diabetes progression.Methods: KDPS employed three intervention strategies: Standard Management (STM) with biannual education; Lifestyle Modification (LSM) with an intensive 6-month program followed by quarterly follow-ups; and Metformin (MET) therapy with up to 1000 mg doses and quarterly visits. KoGES, a prospective nationwide cohort study, investigates genetic and environmental factors in chronic diseases. Participants included individuals with impaired fasting glucose (IFG), impaired glucose tolerance (IGT), or HbA1c levels between 5.7-6.4%. Propensity score matching (PSM) standardized baseline characteristics, and Kaplan-Meier survival analysis compared diabetes progression over time.Results: After PSM, baseline characteristics were balanced between KDPS (n=350) and KoGES (n=350) participants. Over a follow-up period of 6 years, the cumulative incidence of diabetes in the KDPS cohort was 63 cases, significantly lower than the 147 cases observed in the KoGES cohort (p<0.01). Survival analysis revealed meaningful differences in survival rates between the two cohorts, providing important insights into strategies for diabetes prevention and management.Conclusion: The findings demonstrate that targeted interventions in the KDPS cohort effectively reduce diabetes incidence compared to the general population represented by KoGES. This study underscores the importance of structured prevention programs in mitigating diabetes risk and provides a robust framework for future comparative analyses.DisclosureS. Yun: None. H. Sang: None. S. Shin: None. J. Choi: None. Y. Yoon: None. S. Chon: None. J. Woo: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-708-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 709-P: Weight Loss among Distance Learning Participants in an
Employer-Based Diabetes Prevention Program-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 709-P
Abstract: Introduction and Objective: Limited data suggest patterns and predictors of weight loss may differ for individuals who participate in the National Diabetes Prevention Program (DPP) via distance learning (DL). We investigated the association of baseline characteristics and factors influencing behavior change with weight loss over time for DL participants in an employer-based DPP.Methods: Between 2020 and 2023, we invited DL participants from the Health Plus DPP to participate in a program evaluation that included baseline assessments of motivation, confidence, social support, willingness to self-monitor, and health literacy as key factors influencing the behavior changes emphasized by the DPP. We also collected baseline participant characteristics consistent with Diabetes Prevention Recognition Program standards. We fit a linear mixed effect model that regressed percent weight loss on all demographics (baseline model) and then added factors influencing behavior change, separately, to estimate their associations with percent weight loss across follow-up times.Results: The median (IQR) baseline BMI for program evaluation participants (n=130) was 34 (30, 40). Median (IQR) weight loss at the end of the program was 3.1% (0%, 7.4%). We observed independent associations between percent weight loss over time and age, race, and education (p<0.01). After adding factors influencing behavior change to the baseline model, the strongest associations (p<=0.01) were observed with controlled regulation (motivation subscale), general motivation, confidence, and health literacy. However, for all demographic and behavioral variables, the 95% CIs for the cross-sectional association with weight loss at 300 days spanned zero.Conclusion: We identified several unique baseline factors associated with percent weight loss over time for DL participants, but there was insufficient evidence to suggest cross-sectional associations with percent weight loss 300 days into the program.Disclosure R. Chakkalakal: Research Support; National Institute of Diabetes and Digestive and Kidney Diseases, Centers for Disease Control and Prevention. L. Miller: None. E.R. Cox: None. B.M. Awalt: None. L. Rolando: None. C. Audet: None. Y. Shi: None. J.S. Schildcrout: None. M.K. Ali: Advisory Panel; Eli Lilly and Company. M.H. Aliyu: None.FundingNational Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health (1R01DK120814)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-709-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 710-P: Comparing Models for Predicting Diabetes Progression and
Cardiovascular Disease in Risk Stratification and Drug Selection for
Prediabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 710-P
Abstract: Introduction and Objective: To compare models predicting diabetes (DM) progression or incident cardiovascular disease (CVD) in risk stratification and treatment heterogeneity identification in patients with prediabetes.Methods: This study included 2,607 patients from the Diabetes Prevention Program (DPP) and the Diabetes Prevention Program Outcomes Study (DPPOS). Patients with prediabetes were stratified based on DM and CVD progression models with optimal predictive performance. Cox regression and logistic regression were used to evaluate the incidence of diabetes, microvascular, and cardiovascular events across different risk and intervention groups.Results: The machine learning-based diabetes progression model in US people (MLPR-US model) achieved an ROC AUC of 0.79 (95% confidence interval [CI], 0.72-0.86) for predicting diabetes progression, while the PREVENT model showed an ROC AUC of 0.73 (95% CI, 0.71-0.76) for predicting CVD events. The risk of diabetes progression, cardiovascular events, and microvascular events increased by 250% (p<0.001), 27% (p=0.043), and 50% (p=0.004) in the DM high-risk group versus their controls. The corresponding figure was -11% (p=0.276), 284% (p<0.001), and 287% (p<0.001) in the CVD high-risk group. A significant treatment-by-group interaction was observed for diabetes progression in both DM and CVD risk groups, with DM high-risk patients benefiting from metformin and lifestyle therapy, while CVD high-risk patients benefited only from lifestyle therapy. No such interaction was found for microvascular or CVD events.Conclusion: The CVD model identified high-risk individuals for cardiovascular and microvascular events but not diabetes progression. The DM model highlighted patients with prediabetes needing lifestyle and metformin therapy to prevent diabetes progression.DisclosureS. Wang: None. Q. Huang: None. Y. Luo: None. L. Ji: None. X. Zou: None.FundingNational Natural Science Foundation of China (T2341011), Noncommunicable Chronic Diseases-National Science and Technology Major Project (2023ZD0508800), Beijing Science and Technology Program (Z181100001618010)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-710-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 711-P: Assessing Caregivers’ Knowledge and Opinions on T1D Antibody
Screening and Teplizumab Infusions-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 711-P
Abstract: Introduction and Objective: The FDA approved teplizumab to delay stage 3 T1D. We investigated opinions of caregivers of children with T1D on antibody screening and teplizumab use.Methods: Caregivers of pediatric patients with T1D (N = 239) completed an online survey. Questions included demographic information, and knowledge and attitudes related to antibody screening and use of teplizumab. Generalized Estimating Equations and logistic regression examined associations among parent and child demographics and attitudes.Results: Most participants were aware that relatives of those with T1D are at higher risk (80.2%), that risk can be predicted (82.4%), and were interested in obtaining labs to determine risk in their other children (81.6%). Most hadn’t heard of teplizumab (62%), but once provided information, were interested in teplizumab for a high-risk child (75.1%). Participants with children on private insurance were more likely to have heard of teplizumab prior to the survey (OR 11.39 (2.59, 50.07)), those with non-Hispanic Black children were less likely (OR 0.34 (0.14, 0.83)). Caregiver age, gender, race/ethnicity, income, and insurance type were not associated with interest in teplizumab (Table 1).Conclusion: Caregiver demographic characteristics were not associated with interest in teplizumab, underscoring the importance of promoting awareness and ensuring equal access to this treatment.DisclosureR.L. Longendyke: None. J. Grundman: Research Support; Dexcom, Inc. P. Dwivedi: None. M. Tran: None. S.L. Holly: None. R. Streisand: None. S. Majidi: Speaker's Bureau; Sanofi.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-711-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 712-P: Understanding Participant Decision Making for Enrolling in an
Intervention Trial to Delay Stage 3 T1D-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 712-P
Abstract: Introduction and Objective: Participant enrollment in the TrialNet ATG Prevention study to delay stage 3 type 1 diabetes among high-risk individuals was much lower than expected; reasons for this were not well understood. This study used qualitative research to explore participant decision making about enrolling in this intervention study.Methods: We conducted semi-structured interviews with both adult participants and caregivers of youth who declined to participate in screening for the study. Interviews were conducted via secure video platform, recorded, transcribed, and then analyzed using content analysis to identify themes associated with the decision to decline participation.Results: 10 adults (80% Female, 60% caregivers, mostly White, Non-Hispanic) were interviewed. Preliminary themes identified include: (1) participants had mixed views about delaying stage 3 T1D diagnosis which may differ from what investigators expect; (2) participants identified study benefits, but they were often outweighed by perceived drawbacks; and (3) study materials were often viewed as overly complex and difficult to understand (Table 1).Conclusion: Qualitative data yielded important, and sometimes surprising, data regarding participant perspectives. Engagement of participant partners throughout the design of future protocols may improve participant recruitment.Disclosure H.K. O'Donnell: Advisory Panel; Sanofi. Other Relationship; Sanofi. A.M. Jimenez-Zambrano: None. E. Paschal: None. C. March: None. L.A. DiMeglio: Stock/Shareholder; Lilly USA LLC. Research Support; Lilly Diabetes. Other Relationship; Lilly USA LLC. Research Support; MannKind Corporation. Other Relationship; Sanofi. Research Support; Zealand Pharma A/S. Consultant; Vertex Pharmaceuticals Incorporated, Tandem Diabetes Care, Inc, Biomea Fusion. Other Relationship; Merck & Co., Inc. K.C. Herold: Consultant; Sanofi, Dompé, Vertex Pharmaceuticals Incorporated, Sonoma, NexImmune. S.B. Johnson: None.FundingNational Institute of Diabetes and Digestive and Kidney Disease (U01DK106993)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-712-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 713-P: Relationship between Magnitude of Weight Loss and Cardiovascular
Outcomes in the Diabetes Prevention Program (DPP) and Its Outcomes Study
(DPPOS)-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 713-P
Abstract: Introduction and Objective: Overweight/obesity are determinants of cardiovascular risk. This post hoc analysis evaluated the effect of magnitude of early weight loss during the Diabetes Prevention Program (DPP) on major adverse cardiovascular events (MACE) in DPP and its Outcomes Study (DPPOS).Methods: The DPP randomized 3,234 adults at high risk for type 2 diabetes to intensive lifestyle intervention (ILS), metformin, or placebo (PBO), and subsequently followed the cohort in the DPPOS. Weight loss at DPP Year 1 was assessed categorically (defined as: weight gain/weight neutral (reference category); >0 to <5% weight loss; 5 to <10% weight loss; and ≥10% weight loss). This analysis includes 3,100 participants with Year 1 weight and who did not experience MACE or death prior to Year 1. Time to first occurrence of MACE (death from cardiovascular causes, non-fatal myocardial infarction, non-fatal stroke) during 22 years of follow-up was assessed using log-rank tests. Risk of MACE was assessed with adjusted Cox proportional hazards models and 95% confidence intervals (aHR; 95% CI) in the overall cohort and in separate treatment groups.Results: Time to first MACE differed by weight loss category (p=0.004) in the overall cohort, with the ≥10% loss weight loss category experiencing significantly lower risk of MACE compared with the weight gain/weight neutral reference category (0.59; 0.37 - 0.94). Weight loss of 5 to <10% in PBO was associated with greater risk of MACE compared with weight gain/weight neutral reference category (2.12; 1.19 - 3.76).Conclusion: Overall, a high magnitude (≥10%) of weight loss over 1 year of intervention was associated with lower risk of MACE in a cohort at high risk for type 2 diabetes, but moderate weight loss in the placebo group was associated with greater risk of MACE. These findings may suggest benefits of intervention-related weight loss and increased risks associated with unintentional or unexpected weight loss.Disclosure V.R. Aroda: Research Support; Applied Therapeutics. Consultant; Applied Therapeutics. Research Support; Boehringer-Ingelheim, Corcept Therapeutics. Consultant; Corcept Therapeutics, Pfizer Inc, AstraZeneca. Research Support; AstraZeneca. Consultant; Mediflix, Novo Nordisk. Research Support; Novo Nordisk. Consultant; Sanofi. Research Support; Rhythm Pharmaceuticals, Inc. Consultant; Fractyl Health, Inc. Research Support; Fractyl Health, Inc., Eli Lilly and Company. Other Relationship; Merck & Co., Inc, AditumBio. Research Support; Amgen Inc. N.P. Malkani: None. L. Doherty: None. M.J. O'Brien: None. D. Dabelea: None. U.N. Ibebuogu: None. W.C. Knowler: None. S. Kuo: None. N.N. Mathioudakis: None. S. Edelstein: None. D. Research Group: None.FundingNational Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health (U01 DK048489, U01 DK048339, U01 DK048377, U01 DK048349, U01 DK048381, U01 DK048468, U01 DK048434, U01 DK048485, U01 DK048375, U01 DK048514, U01 DK048437, U01 DK048413, U01 DK048411, U01 DK048406, U01 DK048380, U01 DK048397, U01 DK048412, U01 DK048404, U01 DK048387, U01 DK048407, U01 DK048443, and U01 DK048400)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-713-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 714-P: Oral Glucose Tolerance Test or Continuous Glucose Monitoring for
Assessment of Prediabetes State-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 714-P
Abstract: Introduction and Objective: The oral glucose tolerance test (OGTT) is ‘gold standard’ for defining carbohydrate metabolism abnormalities. Continuous Glucose Monitoring (CGM) is routinely used in diabetes patients for control assessment and dose adjustment but its role for assessment of prediabetes state is still not clear.The objective of our study is to assess the correlation between results from OGTT and data from CGM in patients with observation for prediabetes and to elucidate the usefulness of CGM in these cases.Methods: 109 patients (57 women, 52 men, mean age 40.01±8.87years) with increased risk for diabetes performed monitoring of blood glucose by using DexcomONE for ten days. At the end of this period, they underwent OGTT. Mean weight was 89.07±12.73kg, mean BMI was 32.86±2.0kg/sq.m. and mean HbA1c 5.58±0.38%.Results: Based on OGTT, 7 patients were diagnosed with diabetes and were excluded from data assessment. 75 patients were with normal fasting and 120th minute glucose. In patients with diagnosed impaired glucose tolerance or with increased fasting glucose, CGM showed increased time above the set range (TAR) of 7.8 mmol/l and e area above the curve (phi=0.78, p<0.05). Comparing the CGM data of patients with diagnosed normal carbohydrate state based on OGTT, showed that in 20% (15 patients) there was higher TAR (>5.0%) and AUC above 7.8 mmol/l and the profile was similar to CGM data of patients with diagnosed prediabetesConclusion: OGTT is omitting approximately 20 % of case with changes in glucose profile and gives false negative results, leading to missing on time recommendation to this patients for life changes. CGM gives more precise results in assessing carbohydrate state.DisclosureT. Totomirova: None. M. Arnaudova: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-714-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 715-P: A Novel Approach for Assessing Treatment Failure vs. Success at
Fixed Time Intervals in T1D Prevention Trials-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 715-P
Abstract: Introduction and Objective: We asked if a binary endpoint for change (∆) from baseline to a fixed timepoint of 1 year could be useful in future trials.Methods: We used 2hr-OGTT data from the negative abatacept prevention trial and the positive teplizumab prevention trial, and from participants in the observational TrialNet Pathway to Prevention Study (PTP) with similar characteristics. Glucose and C-peptide response curves were plotted and vectors for curve movement from baseline to 1 year were used to categorize simultaneous glucose ∆ and C-peptide ∆ as metabolic treatment failure vs. success.Results: PTP participants with ∆glucose>0 and ∆C-peptide<0 from baseline to 1 year were at substantially higher risk for stage 3 T1D than those with ∆glucose<0 and ∆C-peptide>0 (p<0.0001). Based on this, we compared placebo vs. treatment groups in both trials for failure (∆glucose>0 with ∆C-peptide<0) vs. success (∆glucose<0 with ∆C-peptide>0) after 1 year. In the table, the failure vs. success endpoint at 1 year revealed more treatment efficacy than the original endpoints used for each trial, which required 8.0 years to implement for abatacept and 10.5 years to implement for teplizumab.Conclusion: An analytic approach using a binary metabolic endpoint of failure vs. success at a fixed time interval appears to detect treatment effects at least as well as standard primary endpoints with shorter follow-up.Disclosure E.K. Sims: Consultant; Sanofi. Speaker's Bureau; Med Learning Group. Other Relationship; American Diabetes Association. W.E. Russell: None. K.C. Herold: Consultant; Sanofi, Dompé, Vertex Pharmaceuticals Incorporated, Sonoma, NexImmune. D.D. Cuthbertson: None. H.M. Ismail: Consultant; Rise Therapeutics. L.M. Jacobsen: Advisory Panel; Sanofi. B.M. Nathan: None. M.J. Redondo: None. J. Sosenko: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-715-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 716-P: Partnering with Supermarkets to Stop Diabetes for the
Underserved—A Prospective Pilot Study-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 716-P
Abstract: Introduction and Objective: Prediabetes is on the rise, especially among the underserved. This study evaluated the feasibility of a healthcare delivery model that partnered primary care providers (PCP) with supermarket pharmacists to stop diabetes.Methods: This was a 3-month, prospective, single-group pilot study conducted from March to October 2024 in a federally qualified health center. Adults with prediabetes and willing to visit supermarket pharmacists near their residences were included. Individuals unable to communicate independently were excluded. Eligible patients referred by their PCP were monitored monthly by supermarket pharmacists. In addition to theme-based self-care coaching, BMI, blood pressure (BP), and A1c were tracked at baseline and 3 months.Results: Eleven subjects (8 females; 3 males) completed the study. The average age was 50.0±14.5 years with 8 Latinx, 2 Whites, and 1 Asian. Seven patients had a college education, and 6 patients worked full- or part-time. All patients described their general health as fair or good. Mean baseline BMI, BP, and A1c were 29.8 ±6.1 kg/m2, 124/82 ±12/11 mmHg, and 5.8 ±2.5%, respectively. Health status improved for all at 3 months, with 8 reverting to normalcy and none progressing to type 2 diabetes.Conclusion: Collaboration with frontline community partners in supermarkets appeared to improve underserved patients' health and prediabetes status.DisclosureJ.Y. Lee: None. D. Chan: None. P. Gaura: None. A. Tran: None. L. Lao: None. Z. Wallach: None. J.T. Nguyen: None. M. Luhan: None. L. Gibbs: Stock/Shareholder; Moderna, Inc, Johnson & Johnson Medical Devices Companies. J. Mayorga: None.FundingUC END DISPARATIES Pilot Grant (P50MD017366)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-716-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 717-P: Small Molecule Allosteric Activators of SERCA Improve β-Cell
Viability and Calcium Homeostasis-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 717-P
Abstract: Introduction and Objective: Type 2 diabetes mellitus (T2DM) is a chronic metabolic condition where insulin resistance and impaired insulin secretion lead to hyperglycemia. Pancreatic β-cells regulate insulin production and secretion; however, pathological stressors encountered during diabetes development, including endoplasmic reticulum (ER) stress, contribute to decreased β-cell mass and function and altered cell identity. The ER serves as the central Ca2+ storage organelle for the β-cell, and Ca2+ is actively transported from the cytosol into the ER by the sarco/endoplasmic reticulum Ca2+ ATPase (SERCA). We have shown that pancreatic islet expression of SERCA2 is decreased in mouse models of obesity and in organ donors with T2DM. Furthermore, loss of SERCA2 activity impairs insulin secretion and β-cell survival. Here, we determined whether ER stress-induced β-cell death is ameliorated through SERCA activation.Methods: INS-1 cells and human pancreatic islets were used to screen a series of small molecule allosteric SERCA activators to determine the effect on ER Ca2+ dynamics and β-cell viability. Cells and islets were co-treated with tunicamycin (300 nM) and SERCA activators for 24 hours. To determine ER Ca2+ concentrations, cells were transfected with pCMV G-CEPIA1er and imaged using an upright confocal laser scanning microscope. Cell viability was determined by Sytox green, a nucleic acid stain, and quantified with a Sartorius IncuCyte S3/SX1 live cell imaging and analysis system.Results: As expected, tunicamycin treatment of INS-1 cells and islets increased cell death and lowered ER Ca2+ levels; however, when cells were co-incubated with tunicamycin and small molecule SERCA allosteric activators, cell survival was increased and ER Ca2+ levels were maintained compared to cells and islets treated with tunicamycin alone.Conclusion: Our findings suggest that SERCA activation with small molecules holds promise as a therapeutic strategy to treat ER stress-mediated β-cell dysfunction during T2DM.DisclosureD.J. Sanchez Rodriguez: None. T. Kono: None. R. Dahl: None. C. Evans-Molina: Advisory Panel; DiogenX. Research Support; Bristol-Myers Squibb Company, Lilly Diabetes. Advisory Panel; Isla Technologies, Neurodon. Research Support; Neurodon. R.C. Branco: None.FundingFunded by Breakthrough T1D
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-717-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 718-P: DNA Methylation Biomarkers Associated with Weight Loss Response for
Individuals with Prediabetes Based on Korean Diabetes Prevention Study
(KDPS)-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 718-P
Abstract: Introduction and Objective: Weight management is essential for preventing type 2 diabetes, particularly in individuals with prediabetes. DNA methylation (DNAm) serves as a biomarker for capturing metabolic changes and disease progression. This study aimed to discover DNAm biomarkers linked to weight loss response in diabetes prevention interventions for individuals with prediabetes.Methods: We analyzed 168 subjects (ages 30 to 70, BMI ≥ 23 kg/m2) from the KDPS cohort, all with prediabetic conditions. Participants underwent a 6-month intervention in three groups: standard management (STM), lifestyle modification (LSM), metformin (MET). Blood DNAm was assessed using Illumina EPIC v2.0 arrays (697,649 CpG sites post-QC). Differential methylation loci were identified between the 3% weight-loss responders and those who maintained weight post-intervention using SeSAMe package.Results: Weight loss was significantly higher in LSM (1.8 times, p=0.052), and MET (2 times, p=0.028), compared to STM. Among the 3% weight-loss responders, 220 hypermethylated and 1,912 hypomethylated CpG sites exhibited specific DNAm changes (Δβ ≤ 0.03, FDR < 0.05). Reactome pathway analysis highlighted Notch signaling pathway, associated with T2DM and obesity, involving HDAC4, NOTCH2, and NCOR2 genes. Four CpG sites (cg03404471 [OXCT1], cg27133681 [CAMK2G], cg13006177 [SAMD12], cg23968558 [RAI1]) displayed differential methylation between weight-loss responders and weight maintainers (Effect size ≤ 0.02, FDR < 0.1).Conclusion: These findings highlight specific DNAm changes associated with weight loss in diabetes prevention. Long-term studies are needed to validate these findings and explore their potential in personalized diabetes prevention strategies.DisclosureS. Song: None. G. Kim: None. S. Chon: None. A.M. Lindroth: None. J. Lim: None. D. Yoon: None. Y. Park: None.FundingKorea National Institute of Health (2023-NI-006-01)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-718-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 719-P: Oral Disposition Index (oDI) as an Outcome Measure in Type 1
-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 719-P
Abstract: Introduction and Objective: Metabolic endpoints are being explored for treatment response in T1D prevention trials. Measures combining both insulin secretion and sensitivity could be more sensitive markers of treatment effect in clinical trials.Methods: We compared OGTT-derived AUC C-peptide and C-peptide index (CPI) as measures of secretion, and the oDI (AUC Insulin*Matsuda Index) as a measure of β-cell function including both secretion and sensitivity in two TrialNet trials in Stage 1 (TN18, Abatacept for 12 months) and Stage 2 (TN10, Teplizumab for 14 days) T1D. We compared measures over time and after 2 years of treatment between treated and placebo arms.Results: In TN10, Teplizumab had a greater effect on AUC C-peptide (p=0.008) and CPI (p<0.001) compared to placebo after 2 years; oDI did not differ (p=0.241). Conversely, in TN18, oDI was higher in the Abatacept arm compared to placebo (p<0.001) with no differences in AUC C-peptide (p=0.270) and CPI (p=0.194). Further, in TN18, there was a positive change in oDI from baseline in the treated arm (p<0.001), Figure 1.Conclusion: The oDI appears to be more sensitive at detecting differences in Abatacept effect in Stage 1, while C-peptide measures identifies long-term effect of Teplizumab in Stage 2. This could be due to both secretion and sensitivity playing a stronger role in Stage 1, which is better seen over a longer period of time.DisclosureA. Galderisi: None. D.D. Cuthbertson: None. A. Petrelli: None. A. Moran: Research Support; Abbott. Consultant; Abata Therapeutics. Other Relationship; Novo Nordisk. J. Sosenko: None. L.M. Jacobsen: Advisory Panel; Sanofi. I. Libman: None. M.J. Redondo: None. H.M. Ismail: Consultant; Rise Therapeutics.FundingNIDDK (K23DK129799)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-719-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 720-P: Assessing Fairness of QPrediction Models Using UK Biobank Data
-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 720-P
Abstract: Introduction and Objective: Prognostic prediction models play a critical role in the early detection of and interventions related to cardiovascular outcomes. However, many existing models have been shown to exhibit varying performance across demographic subgroups, particularly when fairness is not explicitly addressed in the model design. In this study, we evaluated the performance of established risk prediction models—QRISK3, QRISK-Lifetime, QDiabetes, and QStroke—which estimate 10-year and lifetime risks for cardiovascular disease, diabetes, and stroke, respectively.Methods: For validation, we used data from UK Biobank, a large-scale prospective cohort study comprising 502,269 participants. After applying model-specific exclusion criteria, we analyzed data from 405,980 participants for QRISK3 and QRISK-Lifetime, 458,212 for QDiabetes, and 490,607 for QStroke. Predicted 10-year risks were compared to observed outcomes to evaluate model calibration.Results: Our results indicate consistent overestimation of risks across all models, with minimal differences in calibration across subgroups defined by sex, ethnicity, household income, deprivation levels, and education levels.Conclusion: These findings underscore the importance of continuous evaluation and refinement of risk prediction models to ensure fairness and relevance across diverse populations. Future research will explore the effects of incorporating social determinants of health on models’ performance.DisclosureI. Huynh: None. D. Utochkin: None. T.V. Varga: None.FundingNovo Nordisk Foundation (NNF22OC0075284); The Copenhagen Health Complexity center is funded by TrygFonden
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-720-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 721-P: Oral Nanotherapeutics for Precision Targeting of Antigen-Presenting
Cells for Prevention of Type 1 Diabetes—Preclinical Studies-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 721-P
Abstract: Introduction and Objective: Induction of tolerogenic antigen presenting cells (APCs) is an emerging immunotherapy for type 1 diabetes. Currently, one preventive therapy, Teplizumab, demonstrates efficacy of immune modulation, however avoiding immune-suppressive side effects is critical. In addition, the development of oral immunotherapies are challenging due to poor bioavailability and limited distribution to intracellular targets. Nanocomplexes are a promising strategy to deliver diabetic therapeutics, e.g. oral insulin1, that may be modified to produce an inverse vaccination approach.Methods: Our aim was to develop and demonstrate the efficacy of an oral inverse vaccination nano-formulation (nano-insulin) for prevention of type 1 diabetes in non-obese diabetic (NOD) mice relative to Teplizumab; and show safety and tolerability in non-human primates (NHPs).Results: Nano-insulin (36-720 µg/kg/d) in NOD mice demonstrated a dose dependent delay in the onset of hyperglycaemia and inhibited disease in 68% mice treated out to 300 days. Compared to Tepluzumab (5 µg/d/5d), there was a 25% increase in the efficacy in preventing hyperglycaemia and reducted insulitis. Nano-insulin treated mice showed upregulated T regulatory cells, while Teplizumab showed reduced cytotoxic T cells. Nano-insulin treatment reduced insulin autoantibody production and immune reactive cells activation. Short term in vivo treatment showed upregulation of MHCII-IAg7 in APCs. Validation studies were performed by an external research group in mice. Additional single and multiple ascending dosing studies in NHPs demonstrates safety and tolerability (including immunogenicity).Conclusion: In conclusion, the use of a purpose-built organic nanocomplex for precision antigen delivery to APCs demonstrated efficacy in mice. Leading to this oral formulation to progress to clinical trials in 2025 in Australia.1Hunt, et al.Nat. Nanotechnol. 19, 534-544 (2024).DisclosureN. Hunt: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-721-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 722-P: Diabetes Remission Programs May Not Be an Effective Use of Fixed
Health Care Resources-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 722-P
Abstract: Introduction and Objective: In order to achieve diabetes remission, resources to support intensive lifestyle intervention (ILI) need to be directed towards people with diabetes for whom remission is achievable, i.e. short diabetes duration, lower HbA1c. We aimed to determine if responses to ILI, other than remission, justify this resource allocation.Methods: We analyzed Look AHEAD participants 20–65 years old with BMI 27–45kg/m2. The effect of ILI was assessed after stratification for remission eligibility at baseline (diabetes duration ≤6 years, no insulin). Cox models evaluated the effect of ILI on incidence of cardiovascular disease (CVD), chronic kidney disease (CKD), and mortality, and linear models assessed the effect on weight and HbA1c.Results: There were 3,105 participants - 60% women, median age 58 years old, median follow-up 9 years. At baseline, 54% were eligible for remission. Remission eligibility status did not modify the effect of ILI on CVD, CKD or mortality. ILI led to 2.4 kg greater weight loss (-5.53 kg (95%CI -6.02, -5.03) vs -3.17 kg (95%CI -3.86, -2.49)), and 0.1% greater HbA1c reduction (-0.28% (95%CI -0.33, -0.23) vs -0.17% (95%CI -0.23, -0.11)) in eligible compared to ineligible people (Figure).Conclusion: The small additional benefit of intervention in people eligible for remission, compared to ineligible people, may not be enough to justify restricting resources to such eligible people.DisclosureJ.Y. Gong: None. A. Salim: None. D.J. Magliano: None. J.E. Shaw: Advisory Panel; GlaxoSmithKline plc. Speaker's Bureau; AstraZeneca, Roche Diagnostics, Boehringer-Ingelheim, Zuellig Pharma. Advisory Panel; Novo Nordisk.FundingNHMRC (Investigator Grants and postgraduate scholarship), National Heart Foundation of Australia (postgraduate scholarship), The University of Melbourne (Rowden White scholarship)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-722-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 723-P: Achieving Prediabetes Remission during Lifestyle Intervention Is
More Effective Than Weight Loss for Type 2 Diabetes Prevention-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 723-P
Abstract: Introduction and Objective: Current guidelines recommend weight loss targets for individuals at risk for type 2 diabetes (T2D). Prediabetes is a high-risk state for T2D, and remission of prediabetes during weight loss has additional benefits for T2D prevention. Thus, we hypothesized that reaching glycemic targets is a more effective strategy for T2D prevention than weight loss targets.Methods: We studied 903 individuals with prediabetes from the German Prediabetes Lifestyle Intervention Study for whom data for weight loss and glycemic category classification was available. Glucose regulation was assessed by a 75 g oral glucose tolerance test. Prediabetes remission was defined as return to normal glucose regulation and normalized HbA1c according to ADA criteria. T2D risk was compared between responders and non-responders (R and NR) who lost weight (WL, n=298; < -5% of initial body weight), remained weight stable (WS, n=371; -5-0%) and gained weight (WG, n=234; >0%). Cox regression models were fit with age, sex and intervention intensity as covariates.Results: At baseline, age (p=0.11), fasting glucose (p=0.09), 2-hour glucose (p=0.98) and beta cell function were comparable between all three responder groups. WL-, WS- and WG-response was similarly protective from developing future T2D (HR for WL R vs. WL NR 0.11 [95 CI: 0.03-0.36], p = 0.00026, HR for WS R vs. WS NR 0.40 [95 CI: 0.17-0.93], p = 0.033, HR for WG R vs. WG NR 0.25 [95 CI: 0.09 -0.69], p = 0.0072,). T2D risk did not differ between weight loss strata (HR 0.82 [95 CI: 0.54-1.25], p = 0.36 for WS-R vs WG-R; and HR 0.91 [0.64-1.30], p = 0.61 for WL-R vs WG-R).Conclusion: Prediabetes remission, i.e. glycemic targets rather than weight loss targets, should be the primary treatment goal for T2D prevention.DisclosureA. Sandforth: None. L. Sandforth: None. S. Katzenstein: None. J. Seissler: None. N. Perakakis: Other Relationship; Novo Nordisk, Lilly Diabetes. Advisory Panel; Bayer Pharmaceuticals, Inc. Other Relationship; APOGEPHA, Transmedac Innovations AG, GWT-TUD, Elbe-Gesundsheintszentrum GmbH, Open Exploration. R. Wagner: Speaker's Bureau; Boehringer-Ingelheim, Novo Nordisk. Advisory Panel; Sanofi. Speaker's Bureau; Sanofi. Advisory Panel; Lilly Diabetes. A. Peter: None. R. Lehmann: None. H. Preissl: None. I. Yurchenko: None. J. Szendroedi: Advisory Panel; Novo Nordisk, Lilly Diabetes, Novartis AG, Boehringer-Ingelheim. M. Blüher: Advisory Panel; AstraZeneca. Speaker's Bureau; Amgen Inc. Advisory Panel; Bayer Pharmaceuticals, Inc, Boehringer-Ingelheim. Speaker's Bureau; Daiichi Sankyo. Advisory Panel; Eli Lilly and Company, Novo Nordisk, Nestlé Health Science, Sanofi-Aventis Deutschland GmbH. A. Schürmann: None. S. Kabisch: Research Support; Almond Board California, California Walnut Commission. Other Relationship; JuZo-Akademie, Boehringer-Ingelheim. Research Support; J. Rettenmaier & Söhne. Other Relationship; Lilly Diabetes. Research Support; Wilhelm-Doerenkamp-Foundation. K. Mai: None. P.E. Schwarz: None. M. Heni: Advisory Panel; Amryt Pharma. Speaker's Bureau; Amryt Pharma, AstraZeneca, Boehringer-Ingelheim. Advisory Panel; Boehringer-Ingelheim. Speaker's Bureau; Lilly Diabetes, Novartis AG, Novo Nordisk, Sanofi. M. Roden: Research Support; Boehringer-Ingelheim. Advisory Panel; Echosens. Speaker's Bureau; Madrigal Pharmaceuticals, Inc. Advisory Panel; MSD Life Science Foundation. Board Member; Novo Nordisk. Advisory Panel; TARGET PharmaSolutions, Inc. N. Stefan: Speaker's Bureau; AstraZeneca, Boehringer-Ingelheim. Consultant; Lilly Diabetes. Speaker's Bureau; Lilly Diabetes. Consultant; Pfizer Inc. Speaker's Bureau; Sanofi. Research Support; Sanofi. Speaker's Bureau; Novo Nordisk, GlaxoSmithKline plc. Consultant; GlaxoSmithKline plc. A. Fritsche: Advisory Panel; Abbott. Speaker's Bureau; AstraZeneca. R. Jumpertz von Schwartzenberg: None. A.L. Birkenfeld: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-723-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 724-P: High One-Hour Post-load Plasma Glucose Is an Intermediate Condition
between NGR and IGR-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 724-P
Abstract: Introduction and Objective: Lifestyle intervention (LI) is recommended in people with prediabetes. High 1-hour post-load plasma glucose (1h-PG) predicts T2D risk earlier than current criteria. We hypothesized that high 1h-PG represents an intermediate state between normal glucose regulation (NGR) and impaired glucose regulation (IGR) and that LI is more effective in high 1h-PG.Methods: 318 people from the Tübingen Lifestyle Intervention Program with NGR, IGR [fasting PG≥ 5.6 mmol/L and <7.0 mmol/l or 2-h PG ≥ 7.8 mmol/L and < 11.1 mmol/l]) or high 1h-PG (NGR and 1h-PG ≥ 8.6 mmol/L)) underwent LI (monthly dietary counseling to achieve ≥ 5% weight loss; increased physical activity) for 9 months.Results: At baseline (Table), insulin sensitivity (IS) and beta cell function (BCF) declined progressively from NGR (n=106), to the high1h-PG (n=93) and IGR (n=119) groups. Numerically, liver fat content and visceral adipose tissue volume (VAT) increased from NGT to high 1h-PG and to IGR. Risk of T2D during 12-years follow-up was reduced by 80% (37 - 96 %, p = 0.005) in the high 1h-PG group compared to the IGR group. The odds of remission to NGR were two-fold higher in the high 1h-PG group compared to the IGR group (2.18 [1.13 - 4.28], p = 0.021).Conclusion: High 1h-PG is an intermediate pathophysiological state between NGR and IGR. LI reduces ectopic fat deposition, improves IS and BCF and reduces the risk of incident T2D more in high 1h-PG than in IGR.DisclosureA. Sandforth: None. R. Jumpertz von Schwartzenberg: None. L. Sandforth: None. S. Katzenstein: None. H. Preissl: None. J. Machann: None. F. Schick: None. A. Fritsche: Advisory Panel; Abbott. Speaker's Bureau; AstraZeneca. N. Stefan: Speaker's Bureau; AstraZeneca, Boehringer-Ingelheim. Consultant; Lilly Diabetes. Speaker's Bureau; Lilly Diabetes. Consultant; Pfizer Inc. Speaker's Bureau; Sanofi. Research Support; Sanofi. Speaker's Bureau; Novo Nordisk, GlaxoSmithKline plc. Consultant; GlaxoSmithKline plc. M. Bergman: None. A.L. Birkenfeld: None.FundingGerman Federal Ministry for Education and Research (01GI0925) via the German Center for Diabetes Research (DZD e.V.)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-724-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 725-P: Minimal Weight Loss to Achieve Diabetes Prevention after a
Six-Month Intervention in the Korean Diabetes Prevention Study-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 725-P
Abstract: Introduction and Objective: This study aims to determine the minimum weight loss required for diabetes prevention in the Korean population.Methods: The Korean Diabetes Prevention Study (KDPS), a prospective, multicenter, randomized controlled trial, enrolled prediabetic adults aged 30-70 with a body mass index ≥23 kg/m2 from 2016 to 2022. Participants were assigned to standard management, lifestyle modification, or metformin groups. The primary outcome was the cumulative incidence of diabetes. A survival tree model identified the optimal weight loss threshold, and diabetes incidence was analyzed using Kaplan-Meier curves and Cox regression.Results: Among 701 participants who completed the 6-month intervention, a minimum weight loss threshold of 1.6% was identified for diabetes prevention. Participants achieving ≥1.6% weight loss had significantly higher diabetes-free probabilities over 72 months than those with <1.6% weight loss (p <0.002). After adjusting for sex, age, and metabolic factors, the ≥1.6% weight loss group had a 37-40% lower risk of diabetes, with adjusted hazard ratios of 0.63 (95% confidence interval [CI]: 0.48-0.82; p <0.001) and 0.60 (0.45-0.80; p <0.001).Conclusion: Achieving ≥1.6% weight loss reduces diabetes risk in overweight, prediabetic individuals, supporting the revision of Korea’s diabetes prevention guidelines based on KDPS evidence.DisclosureH. Sang: None. S. Shin: None. J. Choi: None. Y. Yoon: None. S. Chon: None. J. Woo: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-725-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 726-P: Two-Year Follow-up of AVT001 Dendritic Cell Therapy for Type 1
Diabetes—Continued Off-Therapy Functional Effects and Characterization
of Responders-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 726-P
Abstract: Introduction and Objective: AVT001 is an autologous dendritic cell therapy to address correctable dysfunction of HLA-E restricted CD8+ T regulatory pathway in autoimmune diseases. AVT001 treatment demonstrated C-peptide preservation in type 1 diabetes (T1D) at Days 150 and 360. Continued effects through 2 years are reported.Methods: In a phase 1/2, randomized, double-blind, placebo-controlled trial of subjects at least 16 years old, within one year of T1D diagnosis, and with a correctable defect in HLA-E restricted CD8+ T regulatory function, AVT001 (n=16) or placebo (n=9), was administered in three-monthly intravenous infusions. The primary endpoint was safety; efficacy endpoints included C-peptide area under the curve (AUC) during a 4-hour mixed meal, HbA1c and insulin dose.Results: Baseline characteristics were similar between groups. No serious adverse events were reported through D720. C-peptide AUC remained significantly greater in AVT001 versus control through D360 but not at D540/D720. Younger age, lower BMI, higher C-peptide, and lower insulin requirements were associated with C-peptide preservation with AVT001. There was no difference in HbA1c or insulin dose with treatment at any timepoint. Measured T regulatory function improved by D150 after AVT001 and persisted through D720 while regulatory function worsened in the placebo group over time.Conclusion: AVT001 was safe without dose limiting adverse events and treatment was associated with preserved endogenous insulin secretion at D150, but efficacy waned over time. The disconnect between C-peptide and regulatory effects over time warrants further investigation. Future trials are planned to utilize a booster strategy to prolong efficacy.ClinicalTrials.gov number, NCT03895996.Disclosure J.L. Gaglia: Consultant; Vertex Pharmaceuticals Incorporated. Stock/Shareholder; Vertex Pharmaceuticals Incorporated. Consultant; Avotres Inc. Research Support; Avotres Inc. Consultant; Kriya Therapeutics, Imcyse, Diamyd Medical AB. Research Support; Diamyd Medical AB, Sanofi, Biomea Fusion. H.L. Daley: None. N. Bryant: None. D.Y. Kim: None. J. Ritz: Research Support; Gilead Sciences, Inc, Novartis Pharmaceuticals Corporation, Oncternal. Advisory Panel; Astraveus, Garuda Therapeutics, LifeVault Bio, Smart Immune, Tolerance Bio, TriArm Therapeutics. E.E. Fan: None. T. Dong: None. A. Li: Employee; Avotres Inc. J.S. Skyler: Advisory Panel; 4 Immune. Consultant; AbbVie Inc. Advisory Panel; Abvance Therapeutics. Consultant; ActoBiotics. Advisory Panel; ADOCIA. Consultant; AiTA. Board Member; Applied Therapeutics. Advisory Panel; Avotres Inc., Bayer Pharmaceuticals, Inc, Biomea Fusion. Consultant; COUR Pharmaceuticals. Board Member; Dexcom, Inc. Consultant; Eli Lilly and Company. Advisory Panel; Kriya Therapeutics, Levicure. Consultant; Novo Nordisk A/S, Quell Therapeutics. Board Member; SAB Biotherapeutics, Inc. Consultant; Sanofi, Shoreline Biosciences. Advisory Panel; Signos. Consultant; Vertex Pharmaceuticals Incorporated, vTv Therapeutics. Advisory Panel; WiNK. H. Jiang: Employee; Avotres Inc.FundingAvotres Inc.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-726-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 727-P: A Phase 3 Evaluation of CAMP-Biased GLP-1 Analog Ecnoglutide vs.
Dulaglutide in Adults with Type 2 Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 727-P
Abstract: Introduction and Objective: To evaluate the efficacy and safety of ecnoglutide, a cAMP-biased long-acting GLP-1 analog, in adults with type 2 diabetes (T2D).Methods: A randomized, open-label, active-controlled, phase 3 trial of ecnoglutide was conducted at 52 sites across China, enrolling 623 adults with T2D uncontrolled on metformin. Participants were randomized in a 1:1:1 ratio to receive once-weekly ecnoglutide (0.6 or 1.2 mg) or dulaglutide (1.5mg) for a total of 52 weeks, including dose escalation. Primary endpoint was mean change in HbA1c at week 32. Changes in bodyweight as well as safety were also evaluated.Results: At baseline, participants had a mean age of 53.9 years, HbA1c of 8.40% and BMI of 26.9 kg/m2, and the median T2D history of 65.1 months. At 32 weeks, participants receiving ecnoglutide achieved HbA1c reductions of 1.89 to 1.91% from baseline vs 1.65% receiving dulaglutide (P≤0.0002, both doses achieved superiority over dulaglutide). In addition, more participants receiving ecnoglutide achieved HbA1c target of ≤6.5% and weight loss targets of ≥5.0% and ≥10.0% than receiving dulaglutide. Effects of ecnoglutide on glycemic control and bodyweight reduction sustained through the end of study at week 52. Ecnoglutide also significantly reduced triglyceride levels at Weeks 32 and 52. Ecnoglutide was safe and well tolerated. The proportion of participants reporting any adverse event (AE) ranged from 84.5 to 92.8% for ecnoglutide cohorts and 87.4% for dulaglutide cohort. AEs leading to treatment discontinuation were reported in 2.9% of participants receiving ecnoglutide 0.6mg, 3.8% receiving ecnoglutide 1.2mg and 2.9% receiving dulaglutide. The most frequently reported AEs were decreased appetite, diarrhea, and nausea, which were mostly mild to moderate in severity and transient.Conclusion: Once-weekly ecnoglutide was superior to dulaglutide in improving glycemic control and reducing bodyweight in adults with T2D uncontrolled on metformin.DisclosureX. Li: None. Y. He: None. N. Mi: None. H. Wang: None. S. Zhao: None. F. Jiang: Employee; Sciwind Biosciences, PrimeGene Biosciences. M. Yang: Employee; Sciwind Biosciences. S. Bing: Employee; Sciwind Biosciences. Q. Zheng: Employee; Sciwind Biosciences. J. Ning: Employee; Sciwind Biosciences. M. Guo: Employee; Sciwind Biosciences. Y. Bu: Employee; Sciwind Biosciences. L. Guan: Employee; Sciwind Biosciences. Y. Li: Employee; Sciwind Biosciences. L. Yang: None. W. Guo: Employee; Sciwind Biosciences. S. Xu: Employee; Sciwind Biosciences.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-727-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 728-P: Metabolomic Profiling of Obese Patients Treated with Liraglutide
Suggests Its Role in Modulating Inflammation-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 728-P
Abstract: Introduction and Objective: Liraglutide, a derivative of the human incretin glucagon-like peptide-1 (GLP-1), is approved for the treatment of both type 2 diabetes (T2D) and obesity. This study aimed to explore the metabolic benefits of Liraglutide in patients with obesity or overweight, focusing on changes in vital signs, anthropometric measures (such as weight, body mass index, and body composition), biochemical markers, and blood-based metabolomic profiles.Methods: A total of 49 subjects with a BMI greater than 30 kg/m² and no history of T2D were enrolled in the study. Participants were administered a once-daily subcutaneous dose of 3.0 mg liraglutide, along with a reduced calorie diet tailored to their individual estimated basal metabolic rate. Plasma samples were collected at baseline, 12 weeks, and 24 weeks. The primary outcome was the change in body weight, while secondary outcomes included alterations in anthropometric measurements, pro-inflammatory cytokines (IL-1β, IL-6, IL-8, and TNF-α), and plasma metabolome, analysed using Mass Spectrometry (MS).Results: At week 24, participants were categorised based on their weight loss (WL) response: poor responders (<5% WL, n=22), good responders (5-10% WL, n=18), and super-responders (>10% WL, n=9). Compared to non-responders, super-responders showed significant downregulation of phosphatidylcholine and triglycerides (p<0.001), and upregulation of sphingosine 1 phosphate (S1P) (p<0.005). A significant positive correlation was found between IL-6 levels and weight loss (r=0.732, p<0.001). In all super-responders, IL-6 levels were notably decreased, while S1P expression was significantly elevated.Conclusion: In this study, liraglutide administration produced several notable effects in individuals who responded exceptionally well to the treatment. Specifically, it reduced inflammation, as evidenced by an increase in S1P expression, known to have anti-inflammatory properties, and a decrease in IL-6 levels in the super-responders.DisclosureA. Murphy: None. L. Spencer: None. A. Duggirala: None. H.S. Randeva: Advisory Panel; Novo Nordisk. P.G. McTernan: None. G. Tripathi: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-728-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 729-P: Retrospective Effects of GLP-1 Receptor Agonists with and without
Concomitant SGLT2 Inhibitor Use in Diabetic Renal Transplant Recipients
after 12 Months-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 729-P
Abstract: Introduction and Objective: GLP-1RAs & SGLT2i are treatments with benefits extending beyond glycemic control in kidney transplant recipients (KTR). These agents show promise in enhancing metabolic & cardiorenal outcomes in diabetic KTR, but evidence, especially for monotherapy vs. combination use, remains scarce. This study evaluates the effects of GLP-1RAs alone & combined with SGLT2i on metabolic, glycemic, renal, & cardiovascular outcomes in T2D KTR over 12 months.Methods: Retrospective cohort study of KTR with pre-transplant T2D. Baseline and 12-month data on metabolic, glycemic, renal, & CV outcomes were analyzed. The 2nd drug was initiated 3-9 months after the 1st. Paired t-tests were used, results expressed as mean±SEM.Results: 18 patients (59±2.7 yrs, 83% male) were studied. 12 (66.7%) received GLP-1RAs and 6 (33.3%) GLP-1RA+SGLT2i. GLP-1RA monotherapy significantly improved BMI (p<0.01), FPG (p=0.03), & A1c (p=0.07). No changes in BP, HR, Total Cholesterol, or HDL noted. Combination therapy showed significant improvements in LDL (p=0.08), eGFR (p=0.04), BUN (p<0.01), & Tacrolimus levels (p=0.05). No patients discontinued therapy due to side effects.Conclusion: GLP-1RAs & SGLT2i are effective & safe for T2D KTR, GLP-1RA improving glycemic & weight outcomes, while combination therapy offers added renal and lipid benefits, suggesting synergistic effects warranting further study.DisclosureF.M. Acosta: None. B. Hu: None. C. Manikkuttiyil: None. P. Frausto: None. M. Escobar Vasco: None. C. Solis-Herrera: Advisory Panel; Novo Nordisk, Bayer Pharmaceuticals, Inc.FundingUTHSA LSOM Pilot Grant
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-729-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 730-P: Efficacy and Safety of Tirzepatide Added to Basal Insulin in
Chinese Patients with Type 2 Diabetes (SURPASS-CN-INS)-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 730-P
Abstract: Introduction and Objective: Study SURPASS-CN-INS assessed efficacy and safety of tirzepatide (TZP) vs. placebo (PBO) in patients with T2D as an add-on to titrated insulin glargine alone or in combination with metformin with or without sodium-glucose transport protein 2 inhibitor.Methods: In this double-blind, PBO-controlled, 40-wk Phase 3 study, 257 patients with T2D (mean baseline [BL] age 56.7 y; T2D duration 12.1 y; HbA1c 8.71%; BMI 27.1 kg/m2) were randomized (1:1:1:1) to TZP (5 mg, 10 mg, 15 mg) or PBO. Primary efficacy measures included mean change in HbA1c from BL to 40 wk. Secondary measures included change in body weight (BW), fasting serum glucose (FSG) and proportion of patients achieving HbA1c targets.Results: All 3 TZP doses were superior to PBO in change from BL in HbA1c, BW, FSG and proportion of patients achieving all HbA1c targets at 40 wk (except for HbA1c target of <5.7% for TZP 5 mg, Table). TZP was generally well tolerated and the most common adverse events were gastrointestinal and generally mild to moderate in severity. Level 2 hypoglycemia incidence (<54 mg/dL) did not differ between TZP and PBO. No events of level 3 (severe) hypoglycemia were observed.Conclusion: TZP demonstrated superior and clinically meaningful improvements in glycemic control and BW loss without increasing hypoglycemia vs. PBO in Chinese patients with T2D when added to titrated basal insulin.Disclosure L. Guo: Research Support; Abbott, AstraZeneca, Bayer Pharmaceuticals, Inc, Eli Lilly and Company, Innovent Biologics, Merck & Co., Inc, MSD Life Science Foundation, Novo Nordisk A/S, Sanofi, Jiangsu Hengrui Pharmaceuticals Co., Ltd, Tonghua Dongbao. X. Dong: None. J. Ma: None. M. Liu: None. Y. Lu: None. H. Wang: None. Q. Li: None. L. Li: None. Y. Deng: Employee; Lilly Diabetes. J. Xu: None.FundingEli Lilly and Company
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-730-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 732-P: Real-World Impact of Oral Semaglutide (SEMA) vs. DPP-4 Inhibitors
on Weight, BMI, and HbA1c Outcomes in Type 2 Diabetes (T2D)—An
Observational Study (PAUSE)-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 732-P
Abstract: Introduction and Objective: To assess the real-world effectiveness of oral sema on weight, BMI, and HbA1c outcomes among adults with T2D in the US, and compare it with DPP-4is.Methods: This observational study of adults with uncontrolled T2D (HbA1c ≥7%) initiating oral sema or DPP-4is (Oct 2019-Apr 2023; first prescription = index) used linked data from IQVIA PharMetrics® Plus adjudicated claims and Ambulatory Electronic Medical Records databases. Changes in weight, BMI and HbA1c outcomes from baseline to 6 months post-index were assessed for oral sema overall and in three subgroups: persistent (≤60-day gap in treatment), receiving dose ≥7 mg, and both persistent and receiving dose ≥7 mg. Furthermore, after inverse probability of treatment weighting (IPTW) for oral sema vs DPP-4is, a logistic regression model was used to evaluate adjusted outcomes.Results: In the overall oral sema sample (n=378) and subgroups, a significant mean reduction from baseline was seen in all outcomes (Figure). Post-IPTW, oral sema (n=259) was associated with significantly higher odds vs DPP-4is (n=486) in achieving composite post-index HbA1c <7% and ≥5% weight loss (odds ratio = 3.08; p<0.0001).Conclusion: Adults with T2D initiating oral sema had significant decreases in weight, BMI and HbA1c after 6 months, and higher odds of achieving the composite target vs DPP-4is.Disclosure J. Amamoo: Employee; Novo Nordisk. R.P. Doshi: None. J. Noone: Employee; Novo Nordisk. L. Xie: None. M. Guevarra: Employee; Novo Nordisk. V. Divino: Employee; IQVIA Inc. J. Chen: None. A.A. King: None.FundingNovo Nordisk Inc.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-732-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 733-P: Efficacy of a Novel Oral Amylin Analog and the Development of an
Oral GLP-1/Amylin Coformulated Tablet to Produce High In Vivo Plasma
Exposures-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 733-P
Abstract: Introduction and Objective: GLP-1 and amylin peptide hormones independently reduce food intake, delay gastric emptying, and decrease glucagon release. Combination of GLP-1 and amylin analogs promotes greater weight loss and glycemic control than either agent alone. Here we assessed the in vivo efficacy of a novel oral amylin analog (VRB103) in rodent models, as well as pharmacokinetics (PK) of the first oral co-formulation of GLP-1, amylin, and a proprietary permeation enhancer (T2026), showing improved oral bioavailability in cynomolgus monkeys.Methods: VRB103 was administered via single daily subcutaneous injection either alone or in combination with VRB101 (GLP-1 analog Ecnoglutide) in Sprague-Dawley (SD) rats to evaluate its efficacy in reducing body weight (BW). Separately, an oral co-formulated tablet of VRB103, VRB101, and T2026 was dosed daily in cynomolgus monkey for 7 days and PK samples were collected and analyzed.Results: In SD rats, VRB103 alone decreased BW by 0.3%, 3.8% and 9%, 24 hours after a single subcutaneous injection of 5 nmol/kg, 25 nmol/kg and 125 nmol/kg, respectively, while the control group gained 4.7% in BW. Combination of 5 nmol/kg VRB103 and 5 nmol/kg VRB101 induced a 7.4% BW loss in the same model, demonstrating superior efficacy of the GLP-1/amylin combination. Oral PK study with a co-formulated tablet containing VRB103, VRB101 and T2026 was conducted in cynomolgus monkeys. After once-daily dosing for 7 days, similarly high plasma exposures were achieved for VRB103 (AUC0-168h = 79,352 h*ng/ml) and VRB101 (AUC0-168h = 93,249 h*ng/ml).Conclusion: In a preclinical model, the combination of the amylin analog VRB103 and VRB101 demonstrated a synergistic effect on body weight reduction. Both VRB103 and VRB101 achieved high plasma exposures in cynomolgus monkeys when dosed orally from a single co-formulated tablet containing VRB103, VRB101, and T2026, supporting continued development of the oral GLP-1/amylin combination for the treatment of obesity and type 2 diabetes.Disclosure H. Zou: Employee; Sciwind Biosciences. X. Wu: Employee; Sciwind Biosciences. W. Guo: Employee; Sciwind Biosciences. J. Deng: None. C.L. Jones: Employee; Sciwind Biosciences, Verdiva Bio. S. Trieu: Advisory Panel; Novo Nordisk. Employee; Verdiva Bio. R. Ho: Employee; Verdiva Bio. Consultant; Beacon Therapeutics, Aiolos Bio. M. Eid: Employee; Verdiva Biosciences, Boehringer-Ingelheim. J. Hughes: Employee; GlaxoSmithKline plc. W. Zhong: None. M. Fenaux: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-733-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 734-P: VRB101 Is a Potent Oral GLP-1 Tablet with Once-Weekly Dosing
Potential-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 734-P
Abstract: Introduction and Objective: VRB101 is an oral tablet formulation of ecnoglutide, a cAMP-biased, long-acting GLP-1 analog being developed for the treatment of obesity and type 2 diabetes. VRB101 is formulated with a proprietary permeation enhancer, T2026, with improved oral bioavailability. Phase 1 clinical efficacy, safety and tolerability data were presented previously. Here we present pharmacokinetic (PK) analysis of 30 mg daily dose of VRB101 and the modeled PK data supporting the potential of VRB101 as a once-weekly (QW) oral GLP-1 tablet for the treatment of obesity.Methods: We conducted a randomized, double-blind, placebo-controlled Phase 1 study in healthy adults with and without obesity. Participants were randomized to receive VRB101 escalated to the target doses of 7, 15, or 30 mg QD for up to 6 weeks. PK samples were collected, including up to 7 days after the last daily dose. We used the data to model the PK profile of QW dosing with VRB101.Results: After the last 30 mg daily oral dose of VRB101, PK samples were collected up to 168 hours post-dosing and PK parameters for the 7-day period were calculated. This 7-day PK profile was then used to model the steady state PK of 60 mg, 90 mg and 120 mg QW dosing. The PK model projected 60 mg QW dose to reach a steady state weekly exposure (AUC 0-168h) of 40,500 h*ng/mL, 90 mg QW dose to reach exposure of 58,000 h*ng/mL, and 120 mg QW dose to reach exposure of 77,000 h*ng/mL. These exposures are nearing or exceeding the weekly exposure achieved by 2.4 mg subcutaneous semaglutide or 2.4 mg subcutaneous ecnoglutide.Conclusion: This data supports the rationale for VRB101 to be a QW oral GLP-1 treatment. Compared with subcutaneous injections, oral QW 90 mg and 120 mg VRB101 are projected to match or exceed the weekly exposures of subcutaneous GLP-1 injections. VRB101 is expected to exert potent weight lowering while improving adherence via a more patient-friendly dosing regimen. Once-weekly oral administration represents an opportunity towards more scalable treatment option than currently available injectable GLP-1 receptor agonists.DisclosureM. Fenaux: None. E. Adegbite: Employee; Sciwind Biosciences, Verdiva Biosciences. K. Junaidi: None. W. Guo: Employee; Sciwind Biosciences. J. Deng: None. C.L. Jones: Employee; Sciwind Biosciences, Verdiva Bio. W. Zhong: None. S. Trieu: Advisory Panel; Novo Nordisk. Employee; Verdiva Bio. R. Ho: Employee; Verdiva Bio. Consultant; Beacon Therapeutics, Aiolos Bio. M. Eid: Employee; Verdiva Biosciences, Boehringer-Ingelheim.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-734-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 735-P: Impact of Glucagon-Like Peptide 1 Receptor Agonists (GLP-1RAs) on
Survival among Cancer Survivors with Type 2 Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 735-P
Abstract: Introduction and Objective: There is a lack of evidence regarding the impact of GLP-1 receptor agonist (GLP-1RA) use on survival among cancer survivors with type 2 diabetes (T2D).Methods: Using 2013-2020 national Medicare Claims data, we identified older adults with T2D who coexist with one of nine obesity-associated cancers (thyroid, pancreatic, bladder, colorectal, lung, kidney, breast, endometrial, and prostate cancer) for at least one year (n=28,232). We further identified new users of GLP-1 RA, sodium-glucose cotransporter 2 inhibitors (SGLT2i), and dipeptidyl peptidase 4 inhibitors (DPP4i) and followed up with them until death or 12/31/2020. We used 1:1 propensity score matching to control for potential confounding at baseline and Cox proportional hazard models to estimate hazard ratios (HRs) and 95% confidence intervals (CI) for mortality risk.Results: In the GLP-1 RA vs. SGLT2i cohort (n=2553 pair), GLP-1RA users had a similar mortality risk with SGLT2i users (HR, 1.03 [95%CI, 0.85-1.23]). In the GLP-1 RA vs. DPP4i cohort (n=2564 matched pairs), GLP-1RA was associated with a lower risk of mortality compared to DPP4i users (HR, 0.60 [95%CI, 0.51-0.70]). Figure 1 presents the Kaplan-Meier plots of cumulative incidence of mortality.Conclusion: GLP-1RA might be associated with improved survival compared to DPP4i among cancer survivors with T2D.DisclosureY. Lu: None. H. Dai: None. H. Tang: None. W.T. Donahoo: None. T.J. George: Consultant; BillionToOne, Nihon Medi-Physics, Kahr Medical, Avammune Therapeutics, Exact Sciences, Summit Therapeutics, Arbele. Y. Guo: None. J. Guo: None. J. Bian: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-735-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 736-P: Association of Glucagon-Like Peptide 1 Receptor Agonists with
Cancer Risk in Older Adults with Type 2 Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 736-P
Abstract: Introduction and Objective: The real-world evidence on the association between glucagon-like peptide 1 receptor agonists (GLP-1RAs) and cancer risk remains limited and mixed.Methods: In 2013-2020 national Medicare Claims data, we included cancer naïve patients with type 2 diabetes (T2D). We identified those who initiated GLP-1 RA, sodium-glucose cotransporter 2 inhibitor (SGLT2i), or a dipeptidyl peptidase 4 inhibitor (DPP4i) and conducted 1:1 propensity score matching for confounding adjustment. Cox proportional hazard models were used to estimate hazard ratios (HRs) of nine obesity-associated cancers (thyroid, pancreatic, bladder, colorectal, lung, kidney, breast, endometrial, and prostate cancer).Results: In the matched GLP-1RA vs. SGLT2i cohort (n=21,362 pairs), GLP-1RA users had similar overall cancer risk with SGLT2i users (HR, 1.03 [95% CI, 0.95-1.12]), but were associated with an increased kidney cancer risk (HR, 1.43 [1.06 to 1.92]). In the matched GLP-1RA vs. DPP4i cohort (n=20,962 pairs), the GLP-1RA vs. DPP4i comparison showed no significant difference in overall cancer risk (HR, 0.96 [0.89-1.04]), but revealed a significantly elevated endometrial cancer risk (HR, 1.55 [1.01-2.37]).Conclusion: GLP-1RAs might be associated with an increased risk of certain cancer types. Future studies are needed to validate the potential tumorigenic risk associated with GLP1-RAs.DisclosureY. Lu: None. H. Dai: None. H. Tang: None. W.T. Donahoo: None. T.J. George: Consultant; BillionToOne, Nihon Medi-Physics, Kahr Medical, Avammune Therapeutics, Exact Sciences, Summit Therapeutics, Arbele. Y. Guo: None. J. Guo: None. J. Bian: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-736-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 737-P: HDM1002 in Chinese Adults with Overweight or Obesity—A
Randomized, Placebo-Controlled, Four-Week, Phase 1b Study-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 737-P
Abstract: Introduction and Objective: HDM1002 is a novel, orally bioavailable non-peptide agonist of glucagon-like peptide 1 receptors. This study is to evaluate safety, tolerability, pharmacokinetics (PK), and body weight reduction of HDM1002 in Chinese overweight or obesity participants.Methods: In this Phase 1b double-blind, placebo-controlled multi-ascending dose study, we enrolled adult (18~60 years) non-diabetic participants with obesity or overweight (BMI 24.0~36.0 kg/m2). Participants were randomly assigned at 5:1 ratio to receive HDM1002 at one of the dose levels (50 mg QD, 100 mg QD, 200 mg QD, 100 mg BID, or 400 mg QD) or placebo for 4 weeks. Dose titration was performed in all cohorts except for 50 mg QD.Results: Of the 60 subjects enrolled (mean body weight 74.1~90.8 kg across cohorts), 58 completed 4 weeks of treatment. The most common treatment-emergent adverse events (TEAEs) were gastrointestinal tract-related nausea (54.0%) and vomiting (30.0%). All TEAEs were mild to moderate. There were no deaths or serious AEs. Two participants discontinued treatment due to TEAE (vomiting and metabolic acidosis), and 4 subjects experienced dose reduction due to TEAE. After multiple doses, the Cmax increased dose proportionally and the AUC increased slightly more than dose proportionally from 50 mg QD to 400 mg QD (the 95% confidence intervals of β were 0.772 to 1.266 for Cmax, and 1.124 to 1.587 for AUC0-24 h by a power model analysis). Slight accumulation was observed at higher doses over 28-day treatment. Dose-dependent body weight reduction was observed on Day 29, ranging from -4.3 kg to -6.1kg in mean body weight change and -4.9% to -6.8% in percentage change for doses ≥200mg per day.Conclusion: HDM1002 demonstrated an acceptable safety profile and favorable PK profiles. Significant body weight reduction from placebo has been observed for 28 days treatment, which supports further clinical development of HDM1002 in overweight or obesity indication.Disclosure H. Xu: Research Support; HuaDong Pharmaceutical Co., Ltd. W. Hu: None. L. Zhao: None. H. Gao: Employee; HuaDong Pharmaceutical Co. Ltd. D. Liu: None. L. Shen: Employee; HuaDong Pharmaceutical Co., Ltd. G. Zhang: Employee; HuaDong Pharmaceutical Co., Ltd. L. Zhong: Employee; HuaDong Pharmaceutical Co.,Ltd. J. Liu: None. J. Xu: None. X. Li: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-737-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 738-P: Efficacy and Safety of Efsubaglutide Alfa in Patients with Obesity
or Overweight—A Phase 2 Study-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 738-P
Abstract: Introduction and Objective: Efsubaglutide Alfa (Suba) is a novel long-acting GLP-1RA. This trial aimed to evaluate its efficacy and safety in overweight/obese participants (pts) with inadequate body weight (BW) control despite lifestyle interventions.Methods: This double-blind, placebo (PBO)-controlled trial (NCT06732960) randomized pts into Suba or PBO groups in 8:2 across five dose groups (5, 7.5, 10, 15, and 20 mg). Pts underwent biweekly dose escalation to achieve target doses, and maintained for 4 weeks for efficacy and safety evaluation. The primary endpoints were the BW change (%) from baseline and the proportion of pts achieving ≥5% weight loss after 4 weeks at target doses.Results: 50 pts were enrolled (mean age: 36.3 years; mean BMI: 33.0 kg/m²). The mean BW reduction by Suba was -7.2% (-6.5 kg) vs. PBO -0.9% (-0.5 kg). 84.6% of pts in Suba groups achieved ≥5% weight loss (PBO: 0%). Mean fat mass decreased by 4.5 kg (13.1%) (PBO: -0.2 kg, -1.2%), and the ratio of muscle-to-fat mass increased significantly by 19.7% (PBO: 0.6%). Treatment-related adverse events were mostly mild to moderate gastrointestinal, with no premature discontinuations, SAEs, or hyperglycemia.Conclusion: Suba showed a favorable safety profile and significant weight loss in overweight/obese pts. Most pts achieved clinically meaningful weight loss target, indicating Suba's potential as an effective weight management option.DisclosureY. Bao: None. J. Zhou: None. F. Gao: None. A. Shao: Employee; Innogen Pharmaceutical Co., Ltd. Y. Xu: Employee; Innogen Pharmaceutical Co., Ltd. Q. Wang: Employee; Innogen PharmaceuticalCo., Ltd. W. Jia: None.FundingThis study was sponsored by Innogen Pharmaceutical Co. Ltd.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-738-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 739-P: Post Hoc Analysis of Efsubaglutide Alfa Monotherapy and Combined
Therapy with Metformin in T2D Patients by Baseline Characteristics-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 739-P
Abstract: Introduction and Objective: Efsubaglutide Alfa (Suba) is a novel long-acting GLP-1RA. This post hoc analysis of T2D patients in trials investigating the efficacy of Suba’s monotherapy or combined with metformin, stratified by baseline (BL) characteristics.Methods: Patients aged ≥18 years, were randomized to receive 24-week Suba 1 mg, 3 mg, or placebo as monotherapy (Mean baseline HbA1c: 8.73% ± 0.72%) or co-administered with metformin (8.67% ± 0.75%). The estimated change from BL in HbA1c was analyzed stratified by BL characteristics, including age, BMI, gender, and HbA1c.Results: Total of 796 patients were evaluated, whose baseline characteristics were similar across all subgroups. Greater reductions in HbA1c were observed with Suba, nevertheless as monotherapy or in combination with metformin, across all BL subgroups, with significantly higher proportion of patients achieved HbA1c <7% and a metabolic composite endpoint compared to placebo.Conclusion: Significant reductions in HbA1c were achieved with Suba treatment, the monotherapy and the combined therapy, nevertheless their age, BMI, gender, and HbA1c.Disclosure Y. Xu: Employee; Innogen Pharmaceutical Co., Ltd. Y. Duan: Employee; Innogen Pharmaceutical Co., Ltd. L. Zhang: Consultant; Innogen Pharmaceutical Co., Ltd. Q. Zhou: None. Y. Li: None. D. Zhu: Consultant; Innovent Biologics. W. Jia: None. Q. Wang: Employee; Innogen PharmaceuticalCo., Ltd.FundingThis study was sponsored by Innogen Pharmaceutical Co. Ltd.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-739-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 740-P: Diabetes Remission in Drug-Naïve Patients with Type 2 Diabetes
(T2D) after Efsubaglutide Alfa Treatment-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 740-P
Abstract: Introduction and Objective: Efsubaglutide Alfa (Suba), a novel long-acting GLP-1RA was evaluated for its ability to achieve stable glycemic control and drug-free diabetes remission in drug-naïve T2D patients.Methods: Enrolled patients who had completed a 52-week treatment with Suba and achieved stable glycemic control (HbA1c <7%) without any antidiabetic medication. The primary endpoint was diabetes remission (HbA1c <6.5%) at three months post-treatment, as defined by the 2021 American Diabetes Association (ADA) criteria. Kaplan-Meier (KM) analysis was employed to estimate the probability of maintaining HbA1c <7% over one-year post-treatment. Continuous glucose monitoring (CGM) assessed changes in time in range (TIR). Factors contributing to diabetes remission were analyzed using logistic regression and subgroup KM analyses.Results: 29 participants enrolled, at 3 months post-discontinuation, the diabetes remission rate was 60%. The probabilities of maintaining HbA1c <7% at 6- and 12-months post-treatment were 58.1% (95% CI: 39.0%-73.1%) and 41.4% (95% CI: 24.0%-58.0%), respectively. Suba treatment during the 52-week period significantly improved TIR (baseline: 46.4%; 52-week: 89.1%). TIR levels post-treatment were 70.1% at 3 months, 68.1% at 6 months, and 64.1% at 12 months. Patients who achieved remission had relatively lower baseline HbA1c and higher BMI prior to treatment, demonstrating significantly greater reductions in waist circumference (-3.3cm) and postprandial glucose levels compared to those who did not remit. Post-treatment HbA1c levels and improvements in HOMA-β scores were strongly associated with a higher probability of remission (p=0.03 and 0.05, respectively). Body weight remained stable for one-year post-treatment without rebound.Conclusion: Suba demonstrated efficacy in achieving stable glycemic control and drug-free diabetes remission. Enhanced β-cell function emerged as a key factor contributing to long-term remission.DisclosureR. Sun: None. Y. Sun: Employee; Innogen Pharmaceutical Co., Ltd. Y. Xu: Employee; Innogen Pharmaceutical Co., Ltd. Q. Wang: Employee; Innogen PharmaceuticalCo., Ltd. J. Ma: None.FundingThis study was sponsored by Innogen Pharmaceutical Co. Ltd.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-740-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 741-P: Impact of Virtual Patient Simulation on Improving T2D Treatment
Intensification by PCPs-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 741-P
Abstract: Introduction and Objective: This study examines the impact of an online, virtual patient simulation (VPS)-based continuing medical education (CME) activity as part of a larger curriculum on PCP treatment intensification in people with uncontrolled T2D.Methods: The intervention was two different patient scenarios in a VPS open ended platform. Tailored clinical guidance (CG), based on guidelines followed each decision, with ability to modify to decisions. Decisions were collected post-CG and compared with each user’s baseline (pre-CG) decisions using a McNemar’s test to determine P values. The activity posted January 2024 and data were collected through April 2024.Results: 653 completed case 1 and 497 completed case 2. Case 1: 45 YO with T2D x 1 year (HbA1c 8.5%). Screening/monitoring: 24% improvement (P<.001; baseline 44%). Recognizing uncontrolled T2D: 46% improvement (P<.001; baseline 1%). Guideline-based treatment: 27% improvement (P<.01; baseline 46%). Comprehensive treatment: 49% absolute improvement (P<.001; baseline 15%). Case 2: 58 YO with T2D, obesity, and CVD. Screening/monitoring: 14% improvement (P<.001; baseline 68%). Recognizing uncontrolled T2D: 38% improvement (P<.001; baseline 9%). Guideline-based treatment: 27% improvement (P<.01; baseline 46%). Comprehensive treatment: 39% improvement (P<.001; baseline 21%). Rationales for ordering GLP-1-based therapy: patient profile (55%) and efficacy (49%). Rationales for NOT ordering GLP-1-based therapy: cost (38%) and unfamiliar with use (23%). Gaps: 53% of PCPs don't recognize uncontrolled T2D, which can lead to clinical inertia. 38% of PCPs need improved skills on use of GLP-1-based therapies.Conclusion: VPS that engages PCPs in a practical learning experience can improve evidence-based clinical decisions related to recognizing and treating uncontrolled T2D. While the simulation was successful at improving guideline-based care, the largest persistent gaps were related to recognition of uncontrolled T2D.DisclosureA. Larkin: None. A. Prasanna: None. A. Le: None.FundingIndependent educational grant from Lilly
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-741-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 742-P: Impact of Virtual Patient Simulation on Improving T2D Diagnosis and
Management-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 742-P
Abstract: Introduction and Objective: This study examines the impact of online, virtual patient simulation (VPS)-based continuing medical education (CME) on performance related to diagnosis and management of T2D by diabetologists/endocrinologists (D/Es) and primary care physicians (PCPs).Methods: Intervention was 2 patient scenarios presenting in a VPS. Clinical guidance (CG) based on evidence was provided following each decision, followed by the opportunity to modify the decision. Decisions were collected post-CG and compared with each user’s baseline (pre-CG) using a McNemar’s test to determine P values. Data collected January-April 2024.Results: 37 D/Es and 303 PCPs were included. Case 1: 45 YO male with T2D with fatigue, shaking, sweating, and weight gain. D/Es: Diagnose uncontrolled T2D: 27% absolute improvement (P<.01; baseline 38%), Guideline-based treatment: 27% absolute improvement (P<.01; baseline 46%), PCPs: Diagnose uncontrolled T2D: 27% absolute improvement (P<.001; baseline 32%), Guideline-based treatment: 30% absolute improvement (P<.001; baseline 21%). Case 2: 50 YO woman with mild fatigue D/Es: Diagnose T2D: 45% absolute improvement (P<.001; baseline 17%) Guideline-based treatment: 38% absolute improvement (P<.001; baseline 33%). PCPs: Diagnose T2D: 44% absolute improvement (P<.001; baseline 18%) Guideline-based treatment: 25% absolute improvement (P<.001; baseline 22%). Top Rationales for Prescribing GLP-1 RAs were guidelines: (40%) and efficacy (37%). Top Rationales for NOT Prescribing GLP-1 RAs were Cost (14%) and Unfamiliar with use (11%). Continued Gaps: 50% of PCPs and 30% D/Es failed to select guideline-recommended treatment, with biggest gaps in case 2 (patient with newly diagnosed T2D), demonstrating a need for additional education on first-line treatment.Conclusion: VPS can improve evidence-based clinical decisions by D/Es and PCPs related to diagnosis and management of T2D. Continued gaps were identified for future educational initiatives.DisclosureA. Larkin: None. M. LaCouture: None. A. Le: None.FundingIndependent educational grant from Novo Nordisk.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-742-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 743-P: Efficacy and Safety of VCT220 in Chinese Adults with Overweight or
Obesity-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 743-P
Abstract: Introduction and Objective: To investigate the efficacy, safety, and tolerability of VCT220, a novel oral, small molecule once-daily glucagon-like peptide-1 receptor agonist, in Chinese nondiabetic adults with overweight or obesity.Methods: In this double-blind phase 2 randomized study, 250 Chinese adults with a BMI ≥28 kg/m2, or 24-28 kg/m2 accompanied by at least one obesity-related comorbidity were randomized 3:1 to 80mg, 120 mg, 160mg cohort to receive VCT220 or matching placebo. 160mg cohort was further divided (1:1)into fast or slow titration group. Primary endpoint was percentage change from baseline to week 16 in body weight(BW).Results: At baseline, mean BW was 91.76 kg, BMI was 32.03 kg/m2, and 93.6% of participants had a BMI ≥28 kg/m2. At week 16, mean percentage change in BW, the percentage of participants achieving ≥5%, or ≥10% weight loss target, mean change in waist circumference (WC) and blood pressure (BP) were significantly greater with all VCT220 doses vs placebo (Figure). Most commonly reported AEs were GI-related and mild to moderate in severity, with 98.0% of participants demonstrating good compliance. No drug related serious AEs was reported.Conclusion: This study showed VCT220 was safe and led to robust and clinically meaningful BW reduction and improvements in cardiac risk factors including BP and WC. These findings support further development of VCT220 as a oral treatment option for weight management.DisclosureL. Ji: None. L. Gao: Research Support; Sciwind Biosciences. C. Meng: None. X. Zhang: None. J. Huang: Employee; Suzhou Vincentage Pharma Co., Ltd. B. Li: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-743-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 744-P: Efficacy and Safety of BGM0504 in Chinese Patients with Obesity—A
Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase 2 Trial-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 744-P
Abstract: Introduction and Objective: BGM0504 is a dual agonist targeting glucagon-like peptide-1 receptor (GLP-1R) and glucose-dependent insulinotropic polypeptide receptor (GIPR). This study evaluated the safety and efficacy of BGM0504 in Chinese patients with obesity during multiple-dose administration (s.c. injection).Methods: This randomized, double-blind, placebo-controlled study included 120 Chinese adults with obesity. Participants were randomized into four groups: BGM0504 5 mg (n=30), 10 mg (n=30), 15 mg (n=30), or placebo (n=30). The study consisted of a titration phase (2-6 weeks), 24-week treatment with once-weekly dosing, and a 2-week follow-up. It was registered with the Chinese NMPA (CTR20233198).Results: From baseline to week 24, least-squares mean (LSM) percentage changes in body weight relative to placebo were: <ul> <li>5 mg group: −10.77% (95% CI: −12.93 to −8.61), −10.2 kg (−12.3 to −8.2)</li> <li>10 mg group: −16.21% (95% CI: −19.20 to −13.23), −15.5 kg (−18.3 to −12.6)</li> <li>15 mg group: −19.78% (95% CI: −23.02 to −16.54), −20.1 kg (−23.4 to −16.8)</li> </ul> Reductions in waist circumference ranged from −8.0 cm to −12.98 cm (p < 0.001). Significant weight reductions of ≥5%, ≥10%, and ≥15% were observed in all BGM0504 groups (p < 0.001), with ≥20% reductions achieved in the 10 mg and 15 mg groups (p < 0.05). Improvements in systolic blood pressure ranged from −11.60 to −13.03 mmHg and diastolic blood pressure from −5.98 to −7.50 mmHg (p < 0.05). Secondary outcomes further supported the efficacy of BGM0504. All doses were well tolerated, with common adverse events.Conclusion: BGM0504 demonstrates significant potential for weight management and metabolic risk reduction in overweight and obese non-diabetic individuals.Disclosure J. Yuan: Employee; BrightGene Bio-Medical Technology Co., Ltd. Y. Huang: Employee; BrightGene Bio-Medical Technology Co., Ltd. H. Ding: Employee; BrightGene Bio-Medical Technology Co., Ltd. D. Xie: Employee; BrightGene Bio-Medical Technology Co., Ltd. X. Jiang: Consultant; BrightGene Bio-Medical Technology Co., Ltd. X. Yuan: None. Z. Cao: None. G. Yang: None. L. Ji: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-744-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 745-P: Efficacy and Safety of RAY1225 Once Every Two Weeks in Chinese
Adults with Obesity or Overweight (REBUILDING-1)-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 745-P
Abstract: Introduction and Objective: To investigate the efficacy, safety, and tolerability of RAY1225, a novel once every two weeks GLP-1 and GIP receptor dual agonist, in Chinese nondiabetic adults with overweight or obesity.Methods: This phase 2 double-blind, randomized, placebo-controlled trial included 2 parts. The target dose of part A was 3mg,6mg, and that of part B was 9mg and above with dose escalation and extension. Chinese nondiabetic adults with a BMI ≥28 kg/m2, or 24-28 kg/m2 accompanied by at least one obesity-related comorbidity were randomized. In part A, eligible participants were randomly assigned 1:1:1 to receive 3mg,6 mg RAY1225 injection or placebo subcutaneously once every two weeks for 24 weeks. In part B, the randomization ratio was 4:1 to receive 9 mg (or above dose) or placebo. The primary endpoint was the percentage change from baseline to week 24 in weight.Results: A total of 132 participants were analyzed from part A and part B with dose escalated up to 9mg till now. At baseline, the mean (standard deviation) body weight was 91.07 (15.09) kg, BMI was 32.33 (3.98) kg/m2, and about 89.4% of participants had a BMI≥28 kg/m2. The mean percentage change in weight at week 24 was -10.06% (95% confidence interval, -11.63 to -8.49) with 3mg of RAY1225, -12.97% (-14.51 to -11.43) with 6mg, and -13.05% (-16.20 to -9.91) with 9mg and -3.62% (-5.19 to -2.05) with placebo (P<0.001). About 73.2% to 95.1% of participants in the RAY1225 group achieved ≥5% weight loss, compared with 30.0% in the placebo.(P<0.05). In addition, RAY1225 is also beneficial in the improvement of cardiometabolic indexes. The most common adverse events (AEs) with RAY1225 were gastrointestinal, most were mild to moderate in severity, occurring primarily during dose escalation. No drug related serious AEs occurred..Conclusion: This study showed RAY1225 once every two weeks subcutaneous injection was safe and achieved robust body weight reduction in Chinese adults with overweight or obesity.DisclosureL. Ji: None. L. Yan: None. L. Gao: Research Support; Sciwind Biosciences. M. Xu: None. X. Dong: None. C. Wang: None. Y. Zhu: None. J. Li: Employee; Guangdong Raynovent Biotech Co., Ltd. Y. Peng: Employee; Raynovent. H. Li: Employee; Guangdong Raynovent Biotech Co., Ltd. X. Chen: Employee; Guangdong Raynovent Biotech Co., Ltd.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-745-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 746-P: Time in Tight Range with Oral Semaglutide as an Add on to SGLT2i
and Metformin Combination in People with Type 2DM—Real-World Evidence
from India-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 746-P
Abstract: Introduction and Objective: Background:Time in tight range is a novel concept to analyse oral semaglutide efficacy in people with type 2 diabetes mellitus (T2DM). This study evaluates the effect of oral semaglutide as an add-on to SGLT2i + metformin therapy on glycemic variability (GV).Methods: Methods: The study included patients with T2DM, on SGLT2i and metformin and on cgms with freestyle libre (sensor usage of at least 40%). GV, time in range (TIR- (> 70% within 70-180 g/dl)), time above range (TAR-(<25% with >180 mg/dl)) and time in tight range (TITR- (>50% within 70-140 mg/dl) ) were recorded and compared for 14 days on SLGT2i and Metformin and 14 days with add-on oral semaglutide, using LibreviewResults: Results: The study included 10 patients. Following two weeks with oral semaglutide, GV reduced. Two patients with poor GV achieved the target (< 36%). Compared to baseline, 8/10 (vs 2/10), 7/10 (vs2/10) achieved target TIR, TAR respectively. All patients showed a significant improvement in TITR (figure 1). The number of hypoglycemic events TBR reduced in 3 patients (baseline- 4, 3 and 1 events) to none and, increased among 4 patients (0 to 1, 0 to 5, 1 to 3 and 1 to 6). Two were level-2 hypoglycemia (53 and 52 mg/dl).Conclusion: Conclusion: Oral semaglutide is an effective add-on to Metformin and SGLT2i to improve glycemic control, especially time in tight range.DisclosureS.A. Patange: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-746-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 747-P: Bedtime NPH Insulin and DPP-4 Enzyme Inhibitor (sitagliptin)
Increase Cholesterol Removal from Macrophages-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 747-P
Abstract: Introduction and Objective: Cardiovascular disease is largely linked to hyperglycemia and alterations in lipoprotein functions. We evaluated the effect of treatment with bedtime NPH insulin or sitagliptin on cholesterol efflux from patients with T2DM.Methods: Thirty-two patients with T2DM, inadequately controlled with metformin and glibenclamide were randomly assigned to 6-month complementary treatment with bedtime NPH insulin or sitagliptin. At baseline and after treatments, glucose, C-peptide, free fatty acids (FFA), and triglycerides were determined at fasting and 2 hours after a meal, besides fasting lipid and HbA1c levels. Serum ApoB-rich lipoproteins (VLDL and LDL) were precipitated by dextran sulfate/magnesium chloride. Macrophages enriched with acetylated LDL and 14C-cholesterol were incubated with serum containing only HDL (2%) for 4 h to determine cholesterol efflux (n=4). Control incubations were performed with culture medium only, without serum. Analyses used Student's t-test and Pearson's correlation.Results: The sitagliptin (n=16) and bedtime NPH insulin (n=16) groups did not differ in age, body mass index, diabetes duration, plasma glucose, Triglycerides, FFA and C-peptide concentrations (before and 2 h after a meal). There was a similar reduction in HbA1c in both groups. Cholesterol levels did not change. The 14C-cholesterol efflux increased in both groups, after 6-month treatment (14.08 ± 1.93 vs. 15.74 ± 2.67% in the NPH group and 14.80 ± 1.37 vs. 15.79 ± 1.40% in the sitagliptin group, P<0.05). There was no difference in the % of cholesterol efflux between groups. A negative correlation was observed between the % of cholesterol efflux and the plasma concentration of FFA in both groups (r= -0.345; p=0.0053).Conclusion: six-month treatment with NPH insulin or sitagliptin increased the capacity of apoB-depleted serum to mediate the removal of cholesterol from macrophages, which may contribute to the prevention of cardiovascular disease in DM. Supported by FAPESP, FMUSP, CNPqDisclosureA.S. Santos: None. M.S. Santana: None. P.S. Takakura: None. D. Ribeiro: None. M. Correa-Giannella: None. M. Passarelli: None. M. Rossi: None.FundingSao Paulo Research Foundation FAPESP(2022/16441-5); Faculty of Medicine of the University of S'o Paulo3-CNPQ- National Council for Scientific and Technological Development
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-747-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 748-P: Noninvasive Tests of Central Adiposity Correlate with Reductions in
MRI-Measured Visceral Adipose Tissue Mass in Subjects with Overweight or
Obesity Treated with Pemvidutide-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 748-P
Abstract: Introduction and Objective: Pemvidutide is a GLP-1/glucagon dual receptor agonist in development for the treatment of obesity and metabolic dysfunction-associated steatohepatitis. We examined the potential of non-invasive tests of central adiposity for estimating changes in visceral adipose tissue (VAT) mass.Methods: Subjects with overweight (BMI 27.0-29.9 kg/m2) and at least one obesity-related comorbidity or obesity (BMI >30.0 kg/m2) were randomized 1:1:1:1 to pemvidutide (1.2, 1.8, 2.4 mg) or placebo administered weekly by the subcutaneous route for 48 weeks. Changes in waist-to-height ratio (WHtR) and body roundness index (BRI) were compared to changes in VAT assessed in a body composition substudy using magnetic resonance imaging (MRI).Results: A total of 67 subjects participated in the MRI substudy. Mean baseline age, weight, BMI, VAT mass, WHtR and BRI were 53 yrs, 100.1 kg, 36.2 kg/m2, 4.9 kg, 0.67, and 7.31, respectively. VAT mass decreased by up to 28.3% at the 2.4 mg dose at Week 48. Percent changes in BRI and WHtR strongly correlated with percent changes in VAT (Figure 1A and 1B; root mean square error: 12.5% and 12.7%, respectively).Conclusion: BRI and WHtR may be useful for estimating VAT mass changes resulting from pemvidutide treatment.Disclosure S. Tomah: Employee; Altimmune Inc. Stock/Shareholder; Altimmune Inc. M. Harris: Employee; Altimmune Inc. J.J. Suschak: Employee; Altimmune Inc. J. Yang: Employee; Altimmune Inc. M.S. Roberts: Employee; Altimmune Inc. S.K. Browne: Employee; Altimmune Inc.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-748-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 749-P: Integrated Analysis Supports Cardiovascular Safety and Risk
Reduction with Pemvidutide Treatment-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 749-P
Abstract: Introduction and Objective: Pemvidutide is a GLP-1/glucagon dual receptor agonist in development for the treatment of obesity and metabolic dysfunction-associated steatohepatitis. Pemvidutide reduces cardiovascular (CV) disease risk factors (excess adiposity, total and LDL cholesterol, cardio-inflammatory lipids, visceral adipose tissue, liver fat content). In this study, its effects on parameters of CV safety were assessed.Methods: Systolic (SBP) and diastolic (DBP) blood pressure, heart rate (HR) and rate pressure product (RPP) were assessed in integrated analyses across 5 clinical trials. In a separate QT study, healthy volunteers receiving single ascending doses (SAD) up to 4.8 mg and multiple ascending doses (MAD) up to 3.0 mg once weekly for 12 weeks underwent continuous ECG recordings, and Friderica-corrected QT intervals (QTcF) were assessed by linear time-matched concentration-QTc analysis.Results: In integrated analyses, reductions in SBP and DBP up to 13.0 mmHg and 6.5 mmHg, respectively, were observed without dose-related or clinically meaningful effects on RPP or HR or imbalances in cardiac adverse events. In QTc analyses, mean (90% CI) predicted placebo-corrected change in QTcF (∆∆QTcF) was <10 ms at all pemvidutide concentrations (Figure 1).Conclusion: Pemvidutide reduces SBP and DBP without clinically meaningful effects on QTc or HR and no imbalances in cardiac adverse events.Disclosure S. Tomah: Employee; Altimmune Inc. Stock/Shareholder; Altimmune Inc. J. James: Consultant; Altimmune Inc. S.K. Browne: Employee; Altimmune Inc. B. Darpo: None. M.S. Roberts: Employee; Altimmune Inc. J.J. Suschak: Employee; Altimmune Inc. L. He: None. J. Yang: Employee; Altimmune Inc. M. Harris: Employee; Altimmune Inc.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-749-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 750-P: ASC30, an Oral GLP-1R Biased Small Molecule Agonist in Participants
with Obesity—A First-in-Human Single Ascending Dose Study-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 750-P
Abstract: Introduction and Objective: ASC30 is an oral GLP-1R biased small molecule agonist without β-arrestin recruitment, discovered and developed in-house at Ascletis. ASC30 has unique and differentiated properties that enable the administration of one small molecule as both a once-monthly subcutaneous injection and a once-daily oral tablet. The current study assessed safety, tolerability and pharmacokinetics of ASC30 oral tablet in a first-in-human single ascending dose study.Methods: This was a randomized, double-blind, placebo-controlled single ascending dose study in participants with a BMI of 30-40 kg/m². A total of 40 eligible participants were enrolled in a 6:2 ratio to receive ASC30 tablets at doses of 2 mg, 5 mg, 10 mg, 20 mg, or 40 mg, or matching placebo.Results: All AEs were mild (70.3%) to moderate (29.7%) in severity and consistent with GLP-1RA class. No SAEs or clinically significant changes in labs, including liver enzymes, due to study drug were observed. Table 1 shows preliminary pharmacokinetic analyses, which support once-daily oral dosing.Conclusion: ASC30 tablet exhibited a good safety and tolerability profile in this SAD study. Based on its superior PK profile, enhanced potency as a GLP-1 RA, and favorable safety profile, ASC30 tablet once-daily, has the potential to be the best-in-class oral GLP-1R small molecule agonist.Disclosure J. Wu: Employee; Ascletis Pharma (China) Co., Limited. V. Wang: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-750-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 751-P: The Risk of Acute Pancreatitis and Biliary Events after Initiation
of GLP-1RA, SGLT2i, or DPP-4i in Patients with T2D-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 751-P
Abstract: Introduction and Objective: Patients with type 2 diabetes (T2D) are at increased risk of acute pancreatitis (AP) and biliary events. Existing evidence is mixed regarding the association between second-line diabetes medications and AP and biliary events.Methods: Using Medicare and 2 U.S. private health plans (2014-2021), we identified three pairwise cohorts of propensity score (PS) fine stratification-weighted patients aged ≥18 years (≥66 years in Medicare) with T2D without a history of AP and biliary disease who initiated GLP-1RA, SGLT2i or DPP4i (Table). PS was estimated by time (2014-2018; 2019-2021) using 92 covariates. We calculated HRs with 95% CIs for the risk of hospitalization for AP or biliary events. We tested the robustness of our findings using different PS-based methods (Table).Results: Over a mean follow-up of ~10 months, the risk of AP was similar across three medication classes (Table). Compared to SGLT2i, initiators of GLP-1RA or DPP4i had a 15% and 22% increase in risk of biliary events, respectively, though the absolute magnitude of the increase in risk was limited (< 1 additional biliary event per 1,000 person-years). Results were consistent across four PS-based methods.Conclusion: In patients with T2D, initiation of GLP-1RA or DPP4i was associated with a higher risk of biliary events compared to SGLT2i, with no observed difference in the risk of AP between medications.DisclosureY.E. Fang: None. H. Tesfaye: None. J. Ortega-Montiel: None. J.M. Paik: None. E. Patorno: Research Support; National Institute of Diabetes and Digestive and Kidney Diseases, Patient-Centered Outcomes Research Institute, Food and Drug Administration (FDA), Boehringer-Ingelheim. Other Relationship; UpToDate.FundingPatient-Centered Outcomes Research Institute (DB-2020C2-20326)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-751-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 752-P: Efficacy and Safety of Bofanglutide (GZR18), a Biweekly GLP-1RA,
Compared with Semaglutide in Chinese Patients with T2D-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 752-P
Abstract: Introduction and Objective: Efforts have focused on developing GLP-1 RAs with less frequent dosing to improve patient acceptance and adherence in managing T2D. This randomized, open-label, phase 2b trial aimed to evaluate the efficacy and safety of a novel bi-weekly (Q2W) GLP-1 RA, bofanglutide (GZR18), compared to once-weekly (QW) semaglutide (SEMA, Ozempic®) in Chinese patients with T2D.Methods: A total of 272 eligible adult patients (HbA1c 7-11%) who were drug-naïve or on stable treatment with OADs were randomized 1:1:1:1:1 into one of four GZR18 groups (12, 18, 24 mg Q2W and 24 mg QW) or the SEMA group (1 mg QW) for 24 weeks. The primary endpoint was HbA1c change from baseline to week 24. Safety was assessed by the incidence of treatment-emergent adverse events (TEAEs).Results: The LSM HbA1c reductions were greater in GZR18 groups (-1.87% to -2.32%) than in the SEMA group (-1.6%), with significant treatment differences in two GZR18 groups (18 mg Q2W and 24 mg QW) vs. SEMA (P<0.001). GZR18 also surpassed SEMA in most secondary efficacy measures, including body weight. The most common TEAEs were Grade 1-2 gastrointestinal AEs. No Grade 3 or higher AEs or severe hypoglycemia were related to GZR18.Conclusion: In Chinese patients with T2D, GZR18 Q2W showed a comparable or superior HbA1c and weight reduction than SEMA 1mg QW. This study warrants phase 3 trials of bi-weekly dosing of GZR18 in treating T2D.DisclosureH. Wu: None. M. Liu: None. Z. Cheng: None. L. Lu: None. H. Cai: None. J. Liu: None. J. Liu: None. Y. Zheng: None. S. Wang: None. J. Zhao: None. W. Yang: None. T. Xie: None. Y. Li: None. A. He: None. S. Carter: None. W. Chen: None. Z. Gan: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-752-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 753-P: Safety, Tolerability, PK, and Efficacy of MET097—A
Next-Generation Nutrient-Stimulated Hormone Peptide Analog for Chronic
Weight Management-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 753-P
Abstract: Introduction and Objective: MET097 was designed to be a highly potent, fully biased, ultra-long acting GLP-1 receptor agonist. The safety, tolerability, PK, and weight loss of single and multiple ascending doses (SAD/MAD) of MET097 were evaluated in adults with overweight or obesity.Methods: Our Ph1, single-center, randomized, double-blind, placebo-controlled study had 7 SAD (MET097 0.16 to 1.6 mg) and 6 MAD cohorts. In 5 MAD cohorts, participants received titration-free, weekly SC MET097 injections (0.2, 0.4, 0.8, 1.0, and 1.2 mg) for 5 wk. A 6th MAD cohort received MET097 0.8 mg for 4 weeks, then 1.6 mg.Results: In the SAD (N=60), preliminary PK data showed linear behavior with a mean half-life (t1/2) of ~360 hrs. In the MAD, we enrolled 62 participants (mean age 38 yrs, ~50% female, mean BMI 31.9 kg/m2). MET097’s safety/tolerability profile was consistent with the GLP-1RA class. No AE-related discontinuations occurred. Common GI AEs (nausea/vomiting) were mostly mild and within the first few weeks of dosing. By day 36, MET097 caused dose-dependent clinically meaningful weight loss (Fig 1), which was maintained through day 85, 8 wks after the last dose.Conclusion: MET097, an ultra-long acting GLP-1RA, results in significant weight loss sustained 8 wks post-treatment. Ongoing Ph2 studies will evaluate weekly and monthly dosing regimens with and without titration.Disclosure M. Stroh: Employee; Metsera, Intellia Therapeutics. J.S. Minnion: Stock/Shareholder; Metsera. Employee; Zihipp. S. Ranck: None. S. Kolluri: Employee; Metsera. A. Seddighzadeh: Employee; Metsera Inc, PharmaEssentia. R. Stoekenbroek: Employee; Metsera. J. Mallory: Employee; Metsera, Kriya Therapeutics. S.P. Marso: Employee; Metsera. Stock/Shareholder; Metsera.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-753-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 754-P: Development of a Novel One-Month Long-Acting Injectable Semaglutide
(IVL3021) and Tirzepatide (IVL3024) with Well-Controlled Pharmacokinetic
Profiles and Enhanced Quality of Life Window-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 754-P
Abstract: Introduction and Objective: Microsphere-based long-acting injectables (LAIs) have been used to replace frequent treatments with extended therapies. The core technology in LAIs lies in controlling release profiles to enhance compliance, effectiveness, and safety by reducing bursts and maintaining therapeutic drug concentration. This study focuses on semaglutide (Sema), a GLP-1 receptor agonist for diabetes and obesity. Despite its effectiveness, Sema is associated with gastrointestinal AEs, a common issue for GLP-1 agonist users. Other LAIs also face challenges, such as fluctuations in plasma drug levels leading to GI troubles. These underscore the need for a stable, controlled delivery system. Encapsulating Sema into microparticles for controlled release is challenging due to its unique characteristics but is essential for improving quality of life (QOL) and outcomes.Methods: We present IVL3021, a one-month LAI of Sema developed with IVL-DrugFluidics® technology. Its morphology was examined via SEM, and size distribution was analyzed using PSA. Encapsulation efficiency (EE%) was determined by HPLC. Non-clinical studies in minipigs and rats evaluated pharmacokinetic (PK) profiles and optimized the formulation. Human PK predictions using non-clinical data determined an appropriate clinical dose.Results: IVL3021 exhibits smooth, uniform morphology with high encapsulation efficiency (>97.0%). Preclinical studies showed IVL3021 sustains plasma Sema concentrations for 4 weeks without burst release. Human PK simulations demonstrated stable plasma exposure, minimizing GI AEs and providing consistent therapeutic effects. Another GLP-1 receptor-targeting drug, tirzepatide LAI, is also under development.Conclusion: In conclusion, IVL3021 shows promis as a one-month LAI for managing obesity and diabetes. Further preclinical evaluations are underway.DisclosureJ. Kim: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-754-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 755-P: Metabolic Adaptation of Liver with Treatment of HM15275, a
Long-Acting GLP-1/GIP/Glucagon Triple Agonist, Supporting Lean Mass
Preservation-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 755-P
Abstract: Introduction and Objective: Weight-loss quality (WLQ) has emerged as a challenge in developing GLP-1-based therapies. Previous nonclinical studies demonstrated that HM15275 achieved superior WLQ compared to Tirzepatide (TZP), a GLP-1/GIP dual agonist. This study aimed to extract mechanistic insights of different WLQ from altered metabolic pathways influenced by either treatment.Methods: RNA sequencing was conducted on liver from diet-induced obese (DIO) mice treated with HM15275 or TZP for 11 days. Biological processes affected by the treatment were identified using Gene Set Variation Analysis (GSVA) and pathways from MSigDB, including Hallmark, KEGG, Reactome, Wikipathways, and Gene Ontology.Results: HM15275 sustained fat metabolic pathways, including fatty acid beta-oxidation and transport, while down-regulated in TZP, contributing to greater fat mass loss under fasting-related metabolic challenges. HM15275 suppressed amino acid catabolic pathways relative to TZP, supporting lean mass preservation. HM15275 activated pathways related with glucose generation greater than TZP revealed by enrichment of gluconeogenesis and lactate recycling pathway, however, fasting blood glucose remained lower than vehicle treated implying limited effect on glucose intolerance. Furthermore, HM15275 downregulated ketone body synthesis compared to TZP, priming production of glucose rather than ketone body.Conclusion: HM15275 induces significant metabolic adaptations in liver, explaining improved WLQ compared with TZP. By preserving fat metabolism, suppressing amino acid catabolism, and enhancing gluconeogenesis and lactate recycling, HM15275 promotes greater fat mass loss with preserving lean mass. Furthermore, by prioritizing glucose generation over ketogenesis, HM15275 supports efficient energy metabolism without causing glucose intolerance. These findings imply heterogenous metabolic adaptation under different anti-obesity drugs explaining their WLQ.Disclosure H. Lee: Employee; Hanmi Pharm. Co., Ltd. S. Park: None. Y. Kim: None. Y. Kim: None. J. Kim: None. D. Lee: None. J.A. Kim: None. S. Bae: None. S. Lee: None. H. Chon: Employee; Hanmi Pharm. Co., Ltd. I. Choi: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-755-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 756-P: Real-World Data Comparing the Effectiveness of Injectable vs. Oral
Semaglutide—Association of British Clinical Diabetologist (ABCD)
National Audit-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 756-P
Abstract: Introduction and Objective: Semaglutide is the only Glucagon-like-peptide 1 agonist (GLP-1a) currently available in both injectable and oral forms. Although the PIONEER study has shown similar efficacy in HbA1c and weight reduction with oral semaglutide vs injectable liraglutide, data comparing the efficacy between oral and injectable semaglutide remains limited. Thus, we have conducted a real-world analysis to compare the effectiveness between the two.Methods: Data was obtained from ABCD national audit and analysed by STATA using linear regression analysis with baseline weight and HbA1c as key variables.Results: There were 1484 people on injectable Semaglutide (49.2% female, mean age 58.9+/-10.9 years) and 636 on oral semaglutide (40.2% female, mean age 58.92 +/-12.86 years). Results are summarized in Table 1. HbA1c reduction was significantly greater with injectable compared with oral. The effectiveness of oral and injectable semaglutide on other outcomes were comparable. The mean follow-up time was 413 +/-342 days in oral and 180 days in injectable group.Conclusion: With the UK real-world data, both oral and injectable Semaglutide effectively reduce HbA1c levels in people with T2DM. Injectable semaglutide produced greater Hba1c reduction compared with oral. These findings support personalized treatment choices based on individual needs.DisclosureK. Su Khin: None. T.S. Crabtree: Other Relationship; Abbott, Dexcom, Inc., Eli Lilly and Company, Insulet Corporation. A.L. Liarakos: Other Relationship; Dexcom, Inc. V. Oguntolu: None. K. Adamson: Speaker's Bureau; AstraZeneca. A. Gough: None. G. Ratnayake Mudiyanselage: None. E.G. Wilmot: Research Support; Abbott. Speaker's Bureau; Abbott. Advisory Panel; Abbott. Speaker's Bureau; AstraZeneca. Advisory Panel; Dexcom, Inc. Speaker's Bureau; Dexcom, Inc., Eli Lilly and Company. Advisory Panel; Eli Lilly and Company. Research Support; embecta. Advisory Panel; embecta. Research Support; Insulet Corporation. Speaker's Bureau; Insulet Corporation. Advisory Panel; Insulet Corporation, Medtronic. Speaker's Bureau; Novo Nordisk. Advisory Panel; Novo Nordisk. Research Support; Novo Nordisk. Advisory Panel; Roche Diabetes Care, Sanofi. Speaker's Bureau; Sanofi. Advisory Panel; Sinocare Inc. Speaker's Bureau; Ypsomed AG. I.R. Idris: None. R.E. Ryder: Speaker's Bureau; Abbott, AstraZeneca, GI Dynamics. Consultant; GI Dynamics. Other Relationship; Novo Nordisk. Speaker's Bureau; Besins Healthcare.FundingAssociation of British Clinical Diabetologists
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-756-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 757-P: Comparative Glycemic Effectiveness of Four Second-Line
Glucose-Lowering Medications in Type 2 Diabetes Mellitus-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 757-P
Abstract: Introduction and Objective: The GRADE trial compared four glucose-lowering drugs for HbA1c reduction in individuals with type 2 diabetes mellitus (T2DM) on metformin monotherapy but lacked a sodium-glucose cotransporter-2 inhibitor (SGLT-2i) arm. We emulated GRADE including SGLT-2i & excluding insulin.Methods: In a US commercial claims database (2014-2023), we used propensity score weighting to balance 87 baseline covariates in eligible patients (T2DM, age ≥30 years, on metformin monotherapy, baseline HbA1c 6-9%); 5,489 initiated SGLT-2i, 3,617 glucagon-like peptide-1 receptor agonists (GLP-1RA), 5,069 dipeptidyl peptidase 4 inhibitors (DPP-4i), & 11,148 sulfonylureas (SU). We estimated HR & 95% CI for primary (HbA1c ≥7%) & secondary outcomes (major adverse cardiovascular events (MACE), heart failure hospitalization (HHF), severe hypoglycemia).Results: GLP-1RA had the lowest risk of primary outcome (HR 0.63;0.58-0.68, HR 0.71;0.65-0.76, and HR 0.67;0.61-0.72 vs. SGLT-2i, SU, and DPP-4i, respectively). SGLT-2i had risk comparable to DPP-4i (HR 1.06;0.99-1.13) but higher than SU (HR 1.12;1.06-1.18). MACE outcome had no differences but SGLT-2i had reduced HHF risk vs. SU. Hypoglycemia was rare with the highest risk for SU.Conclusion: When added to metformin in patients with T2DM, GLP-1RA achieved better glycemic control than SU and DPP-4i, as seen in GRADE, and vs. SGLT-2i.DisclosureA. Ray: None. S. Kattinakere Sreedhara: None. J.M. Paik: None. S. Cromer: Other Relationship; Johnson & Johnson Medical Devices Companies. Advisory Panel; Alexion Pharmaceuticals, Inc. Consultant; Wolters Kluwer Health, Patient Square Capital. K. Bykov: None. G. Hahn: None. D.J. Wexler: Other Relationship; Novo Nordisk. E. Patorno: Research Support; National Institute of Diabetes and Digestive and Kidney Diseases, Patient-Centered Outcomes Research Institute, Food and Drug Administration (FDA), Boehringer-Ingelheim. Other Relationship; UpToDate.FundingPatient Centered Outcomes Research Institute (DB-2020C2-20326)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-757-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 758-P: Titration to Maintenance Doses of GLP-1R Agonists for Overweight
and Obesity Is Suboptimal for Majority of Patients—Evidence from a
Real-World Claims Dataset-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 758-P
Abstract: Introduction and Objective: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) represent a paradigm shift in treating obesity. The substantial weight loss observed in clinical trials improves weight-related comorbidities. However, weight loss reported in the real world has been less than that seen in clinical trials. One hypothesis for this gap is that patients may not complete the complex multistep titration required to reach the higher maintenance doses associated with maximal benefit. This study aimed to assess the real-world practice of titration and quantify the percentage of patients who achieve maintenance dosing.Methods: We used the Komodo US claims administrative dataset to identify a cohort of adults with at least 1 claim for initiation dose (0.25 mg) of the GLP-1RA semaglutide SC indicated for weight loss (by NDC) from Jun 2021-Aug 2023. Patients were assessed for claims for escalation and maintenances doses of semaglutide between Jun 2021-Aug 2024 using 35- and 70-day windows for dose increases, as well as having a claim for a maintenance dose at any point during follow-up.Results: Data from 655,419 patients were included. Most (80%) were female, and 81% had commercial insurance. When considering 35-day titration, a significant drop-off was observed with each step, with 19% reaching a 1.7 mg dose and 15% reaching a 2.4 mg dose. Over a slower, 70-day titration schedule, 31% and 24% achieved 1.7 and 2.4 mg, respectively. At any point during follow-up, 50% had a claim for 1.7 mg and 40% for 2.4 mg.Conclusion: Fewer than half of patients initiating semaglutide for weight loss ever receive the top maintenance dose studied in pivotal trials and associated with the greatest clinical benefit. This suggests that the complex multistep titration scheme presents implementation challenges in real-world practice that may limit its effectiveness at delivering optimal weight loss and improved health outcomes.Disclosure S. Armstrong: Employee; Metsera. L. Mostovoy: Consultant; Metsera. G. Gaich: Employee; 89bio, Inc. Stock/Shareholder; 89bio, Inc. Employee; Metsera, Inc. M.A. Noor: Employee; Metsera, Olatec.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-758-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 759-P: Effects of Once-Weekly Utreglutide (GL0034) in Individuals with
Overweight and Obesity on Lipid Metabolism—A 10-Week Exploratory
Proof-of-Concept Study-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 759-P
Abstract: Introduction and Objective: Utreglutide (UTG, GL0034), a once weekly glucagon-like peptide-1 receptor agonist, demonstrated body weight (BW) reduction up to 3.3 kg after single dose and improvements in cardio-metabolic biomarkers after multiple ascending doses in obese subjects. This phase 1 trial assessed the safety and efficacy of UTG in overweight and obese subjects.Methods: The study enrolled 20 male and female subjects with BMI between 28 and 45 kg/m2, which were randomized (16:4) to weekly subcutaneous UTG or placebo following an up-titration scheme (1x0.4, 2x0.8, 3x1.4, 4x2.0 mg).Results: At visit 11, BW reduction after UTG treatment was 6.8%; leptin, LDL, apolipoprotein B, total cholesterol, non-HDL and hs-CRP were significantly reduced by 28.1%, 13.4%, 17.7%, 12.1%, 15.4% and 30.8% respectively. HbA1c reduction was significant on visit 10. Reduction of hs-CRP along with LDL may confer added benefit to patients with obesity or obesity and T2DM with cardiovascular risk linked to increased inflammatory markers. Gastrointestinal adverse events were consistent with the class. Lipase and amylase levels were unaffected (Table).Conclusion: In individuals with overweight and obesity, once weekly UTG dosing for ten weeks, demonstrated clinically relevant changes in BW and biomarkers of cardio-metabolism with an overall good tolerability.Disclosure R. Thennati: Employee; Sun Pharmaceutical Industries Ltd. V.S. Burade: None. M. Natarajan: None. P. Shahi: None. R. Nagaraja: None. P. Battisti: None. T. Duvauchelle: Consultant; Sun Pharmaceutical Industries Ltd, Bioprojet. B. Thorens: Advisory Panel; Sun Pharmaceutical Industries Ltd. R.E. Pratley: Consultant; AbbVie Inc. Stock/Shareholder; Altanine, Inc. Consultant; Amgen Inc, AstraZeneca. Other Relationship; Bayer AG, Bayer Pharmaceuticals, Inc, Biomea Fusion. Consultant; Boehringer-Ingelheim. Other Relationship; Carmot Therapeutics, Inc, Corcept Therapeutics, Dompé, Eli Lilly and Company, Endogenex. Consultant; Endogenex. Other Relationship; Fractyl Health, Inc., Gasherbrum Bio, Inc. Consultant; Genprex, Getz Pharma, Hanmi Pharm. Co., Ltd, Intas Pharmaceuticals Ltd, Lexicon Pharmaceuticals, Inc, Lilly USA LLC. Speaker's Bureau; Lilly USA LLC. Other Relationship; Metavention, Novo Nordisk, Novo Nordisk. Speaker's Bureau; Novo Nordisk. Other Relationship; Pfizer Inc, Poxel SA. Consultant; Regeneron Pharmaceuticals. Other Relationship; Sanofi. Consultant; Scholar Rock. Other Relationship; Sun Pharmaceutical Industries Ltd. T. Vilsbøll: Advisory Panel; Boehringer-Ingelheim, AstraZeneca, Bristol-Myers Squibb Company, Carmot Therapeutics, Inc. Research Support; Dexcom, Inc. Advisory Panel; Eli Lilly and Company, GlaxoSmithKline plc. Speaker's Bureau; Medscape. Advisory Panel; Novo Nordisk, Sun Pharmaceutical Industries Ltd, Roche Diabetes Care, Amgen Inc, Sanofi, Zealand Pharma A/S.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-759-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 760-P: Real-World Efficacy of Combined SGLT2i and GLP-1RA Therapy in
Elderly Patients with Type 2 Diabetes and Obesity-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 760-P
Abstract: Introduction and Objective: Type 2 Diabetes (T2D) is a highly prevalent health condition in people older than 70 yrs, but they are still underrepresented in RCTs evaluating medications for T2D, as the combined SGLT2i/GLP1-RA therapy. The aim of this real-world, observational, prospective study was to compare the efficacy of combined SGLT2i/GLP1-RA therapy with that of SGLT2i and GLP1-RA monotherapy in improving glycaemic compensation and body weight (BW), in patients aged ≥70 yrs with T2D and obesity.Methods: Patients aged ≥ 70 yrs, with T2D, BMI ≥ 30 kg/m2 and suboptimal glycaemic control, treated with SGLT2i (Group 1), GLP1-RA (Group 2) and combined SGLT2i/GLP1-RA (Group 3) were considered for the study. Data were analysed at baseline (T0), 6 months (T1) and 12 months (T2) after the start of treatment.Results: Out of 94 patients, 25 patients (9 F/16 M, 76.5±3.9 yrs, BMI 31.7±4.3 Kg/m2) in the Group 1, 38 patients (11 F/27 M, 75.8±4.1 yrs, BMI 32.9±4.6 Kg/m2) in the Group 2, 31 patients (10 F/21 M, 77.1±4.9 yrs, BMI 32.9±2.9 Kg/m2) in the Group 3 were included in the study. In all 3 groups, a significant reduction in BMI was observed after 1 year of treatment compared to baseline, with no significant differences in efficacy between the 3 types of intervention [ΔBMI: -1.44±0.26 (Group 1) vs -1.33±0.28 (Group 2) vs -1.33±0.27 (Group 3)]. GLP1-RA treatment was more effective than SGLT2i in reducing HbA1c in this population [ΔHbA1c: -9.8±2.2 (group 2) vs -2.2±1.8 (group 1), p=0.026]. Although not significant, an overlapping trend was observed for the combined SGLT2i and GLP1-RA therapy [ΔHbA1c: -9.5±3.9 (group 3)].Conclusion: Combined SGLT2i/GLP1-RA therapy was not shown to be superior to monotherapy in improving glycaemic control, likely due to lower efficacy of SGLT2i in the elderly population, as previously described. One possible explanation could be a physiological reduction in GFR in elderly population. All 3 interventions were effective in controlling BW for up to 1 year.DisclosureA. Ferrulli: None. P. Senesi: None. L. Luzi: Speaker's Bureau; A. Menarini Diagnostics, Amgen Inc. Research Support; Boehringer-Ingelheim. Advisory Panel; Eli Lilly and Company. Speaker's Bureau; Eli Lilly and Company. Research Support; Medtronic. Speaker's Bureau; Novartis AG, Novo Nordisk.FundingRicerca Corrente - IRCCS MultiMedica
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-760-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 761-P: The Novel Dual GIP and GLP-1 Receptor Agonist Tirzepatide Attenuate
-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 761-P
Abstract: Introduction and Objective: Colorectal cancer (CRC) is a leading cause of cancer mortality while diabetes is a recognized risk factor for CRC. Here we reported that tirzepatide (TZP), a novel promising injectable drug for treatment of type 2 diabetes, has an anti-CRC effect.Methods: In vivo, The anti-colorectal cancer effect was validated in various colorectal cancer models, including patient-derived xenograft (PDX) colon cancer models. Spatial metabolomics was used to detect changes in metabolic products in the tumor and adjacent non-tumor regions in mice.Results: We showed that TZP inhibited proliferation of CRC cells and suppressed the growth of CRC tumors in multiple murine models in vivo. Spatial metabolomics in orthotopic CRC demonstrated that the glycolysis level was significantly increased in tumor areas compared to the adjacent normal areas, while TZP inhibited glycolysis in tumor tissues, characterized by reduced glucose metabolism products and mRNA expressions of the key rate-limiting enzyme of glycolysis, PFKFB3 and PFK1. Further investigation demonstrated that TZP enhanced the ubiquitination and degradation of HIF-1α, which in turn inhibited PFKFB3-PFK1-mediated glycolysis, leading to energy deprivation and anti-tumor effects.Conclusion: Our study has identified the novel anti-colon cancer effect of TZP and HIF-1α mediated glucose regulation as a therapeutic target of CRC which supporting further preclinical trials.DisclosureY. Zhang: None. Y. Xie: None. C. Zheng: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-761-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 762-P: Semaglutide Improves Intestinal Barrier Function in T2D—A
Double-Blind Randomized Controlled Trial (RCT)-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 762-P
Abstract: Introduction and Objective: T2D is associated with impaired intestinal barrier function, contributing to endotoxemia and inflammation. We hypothesized that GLP-1 receptor agonists improve intestinal barrier integrity in T2D.Methods: In a 16-week double-blind RCT, individuals with T2D on metformin were randomized to receive subcutaneous semaglutide (1 mg weekly) or placebo. The primary outcome, intestinal permeability, was assessed via the urinary lactulose-to-mannitol ratio (LMR) within six hours of ingestion at baseline, week 8, and week 16. Secondary outcomes included serum hsCRP and fecal calprotectin as inflammatory markers. Data were analyzed using Wilcoxon rank-sum and Welch’s t-test for raw and log-transformed values, respectively.Results: Baseline characteristics were similar between groups (mean age 57 years, BMI 34.2 kg/m², HbA1c 6.6%, T2D duration 6.3 years) among 46 participants. Semaglutide reduced LMR significantly at week 8 (p=0.015) and showed borderline significance at week 16 (p=0.053). No significant changes in hsCRP or calprotectin were observed. (Figure)Conclusion: Semaglutide improves intestinal barrier function in T2D, potentially contributing to its anti-inflammatory effects.DisclosureM. Rezaei: None. V. Singh: None. C. Baker: None. J.C. Onyiah: None. N. Rasouli: Advisory Panel; Novo Nordisk. Research Support; Novo Nordisk. Advisory Panel; Eli Lilly and Company. Research Support; Eli Lilly and Company.FundingNovoNordisk Investigator-Sponsored Studies; NIH/NCATS Colorado CTSA (UM1 TR004399)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-762-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 763-P: Glycemic Control, Weight Reduction, and Safety with CT-388, a
Signal-Biased Dual GLP-1/GIP Receptor Agonist—Results from a 12-Week
Cohort in Adults with Obesity and Type 2 Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 763-P
Abstract: Introduction and Objective: In a phase 1 study (NCT04838405), CT-388 demonstrated a placebo (pbo)-adjusted (adj) weight loss (WL) of 18.8% after 24 weeks in adults with obesity without T2D. Here, we present safety, tolerability, and pharmacodynamic results from an additional cohort of adults with obesity and T2D.Methods: Adults with obesity and T2D (n=19) treated with diet/exercise alone or with metformin, and HbA1c 7.0%−10.0% at baseline (BL) were randomized (4:1) to either once-weekly subcutaneous CT-388 22 mg or pbo over 12 weeks. Key endpoints included change from BL in HbA1c, % WL, and adverse events (AEs). Descriptive statistics and linear mixed-effect models for repeated measures were employed.Results: Among 14 patients (pts) taking CT-388 and 5 taking pbo, BL mean (SD) age was 47 (9) vs 42 (14) years; HbA1c, 8.7% (1.1) vs 9.4% (0.6); and body weight, 95 (14) vs 96 (11) kg, respectively. At 12 weeks, CT-388 and pbo treatment led to a reduction in HbA1c of 3.0% and 0.2%, respectively (pbo-adj least squares mean [LSM] of 2.8% [95% CI: 2.1-3.6%]). Among CT-388-treated pts, 100% (n=14/14) and 50% (n=7/14) achieved HbA1c thresholds of ≤6.5% and <5.7%, respectively. CT-388 and pbo treatment led to a % WL of 8.6% and 1.2% at 12 weeks, respectively (pbo-adj LSM of 7.4% [95% CI 4.9-9.8%]). Among pts taking CT-388, 100% (n=14/14) achieved WL of ≥5%. There were no serious AEs, or AEs leading to discontinuation. GI AEs were the most frequent, with the majority being mild and transient. No clinically notable changes in laboratory or vital signs were noted.Conclusion: In a T2D cohort with obesity, CT-388 led to clinically meaningful improvements in glycemic control, including normalizing dysglycemia, and WL over 12 weeks. Safety/tolerability were in line with incretin-based therapies in similar stages of development. A phase 2 study of CT-388 in pts with T2D has been initiated (NCT06628362).Disclosure A. Steinberg: Employee; Genentech, Inc. Stock/Shareholder; Viking Therapeutics, Pfizer Inc. Employee; Roche Pharmaceuticals, Axcella Health Inc, Carmot Therapeutics, Inc. F.A. Argüelles-Tello: None. L.L. Sánchez-Sánchez: None. W.G. Ortiz: None. M.A. Elliott: Employee; Carmot Therapeutics, Inc. J. Wu: Employee; Roche Pharmaceuticals, Carmot Therapeutics, Inc. J. Zhu: Employee; Genentech, Inc. E. Shearer-Kang: Employee; Genentech, Inc. L. Acosta: None. J.R. Willis: Employee; Genentech, Inc. M. Chakravarthy: Employee; Carmot Therapeutics, Inc, Roche Pharmaceuticals, Genentech, Inc.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-763-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 764-P: Long-Term (24-Month) Follow-up of Indian T2DM Patients on Oral
Semaglutide-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 764-P
Abstract: Introduction and Objective: Semaglutide, a glucagon-like peptide-1 receptor agonist, in its oral form can be helpful in improving glycemic parameters and reducing weight in patients with diabesity but it's real world long term data is scanty, especially from Indian subcontinent.Methods: A prospective, observational cohort study across multiple centers from India capturing the 24 months follow-up treatment patterns of routine clinical use of oral semaglutide since its launch in India in Jan 2022. Subjects with type 2 diabetes and on-label prescription for oral semaglutide who continue treatment for 24 months were included.Results: The study included 109 patients (65 males); mean age (±standard deviation) 54.63 (±10.32) years; mean body mass index of 30.39 (±5.09); mean body weight of 88.83 (±10.12) kg and mean glycosylated hemoglobin (HbA1c) of 9.06 (±1.61). At the 24 months follow-up, 40.8% and 45.9% were on 7 mg and 14 mg doses, respectively. The mean reduction in HbA1c and body weight between baseline and 24 months follow-up were 1.63% and 4.85 kg respectively (P < 0.0001 for both). The most common side effects of oral semaglutide monotherapy were generalized weakness, nausea, dryness of mouth, and diarrhea. No hypoglycemia, other serious adverse events were reported.Adherence to therapy at the end of 24 months was 72%.Conclusion: The use of oral semaglutide in Indian T2D patients study shows significant improvement in glycemic parameters and body weight in Indian patients when initiated and continued over the period of 24 months since its launch.Oral Semaglutide remains a popular choice among those living with T2DM who do not prefer injectables as evident from the lower the drop-out rates and higher adherence at the end of 24 months.DisclosureS. Bhattacharyya: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-764-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 765-P: Therapeutic NuSH Cocktails—Coadministration of Ultra-Long-Acting
GLP-1, GIP, Glucagon, and Amylin Peptide Analogs Induce Profound Weight
Loss in DIO Mice-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 765-P
Abstract: Introduction and Objective: We hypothesized that NuSH cocktails may enhance weight loss efficacy and improve tolerability. We designed ultra-long acting (ULA) GLP-1, GIP, glucagon, and amylin peptide analogs to be mixable for convenient coadministration. We sought preclinical proof of concept of their mixability and concerted efficacy.Methods: ULA analogs of human GLP-1, GIP, glucagon, and amylin afforded MET-097, MET-034, MET-067, and MET-233, respectively—a peptide combo we call M4. We assessed the PK of coformulated M4 after single administration in minipigs and body weight loss after chronic administration in rats. The M4 (25 nmol/kg total peptide) effects on body weight and food intake were compared to retatrutide (26 nmol/kg).Results: In minipigs, M4 peptides had similar half-lives (range: 87-114 h). Chronic M4 administration to rats over 25 d induced >25% body weight loss, significantly more than the M2 combo of discrete GLP-1R and amylin agonists and also more than retatrutide.Conclusion: M4 peptides may allow for infrequent coadministration in humans. Results from chronic M4 administration to rats confirm that engaging multiple mechanisms can achieve more weight loss. Further, a polymolecular approach allows adjusting of individual agent dose levels to enhance M4’s efficacy to tolerability window, even in a semipersonalized way.Disclosure R. Hansford: Employee; Metsera. C. Hinds: Employee; Metsera, Zihipp. W.J. Adams: Employee; Metsera.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-765-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 766-P: GLP-1RA, Oral Formulation and Its Preclinical Evaluations
-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 766-P
Abstract: Introduction and Objective: The remarkable efficacy of GLP-1RAs, which has had a significant impact in real world, is gradually advancing towards firstly once-a-month injectable sustained release formulation and ultimately moving toward oral formulations. However, oral GLP-1RAs, which leverages SNAC technology, still face challenges like lower bioavailability and efficacy. To address challenges, this study explores encapsulating GLP-1RA in mesoporous nanoparticles to enhance drug loading and bioavailability, along with conducting preclinical evaluations of the proposed formulation.Methods: Semaglutide was dissolved and loaded into mesoporous nanoparticles with varying sizes, shapes, and surface modifications. Among several candidates, the top five and further two candidates, BACH01001 and BACH01002, were chosen based on their capability to meet the target candidate profile (TCP). The PK and PD profiles of candidates were subsequently assessed in small animal models.Results: Among the two candidates, BACH0101, an aminated mesoporous nanoparticle, achieved high drug loading efficiency (>90%), a short reaction time (<1 hour), and a favorable drug release profile, meeting its TCP criteria. In contrast, BACH0102, a larger particle (3 µm), showed lower loading efficiency (~70%) but was better suited for enteric coating in oral formulations. Both candidates demonstrated significantly higher bioavailability (Cmax, AUC) and pharmacodynamic profiles equivalent to or better than comparator’s oral semaglutide.Conclusion: Recent formulation studies of BACH01 underscore the strong potential of BioArcher’s technology in revolutionizing oral peptide drug delivery, including other GLP-1RAs. The results from formulation, preclinical evaluations, and scalable production provide a compelling rationale for successful clinical development. This innovative approach positions BACH01 as a promising therapeutic option for patients managing diabetes, obesity, and other chronic diseases.Disclosure J. Jung: Board Member; BioArchers, Inc. J. Lee: Board Member; BioArchers, Inc. G. Kim: Board Member; BioArchers, Inc.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-766-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 767-P: No Effect of Food or Proton Pump Inhibitor on the Pharmacokinetics
of TERN-601, an Oral Small Molecule GLP-1 Receptor Agonist-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 767-P
Abstract: Introduction and Objective: TERN-601 is a novel once-daily oral small molecule GLP-1 receptor agonist, in development for chronic weight management. This Phase 1 study was conducted to evaluate the effect of food and a proton pump inhibitor (PPI) on the pharmacokinetics (PK) of TERN-601.Methods: In Period 1, healthy participants (N=10) were randomized 1:1 to receive two single doses of TERN-601 (500 mg): in the fed (high-fat/calorie) or fasted state on Day 1, then in the opposite prandial state on Day 4. In Period 2, all received rabeprazole (20 mg QD) (PPI) on Days 1-4, then TERN-601 and rabeprazole on Day 5. PK samples were collected up to 48 hours after each TERN-601 dose. Safety assessments were performed throughout the study.Results: All participants completed the study without adverse events or clinically meaningful changes in vital signs, ECGs, or laboratory values. No change in t1/2 or Tmax. AUCinf increased 18% in the fed state and decreased 11% with a PPI compared to TERN-601 alone, fasted. TERN-601 Cmax decreased 18% in the fed state compared to the fasted state; no change when administered with a PPI.Conclusion: TERN-601 appeared safe and well-tolerated. Neither food nor a PPI had clinically meaningful effects on the PK of TERN-601, supporting the administration of TERN-601 without restriction of food or acid reducing agents.Disclosure C.H. Nelson: Employee; TERNS Pharmaceuticals. Stock/Shareholder; TERNS Pharmaceuticals, Gilead Sciences, Inc. C. Jones: Employee; TERNS Pharmaceuticals. E. Kwan: Employee; TERNS Pharmaceuticals. E.N. Castelloe: Consultant; TERNS Pharmaceuticals, Ascendis Pharma A/S, Artelo Biosciences, Dianthus Therapeutics, Soleno Therapeutics, Plexium, Sustained Therapeutics, Virogenics, Nobias Therapeutics. T. Marmon: None. E.T. Kuriakose: Employee; TERNS Pharmaceuticals.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-767-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 768-P: Glucagon-Like Peptide 1 Receptor Agonists and the Risk of
Motility-Related Gastrointestinal Adverse Events—A Cohort Study-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 768-P
Abstract: Introduction and Objective: To assess if glucagon-like peptide-1 receptor agonist (GLP-1 RA) compared with sodium-glucose cotransporter 2 inhibitors (SGLT-2i), is associated with an increased risk of motility-related gastrointestinal (GI) adverse events.Methods: From two US commercial healthcare databases, we used 1-1 propensity score matching on >150 potential confounders to identify a cohort of adults with type 2 diabetes who initiated GLP-1 RA or SGLT-2i between Oct/2016-Aug/2024. The primary outcome was a composite of severe constipation, gastroparesis, and bowel obstruction. We calculated incidence rates and the hazard ratio (HR) with 95% confidence interval (CI) for the primary composite outcome.Results: Among 313,342 matched pairs of GLP-1 RA and SGLT-2i initiators (mean age 60 years; 45% female), followed on treatment for a median of 6.5 months, incidence rates of the composite outcome were 10.2 among GLP-1 RA versus 7.5 among SGLT-2i initiators per 100 person-years. The rate was significantly higher among GLP-1 RA versus SGLT-2i initiators (HR 1.37, 95% CI 1.30 to 1.45) for the composite event and for each of its individual components.Conclusion: We observed an increased risk of motility-related GI events associated with GLP-1 RA compared to SGLT-2i. These findings inform the risk benefit assessment by clinicians before initiating these treatments.DisclosureW. Alkabbani: None. S. Crisafulli: None. J.M. Paik: None. A. Tavakkoli: Consultant; Vertex Pharmaceuticals Incorporated, AltrixBio. K. Bykov: None. R. Glynn: Research Support; Amarin Corporation, Kowa Company, Ltd, Novartis Pharmaceuticals Corporation. D.J. Wexler: Other Relationship; Novo Nordisk. E. Patorno: Research Support; National Institute of Diabetes and Digestive and Kidney Diseases, Patient-Centered Outcomes Research Institute, Food and Drug Administration (FDA), Boehringer-Ingelheim. Other Relationship; UpToDate.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-768-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 769-P: Bofanglutide (GZR18), a Novel GLP-1RA, Improved Glycemic Control
and Cardiometabolic Risk Factors in Chinese Patients with T2D-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 769-P
Abstract: Introduction and Objective: This randomized, double-blind, placebo-controlled, dose-escalation phase 2a trial aimed to assess the safety and efficacy of a novel GLP-1 RA, bofanglutide (GZR18), in Chinese adults with T2D.Methods: Thirty-six adults with T2D inadequately controlled with lifestyle management and/or non-compliance with OADs were randomized 3:1 to receive either GZR18 or placebo once-weekly for 23 weeks, with a dose escalating from 1.5 mg to 13 mg. Safety endpoints, including treatment-emergent adverse events (TEAEs) and gastrointestinal AEs, were evaluated. Key efficacy endpoint was HbA1c change from baseline to week 23.Results: By week 23, the GZR18 group exhibited a greater reduction in HbA1c of -1.81 % compared to 0.12 % in the placebo group, along with significant reductions in body weight (-9.25 %), waist circumstance (-5.31 cm), SBP (-15.4 mmHg) and blood lipids. The most common TEAEs were Grade 1-2 gastrointestinal AEs. No hypoglycemia or serious adverse events related to GZR18 were observed.Conclusion: GZR18 was well-tolerated in Chinese patients with T2D, demonstrating significant HbA1c reductions alongside comprehensive benefits for body weight, blood pressure and blood lipid profiles. These findings further support the exploration of GZR18's dosing frequency in the phase 2b trial and cardiometabolic outcomes in future GZR18 clinical trials.DisclosureW. Li: None. M. Liu: None. R. Dong: None. X. Wang: None. J. Zhao: None. L. Zhao: None. A. He: None. T. Xie: None. Y. Li: None. H. Wu: None. S. Carter: None. Z. Gan: None. W. Chen: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-769-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 770-P: Persistence of Prescription Gaps of SGLT2i and GLP-1RA in Type 2
Diabetes and Cardiorenal Disease—A Current Global Perspective-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 770-P
Abstract: Introduction and Objective: Large gaps persist in guideline-indicated prescription of cardiorenal protective medications (CRPM), namely SGLT2i and GLP-1RA, in people with T2D and cardiorenal disease, despite strong data and guidance for their use.Methods: We evaluated the treatment gap (Jan 2019-Dec 2024) in prescribing CRPM to people with T2D and cardiorenal disease using an EHR data aggregation initiative (Cosmos by Epic Systems) spanning 283 health systems across 49 US states and the Middle East. Eligible patients (N=7,800,815) had T2D and received care from either endocrinology, cardiology, nephrology, or primary care since 2019 (first guidelines with CRPM). Eligibility subgroups were defined using ADA 2022 Standards of Care. Current and past prescriptions for CRPM were extracted.Results: Eligibility subgroups included: ASCVD (N=2,367,381) - ‘SGLT2i or GLP1RA’; HF or CKD stage 3 (N=1,815,645) - ‘SGLT2i Only’; ASCVD and HF or CKD stage 3 (N=2,636,753) - ‘SGLT2i primary’; CKD stage 4/5 (N=981,022) - ‘GLP1RA Only’. The ever prescribed treatment gap ranged from 66.4% (SGLT2i primary) to 80.5% (GLP-1RA only) (Fig 1A). The treatment gap was higher for currently prescribed across all subgroups, ranging from 73.5% to 86.8% (Fig 1B).Conclusion: Current CRPM treatment gap is >73%, five years after the guidelines incorporated these recommendations for people with T2D.DisclosureS. Agarwal: None. Y.A. ElNakieb: None. M.A. Basit: Advisory Panel; Pfizer Inc. M.E. Bowen: Research Support; Boehringer-Ingelheim. K. Marble: None. C. Mai: None. J. Pak: None. I. Lingvay: Consultant; Abbvie, Altimmune, Amgen, Alveus Tx, Antag Tx, Astra Zeneca, Bayer, Betagenon AB, Bioio Inc., Biomea, Boehringer-Ingelheim, Carmot, Cytoki Pharma, Eli Lilly, Intercept, Janssen/J&J, Juvena, Keros Ther, Novo Nordisk, Pharmaventures, Pfizer, Regeneron, Roche, Sanofi, Shionogi, Source Bio, Structure Therapeutics, TARGET RWE, TERNS Pharma, The Comm Group, WebMD, and Zealand Pharma. Research Support; Novo Nordisk, Sanofi, Boehringer-Ingelheim.FundingThis study was supported by BI. BI had no role in the design, analysis or interpretation of the results in this study. BI was given the opportunity to review the manuscript for medical and scientific accuracy as it relates to BI substances, as well as intellectual property considerations.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-770-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 771-P: Meta-analysis of hsCRP's Effect on Cardiovascular Outcome among
GLP-1RAs–Based Clinical Trials-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 771-P
Abstract: Introduction and Objective: Certain cardiovascular outcome trials (CVOTs) indicated that GLP-1RAs may offer a potential cardiovascular protection effect, but the current results are inconsistent. GLP-1RAs have been shown to reduce hsCRP, despite the unclear relationship between hsCRP and cardiovascular risk. This meta-analysis evaluates whether the changes in hsCRP influence the 3-point major adverse cardiovascular events (3P-MACE) in CVOTs.Methods: A meta-analysis of randomized controlled trials comparing GLP-1RAs with placebo was performed. PubMed, Embase, Web of Science, and the Cochrane Library were searched up to Dec. 2024. The primary outcomes were changes in hsCRP and 3P-MACE. The value changes in hsCRP were analyzed by mean differences (MD) and standard deviations, and the percentage changes were analyzed by two sample t-test between studies w/ and w/o MACE protection. Linear regression was used to assess hsCRP's impact on cardiovascular mortality.Results: We identified 7 studies, 5 of which reported hsCRP value changes. Pooled result indicated that GLP-1RAs significantly reduced hsCRP compared to placebo, and the reduction was greater in cardiovascular protective studies (MD = -0.44, 95%CI -0.57 ~ -0.31) versus non-protective studies (MD = -0.38, 95%CI -0.44 ~ -0.32). A two sample t-test on hsCRP percentage changes from 5 studies (with available MACE data) showed a significant reduction in hsCRP in MACE-protective studies (P = 0.0386). Linear regression indicated that the hsCRP reduction didn’t improve mortality (P = 0.0551).Conclusion: This meta-analysis shows that GLP-1RAs could significantly reduce hsCRP, with a larger effect in MACE-protective studies. However, hsCRP's impact on cardiovascular mortality is marginally insignificant, possibly due to missing data and small sample sizes. It would be worthwhile to further explore the underlying mechanism of GLP-1RAs’ additional cardiovascular benefits by lowering hsCRP and improving inflammatory state.DisclosureL. Luo: None. Y. Luo: None. L. Ji: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-771-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 772-P: Cognitive Outcomes in Adults Treated with GLP-1 Receptor Agonists
Compared with Nonusers—A Retrospective Chart Review-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 772-P
Abstract: Introduction and Objective: GLP-1 receptor agonists (GLP-1 RAs) are recognized for glycemic and metabolic benefits in type 2 diabetes and obesity. Emerging evidence suggests neuroprotective effects via GLP-1 receptor expression in key brain regions. This study evaluated whether GLP-1 RA therapy is associated with measurable changes in cognitive function via MMSE.Methods: This retrospective cohort study used de-identified EMRs from the Gonzaba Medical Group. Adults aged ≥18 years with ≥2 MMSE assessments and complete confounder data were included (n = 529). The intervention group received GLP-1 RAs, while the comparator group met identical criteria but excluded GLP-1 RA use. Linear regression analyzed relationships between GLP-1 RA use, MMSE scores, and confounders.Results: The population was predominantly female (57%), diabetic (53%), and Hispanic (96%), with a mean age of 74 years and BMI of 29.7 kg/m². At baseline, the GLP-1 RA group exhibited significant differences from the control group, including higher MMSE, longer assessment intervals, more diabetics, lower age, and higher BMI, resulting in baseline confounding.GLP-1 RA-treated subjects showed a BMI reduction of 0.91 kg/m² (p<0.01) versus controls. Cognitive decline occurred in all groups. In the GLP-1 RA group, each 1 kg/m² BMI decrease was associated with a 0.067-point MMSE increase, though not statistically significant (p=0.69).Conclusion: Baseline confounding highlights the need for better control in future studies. Improvement in MMSE scores among GLP-1 RA-treated subjects suggests that weight loss may be critical to achieving proposed neuroprotective effects. Findings warrant further exploration in randomized controlled studies.DisclosureC.A. Dehn: None. L. Ballester: Research Support; NeuroBo Pharmaceuticals, Inc, Biogen, Boston Pharmaceuticals, Vigil Neuroscience, BioXcel Therapeutics, Braeburn Pharmaceuticals, Ceruvia Lifesciences, Karuna Therapeutics, Ensysce Biosciences, Fulcrum Therapeutics, Xgene Pharmaceuticals, Urica Therapeutics, Crystalys Biotherapeutics, TLC Biosciences, PainReform, LTD Therapeutics Inc, Kenvue, Graviton Bioscience, Gate Bioscience, Antibe Therapeutics, Park Therapeutics, ProMIS Neurosciences. M. Paulos: None. V.G. Gonzaba: None. E. Tireman: None. T.A. Karnes: None. W. Martin: Employee; Alkermes, Inc. Advisory Panel; Axial Therapeutics. S.L. Schwartz: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-772-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 773-P: Effect of Glucagon-Like Peptide 1 Receptor Agonists Compared with
Basal Insulin in Severely Uncontrolled Type 2 Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 773-P
Abstract: Introduction and Objective: Glucagon-like Peptide-1 receptor agonists (GLP1s) are comparable to insulin for the treatment of T2D and promote weight loss. There are limited data to guide GLP1 use in severely uncontrolled T2D (A1C ≥10%).Methods: We conducted a retrospective cohort study of 1,518 adults with T2D who were ordered a GLP1 or basal insulin within 3 months of an A1C ≥10%. Data were collected at 6±3 month intervals after the first drug order and up to one month after expiration of the last drug order or a medication lapse of >1 month. Subjects taking both a GLP1 and basal insulin were excluded. Comparisons were made using the Wilcoxon rank sum or signed rank tests.Results: The mean age of the cohort was 57.8±12.1 years. 49.5% of subjects were female, 43.9% were Black, 22.1% White, and 31.0% Hispanic. Subjects were followed for a median of 22.4 months. People in both the GLP1 and basal insulin groups had significantly lower A1C at the end of study, with the GLP1 group having a significantly greater A1C reduction compared to basal insulin (Table). Subjects in the GLP1 group had significant reductions in body weight and BMI compared to baseline, while those in the basal insulin group did not (Table).Conclusion: In a racially and ethnically diverse population, GLP1s may be associated with weight loss and greater A1C reduction relative to basal insulin in people with severely uncontrolled T2D.DisclosureJ. Student: None. M. DSilva: None. D. Novikov: None. M. Ahmad: None. X. Lu: None. D. Yu: None. D.J. Rubin: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-773-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 774-P: Robust Antiobesity Effect and Mechanistic Insights of HM15275, a
Novel Long-Acting GLP-1/GIP/Glucagon Triple Agonist in Animal Model of
Obesity-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 774-P
Abstract: Introduction and Objective: Obesity has reached epidemic proportions globally, posing a critical public health crisis. To address this, HM15275, a novel long-acting GLP-1/GIP/Glucagon triple agonist was developed, demonstrating potent weight loss and glycemic control in prior preclinical studies. The present study further investigates the effects of HM15275 on body weight and body composition over an extended period and its underlying mechanisms.Methods: The effect of HM15275 on body weight and body composition were assessed in DIO mice. To investigate the weight loss mechanism of HM15275, pair-fed and energy balance studies were conducted, and mesenteric white adipose tissue (mWAT) was subjected to immunohistochemistry. Tirzepatide (TZP) and retatrutide (RETA, in-house synthesis) served as comparative controls.Results: In DIO mice, HM15275 treatment for 3 weeks resulted in a greater weight loss (-39.9% vs. D0) than TZP (-25.3% vs. D0). Switching from TZP to HM15275 at week 2 led to further weight loss. Mechanistically, a pair-fed study revealed that HM15275 induced both food intake-dependent and -independent weight loss in which, latter was driven by increased energy expenditure. HM15275 also enhanced expression of PGC-1α and UCP-1 in mWAT, being more pronounced than TZP, which indicates stronger fat browning effect. Furthermore, longer treatment of HM15275 for 6 weeks significantly reduced more body weight than RETA. Notably, greater fat mass reduction and no difference in lean mass by HM15275 contributed to more improved weight loss quality compared to RETA.Conclusion: In conclusion, HM15275 demonstrates potent weight loss with improved weight loss quality in DIO mice. Also, comprehensive elucidation of the underlying mechanism of action has been demonstrated. Clinical translation of such findings is under investigation in an ongoing phase 1, 4-week multiple ascending dose (MAD) study in obese patients.DisclosureS. Park: None. Y. Kim: None. J. Kim: None. S. Lee: None. E. Park: None. D. Lee: None. J.A. Kim: None. S. Hong: None. S. Bae: None. S. Lee: None. I. Choi: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-774-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 775-P: Mazdutide, a Dual GLP-1R/GCGR Agonist, Reduces Hyperuricemia by
Modulating Energy and Lipid Metabolism and Inhibiting Hepatic Purine
Metabolism-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 775-P
Abstract: Introduction and Objective: Mazdutide (IBI362) is a dual agonist of GLP-1R and GCGR. Previous studies indicated that it significantly reduces serum uric acid levels in hyperuricemic rats compared to semaglutide. This study aims to further clarify the mechanism by which Mazdutide lowers uric acid in these rats.Methods: A hyperuricemia model was established in SD rats by administering adenine and potassium oxonate via gavage for 24 days following a 4-week high-fat diet starting at 8 weeks of age. After successful modeling, the rats were randomly divided into 8 groups. Following an 18-day intervention, we conducted single-nucleus RNA-Seq (snRNA-Seq) and metabolomic analyses.Results: SnRNA-Seq analysis shows that mazdutide increases GCGR expression in hepatocytes, while semaglutide slightly inhibits it. In hyperuricemic rats, fatty acid oxidation genes (Cpt1a, Fabp1, Apoa1, Acox1, Acaa1a) are significantly reduced, but mazdutide treatment markedly increases their expression. Conversely, Fatty acid synthesis genes (Acaca, Fasn) and glucose/purine metabolism genes (Pklr, G6pc1, Glul, Gckr, Gk, Nt5e, Ppat) are downregulated, Metabolomic analysis reveals that mazdutide lowers metabolites, including glucose, glucose-6-phosphate, L-glutamine, xanthosine, adenosine, uric acid and numerous other metabolites,consistent with control trends. Indicating a metabolic shift towards fatty acid oxidation and reduced production and utilization of purine precursors.Conclusion: Mazdutide significantly lowers serum uric acid levels in hyperuricemic rats by enhancing fatty acid oxidation and regulating energy metabolism in hepatocytes, ultimately reducing purine precursor production and utilization.Compared to Semaglutide, Mazdutide offers more substantial benefits in lowering uric acid levels.DisclosureY. Ren: None. Y. Zhang: None. C. Liu: None. Z. Chen: None. X. Li: None. Y. Zhang: None. Y. Ma: None. X. Chen: None. H. Jiang: None.FundingMedical Science and Technology Research and Development Plan Major Project Jointly Constructed by the Henan Province and Ministerial Departments in China (No. SBGJ202301010)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-775-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 777-P: The Dual Glucagon and Glucagon-Like Peptide 1 Receptor Agonist
Mazdutide Outbalanced Glucagon-Like Peptide 1 Receptor Agonist Semaglutide
Monotherapy in Improving Mice Liver Fat Accumulation-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 777-P
Abstract: Introduction and Objective: This study aimed to explore the mechanism of the dual GCGR/GLP-1R agonist mazdutide for improving liver fat accumulation compared to the GLP-1R agonist semaglutide.Methods: Mazdutide (30 nmol/kg per week) or semaglutide (30 nmol/kg every other day) was administrated subcutaneously for 8 weeks in diet-induced obesity mice to maintain a comparable level of glycemic control. Parameters associated with body weight, hepatic fat accumulation, and transcriptomic results were analyzed.Results: Mazdutide treatment reduced body weight to a greater extent than semaglutide treatment (40.1% vs 28.1%, P < 0.001), with a lower fat mass percentage trend (11.2% vs 15.6%, P = 0.116). Lower serum TG (0.56 vs 0.80 mmol/L, P = 0.006), TC (2.85 vs 3.97 mmol/L, P < 0.001), and LDL-C (0.32 vs 0.62 mmol/L, P < 0.001) levels were shown in the mazdutide group, along with a reduction in liver TC level (0.05 vs 0.06 μmol/mg protein, P = 0.045). Liver H&E and Oil red O staining further confirmed the above results. Liver RNA-sequencing and KEGG enrichment analysis showed that mazdutide predominantly activated oxidative phosphorylation and fatty acid degradation pathways, and lipid metabolism-related genes such as Ehhadh, Cyp4a14, Hadha, Fgf21, and Gdf15 were upregulated, indicating that it facilitated fatty acid oxidation in the liver compared to semaglutide. We further screened differentially expressed transcription factors (TF) through the TRRUST database and found that activating transcription factor 3 (Atf3) upregulated in the mazdutide treatment group might be the functional TF regulating lipid degradation in the liver.Conclusion: The dual GCGR/GLP-1R agonist mazdutide exhibited a better efficacy in body weight loss and liver fat accumulation alleviation compared to the GLP-1R agonist semaglutide monotherapy potentially due to its promotion of fatty acid oxidation via ATF3.DisclosureQ. Wu: None. T. Wei: None. X. Cui: None. J. Yang: None. R. Wei: None. T. Hong: None.Fundingthe Noncommunicable Chronic Diseases-National Science and Technology Major Project (2023ZD0506900, 2023ZD0507000); the National Natural Science Foundation of China (82170875); the Bethune Charitable Foundation (BFC-0XM-JC-20240607-01)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-777-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 778-P: Pemvidutide, a Balanced GLP-1/Glucagon Dual Receptor Agonist,
Enhances Reverse Cholesterol Transport in a Golden Syrian Hamster Model-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 778-P
Abstract: Introduction and Objective: Pemvidutide is a long-acting, peptide-based GLP-1/glucagon dual receptor agonist that elicits significant reductions in body weight and serum lipids in preclinical and clinical studies. Reverse cholesterol transport (RCT) is an important process for removing excess cholesterol from peripheral tissues. Preclinical studies have suggested that glucagon may enhance the elimination of cholesterol, possibly due to enhanced RCT. Here, we investigated the effects of pemvidutide on RCT via cholesterol excretion in a preclinical model.Methods: Obese male Golden Syrian hamsters were treated daily with pemvidutide or vehicle for 35 days. On Day 35, macrophages labelled with 3H-cholesterol were injected intraperitoneally, and the appearance of the 3H-cholesterol in plasma, liver, and feces was quantitated over 72 hours. In an independent study, changes in the hepatic expression of genes involved in cholesterol transport were measured by reverse transcription-polymerase chain reaction (RT-PCR) following pemvidutide treatment.Results: Pemvidutide treatment significantly reduced total plasma triglycerides, total cholesterol, and LDL-cholesterol as compared to vehicle controls. Specifically, pemvidutide significantly reduced plasma 3H-cholesterol and increased the excretion of 3H-cholesterol and its metabolites in feces over 72 hours. RT-PCR analysis showed significantly increased hepatic gene expression of the cholesterol transporters ABCG5 and ABCG8 in the pemvidutide treated group compared to vehicle.Conclusion: Pemvidutide treatment increased excretion of cholesterol into feces and upregulated transporters of cellular cholesterol in the liver, consistent with increased RCT. These findings suggest that in addition to other mechanisms, pemvidutide improves serum cholesterol through enhanced cholesterol excretion.Disclosure M. Lucca Andrade: Employee; Altimmune Inc. J.J. Suschak: Employee; Altimmune Inc. B. Georges: Employee; Altimmune Inc. F. Briand: Employee; PHYSIOGENEX. Stock/Shareholder; PHYSIOGENEX. M.S. Roberts: Employee; Altimmune Inc.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-778-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 779-P: Cardiovascular Outcomes Associated with Dulaglutide, Exenatide,
Liraglutide, and Semaglutide in Adults with Type 2 Diabetes at Moderate
Cardiovascular Risk-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 779-P
Abstract: Introduction and Objective: Glucagon-like peptide-1 receptor agonist (GLP-1RA) agents have demonstrated cardiovascular disease (CVD) benefits in adults with type 2 diabetes (T2D) at high and moderate CVD risk. However, their head-to-head comparative risk of cardiovascular outcomes is unknown.Methods: We conducted a clinical trial emulation comparing CVD outcomes between patients treated with four GLP-1RAs. Using medical and pharmacy claims data from commercial, Medicare Advantage, and traditional Medicare plans between 2019-2021 for adults ≥21 years with T2D and moderate CVD risk (estimated 1-5% annualized risk of a major cardiovascular event [MACE: myocardial infarction, stroke, or death]) who initiated dulaglutide, exenatide, liraglutide, or semaglutide, we used propensity score inverse probability of treatment weighted Cox proportional hazards models to compare the hazard of MACE, expanded MACE (MACE plus heart failure hospitalization or arterial revascularization), each component of expanded MACE, and hospital/emergency department visits for hypoglycemia.Results: We identified 36,656 patients initiating dulaglutide (mean age 64.5 ± 8.5 years, 46.8% male), 4,530 initiating exenatide (64.7 ± 8.2 years, 47.3% male), 9,794 initiating liraglutide (64.7 ± 8.3 years, 45.4% male), and 34,163 initiating semaglutide (64.4 ± 8.5 years, 46.6% male). Compared to dulaglutide, semaglutide was associated with lower hazard of MACE (HR 0.86, 95% CI 0.80-0.94), expanded MACE (HR 0.92, 95% CI 0.88-0.97), death (HR 0.84, 95% CI 0.74-0.94), stroke (HR 0.84, 95% CI 0.72-0.99), and arterial revascularization (HR 0.93, 95% CI 0.88-0.99). Liraglutide was associated with a lower hazard of death when compared to dulaglutide (HR 0.77, 95% CI 0.63-0.95).Conclusion: Semaglutide may be the GLP-1RA associated with the greatest cardiovascular risk reduction in patients with T2D at moderate CVD risk.DisclosureS. Sklepinski: None. J. Herrin: None. K. Swarna: None. J.J. Neumiller: Advisory Panel; Proteomics International. R.J. Galindo: Consultant; Abbott, AstraZeneca. Advisory Panel; Bayer Pharmaceuticals, Inc, Boehringer-Ingelheim. Consultant; Dexcom, Inc., Eli Lilly and Company, Medtronic. Research Support; National Institute of Diabetes and Digestive and Kidney Diseases. Consultant; Novo Nordisk. Research Support; Novo Nordisk, Boehringer, Dexcom. G. Umpierrez: Research Support; Abbott, Dexcom, Inc., Bayer Pharmaceuticals, Inc, Corcept Therapeutics. Advisory Panel; Dexcom, Inc., GlyCare Health. J. Ross: Research Support; Janssen Pharmaceuticals, Inc. Y. Deng: None. E. Polley: None. B. Maron: Advisory Panel; Actelion. Research Support; Deerfield Corporation. Board Member; Tenax. Research Support; Montgomery County, Maryland,. R.G. McCoy: Consultant; Wolters Kluwer Health, Yale New Haven Health System. Research Support; American Diabetes Association. Other Relationship; American Diabetes Association.FundingPCORI Award (PCS-1409-24099)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-779-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 780-P: Comparative Risk of Adverse Pancreatic Events with Second-Line
Glucose-Lowering Therapies in Adults with Type 2 Diabetes at Moderate
Cardiovascular Disease Risk-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 780-P
Abstract: Introduction and Objective: Pancreatitis and pancreatic cancer are important causes of morbidity and mortality, particularly in people with type 2 diabetes (T2D). Evidence of potential adverse pancreatic events with glucagon-like peptide-1 receptor agonists (GLP-1RAs) and dipeptidyl peptidase-4 inhibitors (DPP-4is) has been mixed and has not included comparison to other commonly used glucose-lowering medications other than metformin.Methods: We emulated an idealized trial using de-identified administrative claims data from OptumLabs Data Warehouse and the Medicare fee-for-service 100% sample to estimate the comparative risks of incident acute pancreatitis and pancreatic cancer among adults with T2D and moderate cardiovascular risk. Propensity score inverse probability of treatment weighting was used to emulate treatment assignment to GLP-1RA, DPP4i, sodium-glucose cotransporter 2 inhibitor (SGLT2i), or sulfonylurea.Results: The weighted study cohort included 388,262 patients starting either a DPP-4i inhibitor (N=82,079), a GLP-1RA (N=44,084), an SGLT2i (N=56,463), or a sulfonylurea (N=205,636). SGLT2i use was associated with lower risk of acute pancreatitis compared to DPP4i (HR 0.82; 95% CI 0.68-0.98), while sulfonylurea use was associated with higher risk compared to GLP-1RA (HR 1.28; 95% CI 1.03-1.56) and SGLT2i (HR 1.32; 95% CI 1.12-1.57). There was no association between GLP-1RA use and acute pancreatitis risk relative to DPP4i or SGLT2i. The risk of pancreatic cancer was lower with GLP-1RA compared to DPP4i (HR 0.56; 95% CI 0.40-0.77), and was higher with SGLT2i and with sulfonylurea when compared to GLP-1RA (HR 1.67; 95% CI 1.12-2.49 and HR 1.60; 95% CI 1.17-2.19, respectively).Conclusion: GLP-1RA therapy was not associated with increased risk of adverse pancreatic outcomes. The observed lower risk of acute pancreatitis in patients treated with SGLT2i requires further exploration.DisclosureU. Kalathiya: None. J. Herrin: None. K. Swarna: None. J.J. Neumiller: Advisory Panel; Proteomics International. R.J. Galindo: Consultant; Abbott, AstraZeneca. Advisory Panel; Bayer Pharmaceuticals, Inc, Boehringer-Ingelheim. Consultant; Dexcom, Inc., Eli Lilly and Company, Medtronic. Research Support; National Institute of Diabetes and Digestive and Kidney Diseases. Consultant; Novo Nordisk. Research Support; Novo Nordisk, Boehringer, Dexcom. G. Umpierrez: Research Support; Abbott, Dexcom, Inc., Bayer Pharmaceuticals, Inc, Corcept Therapeutics. Advisory Panel; Dexcom, Inc., GlyCare Health. J. Ross: Research Support; Janssen Pharmaceuticals, Inc. Y. Deng: None. E. Polley: None. M. Mickelson: None. R.G. McCoy: Consultant; Wolters Kluwer Health, Yale New Haven Health System. Research Support; American Diabetes Association. Other Relationship; American Diabetes Association.FundingPatient-Centered Outcomes Research Institute Award (PCS-1409-24099)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-780-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 781-P: Structural Modeling of GLP-1R Variants Interactions with
Tirzepatide Using AI Tools—A Precision Diabetes Management Method-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 781-P
Abstract: Introduction and Objective: Tirzepatide (TZP), a dual GIP-R and GLP-1R agonist, has demonstrated outstanding efficacy in glycemic control and weight loss. Structural studies have demonstrated the binding mechanism between tirzepatide and the GLP-1R-wilt type (WT). However, since population studies have demonstrated multiple SNPs on the GLP-1R, the mechanisms of TZP binding to GLP-1R variants have yet to be investigated. This study illustrates the interaction dynamics between TZP and GLP-1R variants and provides insight into the change in binding mechanisms and affinities between TZP and GLP-1R WT and variants.Methods: Common variants of the GLP-1R from gnomAD database were chosen for this study. The GLP-1R variant structures bound to TZP were modeled with AI modeling too AlphaFold 3.0, and the conformational stability and dynamic features of the GLP-1R-TZP complexes were subjected to molecular dynamic (MD) simulations. Moreover, we investigated the binding free energy using molecular mechanics-generalized Born surface area (MM/GBSA) to calculate binding energies.Results: The binding energies of the GLP-1R WT bound to TZP (-168 kcal/mol) demonstrated a more robust binding affinity than GLP-1R-R131Q (-155 kcal/mol), GLP-1R-L260F (-161 kcal/mol), GLP-1R-G168S (-148) and GLP-1R-A316T (-139 kcal/mol).Conclusion: In summary, our research offers structural insights into the GLP-1R TZP interaction, with different variants that could potentially approach T2D and obesity, potentially leading to improved patient outcomes through tailored therapy selection based on individual genetic profiles.DisclosureA. Mohammad: None. M.H. Dashti: None. F. Almulla: None. J. Abubaker: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-781-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 782-P: Once-Weekly Semaglutide vs. Placebo for the Treatment of Type 2
Diabetes and Chronic Kidney Disease in Denmark—A Long-Term
Cost-Effectiveness Analysis Based on Flow-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 782-P
Abstract: Introduction and Objective: The FLOW clinical trial recently demonstrated that glucagon-like peptide-1 receptor agonist once-weekly semaglutide 1 mg was associated with kidney- and cardio-protective effects compared with placebo in addition to standard of care (SoC) in people with type 2 diabetes (T2D) and chronic kidney disease (CKD). This study assessed the long-term cost-effectiveness of semaglutide versus placebo in people with T2D and CKD in Denmark, based on outcomes from FLOW.Methods: Life expectancy, quality-adjusted life expectancy, cumulative incidence of diabetes-related complications, and costs were projected over a lifetime time horizon using the PRIME T2D Model. Baseline cohort characteristics and changes in risk factors with semaglutide and placebo were taken from FLOW, with extrapolation over 60 years. Outcomes were assessed for the full population and subgroups receiving/not receiving sodium-glucose cotransporter-2 inhibitors (SGLT2i) at baseline. Quality-of-life disutilities and Denmark-specific costs (expressed in 2023 euros [EUR]) were applied to capture the impact of diabetes-related complications and pharmacy costs.Results: Treatment with semaglutide was projected to improve long-term quality-adjusted life expectancy by 0.60, 0.44 and 0.62 quality-adjusted life years (QALYs) compared with placebo in the full population and subgroups receiving/not receiving SGLT2i, respectively. Semaglutide was associated with long-term, per-person cost savings of EUR 814 in the full population and EUR 1,236 in those not receiving SGLT2i, and a cost increase of EUR 1,140 in those receiving SGLT2i. Differences were driven by a reduced incidence of end-stage renal disease with semaglutide versus placebo.Conclusion: Adding semaglutide to SoC was projected to be highly cost‐effective over the long term in people with T2D and CKD in Denmark, based on data from FLOW.Disclosure P. Rossing: Speaker's Bureau; Abbott. Advisory Panel; AstraZeneca, Bayer Pharmaceuticals, Inc, Boehringer-Ingelheim, Gilead Sciences, Inc, Novo Nordisk. Other Relationship; Lexicon Pharmaceuticals, Inc. Speaker's Bureau; Daiichi Sankyo. M. Lindhardt: Advisory Panel; AstraZeneca. Speaker's Bureau; AstraZeneca. Advisory Panel; Bayer Pharmaceuticals, Inc, Boehringer-Ingelheim. Speaker's Bureau; Boehringer-Ingelheim. Advisory Panel; Novo Nordisk, GlaxoSmithKline plc. Other Relationship; Novo Nordisk A/S, AstraZeneca, Eli Lilly and Company, Amgen Inc, Bayer Pharmaceuticals, Inc, Janssen Pharmaceuticals, Inc, Merck Sharp & Dohme Corp. C.K. Tikkanen: Employee; Novo Nordisk. J. Menon: Employee; Novo Nordisk. J. Cattin: None. B. Hunt: Other Relationship; Novo Nordisk. S.J.P. Malkin: Other Relationship; Novo Nordisk. B. Chubb: Employee; Novo Nordisk A/S. Stock/Shareholder; Pfizer Inc. T. Damgaard: Employee; Novo Nordisk A/S, LEO Pharma A/S, Stada Nordic A/S. R. Borg: Advisory Panel; AstraZeneca. Consultant; AstraZeneca. Research Support; AstraZeneca. Advisory Panel; Boehringer-Ingelheim. Consultant; Boehringer-Ingelheim. Research Support; Boehringer-Ingelheim. Consultant; Novo Nordisk A/S. Advisory Panel; Novo Nordisk A/S, Bayer Pharmaceuticals, Inc. Consultant; Bayer Pharmaceuticals, Inc.FundingThe study was supported by funding from Novo Nordisk A/S
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-782-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 783-P: Elucidating the Benefit of Pump-Delivered Subcutaneous GLP-1R
Agonist—Exploratory Study in the DIO Mouse-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 783-P
Abstract: Introduction and Objective: Recent advances in GLP-1R agonist (GLP-1Ra) therapies have transformed diabetes and obesity management. Yet, gastrointestinal side effects and rigid weekly dosing regimens hinder patient adherence, leading to suboptimal outcomes in a real-world setting. We evaluated pump-delivered GLP-1Ra as an alternate treatment approach.Methods: We conducted a 28d study of continuous pump-delivered subcutaneous (SC) short-acting GLP-1Ra (exenatide) in diet-induced obese (DIO) mice (n=60; post-21-week high-fat diet, 60% kcal). We included two control arms: daily SC dosing of vehicle (VEH) or semaglutide (SEMA, 20 nM/kg/day) and three exenatide arms: low basal (LOB, 50 µg/kg/day), low basal + bolus (LBB, basal 30 + bolus 20 µg/kg/day), and high basal + bolus (HBB, basal 50 + bolus 20 µg/kg/day). Basal dosing continued throughout, while bolus and control treatments were given daily at the feeding cycle start. Body weight and food intake were monitored daily, with an oral glucose tolerance test (OGTT) on day 27. Standard t-test analyses were performed.Results: SEMA reduced food intake during initiation (0-5d) to 42% of VEH (p<0.01; SEMA 0.86±0.13, VEH 2.04±0.17 g/day), with intermediate reductions in exenatide arms (LOB 1.32±0.20, LBB 1.50±0.21, HBB 1.21±0.19 g/day). By day 28, SEMA (24.5±1.4%) and HBB (17.3±1.9%) achieved the greatest body weight reductions (p<0.01 vs VEH 4.7±1.2%; LOB 13.9±1.7%, LBB 13.7±1.3%). HBB and LBB attenuated plasma glucose excursion during OGTT (p<0.05; at 60min HBB 167±7, LBB 169±8, VEH 196±8 mg/dl).Conclusion: Pump-delivered GLP-1Ra exhibits favorable body weight and glycemic effects in DIO mice, with a less abrupt initial suppression of food intake than SEMA. Bolus GLP-1Ra also reduced post-caloric challenge glycemic excursion. GLP-1Ra delivered by a basal-bolus pump may represent an alternative for patients seeking GLP-1Ra clinical benefit with greater dosing flexibility. Further clinical evaluation is warranted.DisclosureL. Thisted: None. M. Feigh: None. D.G. Maggs: None.FundingModular Medical
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-783-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 784-P: The First Real-World Experience of the Effectiveness and Safety of
Tirzepatide in Improving Metabolic Parameters in Type 2 Diabetes—A
Six-Month Observational Study from India-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 784-P
Abstract: Introduction and Objective: Tirzepatide, a novel dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist, has demonstrated significant efficacy in improving glycemic control and promoting weight loss in type 2 diabetes (T2DM) management and is approved in India since July 2024. This study aimed to evaluate the effects of a six-month intervention on key metabolic parameters, including body mass index (BMI), glycated hemoglobin (HbA1c), and waist circumference (WC). Additionally, the study explored correlations between changes in these parameters and clinical variables, such as treatment dose and liver enzymes (SGOT, SGPT), to assess tirzepatide's efficacy in improving metabolic health.Methods: Baseline and six-month follow-up data were collected from participants undergoing treatment with tirzepatide. Paired t-tests were used to analyze changes in BMI, HbA1c, and WC, while correlation analyses explored relationships between these changes and treatment doses.Results: Significant reductions in BMI (ΔBMI = −10.90 ± 3.45, p < 0.001), HbA1c (ΔHbA1c = −1.48 ± 0.87, p < 0.001), and WC (ΔWC = −8.15 ± 3.20, p < 0.01) were observed. A positive correlation was found between BMI and HbA1c reductions (r = 0.51, p = 0.002), as well as between treatment dose and changes in BMI (r = 0.43, p = 0.015) and HbA1c (r = 0.47, p = 0.010). SGOT and SGPT trends suggested potential metabolic associations.Conclusion: Tirzepatide demonstrated significant improvements in BMI, HbA1c, and WC, with dose-dependent effects and correlations between metabolic changes in Indian T2DM patients. These findings highlight the intervention's potential to enhance metabolic health. Further research with larger cohorts and comprehensive data collection is warranted to validate these results.DisclosureP.M. Chawla: None. M.S. Chawla: Advisory Panel; Eli Lilly and Company, Novo Nordisk, Abbott, Sanofi, Lupin Pharmaceuticals, Inc, Medtronic, Cipla, Merck & Co., Inc. A. Shaikh: None. B.D. Saboo: None. S.S. Samajdar: None. S. Mukherjee: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-784-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 785-P: First Report on the Small Molecule Oral GLP-1 Receptor Agonist
RGT-075 in Obesity—A Randomized, Placebo-Controlled Phase 2a
Proof-of-Concept Twelve-Week Study-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 785-P
Abstract: Introduction and Objective: GLP-1 RA peptides are highly effective treatments for type 2 diabetes (T2D) and obesity. However, mainly injectable options are available except for oral semaglutide. RGT-075 is a novel, non-peptide, small molecule oral GLP-1 RA being developed as a treatment for adults with obesity.Methods: This phase 2a, randomized, double-blind trial (NCT06277934) involved adults with obesity (BMI ≥ 30 kg/m²) or overweight (BMI ≥ 27 kg/m²) with at least one comorbidity and no T2D (HbA1c < 6.5%). Participants (N=73) were randomly assigned to either 125 mg of RGT-075 or placebo once daily for 12 weeks, with a 6-week dose titration (from 15 to 125 mg QD) followed by a 6-week dose maintenance period (125 mg QD).Results: Baseline characteristics were generally comparable between the groups (mean age 50.2 yrs, Weight 102.5 kg, BMI 37.1 kg/m²). Out of the total participants, 50 received RGT-075, and 23 received placebo. At week 12, the LS mean percentage change in body weight was -5.4% with RGT-075 (no plateau) compared to -0.45% with placebo (p < 0.0001). In addition, a significant and clinical meaningful reduction of systolic (-10.8 mmHg (placebo adjusted), p = 0.0022) and diastolic (-4.9 mmHg (placebo adjusted), p = 0.0371) blood pressure was observed. There was no increase in pulse rate. The most frequently reported adverse events in the RGT-075 group were nausea (40%) and vomiting (24%), which were mild or moderate. No liver abnormalities or other serious adverse events related to RGT-075 were observed. The discontinuation rate due to adverse events (AEs) was 4% for both RGT-075 and placebo. The pharmacokinetic profile supported once-daily (QD) oral dosing.Conclusion: RGT-075, a small molecule oral GLP-1 RA, demonstrated a significant weight reduction with robust blood pressure changes and a safety profile consisted with the GLP-1 RA class. These findings support further clinical development of RGT-075.Disclosure J. Rosenstock: Advisory Panel; Amgen Inc. Research Support; Amgen Inc. Advisory Panel; Applied Therapeutics. Research Support; Applied Therapeutics, AstraZeneca. Advisory Panel; Bayer Pharmaceuticals, Inc, Biomea Fusion, Corcept Therapeutics, Eli Lilly and Company. Research Support; Eli Lilly and Company. Advisory Panel; Hanmi Pharm. Co., Ltd. Research Support; Merck & Co., Inc, Novartis AG. Advisory Panel; Novo Nordisk. Research Support; Novo Nordisk, Pfizer Inc. Advisory Panel; Regeneron Pharmaceuticals. Research Support; Regeneron Pharmaceuticals, Regeneron Pharmaceuticals. Advisory Panel; Regor Therapeutics, Roche Pharmaceuticals, Sanofi. Research Support; Sanofi. Advisory Panel; Structure Therapeutics, Inc, Zealand Pharma A/S. D. Lender: None. F. Raiser: None. D. Guzman: None. K.O. Crawford: Consultant; Structure Therapeutics, Inc. J. Lin: None. F. Sun: None. Q. Cai: Employee; Regor Therapeutics. F. Liu: Employee; Regor Pharmaceuticals Inc. M. Grimm: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-785-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 786-P: Demographic and Clinical Characteristics Associated with Real-World
Persistence on Semaglutide for Weight Management in the USA-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 786-P
Abstract: Introduction and Objective: Persistence with the injectable glucagon-like peptide-1 receptor agonist (GLP-1RA) semaglutide for weight management has been studied extensively, but drivers of persistence are not well characterized. We sought to identify predictors of persistence in a US real-world population.Methods: Adults (≥18 years old) who had a first claim for semaglutide for weight management (index date) between June 4, 2021 and July 1, 2023 were identified in the IQVIA Ambulatory Electronic Medical Records database, linked to PharMetrics® Plus. Individuals required ≥1 year of continuous enrollment pre-index and ≥1 year of follow-up data. Individuals with previous bariatric surgery were excluded. Discontinuation was indicated by >90 days not covered by the medication. Factors associated with persistence were identified using logistic regression.Results: In total, 42,028 individuals were included. Overall, 78.9% were women and 85.5% were aged ≥35 years; 39.5% had hypertension and 9.4% had T2D. At month 12, 38% were persistent on semaglutide. Predictors associated with persistence (p<0.05) were previous use of liraglutide for weight management (odds ratio [OR] 1.69), age ≥35 years (OR 1.63), and, among people with diabetes, use of other GLP-1RAs (OR 1.21). The following factors were negatively associated with persistence (p<0.05): male sex (OR 0.93), previous use of phentermine (OR 0.87), insulin use in people with diabetes (OR 0.79), and preexisting comorbidities (OR: musculoskeletal pain, 0.95; cerebrovascular disease, 0.84; ischemic heart disease, 0.84; T2D, 0.79; peripheral artery disease, 0.73).Conclusion: In a US real-world population, familiarity with the GLP-1RA class of medications appeared to help with persistence. An additional focus for obesity management with semaglutide should be to provide guidance on what to expect on the treatment journey, in particular for patients at higher risk of discontinuing treatment.Disclosure W.H. Polonsky: Consultant; Abbott. Research Support; Abbott. Consultant; Dexcom, Inc. Research Support; Dexcom, Inc. Other Relationship; Ascensia Diabetes Care. R. Arora: Employee; Novo Nordisk, IQVIA Inc. J. Fernandes: Employee; Novo Nordisk A/S. Stock/Shareholder; Novo Nordisk A/S. T. Arnaut: Employee; Novo Nordisk A/S, Roche Diabetes Care.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-786-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 787-P: GLP-1 Receptor Agonists as Monotherapy Lowered BMI Z-Score in Youth
Newly Diagnosed with Type 2 Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 787-P
Abstract: Introduction and Objective: The efficacy of glucagon-like peptide 1 receptor agonists (GLP-1RA) as monotherapy in newly diagnosed youth with type 2 diabetes (YT2D) is unknown. We hypothesize that GLP-1RA are superior to metformin in HbA1c and BMI reduction in YT2D.Methods: This retrospective review extracted data from YT2D from one urban pediatric hospital. Inclusion criteria included age <21, prescription of GLP1-RA or metformin at diagnosis between September 2019 and December 2023. Study observation (up to one year) excluded visits that included concurrent use of metformin and GLP-1RA. Linear regression models comparing monthly changes in HbA1c and BMI z-score adjusted for initial BMI z-score and HbA1c, gender, and age.Results: The GLP-1RA group was majority female (GLP-1RA [n=12] 84%, metformin [n=118] 50%). The median age of the entire cohort was 14.6 years [IQR 13.0, 16.5] and study duration was 242 [143, 315] days. Monthly HbA1c change was comparable between the groups: GLP-1RA -0.16 [-0.23, -0.11], metformin -0.11 [-0.23, -0.04]. Monthly BMI z-score change favored the GLP-1RA group: GLP-1RA -0.02 [-0.04, -0.01], metformin -0.01 [-0.02, 0.00]. In regression analysis, GLP1-1RA showed greater reductions of BMI z-score (β = -0.031, p = 0.036) but not HbA1c (β = -0.09, p = 0.35).Conclusion: Compared to metformin, GLP-1RA monotherapy in newly diagnosed YT2D lowered BMI z-score but had comparable effect in HbA1c. A randomized controlled study is needed to validate these preliminary findings.DisclosureI. Tejeji: None. T. Zeier: None. N.T. Chang: Consultant; Novo Nordisk. J. Smith: None. L.C. Chao: None.FundingNational Institute of Diabetes and Digestive and Kidney Diseases (1R25DK113652)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-787-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 788-P: A Twelve-Week Trial of MET097—A Potent and Ultra-Long-Acting
GLP-1 Receptor Agonist-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 788-P
Abstract: Introduction and Objective: MET097 is a fully biased, ultra-long acting glucagon-like peptide-1 receptor agonist (GLP-1RA). In Ph1, subcutaneous administration of 5 once-weekly doses of MET097 resulted in mean weight loss of up to 7.5%, which persisted 8 weeks after the last dose. Here, the efficacy and tolerability of MET097 were evaluated over 12 weeks.Methods: A Ph2, multicenter, randomized, double-blind, placebo (PBO)-controlled trial enrolled adults with overweight/obesity (BMI 27-38 kg/m²). The primary endpoint was percent change in baseline body weight at Day 85, analyzed using MMRM. Participants were randomized to once-weekly MET097 or PBO in five dosing cohorts: four titration-free groups (0.6, 0.8, 1.0, 1.2 mg) and one dose-escalation group (0.4/0.8/1.2 mg each taken for 4 weeks).Results: A total of 120 participants had a mean age of 41 yrs, mean BMI of 31.2 kg/m2, and were ~52% female. Most common AEs were GI-related (nausea, vomiting, constipation, and diarrhea), generally dose dependent, and mild/moderate. The dose-escalation group had 5% nausea and 10% vomiting rates. The estimated mean treatment difference from PBO at Day 85 ranged from 6.3% to -11.3% (Fig 1).Conclusion: This 12-week trial demonstrated substantial weight loss with titration-free weekly dosing. Additionally, the two-step escalation arm was exceptionally well tolerated.Disclosure R. Stoekenbroek: Employee; Metsera. J. Bisch: None. S. Kolluri: Employee; Metsera. M.A. Noor: Employee; Metsera, Olatec. J. Mallory: Employee; Metsera, Kriya Therapeutics. R. Cunningham: Employee; Metsera. B. Hubbard: Employee; Metsera. S.P. Marso: Employee; Metsera. Stock/Shareholder; Metsera.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-788-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 789-P: The Use of Antiobesity Medications and the Increased Risk of
Alopecia—A Meta-analysis of Randomized Controlled Trials-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 789-P
Abstract: Introduction and Objective: Alopecia is a potential adverse event of anti-obesity medications (AOMs). Rapid weight loss may result in deficiencies of key nutrients and act as a physiological stressor, potentially disrupting hair growth cycles and increasing hair shedding. This study aimed to evaluate the association between AOMs and risk of alopecia.Methods: PubMed, EMBASE, Cochrane Library, and Clinicaltrial.gov were searched from inception to December 2024. Randomized controlled trials (RCTs) that compared AOMs with placebo or active controls and reported alopecia events were included. The results were computed as odds ratios (OR) with 95% confidence intervals (CI) in random-effect model. Meta-regression analyses were performed to address potential influencing factors.Results: In total, 10 RCTs with 22840 participants were included. Compared with non-users, the use of AOMs was associated with an increased risk of alopecia (OR=3.12, 95%CI, 1.90 to 5.14). The risk of alopecia was much higher in the subgroup with obesity (OR=3.89, 95%CI, 2.37 to 6.37) when compared with the subgroup without obesity (OR=0.68, 95%CI, 0.16 to 2.86, p for subgroup difference=0.02). Meta-regression analyses suggested that greater body weight reduction percentage (β=-0.13, p=0.05) and greater body weight absolute reduction (β=-0.23, p=0.03) were associated with a higher risk of alopecia. However, younger age was associated with an elevated risk of alopecia (β=-0.20, p=0.02).Conclusion: AOMs were associated with an increased risk of alopecia, and the risk of alopecia increased with greater weight reduction. Our findings highlight the need for caution regarding the effects of rapid weight loss on hair health.DisclosureR. Jiao: None. C. Lin: None. Z. Li: None. Y. Guo: None. F. Lyu: None. W. Yang: None. X. Cai: None. L. Ji: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-789-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 790-P: Paradigm Shifts in GLP-1 Receptor Agonist Use Amongst Patients with
Type 2 Diabetes in the United States-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 790-P
Abstract: Introduction and Objective: GLP-1 receptor agonists (GLP-1s) are becoming an increasingly popular diabetes therapy management option for people with type 2 diabetes (T2s) in the U.S. This research sought to characterize changes within the populations and expectations of T2s starting GLP-1s over the past 3 years.Methods: T2s who reported starting a GLP-1 in the past year were surveyed in 2021 (n=200) and 2024 (n=442) on HbA1c, BMI and diabetes-related comorbidities, as well as expected improvements to their health with respect to their GLP-1 use. Additionally, n=576 T2s who reported never having taken a GLP-1 despite being a risk at cardiovascular disease (CVD) were surveyed on why they had never tried this therapy.Results: The health profiles of T2s new to a GLP-1 saw no significant shifts from 2021 to 2024, except for HbA1c; the percentage of those at or below the clinical recommendation of 7.0% increased significantly (46% to 58%, p<0.05). Expected health improvements corroborated this shift, as a significantly lower proportion of respondents reported starting a GLP-1 to improve their glycemic control (84% to 75%, p<0.05). Notably, the proportion of those taking GLP-1s for weight loss increased significantly (59% to 70%, p<0.05), despite no change in the percentage of those with a BMI ≥30. Of T2s at risk of CVD who had never taken a GLP-1, 39% reported never having discussed GLP-1s as an option to improve their heart health with their HCP and 21% reported no awareness of the cardiovascular benefits of GLP-1s. This aligns with data found with respect to T2s new to a GLP-1 - over the past 3 years, the proportion of those new to a GLP-1 with heart problems and the percentage of those who reported starting a GLP-1 to improve their heart health has not changed.Conclusion: Results show that paradigms with respect to GLP-1 use amongst T2s has shifted from being a therapy mainly for diabetes management to being primarily for weight management, while auxiliary benefits of GLP-1s, including lowering CVD risk, may not be well understood by the T2 patient population.Disclosure J. Lee: Employee; dQ&A. A. Beltran: Research Support; Abbott, Dexcom, Inc., Eli Lilly and Company, diaTribe, Insulet Corporation, Medtronic, Ascensia Diabetes Care, Tandem Diabetes Care, Inc, Sequel Med Tech, Beta Bionics, Inc, Zucara Therapeutics. T. Bell: Research Support; Abbott, Dexcom, Inc., Tandem Diabetes Care, Inc, Medtronic, MannKind Corporation, Insulet Corporation, CeQur, Beta Bionics, Inc, Eli Lilly and Company, Ypsomed AG. T.L. Bristow: None. R. Wood: Other Relationship; Abbott, diaTribe, Glooko, Inc, Dexcom, Inc., Medtronic, Lilly Diabetes, Insulet Corporation, Sanofi-Aventis U.S., Tandem Diabetes Care, Inc, Zucara Therapeutics.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-790-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 791-P: Study of Serum Adiponectin Levels in Type 2 Diabetes Mellitus
Patients and Its Correlation with Clinical Parameters-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 791-P
Abstract: Introduction and Objective: Low adiponectin levels are predictive markers for T2DM development and contribute to increased cardiovascular risk. Adiponectin-targeted therapies may improve metabolic outcomes in T2DM. This study examines adiponectin levels among T2DM patients, focusing on variations across treatment regimens.Methods: This cross-sectional study included adults aged 40-70 years which are divided into three groups: newly diagnosed T2DM patients not on oral antidiabetic drugs (group 1), patients on glimepiride and metformin (group 2), and those on vildagliptin and metformin (group 3). Coronary risk and atherogenic risk were calculated. Quantitative variables were compared between groups using Student's t-test or Mann-Whitney U test in SPSS 21.Results: The study included 76 patients, divided into three groups: 13 in Group 1, 33 in Group 2, and 30 in Group 3. Adiponectin levels in the group 1, group 2 and group 3 were 10.96μg/ml, 11.09μg/ml and 11.58μg/ml respectively but was not statistically significant. However, the adiponectin levels between the sub-groups at the high dose vildagliptin/metformin (100mg) combination was significant (p=0.045) compared to lower dose. The coronary risk index and atherogenic index was lowest in group 3 compared to group 1 and group 2 but was not statistically significantConclusion: The combination of vildagliptin (100mg/day) and metformin (1000mg/day) significantly increased adiponectin levels, suggesting its potential anti-atherogenic effect by elevating HDL-C and reducing the coronary risk index. This study suggests DPP-4 inhibitors may help improve adiponectin levels, but larger studies are needed to confirm these findings and guide clinical recommendationsDisclosureA. Reddy: None. M.M. Prabhu: None. R. Suvarna: None. S. Nagaraju: None. P.A. Kamath: None.FundingInstitutional Resident research
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-791-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 792-P: Effect of Bone Metabolism and the Efficacy of Evogliptin and
Dapagliflozin for Blood Sugar in the Menopause Female Patients with Type 2
Diabetes—A Multicenter Randomized Exploratory Clinical Trial-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 792-P
Abstract: Introduction and Objective: Postmenopausal women with diabetes are susceptible to osteoporosis, and the appropriate choice of antidiabetic medication is important not only for glycemic control but also for osteoporosis prevention. This study evaluated the effects of Evogliptin and Dapagliflozin on bone metabolism in postmenopausal women with T2DM and compared their glucose-lowering effects.Methods: This multicenter, randomized clinical trial enrolled postmenopausal women with T2DM. Participants were assigned to receive either Evogliptin or Dapagliflozin for 48 weeks. Changes in Bone mineral density (BMD) and bone turnover markers were primary outcomes, and diabetes-related indices were secondary outcome.Results: After 48 weeks, no significant intergroup differences in BMD changes were observed for the L1-L4 spine and total hip. However, for the femoral neck, the Evogliptin group showed a change of 0.00 ± 0.02 (p = 0.9620) versus -0.02 ± 0.04 (p = 0.0275) in the Dapagliflozin group, yielding a significant intergroup difference (p = 0.0402). Similar trends were noted in T-score, with significant intergroup differences at the femoral neck (p = 0.0337) and total hip (p = 0.0011). BMI decreased by -0.42 ± 0.95 in the Evogliptin group and -1.14 ± 1.07 in the Dapagliflozin group, with a significant intergroup difference (p = 0.0085).For diabetes-related indices (HbA1c, fasting blood glucose, etc.), no significant differences were observed between groups at any time point.Conclusion: In postmenopausal patients with T2DM, Evogliptin demonstrated a more favorable safety profile regarding BMD compared to Dapagliflozin. Dapagliflozin resulted in small but significant reductions in BMD or T-score at non-vertebral bone, due at least in part to weight loss. These findings provide evidence for selecting appropriate antidiabetic medications in postmenopausal women with osteoporosis.Disclosure H. Ryu: Other Relationship; Dong-A ST. K. Baek: None. H. Chung: None.FundingDong-A ST
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-792-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 793-P: Disparities in Adoption of Drugs with Cardiovascular and Renal
Benefits-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 793-P
Abstract: Introduction and Objective: The novel diabetes drug classes, glucagon-like receptor peptide 1 receptor agonists (GLP-1RA) and sodium-glucose transporter 2 inhibitors (SGLT2i), reduced macrovascular and renal risk in landmark trials published in 2015 and 2016. However, adoption of GLP-1RA and SGLT2i in the type 2 diabetes population has been slow and favors healthier, socio-economically privileged, and non-Hispanic White groups. My objective is to update the literature on disparities in adoption of GLP-1RA and SGLT2i.Methods: I utilized electronic medical record (EMR) data from 2016-2023 at a large academic institution. Adults aged 18-85 with type 2 diabetes were included. The outcome of adoption was defined an order in the dataset for GLP-1RA or SGLT2i. The main predictor was self-reported race and ethnicity. Covariates included demographics, patient health, provider specialty, and clinic setting. I employed multi-level linear probability models.Results: 8,063 patients were included in the dataset. Of these, 43% had an order for an SGLT2i or GLP-1RA medication during the period. In unadjusted analyses, 41% of non-Hispanic White, 39% of non-Hispanic Black, 47% of Hispanic, and 35% of Asian patients received either class of medication. After adjustment for demographics, patient health, provider specialty, and clinic setting, Asians were 3 percentage points less likely to receive medication (SE=0.01, P=0.01); blacks had a non-significant 2 percentage point lower rate of receiving the medications, while Hispanics were even.Conclusion: Use of either drug has surged to 43% of all patients with type 2 diabetes. Racial and ethnic disparities are attenuated, except in the Asian American population, in which moderately lower rates use of the novel drugs was observed. This may be due to a combination of increased clinical inertia for this population among providers, or due to patient preferences or tolerance for the drugs. Further research is necessary to elucidate this trend and ensure the equitable use of effective novel medications for all populations.DisclosureH.A. Torres: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-793-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 794-P: MET-097: Preclinical Characterization of a Potent and
Ultra-Long-Acting GLP-1 Receptor Agonist-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 794-P
Abstract: Introduction and Objective: MET-097 is a potent, fully Gs protein biased glucagon-like peptide-1 receptor agonist (GLP-1RA) currently in phase 2 development for overweight and obesity. Using HALO™ technology, MET-097 was engineered for sustained half-life (t1/2) to potentially allow less frequent dosing. Here we describe the pharmacology of MET-097 in preclinical species in comparison to other NuSH therapies.Methods: The pharmacokinetics of MET-097 were determined after single and repeat subcutaneous (SC) administration to rats and pigs. The impact of MET-097 on weight was measured in DIO mice over 22 d and compared to equimolar doses of semaglutide, tirzepatide, and other multi-agonists.Results: The t1/2 of MET-097 was determined to be 24 h in rats and 99 h in pigs, both longer than the t1/2of semaglutide (7.2 h and 46.1 h, literature values). Daily SC administration led to body weight loss that was significantly greater for MET-097 than for semaglutide and tirzepatide (all P values <0.001). At one-third the dose in DIO mice, MET-097 was equally effective as semaglutide and tirzepatide for body weight loss.Conclusion: Preclinical characterization of MET-097 suggests best-in-class efficacy and an ultra-long t1/2 for MET-097. The long t1/2 of MET-097 may unlock versatile dosing options and scalability advantages due to superior weight loss per mg of peptide.Disclosure C. Hinds: Employee; Metsera, Zihipp. J.S. Minnion: Stock/Shareholder; Metsera. Employee; Zihipp. G. Zoumpoulidou: Employee; Metsera.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-794-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 795-P: Efficacy and Safety of RAY1225 Once Every Two Weeks in Chinese
Adults with Type 2 Diabetes (SHINING-1)-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 795-P
Abstract: Introduction and Objective: To investigate the efficacy, safety, and tolerability of RAY1225, a novel once every two weeks GLP-1 and GIP receptor dual agonist, in Chinese adults with Type 2 diabetes (T2DM).Methods: This phase 2 double-blind, randomized, placebo-controlled trial included 2 parts. The target dose of part A was 3mg,6mg, and that of part B was 9mg and above with dose escalation and extension. Chinese T2DM adults naive or uncontrolled on Metformin, alpha-glucosidase or SGLT-2 inhibitors with a 7.0% ≤ HbA1c ≤11.0% were randomized. In part A, eligible participants were randomly assigned 1:1:1 to receive 3mg, 6mg RAY1225 or placebo subcutaneously once every two weeks for 24 weeks. In part B, the randomization ratio was 4:1 to receive 9 mg (or above dose) or placebo. The primary endpoint was the change in HbA1c at week 24.Results: A total of 132 participants were analyzed from part A and part B with dose escalated up to 9mg till now. At baseline, the mean (standard deviation) HbA1c was 8.10 (1.03) %, body weight was 77.73 (15.41) kg, BMI was 28.33 (4.18) kg/m2, and about 38.0% of participants naive to antidiabetic drugs. The reduction in HbA1c from baseline to week 24 was -1.67% (95% CI -1.91 to -1.42), -2.07% (-2.32 to -1.83), -2.24% (-2.78 to -1.70) in the 3 mg, 6mg and 9 mg, respectively, versus -0.23% (-0.47 to 0.01) with placebo (P<0.0001). More participants on RAY1225 achieved HbA1c<7% targets(80.0~100.0% Vs. 32.4%, P<0.001). All RAY1225 doses led to superior body weight reduction at week 24. In addition, RAY1225 is also beneficial in the improvement of cardiometabolic indexes. The most common adverse events (AEs) with RAY1225 were mild to moderate gastrointestinal AEs, occurring primarily during dose escalation. No severe hypoglycemia was reported, and no drug related serious AEs occurred.Conclusion: This study showed RAY1225 once every two weeks subcutaneous injection was generally well tolerated and demonstrated superior reduction in HbA1c in Chinese adults with T2DM.DisclosureL. Ji: None. L. Gao: Research Support; Sciwind Biosciences. X. Dong: None. X. Huang: None. X. Zhang: None. Y. Zheng: None. C. Wang: None. L. Yan: None. J. Li: Employee; Guangdong Raynovent Biotech Co., Ltd. Y. Peng: Employee; Raynovent. H. Li: Employee; Guangdong Raynovent Biotech Co., Ltd. X. Chen: Employee; Guangdong Raynovent Biotech Co., Ltd.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-795-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 796-P: Interactive Education Increases Likelihood of Guideline-Based
Incretin Therapy Prescribing in T2D-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 796-P
Abstract: Introduction and Objective: To align with evidence-based practice, diabetes care plans must prioritize weight loss in comprehensive management. However, primary care providers often do not implement effective weight loss strategies in diabetes care. The objective of this study was to determine the impact of an interactive educational program on changes in knowledge, competence, and self-reported performance with weight management in diabetes care.Methods: In 2023, physicians, NPs, and PAs in primary care participated in either an in-person or live virtual interactive, case-based educational program focused on the guidelines and strategies for prioritizing weight loss in comprehensive diabetes management. Participants responded to a series of case-based, multiple-choice questions before, after, and 3-months following the program to assess changes in knowledge, competence, and self-reported performance.Results: Learners (n=1025) had statistically significant increases across the domains of knowledge, competence, self-reported performance from baseline to post-survey (p<0.001) and further increases in the 3-month follow-up survey.Conclusion: Case-based, interactive educational formats are effective strategies for increasing primary care provider knowledge, competence, and performance with prioritizing weight loss in diabetes management.DisclosureE. Brechtelsbauer: None. R.L. Black: None. P. Langdon: None.FundingLilly USA (A-33818)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-796-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 797-P: Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of
HRS9531 Tablet, an Oral Dual GLP-1/GIP Receptor Agonist, in Healthy
Participants—A Phase 1 Study-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 797-P
Abstract: Introduction and Objective: HRS9531 injectable formulation, a dual GLP-1 and GIP receptor agonist, showed promising glycemic control and weight loss efficacy in phase 2 trials. Administration of HRS9531 tablet instead of an injectable formulation can improve patient convenience, acceptance, and adherence. This study evaluated the safety of HRS9531 tablet with single ascending dose (SAD) and determined an initial acceptable dose with multiple ascending dose (MAD) in healthy participants.Methods: In the SAD, healthy participants were randomized (3:1) to receive single dose of HRS9531 tablet (3, 10, 25 or 50 mg) or placebo. In the MAD, healthy participants were randomized (4:1) to receive HRS9531 tablet (10 mg or 10mg/25 mg [each dose for 2 weeks]) or placebo daily for 4 weeks. The primary endpoints for both parts were safety and tolerability.Results: A total of 32 and 40 participants were enrolled in SAD and MAD, respectively. All treatment emergent adverse events (TEAEs) were mild or moderate in severity in participants treated with HRS9531. The most common TEAEs in SAD were gastrointestinal (nausea, vomiting and abdominal distension) and in MAD were hyperuricemia, hypertriglyceridemia, and nausea. No serious adverse events or hypoglycemic episodes were reported. Exposure of tablet HRS9531 generally increased with the dose and the disposition after absorption is in line with the injectable formulation, with an elimination half-life of approximately ~168 hours. In MAD, the mean weight loss on Day 29 was 3.8 kg (4.7%) and 4.4 kg (5.4%) in the 10 mg and 10/25 mg groups, respectively, versus 1.6 kg (1.9%) in the placebo group. Fasting plasma glucose levels decreased in a dose-dependent manner.Conclusion: HRS9531 tablet showed a favorable safety and tolerability profile, with noticeable reductions in body weight and glucose levels. Results support further clinical development of HRS9531 tablet for metabolic disorders.DisclosureW. Hu: None. Y. Du: None. Q. Zhang: None. H. Chen: None. L. Zheng: None. X. Yu: None. J. Wu: None. J. Wang: Employee; Jiangsu Hengrui Pharmaceuticals Co., Ltd. Y. Wang: Employee; Jiangsu Hengrui Pharmaceuticals Co., Ltd. X. Lin: None. L. Li: None.FundingJiangsu Hengrui Pharmaceuticals Co., Ltd.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-797-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 798-P: Semaglutide Effect during Mixed-Meal Tolerance Test (MMTT) with
Fully Closed-Loop Therapy in Type 1 Diabetes (T1D)-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 798-P
Abstract: Introduction and Objective: We assessed glycemia, insulin needs, and C-peptide levels with semaglutide after MMTT in type 1 diabetes.Methods: This is a sub-analysis of a randomized crossover trial assessing semaglutide vs. placebo with automated insulin delivery (AID) in adults with T1D (NCT05205928). Participants performed a MMTT with 6 mL/kg of Boost, while using fully-closed-loop AID, after 12 weeks of semaglutide and placebo, in random order. Plasma glucose and C-peptide levels were measured over 120 minutes. C-peptide levels <0.003 nmol/L assumed to be 0 nmol/L. Paired t-test was performed for parametric comparisons, with Wilcoxin signed-rank test for non-parametric comparisons.Results: Ten participants completed the MMTT, with 8 having C-peptide levels and 7 having pump data; 40% were female, with age 47 (SD 14) years and T1D duration 29 (11) years. All but one had baseline C-peptide of < 0.003 pmol/L. Semaglutide reduced glucose AUC compared to placebo (p=0.006), but C-peptide AUC was not different between arms (p=0.35). Despite having lower glucose AUC, the insulin delivery by the AID was lower for semaglutide than placebo (p = 0.024).Conclusion: Semaglutide reduced glucose AUC during fully closed-loop therapy after weight-adjusted meal replacement, with less insulin output required from the AID. Further studies are needed to understand mechanistic of effects.Disclosure M. Pasqua: Speaker's Bureau; Abbott, Sanofi, Medtronic. J. Doumat: None. A. Jafar: None. M. Tsoukas: Speaker's Bureau; Novo Nordisk, Eli Lilly and Company, Boehringer-Ingelheim, Janssen Pharmaceuticals, Inc, Sanofi. A. Haidar: Research Support; Tandem Diabetes Care, Inc. Consultant; Eli Lilly and Company, Abbott. Research Support; ADOCIA, Dexcom, Inc., Ypsomed AG, Bigfoot Biomedical, Inc.FundingCanada Research Chair in Artificial Pancreas Systems.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-798-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 799-P: Cellular Characterisation of Signalling and Receptor Trafficking
Induced by MET-097, a G Protein-Biased GLP-1R Agonist-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 799-P
Abstract: Introduction and Objective: The ultra-long acting GLP-1R mono-agonist peptide MET-097 is in Phase 2 development for overweight and obesity. Earlier investigation indicated MET-097 is a G protein-biased agonist, contrasting with the balanced agonist semaglutide. We aimed to further elucidate the signalling and trafficking profile of MET-097.Methods:In vitro BRET-based biosensors were used to compare clinically relevant GLP-1R agonists.Results: Compared to reference agonists (GLP-1/exendin-4/semaglutide), MET-097 acted as a partial agonist for Gαs and Gαq recruitment at both the plasma membrane (36% and 22% of exendin-4) and endosomal compartments (34% and 37% of exendin-4), yet still showed full cAMP response (115% of exendin-4). A pronounced reduction in β-arrestin-2 recruitment (17% of exendin-4) was also observed, indicating efficacy-driven G protein bias. Interestingly, β-arrestin-2 recruitment was out of proportion with hGLP-1R internalisation (68% of exendin-4), suggesting additional mechanisms for internalisation. Similar responses were observed with retatrutide, tirzepatide, orforglipron and danuglipron.Conclusion: We speculate the pharmacological attributes of MET-097 may contribute to a unique pharmacodynamic profile. Of particular interest will be to align these attributes with the efficacy and tolerability observed in clinical trials.Disclosure B.P. Baxter: Research Support; Metsera. S. Bloom: Research Support; Metsera. Employee; Metsera. Stock/Shareholder; Metsera. Other Relationship; Zihipp. B. Jones: Research Support; Metsera. Consultant; Metsera. Research Support; Eli Lilly and Company.FundingMetsera
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-799-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 801-P: Bioequivalence of Insulin Efsitora Alfa (Efsitora) U-500 and U-1000
Formulations-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 801-P
Abstract: Introduction and Objective:Background: Efsitora is a novel basal insulin designed for once-weekly administration. The U-1000 formulation (1000 Units/mL) is an alternate dose strength of efsitora that provides an option for patients with diabetes who require a higher basal insulin dose.Methods:Methods: This randomized, double-blind, 2-period, 2-sequence crossover study (NCT05615532) assessed the pharmacokinetics (PK) after a 100 U subcutaneous dose of U500 or U1000 efsitora in 66 healthy subjects (mean ± SD age 44.8 ± 10.6 y). Blood was sampled for pharmacokinetics for 65 days (~9 weeks) post-dose.Results:Results: Similar mean PK profiles were observed after dosing U-500 or U-1000 formulation of efsitora (Figure 1). All 90% CIs for the ratios of total efsitora exposure or maximum efsitora concentration of U-500 and U-1000 formulation were contained within the established bioequivalence (BE) limits 0.80 to 1.25. The tolerability of the U-500 and U-1000 efsitora formulations were comparable.Conclusion:Conclusion: This study demonstrated that U-500 and U-1000 efsitora formulations were BE, supporting the ability of patients to transfer between U-500 and U-1000 in a 1:1 unit conversion.Disclosure J. Leohr: Employee; Eli Lilly and Company. A. Ghosh: None. D.G. Waters: Employee; Eli Lilly and Company. T. Fukuda: Employee; Eli Lilly and Company. S. Suriyapperuma: Employee; Eli Lilly and Company.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-801-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 802-P: Steady-State Pharmacokinetics and Glucodynamics of Once-Weekly
Insulin Efsitora Alfa (Efsitora) in Individuals with Type 2 Diabetes (T2D)
-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 802-P
Abstract: Introduction and Objective: Efsitora is a novel basal insulin designed for once-weekly administration.Methods: This multiple-dose, euglycemic clamp study assessed steady-state pharmacokinetics (PK) and glucodynamics of efsitora in 56 adults with T2D without prior insulin treatment (mean [±SD] age, 61.9 ± 5.98 years; HbA1c, 7.1 ± 0.64%; BMI, 31.7 ± 3.20 kg/m2). After a lead-in period with once-daily degludec for dose-finding, eligible participants received a one-time starting dose of 12 U/kg efsitora and weekly doses of 4 U/kg for 9 weeks. After the last dose of efsitora, 24-hour clamps were conducted on Days 1, 4, and 7.Results: Clinical steady-state (90% of trough steady-state) was achieved for efsitora between the 3rd and 5th weekly dose using a one-time starting dose. At steady-state, the model-predicted glucose infusion rate profile over the weekly dosing interval demonstrated a stable glucose-lowering effect of efsitora (Figure 1). The maximum glucose infusion rate occurred on Day 4 with low day-to-day variability. Efsitora was safe and well tolerated, as observed in prior studies.Conclusion: Efsitora demonstrated a flat and prolonged PK profile providing a constant level of insulin and as a result a stable glucose lowering response across the weekly dosing interval.Disclosure J. Leohr: Employee; Eli Lilly and Company. O. Klein: None. T. Heise: Research Support; ADOCIA, Afon Technology, AstraZeneca, Altimmune Inc, Biocon, BIOTON, Civica Foundation, Eli Lilly and Company, Zealand Pharma A/S, Betagenon, Cass Pharmaceuticals, Novo Nordisk A/S, Corteria, Zealand Pharma A/S, Cytoki, Enyo Pharma, Gan & Lee Pharmaceuticals, Genova, Nanexa, Neodyne, SamChunDang Pharma. Co., Spiden, Sun Pharmaceutical Industries Ltd. Speaker's Bureau; Eli Lilly and Company, Novo Nordisk A/S. Consultant; Gan & Lee Pharmaceuticals. J.M. Bue-Valleskey: Employee; Eli Lilly and Company. S. Suriyapperuma: Employee; Eli Lilly and Company. M.G. Case: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. D.G. Waters: Employee; Eli Lilly and Company. E.J. Pratt: Employee; Eli Lilly and Company. E. Zijlstra: None. H. Linnebjerg: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-802-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 803-P: Success of Virtual Patient Simulation on Improving Basal Insulin
Initiation in People with T2D-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 803-P
Abstract: Introduction and Objective: This study examines the impact of online, virtual patient simulation (VPS)-based continuing medical education (CME) on performance related to basal insulin initiation in T2D by primary care physicians (PCPs) and diabetologists/endocrinologists (D/Es).Methods: The intervention was 1 patient case in a VPS open-ended platform. Tailored clinical guidance (CG) based on guidelines was provided after each decision with the option to modify the decisions. Decisions were collected post-CG and compared with each user’s baseline (pre-CG) decisions using a McNemar’s test to determine P values. The activity posted October 27, 2023 and data were collected for 1 year.Results: 324 PCPs and 67 D/Es were included. Case: 48 YO with HTN and T2D (current A1c 8.7%). PCPs: Initiate basal insulin therapy: 36% absolute improvement (P<.001; baseline 6%). Of PCPs who initiated basil insulin, 70% prescribed a dose in the guideline-recommended range (25% prescribed a dose higher than recommended by guidelines). D/Es: Initiate basal insulin therapy: 30% absolute improvement (P<.001; baseline 13%). Of D/Es who initiated basil insulin, 29% prescribed a dose in the guideline-recommended range (70% prescribed a dose higher than recommended by guidelines). Top PCP rationale for selecting either glargine/degludec was efficacy, followed by duration of action, compared to duration of action, followed by efficacy, for D/Es. Top rationale for NOT selecting glargine/degludec among PCPs was lack of familiarity with basal insulin compared to avoiding side effects or patient reluctance among D/E. Continued Gaps: 57%-58% of both PCPs and D/Es failed to initiate basal insulin despite clinical guidance.Conclusion: VPS that immerses and engages specialists in an authentic and practical learning experience can improve evidence-based clinical decisions by PCPs and D/Es related to initiation of basal insulin in T2D. Continued gaps were identified for future educational initiatives.DisclosureA. Larkin: None. M. LaCouture: None.FundingIndependent educational grant from Novo Nordisk
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-803-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 804-P: A1C and Hypoglycemia Outcomes with Once-Weekly IcoSema vs.
Comparators in T2D by Kidney Function-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 804-P
Abstract: Introduction and Objective: This post hoc analysis assessed treatment outcomes of IcoSema (a once-weekly combination of basal insulin icodec [icodec] and semaglutide) vs icodec (COMBINE 1), semaglutide 1.0 mg (COMBINE 2), and daily basal-bolus therapy (insulin glargine U100 + insulin aspart) (COMBINE 3) in adults with T2D by kidney function subgroups.Methods: Treatment outcomes were assessed by kidney function subgroup at baseline (eGFR ≥90; 60-<90; 30-<60; <30; all mL/min/1.73m2) by trial.Results: For IcoSema vs comparators, there were no meaningful interactions between treatment and kidney function subgroup for A1C reduction (baseline to week 52; Fig), rates of combined clinically significant or severe hypoglycemia (only assessed for COMBINE 1 and 3), and achievement of A1C <7% at week 52 without weight gain and without combined clinically significant or severe hypoglycemia. Estimated treatment differences/ratios for these outcomes were generally consistent, with no clear trend across kidney function subgroups.Conclusion: For IcoSema vs comparators, A1C reductions, combined clinically significant or severe hypoglycemia rates, and achievement of A1C <7% without weight gain and combined clinically significant or severe hypoglycemia were generally consistent across kidney function subgroups.DisclosureL. Ji: None. M. Benamar: Employee; Novo Nordisk A/S. B. Harvey: Employee; Novo Nordisk A/S. A. Navarria: Employee; Novo Nordisk A/S. Stock/Shareholder; Novo Nordisk A/S. P. Ponzani: Speaker's Bureau; Eli Lilly and Company. Advisory Panel; Novo Nordisk. Research Support; Novo Nordisk, Novartis AG, Bayer Pharmaceuticals, Inc, AstraZeneca. Speaker's Bureau; Menarini. Advisory Panel; Sanofi. Speaker's Bureau; Sanofi. A. Unnikrishnan: Speaker's Bureau; Eli Lilly and Company, Mankind Pharma Ltd, Novo Nordisk, Sanofi. R.R. Rea: None.FundingNovo Nordisk A/S
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-804-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 805-P: Early Glycemic Improvement When Switching to iGlarLixi from
Premixed Insulins (PI) in Adults with Type 2 Diabetes (T2D)—A Post Hoc
Analysis of Soli-SWITCH-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 805-P
Abstract: Introduction and Objective: Maintaining glycemic control when de-intensifying insulin therapy is key to prevent the need for rescue therapy and long-term complications in adults with T2D. This post hoc analysis of Soli-SWITCH assessed glycemic parameters up to Week 12 after switching from PI to iGlarLixi (insulin glargine 100 U/mL + lixisenatide).Methods: Soli-SWITCH (EudraCT: 2021-003711-25) was a Phase 4, 24-week, single-arm study. Adults with T2D switched from once- or twice-daily PI to once-daily iGlarLixi at baseline. The mean change in A1c and mean 7-point self-measured plasma glucose (SMPG) from baseline to Week 12, weekly mean fasting SMPG and mean daily insulin dose to Week 12 were assessed.Results: A total of 162 participants received iGlarLixi. Least squares mean change (LSMC) in A1c from baseline (8.5%) to Week 12 was -1.2% (95% CI, -1.3, -1.1). From baseline (184.0 mg/dL) to Week 12, LSMC in mean 7-point SMPG was -44.5 mg/dL (95% CI -48.9, -40.0). A mean fasting SMPG target of 80-130 mg/dL, recommended by the American Diabetes Association, was met at Week 3 and continued to improve to Week 12 (Figure 1). Mean daily insulin doses from screening to Week 12 are shown in Figure 1.Conclusion: In adults with T2D who switched from PI to iGlarLixi, glycemic control improved in the first weeks of transitioning (Weeks 0-3) and continued to improve to Week 12.Disclosure M. Haluzik: Research Support; Sanofi. Advisory Panel; Eli Lilly and Company. Speaker's Bureau; Novo Nordisk, Abbott. Advisory Panel; AstraZeneca. Speaker's Bureau; GlaxoSmithKline plc, Amgen Inc. Advisory Panel; Bausch Health. F. Lauand: Employee; Sanofi. K. Djaballah: Employee; Sanofi. L. Melas-Melt: None. A. Malha: Advisory Panel; Novo Nordisk. Other Relationship; Sanofi. M. Almehthel: Advisory Panel; Novo Nordisk. Speaker's Bureau; Novo Nordisk. Research Support; Novo Nordisk. Advisory Panel; Sanofi. Speaker's Bureau; Sanofi. Research Support; Sanofi. Speaker's Bureau; Lilly Diabetes. Advisory Panel; Abbott. Speaker's Bureau; Abbott. Advisory Panel; Dexcom, Inc. Speaker's Bureau; Bayer Pharmaceuticals, Inc. S. Yoo: None. J. Kesavadev: None. R. Sari: None.FundingSanofi
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-805-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 806-P: Glycemic Outcomes When Switching to iGlarLixi from Premixed Insulin
(PI) in People with Type 2 Diabetes (T2D) by iGlarLixi Pen
Subgroups—Post Hoc Analysis of Soli-SWITCH-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 806-P
Abstract: Introduction and Objective: Soli-SWITCH (EudraCT number 2021-003711-25) was a single-arm study that assessed the efficacy and safety of once-daily iGlarLixi (insulin glargine 100 U/mL + lixisenatide) in adults with T2D switching from once- or twice-daily PI. Two iGlarLixi pens were available, the 2:1 pen and 3:1 pen, to allow titration up to 60 dose-steps. This post hoc analysis of Soli-SWITCH assessed glycemic outcomes by iGlarLixi pen subgroup.Methods: Data were analyzed by iGlarLixi pen subgroup, defined by the pen participants used most during the study. At baseline (BL), participants initiated either the 2:1 pen or 3:1 pen depending on their previous total PI dose (dose adjustable during study). Mean change in HbA1c, fasting plasma glucose (FPG), post-prandial glucose (PPG) and percentage of participants without glycemic control deterioration from BL to Week 24 were assessed.Results: See Table 1. A total of 162 participants enrolled. BL characteristics differed between pen subgroups, including BMI. Across pen subgroups, HbA1c, FPG and PPG improved from BL to Week 24.Conclusion: In people with T2D switching from PI, glycemic improvements were similar across iGlarLixi pen subgroups, despite differences in BL characteristics. This highlights the flexibility of iGlarLixi to adapt to insulin dose needs and optimize Lixi dosage.Disclosure M. Haluzik: Research Support; Sanofi. Advisory Panel; Eli Lilly and Company. Speaker's Bureau; Novo Nordisk, Abbott. Advisory Panel; AstraZeneca. Speaker's Bureau; GlaxoSmithKline plc, Amgen Inc. Advisory Panel; Bausch Health. F. Lauand: Employee; Sanofi. S. Servera: Employee; Sanofi. L. Melas-Melt: None. K. Cypryk: Advisory Panel; Abbott. Research Support; Novo Nordisk. Speaker's Bureau; Novo Nordisk, KRKA, Eli Lilly and Company, Merck Sharp & Dohme Corp, Boehringer-Ingelheim, AstraZeneca, Sanofi. M. Almehthel: Advisory Panel; Novo Nordisk. Speaker's Bureau; Novo Nordisk. Research Support; Novo Nordisk. Advisory Panel; Sanofi. Speaker's Bureau; Sanofi. Research Support; Sanofi. Speaker's Bureau; Lilly Diabetes. Advisory Panel; Abbott. Speaker's Bureau; Abbott. Advisory Panel; Dexcom, Inc. Speaker's Bureau; Bayer Pharmaceuticals, Inc. J. Kesavadev: None. R. Sari: None.FundingSanofi
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-806-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 807-P: Comparable Glycemic Control of Once-Weekly Insulin GZR4 Relative to
Once-Daily Insulin Degludec in Insulin-Naïve Chinese Subjects with T2D-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 807-P
Abstract: Introduction and Objective: Once-weekly (QW) insulin aims to reduce treatment burden by lowering injection frequency, potentially enhancing treatment acceptance and adherence. This trial evaluated the efficacy and safety of a novel QW insulin analog GZR4 versus once-daily (QD) insulin degludec (IDeg) in insulin-naïve subjects with T2D inadequately controlled by OADs.Methods: In this open-label, treat-to-target phase 2 trial, 83 eligible subjects with HbA1c between 7.5% and 10.0% were randomized in a 1:1 ratio to receive either GZR4 or IDeg treatment for 16 weeks. The primary endpoint was the change in HbA1c from baseline to week 16. Safety endpoints, including hypoglycemia and TEAE, were evaluated.Results: The LSM HbA1c reduction was comparable between GZR4 and IDeg groups (−1.50% vs. -1.48%, p = 0.902). GZR4 group showed a similar proportion of achieving HbA1c goals and FPG reduction compared to IDeg, but with a half lower weekly insulin dosage at steady state than IDeg (80.6 vs 165.8 U/week, p<0.001). TEAEs were mild and similar between groups, with low and comparable rates of level 2 hypoglycemia. No SAEs were deemed related to GZR4.Conclusion: GZR4 demonstrated comparable efficacy and safety profiles to QD IDeg in subjects with T2D, achieving similar outcomes with a lower insulin dose. GZR4 is promising to be a safe and effective QW insulin in diabetes management.DisclosureL. Chen: None. X. Dong: None. H. Wang: None. H. Shu: None. Z. Cheng: None. X. Deng: None. G. Wang: None. J. Zhao: None. C. Hao: None. T. Xie: None. A. He: None. Y. Li: None. H. Wu: None. S. Carter: None. W. Chen: None. Z. Gan: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-807-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 808-P: Superior Glycemic Control Achieved with Once-Weekly Insulin GZR4
Compared with Once-Daily Insulin Degludec in Insulin-Treated Chinese
Subjects with T2D-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 808-P
Abstract: Introduction and Objective: Once-weekly (QW) insulins have emerged as a research focus due to their potential to enhance treatment acceptance and adherence by reducing injection frequency. This trial studied the efficacy and safety of a novel QW insulin analog GZR4 versus once-daily (QD) insulin degludec (IDeg) in basal insulin-treated subjects with T2D inadequately controlled by OADs.Methods: In this open-label, treat-to-target phase 2 trial, 96 eligible subjects with HbA1c from 7.5 to 10.0% were randomized in a 1:1 ratio to receive either GZR4 or IDeg treatment for 16 weeks. The primary endpoint was HbA1c change from baseline to week 16. Safety endpoints, including hypoglycemia and TEAE, were evaluated.Results: The LSM HbA1c reduction was significantly higher in the GZR4 than in the IDeg group (−1.26% vs. −0.87%, p< 0.01). The proportion of subjects achieving HbA1c <7% was higher in GZR4 group. GZR4 group showed a strikingly lower weekly insulin dosage at the steady state than IDeg group ( 88.7 vs. 218.2 U/week, p<0.001). Incidences of TEAEs were similar between the two treatments. GZR4 group showed a slightly higher level 2 hypoglycemia than IDeg group.Conclusion: GZR4 demonstrated superior HbA1c reduction after 16 weeks of treatment in insulin-treated subjects with T2D and is promising to be a safe and effective QW basal insulin in diabetes management.DisclosureL. Chen: None. X. Dong: None. H. Wang: None. H. Shu: None. Z. Cheng: None. X. Deng: None. G. Wang: None. J. Zhao: None. C. Hao: None. T. Xie: None. A. He: None. Y. Li: None. H. Wu: None. S. Carter: None. Z. Gan: None. W. Chen: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-808-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 810-P: Insulin Efsitora Alfa vs. Insulin Degludec in Adults with
Insulin-Naïve T2D (QWINT-2)—A Japan Subgroup Analysis-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 810-P
Abstract: Introduction and Objective: QWINT-2 met its primary endpoint, with once weekly efsitora noninferior to once-daily degludec in reducing HbA1c at 52 weeks when added to existing noninsulin glucose-lowering agents in insulin-naïve adults with T2D. A Japan subgroup analysis is shown.Methods: QWINT-2 (NCT05362058) was a phase 3, randomized, parallel-design, open-label study. Participants were randomized 1:1 to efsitora or degludec. All Japan participants were included in this analysis. Endpoints included change in HbA1c from baseline to week 52, time in glucose range (TIR) (70-180 mg/dL), and incidence and rate of level 2 (glucose <54 mg/dL) or level 3 (severe) hypoglycemia.Results: Of 144 participants, 71 were randomized to efsitora and 73 to degludec. Changes in HbA1c and TIR are shown (Figure). Incidence of level 2 or 3 hypoglycemia from weeks 0-52 was 15 (21%) with efsitora and 13 (18%) with degludec. Mean rate of level 2 or 3 hypoglycemic events per year was 0.37 (SE: 0.106) for efsitora and 0.36 (SE: 0.128) for degludec from weeks 0-52. There were two episodes of level 3 hypoglycemia with degludec from weeks 0-52. Incidence of treatment-emergent adverse events was similar across groups.Conclusion: Once-weekly efsitora was comparable to once-daily degludec in reducing HbA1c in insulin-naïve Japan participants with T2D. Efficacy and safety were consistent with the overall study population.Disclosure M. Yoshino: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. Y. Takita: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. R. Nasu: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. L. Firmino Goncalves: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. J.M. Bue-Valleskey: Employee; Eli Lilly and Company. A. Kiyosue: None.FundingThis study was supported by Eli Lilly and Company.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-810-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 811-P: Once-Weekly Insulin SHR-3167 vs. Insulin Glargine U100 (IGlar U100)
in Healthy Subjects-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 811-P
Abstract: Introduction and Objective: This trial assessed the PD, PK, and safety of SHR-3167 vs IGlar U100 in healthy subjects.Methods: This was an open-label, two-period, single-sequence trial. Sixteen healthy males were enrolled into two cohorts. Both cohorts received a single injection of IGlar U100 (0.4 U/kg), following a 7-day washout, and then received a single injection of SHR-3167 at 0.3 and 0.6 mg/kg, respectively. Subjects underwent a 24-h euglycemic glucose clamp on Day 1 after IGlar U100 injection, and three clamps after SHR-3167 injection including a 24-h clamp on Day 7. Primary endpoint was the area under the curve for glucose infusion rate (AUCGIR).Results: In each cohort, eight subjects received IGlar U100, and seven received SHR-3167. Mean coefficient of variation in blood glucose (BG), deviation from the target BG, and rate of off-target in BG during the clamp were 3.9%, 3.1%, and 1.6% for IGlar U100, 2.8%, 2.5%, and 0.1% for SHR-3167 at 0.3 mg/kg, and 3.4%, 2.5%, and 1.6% for SHR-3167 at 0.6 mg/kg with high clamp quality. C-peptide levels were consistently lower than baseline levels during all the clamp periods. Mean AUCGIR,0-24h was 3357.6 mg/kg for IGlar U100 on Day 1, 1889.7 mg/kg for SHR-3167 at 0.3 mg/kg, and 3546.8 mg/kg for SHR-3167 at 0.6 mg/kg on Day 7, indicating an approximately linear dose-glucose-lowering effect for SHR-3167, and showing similar AUCGIR between SHR-3167 at 0.6 mg/kg and IGlar U100. Cmax of SHR-3167 was achieved at 3 days, and the geomean t1/2 was 10.8 to 12.1 days. The Cmax and AUC0-∞ of SHR-3167 were 27.4 nmol/L and 593 day*nmol/L at 0.3 mg/kg, and 55.5 nmol/L and 1050 day*nmol/L at 0.6 mg/kg. SHR-3167 exposure increased proportionally within the investigated dose range. Only one subject who received SHR-3167 at 0.6 mg/kg reported asymptomatic hypoglycemia. SHR-3167 was safe and well tolerated.Conclusion: The PD/PK profiles, and safety of SHR-3167 support its potential as once-weekly regimen for glycemic management.DisclosureC. Tang: None. L. Wan: None. H. Chen: Employee; Jiangsu Hengrui Pharmaceuticals Co., Ltd. X. Wu: Employee; Jiangsu Hengrui Pharmaceuticals Co., Ltd. K. Shen: Employee; Jiangsu Hengrui Pharmaceuticals Co., Ltd. Y. Dong: Employee; Jiangsu Hengrui Pharmaceuticals Co., Ltd. Y. Ma: Employee; Jiangsu Hengrui Pharmaceuticals Co., Ltd.FundingJiangsu Hengrui Pharmaceuticals Co., Ltd (sponsor)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-811-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 812-P: Comparison of Efficacy of Short-Acting Human Insulin and
Fast-Acting Insulin Analog after High- and Low-Carbohydrate Meal—Do the
Pharmacokinetic Differences Matter'-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 812-P
Abstract: Introduction and Objective: Fast-acting insulin analogs (FIA) have earlier and higher peak and shorter duration of action as compared with short-acting human insulin (SHI). Therefore, their pharmacokinetic profile would rather reflect glycemic profile after high-carbohydrate meal (HCM), whereas delayed and longer action of SHI would rather reflect glycemia after low-carbohydrate meal (LCM).Methods: In a cross-over, open label study we administered SHI (Gensulin R, Bioton) or FIA (Apidra, Sanofi), both in the same dose 15 minutes before high- and low-carbohydrate standard morning meal, in a random sequence during four days, in 30 insulin-treated persons with type 2 diabetes. Blood glucose was assessed before and every 30 minutes after meal.Results: In contrary to the expectation, there were no significant differences of glycemic profile after administration of SHI vs FIA after LCM as well as after HCM. However, median increments of glucose concentrations and measures of dispersion were lower after LCM, independently of administered insulin formulation (Fig.1).Conclusion: The results suggest that in persons with type 2 diabetes the composition of meal may be more important to achieve better postprandial glucose values and better glucose control than use of fast-acting insulin analog instead of short-acting human insulin.Disclosure M. Matalowski: Other Relationship; Zentiva Polska Sp. z o.o., Novo Nordisk. M.M. Lukawska-Tatarczuk: None. M. Hall: None. I.E. Towpik: Other Relationship; AstraZeneca, Novo Nordisk, Lilly Diabetes, Sanofi. Research Support; AstraZeneca. M. Masierek: Employee; BIOTON S.A. M. Walicka: Speaker's Bureau; Sanofi, Eli Lilly and Company, Teva Pharmaceutical Industries. E. Franek: Speaker's Bureau; Amgen Inc, AstraZeneca. Research Support; BIOTON. Speaker's Bureau; Boehringer-Ingelheim, Merck Sharp & Dohme Corp, Sanofi.FundingBioton SA
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-812-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 813-P: Machine Learning–Based Prediction Models for Initial Insulin Pump
Dosing in Type 2 Diabetes Patients-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 813-P
Abstract: Introduction and Objective: Accurate initial insulin dosing is essential for optimal glycemic control in type 2 diabetes patients with insulin pumps. Traditional weight-based estimations lack precision due to the heterogeneity of type 2 diabetes, underscoring the need for advanced predictive approaches. This study developed machine learning models to enhance the accuracy of initial premeal and basal dose predictions.Methods: Data from 1,245 patients at the First Affiliated Hospital of Guangxi Medical University were used for model construction and internal validation, and 60 patients from Sun Yat-sen Memorial Hospital for external validation. Adults aged 18-79 years with type 2 diabetes who initiated insulin pump therapy were included, with data collected during the first 24 hours following admission. Patients with severe comorbidities, acute complications, or organ failure were excluded. A stacked ensemble framework combining random forest, XGBoost, GBM, SVM, and Bayesian regression was used. Model 1 predicts premeal insulin doses, and Model 2 basal doses based on Model 1’s outputs. Performance was evaluated using RMSE, MAE, and MAPE.Results: Model 1 achieved an RMSE of 1.10 IU, MAE of 0.79 IU, and MAPE of 19.10% for internal validation, and an RMSE of 1.21 IU, MAE of 0.88 IU, and MAPE of 17.83% for external validation. Model 2 achieved an RMSE of 2.31 IU, MAE of 1.80 IU, and MAPE of 18.66% for internal validation, and an RMSE of 3.89 IU, MAE of 3.21 IU, and MAPE of 23.47% for external validation. Compared to traditional methods, machine learning models significantly reduced RMSE, MAE, and MAPE in both premeal and basal dose predictions. The prediction models are available as a web-based calculator at https://rongxi.shinyapps.io/Pump/.Conclusion: The machine learning models accurately predict initial insulin pump dosing and outperform traditional methods, offering a practical tool for optimizing therapy in type 2 diabetes patients with insulin pump treatment.DisclosureM. Tang: None. X. Wang: None. X. Rong: None.Fundingthe Clinical Research 'Climbing' Program of the First Affiliated Hospital of Guangxi Medical University (YYZS2023010); Guangxi Medical University Student Innovation and Entrepreneurship Training Program Project (X202310598348 and S202410598192)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-813-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 814-P: Efficacy and Safety of Switching to Iglarlixi from Premix Insulin
Regimen in Patients with T2DM—Real-World Experience-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 814-P
Abstract: Introduction and Objective: The Soli-SWITCH study assessed the efficacy and safety of switching to iGlarLixi, an injectable fixed-ratio combination therapy of insulin glargine 100 U/mL + lixisenatide, in people with T2DM uncontrolled on premix insulin in a clinical trial setting. The aim of the study is to assess the efficacy and safety of such transition of regimen in a real world setting.Methods: Patients with T2DM who switched from premix insulin regimen to iGlarLixi in Taipei Veterans General Hospital from July 2020 to February 2023 were enrolled. FPG and HbA1c were assessed at baseline, three and six months following transition. HOMA-IR was also calculated. Demographic information and other diabetes-related biochemical indices were collected.Results: A total of 42 patients with a mean age of 68.9 ± 10.8 years switched from premix insulin regimen to iGlarLixi. The baseline FPG was 159.0 ± 58.1 mg/dL, HbA1c was 8.5 ± 2.0% on premix insulin dose of 43.1 ± 21.8 units. After 6 months, HbA1c was 7.86±1.61%, with 29.7% achieving HbA1c <7.0%. Injection frequency decreased from 2.1±0.5 to 1.3±0.7 times (p<0.001) and total insulin dose lowered from 43.9±22.2 to 25.4±16.9 units (p<0.001). Among them, 31.0% (n=13) changed regimen due to hypoglycemia and 69.0% (n=29) switched due to uncontrolled hyperglycemia, defined as a HbA1c ≥7.5%. For the group with HbA1c ≥7.5%, a significant reduction in HbA1c was observed at 6 months (9.4±1.5% to 8.3±1.6%, p=0.01). Patients with total daily dose of 40-50 units of premix insulin experienced the greatest HbA1c reduction, from 10.0±1.8% to 8.3±1.4% (p = 0.037). A multivariate logistic regression considering age, gender, diabetes duration, premix total daily dose, and HOMA-IR identified HOMA-IR as a significant factor (p = 0.049) for achieving HbA1c < 7.5% at 6 months.Conclusion: Switching from premix insulin to iGlarLixi in patients with T2DM serve as a safe and effective approach to simplify treatment complexity and improve glycemic control.DisclosureC. Huang: None. S. Yang: None. H. Chen: None.FundingNational Science and Technology Council, R.O.C (NSTC 112-2314-B-075 -025 -)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-814-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 815-P: CGM-Derived Model-Based Postprandial Glucose with IcoSema vs. Other
Insulin Regimens—A Post Hoc Analysis of COMBINE 1 and 3-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 815-P
Abstract: Introduction and Objective: This post hoc analysis investigated whether IcoSema, a once-weekly (OW) combination therapy of basal insulin icodec and the GLP-1 analog semaglutide currently in development, offers a postprandial glucose (PPG) control benefit vs other insulin-based regimens.Methods: COMBINE 1 and 3, two 52-week, phase 3a trials, investigated IcoSema vs OW basal insulin (icodec; COMBINE 1) or basal-bolus therapy (glargine U100 + aspart; COMBINE 3) in adults with T2D who were inadequately controlled on daily basal insulin. This analysis evaluated CGM data (Dexcom G6) collected during weeks 48-52 of both trials. To determine the effect of IcoSema vs comparators on PPG parameters, an algorithm based on model-derived estimates of meal intake to identify increases in PPG was used (GRID algorithm).Results: Statistically significantly lower increments in PPG peak and 90-minute PPG peak were seen with IcoSema vs OW basal insulin (Table). There were no statistically significant differences in AUC90min with IcoSema vs OW basal insulin. No statistically significant differences were observed in CGM-derived PPG parameters with IcoSema vs basal-bolus therapy.Conclusion: Based on post hoc modelling using CGM data, IcoSema showed statistically significantly better PPG control vs OW basal insulin and similar PPG control vs basal-bolus therapy.Disclosure C. De Block: Consultant; Abbott, AstraZeneca, Boehringer-Ingelheim, A. Menarini Diagnostics, Eli Lilly and Company, Insulet Corporation, Medtronic, Novo Nordisk. M. Asong: Employee; Novo Nordisk A/S. A. Fu: None. R. Maltesen: Employee; Novo Nordisk A/S. F. Giorgino: Advisory Panel; Abbott. Consultant; Amgen Inc. Advisory Panel; AstraZeneca, Bayer Pharmaceuticals, Inc, Biomea Fusion, Boehringer-Ingelheim, Daiichi Sankyo, Eli Lilly and Company. Research Support; Eli Lilly and Company. Board Member; European Association for the Study of Diabetes. Consultant; Medtronic. Advisory Panel; Mundipharma, Novo Nordisk, Roche Diabetes Care. Research Support; Roche Diabetes Care. Advisory Panel; Sanofi.FundingNovo Nordisk A/S
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-815-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 816-P: Efficacy and Hypoglycemia Outcomes with Once-Weekly Insulin Icodec
vs. Once-Daily Basal Insulin in T2D by Diabetes Duration—ONWARDS 1–5-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 816-P
Abstract: Introduction and Objective: This post hoc analysis assessed efficacy and hypoglycemia outcomes with once-weekly insulin icodec (icodec) vs once-daily (OD) basal insulin comparators in insulin-naive (ONWARDS 1, 3, 5) and insulin-experienced (ONWARDS 2, 4) adults with T2D by diabetes duration at baseline.Methods: Treatment outcomes were analyzed, by trial, across baseline T2D duration subgroups (<5, 5-<10, 10-<15, ≥15 years).Results: Overall, a numerically greater reduction in A1C was seen with icodec vs OD comparators across T2D duration subgroups in all trials, except for certain subgroups in ONWARDS 3 and 4 (Figure). There was no statistically significant treatment by T2D duration subgroup interaction in any trial for change in A1C from baseline to planned end of treatment (EOT). Rates of clinically significant or severe hypoglycemia were low across arms except in ONWARDS 4, where rates were numerically higher in both arms across subgroups. There was no statistically significant treatment by T2D duration subgroup interaction in any trial for the achievement of A1C <7% at EOT without clinically significant or severe hypoglycemia in the prior 12 weeks.Conclusion: Efficacy and hypoglycemia outcomes for icodec vs OD comparators were overall similar across T2D duration subgroups.Disclosure A.Y.Y. Cheng: Advisory Panel; Abbott. Speaker's Bureau; Abbott. Other Relationship; American Diabetes Association. Speaker's Bureau; Amgen Inc, AstraZeneca. Advisory Panel; Bayer Pharmaceuticals, Inc. Speaker's Bureau; Bayer Pharmaceuticals, Inc. Advisory Panel; Boehringer-Ingelheim. Speaker's Bureau; Boehringer-Ingelheim. Advisory Panel; Dexcom, Inc., Eisai, Eli Lilly and Company. Speaker's Bureau; Eli Lilly and Company, GlaxoSmithKline plc. Advisory Panel; Insulet Corporation. Speaker's Bureau; Insulet Corporation. Advisory Panel; HLS Therapeutics. Speaker's Bureau; HLS Therapeutics, Medtronic. Advisory Panel; Novo Nordisk. Speaker's Bureau; Novo Nordisk, Pfizer Inc. Advisory Panel; Sanofi. Speaker's Bureau; Sanofi. Consultant; Novo Nordisk, Applied Therapeutics, Vertex Pharmaceuticals Incorporated. L.S. Canani: Advisory Panel; Novo Nordisk. Speaker's Bureau; Novo Nordisk. Research Support; Lilly Diabetes, Amgen Inc. J.K. Lindeløv: Employee; Novo Nordisk A/S. Stock/Shareholder; Novo Nordisk A/S, Lundbeck. S.B. Søgaard: Employee; Novo Nordisk. S.M. Vinther: Employee; Novo Nordisk. C. Mathieu: Advisory Panel; Novo Nordisk, Sanofi, Eli Lilly and Company, Abbott, Medtronic, SAB Biotherapeutics, Inc, Roche Diabetes Care, Vertex Pharmaceuticals Incorporated, Biomea Fusion, Bayer Pharmaceuticals, Inc.FundingNovo Nordisk A/S
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-816-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 817-P: A Weekly Tension Off-Loading Patch for Lipohypertrophy
-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 817-P
Abstract: Introduction and Objective: Besides injection site avoidance, there is no treatment for lipohypertrophy (LH), a common complication of insulin therapy associated with variable, impaired insulin absorption and suboptimal glycemic control. We investigated a tension offloading patch (embrace®, approved to reduce post-incisional scarring) in adults with T1DM and LH.Methods: Participants with T1DM ≥3 years, aged 18-65, and with ≥2 palpable abdominal LH lesions ≥3 cm in longest axis as confirmed by ultrasound were recruited in an exploratory single-arm intervention study. Participants self-applied the thin transparent adhesive patch (4.7 x 12 cm) every ~10 days over the target lesion for 16 weeks. Volumes of the target and a non-treated control lesion were assessed by ultrasound at baseline and weeks 8 and 16. Biopsies of target and control lesions were taken at week 16 for histological analysis in a blinded fashion.Results: Of 29 enrolled participants (mean±SD age 46±11 years, diabetes duration 27±10 years, HbA1c 7.3±0.6%, 4 female, 27 on multiple daily injection, 2 on pump), 27 completed the study. Participants’ average estimated age of both LH lesions was >5 years. Mean target lesion volume decreased from 15.08 mL at baseline to 13.64 mL at 8 weeks to 12.39 mL at 16 weeks (p<0.0001), while comparator lesion volume slightly increased by 0.336 mL (p=0.01). Histology showed less scar-like morphology (automated image analysis of Picrosirius Red staining, p=0.023) and less fat (Oil Red O staining, 6.97 average fold reduction, p=0.001) in target lesions. Out of 332 applications, 13 participants reported a total of 33 site reactions (9.9%), all graded as mild and quickly resolving with no resulting discontinuations.Conclusion: A tension offloading patch applied for 16 weeks was associated with a significant 18% decrease in volume of LH lesions and reduced fibrosis and fat on histology. RCTs are needed to fully assess this first candidate treatment for LH.Disclosure J. DeVries: Research Support; Neodyne, Gan & Lee Pharmaceuticals. Consultant; Gan & Lee Pharmaceuticals. Research Support; Liom. Advisory Panel; Liom. Speaker's Bureau; Novo Nordisk A/S. S. Famulla: Research Support; Neodyne Biosciences. M.S. Stoffel: Research Support; Neodyne Biosciences, Inc. J.L. Guo: Consultant; Neodyne Biosciences. H. Talbott: Consultant; Neodyne Biosciences Inc. L. Hirsch: Consultant; Boehringer-Ingelheim, Neodyne Biosciences, Inc. K.J. Lipman: Employee; Neodyne Biosciences, Inc. J. Jackson: None.FundingNeodyne Biosciences, Inc
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-817-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 818-P: Risk Factors Influencing Insulin Use and Prescription Filling among
REAL-T Study Young Adults with T1D-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 818-P
Abstract: Introduction and Objective: Insulin is essential for managing T1D, yet many young adults face systemic barriers that limit access and consistent use. This study examined factors associated with using less insulin than prescribed and not filling insulin prescriptions over a 12-month period.Methods: A secondary analysis was conducted using data from the Resilient Empowered Active Living Telehealth (REAL-T) study, a randomized controlled trial of young adults with T1D (n=209, ≥1 year since diagnosis, A1c ≥7.5%). Participants self-reported insulin use quarterly over one year by answering: “In the past three months, did you use less insulin than prescribed'” and “Did you not fill an insulin prescription'” Logistic regression was used to examine predictors, including self-education, insurance type (e.g., Medicaid Managed Care [MMC]), unmet social needs, physician contact (from the DSMQ), and residence in a Medicaid non-expansion state. Models adjusted for race/ethnicity and gender.Results: After excluding nine participants with missing data, 200 participants (61% female, 45% Hispanic/Latinx, mean age 24.2 ± 3.8 years) were analyzed. Over 12 months, 48.5% reported using less insulin, and 33.5% reported not filling prescriptions, due to structural barriers. Each additional unmet social need (OR = 1.753, 95% CI: 1.32-2.327, P < 0.001) and living in a Medicaid non-expansion state (OR = 3.373, 95% CI: 1.374-8.278, P = 0.008) increased odds of limited insulin use. For not filling prescriptions, each unmet social need (OR = 1.4, 95% CI: 1.036-1.891, P = 0.029), living in a non-expansion state (OR = 11.771, 95% CI: 4.437-31.228, P < 0.001), and having MMC insurance (OR = 16.178, 95% CI: 2.648-98.846, P = 0.003) increased the odds.Conclusion: Insulin access and use are likely limited by state Medicaid policies, restrictions in Medicaid insurance plans, and unmet social needs. Addressing these barriers is critical for ensuring equitable insulin availability for young adults with T1D.DisclosureN.D. Nnoli: None. Y. Mo: None. J.D. Leite Junior: None. P. Lee: None. J. Raymond: None. D. Fox: None. G. Granados: None. J. Sideris: None. J. Blanchard: None. E. Pyatak: None.FundingNational Institute of Diabetes and Digestive and Kidney Diseases Study (R01DK116719)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-818-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 819-P: Efficacy and Hypoglycemia Outcomes with Once-Weekly Insulin Icodec
vs. Once-Daily Basal Insulin in T2D by Baseline BMI—ONWARDS 1–5-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 819-P
Abstract: Introduction and Objective: This post hoc analysis assessed the efficacy and hypoglycemia outcomes with once-weekly insulin icodec (icodec) vs once-daily (OD) basal insulin comparators in insulin-naive (ONWARDS 1, 3, 5) and insulin-experienced (ONWARDS 2, 4) adults with T2D by baseline BMI.Methods: Treatment outcomes were analyzed, by trial, across baseline BMI subgroups (<25, ≥25-<30, ≥30-<35, ≥35 kg/m2).Results: Overall, a numerically greater reduction in A1C was seen with icodec vs OD comparators across BMI subgroups in all trials, except for certain subgroups in ONWARDS 4 (basal-bolus trial). There was no statistically significant treatment by BMI subgroup interaction in any trial for change in A1C from baseline to planned end of treatment (EOT) (Figure). Rates of clinically significant or severe hypoglycemia were low across arms irrespective of baseline BMI, except in ONWARDS 4 where rates were overall similar between arms across subgroups. There was no statistically significant treatment by BMI subgroup interaction in any trial for the achievement of A1C <7% at EOT without clinically significant or severe hypoglycemia in the prior 12 weeks.Conclusion: Efficacy and hypoglycemia outcomes for icodec vs OD comparators were overall similar across baseline BMI subgroups.Disclosure L.S.S. Canani: Advisory Panel; Novo Nordisk. Speaker's Bureau; Novo Nordisk. Research Support; Lilly Diabetes, Amgen Inc. A.Y. Cheng: Advisory Panel; Abbott. Speaker's Bureau; Abbott. Other Relationship; American Diabetes Association. Speaker's Bureau; Amgen Inc, AstraZeneca. Advisory Panel; Bayer Pharmaceuticals, Inc. Speaker's Bureau; Bayer Pharmaceuticals, Inc. Advisory Panel; Boehringer-Ingelheim. Speaker's Bureau; Boehringer-Ingelheim. Advisory Panel; Dexcom, Inc., Eisai, Eli Lilly and Company. Speaker's Bureau; Eli Lilly and Company, GlaxoSmithKline plc. Advisory Panel; Insulet Corporation. Speaker's Bureau; Insulet Corporation. Advisory Panel; HLS Therapeutics. Speaker's Bureau; HLS Therapeutics, Medtronic. Advisory Panel; Novo Nordisk. Speaker's Bureau; Novo Nordisk, Pfizer Inc. Advisory Panel; Sanofi. Speaker's Bureau; Sanofi. Consultant; Novo Nordisk, Applied Therapeutics, Vertex Pharmaceuticals Incorporated. J.K. Lindeløv: Employee; Novo Nordisk A/S. Stock/Shareholder; Novo Nordisk A/S, Lundbeck. S.B. Søgaard: Employee; Novo Nordisk. S.M. Vinther: Employee; Novo Nordisk. C. Mathieu: Advisory Panel; Novo Nordisk, Sanofi, Eli Lilly and Company, Abbott, Medtronic, SAB Biotherapeutics, Inc, Roche Diabetes Care, Vertex Pharmaceuticals Incorporated, Biomea Fusion, Bayer Pharmaceuticals, Inc.FundingNovo Nordisk A/S
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-819-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 820-P: Insulin Efsitora Alfa (Efsitora) Demonstrates Better Overall Health
State vs. Daily Degludec in Basal-Switch Adults with T2D in QWINT-3-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 820-P
Abstract: Introduction and Objective: The 78-week QWINT-3 trial assessed once-weekly efsitora (n=655) vs once-daily degludec (n=331) in adults with T2D currently on basal insulin. Here, we report the patient reported outcomes (PRO) findings at week 26 (primary timepoint).Methods: TRIM-D assessed 5 domains at baseline and week 26: treatment burden, daily life, diabetes management, compliance and psychological health, including total score. Higher scores indicate a better health state. The DTSQc assessed treatment (tx) satisfaction; SIM-Q evaluated tx complexity; BIE assessed the likelihood of incorporating a study insulin into a participant’s tx routine.Results: All 5 TRIM-D domains had improved scores with greater improvement for efsitora vs degludec at week 26 (Figure). More participants rated efsitora as “very simple” (46%) vs degludec (35%) (p<0.001) on SIM-Q, and “very likely” to incorporate it into their tx routine (efsitora 62% vs degludec 43%; p<0.001) on BIE. DTSQc indicated greater satisfaction score with efsitora (14.9) vs degludec (12.3) (p<.001).Conclusion: Treatment with weekly efsitora resulted in greater tx satisfaction, better overall health state, and reduced tx burden vs degludec in adults with T2D currently treated with basal insulin. Greater satisfaction and perceived improved overall health state may improve adherence and clinical outcomes.Disclosure R.M. Bergenstal: Advisory Panel; Abbott. Research Support; Abbott. Consultant; Abbott. Research Support; Dexcom, Inc. Consultant; Dexcom, Inc., Eli Lilly and Company. Research Support; Eli Lilly and Company. Consultant; Novo Nordisk. Research Support; Novo Nordisk. Consultant; Roche Diabetes Care, Sanofi, Medtronic. Research Support; Medtronic, Insulet Corporation, Hemsley Charitable Trust. Other Relationship; MannKind Corporation. Consultant; Medscape. Research Support; National Institute of Diabetes and Digestive and Kidney Diseases, Tandem Diabetes Care, Inc, UnitedHealth Group. Consultant; Vertex Pharmaceuticals Incorporated, Ascensia Diabetes Care, American Diabetes Association, Hygieia, embecta, Senseonics, Zealand Pharma A/S. A. Philis-Tsimikas: Advisory Panel; Dexcom, Inc. Research Support; Dexcom, Inc. Advisory Panel; Lilly Diabetes. Research Support; Lilly Diabetes. Advisory Panel; Novo Nordisk. Research Support; Novo Nordisk. Advisory Panel; Medtronic, Sanofi. H.W. Rodbard: Consultant; Bayer Pharmaceuticals, Inc. Research Support; Novo Nordisk, Lilly USA LLC. Speaker's Bureau; Lilly USA LLC. Consultant; Endogenex, Kriya Therapeutics. Research Support; Inversago Pharma. S. Gangi: Research Support; Lilly USA LLC. Speaker's Bureau; Lilly USA LLC. Research Support; Abbott Diagnostics, Amgen Inc, Ionis Pharmaceuticals. R.J. Threlkeld: Employee; Eli Lilly and Company. J. Mitra: None. L. Ilag: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. M.B. Davidson: Employee; Eli Lilly and Company. K. Syring: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. F. Gelsey: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-820-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 821-P: Insulin Efsitora Alfa (Efsitora) Demonstrates Better Overall Health
State vs. Daily Degludec in Insulin-Naive Adults with T2D in QWINT-2-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 821-P
Abstract: Introduction and Objective: The 52-week QWINT-2 phase 3 trial demonstrated non-inferiority in HbA1c change from baseline with low, comparable hypoglycemia rates for efsitora, a novel once-weekly basal insulin (N=466), vs degludec (N=462) in insulin-naïve adults with type 2 diabetes (T2D). Here, we report the patient-reported outcomes.Methods: The TRIM-D assessed 5 domains: treatment burden, daily life, diabetes management, compliance, and psychological health, plus a total score indicating overall health. The SIM-Q evaluated treatment complexity, and the BIE assessed likelihood of a participant incorporating study insulin into their routine.Results: At week 52, there were significantly greater improvements in TRIM-D total score and in diabetes management and treatment burden domains with efsitora vs degludec (Figure). On the SIM-Q and BIE, more participants rated efsitora as “very simple” (51%) vs degludec (34%; P<0.001) and “very likely” to incorporate into their treatment routine (50%) vs degludec (38%; P=0.003), respectively.Conclusion: Weekly efsitora treatment resulted in a better overall health state, easier management, and reduced treatment burden vs daily degludec in insulin-naïve adults with T2D, with a greater simplicity perception by the participants. These findings may reduce insulin initiation inertia and delays in T2D management.Disclosure H.S. Bajaj: Research Support; Abbott, Amgen Inc, Anji Pharmaceuticals, AstraZeneca, Boehringer-Ingelheim, Eli Lilly and Company, GlaxoSmithKline plc, Novartis Pharmaceuticals Corporation, Novo Nordisk, Pfizer Inc. C.H. Wysham: Advisory Panel; Abbott. Research Support; AbbVie Inc, Eli Lilly and Company. Speaker's Bureau; MannKind Corporation. Research Support; Novo Nordisk. Speaker's Bureau; Eli Lilly and Company. Research Support; Novo Nordisk, Bayer Pharmaceuticals, Inc. I. Lingvay: Consultant; Abbvie, Altimmune, Amgen, Alveus Tx, Antag Tx, Astra Zeneca, Bayer, Betagenon AB, Bioio Inc., Biomea, Boehringer-Ingelheim, Carmot, Cytoki Pharma, Eli Lilly, Intercept, Janssen/J&J, Juvena, Keros Ther, Novo Nordisk, Pharmaventures, Pfizer, Regeneron, Roche, Sanofi, Shionogi, Source Bio, Structure Therapeutics, TARGET RWE, TERNS Pharma, The Comm Group, WebMD, and Zealand Pharma. Research Support; Novo Nordisk, Sanofi, Boehringer-Ingelheim. T. Vilsbøll: Advisory Panel; Boehringer-Ingelheim, AstraZeneca, Bristol-Myers Squibb Company, Carmot Therapeutics, Inc. Research Support; Dexcom, Inc. Advisory Panel; Eli Lilly and Company, GlaxoSmithKline plc. Speaker's Bureau; Medscape. Advisory Panel; Novo Nordisk, Sun Pharmaceutical Industries Ltd, Roche Diabetes Care, Amgen Inc, Sanofi, Zealand Pharma A/S. L. Firmino Goncalves: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. C. Zhou: Employee; Eli Lilly and Company. M.B. Davidson: Employee; Eli Lilly and Company. A. Knights: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. F. Gelsey: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-821-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 822-P: Efficacy and Hypoglycemia Outcomes with Once-Weekly Insulin Icodec
vs. Once-Daily Basal Insulin in T2D by Baseline A1C—ONWARDS 1–5-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 822-P
Abstract: Introduction and Objective: This post hoc analysis assessed the efficacy and hypoglycemia outcomes with once-weekly insulin icodec (icodec) vs once-daily (OD) basal insulin comparators in insulin-naive (ONWARDS 1, 3, 5) and insulin-experienced (ONWARDS 2, 4) adults with T2D by baseline A1C.Methods: Treatment outcomes were analyzed, by trial, across baseline A1C subgroups (≤8%, >8-≤9%, >9%).Results: Overall, a numerically greater reduction in A1C was seen with icodec vs OD comparators across A1C subgroups in all trials, except for the >8-≤9% and >9% subgroups in ONWARDS 4 (basal-bolus trial) (Figure). There was no statistically significant treatment by A1C subgroup interaction in any trial for change in A1C from baseline to planned end of treatment (EOT). Rates of clinically significant or severe hypoglycemia were low (<1 event/patient-year of exposure) across arms irrespective of baseline A1C except in ONWARDS 4 where rates were numerically higher in both arms across subgroups. There was no statistically significant treatment by A1C subgroup interaction in any trial for the achievement of A1C <7% at EOT without clinically significant or severe hypoglycemia in the prior 12 weeks.Conclusion: Efficacy and hypoglycemia outcomes for icodec vs OD comparators were overall similar across baseline A1C subgroups.Disclosure C. Mathieu: Advisory Panel; Novo Nordisk, Sanofi, Eli Lilly and Company, Abbott, Medtronic, SAB Biotherapeutics, Inc, Roche Diabetes Care, Vertex Pharmaceuticals Incorporated, Biomea Fusion, Bayer Pharmaceuticals, Inc. L.S. Canani: Advisory Panel; Novo Nordisk. Speaker's Bureau; Novo Nordisk. Research Support; Lilly Diabetes, Amgen Inc. J.K. Lindeløv: Employee; Novo Nordisk A/S. Stock/Shareholder; Novo Nordisk A/S, Lundbeck. S.B. Søgaard: Employee; Novo Nordisk. S.M. Vinther: Employee; Novo Nordisk. A.Y. Cheng: Advisory Panel; Abbott. Speaker's Bureau; Abbott. Other Relationship; American Diabetes Association. Speaker's Bureau; Amgen Inc, AstraZeneca. Advisory Panel; Bayer Pharmaceuticals, Inc. Speaker's Bureau; Bayer Pharmaceuticals, Inc. Advisory Panel; Boehringer-Ingelheim. Speaker's Bureau; Boehringer-Ingelheim. Advisory Panel; Dexcom, Inc., Eisai, Eli Lilly and Company. Speaker's Bureau; Eli Lilly and Company, GlaxoSmithKline plc. Advisory Panel; Insulet Corporation. Speaker's Bureau; Insulet Corporation. Advisory Panel; HLS Therapeutics. Speaker's Bureau; HLS Therapeutics, Medtronic. Advisory Panel; Novo Nordisk. Speaker's Bureau; Novo Nordisk, Pfizer Inc. Advisory Panel; Sanofi. Speaker's Bureau; Sanofi. Consultant; Novo Nordisk, Applied Therapeutics, Vertex Pharmaceuticals Incorporated.FundingNovo Nordisk A/S
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-822-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 823-P: AT278, a Novel Ultra-fast Highly Concentrated Insulin Aspart (500
IU/ml), Shows Ultra-fast Properties Independent of BMI-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 823-P
Abstract: Introduction and Objective: High insulin doses are required due to the rise in obesity and insulin resistance, in both type 1 and type 2 diabetes (T2DM). AT278 is a new ultra-rapid formulation of concentrated insulin aspart (500 IU/ml). We compared pharmacodynamics (PD) and pharmacokinetics (PK) of AT278 (500 IU/ml) with insulin aspart (InsAsp, 100 IU/ml) and human insulin (HumIns, 500 IU/ml) in T2DM over a wide range of BMI.Methods: In a randomised, double-blind, crossover, euglycemic clamp study, a single sc injection of 0.5 IU/kg of AT278 was compared to InsAsp, with an additional open comparison to HumIns in 41 adults with T2DM (BMI 25.0 - 38.7 kg/m2).Results: AT278 showed significantly accelerated onset of glucose-lowering effect (AUCGIR,0-60min) compared with InsAsp (TR 2.02) and HumIns (TR 3.91). AT278 showed 5-min earlier onset of appearance and 24 min shorter tEarly50%Cmax compared with InsAsp. PK and PD of HumIns was significantly retarded. Overall insulin exposure and glucose-lowering effect were comparable for all formulations. While BMI had a decelerating effect on the onset PK and PD parameters for InsAsp, AT278 retained all ultra-fast properties regardless of BMI.Conclusion: Concentrated AT278 (500 IU/ml) offers ultra-fast characteristics independent of BMI and thus has the potential to improve quality of life for people with diabetes with high prandial insulin needs.DisclosureE. Svehlikova: None. G. Fluhr: None. B.C. Lackner: None. M. Ratzer: None. D.J. Gerring: None. J. Jezek: None. S.J. Howell: None. L. Zakrzewski: None. S. Murray: Employee; Arecor Ltd. T. Pieber: Consultant; Arecor. Speaker's Bureau; Novo Nordisk A/S. Consultant; Eli Lilly and Company. Advisory Panel; Sanofi. Research Support; AstraZeneca. Advisory Panel; ADOCIA. Speaker's Bureau; Roche Diagnostics.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-823-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 824-P: Uncovering the Bidirectional Glucose-Dependent Relationship of
Insulin and Glucagon—A Meal-Challenge Study in Patients with Type 1
Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 824-P
Abstract: Introduction and Objective: Despite advances in diabetes management, hypoglycemia remains a major barrier to optimal insulin (INS) therapy. INS and glucagon (GCG) exert opposing effects on glycemia: INS potently lowers glucose with diminishing effect as plasma glucose falls, at which time the glucose-raising effect of GCG increases. This interplay suggests that co-administering INS and GCG could narrow postprandial glycemic excursion.Methods: We tested this concept in 15 adults with Type 1 diabetes (7 males, age 34±3 yr, C-peptide <0.03 nM/l, A1C 6.8±0.2%) during 2 separate 6h meal challenges (100g carbohydrate). We infused a biphasic dose of INS IV for 6h either alone (INS) or with co-infused GCG (INS:GCG) at a fixed molar ratio. INS dosing was individualized and matched between visits to control the early glycemic rise and induce a hypoglycemic challenge later.Results: During the initial meal-related glycemic rise, we saw no difference in glucose peak (INS: 219±16, INS:GCG 226±13 mg/dl, p>0.8) or AUC0-180min (INS 1061±80, INS:GCG 1048±51 mg/dl.h). During the later glucose descent phase with INS alone, some patients (9/15) had hypoglycemia <80 mg/dl with a subset (6/9) requiring IV glucose (at a predetermined threshold of 50 mg/dl). During the INS:GCG visit, multiple hypoglycemic parameters improved relative to INS (slower glycemic descent, higher glucose nadir and/or reduced need for IV glucose). Plasma catecholamines during the final hour of hypoglycemia also indicated a greater sympathoadrenal response with INS alone (epinephrine: INS 156±50, INS:GCG 49±14 pg/mL, P=0.01). No GI or cardiovascular adverse events were observed.Conclusion: This study demonstrates the potential benefit of co-administered INS and GCG. While the postprandial glycemic rise was unaffected by the addition of GCG, GCG protected against hypoglycemia. Co-administration of INS and GCG has the potential to limit postprandial glycemic excursions, addressing a key hindrance to optimal glycemia.DisclosureG. Kraft: None. A. Severtson: None. M. Scott: None. J.M. Gregory: Advisory Panel; vTv Therapeutics. Consultant; DRI Capital Inc., Beckman Coulter Inc. Other Relationship; MJH Life Sciences. Advisory Panel; Medtronic, Sanofi. S.R. Smith: Advisory Panel; Boehringer-Ingelheim, Novo Nordisk. Consultant; Zealand Pharma A/S. Advisory Panel; Amgen Inc. Research Support; Abvance Therapeutics. A.D. Cherrington: Other Relationship; Abvance Therapeutics. Advisory Panel; AdipoPharm. Research Support; Alnylam Pharmaceuticals, Inc. Other Relationship; Fractyl Health, Inc., Novo Nordisk. Advisory Panel; Portal Insulin, Sekkei Bio, Sensulin Labs, LLC. Research Support; SFC Fludics, Inc. Consultant; Thetis Pharmaceuticals, LLC. B.W. Bode: Research Support; Lilly USA LLC, Biomea Fusion, Abbott, Abvance Therapeutics, Carmot Therapeutics, Inc. Advisory Panel; Beta Bionics, Inc. Research Support; Medtronic. Speaker's Bureau; Sanofi, IQVIA Inc. Advisory Panel; Vertex Pharmaceuticals Incorporated. Research Support; CeQur. D.G. Maggs: None.FundingT1D Exchange
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-824-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 825-P: AI-Based Optimization of Patient Eligibility for Oral Insulin
Treatment—A Post Hoc Analysis to Identify Responders-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 825-P
Abstract: Introduction and Objective: In a Phase III, randomized, placebo-controlled, multi-center study in which T2DM patients were treated with oral insulin for 26 weeks, the primary endpoint defined as a decrement of 0.6% HbA1c by end of treatment was not met. A post-hoc analysis aimed to identify subpopulations with substantial clinical responses to treatment.Methods: Explainable AI (XAI) and Phase II data (n=206) collected with the same oral insulin formulation were used to train a model to estimate the expected treatment effect in the Phase III trial (n=489). The analysis also sought to identify causal interrelations among markers that could explain treatment-disease mechanisms and recommend responder profiles. Profiles were validated using real-world data (RWD) of ~2,200 T2DM patients to guarantee sufficient representation in the T2DM patient population.Results: XAI-identified demographic (e.g., age, sex), clinical (e.g., BMI), and biological (e.g., baseline HbA1c) markers provided optimal responder profiles that enabled ~1% HbA1c reduction over placebo. Profiles derived based on Phase II data were similarly accurate on Phase III data (ρ=0.96).Conclusion: Variability in response to oral insulin can be minimized by segmenting the population based on BMI and other clinical and biological markers. These findings will inform eligibility criteria for a newly planned Phase III study.Disclosure R. Eldor: Consultant; Oramed Pharmaceuticals. Speaker's Bureau; Novo Nordisk, Lilly Diabetes, Sanofi, Medtronic. Stock/Shareholder; Oramed Pharmaceuticals. Speaker's Bureau; Novartis Pharmaceuticals Corporation, Boehringer-Ingelheim. M. Kidron: Board Member; Oramed Pharmaceuticals. Employee; Oramed Pharmaceuticals. Stock/Shareholder; Oramed Pharmaceuticals. R.H. Wolf: Other Relationship; Oramed Pharmaceuticals. S. Chaim: None. R. Giami: Other Relationship; Oramed Pharmaceuticals. B. Lerner: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-825-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 826-P: Comparison of Pharmacodynamics and Pharmacokinetics of Insulin
Aspart and Faster-Acting Insulin Aspart around Continuous Moderate
Intensity Exercise in Adults with Type 1 Diabetes—A Randomised
Controlled Trial-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 826-P
Abstract: Introduction and Objective: To compare the effect of reduced dose insulins aspart and faster aspart administration on pharmacodynamics (PD) and pharmacokinetics (PK) around continuous moderate-intensity cycling in adults with type 1 diabetes (T1D).Methods: After ethical approval, 44 adults with T1D (30 males, age 39±13 years, BMI 24±3.5 kg/m2, duration diabetes 15±12 years, HbA1c 51.5±10.5 mmol/mol; 6.9±1.0%), completed a four-arm, double blind randomised crossover trial. Primary outcome was a comparison of aspart or faster acting aspart for the same pre- and post-exercise insulin dose reduction on PD between exercise onset and end. Participants administered a 50% (4.9±5.2 IU) or 75% (2.5±2.6 IU) reduced dose of aspart (IAsp-50 or IAsp-75) or faster-acting aspart (Fiasp-50 or Fiasp-75) alongside a carbohydrate drink (1 g/kg bm) 1-h pre and 2-h post 45 min morning cycling (60.5±0.8 %VO2max). Participants maintained usual morning insulin degludec. Cardio-respiratory and metabolic responses were characterised with plasma glucose (PD) and serum insulin (PK) measured in 5-15 min epochs.Results: Following insulin administration, serum insulin increased more in both Fiasp arms compared to equivalent dose IAsp arms (p<0.001), but plasma glucose (PG) was similar (ns). Insulin type did not alter PD from exercise onset to end (IAsp-50 -5.1±3.0; Fiasp-50 -4.0±2.8 mmol/L (ns) and IAsp-75 -3.4±3.3; Fiasp-75 -2.8±3.3 mmol/L, ns). PG reductions from exercise onset to end were greater in both 50% reduced treatment arms compared with 75% reduced equivalents (both P≤0.05). PK/PD characteristics were similar between insulins over 4 h recovery when another equivalent dose was administered 2h post-exercise (ns).Conclusion: Reduced insulin aspart or faster-acting aspart showed similar PD/PK characteristics around continuous moderate intensity cycling in adults with T1D.DisclosureR.M. Bracken: None. J. Pitt: None. O.M. McCarthy: None. S.C. Bain: Research Support; Novo Nordisk A/S, Lilly Diabetes. Speaker's Bureau; Menarini, AstraZeneca. Research Support; Boehringer-Ingelheim, Abbott Diagnostics, Amgen Inc. O. Moser: Advisory Panel; Sanofi. Research Support; Sanofi. Speaker's Bureau; Sanofi, Novo Nordisk. Research Support; Novo Nordisk. Advisory Panel; Dexcom, Inc. Research Support; Dexcom, Inc. Speaker's Bureau; Dexcom, Inc. H. Sourij: Advisory Panel; Eli Lilly and Company. Speaker's Bureau; Eli Lilly and Company. Research Support; Eli Lilly and Company. Advisory Panel; Boehringer-Ingelheim. Speaker's Bureau; Daiichi Sankyo. Advisory Panel; Novo Nordisk A/S. Speaker's Bureau; Novo Nordisk A/S. Advisory Panel; Novartis AG, Amarin Corporation, Amgen Inc.FundingInvestigator Initiated Study, Novo Nordisk A/S.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-826-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 827-P: Patient-Reported Outcomes with Use of Inhaled Technosphere Insulin
(TI)-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 827-P
Abstract: Introduction and Objective: The INHALE-3 randomized trial (N=123) demonstrated HbA1c levels with a regimen of TI plus insulin degludec were non-inferior compared with a usual-care control group (about half using AID and half MDI). Although no significant differences between groups on patient-reported outcome (PRO) surveys were seen, it is important to evaluate differences in those with increased versus decreased HbA1c levels after switching to the TI-degludec regimen.Methods: Surveys, completed prior to initiating TI-degludec and after 13-17 weeks, included Diabetes Distress Scale (DDS-17), Hypoglycemia Confidence Scale (HCS), Diabetes Constraints Scale (DCS), and Insulin Treatment Satisfaction Questionnaire (ITSQ).Results: HbA1c improved by ≥0.5% in 33 and worsened by ≥0.5% in 24 participants. Participants who improved reported feeling more distressed about diabetes (DDS), more limited and constrained (DCS) and less satisfied with their insulin regimen at baseline and had greater improvement in PRO scores compared with participants who worsened (Table).Conclusion: Participants who had poorer glycemic control and greater dissatisfaction with diabetes and with their insulin regimen at baseline showed more improvement in glycemic control and PROs, perhaps reflecting a greater openness to trying a different insulin delivery regimen.DisclosureK. Ruedy: None. P. Calhoun: None. R. Bailey: None. W.H. Polonsky: Consultant; Abbott. Research Support; Abbott. Consultant; Dexcom, Inc. Research Support; Dexcom, Inc. Other Relationship; Ascensia Diabetes Care. I.B. Hirsch: Research Support; Dexcom, Inc., Tandem Diabetes Care, Inc, MannKind Corporation. Consultant; Abbott, Roche Diabetes Care, Hagar. K.K. Hood: Consultant; Sanofi. Advisory Panel; MannKind Corporation. Consultant; Havas Health. Research Support; embecta. R.W. Beck: Research Support; Insulet Corporation. Consultant; Insulet Corporation. Research Support; Tandem Diabetes Care, Inc, Beta Bionics, Inc, Dexcom, Inc., Bigfoot Biomedical, Inc, Abbott, embecta, Sequel Med Tech, MannKind Corporation. Consultant; Novo Nordisk, Vertex Pharmaceuticals Incorporated, Hagar, Ypsomed AG, Zucara Therapeutics, Abata Therapeutics, Eli Lilly and Company.FundingMannKind
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-827-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 828-P: Fixed-Dose Titration of Insulin Efsitora Alfa Demonstrates Greater
Patient Preference vs. Daily Glargine in Insulin-Naïve Adults with T2D in
QWINT-1-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 828-P
Abstract: Introduction and Objective: QWINT-1 evaluated novel fixed-dose titration of weekly efsitora (n=397) vs daily glargine U100 (n=398) in insulin naïve adults with T2D. We report patient-reported outcomes to assess patient perspectives and satisfaction.Methods: The TRIM-D assessed treatment burden, daily life, diabetes management, compliance, and psychological health, plus total score. The DTSQc assessed change in treatment satisfaction; SIM-Q evaluated complexity; BIE assessed likelihood of incorporating a study insulin into a participant’s treatment routine.Results: At week 52, improvements in all TRIM-D scores occurred in both arms; burden score improved to a significantly greater extent with efsitora vs glargine (Figure). DTSQc satisfaction was modestly but significantly greater with efsitora vs glargine (mean 15.1 vs 14.5; P=0.029). On SIM-Q, a similar proportion of participants using efsitora (54%) and glargine (49%) rated weekly insulin treatment as “very simple”. On BIE, more participants were “very likely” to incorporate efsitora into their routine (63%) vs glargine (50%; P=0.005).Conclusion: In insulin naïve adults with T2D, efsitora improved health outcomes across a variety of domains and reduced treatment burden. More participants receiving efsitora vs glargine indicated that they were “very likely” to use their study treatment.Disclosure E. Miller: Advisory Panel; Abbott, Abbott Diagnostics. Other Relationship; American Diabetes Association. Speaker's Bureau; Bayer Pharmaceuticals, Inc, Boehringer-Ingelheim, Corcept Therapeutics, Eli Lilly and Company. Advisory Panel; Insulet Corporation, embecta. Speaker's Bureau; Novo Nordisk. Research Support; Abbott. J. Rosenstock: Advisory Panel; Amgen Inc. Research Support; Amgen Inc. Advisory Panel; Applied Therapeutics. Research Support; Applied Therapeutics, AstraZeneca. Advisory Panel; Bayer Pharmaceuticals, Inc, Biomea Fusion, Corcept Therapeutics, Eli Lilly and Company. Research Support; Eli Lilly and Company. Advisory Panel; Hanmi Pharm. Co., Ltd. Research Support; Merck & Co., Inc, Novartis AG. Advisory Panel; Novo Nordisk. Research Support; Novo Nordisk, Pfizer Inc. Advisory Panel; Regeneron Pharmaceuticals. Research Support; Regeneron Pharmaceuticals, Regeneron Pharmaceuticals. Advisory Panel; Regor Therapeutics, Roche Pharmaceuticals, Sanofi. Research Support; Sanofi. Advisory Panel; Structure Therapeutics, Inc, Zealand Pharma A/S. F.C. Perez Manghi: None. L. Sauque-Reyna: None. C.J. Child: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. Q. Wang: Employee; Eli Lilly and Company. M.B. Davidson: Employee; Eli Lilly and Company. A. Knights: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. F. Gelsey: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-828-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 829-P: Once-Weekly Insulin SHR-3167 in Healthy Subjects and Type 2
Diabetes Mellitus Participants—A Phase 1, Randomized, Single- and
Multiple-Ascending Dose Study-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 829-P
Abstract: Introduction and Objective: SHR-3167, a novel once-weekly insulin, is designed to provide a long-acting option. Here, we present the outcomes of a phase 1 trial of SHR-3167 in healthy subjects and type 2 diabetes mellitus (T2DM) participants (pts).Methods: This randomized, multicenter, phase 1 trial comprised a placebo-controlled, double-blind single ascending dose (SAD) part and a positive-controlled, open-label multiple ascending dose (MAD) part. In SAD, 28 healthy volunteers were randomized (3:1) to receive a subcutaneous (sc) injection of SHR-3167 (0.5, 2, 8, and 20 mg) or placebo, and 16 T2DM pts inadequately controlled with oral antidiabetic drugs were randomized (3:1) to receive SHR-3167 (25 and 50 mg, sc) or placebo. In MAD, 18 T2DM pts on daily basal insulin were randomized (2:1) to switch to weekly SHR-3167 (10 and 20 mg, sc) or daily insulin glargine (IGlar, sc) for 6 weeks. Primary endpoints were safety and tolerability.Results: The majority of adverse events (AEs) were mild, and no serious treatment-related AEs were reported. Following fixed dose of SHR-3167, hypoglycemia occurred in 4 of 24 (16.7%) T2DM pts (3 pts in level 1; 1 pt in level 2). In SAD, median Tmax of SHR-3167 was 3.0-5.5 days, and geometric mean t1/2 was 10.4-11.9 days. SHR-3167 exposure increased almost proportionally in T2DM pts. Steady state concentration was reached around 6 weeks after administration in MAD. In T2DM pts in SAD, fasting plasma glucose (FPG) continuously decreased from baseline over 15 days. Mean FPG reduction on day 8 was 2.1 and 2.3 mmol/L with SHR-3167 at 25 and 50 mg, compared with 0.9 mmol/L with placebo. In MAD, SHR-3167 had a dose-dependent manner in decreasing HbA1c. Reduction in HbA1c on day 43 was 0.60% with SHR-3167 at 20 mg and 0.33% with SHR-3167 at 10 mg, compared with 0.37% with IGlar.Conclusion: Once-weekly insulin SHR-3167 showed good tolerability, favorable pharmacokinetics, and evident glucose-lowering effects.DisclosureY. Liu: None. H. Zhou: None. C. Meng: None. T. Pan: None. Y. Wang: None. K. Shen: Employee; Jiangsu Hengrui Pharmaceuticals Co., Ltd. Y. Dong: Employee; Jiangsu Hengrui Pharmaceuticals Co., Ltd. M. Zeng: Employee; Jiangsu Hengrui Pharmaceuticals Co., Ltd. L. Xiang: Employee; Jiangsu Hengrui Pharmaceuticals Co., Ltd. Y. Ma: Employee; Jiangsu Hengrui Pharmaceuticals Co., Ltd.FundingJiangsu Hengrui Pharmaceuticals Co., Ltd.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-829-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 830-P: CGM-Based Outcomes in Adults with T2D Receiving IcoSema vs.
Comparators—Post Hoc Analysis of COMBINE 1 and 3-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 830-P
Abstract: Introduction and Objective: IcoSema is a once-weekly combination therapy of insulin icodec (icodec) + semaglutide. This post hoc analysis assessed CGM outcomes with IcoSema vs comparators using blinded CGM data from two 52-week, phase 3a trials (COMBINE 1, 3) in T2D.Methods: Adults with T2D inadequately controlled on basal insulin were randomized 1:1 to IcoSema or comparator (COMBINE 1: icodec; COMBINE 3: basal-bolus therapy [BBT], insulin glargine U100 + insulin aspart). CGM-based time in tight range (TiTR, 70-140 mg/dL); achievement of the composite outcome (>70% time in range + <25% time above range + <4% time <70 mg/dL); glycemic variability (CV%); and duration of overall hypoglycemic episodes (<70 mg/dL for ≥15 consecutive min) were assessed between weeks 48-52.Results: Mean percentage of TiTR was significantly higher with IcoSema vs icodec (p<0.0001), and similar vs BBT (p=0.81). Significantly more participants achieved the composite outcome with IcoSema vs icodec (p<0.0001) or BBT (p=0.004). Across arms, the geometric mean of CV% was <36% and median duration of overall hypoglycemic episodes was similar.Conclusion: Between weeks 48-52, TiTR was significantly higher with IcoSema vs icodec and similar vs BBT. More participants on IcoSema vs comparators achieved the CGM composite outcome, CV% was <36% and median overall hypoglycemia duration was similar between arms.Disclosure C. Irace: Board Member; Abbott, Novo Nordisk. Consultant; Roche Diabetes Care, Medtronic, Sanofi. V. Cejvanovic: Employee; Novo Nordisk A/S. Stock/Shareholder; Novo Nordisk A/S. J.H. Larsen: Employee; Novo Nordisk A/S. Stock/Shareholder; Novo Nordisk A/S. T.M.P. Rocha: Employee; Novo Nordisk A/S. Y. Terauchi: Speaker's Bureau; Merck & Co., Inc, Boehringer-Ingelheim, Mitsubishi Tanabe Pharma Corporation, Novo Nordisk, Eli Lilly and Company, Sanofi, Sumitomo Dainippon Pharma Co., Ltd, AstraZeneca, Astellas Pharma Inc, Kowa Company, Ltd. Research Support; Boehringer-Ingelheim, Sumitomo Dainippon Pharma Co., Ltd, Eli Lilly and Company. Advisory Panel; Novo Nordisk, Eli Lilly and Company, Mitsubishi Tanabe Pharma Corporation, Astellas Pharma Inc, Sanofi, Dexcom, Inc. C. Mathieu: Advisory Panel; Novo Nordisk, Sanofi, Eli Lilly and Company, Abbott, Medtronic, SAB Biotherapeutics, Inc, Roche Diabetes Care, Vertex Pharmaceuticals Incorporated, Biomea Fusion, Bayer Pharmaceuticals, Inc.FundingNovo Nordisk A/S
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-830-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 831-P: Comparison of Glargine 100, Glargine 300, and Degludec in Fasting
during Ramadan-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 831-P
Abstract: Introduction and Objective: Fasting during Ramadan presents challenges for people with type 1 diabetes due to prolonged fasting and altered meal patterns. This study evaluates the efficacy and safety of Glargine 100, Glargine 300, and Degludec in managing glycemic control during Ramadan fasting, using continuous glucose monitoring (CGM) and survey data.Methods: This multicenter study included 222 participants with type 1 diabetes, stratified into three insulin regimens: Glargine 100 (n=51), Glargine 300 (n=29), and Degludec (n=142). Key metrics from CGM data included time in range (TIR), average glucose, glucose variability, and hypoglycemic events. Hypoglycemia was analyzed across fasting-critical time blocks (e.g., pre-Sahur, pre-Iftar). Surveys captured insulin adjustments and fasting interruptions.Results: TIR was 43.88% for Degludec, 48.00% for Glargine 100, and 37.93% for Glargine 300 (p=0.146). Average glucose levels were 199.11 mg/dL for Degludec, 188.04 mg/dL for Glargine 100, and 215.29 mg/dL for Glargine 300 (p=0.113). Very high glucose range (>250mg/dl) was 25.43% for Degludec users, 20.25% for Glargine 100 users, and 34.29% for Glargine 300 users (p=0.037). Mean number of Hypoglycemia events by time blocks; pre-Sahur: 1.52 for Degludec, 2.86 for Glargine 100, and 2.54 for Glargine 300 (p<0.005); pre-Iftar: 1.90 for Degludec, 2.61 for Glargine 100, and 0.29 for Glargine 300 (p=0.005). Pre-Iftar glucose levels were 126.11 mg/dL for Degludec, 138.83 mg/dL for Glargine 100, and 196.00 mg/dL for Glargine 300 (p=0.030). Fewer dose adjustments were reported with Degludec.Conclusion: This study highlights differences in insulin regimens during Ramadan fasting. Degludec provided consistent glucose levels and fewer hypoglycemic events, especially during fasting periods. Glargine 100 showed better TIR but more hypoglycemia, while Glargine 300 minimized hypoglycemia but had higher hyperglycemia. Tailored insulin regimens are essential for safe and effective Ramadan fasting.DisclosureR. Alamoudi: None. N. Aljohani: None. R. Almutairi: None. A.K. Shukri: None. M.A. Almehmadi: None. O. Yamani: None. M.M.H. Kallash: None. M.A. Khan: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-831-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 832-P: Adding Subcutaneous Basal Insulin to Insulin Pump Therapy in Adults
with Type 1 Diabetes and Recurrent Diabetic Ketoacidosis-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 832-P
Abstract: Introduction and Objective: Diabetic ketoacidosis (DKA), particularly when recurrent, is a leading cause of death in people with type 1 diabetes (T1D) <50 years of age. Our objective was to assess the glycemic impact of adding subcutaneous basal insulin to insulin pump therapy in adults with T1D and recurrent DKA.Methods: We retrospectively reviewed electronic health records of six adults with T1D and recurrent DKA who were treated concurrently with subcutaneous basal insulin and insulin pump therapy. We collected demographic, laboratory, and continuous glucose monitoring (CGM) data, reviewed provider notes, and conducted an intention-to-treat evaluation using descriptive statistics.Results: The cohort included six adults (three women, three men; age 40 ± 12 years, mean ± SD) with T1D (duration 11 ± 10 years) and recurrent DKA (mean 2.6 DKA events per person in the prior three years). All used insulin pump therapy (automated insulin delivery) and a CGM. Due to high DKA risk, all started once daily subcutaneous basal insulin (degludec or glargine, mean dose 0.12 units/kg) in addition to insulin pump therapy. We compared CGM metrics in the 90 days before versus after initiating subcutaneous basal insulin with pump therapy, finding improvements in mean time in range (36% to 47%) and mean time with glucose >250 mg/dL (34% to 24%), and no change in mean time with glucose <70 mg/dL (2%). Comparing the one year before versus after subcutaneous basal insulin initiation, mean HbA1c decreased from 9.4% to 7.5% and mean DKA events per person decreased from 1.5 to 0.5. Two adults discontinued subcutaneous basal insulin due to concern for hypoglycemia, though neither experienced a severe hypoglycemic event.Conclusion: In six adults with T1D and recurrent DKA, concurrent treatment with once daily subcutaneous basal insulin and insulin pump therapy improved glycemia and reduced DKA events. These findings warrant validation in a larger retrospective or prospective trial.DisclosureJ.K. Batth: None. B.W. Langworthy: None. A. Kumar: None. L.S. Chow: Research Support; Dexcom, Inc. J.D. Kohlenberg: Research Support; Dexcom, Inc. Speaker's Bureau; Med Learning Group.FundingNational NIH K12 Diabetes-Docs: Physician-Scientist Career Development Program' (DiabDocs), (K12DK133995)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-832-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 833-P: Efficacy and Safety of Prandial Technosphere Inhaled Insulin
(Afrezza) Compared with Placebo in Adult Individuals with T2DM—Results
from a Phase III Clinical Trial from India-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 833-P
Abstract: Introduction and Objective: Technosphere® insulin (TI) is currently the only US FDA-approved inhaled insulin delivered as a dry powder to improve glycemic control in adults with DM. Assessing efficacy and safety of TI in different ethnicities is important since the response can be variable. This trial evaluated the efficacy and safety of TI in individuals from India with T2DM, inadequately controlled on oral antihyperglycemic drugs (OADs).Methods: This was a phase III randomized, double-blind, placebo-controlled, parallel-group trial designed to investigate efficacy and safety of TI, over a 24-week treatment period. Individuals with T2DM currently treated with ≥2 OADs and with HbA1c 7.5-10.5% were randomized (2:1) to TI or placebo. The primary endpoint was to compare the change in HbA1c from baseline to week 12 between the two groups.Results: Out of 216 individuals with T2DM enrolled, 133 were randomized to TI and 83 to placebo. Mean age(SD) was 49.86(8.46) years and mean baseline HbA1c(SD) was 8.66(0.77)%. At the end of 12 weeks, there was a statistically significant difference between TI and placebo {-0.417; 95%CI(-0.74, -0.09),p=0.0124} in the mITT population (n=210), with a mean HbA1c(SD) reduction of 0.62(0.10)% in the TI arm vs. a reduction of 0.20(0.12)% in the placebo arm. The most common reported treatment emergent adverse events(TEAEs) were hypoglycemia {TI(25.6%) vs. placebo(16.9%)}, cough{TI(9.0%) vs. placebo(8.4%)}, and pyrexia{TI(5.3%) vs. placebo(8.4%)}. No discontinuation due to TEAEs were reported in any of the treatment groups. No significant differences in lung function were observed between the two groups.Conclusion: TI(Afrezza®) demonstrated a significant reduction in HbA1c in individuals from India with T2DM with no significant differences in lung function observed compared to placebo group. This study reaffirms TI as an effective and safe treatment option for T2DM management.DisclosureK. Kumar: None. M. Mohan: None. H. Gupta: None. S. Agarwal: None. N. Vikram: None. M. Mukhopadhyay: None. V. Viswanathan: None. B. Saboo: None. A. Satyaraddi: None. T. Bandgar: None. F. Farishta: None. M. Chawla: None. V. Ayyar: None. K. Kaiserman: Employee; MannKind Corporation. R. Namjoshi: Employee; Cipla. S. Jadhav: Employee; Cipla. S. Chhowala: Employee; Cipla. R. Iyer: Employee; Cipla Ltd. A. Sugumaran: Employee; Cipla Ltd. S. Sawant: Employee; Cipla Ltd. S. Mohanasundaram: Employee; Cipla Ltd. J. Gogtay: Employee; Cipla Ltd.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-833-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 834-P: A Meta-analysis of Novel Glucose-Lowering Therapies in Kidney
Transplant Recipients with Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 834-P
Abstract: Introduction and Objective: The efficacy of novel therapies like glucagon-like peptide 1 receptor agonists (GLP-1 RA) and sodium-glucose cotransporter 2 inhibitors (SGLT2i) for kidney transplant recipients (KTR) with diabetes remains uncertain. We aimed to perform a systematic review and meta-analysis to assess the efficacy and safety of GLP-1 RA and SGLT2i in these individuals.Methods: PubMed, EMBASE, Cochrane Central, and clinicaltrials.gov were systematically searched for studies using GLP-1 RA or SGLT2i in KTR with diabetes. We computed mean difference (MD) and standardized mean difference (SMD) for continuous outcomes and risk ratio (RR) for binary outcomes, with 95% confidence intervals (CIs). Heterogeneity was assessed using I² statistics. Statistical analyses were performed using Comprehensive Meta-analysis version 3.3.070.Results: We included 22 studies, comprising 5287 participants, of whom 291 underwent GLP-1 RA therapy and 3211 underwent SGLT2i therapy. After 12 months of GLP-1 RA therapy, participants had significantly lower glycated hemoglobin (HbA1c) (SMD: −0.34; 95% CI: −0.60, −0.75; p=0.012), reduced insulin requirement (MD: −7.34 U; 95% CI: −12.42; −2.26; p=0.005), and body weight (MD: −3.25 kg; 95% CI: −5.07, −1.43; p<0.001) but a similar estimated glomerular filtration rate (eGFR). Sixteen percent of individuals experienced adverse gastrointestinal side effects while receiving GLP1-RA. The use of SGLT2i was associated with a significantly reduced HbA1c (SMD: −0.31; 95% CI: −0.49, −0.15; p<0.001), body weight (MD: −2.29 kg; 95% CI: −3.17, −1.41; p<0.001), and adverse cardiovascular events (RR: 0.38; 95% CI: 0.25, 0.57; p<0.001). There were no significant differences in eGFR and genitourinary infections.Conclusion: In KTR with diabetes, the use of GLP-1 RA and SGLT2i was associated with better glycemic control, reduced body weight, and reduced insulin requirement, presenting an acceptable safety profile and optimized care.DisclosureP. Ratan: None. S. Kodalak: None. L. Saldarriaga: None. A.D. Andrade: None. R. Ferreira: None. T. Trevisan: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-834-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 835-P: Assessing the Adverse Drug Reactions for TZIELD (Teplizumab) in
Type 1 DM Patients—A Pharmacovigilance Study-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 835-P
Abstract: Introduction and Objective: Teplizumab, a novel monoclonal antibody, was approved by the U.S. Food and Drug Administration(FDA) in 2022. It is the only monoclonal antibody which is approved by FDA that delays Type 1 Diabetes onset in high-risk individuals by targeting CD3 receptors on T cells and modulating immune-mediated beta cell destruction.Methods: We used the FDA Adverse Event Reporting System (FAERS) to analyze the reported adverse events for Teplizumab. A total of 200 cases were reported since 2023. These cases were analyzed across different age groups to assess variations in safety profiles. Groups included 3-11yrs, 12-17yrs, 18-64yrs, 65-85yrs and those where the age was not specified. We used descriptive statistics to summarize the data and identify common adverse effects.Results: Of the 200 reported cases, 120(60%) cases were reported by health care professionals. Most reported reaction was rash at 49(24.50%), followed by nausea 46(23%), fatigue at 43(21.50%) and headache at 35(17.50%). Sex distribution revealed females with 99(49.50%) cases as compared to male and 31 cases did not have sex specified. Age group wise most adverse events were reported in the group of 18-64yrs which accounted for 105(52.50%) cases. There were no reported deaths over this period.Conclusion: Overall, the pharmacovigilance data for Teplizumab demonstrates a generally favorable safety profile. Most reported side effects include rash and nausea which are consistent with its mechanism of action as the monoclonal antibody and with infusion related reactions. Given the relatively limited experience in pediatric and geriatric population further studies are needed to assess the severity of adverse events in these underrepresented populations. Ongoing surveillance and post marketing data collection are crucial to further assess the long term safety and effectiveness of Teplizumab, ensuring that health care providers can make uniformed decisions regarding its use in their practice.DisclosureA. Sharma: None. D.N. Costa: None. J.P. Scarano: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-835-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 836-P: Glucagon-Like Peptide 1 Receptor Agonists Use during Ramadan
Fasting in People with Type 1 Diabetes—Observational Study-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 836-P
Abstract: Introduction and Objective: The American Diabetes Association (ADA) and European Association for the Study of Diabetes (EASD) recommend glucagon-like peptide-1 receptor agonists (GLP1-RA) for type 2 diabetes, but their use in type 1 diabetes (T1D) is limited. This study compared glycemic metrics and adverse events in fasting and non-fasting people with T1D using GLP1-RA during Ramadan.Methods: This prospective observational study included 20 people with T1D who were on a stable GLP1-RA dose and used continuous glucose monitoring (CGM) devices. Among theme, 10 people fasted (mean age±SD: 36.1±8.9 years; HbA1c: 7.7%±1.1%), while 10 did not fast (mean age±SD: 34.6±8.9 years; HbA1c: 8.2%±1.1%). Outcomes measured the percentage of time spent in the target glucose range (3.9-10 mmol/L), hyperglycemic range (>10 mmol/L), hypoglycemic range (<3.9 mmol/L), glucose variability (CV%), glucose management indicator (GMI), and diabetic ketoacidosis (DKA) incidences. All participants received structured education on the safe use of GLP1-RA.Results: The mean fasting duration was 22.7±4.7days (range: 18-29days). There were no significant differences observed between the fasting and non-fasting groups in target range (47.3±19.3% vs. 50.7±19.3%), hyperglycemic range (49.9±19.4% vs. 47.7±20.8%), hypoglycemic range (2.8±2.3% vs. 1.6±2.3%), glycemic variability (36.8±8.4% vs. 36.0±5.0%) and GMI (7.6±0.5% vs. 7.8±0.9%) (all p≥0.22). No severe hypoglycemia, diabetic ketoacidosis (DKA), or hospitalizations were reported in either group during the fasting period.Conclusion: The use of GLP1-RA in people with T1D during fasting appears to be safe and well-tolerated, with no adverse events reported among those who received structured education. However, further clinical trials are required to confirm these findings.DisclosureE. Taghadom: None. M. Irshad: None. L.G. Sojan: None. D. Alroudhan: None. J. AlKandari: None. E. Al-Ozairi: None.FundingKuwait Foundation for the Advancement of Sciences (KFAS), Kuwait
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-836-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 837-P: Efficacy and Safety of a Novel Oral Small Molecule Glucagon-Like
Peptide 1 Receptor Agonist (HRS-7535) in Type 2 Diabetes Mellitus Patients
Inadequately Controlled by Metformin-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 837-P
Abstract: Introduction and Objective: HRS-7535, an oral small molecule GLP-1RA, is under development for T2DM and obesity. The study evaluated its efficacy and safety in T2DM participants (pts) inadequately controlled on metformin.Methods: In this randomized, double-blind, multicenter phase 2 study, 194 pts were randomized (1:1:1:1:1) to receive once-daily doses of HRS-7535 at 15, 30, 60, 90, or placebo (PBO). The 60 and 90 mg doses were targeted dose via titration. Primary endpoint was change from baseline in HbA1c at wk 16.Results: 177 (91.2%) completed 16-wk treatment period. At baseline, mean age was 52.3 yrs, HbA1c was 8.5%, BMI was 26.7 kg/m², body weight (BW) was 73.4 kg, 59.3% were men, and ~80% were taking ≥ 1500 mg/day metformin. At wk 16, the PBO-adjusted least-squares (LS) mean changes in HbA1c for HRS-7535 doses of 15, 30, 60, and 90 mg were -0.94%, -1.34%, -1.57%, and -1.39%, respectively (P<0.001 for all doses vs. PBO). At wk 16, the LS mean percentage change in BW reached -2.63% for the 90 mg group vs. -1.30% for PBO. At wk 16, HRS-7535 showed dose-related reductions in FPG, 2h-PG, and waist circumference. During the 16-wk treatment, 3.2% of HRS-7535 and 30.8% of PBO pts required rescue therapy. TEAEs occurred in 71.8-84.6% of HRS-7535-treated pts vs. 76.8% with PBO. Most TEAEs were gastrointestinal-related (nausea: 7.7-34.2% on HRS-7535 vs. 2.6% on PBO; diarrhea: 5.1-15.4% vs. 0%; vomiting: 2.6-15.8% vs. 0%), and mild to moderate. 9 pts (5.8%) on HRS-7535 had documented hypoglycemia; no Level 2 or higher events were reported. Pts on HRS-7535 showed a trend toward increased serum amylase and lipase levels, with no cases of pancreatitis observed. At wk 16, pts on HRS7535 had a mean pulse rate increase of 0.21-3.18 bpm from baseline.Conclusion: HRS-7535 significantly resulted HbA1c in Chinese pts with T2DM inadequately controlled on metformin and exhibited an acceptable safety profile consistent with other GLP-1RAs.Disclosure L. Guo: Research Support; Abbott, AstraZeneca, Bayer Pharmaceuticals, Inc, Eli Lilly and Company, Innovent Biologics, Merck & Co., Inc, MSD Life Science Foundation, Novo Nordisk A/S, Sanofi, Jiangsu Hengrui Pharmaceuticals Co., Ltd, Tonghua Dongbao. Z. Sun: None. L. Zhang: None. G. Qin: None. Y. Li: None. Z. Ye: Employee; Jiangsu Hengrui Pharmaceuticals Co., Ltd. Y. Xu: Employee; Jiangsu Hengrui Pharmaceuticals Co., Ltd. C. Shu: Employee; Jiangsu Hengrui Pharmaceuticals Co., Ltd. P. Liu: Employee; Jiangsu Hengrui Pharmaceuticals Co., Ltd.FundingJiangsu Hengrui Pharmaceuticals Co., Ltd.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-837-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 838-P: Changes in Clinical Measures in U.S. Adults with Type 2 Diabetes
(T2D) and Chronic Kidney Disease (CKD) Who Received Once-Weekly (OW)
Semaglutide-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 838-P
Abstract: Introduction and Objective: To assess changes in clinical measures in US adults with T2D and CKD treated with OW semaglutide.Methods: Adults with T2D and CKD who initiated OW semaglutide between Jan 1, 2019 and Jun 30, 2023 were selected from Optum’s de-identified Clinformatics® Data Mart Database. Clinical measures were compared before vs. during OW semaglutide treatment. Changes were described at Month 12, and trajectories were analyzed with mixed models in the overall cohort and subgroups: those 1) ineligible for sodium-glucose cotransporter-2 inhibitor (SGLT2i) due to advanced CKD stages, 2) for whom SGLT2is were suboptimal indicated by treatment switch or augmentation with OW semaglutide after SGLT2i use, and 3) with stage IV CKD or kidney failure.Results: Out of 49,683 patients, 67.6% were aged 65 or older and 56.7% were female. After OW semaglutide treatment, there was a decline in HbA1c (12-month mean change [95% confidence interval]: -1.2% [-1.3%, -1.2%]), increase in estimated glomerular filtration rate (1.6 mL/min/1.73 m2 [1.2, 2.0]), decline in body weight (-6.0 kg [-6.7, -5.4]), and decline in systolic blood pressure (SBP; -2.9 mmHg [-4.1, -1.7]). Similar trends were observed in all subgroups.Conclusion: Real-world patients with T2D and CKD treated with OW semaglutide had improved glycemic control and kidney function and reduced body weight and SBP.Disclosure J. Amamoo: Employee; Novo Nordisk. Y. Wang: Other Relationship; Analysis Group, Inc. H. Liu: Employee; Analysis Group, Inc. M. Sundar: Consultant; Novo Nordisk. Y. Song: Research Support; Novo Nordisk. L. Xie: None. S.J. Mehanna: None. J. Noone: Employee; Novo Nordisk. C. Swift: Employee; Novo Nordisk. Stock/Shareholder; Novo Nordisk. M.R. Weir: Advisory Panel; AstraZeneca, Bayer Pharmaceuticals, Inc, Novo Nordisk, Corcept Therapeutics, Vifor Pharma. Consultant; Intercept Pharmaceuticals, Inc.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-838-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 839-P: Efficacy and Safety of HDG1901 vs. Ozempic in Patients with Type 2
Diabetes (T2D)—A Randomized, Open-Label, Bioequivalence Phase 3 Trial-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 839-P
Abstract: Introduction and Objective: HDG1901 is a biosimilar of semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1 RA). The efficacy and safety of HDG1901 as compared with the the reference semaglutide (Ozempic®) was investigated in a Phase 3 trial.Methods: A total of 490 participants were randomized in a 1:1 ratio to receive weekly dose of either HDG1901 or reference semaglutide for 32 weeks, including 8-week titration and 24-week maintenance treatment at 1mg. Participants with the glycosylated hemoglobin (HbA1c) between 7 and 10.5 % and age of 18-75 years were enrolled. The primary endpoint was the change from baseline in HbA1c at week 32.Results: The least square mean changes from baseline in the HbA1c at Week 32 was -2.047% for HDG1901 group (N=245) and -2.008% for reference semaglutide group (N=245). The treatment difference between this two group was -0.038, the upper and lower bound of the 95% confidence interval for treatment difference was within the equivalence margin of 0.4 % (95%CI: -0.189, 0.112 ). At Week 32, the least square mean changes from baseline in bodyweight was -4.094kg for HDG1901 group and -4.346kg for reference semaglutide group. The incidence of treatment-emergent adverse events (TEAEs) for HDG1901 and reference semaglutide was 81.7% and 90.3%, respectively. High incidence of gastrointestinal related TEAEs were reported in the HDG1901 and reference semaglutide groups (nausea, 9.3% and 14.6%; diarrhea, 16.7% and 17.0%; and vomiting, 7.7% and 9.3%), and were primarily mild to moderate. A minority of participants (2.0% and 2.8%) discontinued treatment due to TEAEs in the HDG1901 and reference semaglutide groups, respectively.Conclusion: In patients with T2D, HDG1901 was equivalent to reference semaglutide with respect to the mean changes from baseline in HbA1c at 32 weeks. HDG1901 was generally well tolerated in this population. It offers an option for the treatment of T2D (ClinicalTrials.gov identifier: NCT06739044).Disclosure L. Guo: Research Support; Abbott, AstraZeneca, Bayer Pharmaceuticals, Inc, Eli Lilly and Company, Innovent Biologics, Merck & Co., Inc, MSD Life Science Foundation, Novo Nordisk A/S, Sanofi, Jiangsu Hengrui Pharmaceuticals Co., Ltd, Tonghua Dongbao. S. Pang: None. Z. Cheng: None. J. Song: Research Support; HuaDong Pharmaceutical Co.,Ltd. H. Ling: None. X. Shi: None. L. Zhang: None. X. Wang: Employee; HuaDong Pharmaceutical Co., Ltd. H. Gao: Employee; HuaDong Pharmaceutical Co. Ltd. L. Shen: Employee; HuaDong Pharmaceutical Co., Ltd. L. Zhong: Employee; HuaDong Pharmaceutical Co.,Ltd. J. Xu: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-839-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 840-P: TN-10 Extension Study—Teplizumab following Stage 3 Type 1
Diabetes Diagnosis in Participants from the TN-10 Trial-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 840-P
Abstract: Introduction and Objective: Teplizumab is the first therapeutic to demonstrate the ability to delay progression from stage 2 to stage 3 type 1 diabetes (T1D). In this extension of the TrialNet stage 2 teplizumab study (TN-10), we followed participants who received a course of teplizumab after developing stage 3 T1D.Methods: TN-10 Extension was a multicenter, single-arm, open-label study of former TN-10 participants previously randomized to a 14-day course of teplizumab or placebo. Participants within 1 year of stage 3 T1D diagnosis received a 12-day course of teplizumab with up to 78 weeks of follow-up.Results: Six participants (aged 12-44 years) received teplizumab; 5 previously received teplizumab and 1 received placebo in TN-10. Five participants received all 12 doses; 1 received 11 doses. The mean time from stage 3 diagnosis to first teplizumab dose was 36.8 weeks. All participants had at least 1 treatment-emergent adverse event (TEAE) and 5 had treatment-related TEAEs. Treatment-related TEAEs reported for ≥50% of participants were headache, nausea, and lymphopenia (n=3 for each). One participant had the treatment-related TEAE of cytokine release syndrome (Grade 1, mild and fully resolved). No TEAEs led to treatment discontinuation. One serious AE, completed suicide, was not considered related to treatment. No hypoglycemia or diabetic ketoacidosis events were reported. Six of 6 participants had anti-drug antibodies and 4/6 had neutralizing antibodies. Mean (SD) HbA1c (%), average daily insulin use (U/kg/day), and C-peptide ln(AUC+1) was 7.22 (1.91) (n=6), 0.34 (0.17) (n=4), and 0.685 (0.209) (n=6) at baseline; and 8.50 (3.79) (n=4), 0.54 (0.36) (n=4), and 0.549 (0.428) (n=4) at Day 546, respectively. One participant met insulin discontinuation criteria.Conclusion: Teplizumab was safe and well tolerated in participants with stage 3 T1D. No new safety signals emerged in participants who received 1 course of teplizumab in stage 2 T1D and then 1 in stage 3 T1D.Disclosure K.C. Herold: Consultant; Sanofi, Dompé, Vertex Pharmaceuticals Incorporated, Sonoma, NexImmune. J.L. Sherr: Consultant; Abbott. Advisory Panel; StartUp Health T1D Moonshot. Research Support; Dexcom, Inc. Advisory Panel; Cecelia Health, MannKind Corporation. Consultant; Insulet Corporation, Vertex Pharmaceuticals Incorporated, Ypsomed AG. Advisory Panel; Medtronic, Vertex Pharmaceuticals Incorporated. M.J. Haller: Advisory Panel; SAB Biotherapeutics, Inc, MannKind Corporation. Consultant; Sanofi. W.E. Russell: None. L. Knecht: Employee; Sanofi. Stock/Shareholder; Sanofi. Employee; Provention Bio, Inc, Provention Bio, Inc, Microbion, Microbion. Stock/Shareholder; Provention Bio, Inc, Provention Bio, Inc, Microbion, Microbion. E. Niemoeller: Employee; Sanofi-Aventis Deutschland GmbH. S. Andjelic: Employee; Sanofi. O. Gonzalez: Employee; Sanofi. Stock/Shareholder; Sanofi. P. Picard: None. P. Gottlieb: Other Relationship; IM Therapeutics. Consultant; Abata Therapeutics, COUR Pharmaceuticals, Imcyse. Research Support; Leona M. and Harry B. Helmsley Charitable Trust. Consultant; Juvenile Diabetes Research Foundation (JDRF). Research Support; National Institute of Diabetes and Digestive and Kidney Diseases. Other Relationship; Sanofi. Research Support; Nova Pharmaceuticals. Consultant; ViaCyte, Inc, GentiBio. Research Support; Provention Bio, Inc, Provention Bio, Inc, Microbion, Microbion. Consultant; SAB.FundingFunding: This study was funded by Sanofi.Acknowledgments: Medical writing support was provided by Amicha Robertson, PhD, of IMPRINT Science, New York, NY, and was funded by Sanofi.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-840-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 841-P: Real-World Effectiveness of Finerenone in Indian Patients with Type
2 Diabetes Mellitus (T2DM) and Chronic Kidney Disease (CKD)-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 841-P
Abstract: Introduction and Objective: Given the inconsistence of real-world treatment with randomized controlled trials (RCTs) and guidelines, the risk of cardiovascular-renal events remains in patients with T2DM and CKD. This study aimed to assess the real-world effectiveness of finerenone in patients with T2DM and CKD across 2 centres in Mumbai, India.Methods: This retrospective study included patients with T2DM and CKD with microalbuminuria. Urinary albumin-to-creatinine ratio (UACR), estimated glomerular filtration rate (eGFR), and serum potassium were recorded at baseline and post-finerenone treatment.Results: Of the 149 patients, mean age was 60.4± 22 yrs,100 were male, mean duration of T2DM was16.87± 13yrs. Of these 80% were on sodium glucose co-transporter type 2 inhibitors,25% on glucagon like peptide receptor agonists, 50% on insulin and 75% on renin angiotensin system antagonists. Baseline UACR was 682 ± 1294.66 mg/g.55% patients had microalbuminuria (30-300mg/g),44% patients had gross proteinuria (>300mg/g). Finerenone was administered at 10mg daily dose for 3 months following which UACR decreased by 58 % 235.59 ± 371.41mg/g. Egfr also showed improvement from 70.16 ± 24.47 to 63.41 ±20.34 ml/min/1.73m2 in patients with baseline egfr of 45-60 ml/mim/1.73m2 (18% of patients). In patients with Egfr >60ml/min/1.73m2 (62.7% of patients ) egfr remained stable. In patients with 25-45 ml/min/1.73m2 egfr remained stable. Serum potassium levels increased marginally from 4.31+_0.37 to 4.48+_0.36 mmol/l and no hyperkalemia was noted.Conclusion: Despite the different treatment background and finerenone use between the real-word clinical practice and RCTs, similar UACR reduction was observed in this study compared to FIGARO-DKD trials. Finerenone might improve proteinuria control and could be a promising treatment option to reduce the risk of cardiovascular-renal events in patients with T2DM and CKD in the integrated management.DisclosureS.A. Patange: None. D. Padhye: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-841-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 842-P: A Novel CRFR2-Selective UCN2 Analog, HM17321, Improves Glycemic
Control across Multiple Preclinical Models-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 842-P
Abstract: Introduction and Objective: Obesity is a major cause of various metabolic diseases, particularly type 2 diabetes (T2D), and most of the T2D patients are overweight or obese. Thus, glycemic control efficacy becomes to be recognized as one of the essential features of anti-obesity medication. HM17321, a novel CRFR2-selective UCN2 was developed for high quality weight management, and its proof of concept was demonstrated in animal models of obesity. Here, the potential benefits of HM17321 on glucose homeostasis and related mode of action was further investigated.Methods: ipGTT was performed in normal mice after single drug administration. In DIO mice, HOMA-IR was determined after 8 weeks treatment of HM17321. To evaluate overall glycemic control effect, db/db mice were administered with HM17321 for 4 weeks, followed by HbA1c measurement and ipGTT. Semaglutide (Sema) was included as a comparative control.Results: In normal mice, single administration of HM17321 significantly reduced BG during ipGTT, indicating its rapid glucose tolerance improvement effects. Similarly, chronic treatment of HM17321 significantly reduced HOMA-IR in DIO mice (8.8 ~ 11.8 vs. 65.7 for DIO vehicle; 11.2 for normal vehicle), indicating its improvement effect on insulin resistance. In line with these findings, 4 weeks treatment of HM17321 in diabetic db/db mice significantly decreased HbA1c and ipGTT AUCBG compared to vehicle. Notably, overall glycemic control effect in db/db mice was comparable to even higher than Sema.Conclusion: Series of nonclinical evaluations clearly demonstrate improvement effects of HM17321 on glucose tolerance and insulin resistance, which eventually leads to HbA1c lowering effect. These results suggest additional benefits of HM17321 in glycemic control in addition to high quality weight management. Further studies will elucidate the mechanisms by which HM17321 contributes to improved glucose homeostasis, including direct improvement of insulin signaling.DisclosureS. Lee: None. E. Kim: None. J. Kim: None. W. Kim: None. E. Park: None. J.A. Kim: None. S. Hong: None. S. Bae: None. S. Lee: None. I. Choi: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-842-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 843-P: A Novel CRFR2 Selective UCN2 Analog, HM17321, Facilitates Weight
Loss and Improves Body Composition across Animal Models of Obesity-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 843-P
Abstract: Introduction and Objective: Incretin drugs effectively promote weight loss, but also cause inevitable lean mass loss, compromising weight loss quality (WLQ). Urocortin-2 (UCN2) shows potential for enhancing lipolysis and muscle hypertrophy, offering a strategy to improve WLQ. To achieve these outcomes, a novel corticotropin-releasing factor receptor-2 (CRFR2) selective UCN2 analog, HM17321, was developed. The present study evaluates the potential effects of HM17321 on body weight (BW) and body composition.Methods: In DIO mice and rats, BW, body composition, muscle tissue and blood parameters were analyzed after chronic treatment of HM17321. Semaglutide (Sema) was included as a comparative control. Monkeys were utilized for potential human translation.Results: In DIO mice, HM17321 treatment significantly reduced BW in a dose-dependent manner. Although BW loss was slightly less pronounced, HM17321 showed a greater fat mass loss compared to Sema. Importantly, unlike Sema, HM17321 significantly increased lean mass and reduced lipid content in muscle tissue, indicating both quantitative and qualitative muscle improvement effect. In addition, HM17321 significantly reduced serum BG, total cholesterol, and ALT. As to the mode of action for this WLQ improvement, HM17321 showed a greater fat mass reduction along with a significant muscle hypertrophic effect compared to pair-fed control, suggesting HM17321’s direct actions on adipose tissue catabolism and skeletal muscle anabolism. The favorable body recomposition was reproduced in DIO rats. Most strikingly, HM17321 treatment was associated with fat mass loss-driven BW loss in monkeys.Conclusion: HM17321 demonstrates robust fat mass reduction and lean mass increasing effect across animal models including monkeys. These findings underscore the potential of HM17321 for high quality weight management, supporting its continued development as a differentiated anti-obesity drug.DisclosureJ. Kim: None. S. Lee: None. E. Kim: None. D. Lee: None. J. Lee: None. H. Kwon: None. E. Park: None. J.A. Kim: None. S. Han: Employee; Hanmi Pharm. Co., Ltd. J. Park: None. S. Hong: None. S. Bae: None. S. Lee: None. I. Choi: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-843-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 844-P: Association between Preoperative GLP-1RA Use and Postoperative
Respiratory Complications in Real-World Patients Undergoing Elective
Surgical Procedures—A Target Trial Emulation Study-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 844-P
Abstract: Introduction and Objective: There have been growing concerns about GLP-1 RA use and the risk of aspiration pneumonia. Mixed results exist regarding aspiration pneumonia risk with perioperative GLP-1 RA use, with limited focus on elective surgical procedures. Therefore, we assessed the association between preoperative GLP-1 RA use and postoperative respiratory complications in patients undergoing elective surgical procedures.Methods: This retrospective cohort study followed the target trial emulation framework and used OneFlorida+ EHR data from Jan 1, 2015, to Jan 31, 2023. Patients undergoing elective surgical procedures were included, excluding emergency/trauma, transplant, neurosurgery, gastric, head and neck surgeries, and/or pregnancy. GLP-1 RA users were defined as those using GLP-1 RAs within a week before surgery, compared to non-users. The primary outcome was postoperative respiratory complications within 7 days, defined as a composite of aspiration pneumonia and respiratory failure. Subgroups included sex, age, race/ethnicity, T2D, obesity, GLP-1 RA type, and duration. Sensitivity analysis followed patients until discharge. Hazard Ratios with 95% CIs were estimated using Cox models in a matched cohort.Results: After propensity matching, 655 GLP-1 RA users and 1855 non-users were included. GLP-1 RA use was associated with increased postoperative respiratory complications (HR: 1.61, 95% CI: 1.08-2.39); 5.5% users vs. 3.5% non-users. The risk remained consistent in sensitivity analysis. Subgroup analysis showed higher risks in adults ≥50 years, patients with T2D, Hispanics, and, particularly, lixisenatide-exenatide users (HR: 2.97, 95% CI: 1.13-7.77), there was no difference in risk by GLP-1 RA duration of action.Conclusion: Preoperative GLP-1 RA use was associated with increased postoperative respiratory complications compared to non-users.Disclosure P. Kotecha: Employee; Takeda Pharmaceutical Company. W.T. Donahoo: None. A. Sharma: None. R.C. Sun: None. C. Yang: None. J. Bian: None. J. Guo: None.FundingNational Institute of Diabetes and Digestive and Kidney Diseases (R01DK133465)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-844-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 845-P: MBX 1416, a Selective GLP-1 Antagonist, Elevates and Sustains Blood
Glucose in Rats without Change in Body Weight-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 845-P
Abstract: Introduction and Objective: MBX 1416 is a selective, reversible glucagon-like peptide-1 receptor (GLP-1R) antagonist being investigated for treating post-bariatric hypoglycemia. In vivo studies examined pharmacokinetic/pharmacodynamic (PK/PD) properties of MBX 1416.Methods: MBX 1416 single subcutaneous dose PK was assessed in Sprague-Dawley rats for dose selection. The GLP-1 antagonist mechanism of action was tested in rats by reversing effects of a potent GLP-1 agonist, semaglutide. Differential effects of MBX 1416 on glucose elevation following glucose challenge in DIO mice vs an unmodified GLP-1 antagonist exendin 9-39 (Ex9) were assessed with an intraperitoneal glucose tolerance test (IPGTT) 24 h post dosing to highlight MBX 1416’s lengthy time action.Results: Dose-proportional plasma MBX 1416 exposures were seen with a single dose (Cmax and AUCinf, ≤2-fold across doses). In healthy rats, MBX 1416 completely abrogated anorectic and weight loss activity of semaglutide but when given alone, had no effect on body weight or food intake vs controls. In DIO mice, MBX 1416 led to a greater glucose excursion in an IPGTT that was sustained 24 hours; in contrast, the GLP-1 antagonist Ex9 showed no activity at 24 h.Conclusion: MBX 1416 demonstrated expected PK/PD effects in rats, increasing blood glucose excursions in DIO mice with no change in food intake or body weight vs vehicle in healthy rats.DisclosureK. Thalluri: None. M.J. Hackett: None. J.J. Pellman: None. A. Joice: None. E. Fabbrini: Employee; Janssen Pharmaceuticals, Inc. Stock/Shareholder; Janssen Pharmaceuticals, Inc. Employee; MBX Biosciences. D. Perez-Tilve: Research Support; MBX Biosciences, Novo Nordisk A/S. Other Relationship; BlueWater LLC, Ghrelco LLC. Consultant; Eli Lilly and Company, Ampeptec. R. DiMarchi: Research Support; MBX Biosciences. M.A. Dorato: Stock/Shareholder; Eli Lilly and Company.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-845-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 846-P: Safety and Pharmacokinetics of MBX 1416, a Glucagon-Like Peptide 1
Receptor Antagonist, in Healthy Volunteers—A Phase 1 Randomized Trial-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 846-P
Abstract: Introduction and Objective: MBX 1416 is a selective, reversible glucagon-like peptide-1 receptor (GLP-1R) antagonist designed to treat post-bariatric hypoglycemia (PBH). We assessed safety, tolerability, and pharmacokinetics (PK) of MBX 1416 in healthy volunteers (HVs).Methods: A double-blind trial (NCT06036784) randomized cohorts 3:1 MBX 1416:placebo (8 HVs/dose level). MBX 1416 was injected subcutaneously in 4 single (SAD; 10-200 mg) or 2 multiple ascending dose (MAD; 10-30 mg weekly) levels. The primary endpoint was safety/tolerability. PK (SAD/MAD) and PD (MAD; glucose and GLP-1 in a mixed meal tolerance test [MMTT]) were assessed. In a third part, single-dose MBX 1416 drug-drug interactions (DDIs) were evaluated vs acetaminophen (to assess gastric emptying [GE]) or rosuvastatin.Results: Overall, 32 (SAD), 23 (MAD), and 14 (DDI) HVs enrolled. MBX 1416 was generally well tolerated (Table). MBX 1416 exposure was dose proportional with median Tmax within 24-48 h and long T1/2 (~90 h) supporting weekly dosing. An apparent increase in GLP-1 peak during MMTT was observed. MBX 1416 resulted in a nonclinically meaningful increase in rosuvastatin Cmax, possibly related to slightly accelerated GE.Conclusion: In HVs, MBX 1416 was generally well tolerated, with PK supporting weekly dosing, PD showing an apparent effect on GLP-1, and minimal DDI with rosuvastatin PK.Disclosure E. Fabbrini: Employee; Janssen Pharmaceuticals, Inc. Stock/Shareholder; Janssen Pharmaceuticals, Inc. Employee; MBX Biosciences. P. Carney: None. A. Koshkina: Stock/Shareholder; Janssen Pharmaceuticals, Inc. Employee; MBX Biosciences. K. Schneider: Employee; MBX Biosciences. S. Azoulay: Employee; MBX Biosciences. Stock/Shareholder; Pfizer Inc, Roivant.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-846-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 847-P: ASC47, a Muscle-Preserving Weight Loss Drug Candidate for Obesity,
in Combination with Semaglutide, Demonstrated Superior Weight Loss to
Semaglutide Monotherapy in a Preclinical Model-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 847-P
Abstract: Introduction and Objective: ASC47 (selective THR-β agonist) is an adipose-targeted, once-monthly subcutaneously (SQ) injected, muscle-preserving weight loss drug candidate for the treatment of obesity, discovered and developed in-house at Ascletis. This study in diet-induced obese (DIO) mice demonstrated a powerful synergy in weight loss and muscle preservation when combining ASC47 and semaglutide.Methods: C57BL/6J mice were fed a high-fat diet for 16 weeks and received different treatments for 28 days. Body weight and food intake were recorded daily. Body composition was assessed by EchoMRI weekly.Results: ASC47 low dose combination 1 demonstrated superior weight loss compared to semaglutide monotherapy, showing an average total body weight reduction of 36.2%, a 56.7% greater reduction in body weight compared to semaglutide monotherapy. At the end of treatment, the percentage of total muscle mass over the total body weight of obese mice treated with ASC47 low dose combination treatments (68.8%) were close to healthy non-obese mice (66.0%), indicating healthy weight loss. Semaglutide monotherapy was unable to restore body composition to healthy levels.Conclusion: ASC47 low dose combination treatments were well tolerated in obese mice and produced a significant and healthy WL.Disclosure J. Wu: Employee; Ascletis Pharma (China) Co., Limited. C. Wu: Employee; an affiliate of Ascletis Pharma (China) Co., Limited,.FundingAscletis Pharma (China) Co., Limited
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-847-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 848-P: The Antidiabetic Medication Treatment Patterns in Chinese Patients
with Type 2 Diabetes—Real-World Evidence from ICaReMe China Registry
Study-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 848-P
Abstract: Introduction and Objective: The global prevalence of type 2 diabetes mellitus (T2DM) is widely recognized to be on the rise. It is of great significance to reveal the current status of antidiabetic therapy in patients with T2DM.Methods: “Real-world Multicenter Registry to Determine Management and Quality of Care of Patients With Type 2 Diabetes in China” (iCaReMe China) is a prospective, multicentric, observational registry study. The study enrolled a total of 9,000 adults with T2DM from 60 hospitals in China from 2023 July to 2024 March, collecting demographic information, treatment patterns, complications, physical examination and laboratory test results.Results: Of the 9,000 participants enrolled, 99.2% were treated with antidiabetic medication, among which, 28.5% of the patients received monotherapy, and 71.5% of them received combination therapy. Metformin was the most frequent antidiabetic medication (59.5%), followed by SGLT2 inhibitor (38.9%), insulin (36.8%), α-glycosidase inhibitor (29.2%), DPP-4 inhibitor (16.8%), GLP-1 receptor agonist (14.9%), sulphonylurea (9.4%), and thiazolidinedione (5.2%). Compared with patients without diabetic complications, higher user percentage of SGLT2 inhibitor (46.9% vs 37.3%, P<0.001; 42.7% vs 38.4%, P=0.002), GLP-1 receptor agonist (20% vs 14%, P<0.001; 17.4% vs 14.4%, P=0.003), insulin (53.9% vs 33.8%, P<0.001; 46.2% vs 34.9%, P<0.001), α-glycosidase inhibitor, DPP-4 inhibitor and sulphonylurea were observed respectively in patients with microvascular and macrovascular diabetic complications.Conclusion: iCaReMe China demonstrated descriptive data on antidiabetic medication treatment patterns in Chinese patients with T2DM. Metformin is the most commonly used antidiabetic medication in Chinese patients with T2DM. The patients with microvascular and macrovascular diabetic complications were more likely to use SGLT2 inhibitors and GLP-1 receptor agonists.DisclosureH. Wu: None. X. Cai: None. W. Yang: None. B. Feng: None. Y. Li: None. M. Liu: None. N. Tong: None. L. Ji: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-848-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 849-P: Eloralintide (LY3841136), a Selective Amylin Mimetic, Lowered Body
Weight with Improved Quality of Weight Loss and GI Tolerability in Rats
Compared with Cagrilintide-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 849-P
Abstract: Introduction and Objective: Non-selective amylin analogs have shown clinical weight loss benefits, though clinical incidence of nausea and vomiting are high and may require prolonged dosing titrations. Moreover, preclinical studies in rats suggest lean mass preservation versus GLP-1 receptor agonists. Herein, we evaluated weight loss efficacy, GI tolerability, and lean-mass preservation in rats administered eloralintide compared to the non-selective amylin analog, cagrilintide.Methods: Peptides were made using automated peptide synthesizers and evaluated in amylin and calcitonin receptor functional and binding assays. PK and conditioned taste avoidance studies performed using lean rats. Weight loss studies were carried out in lean and DIO rats using QNMR to determine body composition.Results: Eloralintide is an amylin peptide analog modified with a C20 fatty diacid moiety that binds to amylin receptors while retaining selectivity from calcitonin receptors. Eloralintide demonstrated prolonged plasma half-life and reduced clearance compared to cagrilintide. In lean rats, eloralintide matched the food intake reductions of cagrilintide, resulting in a similar degree on body weight change, without the same degree of conditioned taste avoidance. In DIO rats, eloralintide lowered body weight primarily by loss of fat mass and with more potent effects for weight loss efficacy, food intake lowering, and fat mass reductions compared to cagrilintide, with head-to-head studies demonstrating reduced loss of lean mass in comparison to cagrilintide.Conclusion: Eloralintide demonstrated preclinical improvements in efficacy, GI tolerability, and quality of weight loss compared to the non-selective amylin analog cagrilintide. These findings support clinical investigation of eloralintide as a weight loss therapeutic.Disclosure D.A. Briere: Employee; Lilly USA LLC. A. Long: Employee; Eli Lilly and Company. D.M. Bullock: None. L. O'Farrell: None. B. Bowen: Employee; Eli Lilly and Company. K. Lansu: Employee; Eli Lilly and Company. T. Coskun: None. J.S. Moyers: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. H. Qu: Employee; Eli Lilly and Company.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-849-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 850-P: Comparision of Efficacy on MASLD between GLP-1RA and SGLT2i—A
Real-World Study-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 850-P
Abstract: Introduction and Objective: Metabolic dysfunction-associated fatty liver disease (MASLD), affects approximately 38% of the global population, with a prevalence as high as 70% among individuals with type 2 diabetes mellitus (T2DM). This study aims to determine the efficacy of glucose-lowering drugs, glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-dependent glucose transporters 2 inhibitors (SGLT-2i), in improving fatty liver in patients with type 2 diabetes.Methods: Patients with T2DM and MASLD from Zhongda Hospital, Southeast University were recruited. Liver fat and fibrosis were assessed using elastography, with a controlled attenuation parameter (CAP) score of ≥244 dB/m defining hepatic steatosis and a liver stiffness measurement (LSM) score of ≥7.85 kPa defining fibrosis. Propensity score matching was used.The primary endpoint was the improvement of fatty liver and the secondary endpoint was the improvement of liver stiffness.Results: The baseline characteristics of new users and non-users of SGLT-2i were balanced. After using SGLT-2i for more than 3 months, there was a significant decrease in liver fat content. But there was no statistical significance on the change of liver stiffness. Similarly, the baseline characteristics of new users and non-users of GLP-1RAs were balanced. After using GLP-1RAs for more than 3 months, both liver fat content and liver stiffness significantly decreased.Conclusion: In real clinical practice, both SGLT2i and GLP1RAs can significantly improve fatty liver in patients with diabetes and MASLD.DisclosureW. Sun: None. L. Li: None.
PubDate: Fri, 13 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-850-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 851-P: A Phase 1, Double-Blind, Placebo-Controlled Single- and
Multiple-Ascending Dose Study of the Novel Lipidated IL-22 Receptor
Agonist CK-0045 in Adults with and without Obesity-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 851-P
Abstract: Introduction and Objective: CK-0045 is a novel long-acting IL-22 receptor agonist with great potential for treatment of patients with metabolic diseases based on preclinical data. Here we present the results of a randomized, double-blind, placebo-controlled, Phase 1 study investigating safety, tolerability, and pharmacokinetics of CK-0045 in healthy participants with and without obesity.Methods: A total of 40 healthy participants were randomized 3:1 to a single subcutaneous dose of 1 - 30 µg/kg CK-0045 or placebo in 5 cohorts in the single ascending dose (SAD) part. In the multiple ascending dose (MAD) part, a total of 36 otherwise healthy participants with obesity (BMI 30 - 39.9) received once-weekly subcutaneous doses of CK-0045 (1.25, 2.5 or 5 µg/kg) or placebo (3:1 ratio) for 6 weeks.Results: CK-0045 was safe at all doses tested, and well-tolerated up to 10 µg/kg in the SAD and 2.5 µg/kg in the MAD. All adverse events were mild or moderate, with dry skin, dry lips, and pruritus being the most frequently reported adverse drug reactions. There were no clinically significant adverse trends in labs, electrocardiograms, or vital signs. CK-0045 treatment resulted in dose-proportional increases in exposure and in target engagement biomarkers. Body weight reductions at week 6 were not dose-dependent but did demonstrate an exposure-dependent relationship when analyzed by CK-0045 exposure tertile (+0.8%, -1.1%, and -1.6%). The weight loss in the highest exposure tertile at week 6 was significantly greater (p=0.04) than in the placebo group (-0.3%). Significant reductions in cholesterol levels were also observed as well as non-significant signals of efficacy on several other metabolic parameters.Conclusion: This Phase 1 study of the novel lipidated IL-22 agonist CK-0045 identified safe and tolerable doses with promising exploratory efficacy trends despite high baseline variability and short treatment duration.Disclosure M. van de Bunt: Employee; Cytoki Pharma. C. Friis: Employee; Cytoki Pharma. F. Cauwberghs: None. R. Jorgensen: Employee; Cytoki Pharma. A. Kjølbye: Employee; Cytoki Pharma.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-851-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 852-P: Factors Associated with the Use of Adjunct-to-Insulin
Glucose-Lowering Agents in Patients with Type 1 Diabetes Mellitus-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 852-P
Abstract: Introduction and Objective: Adjunct-to-insulin metformin, Glucagon-Like Peptide-1 receptor agonists (GLP1-RA), and Sodium Glucose Co-transporter 2 inhibitors (SGLT2i), mostly off-label, are used by people with type 1 diabetes (PwT1D) to address the challenges of glucose control and other outcomes. We investigated the socio-demographic and disease-related characteristics associated with their use.Methods: Cross-sectional comparison of self-reported demographic and clinical variables between adjunct-to-insulin users vs. non-users in the Canadian BETTER registry were made (by Chi square for categorical and Mann-Whitney U test for non-normally distributed continuous variables).Results: Among 1463 participants (67.1% women, median [IQR] age 44.0 years [31.0, 56.0], BMI 25.6 kg/m2 [22.7, 29.1], 30.6% with HbA1c < 7.0%, 45.2% insulin pump users), 221 (15.1%) reported using adjunct-to-insulin medication (metformin 41.2%; GLP1-RA 25.8%; iSGLT2 18.1%; combination 14.9%). Users were older (47.0 [40.0, 56.0] vs. 43.0 [30.0, 56.0] years, p < 0.001), had higher BMI (29.1 [25.2, 33.3] vs. 25.1 [22.5, 28.3] kg/m2, p < 0.001), if multiple daily injection therapy had higher basal insulin dose (0.29 [0.19, 0.41] vs. 0.24 [0.17, 0.31] U/kg/day, p = 0.003) compared to non-users. Adjunct-to-insulin use was also associated with presence of cardiovascular disease (10.9% vs. 6.76%, p = 0.045), use of antihypertensive medication (41.6% vs. 29.1%, p < 0.001), and use of lipid-lowering drugs (65.6% vs. 41.4%, p < 0.001). HbA1c level, diabetes duration, and total daily insulin dosage did not differ between users and non-users. SGLT2i users reported similar diabetic ketoacidosis rates as non-users.Conclusion: The contemporary use of adjunct-to-insulin glucose-lowering drugs is common in adult PwT1D, and strongly associated with the presence of cardiometabolic risk factors.DisclosureJ. Liu: None. M.K. Talbo: Other Relationship; Dexcom, Inc. M. Lebbar: None. V. Messier: None. C. Leroux: None. A. Bonhoure: None. N. Taleb: Speaker's Bureau; Novo Nordisk. B.A. Perkins: Other Relationship; Abbott, Novo Nordisk, Sanofi. Advisory Panel; Abbott, Insulet Corporation, Sanofi, Novo Nordisk, Nephris, Vertex Pharmaceuticals Incorporated. Research Support; Novo Nordisk. A. Brazeau: Speaker's Bureau; Dexcom, Inc. Research Support; Canadian Institutes of Health Research. Speaker's Bureau; Juvenile Diabetes Research Foundation (JDRF). Research Support; Juvenile Diabetes Research Foundation (JDRF), Diabète Québec, Fonds de recherches du Québec-Santé, Mitacs. R.P.R. Rabasa-Lhoret: Advisory Panel; Abbott, Eli Lilly and Company, Novo Nordisk, Sanofi, Insulet Corporation. Other Relationship; Medtronic. Advisory Panel; Bayer Pharmaceuticals, Inc.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-852-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 853-P: Efficacy and Safety of a Novel Dual GLP-1/GIP Receptor Agonist
(HRS9531), in Obese Adults without Diabetes—Up to 52-Week Treatment-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 853-P
Abstract: Introduction and Objective: HRS9531, a dual GLP-1/GIP receptor agonist (RA), has shown promising weight loss efficacy over 24 weeks (wks). This study evaluated its long-term efficacy and safety in obese adults without diabetes up to 52 wks.Methods: Chinese adults with a BMI of 28-40 kg/m² were randomized (1:1:1:1:1) to receive once-weekly (QW) subcutaneous injections of HRS9531 (1.0, 3.0, 4.5, or 6.0 mg) or placebo (PBO) for 24 wks (core treatment), followed by a 28-wk extension. During the extension, doses were maintained for 8 wks, after which all participants (pts) received HRS9531 for 20 wks: the PBO and 1.0 mg groups switched to 3.0 mg QW, while the others were re-randomized to QW or biweekly (Q2W) dosing.Results: Of 249 enrolled pts, 240 (96.8%) completed the 24-wk core treatment; 168 pts entered the extension, and 166 (98.8%) completed the 32-wk PBO-controlled treatment. At wk 32, pts treated with HRS9531 achieved up to a 17.97% reduction in mean body weight (BW) compared to 0.74% in the PBO group, with proportions achieving ≥5% and ≥10% BW reductions as high as 100.0% and 77.6%, respectively, vs. 12.5% and 6.1% in the PBO group. The mean percentage change in BW from wk 32 to wk 52 ranged from -0.76% to 0.01% in the HRS9531 Q2W groups, and from -3.45% to -0.02% in the HRS9531 QW groups. The Q2W dosing effectively maintained weight stability without rebound. TEAEs were reported in 75.5-91.8% of pts across the HRS9531 groups, compared to 85.7% in the PBO group during the 32-wk PBO-controlled treatment. Most TEAEs were mild to moderate, with gastrointestinal events being the most common. No new safety signals for HRS9531 were identified throughout the 52-wk treatment period.Conclusion: HRS9531 treatment led to a notable reduction in BW compared to PBO over 32 wks in obese adults without diabetes. After 32 wks of treatment, Q2W dosing effectively maintained the achieved weight loss. Safety profile of HRS9531 was tolerable and manageable, consistent with other GLP-1/GIP RAs.DisclosureL. Zhao: None. D. Zhu: None. T. Pan: None. D. Wang: None. H. Ling: None. Y. Li: None. H. Cai: None. Z. Cheng: None. D. Liu: None. Y. Hui: None. X. Zhang: None. H. Chen: Employee; Jiangsu Hengrui Pharmaceuticals Co., Ltd. Y. Zuo: Employee; Jiangsu Hengrui Pharmaceuticals Co., Ltd. Y. Sun: Employee; Jiangsu Hengrui Pharmaceuticals Co., Ltd. X. Li: None.FundingJiangsu Hengrui Pharmaceuticals Co., Ltd.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-853-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 855-P: Dorzagliatin Increases Hepatic UDP Glucose Flux via the Direct
Pathway in Type 2 Diabetes—New Glucokinase Activator for Type 2
Diabetes'-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 855-P
Abstract: Introduction and Objective: We have previously shown impaired direct pathway of hepatic UDP glucose flux implying a defect in hepatic glucokinase activity (GKA) in type 2 diabetes (T2D). Dorzagliatin is a new Glucokinase activator not yet approved in the US. This study was done under an FDA IND-159103 to provide mechanistic insight into whether Dorzagliatin enhances GKA in T2D.Methods: Six T2D subjects (age ~69 yrs, BMI ~31.0 kg/m2, FPG ~8.3 mmol/L, HbA1c ~7.4%, 17 years average diabetes duration) were studied before and after 6-week monotherapy with 75 mg twice daily oral Dorzagliatin. All other antidiabetes medications were discontinued prior to study. Subjects underwent a 3-hour hyperglycemic (~9.3 mM) hyperinsulinemic (0.25 mU/Kg/min) clamp at baseline and post treatment. Endogenous glucose production (EGP) and UDP-Glucose flux were estimated using [3-3H] Glucose and [1-14C] Galactose infusions as previously established. 50% dextrose containing [3-3H] Glucose was infused during the clamp to keep specific activity of tracer constant permitting steady state equations for calculation of fluxes.Results: The trial is ongoing. Plasma glucose, insulin and glucagon concentrations were similar during clamp baseline and post treatment. EGP was similar during clamp at baseline and post treatment (8.3±3.6 vs. 9.3±3.0 µmol/KgFFM/min). Total UDP glucose flux was ~30% higher (4.7±1.1 vs. 5.7±2.2 µmol/KgFFM/min) post treatment and was entirely due to increase in the direct pathway (2.4±0.5 vs. 3.1±1.1 µmol/KgFFM/min). No SAEs such as hypoglycemia occurred, and safety labs (LFT, uric acid and TG) remained within normal limits at the end of the trial.Conclusion: The initial data suggest that dorzagliatin increases total UDP-glucose flux through the direct pathway of glycogen synthesis, implying an increase in hepatic GKA in people with T2D. Future larger clinical trials are required to test long term glucose control with this new drug for T2D.DisclosureU.S. Unni: None. A. Hodhod: None. D. Truong: None. B. Gran: None. A. Basu: None. R. Basu: Advisory Panel; Novo Nordisk, Boehringer-Ingelheim.FundingNational Institute of Health (R01 DK029953, R01 DK085516, DK059637 (MMPC) and DK020593 (DRTC).
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-855-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 856-P: Efficacy and Safety of Early Treatment Intensification Guided by
Glycated Albumin in Newly Diagnosed Type 2 Diabetes—A Multicentre,
Randomized Clinical Trial-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 856-P
Abstract: Introduction and Objective: To testify that knowledge of glycated albumin and adjusting anti-diabetic regimens according to GA values result in improved glycemic control in newly diagnosed type 2 diabetes mellitus (T2DM).Methods: Multicentre, Randomized Clinical Trial. Setting: 7 hospitals in China between August 2022 to August 2024. Participants: A total of 200 patients with newly diagnosed type 2 diabetes and unsatisfactory glucose control. Interventions: All the patients were 1:1 randomly assigned to two groups: GA guided therapy group and standard therapy group. In GA guided therapy group, the anti-diabetic treatment regimen will be strengthened when GA value is higher than 16% at 4 weeks, and all the patients were followed up for 12 weeks. Main Outcome Measures: The primary outcome was the achievement rate of HbA1c <7% at week 12. Main secondary outcomes were the achievement rate of HbA1c <6.5%, the change of HbA1c, hypoglycemia, and β-cell function.Results: A total of 200 patients were randomized. There was no significant difference in the achievement rate of HbA1c (< 7%) between GA guided therapy group (64.29%) and Standard therapy group (64.36%) after 12-week of follow-up (P=0.99). However, in Per-Protocol analysis, the achievement rate of HbA1c (< 6.5%) was significantly higher in GA guided therapy group than in Standard therapy group (40.51% vs 25.27%, P=0.03). And the change in HbA1c, HOMA-β, HOMA-IR, body weight reduction were all significantly better in GA guided therapy group than in Standard therapy group.Conclusion: In patients with newly diagnosed type 2 diabetes, the adjustment of the treatment plan according to GA does not affect the proportion of HbA1c<7% 3 months later. However, early initiation of combination therapy guided by GA may leads to further reduction in HbA1c, more improvement in HOMA β and HOMA-IR, and does not increase the risk of hypoglycemia.DisclosureQ. Ren: None. L. Ji: None.FundingAsahi Kasei Pharma Corporation
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-856-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 858-P: Potential Drug Treatment for Type 2 Diabetes Using Glutathione and
S-nitrosoglutathione-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 858-P
Abstract: Introduction and Objective: Oxidative stress in the diabetic state has been of considerable concern over the years. Glutathione (GSH) is an antioxidant that is naturally produced in the body and functions in the antioxidant defense system against reactive oxygen species (ROS). The aim of this study was to investigate the effect of glutathione and S-nitrosoglutathione (GSNO) co-administration on blood glucose metabolism in type 2 diabetic rats.Methods: A type 2 diabetic animal model was successfully developed using 10% fructose solution and a low dose of streptozotocin. A total of thirty Sprague-Dawley rats were equally divided into five groups, namely normal control (NC), diabetic control (DC), GSH, GSNO and the co-administration group (GSH + GSNO). The respective compounds, including saline for the control groups, were administered via oral gavage daily for four weeks. Non-fasting blood glucose (NFBG) concentration was measured weekly. Insulin and total antioxidant concentration were assessed at the end of treatment. Data was analysed using One-way ANOVA where a p-value < 0.05 was considered statistically significant.Results: A noteworthy lowering in NFBG was observed for both the GSH and co-administration groups (p < 0.05), with the latter group having a more pronounced reduction. This was accompanied by a marked increase in insulin concentration for both groups respectively compared to the diabetic control (p < 0.05). Glutathione treatment showed the highest total antioxidant concentration of all the diabetic groups, whereas the co-administration group was comparable to the diabetic control.Conclusion: Co-administration of GSH and GSNO significantly reduced blood glucose concentration in type 2 diabetic rats whilst increasing insulin concentration. Glutathione on its own and in supplementation with S-nitrosoglutathione could prove beneficial in the clinical treatment of type 2 diabetes mellitus.DisclosureA.J. Wright: None. D.A. McGrowder: None. S. Bryan: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-858-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 859-P: GLP-1 Receptor Agonists vs. DPP-4 Inhibitors and SGLT2 Inhibitors
on Liver Outcomes in Metabolic Dysfunction–Associated Steatotic Liver
Disease-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 859-P
Abstract: Introduction and Objective: This study assesses the risk of severe hepatic disease (SHD: cirrhosis, hepatocellular carcinoma, or spontaneous bacterial peritonitis) in type 2 diabetes patients (T2DM) with metabolic dysfunction-associated steatotic liver disease (MASLD) treated with GLP-1RAs versus DPP-4i or SGLT2i.Methods: A retrospective cohort study was performed using MarketScan databases (2017-2021). Eligible T2DM+MASLD patients met 1-year baseline enrollment with no antidiabetic agents other than biguanides/sulfonylureas. Patients having prior SHD, liver transplantation, bariatric surgery, alcohol/drug use, or other liver diseases were excluded. GLP-1RA patients were matched with DPP-4i and SGLT2i patients based on age, sex, treatment year and propensity scores from clinical characteristics. Time-to SHD up to 2-years was compared using Cox proportional hazard regression model where patients were censored with SHD event, disenrollment, or study end.Results: Analysis included 2,656 pairs of patients for the DPP-4 vs. GLP-1RA and 4,311 pairs for the GLP-1RA vs. SGLT2i analyses. GLP-1RA exhibited lower risk than DPP-4i at 1 year (HR 0.34) and 2 years (HR 0.29; both p<0.001). Compared to SGLT2i, GLP-1 RA patients showed higher risk of SHD at 2 years (HR 1.70, p<0.001).Conclusion: The increased risk of SHD with SGLT2i compared to GLP-1 RA needs further investigation.Disclosure J. Sarker: Employee; Merck Sharp & Dohme Corp. E.M. Okpara: None. B. De Los Santos: Employee; Takeda Pharmaceutical Company. M.T. Kim: Other Relationship; Takeda Pharmaceutical Company. K. Kim: Consultant; Renalytix. Other Relationship; Takeda Pharmaceutical Company.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-859-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 860-P: The Impact of a Novel Digital Therapeutics Product on Glycemic
Control among Saudi Patients with Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 860-P
Abstract: Introduction and Objective: Suboptimal glycemic control is a key healthcare challenge, especially in adapting patient education to the digital age. This study evaluated the effectiveness of the digital therapeutics product "Ithnain®" in improving glycemic control in individuals with diabetes.Methods: A three-month education program led by diabetes educators offered interactive learning and personal coaching through a digital platform, collecting data on HbA1C and body weight changes over 12 weeks.Results: Of the 232 participants, 58.2% were female, 29.3% adolescents, and 37.1% adults.The average BMI was 23.4 (SD 6.27), 81.5% had type 1 diabetes, average HbA1C was 8.33% (SD 1.58) and 56.0% attended high session groups (8-12 sessions). Post-education HbA1C significantly decreased (8.33% to 7.88%, p <.001, moderate effect size; Cohen's d = 0.435), while weight reduction was minimal and marginally significant (p = 0.05,Cohen's d = 0.13). Correlation analysis showed a weak but significant positive relationship between session attendance and HbA1C reduction (r = 0.141, p = 0.035), with no significant correlation for weight reduction (r = 0.045, p = 0.497).Conclusion: Given its reported clinical effect and accessibility, this digital therapeutic product is likely effective at the population level. Future studies are needed to assess efficacy for specific diabetes types and long-term effects.Disclosure A.M.K. Bakhsh: Other Relationship; Sanofi. Advisory Panel; Ithanin. A.I. Alsagheir: None. L. Alzubaidi: None. B.S. Binabbas: None. A.A. Al Hayek: None. M.A. Altweiley: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-860-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 861-P: Targeting Activin Type II Receptors—Develop Monoclonal Antibodies
LAE102, LAE103, and LAE123 as Candidate Therapeutics for Muscle Growth and
Fat Reduction-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 861-P
Abstract: Introduction and Objective: Ligands of the TGF-β superfamily including myostatin, activins, and GDFs, are known to negatively regulate skeletal muscle mass and lipolysis via Activin Type II receptors (ActRII) signaling. This study aims to investigate the effects of ActRII receptor antagonist antibodies on promoting muscle growth and fat reduction.Methods: We have developed three monoclonal antibodies: LAE102, specific to ActRIIA; LAE103, specific to ActRIIB; and LAE123, bi-specific to both ActRIIA and ActRIIB. The roles of ActRIIA and ActRIIB signaling in skeletal muscle and adipose tissue are being investigated using cell-based functional assays, lean mouse, and diet-induced obesity mouse models.Results: LAE102, LAE103, and LAE123 are high-affinity functional antagonists. They can completely inhibit the signaling transduced by ligands such as activin A, B, AB, and myostatin, all of which are known to contribute to muscle atrophy. In addition, they also inhibit activin E and GDF3, which promote lipid accumulation. In mouse models, LAE102 alone significantly induced muscle growth and reduced fat mass, while LAE103 had much less effect. Notably, a synergistic effect on muscle increase and fat loss was observed when combining LAE102 with LAE103, achieving the maximal effect comparable to the bi-specific antibody LAE123.Conclusion: The findings indicate that ActRIIA is a major regulator of muscle growth and fat loss. LAE102 shows great potential as muscle preserving weight loss management with a favorable safety profile. On the other hand, LAE123 could be utilized to treat diseases requiring completely inhibition of both ActRIIA and ActRIIB, such as spinal muscle atrophy.DisclosureR. Zhang: None. M. Yang: None. J. Gu: None. M. Hu: None. J. Chen: None. W.A. Li: None. L. Xiaofen: None. X. Zhang: None. C. Lu: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-861-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 862-P: Notch Signaling Inhibitor ADPO-002 Upregulates UCP1 Expression in
Mice and Human Adipose Tissue Explants-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 862-P
Abstract: Introduction and Objective: Brown fat in humans has been associated with a lower risk of obesity and type 2 diabetes. This study investigated the regulation of browning marker UCP1 by a novel γ-secretase inhibitor ADPO-002 in mice in vivo, and in adipose tissue excised from humans with obesity.Methods: Lyophilized PLGA nanoparticles (NP; ~4.5% ADPO-002 w/w, 0.2 and 1 mg) and blank NPs were injected into inguinal white adipose tissue (iWAT) of C57BL/6J mice (N=3/group). After 7 days, iWAT was collected for histology, RNA isolation, and UCP1 mRNA quantification by RT-qPCR (statistics: ANOVA). For the human explant study, adipose tissue was collected from 10 bariatric surgery patients (3 men and 7 women, BMI 41.4±11.5 kg/m2). These tissue samples were cultured and treated with DMSO or 30 µM ADPO-002. The tissue was homogenized after 7 days, and UCP1 expression was quantified via ELISA (ng UCP1/mg total protein, statistics: Wilcoxon paired t test).Results: In mice, 0.2 and 1 mg ADPO-002 NP up-regulated UCP1 mRNA expression by 23-fold (p=0.4387) and 109-fold (p=0.0043), respectively compared to the control group. The browning phenotype was further confirmed by H&E staining. In human omental adipose tissue samples treated with 30 µM ADPO-002 (N=10 subjects) UCP1 protein expression significantly increased compared to the DMSO control (5.8±1.1 vs 3.1±0.7 ng/mg, p=0.0098). In human subcutaneous adipose tissue samples treated with 30 µM ADPO-002 (N=8 subjects) there was a trend for UCP1 protein expression to increase compared to the DMSO control (6.3±1.5 vs 3.8±0.8 ng/mg; p= 0.1094).Conclusion: The results suggest that ADPO-002 has a promising browning effect on mice iWAT and human subcutaneous and omental adipose tissue.Disclosure M. Abedin: Employee; Adipo Therapeutics. K. Benkato: None. M.A. Oswalt: None. C.B. Crawford: None. R.V. Considine: Research Support; Lilly USA LLC, Adipo Therapeutics. M. Deng: Other Relationship; Adipo Therapeutics.FundingIndiana Voucher Program and Adipo Therapeutics
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-862-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 863-P: A Multicenter, Randomized, Open-Label, Controlled Study on
Evaluating the Efficacy and Safety of Switching from Daily DPP-4
Inhibitors to Cofrogliptin in Patients with Type 2 Diabetes Mellitus in
China-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 863-P
Abstract: Introduction and Objective: Cofrogliptin is a novel ultra-long-acting DPP-4 inhibitor (DPP-4i) which could maintain good glycemic control in type 2 diabetes (T2D) patients with 10mg dose once biweekly. This study aims to assess the efficacy and safety of switching daily DPP-4i to cofrogliptin in Chinese T2D patients, focusing on blood glucose fluctuations.Methods: T2D patients previously treated by daily DPP-4i with or without metformin for at least 12 weeks were included. Eligible patients were randomly 1:1 assigned to the daily DPP-4i group (continued their medication) or the cofrogliptin group (switched the daily DPP-4i to biweekly cofrogliptin) for the treatment of 24 weeks. 14-day CGM was conducted from week -2 to 0 and from week 22 to 24. The primary endpoint was the change in time in range (TIR, 3.9-10.0 mmol/L) from baseline to 24 weeks.Results: A total of 64 participants with mean HbA1c of 7.04% and TIR of 83.79% were enrolled. After 24-week treatment, the mean TIR (%) relative to baseline changed by an increase of 0.545 in the cofrogliptin group and a decrease of 9.614 in the daily DPP-4i group. There was a significant difference between the two groups with least-squares (LS) mean difference of 10.159 (95%CI: 3.194, 17.124, P=0.0050). The change in mean glucose (MG, mmol/L) and coefficient of variation (CV, %) from baseline also showed significant difference with LS Mean difference of -1.016 (95%CI: -1.644, -0.388, P=0.0020) and -3.370 (95%CI: -5.998, -0.741, P=0.0129) in favor of the cofrogliptin group. There were no severe hypoglycemia events in both groups and the incidence of adverse events was similar between the two groups.Conclusion: The treatment of switching to cofrogliptin from daily DPP-4i resulted in better maintenance of TIR, MG, and CV in T2D patients, irrespective of metformin co-use, and showed good tolerability and safety. Clinical trial information: NCT06703268.DisclosureC. Pan: None. L. Chen: None. H. Jiang: None. Y. Feng: None. S. Wang: None. J. Zhang: None. Z. Wang: None. Y. Zhou: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-863-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 864-P: Effect of Imeglimin on Periodontitis in Streptozotocin-Induced
Diabetic Rats-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 864-P
Abstract: Introduction and Objective: Diabetes mellitus is known to be associated with a higher incidence and severity of periodontal disease, although the mechanism remains unclear. We and others previously demonstrated the involvement of increased oxidative stress, polyol pathway, and advanced glycation end products on periodontitis in subjects with diabetes like other chronic diabetic complications. Mitochondrial dysfunction is thought to be one of the common mechanisms of diabetic complications. To clarify the impacts of mitochondrial dysfunction on periodontitis in diabetes, we investigated the effect of imeglimin.Methods: Diabetes was induced by intraperitoneal injection of streprozotocin(STZ) in six-week-old male Sprague-Dawley rats. 2 weeks after STZ administration, experimental periodontitis was induced by ligating nylon sutures around the cervical area of maxillary second molar teeth. Imeglimin was administered into Half of the diabetic rats for 2 weeks through an osmotic pump placed in the back skin. Two weeks after the induction of periodontitis, the rats were slaughtered, and maxillary periodontal tissues were collected and analyzed. Micro-CT analysis of maxillary alveolar bone was performed to evaluated alveolar bone loss.Results: Imeglimin did not affect the blood glucose levels in diabetic rats. Periodontitis induced inflammatory cell infiltration of the gingiva.Periodontitis in diabetic rats showed increased inflammatory cell infiltration, increased gene expressions of TNF-α and iNOS in the gingiva, and increased alveolar bone resorption compared to that in normal rats. Administration of imeglimin significantly decreased the gene expressions of inflammatory cytokines and inflammatory cell infiltration in gingiva of diabetic rats. Imeglimin also significantly improved alveolar bone resorption in diabetic rats.Conclusion: These results suggest that mitochondrial dysfunction may be involved in the mechanism of periodontal exacerbation in diabetes mellitus.DisclosureS. Kondo: None. K. Kojima: None. H. Airi: None. K. Katsumata: None. N. Nakamura: None. M. Miyabe: None. S. Sasajima: None. R. Ozaki: None. M. Yamaguchi: None. N. Sawada: None. T. Minato: None. T. Saiki: None. T. Ohno: None. T. Kikuchi: None. A. Mitani: None. K. Naruse: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-864-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 865-P: Efficacy and Safety of a Novel Oral Small Molecule GLP-1RA in
Chinese Obese Adults without Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 865-P
Abstract: Introduction and Objective: HRS-7535, a novel small molecule GLP-1RA, demonstrated promising weight loss (WL) in a phase 1 trial. This phase 2 study evaluated its efficacy and safety in obese adults without diabetes.Methods: In this randomized, double-blind, placebo (PBO)-controlled, multicenter study, 235 participants (pts) (BMI 28-40 kg/m²) were randomized (1:1:1:1:1) to receive oral HRS-7535 at target doses of 30, 60, 120, or 180 mg QD or PBO for 36 wks (a 26-wk core treatment period followed by a 10-wk extension). Primary endpoint was percentage change in body weight (BW) from baseline (BL) at wk 26.Results: At BL, mean BMI is 32.5 kg/m², and mean BW is 91.6 kg; 48.5% of pts were female. At wk 26, the least-squares (LS) mean percentage changes in BW from BL were -2.99% with HRS-7535 30 mg, -7.17% with 60 mg, -6.17% with 120 mg, and -9.36% with 180 mg, vs. -2.50% with PBO. The PBO-adjusted LS mean changes were -0.49% for 30 mg, -4.67% for 60 mg, -3.67% for 120 mg, and -6.87% for 180 mg (P = 0.7091, 0.0005, 0.0061, <0.0001). BW reduction in the 180 mg group was sustained over the 10-week extension; at wk 36, LS mean percentage change in BW from BL was -9.5% with HRS-7535 180 mg vs. -1.4% with PBO; 35.4% of pts on HRS7535 180 mg achieved ≥10% WL vs. 6.5% with PBO. In the PBO-controlled period, TEAEs occurred in 87.2-95.8% of pts on HRS-7535 and 87.0% on placebo. Most common TEAEs with HRS-7535 were gastrointestinal events (nausea:16.7-54.2%, diarrhea: 16.7-21.7%, vomiting: 15.7-37.5%), which were mostly mild to moderate in severity, and occurred more frequently during titration. No trends in elevated liver enzymes were observed. Of 31 pts (13.2%) who discontinued study treatment early, 5 (2.1%), all in HRS-7535 groups, discontinued due to TEAEs.Conclusion: In obese adults without diabetes, HRS-7535 at doses of 60, 120, or 180 mg QD resulted in clinically meaningful and statistically significant reductions in BW at wk 26 compared with PBO. HRS-7535 exhibited a safety profile consistent with other GLP-1 RAs.DisclosureW. Gu: None. L. Zhang: None. L. Li: None. D. Wei: None. L. Qifu: None. Y. Zong: Employee; Jiangsu Hengrui Pharmaceuticals Co., Ltd. C. Shu: Employee; Jiangsu Hengrui Pharmaceuticals Co., Ltd. W. Dai: Employee; Jiangsu Hengrui Pharmaceuticals Co., Ltd. Y. Mu: None.FundingJiangsu Hengrui Pharmaceuticals Co., Ltd
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-865-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 866-P: The Apelin Receptor Agonist Azelaprag Shows Cardioprotective
Effects as Monotherapy and Enhanced Benefits with Semaglutide in a
Diet-Induced Obesity Model of Heart Failure with Preserved Ejection
Fraction-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 866-P
Abstract: Introduction and Objective: Heart failure with preserved ejection fraction (HFpEF) is a significant complication of obesity, yet therapeutic options remain limited. Apelin signaling has positive effects on metabolic and cardiac function. We investigated whether azelaprag, an oral agonist of the apelin receptor, could improve cardiac outcomes alone or in combination with semaglutide in a mouse model of obesity and hypertension-associated HFpEF.Methods: Diet-induced obese (DIO) mice received angiotensin II via minipump and were treated for 2 weeks with vehicle, azelaprag (1.1 g/L in drinking water + 115 mg/kg subcutaneously once daily) and/or semaglutide (10 nmol/kg once per 3 days). Body weight and composition (EchoMRI) were measured throughout the treatment. After 2 weeks, cardiac hypertrophy was identified by left ventricular posterior wall thickness and left ventricular diameter. Expression of genes related to cardiac injury and fibrosis was measured by qPCR in heart tissue.Results: After 2 weeks, both monotherapies showed significant reduction in body weight [azelaprag, 21%, p<0.0001; semaglutide, 19%, p<0.0002] and prevented cardiac hypertrophy. Azelaprag treatment suppressed cardiac BNP expression and reduced pro-fibrotic gene expression. Combination therapy increased weight loss to 36% (p<0.0001 vs. monotherapies) and showed greater reductions in left ventricular diameter (p<0.05 vs either agent alone).Conclusion: Azelaprag demonstrated significant cardioprotective effects in an obesity and hypertension-associated HFpEF model while also promoting substantial weight loss. These benefits were enhanced when combined with semaglutide. The results suggest therapeutic utility of azelaprag as a monotherapy or in combination with a GLP-1R agonist in treating obesity patients at risk for HFpEF or with established disease.Disclosure S. Yan: Employee; BioAge. C. Portillo: Employee; BioAge Labs. Y. Wang: Employee; BioAge Labs. M. Banicki: Employee; BioAge Labs. M. Cochran: Employee; BioAge Labs. A. Banicki: Employee; BioAge Labs. G. Guerrero: Employee; BioAge Labs. C. Rodriguez: Employee; BioAge Labs. A. Ritter: Employee; BioAge Labs. S. Cowdin: None. C. Patil: Employee; BioAge Labs. J. Rebo: None. R. Montgomery: Employee; BioAge Labs. E. Morgen: Employee; BioAge Labs. K. Fortney: Employee; BioAge. P. Rubin: Employee; BioAge Labs.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-866-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 868-P: Attempts to Identify Predictors of Glycemic Control with
Imeglimin—Machine Learning Analysis Using Clinical Trial Data-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 868-P
Abstract: Introduction and Objective: This study utilized machine learning to analyze clinical trial data on imeglimin in type 2 diabetes (T2D) patients, identifying characteristics linked to treatment success with imeglimin therapy.Methods: Data from phase II and III trials of imeglimin monotherapy and a phase III trial with insulin in Japanese T2D patients were analyzed. Machine learning methods, including classification tree and random forest, predicted target HbA1c achievement or treatment response based on baseline characteristics without prior selection. Boruta assessed the significance of each characteristic’s importance.Results: For imeglimin monotherapy, 38.4% of patients achieved the target HbA1c level. Classification tree identified baseline HbA1c, age, and body roundness index {BRI: 364.2 − 365.5 × √(1 − [waist circumference / (2π)]2 / [0.5 × height2])} as independent variables for achieving HbA1c <7%. Patients with HbA1c <7.95% and age >63 had the highest percentage of achieving HbA1c <7% (77.4%). Random forest analysis identified HbA1c, fasting glucose, BRI, BMI, fatty liver index, age, and HOMA-β as significant predictors of achieving HbA1c <7%. For imeglimin and insulin combination therapy, 33.3% of patients achieved treatment response. Classification tree identified BMI, LDL-C, and ALT as independent variables for achieving treatment response. Patients with BMI <25.8, LDL-C <2.68 mmol/L, and ALT <21 U/L had the highest percentage of responders (85.0%). Random forest analysis identified BMI, age, LDL-C, HbA1c, and diastolic blood pressure as significant predictors of responders.Conclusion: Machine learning algorithms were shown to provide a hypothetical, unbiased approach for predicting treatment success in T2D, enhancing the search for predictors. The integration of machine learning in healthcare could empower clinicians to utilize relevant data for optimal and personalized patient care.Disclosure K. Hagi: Employee; Sumitomo Dainippon Pharma Co., Ltd. K. Yoshida: None. K. Kaku: Speaker's Bureau; Astellas Pharma Inc, Eli Lilly and Company, Boehringer-Ingelheim, Kowa Company, Ltd, Mitsubishi Tanabe Pharma Corporation, Novo Nordisk, Sumitomo Dainippon Pharma Co., Ltd, Taiho Pharmaceutical Co. Ltd. H. Watada: Speaker's Bureau; Novo Nordisk, Boehringer-Ingelheim, Sumitomo Pharma, Eli Lilly and Company, Roche Diabetes Care, Merck Sharp & Dohme Corp, Sanwa Kagaku, Daiichi Sankyo. Research Support; Sumitomo Pharma, SBI Pharma, Kowa Company, Ltd, Sanwa Kagaku, Boehringer-Ingelheim. Speaker's Bureau; Kyowa Kirin Co., Ltd, Bayer Pharmaceuticals, Inc, Abbott Japan Co., Ltd, Mitsubishi Tanabe Pharma Corporation. K. Ueki: Consultant; Abbott. Speaker's Bureau; AstraZeneca, Boehringer-Ingelheim, Eli Lilly and Company, Novo Nordisk. Research Support; Sumitomo Dainippon Pharma Co., Ltd. Speaker's Bureau; Sumitomo Dainippon Pharma Co., Ltd. Consultant; Sanofi.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-868-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 869-P: OGAP-Diabetes—Proteomics-Based Target Discovery Platform for
Type 2 Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 869-P
Abstract: Introduction and Objective: Due to the shortcomings of current T2D and obesity therapies, new therapies are required. In previous work, OGAP-Verify (oncology target discovery) has been successfully used to identify new cancer-specific proteins which have been targeted therapeutically and are now in Phase I/II clinical trials. While mRNA can be used to measure gene expression, mRNA only has 40% correlation with protein abundance. This study investigates development of proteomic methods to identify T2D-specific protein pathways which could be exploited therapeutically.Methods: T2D and healthy pancreatic tissues and islets, as well as many normal healthy tissues, were obtained from consenting donors, processed and analysed using quantitative Mass Spectrometry. Proteins were identified and their abundance determined in copies per cell. Up- and down-regulated proteins in T2D islets were identified using bioinformatics.Results: Preliminary results show up- and down-regulation of protein pathways unique to T2D using quantitative proteomics.Conclusion: Results demonstrate the ability of OGAP-Diabetes, a proprietary target discovery platform, to successfully identify new proteins and pathways involved in T2D for therapeutic intervention. This coupled with Artificial Intelligence Machine Learning (AI/ML) based approaches gives new insights into the molecular mechanisms behind T2D pathology.DisclosureJ. Lewis: None. B. Thomas: None. J.C. Allen: None. M. Ameer-Beg: None. M.P. Barnes: None. D.L. Davies: None. M.D. Agarwal: None. A. Houghton: None. C. Rohlff: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-869-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 870-P: Combination Therapy of Icovamenib and Semaglutide Enhances Body
Weight Loss and Glycemic Control While Increasing Lean Mass in a Type 2
Diabetes Animal Model-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 870-P
Abstract: Introduction and Objective: Icovamenib (BMF-219) is an oral, covalent menin inhibitor in clinical development for the treatment of T1D and T2D. Menin is a key negative regulator of beta cell mass and GLP-1 receptor expression. Icovamenib induced durable glycemic control and controlled beta cell proliferation in animal and human islet models. Icovamenib enhanced responsiveness of human islets to GLP-1 receptor agonists while increasing GLP-1 receptor expression and insulin content. Here we assessed the effects of icovamenib in combination with semaglutide in diabetic rats.Methods: Zucker diabetic fatty (ZDF) rats were treated with icovamenib (200mg/kg, QD) or vehicle for 14 days followed by 14 days with low dose semaglutide (0.02mg/kg, QD). The effects of combination therapy vs. single agent semaglutide on glycemic parameters, body weight and body composition were measured.Results: Combination treated ZDF rats displayed significant reductions in fasting and fed blood glucose (BG) levels as early as one week, with 60% reduction in fasting BG at two weeks vs. semaglutide alone. Combination therapy for two weeks substantially improved OGTT (50% AUC reduction ) and HbA1c (1.4% reduction) vs. semaglutide. Insulin resistance (HOMA-IR) declined 75% in the combination therapy arm vs. semaglutide. HOMA-B and c-peptide index were notably improved after one week of combination therapy, indicating enhanced beta cell function. Importantly, combination therapy reduced body weight, exclusively by fat loss. The lean mass fraction was significantly increased (>10%) in the combination arm.Conclusion: Icovamenib enhanced the effects of semaglutide in ZDF rats, demonstrating improved glycemic control, weight loss and lean mass. Assessment of this novel combination in persons with T2D and obesity is warranted, as it may provide greater glycemic and weight loss efficacy while potentially improving the overall side effect profile.Disclosure P. Somanath: Employee; Biomea Fusion. T. Butler: Employee; Biomea Fusion. J.P. Frias: Employee; Biomea Fusion. Stock/Shareholder; Biomea Fusion. Board Member; T1D Exchange. Consultant; Eli Lilly and Company. Speaker's Bureau; Eli Lilly and Company. Research Support; Eli Lilly and Company. Consultant; Novo Nordisk. Research Support; Novo Nordisk. Advisory Panel; Novo Nordisk, Sanofi. Research Support; Sanofi. Consultant; Sanofi. Speaker's Bureau; Sanofi. Research Support; Boehringer-Ingelheim. Advisory Panel; Boehringer-Ingelheim. Consultant; Carmot Therapeutics, Inc, Altimmune Inc. Research Support; Altimmune Inc, Novartis Pharmaceuticals Corporation, Pfizer Inc. Consultant; Pfizer Inc. Research Support; Merck & Co., Inc. Consultant; Merck & Co., Inc. Speaker's Bureau; Merck & Co., Inc. Consultant; Akero Therapeutics, Inc. Research Support; Akero Therapeutics, Inc, 89bio, Inc. Consultant; 89bio, Inc. M. Balakrishnan: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-870-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 871-P: In a Long-Term Preclinical Study, the Novel Antidiabetic Peptide
Insparin Produces Better Glycemic Control Than Pioglitazone and Promotes
Fat Loss-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 871-P
Abstract: Introduction and Objective: Insparin, a protein isolated from human adenovirus Ad36, promotes cellular glucose uptake without overt adverse effects. To eventually seek FDA approval for human trials of Insparin as an antidiabetic agent, here we conducted a long term preclinical study. We determined Insparin’s non-inferiority compared to Pioglitazone (Pio), an established antidiabetic drug.Methods: Six wk old C57BL/6J mice on a high fat diet (HFD) for 14 wk were divided into 4 groups (n=10 each) matched for body weight, % body fat, glucose disposal and HbA1c. Mice received 5 mg/kg bw (Pio) or 0 mg Pio in diet (control group for Pio), 5d / wk SC injections of nanoparticles containing 145 µg (INSP) or 0 µg Insparin (control for INSP) for 8 wk. All groups continued on HFD. Area under the curve (AUC) for blood glucose and serum insulin during the glucose tolerance tests (GTT), HbA1c, body weight and composition, and food intake were determined. Pio and INSP groups were compared to their respective control groups.Results: After 8 wk, INSP group improved glucose AUC (p < 0.0001) and HbA1c (p = 0.03), while Pio improved only HbA1c (p = 0.005). Pio and INSP groups reduced baseline HbA1c by 0.55% and 0.97%, respectively. Pio group reduced AUC for the product of glucose and insulin by 43% (p=0.01) and INSP group by 37% (p=0.14). INSP group reduced food intake (p = 0.003) and body weight gain (p = 0.04) by reducing % fat mass (p = 0.004), but increased % lean mass (p = 0.006). Whereas Pio group increased body weight (p = 0.02) and % fat (p < 0.001) but reduced % lean mass (p < 0.0001) without altering the food intake.Conclusion: Despite HFD, long term treatment with Insparin or Pio improved glycemic control in mice. However, compared to Pioglitazone, Insparin promotes superior benefit for glycemic improvement along with fat loss, a highly desirable property for an antidiabetic agent. The results provide strong support for continued development of Insparin as an antidiabetic agent.DisclosureS. Ranjbar: None. A. Patel: None. V. Hegde: Research Support; American Heart Association, National Institutes of Health, Insparin Therapeutics. N. Dhurandhar: Other Relationship; Insparin. Stock/Shareholder; Insparin. Consultant; Obthera. Other Relationship; Borealis, National Cattleman's Beef Association. Advisory Panel; Medifast.FundingPartly funded by Insparin Inc, and Helen Devitt Jones Foundation
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-871-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 872-P: Efficacy and Safety of Crisugabalin in Chinese Patients with
Diabetic Peripheral Neuropathic Pain and Inadequate Response to
Pregabalin—A Phase 2 Randomized Clinical Trial-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 872-P
Abstract: Introduction and Objective: Most guidelines recommend calcium channel modulators as the initial treatment option for Diabetic Peripheral Neuropathic Pain (DPNP), but there is limited comparative evidence to guide the choice of treatment when patients show inadequate response to one of these modulators. Crisugabalin, a novel third-generation calcium channel modulator, has demonstrated both efficacy and safety in a phase 3 trial. This study aimed to evaluate the efficacy and safety of Crisugabalin in Chinese patients with DPNP who had an inadequate response to Pregabalin.Methods: This multicenter, randomized, double-blind, double-dummy, Pregabalin-controlled phase 2 study included patients aged 18-75 years who had been receiving continuous Pregabalin treatment for over 4 weeks and had an inadequate response (VAS≥60 mm). Subjects were randomized to receive either Crisugabalin (40 mg/day) and Pregabalin (300 mg/day, with a 1- week titration) for a 4-week treatment period. The primary endpoint was the change in VAS from baseline at week 4. Secondary outcomes included changes in ADPS and ADSIS at week 4. AEs were monitored for safety.Results: At week 4, the least squares mean change in VAS from baseline was -14.4 for Crisugabalin (n=44) and -7.1 for Pregabalin (n=46), showing a statistical significant difference in favor of Crisugabalin (P=0.0069). Crisugabalin also demonstrated greater improvements in ADPS and ADSIS compared to Pregabalin. Any-grade TEAEs occurred in 29.5% of subjects receiving Crisugabalin, vs 47.8% of those receiving Pregabalin. Most TEAEs were mild to moderate, with dizziness and somnolence being the most common. These TEAEs were generally self-limiting and did not require additional treatment.Conclusion: In Chinese patients with DPNP who had an inadequate response to Pregabalin, Crisugabalin was superior to Pregabalin in reducing DPNP symptoms and was well tolerated.DisclosureC. Zheng: None. Y. Zhao: None. W. Liu: None. F. Zhang: None. N. Xu: None.FundingThe study was sponsored by Haisco Pharmaceutical Group Co., Ltd
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-872-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 874-P: Efficacy and Safety of a Novel Dual GLP-1/GLP Receptor Agonist in
Chinese Overweight or Obese Adults without Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 874-P
Abstract: Introduction and Objective: HRS9531, a dual GLP-1/GIP receptor agonist (RA), has demonstrated substantial potential for glycemic control and weight loss. This study evaluated the efficacy and safety of HRS9531 in Chinese overweight or obese adults without diabetes.Methods: This randomized, double-blind, placebo (PBO)-controlled phase 2 study enrolled Chinese adults with a BMI of 28.0-40.0 kg/m², or a BMI of 24.0-28.0 kg/m² with at least one weight-related comorbidity. Participants (pts) were randomized to receive once-weekly subcutaneous injections of the target dose of HRS9531 8.0 mg (via titration) or PBO for 36 weeks (wks). Primary endpoint was the percentage change in body weight (BW) from baseline to wk 36.Results: A total of 61 pts were enrolled and randomized to receive either HRS9531 8.0 mg (n=49) or PBO (n=12). Baseline characteristics were generally comparable between two groups. The mean baseline BW was 84.6 kg, and the mean baseline BMI was 31.3 kg/m². At wk 36, the least-squares mean difference in percentage change in BW from baseline, compared with PBO, was -21.1% (95% CI, -25.6% to -16.6%; P<0.0001) for the HRS9531 8.0 mg group. The proportions of pts achieving ≥5%, ≥10%, ≥15%, ≥20%, and ≥25% BW reduction in the HRS9531 8.0 mg group were 93.9%, 91.8%, 87.8%, 59.2%, and 30.6%, respectively, compared to 16.7%, 8.3%, 0%, 0%, and 0% in the PBO group. Additionally, HRS9531 improved waist circumference, BMI, SBP, FPG, fasting serum insulin, HbA1c levels, and reduced triglyceride levels at wk 36 compared to PBO. The majority of TEAEs were mild in severity and gastrointestinal-related, with the most common being diarrhea, nausea, and vomiting. No pts permanently discontinued treatment due to TEAEs.Conclusion: In overweight or obese adults without diabetes, once-weekly subcutaneous HRS9531 significantly reduced BW at wk 36 compared to PBO and demonstrated a manageable safety profile, primarily involving gastrointestinal disorders.DisclosureJ. Zhou: None. Q. Wen: None. H. Ling: None. T. Wu: None. F. Zheng: None. K. He: None. M. Zeng: Employee; Jiangsu Hengrui Pharmaceuticals Co., Ltd. T. Yu: Employee; Jiangsu Hengrui Pharmaceuticals Co., Ltd. L. Wang: Employee; Jiangsu Hengrui Pharmaceuticals Co., Ltd. Y. Wang: Employee; Jiangsu Hengrui Pharmaceuticals Co., Ltd.FundingJiangsu Hengrui Pharmaceuticals Co., Ltd.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-874-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 875-P: Baseline Characteristics for FINE-ONE—A Randomized Phase III
Trial Assessing Finerenone in People with T1D and CKD-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 875-P
Abstract: Introduction and Objective: CKD occurs in 1 of 3 people with T1D, with substantial loss of kidney function in over half and kidney failure in nearly one fourth. Therapies to reduce these outcomes in T1D are urgently needed. The nonsteroidal mineralocorticoid receptor antagonist finerenone, on top of ACEi/ARB, reduced the risk of kidney and heart outcomes in people with CKD and T2D. The FINE-ONE trial (NCT05901831) will assess the efficacy and safety of finerenone in people with T1D and CKD.Methods: FINE-ONE is an ongoing, global, phase III trial with finerenone. Participants (n=220) with T1D and CKD (UACR ≥200-<5000 mg/g and eGFR ≥25-<90 mL/min/1.73 m2), HbA1c <10%, and serum potassium ≤4.8 mmol/L, on a stable dose of ACEi/ARB, will be randomized 1:1 to finerenone (10 or 20 mg od) or placebo. The primary efficacy outcome is the relative change in UACR from baseline over 6 months (trial duration~7.5 months).Results: At baseline, 176 randomized participants with T1D had mean HbA1c of 7.6%, mean eGFR of 60 mL/min/1.73 m2, median UACR of 536 mg/g, mean age of 51 years, and 38% were female (Table). A high proportion had a history of hypertension (82%) and 21% had CVD. The most common race was White (71%), followed by Asian (19%) and Black (7%).Conclusion: FINE-ONE will determine the efficacy and safety of finerenone in a representative population with T1D and CKD at high risk of progressive kidney function loss.Disclosure H.L. Heerspink: Consultant; Alnylam Pharmaceuticals, Inc, Alexion Pharmaceuticals, Inc, AstraZeneca, Bayer Pharmaceuticals, Inc, Boehringer-Ingelheim, Eli Lilly and Company, Janssen Pharmaceuticals, Inc, Novartis AG, Novo Nordisk A/S, Roche Pharmaceuticals, Traveere Pharmaceuticals, Menarini. A.L. Birkenfeld: None. D. Cherney: Consultant; Boehringer Ingelheim-Lilly, Merck, AstraZeneca, Sanofi, Mitsubishi-Tanabe, Abbvie, Janssen, AMGEN, Bayer, Prometic, BMS, Maze, Gilead, CSL-Behring, Otsuka, Novartis, Youngene, Lexicon, Inversago, GSK. Research Support; Boehringer Ingelheim-Lilly, Merck, Janssen, Sanofi, AstraZeneca, CSL-Behring and Novo-Nordisk, Bayer. H.M. Colhoun: Advisory Panel; Novo Nordisk, Bayer Pharmaceuticals, Inc. Stock/Shareholder; Bayer Pharmaceuticals, Inc. Speaker's Bureau; Medscape. Advisory Panel; Sanofi. Research Support; Sanofi, IQVIA Inc, Roche Diagnostics. Stock/Shareholder; Roche Pharmaceuticals. L. Ji: None. C. Mathieu: Advisory Panel; Novo Nordisk, Sanofi, Eli Lilly and Company, Abbott, Medtronic, SAB Biotherapeutics, Inc, Roche Diabetes Care, Vertex Pharmaceuticals Incorporated, Biomea Fusion, Bayer Pharmaceuticals, Inc. P. Groop: Speaker's Bureau; AstraZeneca, Bayer Pharmaceuticals, Inc, Berlin-Chemie AG, Boehringer-Ingelheim. Advisory Panel; Boehringer-Ingelheim. Speaker's Bureau; Novo Nordisk, Menarini. R.E. Pratley: Consultant; AbbVie Inc. Stock/Shareholder; Altanine, Inc. Consultant; Amgen Inc, AstraZeneca. Other Relationship; Bayer AG, Bayer Pharmaceuticals, Inc, Biomea Fusion. Consultant; Boehringer-Ingelheim. Other Relationship; Carmot Therapeutics, Inc, Corcept Therapeutics, Dompé, Eli Lilly and Company, Endogenex. Consultant; Endogenex. Other Relationship; Fractyl Health, Inc., Gasherbrum Bio, Inc. Consultant; Genprex, Getz Pharma, Hanmi Pharm. Co., Ltd, Intas Pharmaceuticals Ltd, Lexicon Pharmaceuticals, Inc, Lilly USA LLC. Speaker's Bureau; Lilly USA LLC. Other Relationship; Metavention, Novo Nordisk, Novo Nordisk. Speaker's Bureau; Novo Nordisk. Other Relationship; Pfizer Inc, Poxel SA. Consultant; Regeneron Pharmaceuticals. Other Relationship; Sanofi. Consultant; Scholar Rock. Other Relationship; Sun Pharmaceutical Industries Ltd. S. Rosas: Other Relationship; American Diabetes Association. Research Support; Bayer Pharmaceuticals, Inc. Advisory Panel; Bayer Pharmaceuticals, Inc, Sanofi. Research Support; AstraZeneca. P. Rossing: Speaker's Bureau; Abbott. Advisory Panel; AstraZeneca, Bayer Pharmaceuticals, Inc, Boehringer-Ingelheim, Gilead Sciences, Inc, Novo Nordisk. Other Relationship; Lexicon Pharmaceuticals, Inc. Speaker's Bureau; Daiichi Sankyo. J.S. Skyler: Advisory Panel; 4 Immune. Consultant; AbbVie Inc. Advisory Panel; Abvance Therapeutics. Consultant; ActoBiotics. Advisory Panel; ADOCIA. Consultant; AiTA. Board Member; Applied Therapeutics. Advisory Panel; Avotres Inc., Bayer Pharmaceuticals, Inc, Biomea Fusion. Consultant; COUR Pharmaceuticals. Board Member; Dexcom, Inc. Consultant; Eli Lilly and Company. Advisory Panel; Kriya Therapeutics, Levicure. Consultant; Novo Nordisk A/S, Quell Therapeutics. Board Member; SAB Biotherapeutics, Inc. Consultant; Sanofi, Shoreline Biosciences. Advisory Panel; Signos. Consultant; Vertex Pharmaceuticals Incorporated, vTv Therapeutics. Advisory Panel; WiNK. K.R. Tuttle: Consultant; Lilly Diabetes, Boehringer-Ingelheim, Novo Nordisk, Pfizer Inc. Other Relationship; AstraZeneca. Consultant; Bayer Pharmaceuticals, Inc, Traveere Pharmaceuticals, ProKidney. R. Lawatscheck: Employee; Bayer Pharmaceuticals, Inc. M.F. Scheerer: Employee; Bayer Pharmaceuticals, Inc. Stock/Shareholder; Bayer Pharmaceuticals, Inc, Novo Nordisk A/S, AstraZeneca, Eli Lilly and Company. J.B. McGill: Advisory Panel; Bayer Pharmaceuticals, Inc. Consultant; Jaeb Center for Health Research. Advisory Panel; Boehringer-Ingelheim, Lilly Diabetes, Novo Nordisk, MannKind Corporation. Research Support; Diagnode, Lexicon Pharmaceuticals, Inc, Biomea Fusion. J. Russell: Employee; Bayer Pharmaceuticals, Inc.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-875-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 876-P: Pulsed Electric Field–Induced Duodenal Recellularization Impact
on Insulin Sensitivity and Beta-Cell Function—Results from REGENT-1, an
Open-Label, Prospective Study in Type 2 Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 876-P
Abstract: Introduction and Objective: T2D Duodenopathy disrupts glucose regulation, presenting a novel therapeutic target. The Re-Cellularization via Electroporation Therapy (ReCET) System uses pulsed electric field (PEF) to induce duodenal regeneration. The REGENT-1 study modelled MMTT data to assess the metabolic effects of ReCET™ on insulin sensitivity (SI), beta-cell function and disposition index (DI)Methods: REGENT-1 is a multi-center, open-label study of endoscopic PEF therapy at three doses in T2D adults on 1-4 non-insulin agents. Group 1) Gen 1 catheter 600V single tx (n=12); Group 2) Gen 1 catheter 600V, double tx (n=18); and Group 3) Gen 2 catheter double tx 750V (n=21). Mixed Meal Tolerance Tests (MMTT) assessed β-cell function (Φtot), SI, and DI.Results: Fifty-one participants (mean age 52.9 years, BMI 31.4 kg/m², HbA1c 8.7%) underwent PEF therapy. Significant improvements in SI, and DI were observed at 12 wks, with further gains by 48 wks (both p<0.05). High-energy treatment showed the greatest DI improvement, with outcomes comparable to Roux-en-Y gastric bypassConclusion: ReCET™ significantly improved SI and DI, with sustained benefits up to 48 weeks. High-energy treatment yielded optimal results. These findings highlight duodenal regeneration as a promising therapeutic target for T2DDisclosure E.I. Ekinci: Research Support; Amgen Inc, Novo Nordisk, Lilly Diabetes, AstraZeneca, Endogenex, Versanis. Advisory Panel; Lilly Diabetes, Novo Nordisk. A. Sartoretto: Research Support; Endogenex. Advisory Panel; Bariatek. Research Support; Erbe Elektromedizin GmbH. Consultant; Boston Scientific Corporation. Speaker's Bureau; Menarini. S. Chandran: None. R. Vaughan: None. B. Holt: None. A.J. Thompson: Other Relationship; Endogenex. G. Cameron: None. B. AbuDayyeh: Other Relationship; Endogenex. Consultant; Boston Scientific Corporation, Metronics, Olympus. R.E. Pratley: Consultant; AbbVie Inc. Stock/Shareholder; Altanine, Inc. Consultant; Amgen Inc, AstraZeneca. Other Relationship; Bayer AG, Bayer Pharmaceuticals, Inc, Biomea Fusion. Consultant; Boehringer-Ingelheim. Other Relationship; Carmot Therapeutics, Inc, Corcept Therapeutics, Dompé, Eli Lilly and Company, Endogenex. Consultant; Endogenex. Other Relationship; Fractyl Health, Inc., Gasherbrum Bio, Inc. Consultant; Genprex, Getz Pharma, Hanmi Pharm. Co., Ltd, Intas Pharmaceuticals Ltd, Lexicon Pharmaceuticals, Inc, Lilly USA LLC. Speaker's Bureau; Lilly USA LLC. Other Relationship; Metavention, Novo Nordisk, Novo Nordisk. Speaker's Bureau; Novo Nordisk. Other Relationship; Pfizer Inc, Poxel SA. Consultant; Regeneron Pharmaceuticals. Other Relationship; Sanofi. Consultant; Scholar Rock. Other Relationship; Sun Pharmaceutical Industries Ltd. M. Drecogna: None. C. Cobelli: None. L.K. Billings: Advisory Panel; Novo Nordisk, Eli Lilly and Company, Sanofi. Consultant; Dexcom, Inc. Advisory Panel; Bayer Pharmaceuticals, Inc. Consultant; Xeris Pharmaceuticals, Inc. Advisory Panel; Amgen Inc. Consultant; Pfizer Inc. C.H. Sorli: Employee; Endogenex. D.N. O'Neal: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-876-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 877-P: Age-Related and Sex Differences in the Effectiveness of Novel
Antidiabetic Agent Imeglimin in Japanese Type 2 Diabetes Patients-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 877-P
Abstract: Introduction and Objective: Imeglimin is a novel antidiabetic agent that possesses a mitochondrial function ameliorating action (insulin secretagogue, insulin-resistance amelioration). Imeglimin has actions that improve the carbohydrate and lipid metabolisms of type 2 diabetes (T2D) patients. In this study, we investigated differences in the effectiveness of imeglimin according to age, and by sex.Methods: We administered imeglimin 2000 mg/day to 52 T2D patients for 3 months, measured their HbA1c, blood lipids, and biochemical parameters before and after administration, and conducted a comparative study of differences in its effectiveness according to age, and by sex, using scatter plots.Results: There was a significant reduction in HbA1c levels in response to imeglimin administration, and the levels of the total cholesterol (TC), non-high-density lipoprotein cholesterol (non-HDL-C), and low-density lipoprotein cholesterol (LDL-C) also decreased. The results of the scatter plot assessments of patient age and percentage change in HbA1c levels did not show any correlations between age and percentage change in any of the parameters. By contrast, when the patients were divided by sex, the results of the investigation of age and percentage change in each of the parameters showed no age-related effects on the changes in HbA1c or blood lipids in male. In female, on the other hand, the reduction in HbA1c level diminished with age, and the decreases in the TC and non-HDL-C levels were enhanced.Conclusion: In this study, we investigated differences in the effectiveness of imeglimin according to age, and by sex. Age had no impact on the effectiveness of imeglimin in the male group. In the female group, on the other hand, the reduction in HbA1c levels diminished with age, and the decreases in both TC and non-HDL-C were enhanced with age. Sex differences were observed in the age-related effects of imeglimin on HbA1c and blood lipids.DisclosureM. Kusunoki: None. F. Hisano: None. S. Matsuda: None. T. Miyata: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-877-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 878-P: A Randomized, Double-Blind, Placebo-Controlled Phase 1 Study of
Adiponectin Agonist (PEG)-BHD1028 in Subjects with Insulin Resistance-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 878-P
Abstract: Introduction and Objective: Low adiponectin levels may contribute to insulin resistance. This first-in-human study evaluated adiponectin receptor agonist (PEG)-BHD1028 in subjects with insulin resistance.Methods: Adults with BMI ≥27 kg/m2, HOMA-IR ≥ 1.8, and HbA1c < 6.5% received subcutaneous injections of (PEG)-BHD1028 or placebo in single-ascending dose (SAD) cohorts (4, 8, 16, 32, and 64 μg/kg) and 28-day multiple-ascending dose (MAD) cohorts (8, 16, and 32 μg/kg QD). Each cohort had 8 subjects, with 2 on placebo. Areas under the curve (AUC) were obtained for insulin c-peptide, insulin, and glucose in a mixed meal tolerance test (MMTT) at Day -1 and Day 28. Body weight, triglycerides, and inflammatory markers were followed. Changes were analyzed by ANOVA (for MMTT) and generalized estimating equations (GEE).Results: The MAD cohort mean age was 49 years, with a body mass index 32, baseline HOMA-IR 3.8, and 42% female. Mild gastrointestinal adverse events occurred on (PEG)-BHD1028 (50%) and placebo (33%) without discontinuations. Drug exposure was proportional to dose. Insulin c-peptide AUC changes were +25% on placebo and -63%, +24%, and +2% on (PEG)-BHD1028 8, 16, and 32 μg/kg doses, p<0.001). Reductions in insulin AUC (p=0.116) and glucose AUC (p<0.001) were also observed, with the greatest percentage change on 8 μg/kg. There were no significant differences between groups in body weight, triglycerides, and inflammatory markers.Conclusion: Adiponectin agonist (PEG)-BHD1028 was well-tolerated with dose-related increases in exposure. Observed effects on insulin c-peptide, insulin, and glucose during the MMTT support further development.Disclosure P. Lapuerta: Consultant; Regeneron Pharmaceuticals, ViaCyte, Inc, Vertex Pharmaceuticals Incorporated, Youngene Therapeutics. B. Kim: Employee; EncuraGen, Inc.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-878-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 879-P: Metformin Improves Brain Glucose Uptake, Network Connectivity, and
Volume Concurrent to Improved Working Memory and Processing Speed in
Insulin-Resistant Older Adults-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 879-P
Abstract: Introduction and Objective: Insulin resistance (IR) increases the risk for Alzheimer’s disease and other dementias. Preclinical studies show that metformin normalizes alterations in brain mitochondrial functions induced by diet-induced IR, specifically in brain regions rich in insulin receptors. Here, we assessed the effect of 10-months of metformin treatment on cognitive function, brain network connectivity, glucose uptake, and regional volume in older people with IR.Methods: Forty participants aged 60-80 years (20 male, 20 female) with abdominal obesity, BMI ≥ 25 kg/m2, and fasting blood glucose of 100-125 mg/dL were studied. Participants were randomly assigned to metformin (2500 mg/d) or placebo (n = 20 per group) for 40 weeks. Pre- and post-treatment measurements included cognition (NIH Toolbox cognitive battery), volumetric MRI, resting-state fMRI, regional glucose uptake (18FDG-PET), and insulin sensitivity (mixed-meal tolerance test; MMTT).Results: Metformin improved processing speed and working memory concurrent to similar directional changes in amygdala and hippocampus volumes. Metformin increased white matter volume in the frontal and temporal lobes. Analysis of functional connectivity showed inverse associations between IR and connectivity strength between numerous brain regions, most notably between frontal and temporal lobe structures, potentially explaining improvement of processing speed. Increased glucose uptake in brain areas rich in insulin receptors, such as the prefrontal cortex, support that metformin enhanced insulin sensitivity in brain regions involved in memory and other cognitive functions as in the whole body noted by MMTT.Conclusion: These results support the notion that metformin ameliorates IR-related alterations in regional connectivity, brain volume, and brain glucose uptake with concurrent improvement of important aspects of cognition.DisclosureG. Ruegsegger: None. H. Jo: None. M.W. Pataky: None. N. Stricker: None. K. Klaus: None. V.J. Lowe: Research Support; Eli Lilly and Company, Siemens Healthcare Diagnostics. J. Port: Consultant; Clario. K. Nair: None.FundingNational Institute of Aging (R21 AG 060139 and R01 062859)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-879-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 880-P: Effects of Energy Dosing on Safety and Efficacy in an Open-Label
Study of Endoscopic Pulsed Electric Field Induced Electroporation in Type
2 Diabetes (REGENT-1 Trial)-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 880-P
Abstract: Introduction and Objective: The ReCET™ System (endoscopic Re-Cellularization via Electroporation Therapy) uses pulsed electric field (PEF), to induce duodenal mucosal apoptotic-like cell death followed by regeneration. We evaluated the intervention energy dose on metabolic outcomes.Methods: REGENT-1 studied PEF therapy at three doses in T2D adults on 1-4 non-insulin agents. Group 1) Gen 1 catheter 600V, single treatment (n=12); Group 2) Gen 1 catheter, 600V, double treatment (n=18); and Group 3) Gen 2 catheter (increased treated surface area [TSA]), double treatment 750V (n=21). Primary endpoint: Serious adverse events (SAEs). Secondary endpoints included metabolic changes at 24 and 48 weeks.Results: One intervention related SAE occurred in 51 participants (age 52.9±7.9 years, BMI 31.4±3.5 kg/m², baseline HbA1c 8.7±0.9%[72±9mmol/mol]). Other device/procedure-related adverse events (76 events in 47/51 participants) were mild and transient. Increased PEF dose (two applications, and higher voltage plus larger catheter diameter) correlated with metabolic improvements at 24 and 48 weeks. (Table 1)Conclusion: PEF-induced duodenal regeneration with the ReCET System resulted in improved metabolic outcomes that were dose-dependent. These promising findings suggest that further research is warranted.DisclosureD.N. O'Neal: None. A. Sartoretto: Research Support; Endogenex. Advisory Panel; Bariatek. Research Support; Erbe Elektromedizin GmbH. Consultant; Boston Scientific Corporation. Speaker's Bureau; Menarini. S. Chandran: None. R. Vaughan: None. B. Holt: None. A.J. Thompson: Other Relationship; Endogenex. G. Cameron: None. B. AbuDayyeh: Other Relationship; Endogenex. Consultant; Boston Scientific Corporation, Metronics, Olympus. R.E. Pratley: Consultant; AbbVie Inc. Stock/Shareholder; Altanine, Inc. Consultant; Amgen Inc, AstraZeneca. Other Relationship; Bayer AG, Bayer Pharmaceuticals, Inc, Biomea Fusion. Consultant; Boehringer-Ingelheim. Other Relationship; Carmot Therapeutics, Inc, Corcept Therapeutics, Dompé, Eli Lilly and Company, Endogenex. Consultant; Endogenex. Other Relationship; Fractyl Health, Inc., Gasherbrum Bio, Inc. Consultant; Genprex, Getz Pharma, Hanmi Pharm. Co., Ltd, Intas Pharmaceuticals Ltd, Lexicon Pharmaceuticals, Inc, Lilly USA LLC. Speaker's Bureau; Lilly USA LLC. Other Relationship; Metavention, Novo Nordisk, Novo Nordisk. Speaker's Bureau; Novo Nordisk. Other Relationship; Pfizer Inc, Poxel SA. Consultant; Regeneron Pharmaceuticals. Other Relationship; Sanofi. Consultant; Scholar Rock. Other Relationship; Sun Pharmaceutical Industries Ltd. C.H. Sorli: Employee; Endogenex. E.I. Ekinci: Research Support; Amgen Inc, Novo Nordisk, Lilly Diabetes, AstraZeneca, Endogenex, Versanis. Advisory Panel; Lilly Diabetes, Novo Nordisk.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-880-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 881-P: BCG Clinical Trial Programs in Advanced Type 1 Diabetes—2025
Update-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 881-P
Abstract: Introduction and Objective: Randomized Phase I-III human clinical trials of the bacillus Calmette-Guérin (BCG) vaccine, originally developed >100 yrs ago to prevent tuberculosis infection, suggest that BCG may protect humans from immune diseases such as type 1 diabetes (T1D) and from some infectious diseases. Immune and metabolic mechanisms account for BCG’s ability to regulate glucose control in T1D, including through correction of underlying aerobic glycolysis defects in white blood cells and gradual induction of regulatory T cells to suppress autoimmunity. Here we provide an update on our institution’s BCG programs.Methods: Over 600 patients with early onset T1D (< 21 yrs of age) have been enrolled in clinical protocols to test BCG’s ability to lower HbA1c, reduce insulin requirements and stabilize blood sugars; 364 have been treated. An additional study in T1D evaluates BCG’s ability to protect from infectious disease. Current pediatric studies use 2 BCG doses; adult trials use 6 doses.Results: Long-term follow-up of a completed, randomized, placebo-controlled Phase I clinical trial in adults with longstanding early onset T1D (no pancreas C-peptide) continues to show that HbA1c values are lowered for 8+ yrs after multi-dose BCG treatment. In two open-label clinical trials in adults with early onset T1D, HbA1c reduction of 10-15% was observed after multi-dose BCG treatment. A randomized, double-blind, placebo-controlled Phase II trial in adults with longstanding early or late onset T1D (n=150) has followed all patients for 5 yrs; read-out is pending. Phase II, double-blind, randomized, placebo-controlled pediatric trials are evaluating BCG in longstanding and new-onset T1D.Conclusion: BCG can work decades after T1D onset by changing glucose metabolism within lymphocytes, independently of the pancreas. Pediatric trials have the advantage of early age of onset and remaining pancreas function in some cases. BCG vaccine therapy may provide a safe and affordable medical intervention in longstanding T1D.DisclosureW. Kuhtreiber: None. J.L. Dorsey: None. N.G. Kartsounis: None. S.E. Bradley: None. E. Jones: None. A.J. Roberts: None. D.A. Mounier: None. H. Hayashi: None. K. Le: None. L. Adams: None. J. Braley: None. D.L. Faustman: None.FundingIacocca Foundation
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-881-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 882-P: Eloralintide, a Selective, Long-Acting Amylin Receptor Agonist for
Obesity—Phase 1 Proof of Concept-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 882-P
Abstract: Introduction and Objective: Eloralintide (Elora; LY3841136) is a potent, long acting once weekly (QW) amylin receptor agonist under development for obesity. Unlike other amylin agonist molecules (e.g. Cagrilintide), it is designed to have minimal calcitonin activity in the clinic.Methods: The 12 wk phase 1, randomized, placebo (PBO) controlled, double blind study evaluated safety, tolerability, PK, and PD of QW SC Elora in participants with obesity or overweight. Participants n=100, mean 44 years old, 29% female, and BMI of 27-43 kg/m2 were randomized to Elora or PBO in 5 multiple ascending dose cohorts.Results: At wk 12, AUC(0-∞), AUCτ,ss, and Cmax were dose proportional with ratios of dose normalized geometric means of 1.2, 1.1, and 1.0, respectively. Mean half-life was 13.9 to 15.8 days. Common treatment emergent adverse events (TEAEs) with Elora were decreased appetite (19%), headache (12%), fatigue (11%), and COVID-19 (11%). Minimal gastrointestinal (GI) events occurred in Elora participants: diarrhea (10%), nausea (8%), and vomiting (4%). Most TEAEs were mild in severity. No deaths and 1 (4%) serious AE unrelated to Elora occurred. At wk 12 with Elora, LS mean percent change in body weight ranged from -2.6 to -11.3%.Conclusion: At 12 wks, Elora QW was well tolerated with minimal GI AEs and resulted in meaningful weight loss. A phase 2 study (NCT06230523) will further explore safety and efficacy of Elora.DisclosureS.N. Bhattachar: None. L. Tham: Employee; Eli Lilly and Company. B. Tidemann-Miller: Employee; Eli Lilly and Company. D.A. Briere: Employee; Lilly USA LLC. H. Qu: Employee; Eli Lilly and Company. A. Haupt: Employee; Lilly Diabetes. Stock/Shareholder; Lilly Diabetes. E.J. Pratt: Employee; Eli Lilly and Company. K.J. Mather: Employee; Eli Lilly and Company.FundingEli Lilly and Company
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-882-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 883-P: Metabolic Endotoxemia and Gut Microbiota Associated with
Therapeutic Responses to Metformin in Type 2 Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 883-P
Abstract: Introduction and Objective: Metformin, the first-line treatment for type 2 diabetes, exerts antidiabetic effects partly through gut microbiota modulation. However, it can also increase Escherichia species capable of inducing endotoxemia via lipopolysaccharide (LPS). This study investigated metabolic endotoxemia, represented by LPS-binding protein (LBP) and its antagonist bactericidal/permeability-increasing protein (BPI), in relation to therapeutic responses to metformin-based therapy.Methods: We recruited 87 subjects from a cohort of type 2 diabetes treated at a medical center in southern Taiwan (from 2016 to 2024). Subjects were stratified into three groups: (1) good control on metformin monotherapy (GM, HbA1c ≤7%), (2) good control with metformin plus dipeptidyl peptidase-4 inhibitors (DPP4i) (GC, HbA1c ≤7% after failure on metformin alone), and (3) poor control on metformin or metformin plus DPP4i (PC, HbA1c >7% but ≤9%). Plasma LBP and BPI levels were measured, and gut microbiota compositions were analyzed via 16S rRNA sequencing.Results: LBP levels were significantly higher in PC compared to GM, in parallel with the higher HOMA-IR in PC. Although BPI levels were similar across groups, elevated LBP in PC indicated greater metabolic endotoxemia. LBP also showed negative correlations with HDL-cholesterol and positive correlations with triglycerides, GPT, CRP, and HOMA-IR. Gut microbiota diversity (Shannon index, representing community evenness) was reduced in GM, with distinct clustering across groups by unweighted UniFrac analysis.Conclusion: Elevated LBP in poorly controlled diabetes highlighted the role of metabolic endotoxemia contributing to insulin resistance. Reduced gut microbiota diversity was observed in type 2 diabetes with durability to metformin monotherapy, suggesting microbial shifts critical to maintaining metformin efficacy. Further analysis of specific microbial changes is warranted.DisclosureW. Hung: None. W. Hung: None.FundingNational Science and Technology Council (112-2314-B-037-070-)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-883-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 884-P: Pharmacokinetic and Pharmacodynamic Drug–Drug Interactions
between Cofrogliptin and Metformin in Healthy Subjects-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 884-P
Abstract: Introduction and Objective: Cofrogliptin is a novel ultra-long-acting DPP-4 inhibitor indicated to improve glycemic control in type 2 diabetes (T2D) as monotherapy or in combination with metformin (MET). This single-center, single-arm, phase I study aims to evaluate the drug interactions between cofrogliptin and MET in healthy subjects.Methods: Healthy subjects received MET monotherapy (Days 1-4), cofrogliptin monotherapy (Days 6-34), and combination therapy with both drugs (Days 38-47) in this study. The primary endpoint was the Pharmacokinetics (PK) interaction between cofrogliptin and MET.Results: A total of 22 healthy subjects were enrolled. After 47 days of treatment, cofrogliptin did not statistically effect the PK or pharmacodynamics (PD) of MET, as the geometric mean ratios (GMRs, MET+cofrogliptin/MET) (90% confidence interval (CI)) for MET AUC0-8h, AUC0-12h, CSS (max), Ae0-8h and Ratio0-8h, were 0.872 (0.809, 0.941), 0.900 (0.834, 0.971), 0.840 (0.743, 0.950), 0.899 (0.782, 1.032) and 0.994 (0.871, 1.136), respectively; and the GMRs (MET+cofrogliptin/MET) (90% CI) for glucose AUEC0-4h, AUEC0-0.5h and ECmax were 0.870 (0.833, 0.908), 0.915 (0.879, 0.952) and 0.866 (0.815, 0.920), respevtively, and 90% CIs all fell within 0.80-1.25. MET did not statistically effect the PK or PD of cofrogliptin as well, as the GMRs (MET+cofrogliptin/cofrogliptin) (90% CI) for cofrogliptin AUCtau and Css(max) were 1.12 (1.072, 1.169) and 1.14 (1.057, 1.220), and the GMRs (MET+cofrogliptin/cofrogliptin) (90% CI) for DPP-4 inhibition ratio AUEC0-168h, ECmax and ECmin were 1.01 (1.003, 1.015), 1.00 (1.001, 1.009) and 1.03 (1.005, 1.040), respectively, and 90% CIs all fell within 0.80-1.25. No deaths, serious adverse events (AEs), or severe hypoglycemia were reported.Conclusion: Cofrogliptin and MET did not exhibit any significant PK or PD drug interaction in healthy Chinese subjects, supporting the combination therapy in clinical practice.DisclosureC. Cui: None. N. Liu: None. H. Li: None. D. Liu: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-884-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 885-P: Sex-Dependent Additive Effects of Dorzagliatin and Incretin on
Insulin Secretion in a Novel Mouse Model of GCK-MODY-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 885-P
Abstract: Introduction and Objective: Glucokinase (GK) catalyses the key regulatory step in glucose-stimulated insulin secretion. Hetero- and homozygous mutations in GCK cause maturity-onset diabetes of the young (GCK-MODY) and permanent neonatal diabetes (PNDM), respectively. Here, we develop a novel hypomorphic Gck allele to explore the utility of glucokinase activators (GKA) and glucagon-like receptor-1 (GLP-1) agonists in these diseases.Methods: Mice encoding an aberrantly spliced Gck mRNA deleted for exons 2 and 3 were generated after genomic insertion of cDNA encoding the fluorescent protein, mCardinal (GenOway, Fr). Metabolic analyses were performed using standard techniques and Ca2+ imaging, in isolated islets from animals crossed onto an Ins1Cre:GCaMP6 reporter line, on a Zeiss LSM 900 Airyscan 2 confocal microscope.Results: Homozygous GckKI/KI mice were smaller than wildtype littermates, displayed frank diabetes (fasting glucose >18 mmol/L; HbA1c ~12%) and a sharp (~65%) reduction in beta cell mass. Heterozygous GckKI/+ mice were mildly glucose intolerant (HbA1c ~5.5%). GK immunoreactivity was reduced by >85%, and glucose-stimulated insulin secretion was undetectable in islets from homozygous knock-in (GckKI/KI) mice. Whilst ineffective in homozygous mice, normal glucose-stimulated Ca2+ dynamics and beta cell-beta cell connectivity in GckKI/+ islets were reversed with the GKA, dorzagliatin. The GLP-1 receptor agonist exendin-4 improved glucose tolerance in male GckKI/+ mice, an action potentiated by dorzagliatin, in male but not female mice. Sex-dependent additive effects of these agents were also observed on insulin secretion in vitro.Conclusion: Combined treatment with GKA and incretin may thus be useful in GCK-MODY or GCK-PNDM, and possibly in more common forms of type 2 diabetes.DisclosureS. Salazar: None. L.F. Delgadillo Silva: None. P. Carapeto: None. K. Dakessian: None. R. Melhem: None. A. Provencher-Girard: None. G. Ostinelli: None. J. Turgeon: None. F. Migneault: None. M.O. Huising: Research Support; Thermo Fisher. G.A. Rutter: Consultant; Sun Pharmaceutical Industries Ltd.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-885-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 886-P: A Novel UCN2 Analog HM17321 with HM15275 Improves Body Composition
in Mouse Model of Obesity-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 886-P
Abstract: Introduction and Objective: Incretin drugs have demonstrated remarkable efficacy in body weight reduction and improving metabolic parameters. However, there may be challenges associated with lean mass loss and long-term health benefits. Urocortin-2 (UCN2) is a corticotropin-releasing factor receptor 2 (CRFR2) agonist and has been known to regulate whole body glucose metabolism, insulin sensitivity and skeletal muscle hypertrophy. In current study, we explore the effects of HM17321, a novel CRFR2 selective UCN2 analog, in combination with HM15275, a GLP-1/GIP/Glucagon triple agonist, on body composition in diet-induced obese (DIO) mice.Methods: DIO mice were subcutaneously injected with vehicle, HM17321 and HM15275 either alone or in combination for 4 weeks. In a second study, DIO mice were initially treated with HM15275 for 3 weeks and then the mice were either continued with HM15275 or switched to HM17321 for an additional 3 weeks. Body weight and food intake were measured during the study, and body composition was determined based on TD-NMR at baseline and after treatment. Skeletal muscle weight and performance were assessed after treatment.Results: HM17321 significantly reduced body weight and fat mass while simultaneously increasing lean mass in DIO mice. Co-administration of HM17321 and HM15275 for 4 weeks led to a greater reduction in body weight and fat mass than either compound alone. Notably, the combination of HM17321 and HM15275 significantly increased skeletal muscle weight and restored muscle function. These effects were observed even with various dose combinations. In line with this, switching to HM17321 maintained fat loss induced by HM15275 while preserving lean mass.Conclusion: The combination of HM17321 and HM15275 resulted in enhanced fat reduction while preserving lean mass, indicating improved body composition during weight loss. These findings suggest that HM17321 could be a promising therapeutic option in combination strategies for treating obesity.DisclosureH. Kwon: None. J.A. Kim: None. S. Lee: None. J. Kim: None. S. Lee: None. I. Choi: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-886-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 887-P: Enhanced Glucagon Signal Suppresses Neurologically Mediated
Meal-Induced Symptoms at Nadir Glucose Levels in Individuals with and
without Gastric Bypass Surgery-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 887-P
Abstract: Introduction and Objective: Gastric bypass surgery (GB) is a treatment for obesity but alters prandial glycemia, increasing the risk of hypoglycemia. Glucagon administration is a potential therapy for post-GB hypoglycemia, but its effects on prandial glycemia or symptoms remain unclear. We investigated the effect of intravenous (IV) glucagon on prandial symptoms in subjects with and without a history of GB.Methods: Eight GB subjects and seven BMI- and age-matched non-operated controls (CN) underwent a mixed meal test, with and without IV glucagon infusion (2 ng/kg/min). Symptoms were measured for 3 hours on a 1-7 scale and categorized into five groups: gastrointestinal (GI; nausea, fullness, rumbling, belching, vomiting, diarrhea), sympathetic nervous system (SNS; shaky, palpitation, anxiety), parasympathetic nervous system (PNS; sweating, hunger, tingling), central nervous system (CNS; tired, warm, confused, weak), and nonspecific (NS; irritability, headache, cold, happy, sad). Symptoms analyzed with Two-way ANOVA with multiple comparisons.Results: Age, BMI, A1C, and baseline symptoms were similar between GB and CN. GI symptoms were significantly higher in GB than CN (p<0.01). GB participants showed higher SNS symptoms (p=0.012), while CN exhibited higher PNS symptoms (p=0.019). CNS and NS symptoms showed no significant differences. Glucagon did not affect glucose levels or GI, SNS, PNS, and NS symptoms. However, glucagon infusion reduced CNS symptoms at nadir glucose levels from 1.88±0.44 to 1.19±0.54 in GB and 1.57±0.40 to 0.29±0.13 in CN (p=0.027).Conclusion: Rerouted gut after GB increased GI and SNS symptoms and reduced PNS symptoms. CNS symptoms associated with nadir glucose are minimized by glucagon infusion without significant changes in glucose. Further research is needed to explore glucagon receptor signals following bariatric surgery, particularly in those suffering from hypoglycemia.DisclosureV. Vargas: None. A. Alamdari: None. A.A. Hansis-Diarte: None. A. Gastaldelli: Advisory Panel; Boehringer-Ingelheim. Consultant; Boehringer-Ingelheim, Novo Nordisk, Merck Sharp & Dohme Corp, Regeneron Pharmaceuticals. Other Relationship; Pfizer Inc, Madrigal Pharmaceuticals, Inc, Echosens, Eli Lilly and Company. Speaker's Bureau; Merck Sharp & Dohme Corp, Eli Lilly and Company, Novo Nordisk. M. Salehi: Advisory Panel; Vognex, Amylyx.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-887-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 888-P: Targeting Toxic Human IAPP Aggregation in Type 2 Diabetes
Development with Antimicrobial Peptides-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 888-P
Abstract: Introduction and Objective: Human islet amyloid polypeptide (hIAPP) is a pancreatic β-cell neuropeptide hormone co-secreted with insulin. However, it is also amyloidogenic. The hypersecretion of hIAPP in pre-diabetes is hypothesised to induce its aggregation, which may contribute to β-cell failure during T2D progression. Currently, no hIAPP aggregation inhibitors have advanced to clinical trials. Our study aims to identify anti-microbial peptides (AMPs) that can inhibit hIAPP aggregation and rescue the pancreatic β-cells from hIAPP-induced toxicity.Methods: Thioflavin T (ThT) binding assay was used to assess AMP inhibition of hIAPP monomer aggregation and secondary nucleated aggregation over 20-40h. The half-maximal inhibitory concentration (IC50) of the selected peptide was then determined via titration with hIAPP. Changes in fibril morphology following AMP addition to hIAPP were visualised through transmission electron microscopy (TEM) after 48h. Selected AMP was then tested in mouse insulinoma cells (MIN6) that were incubated with hIAPP to evaluate their protective effect through a cell viability assay.Results: Six AMPs were tested based on their possible structural affinity with hIAPP aggregates. A helical AMP significantly inhibited the fibrillization of hIAPP monomers for over 40h and reduced secondary nucleated aggregation kinetics. The AMP was found to be a high-affinity inhibitor of hIAPP aggregation with an IC50 of 12.66μM. TEM also showed that hIAPP amyloids formed in the presence of the AMP had shorter and fewer fibrils. Subsequent incubation of 10μM of hIAPP with 20μM of AMP improved MIN6 cell viability and ameliorated hIAPP-induced cytotoxicity.Conclusion: We have validated our ThT kinetic assay with the results of cellular viability experiments to ascertain the effectiveness of AMP in protecting pancreatic β-cells from hIAPP-associated toxicity. Our study underpins the potential of AMPs as a promising tool for therapeutic application in T2D.DisclosureJ. Chen: None. A. Teo: Stock/Shareholder; BetaLife Pte Ltd. S. Bhattacharjya: None.FundingMinistry of Education, Singapore
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-888-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 889-P: Enhancing Glycemic Control through Orlistat Combination Therapy
with Pioglitazone and Metformin in Patients with Obesity Type 2
Diabetes—A Multicenter Randomized Controlled Trial-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 889-P
Abstract: Introduction and Objective: Obesity further impairs blood glucose regulation, so patients with obesity and type 2 diabetes should undergo aggressive weight loss treatment. We aimed to evaluate the efficacy of orlistat in patients with obesity and type 2 diabetes treated with pioglitazone-metformin.Methods: In this double-blind, placebo-controlled, 12-week, multicenter trial, patients aged 18-65 years with type 2 diabetes and a BMI > 28 kg/m² on pioglitazone-metformin. They were randomly assigned to receive placebo or 120 mg orlistat three times daily. The primary endpoint was HbA1c change from baseline to week 12. Secondary endpoints included improvements in blood glucose, HOMA-IR, body weight, and abdominal obesity.Results: After 12 weeks, HbA1c improvement in the orlistat group was not significant. However, insulin resistance improved notably, with HOMA-IR decreasing by -15.6% vs -7.86% in the placebo group (P<0.05). Blood glucose levels also improved significantly; fasting blood glucose dropped by -0.73 vs -0.17 mmol/L (P<0.05). This improvement is linked to orlistat’s weight loss effect. At week 12, the orlistat group had significantly lower BMI (30.16 vs 32.70 kg/m², P<0.001) and reduced subcutaneous fat (246.43 vs 307.38 cm²) and visceral fat (120.70 vs 142.46 cm², P<0.05) compared to the placebo group.Conclusion: Orlistat is effective for patients with obesity and type 2 diabetes who are receiving pioglitazone-metformin therapy, it reduces body weight, improves fat distribution, alleviates insulin resistance, and enhances glycemic control.DisclosureJ. Liu: None. H. You: None. X. Wen: None. Y. Fang: None. L. Bu: None. S. Qu: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-889-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 890-P: Efficacy of Antiobesity Agents on Fat Distribution—A Systematic
Review and Network Meta-analysis of Randomized Controlled Trials-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 890-P
Abstract: Introduction and Objective: Pharmacotherapy offers a potential solution for individuals with overweight and obesity to decrease their body weight. However, there is limited knowledge of the effects of anti-obesity agents on the distribution of body fat.Methods: The PubMed, Embase, and Cochrane Library databases were reviewed for randomized controlled trials (RCTs) of weight-lowering drugs between inception and May 23, 2023. The main results were visceral and subcutaneous adipose tissue (VAT and SAT). Secondary outcomes were altered body weights and waist circumferences. For the statistical analysis, STATA 14.0 was utilized, and the frequentist method was used for random-effect network meta-analyses.Results: A total of 39 articles including 41 RCTs with 2741 patients were included. GLP-1 receptors agonists and SGLT-2 inhibitors were observed to lower VAT (-0.90 [-1.32 to -0.47] and -0.66 [-1.22 to -0.10]) after a mean of 29.4 weeks, while only GLP-1 receptor agonists reduced SAT (-1.01 [-1.58 to -0.43]). Naltrexone-bupropion, GLP-1 receptor agonists, SGLT-2 inhibitors and metformin were found to reduce body weight (-5.60 [-8.64 to -2.56] kg, -4.73 [-5.58 to -3.88] kg, -3.20 [-4.69 to -1.72] kg and -1.93 [-3.01 to -0.85] kg). Lastly, waist circumference was decreased by GLP-1 receptor agonists, metformin, SGLT-2 inhibitors, and naltrexone-bupropion.Conclusion: This analysis demonstrated that GLP-1 receptor agonists may have advantages over other anti-obesity agents in reducing VAT and SAT. SGLT-2 inhibitors were more helpful to reduce VAT. The clinical significance relates to physicians being able to choose appropriate weight-loss agents in accordance with a patient's fat distribution.DisclosureX. Qiao: None. W. Wang: None. L. Guo: Research Support; Abbott, AstraZeneca, Bayer Pharmaceuticals, Inc, Eli Lilly and Company, Innovent Biologics, Merck & Co., Inc, MSD Life Science Foundation, Novo Nordisk A/S, Sanofi, Jiangsu Hengrui Pharmaceuticals Co., Ltd, Tonghua Dongbao. Q. Pan: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-890-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 891-P: Investigating the Protective Mechanism of a Potential Type 1
Diabetes Therapeutic Compound, in Pancreatic Beta Cells—Findings from
Transcriptome Profiling-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 891-P
Abstract: Introduction and Objective: Type 1 diabetes (T1D) is a multifactorial disorder defined by pancreatic beta-cell destruction, ultimately causing insulin deficiency. Thus, T1D patients require lifelong insulin therapy to maintain normal glycemic control. T1D treatment requires protecting pancreatic beta cells from cytokine-induced cell death and restoring insulin secretion, two key properties absent in current therapies. MSB-61 is our lead compound as a future T1D therapeutic. MSB-61 augmented insulin secretion starting at ~4h and protected islets from cell death following cytokine treatment. This study uses RNA sequencing to identify genes associated with the effects of MSB-61 and to determine the possible mechanism of action.Methods: To pursue this aim, islets from CD-1 mice were treated with 10 μM MSB-61, 50 μM MSB-61, or vehicle control for one hour (several hours before insulin effects are observed) and processed for RNA isolation to perform RNA sequencing.Results: Using integrated differential expression and pathway analysis (iDEP), we identified 91 differentially expressed genes (DEGs) from 57,010 genes (including non-coding transcripts). By further limiting the data set to genes that were upregulated more than 5-fold, we limited this set to 19 genes and 3 microRNAs. Notably, 12 of these 19 genes and 2 microRNAs were closely associated with Creb (cAMP response element binding). Among its core target genes are transcription factors such as Fos, FosB, Fosl2, and the Nr4a family (Nr4a1, Nr4a2, and Nr4a3), many of which are identified in our study.Conclusion: This suggests that MSB-61 may exert its protective and stimulatory effects on beta cells by modulating Creb-related transcriptional networks. This study shows that RNA sequencing in drug discovery can identify critical cellular and molecular targets, enabling more focused and effective treatments for T1D,DisclosureP. Khan: None. N. Ajmal: None. K. Corbin: None. X. Tong: None. G. Gu: None. C.S. Nunemaker: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-891-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 892-P: Impact of ReCET Therapy on Continuous Glucose Monitoring (CGM)
Metrics in Type 2 Diabetes—Insights from the REGENT-1 Trial-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 892-P
Abstract: Introduction and Objective: The REGENT-1 trial evaluated the Re-Cellularization via Electroporation Therapy (ReCET™) System, which uses pulsed electric fields (PEF) to regenerate duodenal mucosa and submucosa. We examined the effect of ReCET™ across energy dose cohorts on CGM metrics.Methods: REGENT-1studied endoscopic PEF therapy at three doses in T2D adults on 1-4 non-insulin agents. Group 1) Gen 1 catheter 600V, single treatment (n=12); Group 2) Gen 1 catheter, 600V, double treatment (n=18); and Group 3) Gen 2 catheter (increased treated surface area [TSA]), double treatment 750V (n=21). CGM data were collected using Guardian 3 (Medtronic)Results: Fifty-one participants (mean age 52.9 years, BMI 31.4 kg/m², HbA1c 8.7% [72±9mmol/mol]) underwent PEF therapy. A dose-response effect was evident, with Group 3 yielding the greatest benefit in day and night glucose levels and reduced glycemic variability. Improvements in Group 3 CGM metrics emerged by week 4, peaked by week 24, and were sustained through week 48 (Figure 1). Double treatment with Gen 1 (Group 2) results were intermediate between Groups 1 and 3.Conclusion: ReCET™ treatment was followed by a dose dependent improvement in glycemia. Benefits at the highest dose appeared by week 4 and were durable. Findings highlight PEF-induced duodenal regeneration as a promising approach to improve glycemic control in T2DDisclosureD.N. O'Neal: None. J. Apostolopoulos: None. A. Sartoretto: Research Support; Endogenex. Advisory Panel; Bariatek. Research Support; Erbe Elektromedizin GmbH. Consultant; Boston Scientific Corporation. Speaker's Bureau; Menarini. S. Chandran: None. R. Vaughan: None. B. Holt: None. G. Cameron: None. B. AbuDayyeh: Other Relationship; Endogenex. Consultant; Boston Scientific Corporation, Metronics, Olympus. R.E. Pratley: Consultant; AbbVie Inc. Stock/Shareholder; Altanine, Inc. Consultant; Amgen Inc, AstraZeneca. Other Relationship; Bayer AG, Bayer Pharmaceuticals, Inc, Biomea Fusion. Consultant; Boehringer-Ingelheim. Other Relationship; Carmot Therapeutics, Inc, Corcept Therapeutics, Dompé, Eli Lilly and Company, Endogenex. Consultant; Endogenex. Other Relationship; Fractyl Health, Inc., Gasherbrum Bio, Inc. Consultant; Genprex, Getz Pharma, Hanmi Pharm. Co., Ltd, Intas Pharmaceuticals Ltd, Lexicon Pharmaceuticals, Inc, Lilly USA LLC. Speaker's Bureau; Lilly USA LLC. Other Relationship; Metavention, Novo Nordisk, Novo Nordisk. Speaker's Bureau; Novo Nordisk. Other Relationship; Pfizer Inc, Poxel SA. Consultant; Regeneron Pharmaceuticals. Other Relationship; Sanofi. Consultant; Scholar Rock. Other Relationship; Sun Pharmaceutical Industries Ltd. C.H. Sorli: Employee; Endogenex. E.I. Ekinci: Research Support; Amgen Inc, Novo Nordisk, Lilly Diabetes, AstraZeneca, Endogenex, Versanis. Advisory Panel; Lilly Diabetes, Novo Nordisk.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-892-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 893-P: Long-Term Administration of Dorzagliatin Combined with Sitagliptin
for the Management of Glucose Homeostasis in High-Fat Diet–Induced
Obesity Mice-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 893-P
Abstract: Introduction and Objective: A short-term study in obese T2D patients showed that the combination of dorzagliatin, a glucokinase activator (GKA) and sitagliptin improved glucose controls with increased GLP-1 secretion. This study aims to assess the impact of long-term administration of dorzagliatin and the combination of dorzagliatin/sitagliptin on glucose homeostasis in high-fat diet-induced obesity/diabetes (DIO) mice.Methods: DIO mice were developed following a 6-month high-fat diet. Prior to treatment, mice were evaluated. Mice were then administered dorzagliatin at a dosage of 30 mg/Kg/day, or a combination of dorzagliatin (same dose) and sitagliptin (20 mg/Kg/day) for 30 days. Mice on a standard diet serve as controls.Results: Compared to controls, DIO mice have elevated random and fasting glucose levels, along with higher insulin and glucagon, decreased GLP-1/glucose ratio. On day 30, the glucose levels were all reduced compared to pre-treatment, and the combination therapy was more effective than dorzagliatin alone. Dorzagliatin alone elevated insulin and GLP-1 secretion, the combination resulted in a further increase. The blood chemistry analysis indicated that DIO mice exhibit increased levels of ALT, AST, lipid profiles, and glycated serum protein (GSP). Drug therapy has significantly improved GSP and AST. The combined therapy also improved the LDL levels.Conclusion: DIO mice have impaired GLP-1 secretion, elevated glucose, insulin and glucagon levels. Following 30 days of treatment, glucose levels were improved with increased secretion of insulin, the combination of GKA and DPP4i was superior to dorzagliatin alone with the improved GLP-1 secretion. Those data indicated that, in addition to increased insulin secretion by GKA, the enhanced GLP-1 secretion also played a significant role in improving glucose homeostasis, and the addition of DPP4i amplified these effects.DisclosureD. Han: None. S. Meng: None. R. Li: None. L. Feng: None. L. Chen: None. C. Li: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-893-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 894-P: MET-233 Is an Ultra-Long-Acting Amylin Receptor Agonist
-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 894-P
Abstract: Introduction and Objective: MET-233 is an ultra-long acting (ULA) amylin analog being evaluated in clinical trials for the treatment of obesity. We sought preclinical proof of concept that MET-233, designed to be combined with GLP-1R agonist MET-097, is an effective candidate for obesity treatment.Methods: MET-233 emerged from an amylin analog development program focused on potency, durability, and combinability. The pharmacokinetics of MET-233 and cagrilintide were compared after single administration in pigs. Compatibility of MET-233 and MET-097 for coformulation was assessed, and body weight loss efficacy of MET-233 ± MET-097 was compared to CagriSema after chronic administration in rats.Results: In pigs, the half-life of MET-233 was determined to be 125 h and cagrilintide 83 h. Both MET-233 and MET-097 were soluble across a wide pH range. Chronic administration of MET-233, CagriSema, and MET-233 with MET-097 to rats over 28 d reduced body weight by 17.6%, 14.8%, and 31.2%, respectively.Conclusion: The long half-life of MET-233 observed in pigs suggests that infrequent administration in humans may be achievable. Results from chronic administration to rats indicate that MET-233 is highly effective, and additive impact on body weight was observed when coadministered with MET-097. The potency, durability, and combinability of MET-233 and MET-097 highlight the potential of MET-233 as a differentiated treatment option.Disclosure J.S. Minnion: Stock/Shareholder; Metsera. Employee; Zihipp. C. Hinds: Employee; Metsera, Zihipp. B. Reglinska: Employee; Metsera, Inc.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-894-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 895-P: Proximal Intestinal Mucosal Ablation (PIMA) Eliminates the Need for
Exogenous Insulin in Type 2 Diabetes—Initial STEAM-IE Trial Results-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 895-P
Abstract: Introduction and Objective: Proximal Intestinal Mucosal Ablation (PIMA) is a new endoscopic procedure to treat type 2 diabetes (T2D). PIMA replicates the metabolic benefits of gastric bypass surgery by ablating up to 75 cm of the post-ampullary intestinal mucosa with radiofrequency vapor ablation (RFVA). Similar technologies, limited to 15cm of duodenal mucosa, have attempted to eliminate exogenous insulin in combination with glucagon-like peptide-1 receptor agonists (GLP-1RA) in insulin-requiring (IR)-T2D. We aimed to determine whether PIMA could eliminate exogenous insulin without concomitant GLP-1RA.Methods: A prospective, single-center study (NCT06655740) recruiting patients with IR-T2D on daily long-acting insulin for ≥3 months and glycated hemoglobin (HbA1c) ≤8%. Patients start continuous glucose monitoring (CGM) and then enter a 4-week run-in to ensure stable control. Post run-in, insulin is stopped, and PIMA performed with an endoscope under general anesthesia with a RFVA catheter. RFVA is delivered at a set dose with overlapping (2X) application. Primary outcomes are number of serious adverse events (SAE) and the proportion of patients free of insulin without GLP-1RA at 24 weeks.Results: To date, five patients (median age 52 [IQR 48-56], 60% male) have undergone PIMA. Baseline HbA1c was 6.9% (SD 0.5), body mass index 33.3 kg/m2 (SD 5.7), and diabetes duration 5.2 years. The average insulin dose was 22.4 IU/day (SD 5.9), and median oral diabetic drugs was 1 (IQR 1-2). PIMA was successful in all patients with an average ablation length of 61 cm (SD 2) and procedure time of 51 mins (SD 23). All patients were discharged the next day with no SAEs. All patients are off insulin at a mean follow-up of 30 days (SD 16). The average CGM time in range is 93.2% (SD 7.8) and estimated HbA1c 6.2% (SD 0.5) without GLP-1RA.Conclusion: On early follow-up, PIMA is safe and effective at eliminating exogenous insulin in IR-T2D without need for GLP-1RA.Disclosure B. Norton: Other Relationship; Cook Medical. Research Support; Aqua Medical. A. Papaefthymiou: None. A. Telese: None. P. Vignolo: Research Support; AQUA MEDICAL. P. Marin: None. R. Simons-Linares: None. L. Rodriguez G: None. R. Haidry: None.FundingAqua Medical
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-895-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 896-P: Positive Effect of Acute and Chronic Effects of Oral Ketones in
Subjects with HFrEF and Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 896-P
Abstract: Introduction and Objective: Ketones are energy substrates, serving as a "superfuel" for the heart, skeletal muscle, etc.. Our previous work showed that 3-hour intravenous (IV) exogenous ketones (KE) improved left ventricular function in T2D patients with HFrEF by up to 6%, dose-dependently. However, IV delivery is invasive and impractical for daily use. This study explores acute (3-hour) and chronic (1-week) effects of oral ketones on heart function in T2D patients with HFrEF.Methods: 8 participants with T2D (BMI 23-38 kg/m², HbA1c 6.0-10.0%, eGFR ≥30 ml/min/1.73m², EF <50%) were included. Baseline assessments included a 6-minute walk test (6MWT) and PROMIS Physical Function (PPF) survey. In the acute study, participants consumed two doses of DeltaG-ketone monoester 90 mins. apart. Cardiac MRIs and blood tests were performed pre- and post-dosing. In the chronic study, participants repeated daily ketone dosing for 7 days, with final assessments on day 8.Results: Blood ketone levels significantly increased during the acute phase, peaking at 6±0.3 mmol/L after 3 hours (p<0.0001), without significant changes in glucose (p=0.23). Ejection fraction (EF%) improved significantly during the acute phase (5.0±1.3%) and after 7 days of daily dosing (4.9.±0.6%).Conclusion: Oral KE ingestion shows promise as an adjunct therapy for T2D patients with HFrEF, potentially reducing acute HF admissions and improving mortality. Larger studies are needed to validate these findings.DisclosureF.M. Acosta: None. S. Chidurala: None. P. Frausto: None. G. Marquez Najera: None. A. Moody: None. B. Todd: None. B. Hu: None. C. Rollins: None. D. Juarez: None. M. Escobar Vasco: None. G.D. Clarke: None. C. Solis-Herrera: Advisory Panel; Novo Nordisk, Bayer Pharmaceuticals, Inc.FundingUTHSCSA IIMS/CTSA Pilot Funding
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-896-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 897-P: Efficacy and Safety of Sodium–Glucose Cotransporter 2 Inhibitors
on Solid Organ Transplant Recipients with Diabetes—A Systematic Review
and Meta-analysis-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 897-P
Abstract: Introduction and Objective: Diabetes mellitus is a common complication after solid organ transplant (SOT). Sodium-glucose cotransporter inhibitors (SGLT2i) have shown significant cardio-renal benefits in people with type 2 diabetes. However, their use in SOT recipients remains underexplored in the existing literature. We aimed to perform a systematic review and meta-analysis to evaluate the efficacy and safety of SGLT2i in SOT recipients with diabetes.Methods: PubMed, EMBASE, Cochrane Central, and clinicaltrials.gov were systematically searched for studies using SGLT2i in SOT recipients with diabetes. We computed mean difference (MD) and standardized mean difference (SMD) for continuous outcomes and risk ratio (RR) for binary outcomes, with 95% confidence intervals (CIs). Heterogeneity was assessed using I² statistics. Statistical analyses were performed using Comprehensive Meta-analysis version 3.3.070.Results: Of 1817 identified studies, data from 18 eligible studies containing 5092 participants were pooled. On meta-analysis, SGLT2i was associated with significantly lower glycated hemoglobin (HbA1c) (SMD: −0.36; 95% CI: −0.59, −0.16; p<0.01; I2=90.4%), and body weight (MD: −2.35 kg; 95% CI: −3.0, −1.67; p<0.001; I2=39.3% ) while no difference was noted in estimated glomerular filtration rate. Adverse cardiovascular events were reduced in SGLT2i users (RR: 0.38; 95% CI: 0.25, 0.57; p<0.001; I2= 0%) whereas there was no significant risk of genitourinary infections. There was significant heterogeneity for HbA1c and weight, attributable to population-specific factors, such as time since transplant and concomitant therapies (as glucagon-like peptide 1 receptor agonists).Conclusion: In SOT recipients with diabetes, SGLT2i therapy may be associated with better glycemic control and reduced body weight, presenting an acceptable safety profile and an optimized care.DisclosureP. Ratan: None. S. Kodalak: None. L. Saldarriaga: None. A.D. Andrade: None. R. Ferreira: None. T. Trevisan: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-897-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 898-P: SGLT2 Inhibitors or GLP-1 Receptor Agonists' Development of a
Personalized Treatment Algorithm for Individuals with Type 2 Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 898-P
Abstract: Introduction and Objective: Guidelines recommend GLP-1 receptor agonists (GLP-1-RA) and SGLT2 inhibitors (SGLT2i) for individuals with type 2 diabetes (T2D) at high risk of atherosclerotic cardiovascular disease (ASCVD). We aimed to develop a personalized treatment algorithm to guide the initial decision between these therapies.Methods: Using data from the Diabetes Prospective Follow-up registry (Germany/Austria) we studied individuals with T2D who initiated GLP-1-RA (n=823) or SGLT2i (n=1,566) in a multicenter, real-world setting. Dual users were excluded. Baseline characteristics included age, sex, BMI, eGFR, HbA1c, diabetes duration, and history of ASCVD. Non-fatal ASCVD events (MI, angina, revascularization, stroke, TIA, PAD) were analyzed using dynamic weighted survival modeling to predict the optimal treatment for each individual.Results: Based on a linear decision rule (Figure), the algorithm predicted 48% of individuals to have better ASCVD outcomes with GLP-1-RA and 52% with SGLT2i. GLP-1-RA-optimal individuals had on average a higher BMI (37 vs 31 kg/m²), lower eGFR (71 vs 93 ml/min per 1.73 m2) and less history of ASCVD (9 vs 18%) compared to SGLT2i-optimal individuals.Conclusion: Simple clinical features (BMI, eGFR, history of ASCVD) can guide personalized treatment recommendations to prevent non-fatal ASCVD complications in T2D.DisclosureT. Mori: None. O. Kuss: None. J.K. Mader: Advisory Panel; Abbott. Speaker's Bureau; Abbott. Advisory Panel; Eli Lilly and Company. Speaker's Bureau; Eli Lilly and Company. Stock/Shareholder; elyte Diagnostics. Advisory Panel; embecta. Speaker's Bureau; embecta, Menarini. Advisory Panel; Medtronic. Speaker's Bureau; Dexcom, Inc. Advisory Panel; Dexcom, Inc., Novo Nordisk A/S. Speaker's Bureau; Novo Nordisk A/S. Advisory Panel; Roche Diabetes Care. Speaker's Bureau; Roche Diabetes Care. Advisory Panel; Sanofi. Speaker's Bureau; Sanofi. Advisory Panel; Biomea Fusion, PharmaSens, Tingo Medical. Stock/Shareholder; decide Clinical Software. J. Seufert: Speaker's Bureau; Sanofi-Aventis Deutschland GmbH. Advisory Panel; Boehringer-Ingelheim. Speaker's Bureau; Boehringer-Ingelheim. Research Support; Boehringer-Ingelheim. Advisory Panel; Lilly Diabetes. Speaker's Bureau; Lilly Diabetes. Research Support; Lilly Diabetes. Advisory Panel; Novo Nordisk. Speaker's Bureau; Novo Nordisk. Research Support; Novo Nordisk. R.W. Holl: None. S. Lanzinger: None. J.M. Grimsmann: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-898-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 899-P: Study on the Efficacy and Safety of Henagliflozin Combined with
Continuous Subcutaneous Insulin Infusion in the Treatment of Type 2
Diabetes—A Multicenter, Randomized, Open-Label, Controlled Study-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 899-P
Abstract: Introduction and Objective: The use of sodium-glucose co-transporter 2 inhibitors (SGLT2i) in diabetes treatment is expanding. This study evaluated the efficacy and safety of henagliflozin combined with continuous subcutaneous insulin infusion (CSII) in type 2 diabetes (T2DM) based on continuous glucose monitoring system (CGM).Methods: In this multicenter, randomized, open-Label, controlled study, 210 patients who had T2DM (glycated hemoglobin level of 9% -14% or fasting blood glucose≥11.1 mmol/L) within 5-7 days of hospitalization were randomly allocated in a 1:1 ratio to either the henagliflozin combined with CSII group or the CSII group. The primary endpoint was the time in the range (TIR) of 3.9~10.0 mmol/L blood glucose.Results: The TIR (3.9~10.0 mmol/L) was significantly higher in henagliflozin+CSII group, compared to CSII group (79.99% vs. 74.99%; estimated between-group difference, 5.79 percentage points [95% CI, 2.15 to 9.43]; P=0.005). The time required to achieve target glucose was shorter in henagliflozin+CSII group than in CSII group (Day 3 vs. Day 4). In terms of TAR and insulin dosage, henagliflozin+CSII group was significantly lower than CSII group, respectively (TAR: 19.48% vs. 25.43%, P=0.004; insulin dosage: 0.59U/kg/day vs. 0.66 U/kg/day, P = 0.009). There was no significant difference in the TBR and MAGE between the two groups (TBR 0.68% vs. 0.51%, P = 0.483; MAGE 5.39 mmol/L vs. 5.44 mmol/L, P = 0.805). Additionally, adverse events such as urinary tract infection, diabetic ketoacidosis and hypoglycemia events did not differ between the two groups.Conclusion: Addition of henagliflozin to CSII demonstrated superior glycemic control, shorter time taken to achieve the target glucose, and less insulin dosage compared to CSII in patients with T2DM. The overall safety profile of henagliflozin+CSII is consistent with CSII.DisclosureZ. Huang: None. Y. Wu: None. C. Tang: None. B. Yao: None. X. Xie: None. Q. Yang: None. Y. Qin: None.FundingChina International Medical Foundation (Z-2017-26-2202-4); YLHR Diabetes Metabolism Research Fund Project).
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-899-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 901-P: Systematic Review and Retrospective Cohort Analysis of
SGLT2i-Associated DKA in Patients with Type 2 Diabetes—Insights from
Real-World Data and Meta-summary-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 901-P
Abstract: Introduction and Objective: SGLT2is have been linked to an increased risk of DKA in PwT1D. We performed a systematic review, a meta-summary of existing literature, and a retrospective cohort study on SGLT2i-associated DKA in PwT2D from 4/2018-3/2024.Methods: The systematic review included DKA studies in PwT2D treated with SGLT2i across databases, including PubMed, EMBASE, MEDLINE, Scopus, and Web of Science, as per PRISMA guidelines. The cohort study was conducted in twelve NHS Trust hospitals, using propensity score matching to compare demographics and outcomes of 1,060 DKA episodes among SGLT2i users (n=267) and non-users (n=793).Results: The meta-summary and real-world data indicated that SGLT2i in PwT2D was linked to a higher risk of DKA, with most episodes triggered by factors unrelated to the medication. The real-world data exhibited a shorter duration of DKA and longer hospital stay. However, in a matched population of PwT2D on SGLT2i, there were no significant differences in DKA duration, length of stay, complications, or mortality, suggesting comparable clinical outcomes regardless of SGLT2i use.Conclusion: Our findings emphasize the need for enhanced clinical awareness, risk stratification, and education to manage SGLT2i-related DKA. Further studies are needed to evaluate the safety of restarting SGLT2i post-DKA in PwT2D.DisclosureA. Sharma: None. S. Ali-Baig: None. R. Thayakaran: None. L. Rengarajan: None. N. Chackalaparambil Philip: None. A.A. Abraham: None. P. Narendran: Advisory Panel; Sanofi, Abbott Diagnostics. K. Dhatariya: Advisory Panel; Abbott, AstraZeneca. Speaker's Bureau; Boehringer-Ingelheim, Eli Lilly and Company, Menarini. Advisory Panel; Roche Diabetes Care. Speaker's Bureau; Sanofi. G. Umpierrez: Research Support; Abbott, Dexcom, Inc., Bayer Pharmaceuticals, Inc, Corcept Therapeutics. Advisory Panel; Dexcom, Inc., GlyCare Health. P. Kempegowda: None.FundingNational Institute for Health and Care Research (NIHR) Advanced Clinician Scientist Fellowship.ABCD and Sanofi DKA Collaborative Working Project Grant and Midlands Patient Safety Research Collaboration (PSRC).
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-901-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 902-P: Characterizing Guideline-Based Treatment Concordance among
Individuals with T2DM—A U.S. Cohort Study Using Administrative Claims
from Commercial and Medicare Advantage Health Plans-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 902-P
Abstract: Introduction and Objective: The ADA annually publishes guidance on management of T2DM. Real-world data on the use of guideline-based pharmacological therapy are limited, particularly by risk profile. This study aimed to characterize guideline-based concordant care (GCC) for T2DM overall and among subgroups with cardio-renal-metabolic comorbidities and/or CVD risk factors.Methods: Adults with T2DM were identified from Optum’s de-identified Clinformatics® Data Mart Database (01JAN2021-31MAR2023). Those with continuous enrollment ≥12 months prior and ≥1 month after index (01APR2023) were classified at index into risk profiles of T2DM only; and CKD, ASCVD, HF, CVD risk factors (non-mutually exclusive). GCC was estimated as the percentage of concordant days divided by follow-up days (≤365 days), stratified by insurance status (commercial [COMM] & Medicare Advantage [MAPD]). Age stratification, independent of risk profile, was also explored.Results: A total of 1.7M individuals with T2DM were identified: 17% COMM (n=282,031; mean±SD age 55±10 years; 42% female) and 83% MAPD (n=1,420,773; 73±8.3; 53%). Among the COMM cohort, 51% had T2DM only, 4% had comorbid HF, 8% CKD, 16% ASCVD, and 42% CVD risk factors. Among the MAPD cohort, 12% had T2DM only, 17% had comorbid HF, 31% CKD, 44% ASCVD, and 81% CVD risk factors. Mean±SD GCC was 53±38% among the COMM cohort with T2DM only, 21±34% among those with HF, 31±38% with CKD, 31±38% with ASCVD, and 32±38% with CVD risk factors. Corresponding GCC among the MAPD cohort was 48±40%, 12±27%, 15±30%, 14±29%, and 15±29%, respectively. GCC ranged from 44±39% for those <65 years to 12±28% for those ≥85 years among the COMM cohort, and 32±38% to 7±22% among the MAPD cohort.Conclusion: GCC among the COMM and MAPD T2DM population is suboptimal; those with additional comorbidities and risk factors had particularly low GCC. Efforts to improve GCC may improve patient outcomes.Disclosure K. Guo: Employee; Boehringer-Ingelheim. C. Qian: None. R. Sun: None. M. Knappett: None. B.M.K. Donato: Employee; Boehringer-Ingelheim. S.M. Szabo: Other Relationship; AbbVie Inc. L. Bengtson: Employee; Boehringer-Ingelheim.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-902-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 903-P: The Effect of SGLT2 Inhibitors on Glycemic Control and Renal
Outcomes in Adults with Type 1 Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 903-P
Abstract: Introduction and Objective: Sodium-glucose cotransporter-2 (SGLT2) inhibitors are well-established for type 2 diabetes management due to their glycemic and cardio-renal benefits. However, their role in type 1 diabetes (T1D) is not established as they increase euglycemic ketoacidosis risk. SGLT2 inhibitors are occasionally used off-label as adjuncts in T1D, for their cardio-renal benefits. Here we investigate the impact of SGLT2 inhibitors on glycemic control and renal outcomes among adults with T1D in a real-world clinical setting.Methods: We retrospectively evaluated 103 individuals with T1D (age 55.9±14.2 years, 40.8% female, diabetes duration 27.7±15.9 years, weight 97±27 kg, and BMI 31.4±6 kg/m2) who were prescribed an SGLT2 inhibitor for ≥6 months between 2014 and 2024. Patient data, including weight, A1C, eGFR, creatinine, urine microalbumin/creatinine (UACR) ratio, systolic and diastolic blood pressure were collected at baseline, 3, 6, 12, and 24 months.Results: A1C was reduced at 3, 6,12 and 24 months (-0.37±0.86% at 3 months, p < 0.001; -0.44±0.96% at 6 months, p < 0.001; -0.45±1.07% at 12 months, p < 0.001 and -0.44%±1.5% at 24 months, p<0.05) compared to baseline. UACR ratio decreased only at 3 months (-13±62.5mg/g, p<0.05) compared to baseline. Two patients discontinued SGLT2 inhibitors use due to diabetic ketoacidosis. No significant changes were observed in all other parametersConclusion: These findings suggest that SGLT2 inhibitors use among those with T1D improves glycemic control over two years while transiently improving UACR at 3 months.DisclosureM. Al-Badri: None. A. Barbar Askar: None. M. Fallaha: None. F. Trabzounly: None. J. Jacob: None. S.E. Dhaver: None. O. Hamdy: Research Support; Novo Nordisk, Eli Lilly and Company. Advisory Panel; Abbott Nutrition. A. Mottalib: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-903-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 904-P: Hospitalization Is a Risk Factor for SGLT2i Discontinuation
-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 904-P
Abstract: Introduction and Objective: SGLT2i have major cardiorenal benefits for people with type 2 diabetes. While some guidelines recommend temporarily withholding SGLT2i during hospitalization, limited evidence suggests many people may not restart SGLT2i following discharge. We examined if hospitalization was a risk factor for SGLT2i discontinuation, and if this differed to other diabetes therapy (DPP-4i) not typically withheld in hospital.Methods: We conducted a retrospective cohort study using linked population level data for all adult residents of New South Wales, Australia. We included adults aged 40+ years initiating either SGLT2i or DPP-4i (separately) between 2016 to 2020 and followed up until the earliest: mid 2021 or death. We defined discontinuation as a period of 90 days without a dispensing. We used Cox proportional hazards models to estimate hazard ratios (HR) for the effect of recent hospitalization (within 90 days of discharge, as a time dependent variable) on discontinuation. Models were adjusted for demographic and clinical characteristics.Results: Of people initiating SGLT2i (n=106,098, median age 63 years, 61% male), 42.6% were hospitalized and 63.1% discontinued SGLT2i during follow-up. Discontinuation rates were higher in periods when people had recently been hospitalized (16.7 per 10,000 person-years) compared to periods with no hospitalization (10.1 per 10,000 person-years). This association remained in adjusted models (HR 1.63; 95% CI 1.59-1.66, p <0.001). Of people initiating DPP-4i (n=91,960, median age 66 years, 57% male), 47.6% were hospitalized, and 64.0% discontinued DPP-4i during follow-up. Discontinuation rates were similarly higher around periods of hospitalization (adjusted HR 1.40, 95% CI 1.37-1.43, p <0.001).Conclusion: Hospitalization is a risk factor for SGLT2i and DPP-4i discontinuation. Given their cardiorenal protection, our data should increase clinician awareness to ensure that SGLT2i and other critical medicines are not discontinued following hospitalization.DisclosureT.Y. Milder: None. L. Shepherd: Consultant; AbbVie Inc, IQVIA Inc. S. Pearson: None. H. Råket: None. J. Greenfield: Other Relationship; Novo Nordisk. Speaker's Bureau; Novartis AG, Amgen Inc, Lilly Diabetes, Boehringer-Ingelheim. R.O. Day: None. J. Lin: None. C.A. Pollock: Speaker's Bureau; Amgen Inc. Advisory Panel; AstraZeneca. Speaker's Bureau; AstraZeneca, Boehringer-Ingelheim, CSL Behring. Advisory Panel; CSL Behring, Novo Nordisk A/S. Speaker's Bureau; Novo Nordisk. B. Neuen: Consultant; AstraZeneca, Alexion Pharmaceuticals, Inc, Bayer Pharmaceuticals, Inc, Boehringer-Ingelheim, Novo Nordisk, Traveere Pharmaceuticals. Research Support; Menarini. M. Jun: Research Support; Boehringer Ingelheim and Eli Lilly Alliance. J. de Oliveira Costa: None. S. Stocker: Research Support; Gilead Sciences, Inc. Consultant; Nutromics Pty Ltd, Bellberry Pty Ltd, Virtus Health Pty Ltd, 23strands Pty Ltd. J. Ludington: None. M.O. Falster: Consultant; IQVIA Inc.FundingNational Health and Medical Research Council Ideas grant (grant number: 2002889); National Health and Medical Research Council Medicines Intelligence Centre of Research Excellence (1196900); National Heart Foundation of Australia Future Leader Fellowship (105609)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-904-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 905-P: Variables Associated with Prescription of SGLT2 Inhibitors or GLP-1
Receptor Agonists in Patients with Type 2 Diabetes and Obesity in Spain-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 905-P
Abstract: Introduction and Objective: To analyze glycemic and body weight control in people with type 2 diabetes mellitus (T2DM), and prescribing patterns in primary care.Methods: We reviewed the electronic medical records of 5009 randomly selected T2DM patients, from 70 health centers in Spain. We analyzed results by age group and presence/absence of obesity. A multivariable regression was used to identify variables associated with the use of SGLT2i or GLP-1ra y obesity patients.Results: Regarding treatment, 13.2% of the sample were on lifestyle therapy only, 76.5% received metformin, 37.6% SGLT2i, 32.2% DPP-4 inhibitors, 12.2% GLP-1ra, 18.9% insulin, 6.5% sulfonylureas, and 1.3% glitazones. Glycated Hemoglobin (A1c) was below 7% in 57.7% of patients, and 62.3% met their individualized A1c targets. Overall, 42% of the population had obesity (45.6% of women vs 39.1% of men; p = 0.001). Only 51.5 patients with obesity were treated with SGLT2i or GLP-1ra. Variables associated were: age (younger) (OR 0.70 IC95% 0.63-0.78); number of antidiabetic drugs (higher) (OR 6.20 IC95% 5.27-7.4); dyslipidemia (OR 1.26 IC95% 1.09-1.47) and glycaemic control (better A1c) (OR 0.73 IC95% 0.56-0.94).Conclusion: In Spain, 51.5% of patients with T2DM and obesity were treated with SGLT2i or GLP1ra. This treatment pattern was associated to younger patients, with a higher number of antidiabetic drugs, dyslipidemia, and with better glycaemic control.DisclosureA. Cebrian: None. A. Pérez-Pérez: None. M. Mata-Cases: Advisory Panel; Novo Nordisk. S. Artola: None. F. Alvarez-Guisasola: None. D. Orozco-Beltran: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-905-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 906-P: The Predictive Value of Sirtuins and miRNAs in Cardiac Recovery
after Acute Myocardial Infarction Treated with Empagliflozin-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 906-P
Abstract: Introduction and Objective: SGLT2 inhibitors, primarily used for type 2 diabetes, exhibit cardioprotective effects by improving myocardial metabolism, reducing oxidative stress, and modulating inflammation and fibrosis—key factors in acute myocardial infarction (AMI). This study explores the molecular mechanisms of SGLT2 inhibitors, focusing on non-coding RNAs and sirtuin pathways, to identify biomarkers and strategies for preventing heart failure post-AMI.Methods: We analyzed microRNAs (miRNAs) involved in sirtuin pathways and validated miRNA and sirtuin gene expressions (SIRT1-7) in 243 patients at baseline and after 26 weeks of treatment (486 samples) using qRT-PCR. We also conducted SHAP analysis, miRNA target predictions, and enrichment analyses.Results: Bioinformatics identified interaction networks for SGLT2 (5225 nodes) and SIRT1-7 (top 100 interactors), annotated for oxidative stress, inflammation, fibrosis, and hypoxia-ischemia. Combining miRNA predictions with these networks identified 13 key miRNAs, including hsa-miR-34a-5p, miR-182-5p, and hsa-miR-302a-3p, targeting SIRT and SGLT2-related pathways. Empagliflozin treatment significantly increased SIRT6, SIRT7, and miR-34a while reducing SIRT4 (p<0.05). Baseline SIRT2 and SIRT4 levels independently predicted unfavorable LVEF outcomes (AUC: 0.655, p=0.002), with improved prediction using a panel including miR-182-5p (AUC: 0.786, p=0.0003). NT-proBNP levels were higher in the unfavorable group after 26 weeks, but no baseline differences were observed.Conclusion: Empagliflozin modulates sirtuin and miRNA expression, suggesting cardioprotective effects in AMI. Baseline SIRT2, SIRT4, and miR-182-5p levels predict unfavorable LVEF outcomes, with a combined biomarker panel offering high accuracy. These findings highlight the potential of integrating sirtuins, miRNAs, and clinical biomarkers for improved cardiac outcome management post-AMI.Disclosure A. Nowak-Szwed: Speaker's Bureau; Novo Nordisk. C. Eyileten: None. Z. Wicik: None. S. Ahmadova: None. J. Siller-Matula: None. D. von Lewinski: Speaker's Bureau; Daiichi Sankyo, Novo Nordisk. Research Support; Merck Sharp & Dohme Corp. H. Sourij: Advisory Panel; Eli Lilly and Company. Speaker's Bureau; Eli Lilly and Company. Research Support; Eli Lilly and Company. Advisory Panel; Boehringer-Ingelheim. Speaker's Bureau; Daiichi Sankyo. Advisory Panel; Novo Nordisk A/S. Speaker's Bureau; Novo Nordisk A/S. Advisory Panel; Novartis AG, Amarin Corporation, Amgen Inc. M. Postula: None.FundingEMPATHYtrial 2019/ABM/01/00037NCN 2022/45/N/NZ7/0246
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-906-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 907-P: Clinical Efficacy and Safety of SGLT2 Inhibitors and DPP-4
Inhibitors Combination in Asian Patients with Type 2 Diabetes Inadequately
Treated with Metformin—A Systemic Review and Meta-analysis of Randomised
Controlled Studies-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 907-P
Abstract: Introduction and Objective: To analyze the efficacy, safety and tolerability of SGLT2i and DPP-4i combination vs placebo as add-on or initial therapy in Asian patients with T2DM as available data is heterogenous in Asian population.Methods: Database like MEDLINE, Embase, and Cochrane review was searched until August 2023 to identify trials evaluating the efficacy and safety of combination therapy (SGLT-2i+ DPP-4i and/or metformin) in subjects with Asian origin. Primary outcome was mean difference in glycemic and extra-glycemic effects like body weight and systolic BP, and hypoglycemia risk at least for 24 weeks. A meta-analysis was conducted to measure standardized mean differences (SMD), and other relevant statistics for clinical parameters. Meta-analysis with systemic review was performed using CMA v4 software.Results: A total of nine RCTs were included with 2170 patients (three studies as initial combination, three of SGLT2i as add-on to DPP-4i and three of DPP-4i as add onto SGLT2i in a sequential manner). Overall, the combination of SGLT2i and DPP-4i demonstrated a significant decrease in HbA1c relative to DPP-4i [-0.95% (95% CI: -1.09, -0.81)] or SGLT2i [-0.97% (95% CI: -1.11, -0.83)] compared to placebo. When SGLT2i combined with DPP-4i, either as initial or sequential combination, a marked lowering of HbA1c level was reported. Patients treated in combination treatment revealed the favorable effects on the body weight and systolic BP compared to subjects on DPP-4 inhibitors, but no difference in subjects of SGLT2i arm. There were no statistically significant differences in the incidence of adverse events.Conclusion: SGLT2i and DPP-4i combination show significant glycemic improvement in Asian population. Safety indicators did not show significant differences. More high-quality studies are required to validate these findings.Disclosure M. Khalse: Employee; Lupin Pharmaceuticals, Inc. M.K. Sowmiya: Employee; Lupin Pharmaceuticals, Inc.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-907-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 908-P: The Broader Impact of Sotagliflozin—Meta-analysis of Its Efficacy
in Diabetes Management, Cardiovascular Risk Reduction, and Renal Outcome-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 908-P
Abstract: Introduction and Objective: Sotagliflozin, a dual inhibitor of sodium-glucose co-transporters 1 and 2, represents a promising therapeutic option in diabetes management. Its unique mechanism targets glucose absorption in the intestines and reabsorption in the kidneys, offering benefits beyond glycemic control, including cardiovascular and renal protection. However, variations in study design and outcomes necessitate a comprehensive evaluation of its clinical efficacy and safety. This study aims to assess the impact of Sotagliflozin on glycemic control, cardiovascular and renal outcomes, weight management, and safety. It also evaluates variations across study designs, populations, and comparators.Methods: A systematic review and meta-analysis were conducted following PRISMA guidelines. Data from PubMed, Embase, Cochrane Library, and ClinicalTrials.gov were synthesized. Nineteen studies met the inclusion criteria, comprising randomized controlled trials and observational studies. Outcomes included HbA1c reduction, cardiovascular events, renal outcomes, and safety profiles.Results: Sotagliflozin significantly improved glycemic control with an odds ratio (OR) of 1.085 (95% CI:1.037-1.134) and low heterogeneity (I2 =0.044). While glycemic efficacy was consistent, cardiovascular safety remained uncertain, with a pooled hazard ratio (HR) for myocardial infarction of 1.76 (95% CI: 0.90-2.62). Subgroup analyses revealed variations based on study design, region, and population.Conclusion: Sotagliflozin demonstrates significant benefits in glycemic control and potential advantages in weight management and renal outcomes. However, uncertainties in cardiovascular safety and limited head-to-head comparisons with other therapies highlight the need for further high-quality studies to optimize its clinical use. These findings provide a foundation for advancing diabetes management strategies.DisclosureM. Zeb: None. S.W. Salari: None. A.L. Dabaja: None. S. Kambhatla: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-908-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 909-P: Prevalence and Factors for Treatment Failure with Sodium–Glucose
Cotransporter 2 Inhibitor (SGLT2i) in U.S. Adults with Type 2 Diabetes
(T2D)-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 909-P
Abstract: Introduction and Objective: To assess prevalence and factors for treatment failure with SGLT2i in US adults with T2D.Methods: This was a retrospective cohort study among US adults with T2D who initiated SGLT2i between January 1, 2016 and April 30, 2024, using the Komodo Healthcare MapTM database. Treatment failure occurred if they discontinued SGLT2i, added or switched to another glucose-lowering therapy, or had consecutive HbA1c ≥8% without treatment changes. Time to SGLT2i failure was assessed using cumulative incidence functions. Factors for failure were identified using Cox models. Lastly, incidence of T2D complications and healthcare resource utilization (HCRU) were described.Results: Out of 237,295 new SGLT2i users, 183,485 (77.3%) experienced treatment failure over an average follow-up time of 34 months. The median time to failure was 9.14 months. Risk factors for failure included age ≥75, comorbidities such as hypertension, and experiencing common T2D-related adverse events such as hypoglycemia leading to ER or hospitalization. Lastly, high incidence of T2D complications and HCRU were observed with SGLT2i failure.Conclusion: The study revealed high prevalence and burden of treatment failure with SGLT2i, suggesting the need for timely treatment adjustment for the high-risk population who do not achieve optimal treatment benefit with SGLT2i.Disclosure X. Tan: Employee; Novo Nordisk. Y. Cao: None. Y. Wang: Other Relationship; Analysis Group, Inc. J.M. Boland: None. M. Guevarra: Employee; Novo Nordisk. L. Xie: None. Y. Song: Research Support; Novo Nordisk. M.N. Kwak: Consultant; Novo Nordisk, Endocrine & Diabetes Plus Clinic of Houston.FundingThe study was funded by Novo Nordisk, Inc.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-909-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 910-P: SGLT2 Inhibitor Prescribing among Patients with Diabetes and
Chronic Kidney Disease or Heart Failure in a Primary Care Network-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 910-P
Abstract: Introduction and Objective: SGLT-2 inhibitors (SGLT-2i) reduce heart failure (HF) hospitalization among HF patients and slow kidney disease progression and lower cardiovascular risk among patients with chronic kidney disease (CKD). We estimated the proportion of patients with type 2 diabetes and either HF or CKD with an active prescription for an SGLT2i and identified factors associated with prescribing.Methods: We conducted a cross-sectional analysis of adults with type 2 diabetes seen at one of 40 primary care practices in the mid-Atlantic region in 2023 using electronic health record data. Diabetes and HF were defined using ICD-10 codes while CKD was defined based on Kidney Disease Improving Global Outcomes diagnostic criteria. An SGLT2i prescription was defined as active as of 12/31/2023 or reported as such by the patient. We examined age, gender, race, ethnicity, area deprivation index, insurance class, hemoglobin A1c (A1c), and body mass index, with statistical comparison by ANOVA and Chi-squared tests.Results: Among 23,225 patients with type 2 diabetes seen in primary care, median age was 65 years; 49.1% were white, 36.3% African American, 3.5% Hispanic, and 51% women. 13.7% had CKD and 9.0% had HF. Overall, 20.2% of patients with diabetes had an active SGLT-2i prescription, versus 28.8% and 35.3% for those with CKD and HF, respectively. Patients with CKD or HF prescribed an SGLT2i were younger, and more often male or had A1c >7% compared to those not prescribed (A1c >7%: CKD, 51.5% vs. 36.2%; HF, 44.8% vs. 33.5%, p<0.001 for both comparisons). Among HF patients prescribed an SGLT2i, a greater proportion were African American compared to those not prescribed, which was not seen in CKD (HF, 44.0% vs. 34.8%; CKD, 49.1% vs. 51.1%).Conclusion: Most patients with diabetes and HF or CKD do not currently receive indicated SGLT2i. Interventions are needed to increase prescribing among these patients, particularly among those with adequate glycemic control.DisclosureN.M. Maruthur: None. L. Yanek: None. N.N. Mathioudakis: None. E. Michos: Consultant; Amgen Inc, Boehringer-Ingelheim, Novo Nordisk, Edwards Lifesciences, Eli Lilly and Company, Ionis Pharmaceuticals, NewAmsterdam Pharma, Bayer Pharmaceuticals, Inc, ESPERION Therapeutics, Inc., Arrowhead Pharmaceuticals, Inc. C. Cervantes: None. J. Wu: None. S. Pitts: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-910-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 911-P: Comparative Effectiveness of Empagliflozin vs. DPP-4i on MACE, HHF,
and Mortality across Demographic Factors-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 911-P
Abstract: Introduction and Objective: Clinical trials were not powered to examine if the cardiovascular (CV) benefits of empagliflozin (EMPA) in patients with type 2 diabetes (T2D) are consistent across demographic factors.Methods: Using Medicare data (2014-2020), we compared 1:1 propensity score-matched patients aged ≥65 years with T2D initiating EMPA vs DPP4i for MACE, hospitalization for heart failure (HHF), and mortality, overall and by age, sex, and race or ethnicity, adjusting for 155 baseline confounders. We estimated rate differences (RD) and hazard ratios (HR) with 95% CI, assessing effect heterogeneity via the Wald test.Results: After PS matching, EMPA was associated with decreased risk of MACE [HR=0.77 (0.72, 0.81); RD= -10.10 (-12.38, -7.83)], HHF [HR=0.72 (0.69, 0.76); RD= -17.68 (-20.45, -14.91)], and mortality [HR=0.66 (0.60, 0.72); RD= -8.48 (-10.14, -6.82)] vs DPP4i, with evidence of effect heterogeneity seen only for age on the RD scale (Figure). Specifically, EMPA had greater absolute benefit vs DPP4i in patients aged ≥75 vs 65-74 years, with 17 vs 7 fewer MACE and 25 vs 14 fewer HHF events and 12 vs 6 fewer deaths per 1,000 person-years.Conclusion: This study suggests that EMPA is beneficial for CV events and mortality in subgroups of sex and race or ethnicity, though its absolute benefits vs DPP4i may vary by age, with a higher absolute benefit observed in older adults aged ≥75 vs 65-74 years.Disclosure S. Cromer: Other Relationship; Johnson & Johnson Medical Devices Companies. Advisory Panel; Alexion Pharmaceuticals, Inc. Consultant; Wolters Kluwer Health, Patient Square Capital. H. Tesfaye: None. D.J. Wexler: Other Relationship; Novo Nordisk. A. Freedman: None. C.M. Shay: Employee; Boehringer-Ingelheim. J.M. Paik: None. E. Patorno: Research Support; National Institute of Diabetes and Digestive and Kidney Diseases, Patient-Centered Outcomes Research Institute, Food and Drug Administration (FDA), Boehringer-Ingelheim. Other Relationship; UpToDate.FundingAmerican Diabetes Association (7-21-JDFM-005); This study was supported by a research grant to the Brigham and Women's Hospital from Boehringer Ingelheim. Boehringer Ingelheim had no role in the design, analysis, or interpretation of the results in this study. Boehringer Ingelheim was given the opportunity to review the abstract for medical and scientific accuracy as it relates to Boehringer Ingelheim substances, as well as intellectual property considerations.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-911-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 912-P: The Minimum Frequency of Well-Day Capillary Blood Ketone Testing
Needed for Future Diabetic Ketoacidosis (DKA) Prediction in T1D-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 912-P
Abstract: Introduction and Objective: Routine well-day surveillance of capillary ketone levels in T1D can predict future DKA risk, including in those using sodium glucose-linked transporter inhibitors (SGLTi). We assessed the impact of ketone testing frequency on prediction accuracy using data from the EASE trials.Methods: Data from 1685 participants assigned empagliflozin or placebo were analyzed. Ketone measurements were randomly selected to simulate less frequent testing than the protocol’s 2-3 tests/week. Maximum and other statistics of ketone levels were derived and categorized into 28-day intervals. Gradient Boosting Tree models were trained (80% of participants) and evaluated (remaining 20%) to predict DKA or severe ketosis in subsequent intervals. Areas Under the Receiver Operating Characteristic Curve (AUC) were compared using one-sided DeLong tests.Results: Out of the 11,218 intervals, 600 had DKA or severe ketosis events. Predictive performance decreased with less frequent testing: Biweekly compared to all data (2-3 tests per week) had slightly lower AUC (0.75 vs. 0.81, p = 0.081), but with testing at 21-day intervals, the AUC decreased significantly compared to biweekly (0.65, p = 0.027, Figure 1).Conclusion: To reasonably predict future ketoacidosis risk among T1D users or non-users of SGLTi, ketone testing on well-days every 2 weeks is the recommended strategy.DisclosureY. Zhang: None. D.R. Budhram: None. P. Bapat: None. S. Dhaliwal: None. C. Song: None. D. Scarr: Employee; Medicenna Therapeutics. A.M.K. Bakhsh: Other Relationship; Sanofi. Advisory Panel; Ithanin. N. Verhoeff: None. A. Weisman: None. M. Fralick: None. N. Ivers: None. D. Cherney: Consultant; Boehringer Ingelheim-Lilly, Merck, AstraZeneca, Sanofi, Mitsubishi-Tanabe, Abbvie, Janssen, AMGEN, Bayer, Prometic, BMS, Maze, Gilead, CSL-Behring, Otsuka, Novartis, Youngene, Lexicon, Inversago, GSK. Research Support; Boehringer Ingelheim-Lilly, Merck, Janssen, Sanofi, AstraZeneca, CSL-Behring and Novo-Nordisk, Bayer. G.A. Tomlinson: None. D. Mumford: None. L. Lovblom: None. B.A. Perkins: Other Relationship; Abbott, Novo Nordisk, Sanofi. Advisory Panel; Abbott, Insulet Corporation, Sanofi, Novo Nordisk, Nephris, Vertex Pharmaceuticals Incorporated. Research Support; Novo Nordisk.FundingDiabetes Canada (OG-3-21-5572-BP)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-912-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 913-P: Sodium–Glucose Cotransporter 2 Inhibitor Combined with
Low-Carbohydrate Diets Safely Achieves Moderate Ketosis in Healthy
Volunteers—An Open-Label Pilot Study-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 913-P
Abstract: Introduction and Objective: Very low dietary carbohydrate restriction leads to modest ketogenesis but is inherently difficult to follow and is variably effective, limiting clinical utility. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) modestly increase ketones. This study tested the hypothesis that background use of SGLT2i would reduce the degree of carbohydrate restriction needed to reliably achieve moderate ketosis, without metabolic acidosis, in healthy adults without diabetes.Methods: Seven volunteers (6M/1F, Age: 31.9 ± 9.9 yrs, BMI: 27.9 ± 3.9 kg/m2) completed a closely supervised 28-day inpatient stay and received a fixed dose of SGLT2i daily (open label) combined with increasing carbohydrate restriction. An adaptive study design was used to determine the degree of dietary carbohydrate restriction needed to increase capillary β-hydroxybutyrate to 1.0 mmol/L, in which the percentage of total calories from dietary carbohydrates was progressively reduced weekly from 50%, 30%, 20%, and if needed to 10%.Results: Six participants reached ketosis (defined as capillary β-hydroxybutyrate to 1.0 mmol/L) on SGLT2i and 10% carbohydrate diet and one participant reached ketosis on SGLT2i and 20% carbohydrate diet. Adverse events were mild. The most common symptom was gastrointestinal discomfort. Average blood anion gap from during the last study week was 11± 2 mmol/L. There was no overt metabolic acidosis.Conclusion: Less restrictive low carbohydrate diets with background use of SGLT2i in a highly controlled setting can safely and feasibly achieve moderate ketosis in healthy adults without diabetes. The degree of carbohydrate restriction needed to achieve moderate ketosis with SGLT2i use may vary by individual.DisclosureM. Erickson: None. K. Corbin: None. K. Olszewski: None. R.E. Pratley: Consultant; AbbVie Inc. Stock/Shareholder; Altanine, Inc. Consultant; Amgen Inc, AstraZeneca. Other Relationship; Bayer AG, Bayer Pharmaceuticals, Inc, Biomea Fusion. Consultant; Boehringer-Ingelheim. Other Relationship; Carmot Therapeutics, Inc, Corcept Therapeutics, Dompé, Eli Lilly and Company, Endogenex. Consultant; Endogenex. Other Relationship; Fractyl Health, Inc., Gasherbrum Bio, Inc. Consultant; Genprex, Getz Pharma, Hanmi Pharm. Co., Ltd, Intas Pharmaceuticals Ltd, Lexicon Pharmaceuticals, Inc, Lilly USA LLC. Speaker's Bureau; Lilly USA LLC. Other Relationship; Metavention, Novo Nordisk, Novo Nordisk. Speaker's Bureau; Novo Nordisk. Other Relationship; Pfizer Inc, Poxel SA. Consultant; Regeneron Pharmaceuticals. Other Relationship; Sanofi. Consultant; Scholar Rock. Other Relationship; Sun Pharmaceutical Industries Ltd. J.D. Rabinowitz: Other Relationship; Colorado Research Partners, Bantam Pharmaceuticals, Barer Institute, Rafael Pharmaceuticals, Empress Therapeutics, Marea Therapeutics, Farber Partners, Raze Therapeutics, Sofro Pharmaceuticals, Fargo Biotechnologies, Rutgers Cancer Institute of NJ, University of Pennsylvania Diabetes Research Center, University of Pennsylvania inter-institutional metabolomics core, Rutgers Cancer Institute of New Jersey metabolomics core, Princeton University-PKU Shenzhen, Ludwig Princeton Branch. S.R. Smith: Advisory Panel; Boehringer-Ingelheim, Novo Nordisk. Consultant; Zealand Pharma A/S. Advisory Panel; Amgen Inc. Research Support; Abvance Therapeutics.FundingLudwig Cancer Research Foundation
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-913-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 914-P: Sodium–Glucose Cotransporter 2 (SGLT2) Inhibitors and
Nephrolithiasis—An Updated Meta-analysis-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 914-P
Abstract: Introduction and Objective: SGLT-2i are effective in treating type 2 diabetes (T2DM), promoting weight loss, reducing blood pressure, and lowering cardiovascular risk. Diabetes increases nephrolithiasis risk due to urine acidification and elevated oxalate concentrations. This meta-analysis evaluates the impact of SGLT-2i on nephrolithiasis incidence.Methods: A comprehensive search of Medline, Embase, Google Scholar, Cochrane CENTRAL, Scopus, and clinicaltrials.gov was conducted through November 2024. We included observational studies and RCTs comparing SGLT-2i to other diabetes medications or placebo. The primary outcome was nephrolithiasis incidence after treatment. A random-effects meta-analysis was performed to calculate the pooled odds ratio (OR).Results: Twenty-eight studies (75,371 participants) met the inclusion criteria. The pooled analysis showed that SGLT-2i significantly reduced the risk of nephrolithiasis compared to other medications or placebo (OR: 0.90; 95% CI: 0.83-0.98; p=0.02; I²=0%). This contrasts with a previous meta-analysis that found no association between SGLT-2i and nephrolithiasis.Conclusion: This updated meta-analysis shows that SGLT-2i reduce nephrolithiasis risk in T2DM, suggesting potential benefit for those with recurrent nephrolithiasis. These findings highlight the broader therapeutic benefits of SGLT-2i beyond glucose control.DisclosureZ. Shahzad: None. O. Ijaz: None. B. Ilmaguook: None. R. Ali: None. S.S. Usmani: None. A.A. Khan: None. S. Yasmin: None. A. Moiz: None. F. Samrah: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-914-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 915-P: Risk of Severe Lower Extremity Arterial Disease in Elderly Japanese
Patients with Type 2 Diabetes—A Propensity Score-Matched Model Analysis
of Sodium–Glucose Cotransporter 2 Inhibitors vs. Metformin-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 915-P
Abstract: Introduction and Objective: This study examines the impact of Sodium-glucose cotransporter 2 inhibitors (SGLT2is) and metformin on severe Lower extremity arterial disease (LEAD) progression in elderly patients with type 2 diabetes (T2D). Using propensity score matching, a three-year analysis compares their distinct effects on risk using a real-world claims database.Methods: This retrospective cohort study analyzed insurance data for individuals aged 65 years, using health insurance claims and self-reported health checkup data from the web-based platform kencom by DeSC Healthcare Inc. Severe LEAD was defined as cases requiring revascularization after a LEAD diagnosis. After matching, hazard ratios (HR) for endpoints were analyzed using a Cox proportional hazards model.Results: After matching, baseline variables were similar. Incidence rates were 2.10 and 2.69 per 1,000 person-years for metformin and SGLT2is, respectively. Compared to metformin, SGLT2is showed a higher HR for severe LEAD, especially with diastolic blood pressure (dBP) below 80 mmHg (HR: 1.53) and eGFR between 30-60mL/min/1.73m2 (HR:2.32).Conclusion: The endothelial benefits of metformin, achieved without affecting hemodynamics, may be particularly effective in patients with low dBP or impaired renal function. In elderly patients with T2D, the presence of cardio vascular disease may often lead to the selection of SGLT2is. However, considering the status of LEAD, prioritizing the use of metformin may also be a prudent consideration.DisclosureT. Horii: None. Y. Oikawa: None. A. Shimada: Speaker's Bureau; Sanofi. K. Mihara: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-915-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 916-P: Real-World Use of Sodium–Glucose Transporter 2 Inhibitors among
Youth with Type 2 Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 916-P
Abstract: Introduction and Objective: Clinical trials of sodium-glucose transporter 2 inhibitors (SGLT2i) in youth with type 2 diabetes (T2D) showed significant improvement in HbA1c% and fasting plasma glucose, yet there is limited real-world data on their use. This study sought to assess real-world use and effectiveness of SGLT2i medications in management of T2D in a diverse cohort of youth.Methods: This retrospective study analyzed youth prescribed a SGLT2i for management of T2D at two academic pediatric diabetes centers. Change in HbA1c, BMI, and insulin use from baseline to follow-up were evaluated for those taking SGLT2i. Wilcoxon signed-rank test and McNemar’s test were used to compare paired continuous and categorical variables, respectively.Results: A total of 82 patients with T2D (mean age 17.3 years (SD 1.9), 63% female, 13% Hispanic, 51% non-Hispanic Black, 31% non-Hispanic white, 61% with public insurance) were prescribed SGLT2i. Among the 62 (76%) reporting adherence or partial adherence at a median follow-up of 103-days, median HbA1c decreased from 8.4% to 7.3% (p<0.001). There was a significant reduction in mean BMI from baseline to follow-up (40.3 to 39.8kg/m2, p=0.02). The proportion of patients prescribed basal insulin decreased from 40% to 34% (p=0.13), and prandial insulin use decreased from 22% to 16% (p=0.06).Conclusion: Real-world use of SGLT2i in youth with T2D is associated with decreased HbA1c levels and lower BMI, and may also reduce use of insulin for youth with T2D.DisclosureM. Timkovski: None. R.M. Wolf: Research Support; Novo Nordisk, Lilly Diabetes. Advisory Panel; Uneo. Research Support; Sanofi. D. Patel: None. B. Magella: None. E.A. Brown: None. A.S. Shah: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-916-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 917-P: Real-World Impact of Open Source Automated Insulin Delivery (OS
AID) on Glycemic Variability Reduction-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 917-P
Abstract: Introduction and Objective: Glycemic variability, a key determinant of diabetes-related complications, remains a challenge in diabetes management. Time with rapid glucose change (TRC) has recently been proposed as a metric for assessing glycemic variability. There are no published data addressing the potential for AID to reduce TRC. BCDiabetes has a high volume of clients using OS AID with the apps Loop, iAPS and AAPS, and fully permissioned access to their data for research purposes.Methods: This retrospective analysis included all OS AID clients with paired Time in Range (TIR) at baseline and at 60 days. TIR was measured over 14 days using glucose target 3.9-10.0 mmol/L. TRC was defined as % time with glucose changing at >0.55 mmol/L per 5 minutes. Analysis used paired t-tests, with subgroups of baseline TIR of <50% and >70%.Results: 522 clients were studied of whom 33% were pediatric, 47% male, average age 32 years and average duration of T1 15 years. See Table 1 below.Conclusion: This is the first evidence supporting a role for AID in reducing TRC, particularly in individuals with TIR < 50% and invites validation. With validation TRC might be included in standard CGM reporting. In the future high TRC may be used as a further indication for the use of AID as standard care in T1D.DisclosureA. Alqahtani: None. N. Khan: None. K. Hawke: None. T. Elliott: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-917-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 918-P: Fully Closed Loop (FCL) System Improves Glycemic Control through
Personalized Adaptation of Individual Insulin Needs in Adults, Young
Adults, and Adolescents with Type 1 Diabetes (T1D)-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 918-P
Abstract: Introduction and Objective: The Automated Insulin Delivery as Adaptive NETwork (AIDANET) FCL adjusts its aggressiveness based on glycemic metrics computed from the last 14-days of CGM records, to adapt to the different insulin requirements that individuals may have. The system was tested in a broad cohort of people with T1D. We report changes in glycemic outcomes during home use.Methods: Participants enrolled in a randomized crossover trial across three age cohorts (14-17, 18-25 or 26-60 years) and two HbA1c groups (<8% or 8-12%). Depending on their 1:1 randomization, 2-week usual care data was collected either before or after completing a 5-day hotel stay for AID system training followed by the 7-day at-home period. AIDANET tunes control aggressiveness via a single parameter, defined as estimated Total Daily Insulin (eTDI), adjusted by a change factor (eTDIα) to minimize time below range 70 mg/dL (TBR) and time above range 180 mg/dL (TAR). eTDIα<1 implies a decreased eTDI.Results: Thirty-four participants completed the study. eTDI was reduced (eTDIα<1, Figure) when TBR increased and increased when reduced time in range (with increased TAR) was observed. TBR was reduced from start to end of the home period (-1.62%; p=0.048) while maintaining low TAR via the eTDI modulation.Conclusion: AIDANET adaptation system achieved reduced hypoglycemia by tailoring eTDI to each individual.Disclosure M. Moscoso-Vasquez: Other Relationship; Dexcom, Inc. Research Support; Tandem Diabetes Care, Inc, National Institute of Diabetes and Digestive and Kidney Diseases. D. Flanagan: None. M. Clancy-Oliveri: None. E. Escobar: None. D. Fulkerson: None. G.P. Forlenza: Advisory Panel; Medtronic. Research Support; Medtronic, Dexcom, Inc. Consultant; Dexcom, Inc. Research Support; Insulet Corporation. Consultant; Insulet Corporation. Research Support; Tandem Diabetes Care, Inc. Advisory Panel; Tandem Diabetes Care, Inc. Research Support; Abbott. Advisory Panel; Sequel Med Tech. L. Ekhlaspour: Other Relationship; Medtronic. Advisory Panel; Abbott, Medtronic. Consultant; Jaeb Center for Health Research. Research Support; MannKind Corporation. Speaker's Bureau; Insulet Corporation. Advisory Panel; Sequel Med Tech. Other Relationship; Tandem Diabetes Care, Inc. Research Support; Abbott. Other Relationship; Sanofi. S.A. Brown: Research Support; Dexcom, Inc., Insulet Corporation, Tandem Diabetes Care, Inc, Tolerion, Roche Diabetes Care. Other Relationship; MannKind Corporation. M.D. Breton: Speaker's Bureau; Sinocare Inc, Tandem Diabetes Care, Inc. Consultant; Roche Diabetes Care, Boydsense.FundingBreakthrough Type 1 Diabetes (2-SRA-2023-1275-M-B)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-918-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 919-P: Sex Differences in Glycemic Outcomes Using Fully Automated Closed
Loop (FCL) System in Type 1 Diabetes (T1D)—Insights and Implications-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 919-P
Abstract: Introduction and Objective: Diabetes management and outcomes often differ by sex, influenced by biological and psychobehavioral factors. Our objective was to examine sex differences in glycemic outcomes during the safety and feasibility testing of the AIDANET automated insulin delivery system (AID)Methods: Participants with T1D enrolled in a randomized crossover trial of usual care (overwhelmingly AID with meal bolus, UC) vs the AIDANET system in FCL (without premeal boluses). FCL management consisted of a supervised phase followed by a week of home use. Glycemic metrics for FCL home use compared to UC were analyzed by sex subgroups considering males (M) and females of reproductive age not using contraception (FRA)Results: Of the 34 participants completing the trial, 12 were M and 10 FRA. For M, FCL showed significant improvements in TAR, TAR250 and mean glucose (UC: 185±29.1 mg/dL, FCL:169.2±17.3 mg/dL, p=0.046); and non-inferiority for TIR, TTR 70-140mg/dL (p=0.014) and TBR54. For FRA, FCL showed non-inferiority on mean glucose (UC: 184.3±42.9 mg/dL, FCL:161±14.6 mg/dL, p=0.031), TTR (p=0.030), TAR250 and TBR54; and increased TBR.Conclusion: AIDANET in FCL improved glycemia in males without compromising it in females, while eliminating the need for manual meal boluses. Glycemia could be improved for females with T1D by devising innovative FCL systems that account for the sex differences.Disclosure M. Moscoso-Vasquez: Other Relationship; Dexcom, Inc. Research Support; Tandem Diabetes Care, Inc, National Institute of Diabetes and Digestive and Kidney Diseases. J.Y. Hosseinipour: None. D. Flanagan: None. D. Fulkerson: None. S.A. Brown: Research Support; Dexcom, Inc., Insulet Corporation, Tandem Diabetes Care, Inc, Tolerion, Roche Diabetes Care. Other Relationship; MannKind Corporation. L. Ekhlaspour: Other Relationship; Medtronic. Advisory Panel; Abbott, Medtronic. Consultant; Jaeb Center for Health Research. Research Support; MannKind Corporation. Speaker's Bureau; Insulet Corporation. Advisory Panel; Sequel Med Tech. Other Relationship; Tandem Diabetes Care, Inc. Research Support; Abbott. Other Relationship; Sanofi. G.P. Forlenza: Advisory Panel; Medtronic. Research Support; Medtronic, Dexcom, Inc. Consultant; Dexcom, Inc. Research Support; Insulet Corporation. Consultant; Insulet Corporation. Research Support; Tandem Diabetes Care, Inc. Advisory Panel; Tandem Diabetes Care, Inc. Research Support; Abbott. Advisory Panel; Sequel Med Tech. M.D. Breton: Speaker's Bureau; Sinocare Inc, Tandem Diabetes Care, Inc. Consultant; Roche Diabetes Care, Boydsense. E. Cengiz: Advisory Panel; Novo Nordisk, Arecor Therapeutics, Eli Lilly and Company, Tandem Diabetes Care, Inc, Portal Insulin, MannKind Corporation.FundingBreakthrough T1D (2-SRA-2023-1275-M-B)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-919-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 920-P: The Relationship between Glycemia and Insulin Sensitivity Factor
-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 920-P
Abstract: Introduction and Objective: Insulin sensitivity factor (ISF) is often considered constant in Automated Insulin Delivery systems and other insulin therapies, but ISF varies with glycemia [1]. This study assesses the impact of glycemia (G) on ISF using real-life data.Methods: Data from 11,201 T1D adults using the DBLG1 System since March 2021 was used. G peaks were extracted from days with at least 75% of closed loop, occurring after at least 1h post meal, with COB < 2.5g and G in [50, 400] mg/dL. A G minimum (Gmin) was identified after each peak (Gmax), with a maximum to minimum interval larger than 20min. Then, ISF was calculated as: ISF = (Gmax - Gmin) / CI where CI is the consumed insulin between tmin and tmax, with CI = IOB(tmax) − IOB(tmin) + ∫tmin to tmax (basal(t) + bolus(t) − basalref(t)) dt. IOB is insulin-on-board, basal and bolus are insulin delivered, and basalref is the reference basal rate.Results: Figure 1 shows ISF variation: ISF increases from 65 to 79 mg/dL/U as G rises from 50 to 100 mg/dL, then declining to 35 mg/dL/U at G = 180 mg/dL and below 20 mg/dL/U for G > 300 mg/dL. Insulin doses for G > 340 mg/dL may double compared to a reference ISF of 35 mg/dL/U at G = 180 mg/dL, to account for reduced ISF, while for G ≤ 120 mg/dL doses could be halved to reflect increased ISF.Conclusion: This study highlights glycemia-dependent ISF variability, providing insights to refine insulin therapy and enhance closed-loop systems for better glucose control.Disclosure H.M. Romero-Ugalde: Employee; Diabeloop SA. A. Adenis: Employee; Diabeloop. T. Cartier-Michaud: None. P. Gauthier: Employee; Diabeloop. C. Desir: Employee; DIABELOOP. T. Le Roux-Mallouf: Employee; Diabeloop. E. Huneker: Employee; Diabeloop. P.Y. Benhamou: Employee; Diabeloop SA. Board Member; Eli Lilly and Company, Insulet Corporation, Novo Nordisk.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-920-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 921-P: Impact of Heart Rate and Step Count on Deep Learning Glucose
Prediction Models during Physical Activity-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 921-P
Abstract: Introduction and Objective: Accurate glucose prediction is vital for effective glucose management during physical activity (PA) [1], as PA significantly impacts glucose dynamics. This study evaluates the integration of heart rate (HR) and step count per minute (SCPM) data into deep learning (DL)-based glucose prediction models.Methods: The T1DEXI dataset [2] was used (561 T1D adults assigned to exercise sessions over 4 weeks). Patients were split into training and testing sets. Meal-related data (meal time + 3h) were excluded, and only time periods with reported PA were used for validation. Two DL models [3] were trained: one with glucose data only and the other with glucose, HR, and SCPM, each model with 10 distinct hyperparameter sets to avoid differences due to tuning. Performance on glucose predictions was assessed, on the test set using RMSE, correlation, and the zones A, B, and E of the Clarke error grid.Results: Models with HR and SCPM data outperformed glucose-only models (Table 1) in RMSE (p < 0.001), correlation (p < 0.001), and Zone E (p < 0.01). However, no significant difference was found in the Zone A + Zone B classification (p = 0.92).Conclusion: Including HR and SCPM data significantly improves glucose prediction, though the gain is modest, likely due to variability in patients' responses to PA. It is likely that adding IOB information could further enhance predictive accuracy with HR and SCPM.Disclosure H.M. Romero-Ugalde: Employee; Diabeloop SA. A. Adenis: Employee; Diabeloop. P. Gauthier: Employee; Diabeloop. C. Desir: Employee; DIABELOOP. T. Le Roux-Mallouf: Employee; Diabeloop. E. Huneker: Employee; Diabeloop. P.Y. Benhamou: Employee; Diabeloop SA. Board Member; Eli Lilly and Company, Insulet Corporation, Novo Nordisk.FundingThis publication is based on research using data from 'Jaeb Center for Health Research Foundation that has been made available through Vivli, Inc. Vivli has not contributed to or approved, and is not in any way responsible for, the contents of this publication.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-921-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 922-P: Fear of Hypoglycemia after Ramadan Fasting among People with Type 1
Diabetes—A Multicenter Study from Saudi Arabia-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 922-P
Abstract: Introduction and Objective: Intermittent fasting, including Ramadan fasting, increases the risk of hypoglycemia in people with type 1 diabetes (PWT1D). We examined the prevalence and predictors of fear of hypoglycemia (FOH) after Ramadan in PWT1D who attempted to fast.Methods: Fasting experience, glycemic control, and FOH were evaluated in 159 PWT1D who attempted to fast Ramadan 2024, used CGM for ≥2 weeks, and completed the Hypoglycemia Fear Survey (HFS-II) shortly after Ramadan. Participants were categorized by their scores on the HFS-Behavior (HFS-B) and HFS-Worry (HFS-W) subscales of the survey as follows: (High HFS-B: ≥1.85 vs Low HFS-B: <1.85) and (High HFS-W ≥0.92 vs Low HFS-W: <0.92).Results: Most participants (57%) reported high HFS-W and only 29% reported high HFS-B post-Ramadan. Ramadan CGM metrics were worse in those with high vs low HFS-B (TIR: 56.91% vs 63.98%; TAR>250: 16.57% vs 11.60%; TBR 54-70: 2.76% vs 1.86%; TBR<54: 0.67% vs 0.25%; and GRI: 53 vs 42, respectively, all p<0.05). Proportion of PWT1D achieving TBR target <4% was lower in the high vs low HFS-B groups (25.4% vs 74.6%, respectively, p=0.02). Among those with ≥1 severe hypoglycemia during Ramadan, 85.71% and 64.29% had high HFS-W and high HFS-B, respectively. Automated insulin delivery users had the lowest prevalence of high HFS-B (14.71%) vs other treatment modalities (allp<0.01). Severe hypoglycemia during Ramadan increased the likelihood of high HFS-B (OR: 4.54, 95% CI: 1.24, 16.68) and high HFS-W (OR: 5.42, 95% CI: 1.04, 28.40) after adjusting for age, gender, employment, educational level, insurance status, diabetes duration, TBR, and modality of treatment.Conclusion: Severe hypoglycemia during Ramadan is associated with increased FOH post-Ramadan in PWT1D. Our findings highlight the importance of empowering PWT1D who plan to fast Ramadan with the technology that they need to minimize risk of hypoglycemia during fasting and FOH afterwardDisclosureS. Alharthi: None. M. Alsuhaibani: None. A.M. Almurashi: None. T.H. Almigbal: None. R. Alamoudi: None. H.A. Zarif: Other Relationship; Abbott, Medtronic. A.M. Alhashem: None. M. Almehthel: Advisory Panel; Novo Nordisk. Speaker's Bureau; Novo Nordisk. Research Support; Novo Nordisk. Advisory Panel; Sanofi. Speaker's Bureau; Sanofi. Research Support; Sanofi. Speaker's Bureau; Lilly Diabetes. Advisory Panel; Abbott. Speaker's Bureau; Abbott. Advisory Panel; Dexcom, Inc. Speaker's Bureau; Bayer Pharmaceuticals, Inc. N. Alzaman: None. R. Kalyani: None. M. Al-Sofiani: Advisory Panel; Medtronic. Speaker's Bureau; Insulet Corporation, Abbott, Lilly Diabetes. Advisory Panel; Dexcom, Inc., Roche Diabetes Care. Speaker's Bureau; Sanofi. Research Support; Medtronic. Speaker's Bureau; Vitalaire.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-922-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 923-P: Fasting Experience, Glycemic Control, and Fear of Hypoglycemia in
People with Type 1 Diabetes Using Open-Source vs. Commercial Automated
Insulin Delivery during Ramadan—A Multicenter Study from Saudi Arabia-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 923-P
Abstract: Introduction and Objective: Open-source automated insulin delivery (OS-AID) has been shown to improve glycemic control in people with type 1 diabetes (PWT1D). We compare the effectiveness, safety, and fear of hypoglycemia (FOH) between OS-AID and commercial (C-AID) systems during Ramadan fasting.Methods: We recruited 114 PWT1D fasting during Ramadan 2024 using an AID system [OS-AID (n=7) or C-AID (n=107)] who agreed to share their CGM data from the month of Ramadan and the month before Ramadan. Comparative analyses focused on glycemic metrics and safety.Results: All OS-AID users had ≥bachelor degree and diabetes duration >10 years, compared to C-AID users (63.11% and 50.49%, respectively). Pre-Ramadan, there were no significant differences in the CGM metrics between the OS-AID and C-AID groups except for TBR<70 (3.9% vs 1.8%, respectively, p=0.01). During Ramadan, OS-AID users had significantly lower average glucose (139 vs 154 mg/dL, p=0.04), lower glucose management indicator (GMI) (6.5% vs 7%, p<0.1), lower time above range (TAR >180 mg/dL) (16.6% vs 25.84%, p=0.04), higher time below range (TBR <70 mg/dL) (3.29% vs 1.21%, p<0.01). Severe hypoglycemia events were low in both groups but higher in the OS-AID group (1.14 vs 0.07, p<0.01). There were no significant differences in the number of days during which fasting was broken because of diabetes nor in the levels of FOH post-Ramadan between groups.Conclusion: OS-AID system was as effective as C-AID systems in enabling PWT1D to fast most days of Ramadan and maintain glucose levels within target. In this small cohort, TBR and hypoglycemic events were slightly higher in the OS-AID group, both pre- and during Ramadan. These differences need to be confirmed with larger studies. They are likely driven by multiple factors, including limited healthcare provider support, understanding, and optimization of OS-AID systems during Ramadan.DisclosureS. Alharthi: None. M. Alsuhaibani: None. M. Almehthel: Advisory Panel; Novo Nordisk. Speaker's Bureau; Novo Nordisk. Research Support; Novo Nordisk. Advisory Panel; Sanofi. Speaker's Bureau; Sanofi. Research Support; Sanofi. Speaker's Bureau; Lilly Diabetes. Advisory Panel; Abbott. Speaker's Bureau; Abbott. Advisory Panel; Dexcom, Inc. Speaker's Bureau; Bayer Pharmaceuticals, Inc. T.H. Almigbal: None. A.M. Alhashem: None. R. Alamoudi: None. H.A. Zarif: Other Relationship; Abbott, Medtronic. A.M. Almurashi: None. N. Alzaman: None. S. Hussain: Advisory Panel; Tandem Diabetes Care, Inc, Dexcom, Inc., Medtronic, Sanofi, Vertex Pharmaceuticals Incorporated. Speaker's Bureau; Abbott, Insulet Corporation, Dexcom, Inc., Roche Diabetes Care. M. Al-Sofiani: Advisory Panel; Medtronic. Speaker's Bureau; Insulet Corporation, Abbott, Lilly Diabetes. Advisory Panel; Dexcom, Inc., Roche Diabetes Care. Speaker's Bureau; Sanofi. Research Support; Medtronic. Speaker's Bureau; Vitalaire.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-923-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 924-P: Predictors of Diabetes-Related Distress following Closed-Loop
Initiation in Adults with Type 1 Diabetes in the UK—Insights from the
Association of British Clinical Diabetologists-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 924-P
Abstract: Introduction and Objective: The National Health Service (NHS) England hybrid closed-loop (HCL) pilot provided access to HCL for adults with type 1 diabetes (T1D), managed with an insulin pump and intermittently scanned continuous glucose monitoring, with a HbA1c ≥8.5%. We assessed the factors associated with improved diabetes-related distress (DRD) at follow up.Methods: Anonymized baseline and follow-up data were collected via a secure online tool. We performed logistic regression on variables including age, gender, ethnicity, multiple deprivation index, weight, body mass index, Gold score, HbA1c, sensor glucometrics, number of sensor scans/day, duration of diabetes and pump therapy, two-item diabetes distress score (DDS2), total daily insulin dose (TDD) and %time in HCL. Analysis was performed in SpSS v29.0.Results: Individuals (n = 298; 29 UK diabetes centres) with high DRD (DDS2 ≥3) at baseline with follow-up DDS2 data were included [72% female; 86% White; median age 37 years (IQR 28-49) and diabetes duration 20 years (IQR 14-28); baseline HbA1c 9.5 ± 0.9%]. After 9 months (IQR 6-20), DRD improved (DDS2 <3) in 205/298 (68.8%) (group A) and remained high in 93/298 (31.2%) (group B). Compared with group B, group A had lower baseline DDS2 (3.8 ± 0.8 vs 4.2 ± 0.9, p = 0.001) and TDD (48.2 ± 21.3 vs 55.3 ± 33.0, p = 0.03); no other significant between-group differences were observed. Improved DRD was inversely associated with baseline DDS2 (B=-0.726, p = 0.03) in the multivariable model, and female gender (B= -0.68, p = 0.02), baseline DDS2 (B=-0.44, p = 0.002), and TDD (B=-0.01, p = 0.04) in the univariate models. No other associations were reported.Conclusion: HCL was associated with improvements in DRD in T1D, irrespective of ethnicity, deprivation status, baseline glucose outcomes and hypoglycemia awareness. Additional therapeutic interventions are needed to further reduce DRD in HCL users.Disclosure A.L. Liarakos: Other Relationship; Dexcom, Inc. T.S. Crabtree: Other Relationship; Abbott, Dexcom, Inc., Eli Lilly and Company, Insulet Corporation. T.P. Griffin: Speaker's Bureau; Novo Nordisk A/S, AbbVie Inc, Dexcom, Inc. Advisory Panel; Dexcom, Inc. Speaker's Bureau; Bayer Pharmaceuticals, Inc, Eli Lilly and Company, Abbott. L. Langeland: None. I.C. Cranston: Research Support; Abbott. Speaker's Bureau; Eli Lilly and Company, Novo Nordisk, AstraZeneca. Advisory Panel; Glooko, Inc, Roche Diabetes Care. Speaker's Bureau; Boehringer-Ingelheim, Bayer Pharmaceuticals, Inc. Advisory Panel; Abbott. Speaker's Bureau; Insulet Corporation. S.A.D. Mathara Diddhenipothage: None. J. Elliott: Speaker's Bureau; Abbott. Research Support; Dexcom, Inc. Advisory Panel; Dexcom, Inc. Speaker's Bureau; Dexcom, Inc., Boehringer-Ingelheim, Eli Lilly and Company. Advisory Panel; Glooko, Inc. Speaker's Bureau; Insulet Corporation. Advisory Panel; Roche Diabetes Care. Speaker's Bureau; Sanofi. Advisory Panel; Ypsomed AG. N.J. Furlong: None. J. Cardwell: None. C. Philbey: None. L. Sawyer: None. V.J. Parfitt: Other Relationship; SBK (UK) Ltd. Z.Z. Htike: None. C. Williams: Speaker's Bureau; Abbott, Novo Nordisk. S. Kamaruddin: None. P. Kar: None. R.E. Ryder: Speaker's Bureau; Abbott, AstraZeneca, GI Dynamics. Consultant; GI Dynamics. Other Relationship; Novo Nordisk. Speaker's Bureau; Besins Healthcare. P. Choudhary: Speaker's Bureau; Abbott. Advisory Panel; Dexcom, Inc. Consultant; Insulet Corporation. Advisory Panel; Ypsomed AG, embecta, Sanofi. Speaker's Bureau; Lilly Diabetes, Medtronic. Advisory Panel; Roche Diabetes Care. Consultant; Cambridge Mechatronics. E.G. Wilmot: Research Support; Abbott. Speaker's Bureau; Abbott. Advisory Panel; Abbott. Speaker's Bureau; AstraZeneca. Advisory Panel; Dexcom, Inc. Speaker's Bureau; Dexcom, Inc., Eli Lilly and Company. Advisory Panel; Eli Lilly and Company. Research Support; embecta. Advisory Panel; embecta. Research Support; Insulet Corporation. Speaker's Bureau; Insulet Corporation. Advisory Panel; Insulet Corporation, Medtronic. Speaker's Bureau; Novo Nordisk. Advisory Panel; Novo Nordisk. Research Support; Novo Nordisk. Advisory Panel; Roche Diabetes Care, Sanofi. Speaker's Bureau; Sanofi. Advisory Panel; Sinocare Inc. Speaker's Bureau; Ypsomed AG.FundingAssociation of British Clinical Diabetologists
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-924-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 925-P: Real-World Outcomes of the Integration of Omnipod 5 Insulin Pump
and Freestyle Libre 2 plus Continuous Glucose Monitoring in Adults with
Type 1 Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 925-P
Abstract: Introduction and Objective: Hybrid closed-loop (HCL) therapy has revolutionized the care for people living with type 1 diabetes (pwT1D). The integration of different technology devices evolves rapidly providing individuals with more options and flexibility. We aimed to assess real-world outcomes of the new HCL system integrating the tubeless Omnipod 5 insulin pump with FreeStyle Libre 2 Plus continuous glucose monitoring (CGM) in pwT1D managed with insulin pump or multiple daily insulin injections (MDI) and CGM in a UK diabetes centre.Methods: Clinical data were collected via a secure online tool. CGM metrics, HbA1c, diabetes distress scale (DDS) score and Gold score (hypoglycemia awareness) changes between baseline and follow-up were assessed. Analysis was performed in SpSS v29.0.Results: In total, 41 individuals [59% female; 83% White; median age 40 years (IQR 29-56) and diabetes duration 19 years (IQR 10-31)] were included. After 8 months (IQR 5-9), time in range (TIR) (70-180 mg/dL) increased by 21.1% (45.1 ± 18.3% at baseline vs 66.2 ± 9.5% at follow-up; P <0.001). Time at 181-250 mg/dL and >250 mg/dL reduced by 5.8% and 16.3%, respectively (P <0.001 for both). Time below range (<69 mg/dL) remained unchanged. Stratified by previous insulin therapy, the increase in TIR was similar between insulin pump (n = 31) and MDI (n = 10) users (19.0 % vs 27.6%, p = 0.1). Baseline HbA1c was 8.1 ± 0.9% (65 ± 10 mmol/mol) and reduced by 0.7% (95% CI -1.0, -0.4; P <0.001) (-7 mmol/mol [95% CI -10, -4]; P <0.001) at follow-up. DDS score decreased by 1.7 (95% CI -2.3, -1.0; P <0.001) and Gold score remained unchanged (2.1 vs 1.7, p = 0.4).Conclusion: The HCL system of Omnipod 5 with FreeStyle Libre 2 Plus CGM is associated with improvements in glycemia and diabetes distress. Insulin pump and MDI users can equally benefit from the system.Disclosure A.L. Liarakos: Other Relationship; Dexcom, Inc. K. Su Khin: None. T.S. Crabtree: Other Relationship; Abbott, Dexcom, Inc., Eli Lilly and Company, Insulet Corporation. L. Langeland: None. E. Robinson: None. E.G. Wilmot: Research Support; Abbott. Speaker's Bureau; Abbott. Advisory Panel; Abbott. Speaker's Bureau; AstraZeneca. Advisory Panel; Dexcom, Inc. Speaker's Bureau; Dexcom, Inc., Eli Lilly and Company. Advisory Panel; Eli Lilly and Company. Research Support; embecta. Advisory Panel; embecta. Research Support; Insulet Corporation. Speaker's Bureau; Insulet Corporation. Advisory Panel; Insulet Corporation, Medtronic. Speaker's Bureau; Novo Nordisk. Advisory Panel; Novo Nordisk. Research Support; Novo Nordisk. Advisory Panel; Roche Diabetes Care, Sanofi. Speaker's Bureau; Sanofi. Advisory Panel; Sinocare Inc. Speaker's Bureau; Ypsomed AG.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-925-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 926-P: Automated Insulin Delivery vs. Open-Loop Insulin Delivery during
Ramadan in Patients with Type 1 Diabetes in Saudi Arabia—The Hybrid-Ram
Randomized Controlled Trial-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 926-P
Abstract: Introduction and Objective: Automated insulin delivery (AID) systems, adjusting insulin based on real-time glucose readings, may offer advantages over open-loop insulin delivery (OLID), especially during Ramadan fasting, which poses challenges for individuals with type 1 diabetes (T1D).Methods: This dual-center, open-label, randomized controlled trial compared AID systems (Medtronic MiniMed 780G [M780] and Tandem T-slim Control IQ [TCIQ]) with OLID systems (Medtronic MiniMed 640G or MiniMed VEO insulin pump with Guardian 3/4 sensors or Freestyle Libre sensors) in patients with T1D observing Ramadan. The primary outcome was the difference in Time in Range (TIR) during Ramadan. Secondary outcomes included Time Below Range (TBR), Time Above Range (TAR), and a composite outcome (TIR ≥ 70%, TBR < 5%, and ≤ 2 fast-broken days).Results: Baseline characteristics were similar between groups. The control group (N=55), M780 group (N=20) and TCIQ group (N=24) had average ages of 27.7 ± 6.0, 26.0 ± 9.6 years and 27.1 ± 6.1 years, respectively. Results are presented in the table below.Conclusion: M780 and TCIQ AID systems significantly enhanced glycemic control, patients safety, and adherence to religious practices during Ramadan, providing an effective solution for T1D management during fasting.Disclosure M. Almehthel: Advisory Panel; Novo Nordisk. Speaker's Bureau; Novo Nordisk. Research Support; Novo Nordisk. Advisory Panel; Sanofi. Speaker's Bureau; Sanofi. Research Support; Sanofi. Speaker's Bureau; Lilly Diabetes. Advisory Panel; Abbott. Speaker's Bureau; Abbott. Advisory Panel; Dexcom, Inc. Speaker's Bureau; Bayer Pharmaceuticals, Inc. A. Alqahtani: None. N. Aboalsamh: None. I. Brema: None. M.M. Ahmad: None. N.A. Sharahili: None. A.E. Aljohani: None. S.H. Alzahrani: None. I.A. Alghofaili: None. M. Hassanein: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-926-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 927-P: Unlocking the Predictors of Improved Time in Range for Users of
Automated Insulin Delivery Systems during Ramadan Fasting—Findings from
the Hybrid-Ram Randomized Controlled Trial-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 927-P
Abstract: Introduction and Objective: Automated insulin delivery (AID) systems adjust insulin delivery based on real-time glucose readings, offering potential advantages over open-loop insulin delivery (OLID). Ramadan fasting presents unique challenge for individuals with type 1 diabetes (T1D) due to significant fluctuations in glucose levels. This study aimed to identify the predictor factors associated with achieving better Time In Range (TIR) during Ramadan fasting among individuals living with T1D using AID systems.Methods: We conducted a dual-center, open-label, randomized controlled trial with T1D patients using OLID (Medtronic MiniMed 640G or MiniMed VEO insulin pumps with Guardian 3/4 sensors or Freestyle Libre sensors) who observed Ramadan fasting. Participants were randomly assigned to either an AID system (Medtronic MiniMed 780G SmartGuard or Tandem T-slim Control IQ) or continued with OLID.Results: Baseline characteristics were similar between groups. The control group (N=55) had an average age of 27.7 ± 6.0 years, while the intervention group (N=44) had an average age of 26.6 ± 7.8 years. Females comprised 65% of the control group and 63% of the intervention group. The intervention group achieved a mean TIR of 72.6%, a Time Below Range (TBR) of 1.4%, and a Time Above Range (TAR) of 26%, compared to 55.8%, 3.2%, and 41%, respectively, in the control group (p<0.001 for all comparisons). We performed a logistic regression analysis to explore the predictor factors for changes in TIR. The only variable that predicted changes in TIR was the change in fructosamine levels (beta value -0.3 ± 0.1, p value 0.031). Other factors such as age, sex. baseline HbA1c, baseline weight, and duration of diabetes, did not predict changes in TIR in this cohort.Conclusion: For individuals with T1D using AID systems during Ramadan fasting, changes in fructosamine levels were the only factor that predicted variations in TIR.Disclosure M. Almehthel: Advisory Panel; Novo Nordisk. Speaker's Bureau; Novo Nordisk. Research Support; Novo Nordisk. Advisory Panel; Sanofi. Speaker's Bureau; Sanofi. Research Support; Sanofi. Speaker's Bureau; Lilly Diabetes. Advisory Panel; Abbott. Speaker's Bureau; Abbott. Advisory Panel; Dexcom, Inc. Speaker's Bureau; Bayer Pharmaceuticals, Inc. A. Alqahtani: None. N. Aboalsamh: None. I. Brema: None. M.M. Ahmad: None. A.E. Aljohani: None. N.A. Sharahili: None. S.H. Alzahrani: None. I.A. Alghofaili: None. M. Hassanein: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-927-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 928-P: AI-Based Fully Closed Loop (FCL) Achieves Improved Glycemia vs.
Hybrid Closed Loop (HCL) in People with Type 1 Diabetes (T1D)-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 928-P
Abstract: Introduction and Objective: HCL is the preferred insulin delivery method for people with T1D, however mealtime carbohydrate counting limits benefit. Use of AI to implement automated insulin delivery (AID) algorithms, able to avoid mealtime interactions, could alleviate burden and broaden use. We tested the latest UVA AID neural network-based system (AIDANET) in FCL in a people with T1D.Methods: Adults (>25 y, n=12), young adults (18-25 y, n=10), and adolescents (14-17 y, n=12) were enrolled at three sites to compare AIDANET in FCL to usual care in HCL (NCT06041917). Participants spent 5 days using FCL in a supervised hotel environment followed by 7 days of at-home use. Usual care data was collected randomly for two weeks before or after FCL use. The prespecified primary outcome was difference in mean CGM.Results: Overall, 34 participants (25.4±12.6 y, 62% F, HbA1c 8.0±1.1%) completed the study. Mean CGM significantly improved from 177.9 mg/dL with HCL to 163.8 mg/dL with FCL (-14.1 mg/dL; p=0.013; Table). TIR, TITR, TAR>180, and TAR>250 also significantly improved. TBR<70 and TBR<54 were non-inferior in FCL vs HCL. CV increased in FCL vs HCL but SD did not. Daily meal boluses decreased from 4.0±2.6 to 0.0±0.0 (p<0.001).Conclusion: Fully closed loop therapy with the AIDANET system can significantly improve average glycemia while removing the need for mealtime bolusing for people with T1D.Disclosure G.P. Forlenza: Advisory Panel; Medtronic. Research Support; Medtronic, Dexcom, Inc. Consultant; Dexcom, Inc. Research Support; Insulet Corporation. Consultant; Insulet Corporation. Research Support; Tandem Diabetes Care, Inc. Advisory Panel; Tandem Diabetes Care, Inc. Research Support; Abbott. Advisory Panel; Sequel Med Tech. M. Moscoso-Vasquez: Other Relationship; Dexcom, Inc. Research Support; Tandem Diabetes Care, Inc, National Institute of Diabetes and Digestive and Kidney Diseases. S.A. Brown: Research Support; Dexcom, Inc., Insulet Corporation, Tandem Diabetes Care, Inc, Tolerion, Roche Diabetes Care. Other Relationship; MannKind Corporation. G. Capodanno: None. E. Cengiz: Advisory Panel; Novo Nordisk, Arecor Therapeutics, Eli Lilly and Company, Tandem Diabetes Care, Inc, Portal Insulin, MannKind Corporation. E.C. Cobry: Advisory Panel; Dexcom, Inc. M.D. DeBoer: Research Support; Dexcom, Inc., Tandem Diabetes Care, Inc, Medtronic. R. Wadwa: Consultant; Dexcom, Inc., Tandem Diabetes Care, Inc. Advisory Panel; Provention Bio, Inc, Provention Bio, Inc, Microbion, Microbion, Sequel Med Tech. Research Support; Dexcom, Inc., Eli Lilly and Company, Tandem Diabetes Care, Inc. J.C. Wong: Research Support; Abbott, Dexcom, Inc., Tandem Diabetes Care, Inc. L. Ekhlaspour: Other Relationship; Medtronic. Advisory Panel; Abbott, Medtronic. Consultant; Jaeb Center for Health Research. Research Support; MannKind Corporation. Speaker's Bureau; Insulet Corporation. Advisory Panel; Sequel Med Tech. Other Relationship; Tandem Diabetes Care, Inc. Research Support; Abbott. Other Relationship; Sanofi. M.D. Breton: Speaker's Bureau; Sinocare Inc, Tandem Diabetes Care, Inc. Consultant; Roche Diabetes Care, Boydsense.FundingBreakthrough T1D (2-SRA-2023-1275-M-B)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-928-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 929-P: Assessment of Impact of Online CME and Future Education Needs
Related to Automated Insulin Delivery Use in People with T2D-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 929-P
Abstract: Introduction and Objective: We measured the impact of online continuing medical education (CME) on knowledge and confidence of primary care physicians (PCPs) and diabetologists/endocrinologists (D/Es) on new data for using automated insulin delivery (AID) in people with T2D.Methods: The intervention comprised a 30-min online video-based discussion among 3 expert faculty with downloadable slides. Education effect assessed with a linked and matched pre-/post-assessment design. A paired samples t-test was conducted for significance testing on overall responses and for confidence rating, and a McNemar test was conducted at the question level (5% significance level, P <.05). Data collected October 28, 2024 through December 10, 2024.Results: 206 PCPs and 39 D/Es answered all questions. Overall, 27% of PCPs and 28% of D/Es improved their knowledge/competence (P<.01). On a question-level: 11%-13% of PCPs and 10%-24% of D/Es improved at recognizing clinical trial data (P<.01 for PCPs and P<.05 D/Es). 43% of PCPs and 62% of D/Es had improved confidence in selecting patients with T2D for AID use (P<.01 for both PCPs and D/Es), with average confidence shifts of +78% and +63%, respectively. Continued educational gaps include: 72% of PCPs and 54% of D/Es need additional education on clinical trial data supporting use of AID in T2D and 77% of PCPs and 72% of D/Es need additional education on patient population included in clinical trials.Conclusion: The 10%-24% increase in knowledge and strong confidence improvements demonstrate the success of this online CME on improving clinical knowledge in PCPs and D/Es related to new data for using AID in people with T2D. Baseline knowledge was low and continued gaps large, demonstrating the need for multiple education modalities to improve clinical understanding before PCPs and D/Es can be expected to apply data to practice. Confidence gains show that additional educational opportunities like this activity can help achieve this goal.DisclosureA. Larkin: None. J. Schrand: None. A. Le: None.FundingIndependent educational grant from Insulet Corporation
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-929-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 930-P: The Impact of Insulin Delivery Modality on Fasting Experience,
Glycemic Control, and Fear of Hypoglycemia in the Month of Ramadan in
People with T1D—A Prospective, Multicenter Study from Saudi Arabia-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 930-P
Abstract: Introduction and Objective: Most people with type 1 diabetes (PWT1D) are advised to not fast during Ramadan because of dysglycemia risks. We compared efficacy, safety profiles, and fear of hypoglycemia (FH) during Ramadan fasting in users of 4 insulin delivery modalities.Methods: Four treatment groups were compared: automated insulin delivery (AID) (n=114), sensor augmented pump (SAP) with predictive-low-glucose suspend (PLGS) (n=4), sensor-unintegrated pump (SUP) (n=24), and multiple daily injections (MDI)+continuous glucose monitoring (CGM) (n=136).Results: Pre/during-Ramadan percent time in range (TIR) for the AID, SAP-PLGS, SUP, and MDI-CGM groups was 73.2/73.4, 62/65.5, 57.8/54.6, and 52.1/47.4. The Pre/during Ramadan Glycemia Risk Index (GRI) for the AID, SAP-PLGS, SUP, and MDI-CGM groups was 30/29, 43/35, 52/55, and 60/64. The proportion of PWT1D achieving a “double target of fasting” (fasting was broken ≤2 days because of diabetes and TIR was >70%) for the AID, SAP-PLGS, SUP, and MDI-CGM groups was 46.5%, 25%, 12.5%, and 7.35%. AID system users were 22 times as likely to achieve the double target compared to MDI+CGM users after adjusting for age, gender, employment/insurance status, educational level, and diabetes duration. While the overall FH score did not significantly differ across the four groups (overall p>0.05), AID users had the lowest score and MDI had the highest score on the behavior subscale of the FH survey.Conclusion: Use of AID during Ramadan fasting was associated with fasting the most days of Ramadan, best glycemic control, and the least frequent hypoglycemia avoidance behaviors. The International Diabetes Federation/Diabetes and Ramadan International Alliance risk calculator should assign a lower risk score for AID technology when used by PWT1DDisclosure M. Al-Sofiani: Advisory Panel; Medtronic. Speaker's Bureau; Insulet Corporation, Abbott, Lilly Diabetes. Advisory Panel; Dexcom, Inc., Roche Diabetes Care. Speaker's Bureau; Sanofi. Research Support; Medtronic. Speaker's Bureau; Vitalaire. S. Alharthi: None. M. Alsuhaibani: None. A.M. Alhashem: None. A.M. Almurashi: None. T.H. Almigbal: None. R. Alamoudi: None. H.A. Zarif: Other Relationship; Abbott, Medtronic. N. Alzaman: None. M. Almehthel: Advisory Panel; Novo Nordisk. Speaker's Bureau; Novo Nordisk. Research Support; Novo Nordisk. Advisory Panel; Sanofi. Speaker's Bureau; Sanofi. Research Support; Sanofi. Speaker's Bureau; Lilly Diabetes. Advisory Panel; Abbott. Speaker's Bureau; Abbott. Advisory Panel; Dexcom, Inc. Speaker's Bureau; Bayer Pharmaceuticals, Inc. D.C. Klonoff: Consultant; Synchneuro, Thirdwayv, Tingo, Afon, embecta, Glucotrack, Lifecare, Novo Nordisk, Samsung.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-930-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 931-P: Fasting Experience and Glycemic Control among People with Type 1
Diabetes Using Medtronic 780G vs. Tandem Control-IQ during Ramadan—A
Multicenter Study from Saudi Arabia-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 931-P
Abstract: Introduction and Objective: Fasting during Ramadan puts people with type 1 diabetes (PWT1D) at risk of dysglycemia and diabetic ketoacidosis (DKA). Recent studies have shown the clinical effectiveness of automated insulin delivery (AID) systems in PWT1D who fast during Ramadan. Here, we compare the effectiveness and safety profiles of the Medtronic 780G versus Tandem Control-IQ during Ramadan fasting.Methods: We compared the fasting experience, glycemic control, and fear of hypoglycemia (FOH) between users of Medtronic 780G (n= 82) and Tandem Control-IQ (n= 24) systems who fasted during Ramadan 2024.Results: There were no significant differences in the sociodemographics nor pre-Ramadan glycemic metrics between the Medtronic 780G and the Tandem Control-IQ users. During Ramadan, Medtronic 780G and Tandem Control-IQ users had comparable TIR (72.9% vs 74.2%, p=0.2), TAR (25.8% vs 24.7%, p=0.67), TBR (1.2% vs 1.2%, p=0.93), and GRI (29 vs 29, p=0.97). The mean number of days during which fasting was broken because of hypoglycemia was 2.17 days in the Medtronic group and 1.50 days in the Tandem group (p=0.4). Likewise, the mean number of days during which fasting was broken because of hyperglyemia was 0.29 days in the Medtronic group and 0.18 days in the Tandem group (p=0.56). The composite outcome of “breaking the fast due to diabetes ≤2 days & maintaining TIR >70% during Ramadan” was achieved by 43.9% of Medtronic users and 50.0% of Tandem users (p= 0.60). There were no significant differences in the levels of FOH between the two groups.Conclusion: Medtronic 780G and Tandem Control-IQ users had comparable glucose levels, fasting experience, and FOH during Ramadan. The use of AID, irrespective of its type, appears to mitigate the potential risks associated with fasting in PWT1DDisclosure M. Al-Sofiani: Advisory Panel; Medtronic. Speaker's Bureau; Insulet Corporation, Abbott, Lilly Diabetes. Advisory Panel; Dexcom, Inc., Roche Diabetes Care. Speaker's Bureau; Sanofi. Research Support; Medtronic. Speaker's Bureau; Vitalaire. S. Alharthi: None. M. Alsuhaibani: None. M. Almehthel: Advisory Panel; Novo Nordisk. Speaker's Bureau; Novo Nordisk. Research Support; Novo Nordisk. Advisory Panel; Sanofi. Speaker's Bureau; Sanofi. Research Support; Sanofi. Speaker's Bureau; Lilly Diabetes. Advisory Panel; Abbott. Speaker's Bureau; Abbott. Advisory Panel; Dexcom, Inc. Speaker's Bureau; Bayer Pharmaceuticals, Inc. T.H. Almigbal: None. A.M. Alhashem: None. H.A. Zarif: Other Relationship; Abbott, Medtronic. R. Alamoudi: None. N. Alzaman: None. A.M. Almurashi: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-931-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 932-P: MiniMed 780G System Use in a Real-World United States (U.S.)
Population Aged 65 Years and Older with Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 932-P
Abstract: Introduction and Objective: Management of dysglycemia in older adults with insulin-requiring diabetes can be challenging and automated insulin delivery is reported to improve glycemic outcomes in this population.1,2 The present study evaluated MiniMedTM 780G system (MM780G) performance in a real-world US population aged ≥65 years.Methods: CareLink™ data (up to December 18, 2024) of consenting US MM780G users (N=8,542, aged ≥65 years) were aggregated and assessed. Sensor glucose (SG) metrics including mean time at SG ranges (time in range [TIR], in tight range [TITR], below range [TBR] and above range [TAR]), the glucose management indicator (GMI) and insulin were evaluated. Users and non-users of recommended optimal settings (ROS: 100mg/dL glucose target with 2 hours active insulin time) were compared.Results: Overall TIR was 78.4%, TITR was 51.4%, TBR70 was 0.9%, TAR180 was 20.7%, TAR250 was 3.6% and GMI was 6.8% (Table). Compared to non-ROS users, the TIR and TITR of ROS users were significantly higher (P<0.001), while TAR and GMI were significantly lower (P<0.001) and TBR was unchanged (<1%). Both groups had the same number of daily user-initiated boluses.Conclusion: A US population of older adults using the MiniMedTM 780G system met international consensus glycemic targets and use of ROS enabled many to achieve an even higher level of glycemic control, without any additional manual boluses.Disclosure C.A. Chien: Employee; Medtronic. J. Shin: Employee; Medtronic. M. Liu: Employee; Medtronic. Z. Dai: Employee; Metronics. A. Arrieta: Employee; Medtronic. T.L. Cordero: Employee; Medtronic. A.R. Swensen: Employee; Medtronic, Alcon Laboratories, Inc., Karuna Therapeutics. R.A. Vigersky: Employee; Medtronic.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-932-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 933-P: MiniMed 780G System Users Achieve Consensus Glycemic Goals
Regardless of Size of Carbohydrate Entry-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 933-P
Abstract: Introduction and Objective: Glycemic control in diabetes can differ from person to person and automated insulin delivery (AID) with frequent autocorrections provides more personalized diabetes management. The present study assessed glycemic outcomes and insulin use of MiniMed™ 780G system (MM780G) users with different daily carbohydrate intake.Methods: CareLink™ personal data (as of October 26, 2024) of 19,286 consenting MM780G users (18-80yrs) in the United States (US) who had ≥10 days of sensor use and used recommended optimal settings (ROS, 100 mg/dL glucose target [GT] and 2 hours active insulin time [AIT]) ≥95% of the time were analyzed. Glycemic metrics including time in 70-140 mg/dL (TITR), in 70-180 mg/dL (TIR), below 70 mg/dL and above 180 mg/dL range and insulin use were stratified by quartiles of daily announced CHO.Results: Across increased daily CHO, the total daily dose of insulin (TDD), total bolus and number of CHO entries were greater, while autocorrection insulin (as %TDD) was less (Figure). The highest quartile had the highest mean TITR (57.2%), TIR (81.6%) and insulin-to-carb ratio (8.8±4.6), while the converse was observed for the lowest quartile.Conclusion: Regardless of CHO intake, a majority of MM780G users in the US with ROS achieved consensus-recommended glycemic goals. The MM780G’s unique algorithm permits adaptation to different CHO intake of people with diabetes.Disclosure R.A. Vigersky: Employee; Medtronic. Z. Dai: Employee; Metronics. F. Niu: None. J. Shin: Employee; Medtronic. T.L. Cordero: Employee; Medtronic. J.J.F. McVean: Employee; Medtronic.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-933-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 934-P: Diabetes Technology across the Lifespan (Ages 2–89
Years)—Insights from the Technology Report on Surprising Usage Trends in
Older Age Groups in Austria, Germany, and Switzerland-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 934-P
Abstract: Introduction and Objective: There is a gap in understanding diabetes technology use among older people with type 1 and type 2 diabetes (pwt1d, pwt2d). A survey in Germany, Austria and Switzerland investigated the association between age and diabetes technology use.Methods: Between 2023/11 and 2024/01, pwd and parents of children with diabetes reported their use of CGM and AID systems. Logistic regression identified the impact of age in use of CGM and AID systems.Results: A total of 2292 responses from pwt1d and 613 from pwt2d were analyzed. In pwt1d, CGM use approached 100% with no significant decline with age (OR 0.99, CI 0.98 -1.01, p>0.05); in pwt2d, CGM use increased with age (OR 1.02, CI 1.01 -1.04, p<0.05). AID use in pwt1d was significantly higher in younger age groups OR 0.99, CI 0.98 -0.99, p<0.05), but remained stable up to 80 years in pwt1d older than 30 years, with 31% of those older than 80 years still using AIDs.Conclusion: CGM use is approaching 100% in pwt1d, while it increases with age in pwt2d, possibly due to treatment intensification or safety concerns. AID systems show substantial uptake up to 80 years. Despite potential selection bias, these findings highlight the widespread adoption of diabetes technologies among older PWD and underscore the importance of tailoring technologies to support independent living in older age.Disclosure N. Hermanns: Advisory Panel; Dexcom, Inc., Abbott Diagnostics. Speaker's Bureau; Abbott Diagnostics. Advisory Panel; Roche Diabetes Care. D. Ehrmann: Advisory Panel; Dexcom, Inc. Speaker's Bureau; Dexcom, Inc. Consultant; Roche Diabetes Care. Speaker's Bureau; Roche Diabetes Care, Sanofi, Eli Lilly and Company, Boehringer-Ingelheim. T. Roos: None. L. Heinemann: Consultant; Dexcom, Inc., Roche Diabetes Care. Board Member; Lifecare. Stock/Shareholder; Science Consulting in Diabetes GmbH, Profil Institut für Stoffwechselforschung GmbH, diateam GmbH. Consultant; Indigo. J.K. Mader: Advisory Panel; Abbott. Speaker's Bureau; Abbott. Advisory Panel; Eli Lilly and Company. Speaker's Bureau; Eli Lilly and Company. Stock/Shareholder; elyte Diagnostics. Advisory Panel; embecta. Speaker's Bureau; embecta, Menarini. Advisory Panel; Medtronic. Speaker's Bureau; Dexcom, Inc. Advisory Panel; Dexcom, Inc., Novo Nordisk A/S. Speaker's Bureau; Novo Nordisk A/S. Advisory Panel; Roche Diabetes Care. Speaker's Bureau; Roche Diabetes Care. Advisory Panel; Sanofi. Speaker's Bureau; Sanofi. Advisory Panel; Biomea Fusion, PharmaSens, Tingo Medical. Stock/Shareholder; decide Clinical Software. P. Diem: Board Member; PharmaSens. Advisory Panel; Abbott Diagnostics. M. Resl: Research Support; Dexcom, Inc. Advisory Panel; Abbott. D. Brandt: None. B. Kulzer: Advisory Panel; Abbott, Dexcom, Inc. Consultant; Becton, Dickinson and Company. Other Relationship; Insulet Corporation, AstraZeneca. Board Member; Sanofi-Aventis Deutschland GmbH. Advisory Panel; Roche Diabetes Care, Novo Nordisk.FundingAbbott Diabetes Care, Ascensia, Germany, Dexcom, Germany, Diabetes Center Berne, Roche, Ypsomed
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-934-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 935-P: Personality Traits and Glycemic Control in Type 1 Diabetic Patients
with Different Insulin Therapies-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 935-P
Abstract: Introduction and Objective: Glycemic variability is becoming increasingly important in evaluating effectiveness of treatment in patients with type 1 diabetes. Personality traits may impact daily therapeutic decisions, potentially affecting quality of glycemic control. This study aimed to explore potential relationship between personality traits and glycemic control, and to examine differences across various insulin therapies.Methods: Cross-sectional observational study, 130 type 1 diabetic patients (68 females, 62 males, 43.77±12.81 years, BMI 24.95±4.57 kg/m2, disease duration 23.23±12.39 years, HbA1c 7.04±0.92%), divided in three groups: 1. Multiple daily injections (MDI, n=45); 2. Traditional pumps (TP, n=35); 3. Advanced hybrid closed-loop systems (AHCL, n=50). Personality was assessed through the Personality Inventory for DSM-V questionnaire. Kruskal-Wallis test for independent samples was used to compare continuous variables among three groups. Associations between pairs of variables were analyzed using Spearman’s correlation.Results: AHCL group showed higher emotional lability (p=0.042), perseveration (p=0.005), separation insecurity (p=0.007) and distractibility (p=0.021) than MDI and TP group. The pathological trait of emotional lability (above the 75th percentile) was more frequently present in the AHCL (32%, p=0.029) than MDI and TP group. This trait was associated with an increase in TAR>180 (p=0.035) and GMI (p=0.025), a decrease in TBR<70 (p=0.014). However, glycemic control and metrics were significantly better in the AHCL than MDI and TP group (HbA1c, p=0.03; GRI, p<0.001; TIR, p=0.004; TAR>180, p=0.05; TBR<70, p=0.018, TAR>250, p=0.041; CV, p=0.012; SD, p=0.01).Conclusion: AHCL systems may help mitigating the impact of problematic personality traits, that could interfere achieving an optimal glycemic control.DisclosureE. Resmini: None. A.V. Cornaghi: None. V. Turra: None. E. Zarra: None. E. Cimino: Speaker's Bureau; roche, Abbott. M. Sandri: None. M. Migazzi: None. G. Massari: None. B. Pasquino: None. C. Mascadri: None. S. Madaschi: None. A. Girelli: Consultant; Abbott Diagnostics, Sanofi, Roche Diabetes Care.
PubDate: Fri, 13 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-935-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 936-P: The Effect of Switching the Medtronic MiniMed 780G Insulin Pump to
the “Optimal” Setting-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 936-P
Abstract: Introduction and Objective: The most promising method for insulin delivery in individuals with type 1 diabetes mellitus (T1DM) is the automated insulin pump therapy. In Hungary, the only automated insulin pump reimbursed by the National Health Insurance Company is the Medtronic Minimed 780 G (MM780G) hybrid closed-loop system. Recently, optimal adjustment methods for the MM780G have been established, determining that a glucose target value (GT) of 100 mg/dl and an active insulin time (AIT) of 2 hours are ideal.Methods: We analyzed the settings of our patients using the MM780G and encouraged them to adjust to the optimal settings. We then evaluated sensor data from two weeks before and after the adjustments.Results: Our department's database includes 164 T1DM individuals treated with MM780G, of whom 82 were not yet on optimal settings. Most of these patients (80%) beforehand had a GT of 100 mg/dl; however, their AIT exceeded 2 hours (with 8 cases having AIT >2.5 hours and 74 cases at AIT = 2.5 hours). Adjusting the settings to optimal parameters was recommended for these patients, and 58 of them could successfully be persuaded to change their AIT to 2 hours. After this adjustment, the time spent in the target range (TIR) increased from 73.8% to 77.0%, and the time in the tight range (TITR) rose from 48.7% to 52.3% (p < 0.05 for both). The time spent above the target range also improved significantly, while the time spent below the target range and variability did not change substantially. The glucose management indicator (GMI) showed a slight but significant decrease (p < 0.01) from 6.9% to 6.8%.Conclusion: Our data indicate that even a minor adjustment, such as changing the AIT from ≥ 2.5 hours to 2 hours, can significantly enhance the sensor metrics achieved with the MM780G. The improvement in TIR was attributed to an increase in the time spent in euglycemia, reflected in the TITR.Disclosure J.T. Kis: Speaker's Bureau; Novo Nordisk, Lilly Diabetes, Sanofi, Boehringer-Ingelheim, AstraZeneca, KRKA, Berlin-Chemie AG. C. Fekete: None. K.R. Arapovicsné Kis: None. G.G. Tomasics: None. L. Schandl: None. G. Winkler: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-936-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 937-P: Successful Transition from Multiple Daily Injections (MDI) to
Automated Insulin Delivery (AID)—Real-World Glycemic Outcomes among
People with Diabetes Using the Omnipod 5 AID System-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 937-P
Abstract: Introduction and Objective: Many people who have transitioned to the Omnipod® 5 AID System were previously using MDI for their diabetes management. This analysis evaluated the real-world glycemic benefit of Omnipod 5 use in people with T1D and T2D previously treated with MDI.Methods: A retrospective analysis of CGM and insulin data from US Omnipod 5 users aged ≥2y (T1D) or ≥18y (T2D) who self-reported baseline A1C and transitioned from MDI at onboarding was conducted for those primarily using the 110 mg/dL target setting with sufficient CGM data (≥90 days of data, ≥75% of days with ≥220 readings).Results: A total of 23,906 users (85% T1D, 15% T2D) met the inclusion criteria. For those with baseline A1C <7%, median time in range (70-180 mg/dL) with AID was 75% and 79% in users with T1D ages 2-17y and ≥18y, respectively, and was 82% in users with T2D (Figure). Among this subset of users, median GMI was <7.0%. With AID use, those with baseline A1C 7-9% achieved a GMI of 7.2-7.4%, and users with the highest baseline A1C >9% achieved a GMI of 7.6%. Across all groups, median time <70mg/dL was ≤1.32%, and was substantially lower in T2D compared with T1D.Conclusion: These real-world results demonstrate that people with T1D and T2D previously using MDI may achieve favorable glycemic outcomes across all levels of baseline glycemia with Omnipod 5 use.Disclosure G. Aleppo: Consultant; Dexcom, Inc., Insulet Corporation. Research Support; Insulet Corporation, Fractyl Health, Inc., MannKind Corporation, Tandem Diabetes Care, Inc, WellDoc, EMMES, AbbVie Inc, Bayer Pharmaceuticals, Inc. D. DeSalvo: Consultant; Dexcom, Inc. Advisory Panel; Insulet Corporation. F.J. Pasquel: Consultant; Insulet Corporation. Research Support; Novo Nordisk, Dexcom, Inc., Ideal Medical Technologies, Tandem Diabetes Care, Inc, Insulet Corporation. Consultant; Dexcom, Inc. L.M. Huyett: Employee; Insulet Corporation. Stock/Shareholder; Insulet Corporation. K. Miller: Employee; Insulet Corporation. L. Conroy: Employee; Insulet Corporation. Stock/Shareholder; Insulet Corporation. J.J. Mendez: Employee; Insulet Corporation. Stock/Shareholder; Insulet Corporation. T.T. Ly: Employee; Insulet Corporation. Stock/Shareholder; Insulet Corporation.FundingThis study was funded by Insulet Corporation.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-937-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 938-P: MiniMed 780G System Users Achieve Similar Glycemic Outcomes
Regardless of Socioeconomic Status-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 938-P
Abstract: Introduction and Objective: The area deprivation index (ADI) score is a composite metric of socioeconomic status ranging from 1-30 (least deprived) to 80-100 (most deprived), which is based on income, housing, employment, and education.1 As a higher ADI has been associated with increased dysglycemia,2 the present study assessed real-world MiniMed™ 780G glycemic outcomes across the United States (U.S.) ADI.Methods: CareLink™ personal data (as of October 26, 2024) of 39,387 consenting MM780G users, who lived in the U.S. and had ≥10 days of sensor use, were assessed. Glycemic metrics, insulin, and achieved glycemic targets were stratified from lowest to highest ADI. Metrics included the mean glucose management indicator (GMI) and time within 70-140 mg/dL (TITR), within 70-180 mg/dL (TIR), below 70 mg/dL (TBR) and above 180 mg/dL (TAR).Results: From the lowest to highest ADI, MM780G ROS use (~30%), AHCL use (~87%), and glycemic control trended similarly (Figure). The proportion of users achieving consensus-recommended GMI, TIR and TBR averaged 50%-53%.Conclusion: These data demonstrate that independent of socioeconomic status, a majority of MiniMed™ 780G system users in the U.S. were able to meet consensus glycemic targets.Disclosure J.J.F. McVean: Employee; Medtronic. Z. Dai: Employee; Metronics. M. Liu: Employee; Medtronic. N. Sathiyanathan: None. V. Putcha: Employee; Medtronic. Stock/Shareholder; Medtronic. A. Kinnischtzke: None. J. Shin: Employee; Medtronic. T.L. Cordero: Employee; Medtronic. R.A. Vigersky: Employee; Medtronic.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-938-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 939-P: People with Type 1 Diabetes (T1D) with High Baseline A1Cs
Experience Drastic Glycemic Outcomes from Use of the Automated Insulin
Delivery as Adaptive Network (AIDANET) Fully Closed Loop (FCL) System-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 939-P
Abstract: Introduction and Objective: Use of technology in T1D has often been reserved for those with optimal glucose control and low A1cs, however, those with high A1cs and variable glucose control may benefit most from use of a fully closed loop system. Among the most common reasons for variability are late or missed meal boluses.Methods: We present a case series of three people with T1D with high baseline A1cs (>8.0%) and fear of hypoglycemia. They were enrolled in a multisite, randomized crossover device safety and feasibility trial with use of AIDANET system in FCL as part of a supervised study with transition to home use. Patients were randomized to 14 days of usual care (UC) before or after FCL use.Results: Use of an FCL system drastically increased their time in range (TIR; 70mg/dL-180mg/dL) by 25.19% for case 1, 29.64% for case 2, and 60.87% for case 3. They also experienced a decrease in time below 54 mg/dL and time above 250 mg/dL (figure). Additionally, the FCL system allowed a decrease in diabetes burden by eliminating the need for user-initiated boluses and helped to ease fear of hypoglycemia.Conclusion: In these three cases, use of the FCL system drastically increased TIR as well as decreased time above and below range. Not only did users experience drastic glycemic benefits, but also a decrease in diabetes burden.DisclosureL. Towers: None. E. Escobar: None. A. Narayan: None. J.Y. Hosseinipour: None. M. Moscoso-Vasquez: Other Relationship; Dexcom, Inc. Research Support; Tandem Diabetes Care, Inc, National Institute of Diabetes and Digestive and Kidney Diseases. L. Ekhlaspour: Other Relationship; Medtronic. Advisory Panel; Abbott, Medtronic. Consultant; Jaeb Center for Health Research. Research Support; MannKind Corporation. Speaker's Bureau; Insulet Corporation. Advisory Panel; Sequel Med Tech. Other Relationship; Tandem Diabetes Care, Inc. Research Support; Abbott. Other Relationship; Sanofi. M.D. Breton: Speaker's Bureau; Sinocare Inc, Tandem Diabetes Care, Inc. Consultant; Roche Diabetes Care, Boydsense. G.P. Forlenza: Advisory Panel; Medtronic. Research Support; Medtronic, Dexcom, Inc. Consultant; Dexcom, Inc. Research Support; Insulet Corporation. Consultant; Insulet Corporation. Research Support; Tandem Diabetes Care, Inc. Advisory Panel; Tandem Diabetes Care, Inc. Research Support; Abbott. Advisory Panel; Sequel Med Tech.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-939-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 940-P: Porous Insulin Microneedles for Diabetes Treatment
-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 940-P
Abstract: Introduction and Objective: Patients with type 1 and type 2 diabetes are subjected to insulin injection therapies. Repeated subcutaneous insulin administrations leads to physiological and psychological issues, such as low adherence, infections, subcutaneous nodules, scarring, and so on. Insulin microneedles enables minimally invasive delivery of insulin, reducing adverse effects of insulin therapy in patients. Herein, we designed a porous insulin microneedle that can release insulin in a controlled manner for diabetes treatment.Methods: Porous microneedles were constructed by gelatin methacrylamide loaded with insulin. We characterized the porous insulin microneedles via optical microscopy and scanning electron microscopy. Biocompatibility was evaluated by utilizing CCK8 assays. To observe penetration effects, agarose hydrogel was used for simulating human skin. The release of insulin from the microneedles was investigated by labeling insulin with FITC. Diabetic mouse models were established and treated with porous insulin microneedles, followed by continuous observation of blood glucose levels.Results: The porous microneedles were demonstrated homogeneous microneedle arrays under microscopy. Transversal section of the microneedles had porous structure, capable of loading macromolecules including insulin. It was shown good biocompatibility when culturing with cells. As minimally invasive patches, the fabricated porous insulin microneedles can penetrate through the skin model, which released insulin into the subcutaneous spaces rapidly. Diabetic mouse models were successfully established with high blood glucose levels. Treated with the porous insulin microneedles, the hyperglycemia was ameliorated in diabetic mice.Conclusion: The resultant porous insulin microneedles can delivery insulin efficiently in a minimally invasive manner, reducing high blood glucose levels of diabetic mice. It is innovative for diabetes treatment, drug delivery, and smart medicine.DisclosureJ. Li: None. Z. Huan: None. L. Li: None.FundingNational Natural Science Foundation Major International (Regional) Joint Research Program (82320108003); National Natural Science Foundation (82170845, 82000740, 81970717); Key Research & Developement Program (No.BE2022853); Medical Key Discipline (ZDXK202203) of Jiangsu Province; SEU Innovation Capability Enhancement Plan for Doctoral Students (CXJH_SEU 24223)
PubDate: Fri, 13 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-940-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 941-P: Perceptions and Acceptance of Technology in an Automated Insulin
Delivery Adaptive Network (AIDANET) Fully Closed Loop (FCL) System-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 941-P
Abstract: Introduction and Objective: Patient acceptance of an FCL automated insulin delivery (AID) system has not been previously studied.Methods: Adolescence (14-17yo), young adults (18-25yo), and adults (25-60yo) with type 1 diabetes enrolled in a randomized crossover device safety and feasibility study of the AIDANET system. Users participated in a 5-day supervised hotel stay, followed by 7 days at home. At baseline and after home use, users completed the INSPIRE survey, a measure of expectations of AID, and the Technology Acceptance Scale (TAS), which measures experiences with technology and the benefits and burdens. Paired t-tests were conducted for the whole cohort, each of the three age groups, and low HbA1c (<8.0%) and high HbA1c (8.0-12.0%) subgroups.Results: For the 33 participants (25.5±12.8yrs; 63%F), INSPIRE scores significantly decreased after 11 days of use (p=0.001). Young adults, adolescents, and low HbA1c groups showed significant decreases in INSPIRE scores (p=0.042, 0.006, 0.005, respectively). There was no significant change for adults and high HbA1c groups. TAS scores significantly decreased in adolescences (p=0.028), but remained unchanged in all other subgroups. There were no differences in changes between groups.Conclusion: Additional research is needed to determine user experience and acceptance after longer wear period of the AIDANET system.DisclosureE. Escobar: None. L. Towers: None. G.P. Forlenza: Advisory Panel; Medtronic. Research Support; Medtronic, Dexcom, Inc. Consultant; Dexcom, Inc. Research Support; Insulet Corporation. Consultant; Insulet Corporation. Research Support; Tandem Diabetes Care, Inc. Advisory Panel; Tandem Diabetes Care, Inc. Research Support; Abbott. Advisory Panel; Sequel Med Tech. E.C. Cobry: Advisory Panel; Dexcom, Inc. J.Y. Hosseinipour: None. A. Narayan: None. S.A. Brown: Research Support; Dexcom, Inc., Insulet Corporation, Tandem Diabetes Care, Inc, Tolerion, Roche Diabetes Care. Other Relationship; MannKind Corporation. J.C. Wong: Research Support; Abbott, Dexcom, Inc., Tandem Diabetes Care, Inc.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-941-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 942-P: Pediatric and Adult T1D Glycemic, QoL, and Safety Outcomes of 1,013
Single Clinic Open Source AID Installations-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 942-P
Abstract: Introduction and Objective: Since 2020, BCDiabetes, a public Canadian clinic, has offered clients open source automated insulin delivery (OS AID) & ongoing support at no cost due to OS AID’s lower barrier to entry vs retail.Methods: This retrospective study analyzed client data from 14-day CGM ambulatory glucose profiles before and during use of OS AID. Clients had T1D, used Omnipod pods & Dexcom CGM, and signed a consent to use OS AID via smartphone app: Loop, iAPS or AAPS.Results: 1588 clients had OS AID installed for 1730 patient-years of exposure. 33% were pediatric & 47% were male. For adult & pediatric clients respectively, average age (range) was 42 (18-84) and 12 (2-17) years. T1D duration was 21 years for adults and 3 years for peds. Loop, iAPS & AAPS were used by 75, 10 & 15% respectively. No deaths, 2 DKAs and 8 severe hypoglycemic episodes were reported. Glycemic outcomes for 740 adult and 273 pediatric clients with paired baseline & 90 day CGM data were examined (Table 1). Outcomes by app (Loop, iAPS, AAPS) were near-identical so are pooled here. Quality of Life: 194 adult & 61 pediatric clients had paired QoL data pre- & 90 days post-OS AID. Diabetes Distress fell from 2.47 to 1.97 (p<0.0001), and Device Satisfaction rose from 6.38 to 8.2 (p<0.0001).Conclusion: OS AID systems, when installed and supported by clinicians, were safe, improved glycemia, lowered diabetes distress and improved device satisfaction.DisclosureA. Alqahtani: None. N. Khan: None. G. Klein: None. K. Hawke: None. T. Elliott: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-942-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 943-P: Real-World Performance of the MiniMed 780G System Safe Meal Bolus
Reduction Is Dependent on Multiple Factors-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 943-P
Abstract: Introduction and Objective: The MiniMed™ 780G system (MM780G) safe meal bolus (SMB) reduces the meal bolus amount when post-prandial hypoglycemia is predicted over the ensuing 4 hours. We have shown that the sensor glucose (SG) rate-of-change (ROC) immediately prior to meal bolus has a significant inverse relationship with the amount of insulin delivered.1 The present analysis evaluated the relationship of SMB reduction as a function of modifiable factors (e.g., user input of carbohydrates [CHO] and insulin-to-carb ratio [ICR]) and non-modifiable factors (e.g., ROC and age).Methods: We examined 9 months of CareLink™ data from consenting US MM780G users (N=44,725) ≥18 years (541,243 meals), with baseline SG 100-120mg/dL at mealtime (when no autocorrection was triggered), and excluded CHO input >175g (<0.5% of sample). Metrics were averaged per person.Results: The % of SMB insulin reduction had an inverse relationship with CHO, ICR, ROC and age (Table).Conclusion: Multiple factors determine the % of SMB insulin reduction. There is a strong inverse correlation with CHO when there is a high risk for hypoglycemia. Conjointly, CHO, ICR and ROC factors mitigate the likelihood of PP hypo- and/or hyperglycemia with an appropriate reduction of meal bolus allowing international consensus-recommended targets to be met, even with variable CHO inputs.Disclosure V. Putcha: Employee; Medtronic. Stock/Shareholder; Medtronic. A. Benedetti: None. A. Roy: Employee; Metronics. L.J. Lintereur: Employee; Medtronic. B. Grosman: Employee; Medtronic. K. Turksoy: None. A. Kinnischtzke: None. D. Miller: Employee; Medtronic. T.L. Cordero: Employee; Medtronic. J. Shin: Employee; Medtronic. R.A. Vigersky: Employee; Medtronic.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-943-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 944-P: Use of High-Potency GLP-1 Receptor Agonists with OpenAPS Automated
Insulin Dosing Algorithm Eliminates Need for Meal Announcements to Achieve
Glycemic Goals-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 944-P
Abstract: Introduction and Objective: Type 1 Diabetes (T1D) remains challenging to manage, even with commercial Automated Insulin Dosing (AID) systems. High-potency GLP-1 receptor agonists (GLP-1 RAs), such as Semaglutide and Tirzepatide, are increasingly used in T1D, demonstrating evidence for improved glycemic control and reduced insulin requirements. However, it remains uncertain whether GLP-1 RA therapy can reduce the burden of meal announcements in real-world settings. This study evaluated the impact of GLP-1 RAs on prandial insulin bolus frequency and glycemic control in individuals with T1D using iAPS, an iOS implementation of the OpenAPS algorithm.Methods: A retrospective chart review was conducted for people with T1D seen at Stanford University who used the iAPS system alongside high-potency GLP-1 RAs. Outcomes assessed included prandial insulin bolus frequency and continuous glucose monitor (CGM) time-in-range (TIR).Results: With proper configuration, meal announcements were eliminated in all six participants using the iAPS system with GLP-1 RAs. The mean TIR was 79.72% ± 8.54%, with no reported episodes of diabetes-related ketoacidosis or severe hypoglycemia. Participants who eliminated meal announcements reported a reduced management burden and an improved quality of life.Conclusion: The combination of high-potency GLP-1 RAs with the OpenAPS algorithm, tuned appropriately, can eliminate the need for meal announcements in individuals with T1D while maintaining glycemic targets. Further research is warranted to validate these findings and explore broader applications.DisclosureT. Akcan: None. R.S. Kingman: None. M. Morgan: None. Y. Liu: None. K. Kingston: None. R. Lal: Consultant; Abbott, Biolinq, Capillary Biomedical, Inc, Gluroo, PhysioLogic Devices, Portal Insulin, Sanofi, Tidepool. Advisory Panel; Provention Bio, Inc, Provention Bio, Inc, Microbion, Microbion, Lilly Diabetes. Research Support; Insulet Corporation, Medtronic, Tandem Diabetes Care, Inc, Sinocare Inc.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-944-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 945-P: Improved Glycemic Outcomes with the Omnipod 5 AID System in Adults
with Type 2 Diabetes (T2D) Previously Using Basal without Bolus
Insulin—Subanalysis of the SECURE-T2D Study-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 945-P
Abstract: Introduction and Objective: The SECURE-T2D pivotal trial recently demonstrated safety and efficacy of the Omnipod® 5 Automated Insulin Delivery (AID) System in adults with insulin-treated T2D. This sub-analysis evaluated outcomes in participants previously using basal without bolus insulin.Methods: This multicenter 305-participant single-arm trial enrolled 63 participants with T2D using basal without bolus insulin (mean age 55±11y, 27% Black, 22% Hispanic/Latino, 71% using GLP-1 RA at study entry). After a 14-day standard therapy (ST) phase, participants initiated 13 weeks of AID.Results: A1C decreased by mean (95% CI) 1.2% (0.9%, 1.5%), from 8.6±1.2% at baseline to 7.5±0.8% at study end (p<0.001). Time in range (70-180 mg/dL) increased overall and among those using or not using a GLP-1 RA with AID (Figure). Robust mean time <70 mg/dL was 0.1±0.1% for both ST and AID and was similar in those using and not using GLP-1 RA. Total daily insulin was reduced by 6.3U/day (p=0.04) and weight increased by 0.9kg (p=0.03), with similar changes observed between users and non-users of GLP-1 RA.Conclusion: This cohort of adults with T2D using basal without bolus insulin and not meeting glycemic targets successfully initiated AID, demonstrating the feasibility to bypass initiation of MDI and transition directly to AID in clinical practice.Disclosure A.L. Carlson: Research Support; Abbott, Amgen Inc, Dexcom, Inc., Eli Lilly and Company, Hemsley Charitable Trust, Insulet Corporation. Other Relationship; Medtronic, Novo Nordisk, Tandem Diabetes Care, Inc. Research Support; Sanofi. Advisory Panel; MannKind Corporation. F.J. Pasquel: Consultant; Insulet Corporation. Research Support; Novo Nordisk, Dexcom, Inc., Ideal Medical Technologies, Tandem Diabetes Care, Inc, Insulet Corporation. Consultant; Dexcom, Inc. G.M. Davis: Research Support; Insulet Corporation. D.M. Huffman: None. A.L. Peters: Advisory Panel; Medscape. Consultant; Vertex Pharmaceuticals Incorporated. Research Support; Insulet Corporation, Abbott. Other Relationship; Omada Health. J.C. Parker: Speaker's Bureau; Corcept Therapeutics, Novo Nordisk, Insulet Corporation. L.M. Laffel: Advisory Panel; Boehringer-Ingelheim, Sanofi, MannKind Corporation, Medtronic, Vertex Pharmaceuticals Incorporated, Tandem Diabetes Care, Inc, Insulet Corporation. Research Support; Dexcom, Inc. Advisory Panel; Sequel Med Tech. Other Relationship; Janssen Pharmaceuticals, Inc. Consultant; Arbor Biotech. G. Romeo: None. J. Mathew: None. K.N. Castorino: Research Support; Abbott, Medtronic, Dexcom, Inc., Lilly Diabetes, MannKind Corporation, Eli Lilly and Company, Insulet Corporation. Speaker's Bureau; Dexcom, Inc. Advisory Panel; MannKind Corporation. Speaker's Bureau; Insulet Corporation. D.F. Kruger: Other Relationship; Abbott. Advisory Panel; embecta, MannKind Corporation. Other Relationship; CeQur, Tandem Diabetes Care, Inc, Dexcom, Inc. Research Support; Jaeb Center for Health Research. Other Relationship; Eli Lilly and Company. Advisory Panel; Structure Therapeutics, Inc. Other Relationship; Insulet Corporation, Sequel Med Tech. Advisory Panel; Corcept Therapeutics. K.M. Dungan: Research Support; Abbott Diagnostics, Dexcom, Inc. Consultant; Dexcom, Inc. Other Relationship; UpToDate. Consultant; Oppenheimer & Co. Advisory Panel; Insulet Corporation. Research Support; Insulet Corporation. Board Member; Elsevier, Eli Lilly and Company. Speaker's Bureau; Medscape, Med Learning Group, Impact Education. M. Kipnes: Research Support; Zydus Lifesciences, Zucara Therapeutics, 89bio, Inc, Abbott Diagnostics, AbbVie Inc, Akero Therapeutics, Inc, Amgen Inc, Biomea Fusion, Boehringer-Ingelheim, Biolinq, MannKind Corporation, Eli Lilly and Company, Carmot Therapeutics, Inc, Endogenex, Ionis Pharmaceuticals, Novo Nordisk, Corcept Therapeutics, Insulet Corporation, Fractyl Health, Inc. Advisory Panel; Corcept Therapeutics, AP stem. Other Relationship; Jaeb Center for Health Research. Research Support; Sinocare Inc, Kowa Pharmaceuticals America, Inc, Diamyd. E. Jauch: Research Support; Carmot Therapeutics, Inc, Omnipod. T. Oser: Consultant; Dexcom, Inc. Research Support; Abbott, Insulet Corporation, Dexcom, Inc. Advisory Panel; Medscape. V.N. Shah: Consultant; Dexcom, Inc. Advisory Panel; Sanofi, Novo Nordisk. Consultant; Lilly Diabetes. Advisory Panel; embecta. Consultant; Insulet Corporation. Advisory Panel; Tandem Diabetes Care, Inc, Ascensia Diabetes Care. Research Support; Enable Bioscience. Consultant; Genomelink and Lumosfit. B. Horowitz: Advisory Panel; AbbVie Inc. Research Support; AbbVie Inc. Speaker's Bureau; Eli Lilly and Company. Research Support; Eli Lilly and Company. Speaker's Bureau; Novo Nordisk. Research Support; Novo Nordisk. Speaker's Bureau; Tandem Diabetes Care, Inc. M.L. Warren: Research Support; Medtronic, Insulet Corporation, Abbott. Speaker's Bureau; Lilly Diabetes. Research Support; Lilly USA LLC, Amgen Inc. Speaker's Bureau; Amgen Inc. Advisory Panel; Lilly USA LLC. Research Support; Diasome Pharmaceuticals, Bayer Pharmaceuticals, Inc, Ascendis Pharma A/S, Novo Nordisk. W. Deeb: None. J.B. Buse: Other Relationship; Corcept Therapeutics, Dexcom, Inc., Novo Nordisk. Consultant; Altimmune Inc, Amgen Inc, ApStem, Aqua Medical, AstraZeneca, Boehringer-Ingelheim, CeQur, Eli Lilly and Company, embecta, GentiBio. Other Relationship; Glyscend Therapeutics. Consultant; Insulet Corporation, Medtronic. Other Relationship; Mellitus Health. Consultant; Metsera....
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-945-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 946-P: Efficacy of Ultra-rapid and Rapid-Acting Insulin Analogs in Hybrid
and Advanced Automated Insulin Delivery Systems among People with Type 1
Diabetes—A Systematic Review and Meta-analysis of Randomized Controlled
Trials-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 946-P
Abstract: Introduction and Objective: No systematic review and meta-analysis of randomized controlled trials (RCTs) has been done to compare the effectiveness of ultra-rapid insulin analogs (URIAs) and rapid-acting insulin analogs (RIAs) in hybrid and advanced automated insulin delivery (AID) systems on glycemic metrics among people with type 1 diabetes (T1D).Methods: MedLine, PubMed, Scopus, Web of Science and Cochrane Central Register of clinical trials were searched. Inclusion criteria were RCTs; T1D populations of any age; comparing URIAs (Fiasp® or Lyumjev®) with any type of RIAs; using any type of AID systems. Glycemic outcomes were extracted post-intervention and expressed as mean differences and 95% CIs between two comparators. Results were pooled using a random-effect meta-analysis.Results: Twelve RCTs met the criteria (11 crossover and 7 double-blinded in design; 9 with AID use ≥4 weeks and used Fiasp; 7 used advanced AID systems), involving 504 participants (449 adults; 55 children and adolescents). Overall, meta-analysis showed URIAs compared to RIAs improved absolute time in range 70-180 mg/dL (TIR) by +1.4 % (0.6 to 2.2%; I2= 18.8%, p<0.01) accompanied by a favorable effect on time-below-range (TBR) <70mg/dL by -0.3% (-0.5 to -0.2%; I2= 73.6%, p <0.01). A favorable decrease in TBR <54 mg/dL and coefficient of variation (CV) was also observed in URIAs over RIAs, with the effect size of -0.03% (-0.06 to -0.01%; I2=17%; p = 0.01) and -0.6% (-1.1 to -0.2%; I2=0.0%; p= 0.01).Conclusion: URIAs safely improved glycemia and were comparable to RIAs among T1D people using AID systems. Despite outcomes demonstrating statistical significance, the clinical impact may be small, given the TIR improvement of 1.4% (registration ID: CRD42024578754).DisclosureY. Zhou: None. Y. Ni: None. Z. Lin: None. M. Lei: None. C. Wang: None. X. Yang: None. D. Yang: None. W. Xu: None. J. Yan: None.FundingNoncommunicable Chronic Diseases- National Science and Technology Major Project (2023ZD0508200, 2023ZD0508203).
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-946-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 947-P: Real-World Efficacy of the iLet Bionic Pancreas in Users with Type
1 and Type 2 Diabetes during the First Eighteen Months of Commercial
Availability-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 947-P
Abstract: Introduction and Objective: To analyze the impact of the iLet bionic pancreas on glycemic control in users with type 1 and type 2 diabetes during the first 18 months after FDA clearance (note that the iLet is not currently indicated for use in people with type 2 diabetes).Methods: Commercial users of the iLet who had a pre-iLet HbA1c value available and had at least 3 weeks of iLet data in the cloud were included. Baseline HbA1c values were compared with the glucose management indicator (GMI) values calculated from all available continuous glucose monitoring (CGM) data, both reported as mean±SD [IQR]. Users with type 1 and type 2 diabetes were analyzed separately. The percentage of time with CGM glucose <54 mg/dl during iLet use was calculated for all groups and reported as median [IQR]. The insulin total daily dose per body mass (TDD) was calculated for all groups and reported as mean±SD [IQR].Results: Data from 6,992 commercial users (5,843 with type 1 and 1,012 with type 2 diabetes) were included in the analysis. Users with type 1 diabetes had a baseline HbA1c of 8.7±2.0% [7.2-9.7] and an iLet GMI of 7.3±0.5% [7.0-7.5] (difference: -1.4%). Users with type 2 diabetes had a baseline HbA1c of 9.1±2.0% [7.7-10.2] and an iLet GMI of 7.4±0.6% [7.0-7.6] (difference: -1.7%). The time with CGM glucose <54 mg/dl was 0.3% [0.1-0.7] in users with type 1 diabetes and 0.1% [0.0-0.2] in users with type 2 diabetes. The insulin TDD was 0.8±0.3 U/kg/day [0.6-1.0] in users with type 1 diabetes and 0.9±0.4 U/kg/day [0.6-1.1] in users with type 2 diabetes.Conclusion: The baseline HbA1c values for users with type 2 diabetes were higher, and the decreases from baseline HbA1c to iLet GMI values were larger, than among users with type 1 diabetes. The iLet GMI values achieved by users and insulin TDD per body mass with both type 1 and type 2 diabetes were similar. The time spent <54 mg/dl was lower in users with type 2 diabetes than those with type 1 diabetes.Disclosure S.J. Russell: Employee; Beta Bionics, Inc. Stock/Shareholder; Beta Bionics, Inc. R. Selagamsetty: Employee; Beta Bionics, Inc. E. Damiano: Other Relationship; Beta Bionics, Inc.FundingBeta Bionics, Inc.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-947-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 948-P: Transition of Persons over 65 Years of Age with Type 1 Diabetes to
the MiniMed 780G System—Preliminary Results from a Six-Month,
Single-Center Prospective Randomized Study-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 948-P
Abstract: Introduction and Objective: The effectiveness and safety of the Advanced Hybrid Closed-Loop (AHCL) system in older populations remain uncertain. The primary objective of this study was to assess the efficacy and safety of the MiniMed™ 780G AHCL system in improving glucose control in adults over 65 years of age with type 1 diabetes (T1DM) who were new to this technology.Methods: Thirty-four T1DM patients over the age of 65, were randomized into either the AHCL or Control group. At baseline, both groups utilized the Medtronic Guardian™ 4 sensor. The study is designed to continue for 12 months, with assessments of quality of life, physical and cognitive measures, and vascular status conducted at the conclusion. Here, we present the results of the AHCL group after a 6-month observation period.Results: Four patients withdrew before or on the day of randomization, leaving 30 patients (15 per group) to complete the 6-month observation. In the AHCL group, the mean age was 68.1 ± 5.1 years, diabetes duration was 33.5 ± 16.7 years, BMI was 26.5 ± 3.7, and HbA1c was 7.5 ± 0.9. There were no significant differences between groups in age, T1DM duration, CGM indices, or HbA1c. For 780G users glucose target of 100 mg/dL and an active insulin time of 2 hours were used by 80% and 100% of participants, respectively. The Time in Range for the AHCL group increased from 59.8% at baseline to 77.6% after 1 month, 80,1% after 3 months and remained at 80,1% after 6 months (all p < 0.001). Secondary outcomes showed a reduction in Time Above Range and Time Above Range 2 (p < 0.001), with no change in Time Below Range and Time Below Range 2 (p >0.05). No serious adverse events or diabetic ketoacidosis occurred.Conclusion: These preliminary results indicate that the AHCL system significantly improved glycemic control in older adults with longstanding diabetes. The AHCL system appears to be an effective and safe option for enhancing glycemic management in this population.Disclosure B. Matejko: Research Support; Medtronic. Other Relationship; Medtronic, Dexcom, Inc., Ascensia Diabetes Care, BIOTON, Abbott, Lilly Diabetes, Roche Diabetes Care. Research Support; Roche Diabetes Care. K.M. Cyranka: Speaker's Bureau; Abbott. Research Support; Medtronic. Other Relationship; Novo Nordisk, Dexcom, Inc. Research Support; Sanofi. K. Susul: Research Support; Medtronic. P. Surowiec: Research Support; Medtronic. Other Relationship; AstraZeneca, Merck & Co., Inc. O. Cohen: Employee; Medtronic. M. Malecki: Speaker's Bureau; Novo Nordisk, Lilly Diabetes, Sanofi, Boehringer-Ingelheim, AstraZeneca, Berlin-Chemie AG. Advisory Panel; Abbott, Dexcom, Inc. Speaker's Bureau; Servier Laboratories. Other Relationship; Amryt Pharma. T. Klupa: Speaker's Bureau; Lilly Diabetes, Novo Nordisk, AstraZeneca, Boehringer-Ingelheim, Sanofi. Research Support; Medtronic. Speaker's Bureau; Medtronic, Abbott, Dexcom, Inc.FundingInvestigator Driven Grant (Medtronic): ERP-2022-13079
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-948-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 949-P: Meal Composition and Postprandial Glucose (PPG) Excursions in a
Fully Closed-Loop (FCL) Study-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 949-P
Abstract: Introduction and Objective: Fat and protein content of meals impact PPG excursion in individuals with Type 1 Diabetes (T1D). PPG management can be even more challenging in an FCL system with no premeal boluses. We explored how meal composition may impact glycemic outcomes when managing insulin in FCL.Methods: Thirty-four participants in 3 cohorts (adults, young adults, adolescents) with T1D (14-53 years old, 62% female, HbA1c 8.0±1.1%) tested the University of Virginia neural network-based system (AIDANET) during a five-day FCL study in supervised settings. Study staff recorded each meal's carbohydrate, protein, and fat content using food labels. Linear regression was used to determine the association between meal composition and PPG (4 hours following a meal) CGM metrics, adjusting for gender and age.Results: Overall, 301 meals were included in the analysis. The average carbohydrate, fat, and protein contents of the meals were 63.9 ± 34.8, 32.4 ± 23.3, and 32.6 ±17.5 grams, respectively. Unsurprisingly, larger carbohydrate amounts were associated with larger PPG excursions. There was no association between fat and protein content and the 4-hour incremental area under the curves (AUC). However, the protein content significantly reduced the AUC during the second hour after meal onset (Coefficient -45.53 mg/dl*min, p-value <0.002). AUC during the third and fourth hours after meal onset was significantly increased by fat content (Coefficient 32.57, 44.21, and p-values < 0.018 and 0.002, respectively). Fat also increased time to peak (Coefficient 0.57, p-value <0.003), while protein decreased peak PPG (Coefficient -0.66, p-value < 0.008). Time in range improved with more protein (Coefficient 0.003, p-value<0.025). However, time in tight range was not impacted by fat or protein.Conclusion: Meal composition significantly impacts FCL PPG profiles, and automatically accounting for its effects may further improve glycemic outcomes.Disclosure L. Ekhlaspour: Other Relationship; Medtronic. Advisory Panel; Abbott, Medtronic. Consultant; Jaeb Center for Health Research. Research Support; MannKind Corporation. Speaker's Bureau; Insulet Corporation. Advisory Panel; Sequel Med Tech. Other Relationship; Tandem Diabetes Care, Inc. Research Support; Abbott. Other Relationship; Sanofi. J.Y. Hosseinipour: None. A. Narayan: None. Z.D. Perez: None. V. Holmes: None. M.D. Breton: Speaker's Bureau; Sinocare Inc, Tandem Diabetes Care, Inc. Consultant; Roche Diabetes Care, Boydsense. S.A. Brown: Research Support; Dexcom, Inc., Insulet Corporation, Tandem Diabetes Care, Inc, Tolerion, Roche Diabetes Care. Other Relationship; MannKind Corporation. G.P. Forlenza: Advisory Panel; Medtronic. Research Support; Medtronic, Dexcom, Inc. Consultant; Dexcom, Inc. Research Support; Insulet Corporation. Consultant; Insulet Corporation. Research Support; Tandem Diabetes Care, Inc. Advisory Panel; Tandem Diabetes Care, Inc. Research Support; Abbott. Advisory Panel; Sequel Med Tech. E. Cengiz: Advisory Panel; Novo Nordisk, Arecor Therapeutics, Eli Lilly and Company, Tandem Diabetes Care, Inc, Portal Insulin, MannKind Corporation.FundingBreakthrough T1D
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-949-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 950-P: A Multicenter Retrospective Observational Study of the Safety and
the Effectiveness of the MEDISAFE WITH Patch Insulin Pump—MW-Safety
Study-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 950-P
Abstract: Introduction and Objective: Medisafe WITH is a unique patch pump that allows the insulin reservoir to be removed, and has been used since 2018 (Terumo, Tokyo, Japan). The aim of this study is to evaluate the safety and the effectiveness of this novel device.Methods: We conducted a single-arm, multicenter, retrospective observational study of 26 weeks. Inclusion criteria were individuals with type 1 diabetes who initiated to use Medisafe WITH between June 1, 2019 and June 30, 2023. Exclusion criteria were individuals considered to be unsuitable as subjects by the decision of the investigators. Date of introduction, treatment before and after initiation, and at 26 weeks, information of medical events, and the reasons of discontinuation. The primary outcomes were the incidence of diabetic ketoacidosis (DKA) and severe hypoglycemia (SH) for 26 weeks, and the secondary outcomes included changes in HbA1c, BMI, insulin dose, and information of discontinuation.Results: A total of 135 individuals treated at 20 study facilities in Japan were registered. They were aged 32 ± 15 years with diabetes duration of 10 [4-18] (median [IQR]) years. During the 22,865 person-days of observation, the incidence of DKA was 0.22/1000 person-days [95% CI: 0.08-0.44], and that of SH was 0.13/1000 person-days [0.03-0.34]. The HbA1c levels at 26 weeks were 7.5 ± 1.3%, which was significantly lower than those at baseline (7.8 ± 1.4%) (p = 0.014). Sixteen individuals (11.9%) discontinued during the 26 weeks, and the continuation rate was 88.1%. After discontinuation, 63% switched to insulin pump from other manufactures, and the rest switched to multiple daily insulin injections.Conclusion: When using Medisafe WITH, it is necessary to provide thorough education on carrying insulin pens in case of emergency, real-time CGM or frequent blood glucose measurements, and contacting the manufacturer's call center or medical institution as necessary. (UMIN-CTR: UMIN000055106)Disclosure J. Miura: Speaker's Bureau; Abbott, Dexcom, Inc., Medtronic. Research Support; Terumo Corporation. Speaker's Bureau; Novo Nordisk. T. Murata: Research Support; Medtronic. Speaker's Bureau; Abbott Japan Co., Ltd, Dexcom, Inc. Y. Hirota: Speaker's Bureau; Novo Nordisk, Sanofi, Eli Lilly and Company, Terumo Corporation, Sumitomo Dainippon Pharma Co., Ltd. Research Support; Medtronic, Kyowa Kirin Co., Ltd, Abbott Japan Co., Ltd. M. Toyoda: None. T. Omura: None. T. Kawamura: Speaker's Bureau; Terumo Corporation, Novo Nordisk, Eli Lilly and Company, Medtronic. M. Hirose: None. Y. Tsurutani: None. T. Urakami: Speaker's Bureau; Novo Nordisk, Abbott Japan Co., Ltd, Terumo Corporation. Y. Ishigaki: None. T. Murakami: None. S. Meguro: Speaker's Bureau; Abbott Japan Co., Ltd, Asahi Kasei Pharma Corp., AstraZeneca, Daiichi Sankyo, Eli Lilly and Company, Kaken Pharmaceutical Co., Ltd,, Kowa Company, Ltd, Kyowa Kirin Co., Ltd, LifeScan Diabetes Institute, Mitsubishi Tanabe Pharma Corporation, Mochida Pharmaceutical Co. Ltd,, MSD K.K.,, Boehringer-Ingelheim, Nipro Corporation,, Novo Nordisk A/S, Ono Pharmaceutical Co., Ltd, Sanofi, Sanwa Kagaku Kenkyusho Co. Ltd,, Sumitomo Dainippon Pharma Co., Ltd, Teijin Pharma Limited. Research Support; Asahi Kasei Pharma Corp. M. Sone: None. Y. Aso: None. S. Kamei: None. K. Shiga: None. T. Murakami: None. M. Ogura: Research Support; LifeScan Diabetes Institute. H. Sawaki: None. K. Hara: None. R. Hattori: None. N. Kodani: Speaker's Bureau; Abbott Japan Co., Ltd, Dexcom, Inc., Medtronic. N. Sakane: None.FundingTerumo Company
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-950-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 951-P: MiniMed 780G System Use with Fast-Acting Insulin Aspart by Adults
with T1D-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 951-P
Abstract: Introduction and Objective: Automated insulin delivery with fast-acting insulin aspart (Fiasp™) is demonstrated safe and non-inferior in A1C reduction, compared with rapid-acting insulin (RAI).1 The present study reports on glycemic outcomes and safety of MiniMed™ 780G system (MM780G) use with Fiasp by adults.Methods: Ten centers enrolled adults with T1D (N=116 intention-to-treat, 18-80yrs) who used the MM780G with the Medtronic extended infusion set in a run-in (~2wks) of open loop or automated basal with aspart or lispro (glucose target [GT] of 120mg/dL). This was followed by a 3-month study period of AHCL at a 100, 110 or 120mg/dL GT with Fiasp. Glycemic outcomes and insulin during the last ~6wks of the study (system settings at investigator discretion) were compared to those during run-in. Outcomes with recommended optimal settings (ROS, 100mg/dL GT with 2hrs active insulin time) were, also, assessed and safety was summarized.Results: Study-period AHCL+Fiasp significantly increased time in range (TIR) and significantly reduced A1C, mean sensor glucose (SG) and time spent below and above range, with no change in TDD (Table). ROS use was associated with an even higher TIR and lower A1C, mean SG and TAR. There was one severe hypoglycemia event (unrelated to device) and no DKA.Conclusion: These findings show that Fiasp is safe when used with MM780G AHCL and provides improved glycemic outcomes when compared to RAI with open-loop or HCL use.Disclosure H.K. Akturk: Consultant; Dexcom, Inc., Medtronic, Tandem Diabetes Care, Inc, Novo Nordisk. Research Support; Dexcom, Inc., Medtronic, Tandem Diabetes Care, Inc, Novo Nordisk. J.H. Reed: None. J. Thrasher: Advisory Panel; Medtronic. Board Member; Medtronic. Consultant; Medtronic. Research Support; Medtronic, AstraZeneca, Merck & Co., Inc, Novo Nordisk, Lilly Diabetes, Inversago Pharma. A. Abitbol: Advisory Panel; Novo Nordisk. Research Support; Novo Nordisk. Speaker's Bureau; Novo Nordisk. Advisory Panel; Eli Lilly and Company. Speaker's Bureau; Eli Lilly and Company. Research Support; Eli Lilly and Company. Advisory Panel; Abbott. Research Support; Abbott. Speaker's Bureau; Abbott. Advisory Panel; Dexcom, Inc. Research Support; Dexcom, Inc. Speaker's Bureau; Dexcom, Inc. Research Support; Biomea Fusion. Advisory Panel; Biomea Fusion. Research Support; Zucara Therapeutics, Moderna, Inc, Pfizer Inc, GlaxoSmithKline plc. Advisory Panel; GlaxoSmithKline plc. Speaker's Bureau; Novartis Pharmaceuticals Corporation. Advisory Panel; Novartis Pharmaceuticals Corporation. Research Support; Novartis Pharmaceuticals Corporation. Advisory Panel; Bayer Pharmaceuticals, Inc, Insulet Corporation. Research Support; Medtronic. M.L. Warren: Research Support; Medtronic, Insulet Corporation, Abbott. Speaker's Bureau; Lilly Diabetes. Research Support; Lilly USA LLC, Amgen Inc. Speaker's Bureau; Amgen Inc. Advisory Panel; Lilly USA LLC. Research Support; Diasome Pharmaceuticals, Bayer Pharmaceuticals, Inc, Ascendis Pharma A/S, Novo Nordisk. F.E. Broyles: None. D. Reyes: None. Z. Dai: Employee; Metronics. J. Shin: Employee; Medtronic. T.L. Cordero: Employee; Medtronic. J.J.F. McVean: Employee; Medtronic. A.S. Rhinehart: Employee; Medtronic. Stock/Shareholder; Medtronic. R.A. Vigersky: Employee; Medtronic.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-951-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 953-P: Twenty-Five Hours of Fasting with Automated Insulin Delivery in
Youth with Type 1 Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 953-P
Abstract: Introduction and Objective: Fasting is a tradition in many religions and a lifestyle choice associated with health benefits. On Yom Kippur, the holiest day in Judaism, many individuals observe a 25-hour fast. This study evaluated glycemic control, insulin delivery, and ketone levels in individuals with T1D who chose to fast using Automated Insulin Delivery (AID) systems.Methods: The study included 54 adolescents and young adults: 34 enrolled prospectively with capillary ketone measurement instructions, and 20 retrospectively. Ketones were measured at the end of the 25-hour fast and on a regular morning. Data were collected from medical records, device uploads, and structured questionnaire interviews.Results: Among the 54 participants (mean age 17.3 ± 3.3 years, AID use 1.5 ± 0.8 years, HbA1c 6.8 ± 1%, TIR 71.2 ± 13.7%), 34 used Medtronic 780G, 10 Tandem Control-IQ, and 10 open-source systems. The most common adjustments were a 150 mg/dL exercise target, sleep mode, and basal/target modifications, respectively, for each system, while 11 participants made no changes. Ten mild hypoglycemic events occurred postprandially after the pre-fast meal, treated with 10.4 ± 7.1 grams of carbs, with all continuing fasting. The median ketone measurement, recorded by 31 participants, was 0.4 (0.3, 0.7) mmol/l, compared to 0.1 (0, 0.1) mmol/l on the morning of a regular day. The mild ketosis observed is likely due to fasting and, in a few cases, disruptions in insulin delivery. The average sensor glucose at the end of the fast was 115 ± 39 mg/dL. No instances of severe hypoglycemia or other serious adverse events were reported during any of the fasts.Conclusion: AID systems enable safe fasting with individualized adjustments and effective insulin delivery to suppress ketonuria.Disclosure R. Nimri: Advisory Panel; Tandem Diabetes Care, Inc. Speaker's Bureau; Novo Nordisk, Sanofi, Insulet Corporation, Medscape. Stock/Shareholder; DreaMed Diabetes. Employee; DreaMed Diabetes. Research Support; Geffen Medical. K. Smuel Zilberberg: None. R. Bello: None. N. Fisch-Shvalb: None. M. Phillip: Advisory Panel; Medtronic. Other Relationship; Eli Lilly and Company, Sanofi. Advisory Panel; Sanofi. Other Relationship; Novo Nordisk. Advisory Panel; Novo Nordisk. Other Relationship; Pfizer Inc. Advisory Panel; Pfizer Inc, Insulet Corporation. Other Relationship; AstraZeneca. Advisory Panel; LifeScan Diabetes Institute. Other Relationship; Dompé, Provention Bio, Inc, Provention Bio, Inc, Microbion, Microbion, OPKO, LUMOS. Advisory Panel; embecta, Tandem Diabetes Care, Inc. Consultant; Qulab Medical. Stock/Shareholder; Dreamed Diabetes. Other Relationship; Dreamed Diabetes. Stock/Shareholder; NG Solutions. Other Relationship; NG Solutions.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-953-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 954-P: Time in Range with the Medtronic Extended Infusion Set vs. Standard
Infusion Set for Real-World MiniMed 780G System Users in the United States
(U.S.)-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 954-P
Abstract: Introduction and Objective: Performance of the Medtronic Extended Infusion Set (EIS), which is indicated for up to 7 days of wear, was assessed as a function of wear duration during real-world MiniMed™ 780G system (MM780G) use.Methods: CareLink™ data (from Jan 2024-April 2024) of consenting US MM780G and EIS users of any age (N=948, 14195 sets) were analyzed and compared with those of standard 3-day IS users (N=642, 21544 sets). This dataset included new MM780G users with >80% orders of either set type and IS changes were determined using non-zero cannula fill and reservoir rewind events.1 Time in range (TIR) and occlusion alarm rates were assessed based on the days after a determined IS change.Results: TIR was lowest (~70%) on Day 1 after an IS change, for both sets (Table). It significantly improved (to ~76%) by Day 2 (p<0.001, for both) and remained stable, thereafter. With the EIS, the frequency of Day 1 occurrences was lower and TIR<70% was 73±52 hours/month versus 127±41 hours/month, compared with the standard IS (p<0.001). Overall occlusion rates were significantly lower with the EIS versus the standard set (p=0.001).Conclusion: The EIS reduces diabetes management burden by lowering the overall number of IS insertions compared with a standard set. In this analysis, the EIS had fewer set failures and occlusions, while providing a higher overall TIR and number of days per month with TIR>70%.DisclosureT. Kwa: None. S. Mutapally: None. V. Putcha: Employee; Medtronic. Stock/Shareholder; Medtronic. J. Kiehl: Employee; Medtronic. G. Zhang: Employee; Medtronic. S. Chattaraj: None. T.L. Cordero: Employee; Medtronic. O. Cohen: Employee; Medtronic. R.A. Vigersky: Employee; Medtronic.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-954-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 955-P: A Prospective Analysis of the Canadian Patient Transition
Experience to Two Advanced Hybrid Closed-Loop Insulin Pump Technologies-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 955-P
Abstract: Introduction and Objective: Advanced hybrid closed-loop (AHCL) insulin pump therapy is a significant development in diabetes treatment. We assessed the real-world experience of patients transitioning to two Health Canada-approved AHCL insulin pumps and their effect on diabetes distress.Methods: We evaluated 48 adults with T1D shifting from multiple daily injection, standard pump or hybrid closed loop pump therapy to one of two AHCL systems: Tandem t:slim X2 with Control IQ™ (n=31) or Medtronic MiniMed 780G with SmartGuard™ (n=17). Diabetes distress (measured by the T1-DDS) and HbA1c at baseline and 6 months post-transition were compared using a paired t-test. Participant comfort, trust and satisfaction with AHCL were assessed with 5-point Likert scale questions, free-text surveys and interviews.Results: After 6 months on AHCL, participants (52% female, mean age 46.0 ± 4.1 yrs) exhibited significant diabetes distress reductions in powerlessness (-0.60 ± 0.30, p<0.001), management (-0.71 ± 0.22, p<0.0000001), hypoglycemia (-0.42 ± 0.31, p=0.01), eating (-0.65 ± 0.29, p<0.00001) and total distress (-0.60 ± 0.21, p<0.000001). Moreover, HbA1c was significantly reduced (-0.55 ± 0.20%, p<0.00001). Most participants (87%) did not find AHCL to be too complicated, with 70% noting a reduced workload. Some (23%) participants reported that AHCL was difficult to trust, but 77% felt that their trust improved over time. Most participants (62%) had no challenges transitioning to AHCL. In total, 90% of participants were satisfied with AHCL and would recommend it to others, while 85% felt that AHCL met their expectations. Emerging qualitative themes were increased freedom in eating, fewer lows at night, lower workload and improved glycemic control. Areas for improvement included sensor reliability, sensor longevity and recurrent alarms.Conclusion: Overall, participants benefited from increased glycemic control and decreased diabetes distress with AHCL.DisclosureG. Nirwal: None. J. Adams: None. S. Frojmovic: None. T. Chang: None. A. Dissanayake: None. J. MacKenzie-Feder: Advisory Panel; Pfizer Inc, Recordati. B. Schroeder: None. A. White: Speaker's Bureau; Boehringer-Ingelheim. Advisory Panel; Eli Lilly and Company. Other Relationship; Medtronic. Advisory Panel; Novo Nordisk. M. Pawlowska: Advisory Panel; Medtronic, Amgen Inc.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-955-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 956-P: Impact of Early Use of Open-source Automated Insulin Delivery
Systems with the Implementation of Standard Initiation Protocol among
Recently Diagnosed People with Type 1 Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 956-P
Abstract: Introduction and Objective: To assess the impact of early use of open-source automated insulin delivery (OS-AID) systems (start <6 months after diagnosis) with the implementation of standard initiation protocol among people with type 1 diabetes (T1D).Methods: T1D people who initiated OS-AID within 6 months of diagnosis were recruited. Initiation protocol was then implemented by a community team of trained healthcare providers/educators and technology experts during the first month. Education modules included: 1) general knowledge of diabetes and OS-AID; 2) in-person training and online videos refreshment; 3) frequent education on system onboarding and troubleshooting. Key glycemic outcomes prior and after OS-AID use were analyzed.Results: A total of 70 T1D (female, 62.9%) were included, consisting of 39 children and 31 adults. Median age and diabetic duration were 14.8 (9.2,33.8) years and 1.4 (0.7,3.4) months. Before initiation, HbA1c was 8.6 (6.80,11.35) % with 77.1% not achieving goals of <7%. Since initiating for the first month, mean TIR was 83.9±8.0% with the majority (95.7%, 67/70) achieving TIR>70%, followed by time below range 70 mg/dL (TBR70) of 2.5 (1.4,3.8) %. After 3 months, both TIR and TBR70 remained similar of 83.8±8.3% and 3.4 (1.8,4.1) % (P>0.05). Additionally, available HbA1c (n=43) also significantly improved by 2.6% from 9.1±3.0% to 6.5±1.1% (P<0.01). For those who had used for 6 months (n=46) and up to 12 months (n=35), 87.0% and 85.7% still achieved TIR>70% without increased TBR70.Conclusion: Evident glycemic benefits during 3 months were observed after the early use of OS-AID systems with the implementation of standard education among recently-diagnosed people with T1DM. Long-term benefits need further investigation.DisclosureY. Ni: None. Y. Zhou: None. M. Lei: None. Z. Lin: None. C. Wang: None. X. Yang: None. D. Yang: None. W. Xu: None. J. Yan: None.FundingNoncommunicable Chronic Diseases-National Science and Technology Major Project (2023ZD0508200, 2023ZD0508203)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-956-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 957-P: Impact of Bolus Timing on Glucose Control
-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 957-P
Abstract: Introduction and Objective: Achieving optimal postprandial glucose control is a primary goal in managing type 1 diabetes. While insulin delivery prior to meals is recommended for tighter glucose control, many individuals do not adhere to this practice for various reasons. Meal announcements in conjunction with Advanced Hybrid Closed Loop (AHCL) systems play a pivotal role in determining post-meal glucose excursions. This study evaluated the impact of meal bolus timing with an AHCL system by assessing the effect of different bolus schedules on postprandial glucose levels following a medium-sized meal.Methods: A group of thirteen people with type 1 diabetes, aged 42.8±13.6 years, with a baseline hemoglobin A1c of 6.9±0.67%, participated in this study. Participants completed meal tests representing four bolus timing strategies: administration ten minutes before the meal, delivery at meal onset, reduced bolus by 50% delivered thirty minutes after the meal, and reduced bolus by 50% delivered sixty minutes after the meal.Results: The study revealed that bolusing at meal onset yielded comparable Time in Range (TIR) compared to the ten-minute pre-meal bolus approach (82.2% vs. 77.4%, p=0.5), while significantly reducing time spent in hypoglycemia (p=0.016).Conclusion: These findings underscore the potential of AHCL systems utilizing real-time sensor glucose measurements to eliminate pre-meal bolusing requirements, thereby enhancing postprandial glycemic control and reducing the management burden for people with type 1 diabetes. This research illuminates innovative approaches to optimize glucose management.Disclosure M. Laron Hirsh: Consultant; Medtronic. A. Benedetti: None. A. Roy: Employee; Metronics. B. Grosman: Employee; Medtronic. O. Cohen: Employee; Medtronic. A. Tirosh: Advisory Panel; Abbott. Speaker's Bureau; AstraZeneca, Eli Lilly and Company. Advisory Panel; Sanofi. Research Support; Medtronic. Advisory Panel; Novo Nordisk A/S. Consultant; Radella Pharma, Dreamed Diabetes.FundingMedtronic
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-957-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 958-P: Impact of Insulin Therapy Technology on Health-Related Quality of
Life in Adults with Type 1 Diabetes—A Health Utility Study of Five Forms
of Therapy-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 958-P
Abstract: Introduction and Objective: Insulin therapy for type 1 diabetes (T1D) has different burdens and impacts users daily living differently, dependent on the method used. This study aimed to quantify differences in health-related quality of life (HRQoL) for people living with T1D using 5 different insulin-delivery modalities by generating health utility estimates.Methods: Health state vignettes were developed through interviews with people with T1D and a literature review, validated by experts. These described the lived experiences of using multiple daily injections (MDI), tubed and tubeless insulin pump therapy (IPT), and tubed and tubeless automated insulin delivery (AID), all alongside continuous glucose monitoring. Time-trade-off methodology was then employed to elicit utility values for the health states on a scale between 1 and 0, where higher is better HRQoL, with members of the general public from the UK.Results: The demographics of participants (N=110) were representative of the UK general population for age, gender, education, employment, region. From lowest to highest, utility values (mean ±SD) were tubed IPT (0.73 ±0.23), MDI (0.77 ±0.20), tubeless IPT (0.81 ±0.18), tubed AID (0.82 ±0.17), and tubeless AID (0.91 ±0.13). The increase of tubeless versus tubed IPT (+0.082), and tubeless versus tubed AID (+0.086), was consistent (both p<0.05). The utility increase of AID versus IPT for tubeless pumps and AID versus IPT for tubed pumps was also consistent, +0.10 and +0.096 respectively (both p<0.05). The increase between tubed IPT to tubeless AID (+0.18, p<0.05) matched the sum of the increase for AID versus IPT therapies, plus the increase with tubeless versus tubed pump therapies.Conclusion: Tubeless AID was associated with a significantly higher health utility in T1D, indicating improved HRQoL for users. Both AID capability and tubeless pump design appear to contribute to the appraised differences with other technologies.Disclosure J. Elliott: Speaker's Bureau; Abbott. Research Support; Dexcom, Inc. Advisory Panel; Dexcom, Inc. Speaker's Bureau; Dexcom, Inc., Boehringer-Ingelheim, Eli Lilly and Company. Advisory Panel; Glooko, Inc. Speaker's Bureau; Insulet Corporation. Advisory Panel; Roche Diabetes Care. Speaker's Bureau; Sanofi. Advisory Panel; Ypsomed AG. C.D. Hopley: Employee; Insulet Corporation. Stock/Shareholder; Becton, Dickinson and Company, embecta, Insulet Corporation. M. Tomas: Employee; Insulet Corporation, Janssen Pharmaceuticals, Inc. M. Littlewood: Employee; Insulet Corporation. Stock/Shareholder; Abbott.FundingThis study was funded by Insulet Corp
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-958-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 959-P: Effective Utilization of Advanced Devices for Elderly People to
Safely Continue Self-Administration of Insulin-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 959-P
Abstract: Introduction and Objective: Elderly patients often struggle with insulin (IN) self-injection. For those that require basal-bolus therapy, safe self-injection is challenging without family support, often necessitating institutional care. To reduce family burden, advanced devices like smart pens (SPs) were introduced. This report describes four cases.Methods: The SP was introduced to four elderly patients undergoing insulin therapy, and a before-and-after analysis was conducted.Results: Case 1: 86-year-old man with T1DM (living alone): SP revealed missed and duplicate injections. With log checking by family during visits, errors decreased and self-injection continued.Case 2: 86-year-old woman with insulin-dependent T2DM (living with family): SP detected errors leading to a dementia diagnosis. Family support continued after identifying hyperglycemia and hypoglycemia.Case 3: 74-year-old woman with T1DM: SP revealed injection mistakes despite no dementia. Family support improved following device introduction.Case 4: 83-year-old man with T2DM: SP identified frequent missed injections, prompting the patient's wife to take over injection management. Discussion and Challenges: SPs enhance self-injection safety and support family involvement. They highlight injection errors and improve intervention timing. However, their use is limited for patients who are unfamiliar with digital tools, requiring further innovation.Conclusion: Smart pens reduce the burden on family and improve self-injection safety in elderly patients. They also facilitate addressing dementia and rethinking family support systems. Future efforts should focus on making devices more accessible and expanding societal support.DisclosureH. Tsuru: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-959-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 960-P: Real-World Clinical Outcomes of the Omnipod 5 Hybrid Closed-Loop
System in Type 1 Diabetes—Findings from a Major UK Center-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 960-P
Abstract: Introduction and Objective: Omnipod 5 (OP5) is an innovative, tubeless, automated insulin delivery system introduced in the UK in 2023. We assessed real-world clinical outcomes in individuals with type 1 diabetes (T1D) following OP5 initiation at Sheffield Teaching Hospitals.Methods: We conducted a single-center, retrospective study of people with T1D using OP5. Case records were reviewed for baseline characteristics, tolerability, and anthropometric data. Glycemic metrics were retrieved from continuous glucose monitoring cloud-based applications. Two-tailed, paired t-tests were used to analyze glycemic metrics at 3 months, with results presented as median (IQR) or mean (95% CI).Results: One hundred adults were included (63% female). Median age was 28 years (23.0-32.8), BMI 25.5 kg/m² (22.3-30.0) and diabetes duration 16 years (9.0-24.8). Over half (52%) transitioned from multiple daily injections. At 3 months (n=96), mean time >250.2 mg/dL decreased from 28.8 to 18.0% (7.0-14.5, p<0.001), time in range 70-180 mg/dL increased from 43.0 to 56.7% (9.5-17.8, p<0.001) and time <54mg/dL reduced from 0.7 to 0.4% (0.1-0.5, p=0.04). Coefficient of variation increased from 35.4 to 36.0% (0.7-2.0, p=0.421, n=93) and mean weight 74.4 to 76.2 kg (1.2-2.7, p<0.001, n=56). Median time in automated mode was 97% (80.5-100, n=97). HbA1c fell from 8.4 to 7.6% (2.7-3.2, p<0.001, n=88), with a median follow-up of 225 days (122-319). Six individuals discontinued OP5 use, with adverse events comprising problematic hypoglycemia (n=9), skin site reactions (n=9), recurrent pod failure (n=6) and alarm fatigue (n=4). No hospital attendances due to severe hypoglycemia were recorded.Conclusion: OP5 use significantly improves glycemic control within 3 months, yielding meaningful reductions in HbA1c at 6 months and promising real-world tolerability. Future research should assess the durability of these outcomes and user experience to optimize effectiveness.DisclosureE. McNally: None. I. Goodman: None. S.A. Berry: Research Support; Tandem Diabetes Care, Inc. J. Maliekkal: None. D. Saeed: None. A. Iqbal: Speaker's Bureau; Lilly Diabetes. Research Support; Abbott, Dexcom, Inc. Speaker's Bureau; AstraZeneca, Boehringer-Ingelheim. Research Support; Tandem Diabetes Care, Inc. J. Elliott: Speaker's Bureau; Abbott. Research Support; Dexcom, Inc. Advisory Panel; Dexcom, Inc. Speaker's Bureau; Dexcom, Inc., Boehringer-Ingelheim, Eli Lilly and Company. Advisory Panel; Glooko, Inc. Speaker's Bureau; Insulet Corporation. Advisory Panel; Roche Diabetes Care. Speaker's Bureau; Sanofi. Advisory Panel; Ypsomed AG.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-960-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 961-P: Efficacy and Safety of Inhaled vs. Subcutaneous Insulin—A
Meta-analysis-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 961-P
Abstract: Introduction and Objective: Inhaled insulin offers a non-invasive, patient-friendly alternative to SQ insulin. This meta-analysis was carried out to determine the efficacy, side effects, and clinical applicability of inhaled insulin in both Type 1 and Type 2 DM.Methods: RCTs were obtained from PubMed, Cochrane, Embase, and WOS databases comparing inhaled insulin with SQ insulin in Type 1 or Type 2 DM patients. Trials involving animals, crossover designs, comparisons of inhaled insulin with oral anti-diabetic drugs, and those lasting less than 12 weeks were excluded. Data on HbA1c, fasting blood glucose, body weight, and pulmonary function were analysed using RevMan 5.4 with p < 0.05 considered statistically significant and a 95% confidence interval [95% CI].Results: Analysis of 19 RCTs revealed that a non-significant number of patients using inhaled insulin achieved a HbA1c <7% with a significant reduction in weight and fasting blood glucose (Mean difference (MD): -22.12 [-29.29, -14.95]) when compared to SQ insulin. However, inhaled insulin was associated with a significant decrease in DLCO (MD: -0.44 [-0.78, -0.11]) and FEV1 (MD: -0.03 [-0.04, -0.01]).Conclusion: Inhaled insulin offers a promising alternative to SQ insulin, with comparable glycemic control, improved fasting glucose and weight management. However, further studies are needed to assess its impact on pulmonary function and enhance its safety profile.DisclosureA. Awan: None. A. Ahmad: None. W. Sultan: None. H. Saleem: None. A. Khan: None. S. Ali: None. M. Daniyal: None. M. Rahman: None. M. Khakwani: None.
PubDate: Fri, 13 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-961-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 962-P: Evaluating Type 1 Diabetes (T1D) Care across All Ages with the
Automated Insulin Delivery Adaptive Network (AIDANET) System in Fully
Closed Loop (FCL)-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 962-P
Abstract: Introduction and Objective: The AIDANET system uses an adaptive algorithm that removes the need for meal announcement. This may help address age-specific obstacles in T1D, as older people may struggle with diabetes technology, while younger people face hormonal changes and inconsistencies in premeal dosing. Given these challenges, the glycemic outcomes of the AIDANET system in FCL were evaluated across three age groups.Methods: This study was a randomized, crossover trial evaluating the safety and feasibility of the AIDANET system. Sensor glucose data was collected from: Adolescents (14-17 y), Young Adults (18-25 y), and Adults (26-60 y). Participants used the system in FCL during a supervised hotel setting for 5 days followed by a 7-day home period. Each cohort underwent a 14-day usual care (UC) period.Results: The Adult cohort had a significant increase in TIR and TITR by 8.0% and 9.0%, respectively (Table). TAR180 also significantly decreased by 8.1%. Young Adults exhibited non-inferior results for TBR54 between UC and FCL. For Adolescents, TIR, TITR, TAR180, TAR250, and TBR54 values were non-inferior between UC and FCL.Conclusion: Adults significantly improved their glycemic outcomes with short-term use of the FCL system. Future research with long-term wear may be needed to give the system more time to adapt to the unique needs of all age groups.DisclosureJ.Y. Hosseinipour: None. G.P. Forlenza: Advisory Panel; Medtronic. Research Support; Medtronic, Dexcom, Inc. Consultant; Dexcom, Inc. Research Support; Insulet Corporation. Consultant; Insulet Corporation. Research Support; Tandem Diabetes Care, Inc. Advisory Panel; Tandem Diabetes Care, Inc. Research Support; Abbott. Advisory Panel; Sequel Med Tech. L. Ekhlaspour: Other Relationship; Medtronic. Advisory Panel; Abbott, Medtronic. Consultant; Jaeb Center for Health Research. Research Support; MannKind Corporation. Speaker's Bureau; Insulet Corporation. Advisory Panel; Sequel Med Tech. Other Relationship; Tandem Diabetes Care, Inc. Research Support; Abbott. Other Relationship; Sanofi. J.C. Wong: Research Support; Abbott, Dexcom, Inc., Tandem Diabetes Care, Inc. E. Escobar: None. E.C. Cobry: Advisory Panel; Dexcom, Inc. M. Moscoso-Vasquez: Other Relationship; Dexcom, Inc. Research Support; Tandem Diabetes Care, Inc, National Institute of Diabetes and Digestive and Kidney Diseases. S.A. Brown: Research Support; Dexcom, Inc., Insulet Corporation, Tandem Diabetes Care, Inc, Tolerion, Roche Diabetes Care. Other Relationship; MannKind Corporation.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-962-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 963-P: Use of a Fully Closed Loop (FCL) System Improves Glycemic Outcomes
-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 963-P
Abstract: Introduction and Objective: The Automated Insulin Delivery as an Adaptive NETwork FCL system may improve glycemic outcomes while reducing burden by eliminating meal announcement. Continuous glucose monitoring (CGM) metrics were compared in users with T1D using the FCL system who had high or low baseline A1c.Methods: Youth and adults with T1D were enrolled in a randomized crossover study with a supervised hotel stay followed by 7 days of home use in FCL compared to usual care (UC). Half were selected with baseline A1c <8% (low A1c) and half with baseline A1c 8-12% (high A1c). CGM metrics were analyzed by A1c subgroups.Results: Thirty-four participants (25.4±12.6 years, 62% female) completed the study. Those with high A1c showed non-inferiority of FCL vs UC on all CGM metrics and lower mean glucose with FCL (Table). Time in 70-180 mg/dL, in 70-140 mg/dL, >180 mg/dL, and >250 mg/dL showed significant improvement with FCL in the high A1c group. Those with low A1c had statistically equivalent mean glucose and time <54 mg/dL with FCL vs UC; other CGM metrics were inconclusive.Conclusion: Use of a FCL system results in significant improvement in CGM metrics in those with less optimal glycemic management, while not deteriorating control in those with more optimal A1c. FCL systems have the potential to make the most impact in those with challenges in meeting glycemic goals.Disclosure J.C. Wong: Research Support; Abbott, Dexcom, Inc., Tandem Diabetes Care, Inc. M. Moscoso-Vasquez: Other Relationship; Dexcom, Inc. Research Support; Tandem Diabetes Care, Inc, National Institute of Diabetes and Digestive and Kidney Diseases. L. Ekhlaspour: Other Relationship; Medtronic. Advisory Panel; Abbott, Medtronic. Consultant; Jaeb Center for Health Research. Research Support; MannKind Corporation. Speaker's Bureau; Insulet Corporation. Advisory Panel; Sequel Med Tech. Other Relationship; Tandem Diabetes Care, Inc. Research Support; Abbott. Other Relationship; Sanofi. S.A. Brown: Research Support; Dexcom, Inc., Insulet Corporation, Tandem Diabetes Care, Inc, Tolerion, Roche Diabetes Care. Other Relationship; MannKind Corporation. M.D. Breton: Speaker's Bureau; Sinocare Inc, Tandem Diabetes Care, Inc. Consultant; Roche Diabetes Care, Boydsense. G.P. Forlenza: Advisory Panel; Medtronic. Research Support; Medtronic, Dexcom, Inc. Consultant; Dexcom, Inc. Research Support; Insulet Corporation. Consultant; Insulet Corporation. Research Support; Tandem Diabetes Care, Inc. Advisory Panel; Tandem Diabetes Care, Inc. Research Support; Abbott. Advisory Panel; Sequel Med Tech.FundingBreakthrough T1D
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-963-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 964-P: Reducing Discordance between GMI and A1C Using AI
-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 964-P
Abstract: Introduction and Objective: GMI is increasingly relied upon in clinical practice as a surrogate for A1c. However absolute discordance >0.5% is common between GMI & A1c. GMI also tends to overestimate at lower A1c (<7.0) and underestimate at higher A1c (>8.0). BCDiabetes, a public Canadian clinic, has permissioned access to anonymized client data: more than 3,000 of its clients use CGM 365 days per year & have A1c measured intermittently.Methods: Prior to 2024-Sep-30, 2922 pairs of 90 days of CGM data & A1c values measured on the 90th day of CGM from 1508 patients, were used to build two machine learning (ML) models designed to minimize discordance in GMI vs A1c. Post 2024-Sep-30, 270 analogous pairs from 268 different clients with 90 days of CGM data & A1c values, were used to test the two ML models against the Bergenstal equation (2018) & an analogous linear regression equation developed with the same training data.Results: The Bergenstal equation showed a mean absolute difference of 0.43, with 37% of participants demonstrating discordance; the BCDiabetes equation was minimally higher than Bergenstal. Both ML models outperformed the Bergenstal equation with ML Model 2 reducing the relative risk of discordance compared to Bergenstal by 18% (Figure 1).Conclusion: AI modeling of GMI vs A1c promises to reduce discordance. With validation of such models and their adoption into clinical practice, GMI will become a more reliable indicator of A1c.DisclosureA. Alqahtani: None. G. Netto Flores Cruz: Employee; BiomeHub. N. Khan: None. K. Hawke: None. T. Elliott: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-964-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 965-P: Enhancing Diabetes Device Performance—Predictive Maintenance
through Smart Sensor Integration-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 965-P
Abstract: Introduction and Objective: Wearable devices like continuous glucose monitors improve diabetes management, but sensor wear, environmental factors, and calibration errors affect performance. This study explores how predictive maintenance with smart sensors can reduce failures, extend lifespan, and ensure accuracy.Methods: A system was developed to monitor temperature, battery health, and calibration with smart sensors. Correlation analysis identified key performance factors. Machine learning models predicted issues for timely intervention. Explainable AI techniques, including SHapley Additive Explanations, were used to interpret model outputs. The system was compared to devices without predictive maintenance.Results: Analysis revealed a strong relationship between calibration errors and downtime (r = 0.82, p < 0.01). Predictive maintenance reduced device failures by 30%, increased uptime by 40%, and cut costs by 50%. Early detection addressed 90% of potential failures before impacting performance. These improvements led to higher reliability, optimized usage, and reduced unplanned malfunctions, extending device lifespans.Conclusion: Smart sensor-based predictive maintenance enhances device reliability, reduces costs, and improves quality of life. This approach offers a sustainable, patient-focused solution for managing medical devices.DisclosureS.I. Hasan: None. M. Hossan: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-965-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 966-P: Real-World Impact of AI-driven CGM Platform on Glycemic Status in
Type 2 Diabetes—A Retrospective Study-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 966-P
Abstract: Introduction and Objective: Artificial intelligence (AI)-powered diabetes management platforms integrating CGM technology represent a promising advancement in healthcare. This study evaluates the effectiveness of AI-integrated SDRMP platform in improving glycemic control.Methods: A 100-day retrospective study of 1752 individuals (1357 male, 395 female; mean age 50.22±11.33 years) assessed the impact of personalized interventions on glycemic control. Parameters including Time in Range (TIR), Time Below Range (TBR), and Time Above Range (TAR) were assessed using CGM, along with HbA1c, fasting blood sugar (FBS), and weight. These measurements were taken at baseline and re-evaluated after an average of 100 days to monitor improvements and track progress.Results: Participants demonstrated significant changes in TBR and TAR, decreasing from 7.46±10.9% and 49.89±29.6% to 5.34±11.1% (p<0.001) and 45.33±30.57% (p<0.01), respectively. Conversely, TIR exhibited an increase from 45.74±26.71% to 49.31±27.5% (p<0.05). During this period, the participant further experienced reductions in HbA1c, FBS, and weight from 8.75±1.71%, 162.55±58.20 mg/dL and 76.60±14.6 kg, to 7.50±1.2%, 132.19±42.19 mg/dL and 75.11±14.4 kg, respectively, all achieving statistical significance of p<0.001.Conclusion: Daily CGM trend-associated insights with intervention led to significant improvements in glycemic control, evident in substantial improvements in TIR, TBR, TAR, HbA1c, FBS, and weight, highlighting its effectiveness in optimizing metabolic outcomes and diabetes management.DisclosureS. Kumar: None. A.M. Raymond: None. A. Sequeira: None. J.J. J: None. C. Goyal Mehra: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-966-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 967-P: Decipher Y-Health Platform—Impact of Continuous Glucose
Monitoring vs. Self-Monitored Blood Glucose on Glycemic Parameters and
Behaviour Change through 12-Week Metabolic Review Program-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 967-P
Abstract: Introduction and Objective: Y Health is an Artificial Intelligence(AI) empowered digital health platform designed to improve metabolic health parameters. Recent advances in continuous glucose monitoring(CGM) have created opportunities for scalable metabolic health interventions, yet their clinical validation remains limited. This randomized controlled trial aimed to evaluate CGM metrics in optimizing glycemia parameters and behavioral outcomes in healthy Asian-Indian adults.Methods: Healthy Adults (N=1123, age 25-65years, 641women and 482men) with BMI ≥25 kg/m² and HbA1c 5.7-6.5% were randomized to intervention (n=562, CGM monitoring) or control (n=561, SMBG) groups for 12 weeks. Sample size provided 90% power to detect 10% TIR difference (α=0.05). Using Dexcom G6 (MARD 9.8%), we analyzed: Time in Range (70-180 mg/dL), Coefficient of Variation (CV%), and Mean Amplitude of Glycemic Excursions (MAGE). Secondary outcomes included HbA1c and behavioral metrics. Statistical analysis used mixed-effects models with Bonferroni correction.Results: The intervention group demonstrated significant improvements vs. controls: TIR increased from 65% to 83% (Δ=18.0%, 95% CI [15.2, 20.8], p<0.001)CV% decreased from 36% to 25% (p<0.001)MAGE reduced from 94 mg/dL to 65 mg/dL (p<0.001)Post-meal glucose excursions decreased 47% (p<0.001)HbA1c reduction: 0.48% (95% CI [0.42, 0.54]) Behavioral adaptations showed:Meal timing optimization: 85% adherenceExercise-related glucose variability-: 58% improvementNocturnal glucose variability: 62% improvement. No severe hypoglycemic events occurred.Conclusion: CGM-based monitoring demonstrates robust efficacy in optimizing metabolic health outcomes, with clinically significant improvements in glycemic control and behavioral adaptation. These findings support CGM's clinical validity for scalable metabolic health managementDisclosure B.M. Makkar: Speaker's Bureau; Abbott Diagnostics, Abbott Nutrition, Eli Lilly and Company, Novo Nordisk. Advisory Panel; Novo Nordisk. Speaker's Bureau; Sanofi. Advisory Panel; Lupin Pharmaceuticals, Inc, USV Private Limited. Speaker's Bureau; USV Private Limited, Sun Pharmaceutical Industries Ltd. V. Solanki: None. S.K. Singla: None. R. Chhabra: None. A.A. Shaikh: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-967-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 969-P: Bridging the Digital Divide—A Scoping Review of Barriers and
Facilitators to Technology Use in Underrepresented Racial and Ethnic
Adolescents and Young Adults with Type 1 Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 969-P
Abstract: Introduction and Objective: Underrepresented racial and ethnic groups with type 1 diabetes (T1D) in the United States are less likely to use technologies (e.g., insulin pumps, continuous glucose monitors), and this may be associated with poorer outcomes. This scoping review assessed barriers and facilitators to technology use among these populations.Methods: A systematic database search was conducted in PubMed, CINAHL, EMBASE, PsycINFO, Scopus, and Web of Science from inception through October 2024. The inclusion criteria were primary quantitative or qualitative studies published in English that addressed diabetes technology and targeted adolescents and young adults (12-36 years) with T1D from underrepresented racial and ethnic groups. Two independent reviewers identified articles for inclusion, extracted data, and assessed quality with the Mixed Methods Appraisal Tool. The Social Ecological Model guided the thematic coding and deductive synthesis.Results: Out of 1,704 references, 9 articles met the inclusion criteria. The most prevalent barriers to technology use were financial limitations, inadequate knowledge, limited patient-provider communication, insurance coverage restrictions, and lack of peer and family support. There were also cultural (e.g., skepticism, misconceptions) and psychosocial barriers (e.g., fear of change, stigma associated with visible devices, systemic racism). Facilitators included increased familiarity and peer support, positive experiences and involvement, effective communication, community-based education initiatives, insurance, and systemic advocacy.Conclusion: The review highlights persistent inequities in diabetes technology use among minority groups with T1D. However, several factors that facilitate technology use have been identified and may drive the development of targeted interventions to address disparate outcomes.DisclosureE. Peprah Osei: None. S.M. Campos: None. P. Martyn-Nemeth: Stock/Shareholder; Pfizer Inc.FundingUniversity of Illinois Chicago, College of Nursing, Catalyst Award
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-969-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 970-P: Perspectives from Caregivers of Older Adults with Insulin-Treated
Diabetes Regarding Remote CGM Education and Support-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 970-P
Abstract: Introduction and Objective: Despite proven benefits of continuous glucose monitoring (CGM) in older adults with insulin-treated diabetes, adoption remains suboptimal. While caregivers are integral to technology adoption in this population, their experiences are poorly characterized. The REST (Readiness, Education and Sustainability for CGM Technology adoption) study facilitates CGM adoption and sustained use in older adults through virtual education and support. We examined caregivers’ views in REST.Methods: Semi-structured interviews were conducted with caregivers supporting older adults (≥65 years) with insulin-treated diabetes during CGM adoption through remote education. Interviews were analyzed using grounded theory methodology by independent coders using qualitative analysis software (MaxQDA).Results: Ten caregivers were interviewed (90% family member, 10% paid caregiver). All reported positive experiences with CGM, needing 2-4 weeks to adapt to this new technology. Analysis revealed 4 key themes: (1) technology use (60% reporting adoption challenges with alarm customization and socialization impact; 50% reporting sleep disruption); (2) safety monitoring (90% reported improved ability to track glucose patterns with perceived safety benefits during participants’ physical activity and sleep), (3) behavioral changes (70% noting perceived improved dietary awareness; 60% reporting perceived greater engagement in diabetes self-management by participants), and (4) care relationships (40% reported perceived increase in participant independence and decrease in caregiver stress).Conclusion: These data show that CGM adoption through remote education with caregiver engagement yields high satisfaction while improving perception of safety, care behaviors and relationships. Findings suggest benefits of CGM use for the caregivers of older adults with diabetes on complex insulin regimens, providing further support for the widespread use of this technology.DisclosureA. Adam: None. M. Savory: None. C. Slyne: None. H. Brabant: None. J.D. Bulger: None. N. Krakoff: None. S. Kasetti: None. C. Mahoney: None. M. Munshi: Advisory Panel; Abbott, Medtronic. Research Support; Dexcom, Inc. Advisory Panel; Sanofi. R.S. Weinstock: Research Support; Amgen Inc, Eli Lilly and Company, Tandem Diabetes Care, Inc, Diasome Pharmaceuticals, Insulet Corporation, MannKind Corporation, Dexcom, Inc. E. Toschi: Consultant; Vertex Pharmaceuticals Incorporated, Sequel Med Tech. Research Support; Dexcom, Inc.FundingThis work is supported by funding from The Leona M. and Harry B. Helmsley Charitable Trust
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-970-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 971-P: The Application of Continuous Glucose Monitoring System as an
Educational Tool in Newly Diagnosed Patients with Type 2
Diabetes—Preliminary Results from a Single-Center RCT-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 971-P
Abstract: Introduction and Objective: In recent years convincing evidence has emerged that the use of CGM can be treated as a therapeutic method in patients with T1DM and T2DM treated intensively with insulin. The objective of the study is to examine the impact of the short-time use of the Freestyle Libre 2 CGM system in newly diagnosed T2DM on glycemic control and quality of life.Methods: We have initiated an unblinded, randomized, controlled trial. The study scheme is shown in Figure 1. The primary end-point is a change in the HbA1c% level between the study groups after 1 year. Secondary outcomes are changes in QoL assessed in psychological questionnaires.Results: To date, we have randomized 31 individuals with T2DM (16 in the intervention group, 15 in the control group). Currently, the study was completed by 20 men and 11 women. At the study entry, the mean age was 48.61 ±10.70 years, BMI 32.23 ±5.31 kg/m2, HbA1c 6.37% ±1.21%. At month 12 of the study, the HbA1c% level was 6.02% ± 0.57 and 5.97% ± 0.92 (p=0.852), in the intervention and control group, respectively. There was no difference in the secondary outcomes.Conclusion: The initial results of this RCT showed no evidence that the short-time use of the CGM system in newly diagnosed T2DM affected glycemic control after the intervention. However, in both study arms we observed excellent glycemic control.Disclosure M. Plonka-Stepien: Other Relationship; Novo Nordisk. K.M. Cyranka: Speaker's Bureau; Abbott. Research Support; Medtronic. Other Relationship; Novo Nordisk, Dexcom, Inc. Research Support; Sanofi. A. Drynda: None. M. Szymanowski: None. M. Kwiatkowska: None. M. Kania: Consultant; Novo Nordisk A/S. Other Relationship; Takeda Pharmaceutical Company. Consultant; PTC. M. Malecki: Speaker's Bureau; Novo Nordisk, Lilly Diabetes, Sanofi, Boehringer-Ingelheim, AstraZeneca, Berlin-Chemie AG. Advisory Panel; Abbott, Dexcom, Inc. Speaker's Bureau; Servier Laboratories. Other Relationship; Amryt Pharma.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-971-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 972-P: A Continuous Glucose Monitor–Derived Adjustment Factor Applied to
HbA1c—Implications for Improved Clinical Decision Making-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 972-P
Abstract: Introduction and Objective: Agreement between labHbA1c and average CGM readings via glucose management index is around 82%. We examined how much of the difference between the two can be linked to demographic/personal factors such as age/sex/weight. This might then provide an adjustment factor to improve clinical decisions on the level of glycaemia than labHbA1c alone.Methods: Expected HbA1c (E-HbA1c) was derived for T1D individuals from a regression between average glucose levels taken from CGM and compared with labHbA1c. The ratio of E-HbA1c over labHbA1c was then regressed against the patient characteristics including age/sex/BMI/T1D duration/smoking status/+oral adjunct. The results of this regression were applied to hypothetical patients of various sex/age/BMI to establish the E-HbA1c assuming a labHbA1c=48mmol/mol (6.5%).Results: 109 HbA1c values (average 62 mmol/mol)(7.8%) from 89 individuals (average age=47years, 50% males, BMI=28kg/m2) were analyzed (2,150-9,950 glucose readings/individual), with average 10.3 mmol/l (185 mg/dL). Multiple regression linking E-HbA1c/labHbA1c Ratio found only age/sex/BMI with sufficient significance p<0.001 and r2=0.20 with resulting equation: Ratio=1.236-0.0019xAge-0.0042xBMI-0.05Class Male (=1).Applying the ratio to labHBA1c=48mmol/mol (6.5%) (derived for a Female, Age=25, BMI=25 gives an E-HBA1c=52mmol/mol (6.9%) (under diagnosis on the basis of labHbA1c), while for a man age=80, BMI=40 gives an E-HbA1c=44.3mmol/mol (6.2%) (over diagnosis).Conclusion: We accept these readings were taken from T1D. The link between RBC and BG varies due to many factors. This difference to the original labHbA1c result is sufficient for different clinical decisions to be made in the context both of screening and monitoring when E-HbA1c vs labHbA1c is applied. CGM might allow for individualized HbA1c targets.DisclosureA.H. Heald: None. M. Stedman: None. E.B. Jude: Research Support; Abbott Diagnostics. Speaker's Bureau; AstraZeneca, A. Menarini Diagnostics, Novo Nordisk. Research Support; Sanofi. B. Mankovsky: Speaker's Bureau; Bayer Pharmaceuticals, Inc, AstraZeneca, Novo Nordisk, Boehringer-Ingelheim, Sanofi, Novartis Pharmaceuticals Corporation. A.N. Paisley: None. H.H. Habte-Asres: None. J.M. Gibson: None. M.B. Whyte: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-972-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 973-P: Initiation of Dexcom CGM Is Associated with Improved Renal Outcomes
in Adults with Chronic Kidney Disease (CKD) on Insulin Therapy-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 973-P
Abstract: Introduction and Objective: A recent consensus statement advocated for wider use of CGM in people with CKD and emphasized the need for additional research. This study evaluated the impact of initiating Dexcom CGM on the progression of CKD in adults using insulin.Methods: A retrospective analysis using Truveta-provided de-identified EMR data was conducted. We identified insulin-using adults with T1D or T2D with eGFR of 15-89 mL/min/1.73m2 who initiated Dexcom G-series CGM between 08/01/2018 and 12/31/2023 (index date=first CGM claim). The control group included CGM non-users, assigned an index date based on their first outpatient encounter with an eGFR. Exclusion criteria included cirrhosis, pregnancy, prior CGM use, anemia, dialysis, renal transplant, and Elixhauser score ≥10. CKD progression was defined as an increase in CKD stage. Change in eGFR was assessed as the difference between baseline eGFR (within 12 months of index date) and 3 years. Multivariate linear regression estimated the association between the initiation of Dexcom CGM and change in eGFR. Covariates included demographics, baseline eGFR and A1c, diabetes type, history of hypertension or micro/macrovascular complications, and use of SGLT2, GLP-1 RA or RAASi therapy.Results: A total of 65,839 adults with CKD on insulin therapy were identified (633 Dexcom CGM users; 65,206 CGM non-users). At 3 years, 24.8% of Dexcom CGM users experienced CKD progression vs. 34.8% of CGM non-users (p<0.01). Among CGM non-users, the 3 year change in eGFR was -8.58 mL/min/1.73m². After adjustments, initiating Dexcom CGM was associated with an improvement of 1.21 mL/min/1.73m2, which is a 14% reduction in the rate of progression (p<0.05).Conclusion: Our findings show that using Dexcom CGM is associated with a significant reduction in kidney disease progression among adults with CKD using insulin. This evidence supports the recent consensus statement supporting CGM use in individuals with CKD.Disclosure K. Hannah: Employee; Dexcom, Inc. C. Chen: Employee; Dexcom, Inc. M. Tressler: Employee; Dexcom, Inc. J. Castle: Employee; Dexcom, Inc. Stock/Shareholder; Dexcom, Inc. G.J. Norman: Employee; Dexcom, Inc.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-973-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 974-P: Glucose Data Extraction from Continuous Glucose Monitoring
Documents Using Natural Language Processing-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 974-P
Abstract: Introduction and Objective: Continuous glucose monitoring (CGM) is growingly used in diabetes clinical and research settings; however, manually extracting the valuable data (e.g., time above, in, or below range) from CGM reports is time-consuming. Natural language processing (NLP) is an automatic approach to extracting data from unstructured sources (e.g., images), but its application in CGM remains unexplored. We aimed to evaluate the accuracy of extracting CGM data using NLP. This work is crucial to automatically obtaining valuable data from CGM reports.Methods: We analyzed 23,319 CGM reports from the EHR at NYU Langone Health 2012-2022. The steps of our algorithm pipeline consist of: 1) perform optical character recognition (OCR) to obtain textual data; 2) determine the type of document based on keywords in OCR results; 3) extract variables of interest from the text according to the specific types of documents; 4) save the extracted information into a CSV file. Two experts in using CGM for research and clinical practice conducted an independent manual review of 1% of the documents. We calculated accuracy (correct extraction of CGM data ) by comparing the algorithm against manual review.Results: Among the 23,319 documents analyzed, 36.8% were Freestyle Libre and 63.2% Dexcom. In our preliminary experiments, we randomly selected 10 reports and tested PaddleOCR and easyOCR for information recognition. We finally chose PaddleOCR as it demonstrated a text block recognition accuracy of 99.64% (546/548), which significantly outperformed easyOCR that achieved only 94.89% (520/548). For information extraction, the agreement in evaluating Libre results between two experts was 99.93%. When comparing algorithm accuracy with manual review, the accuracy for Libre was 99.87%, and for Dexcom was 100.00%.Conclusion: Using an NLP approach to extract value glucose data from CGM reports is feasible and accurate, which is useful for clinical practice and diabetes research.DisclosureY. Zheng: None. Y. Song: None. E. Iturrate: None. B. Wu: None. S. Zweig: None. S.B. Johnson: None.FundingNew York Regional Center for Diabetes Translation Research (NY-CDTR) Pilot and Feasibility (P&F) Program Funding (P30DK111022-08 )
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-974-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 975-P: Housing Status and Glucose Variability in Type 2 Diabetes
-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 975-P
Abstract: Introduction and Objective: Housing instability is a key social determinant of health. While the link between housing and diabetes outcomes, such as HbA1c, is gaining attention, limited data exist on the relationship between housing status and glucose variability (GV) measured by continuous glucose monitoring (CGM).Methods: Participants (n=99) with type 2 diabetes completed demographic surveys. The following GV parameters over a 14-day period were assessed using CGM: coefficient of variation (CV) for glucose (target CV ≤36%), Time in Range (TIR, 70-180 mg/dL, target TIR ≥70%), J-Index (target 10-20), and Time Below Range (TBR, target <4%). Analysis of Variance (ANOVA) with post-hoc comparison were performed.Results: About 60% were women with mean age of (M)±SD: 59.8±11.2 years (Non-Hispanic [NH]White, 72.7%; NH Black, 18.2%; NH Asian 3%). About 70% owned a house, 6% rented a house, 18% rented an apartment, and 6% had unstable housing. Individuals without stable housing had significantly greatest CV levels (34.00±8.34%), compared to those with homeownership (25.67±7.22%) (P=0.02). TIR differed significantly across housing status (P<0.01): individuals who owned a house had the highest TIR levels (83.04±16.38%), while those renting an apartment had the lowest (49.72±37.96%). The J-Index was also significantly lower for individuals who owned a house (29.17±15.46) compared to those renting a house (71.89±93.38) or renting an apartment (66.85±47.99)(P<0.01). Individuals without stable housing had significantly higher TBR (10.00±12.87%)(P<0.01), indicating more hypoglycemic exposures compared to individuals owning a house (3.12±4.80%), renting a house (1.67±1.37) or renting an apartment (1.06±2.21%).Conclusion: Homeownership was associated with greater TIR and lower J-Index.Individuals without stable housing experienced greater CV and lower TIR and increased TBR compared to those with stable housing. Addressing housing instability may be important to improve diabetes management.DisclosureS. Nam: None. M. Lee: None. R. Whittemore: None. G.I. Ash: Other Relationship; Calm.com. S. Jeon: None. A. Domínguez Navarro: None. S.A. Weinzimer: Research Support; Abbott.FundingNational Institutes of Health (NIH) (R01DK132069)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-975-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 976-P: Data Privacy and Trust Concerns among Adolescent and Young Adults
(AYAs) with T1D Using Hybrid-Closed Loop Systems-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 976-P
Abstract: Introduction and Objective: Existing hybrid-closed loop (HCL) systems use physiologically based control algorithms to regulate insulin delivery, but context-aware sensing technologies introduce potential to model cognitive/behavioral aspects that affect users’ glucose levels and self-management strategies. These novel inputs can improve the efficacy of HCLs but potentially introduce privacy and trust concerns given the personal nature of these data.Methods: Adolescents and young adults (n=15; 20.1y [15-24]; 26.7% M; 40% NHW) were interviewed to explore trust and privacy concerns around incorporating potential data inputs from smartphone sensors and cloud-based sources into their HCL systems. We asked in particular about concerns with sharing these additional data with stakeholders involved in their T1D management. Transcripts were iteratively analyzed, combining deductive coding based on ecological systems theory and inductive open-coding before performing axial coding to cluster codes into larger categories.Results: Participants reported few privacy concerns about use of their personal data and were willing to forgo privacy for benefits to themselves, their loved ones, or the diabetes community. However, trust—both in the efficacy of the HCL system and in others’ assessment of an individual’s T1D self-management practices—arose as a concern when considering willingness to incorporate additional personal data into these systems. Properties of data being shared, including the data’s relevancy, sensitivity, novelty, framing and granularity, and the nature of their relationships within their social and medical spheres interact to influence perceptions of trust.Conclusion: Adjustable levels of control are integral to patients’ experiences in managing T1D. Opportunities exist for tailoring HCL systems’ interfaces to reflect nuances in data sharing preferences, especially as the breadth of data that these systems use increases in the future.DisclosureZ. Fisher: None. T. Xu: None. E. Jost: Other Relationship; Tandem Diabetes Care, Inc. G.P. Forlenza: Advisory Panel; Medtronic. Research Support; Medtronic, Dexcom, Inc. Consultant; Dexcom, Inc. Research Support; Insulet Corporation. Consultant; Insulet Corporation. Research Support; Tandem Diabetes Care, Inc. Advisory Panel; Tandem Diabetes Care, Inc. Research Support; Abbott. Advisory Panel; Sequel Med Tech. S. Voida: None.FundingNational Institutes of Health (R01AT012288)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-976-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 977-P: Multisensing Implantable Automated Insulin Delivery
System—Expectations of Parents, People with Type 1 and Type 2 Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 977-P
Abstract: Introduction and Objective: A potential evolution of AID systems is the intraperitoneal route and consideration of ketones and lactate. The development of an implantable AID system with multi-metabolite sensing should consider the expectations of people with diabetes.Methods: In an online survey, parents of children with type 1 diabetes and adults with type 1 and type 2 diabetes were introduced to such a AID system. They were asked 1) how often they would still want to check the system, 2) the maximum number of daily input they may be required to make so that the AID is still perceived as unobtrusive, 3) how helpful and burdensome the constant access to lactate and ketones would be.Results: Data from 526 participants were analyzed (465 type 1, 44 type 2, 17 parents; all with CGM). Parents would check the AID 5.5±3.2 times/day, adults with type 1 diabetes 5.0±3.2 times and adults with type 2 diabetes 4.3±3.4 times (p=.12). The maximum daily user input was 4.1±2.5 for parents, 3.6±2.1 for type 1 and 3.0±1.7 for type 2 diabetes (p=.11). Perceived helpfulness and burden of lactate and ketone measurement was moderate, except for parents’ ratings of ketones (Figure; all p>.05).Conclusion: Perceptions towards an implantable AID system were comparable between the groups. A rather high amount of manual input would still be tolerated. More information on the helpfulness of lactate and ketones is needed.Disclosure D. Ehrmann: Advisory Panel; Dexcom, Inc. Speaker's Bureau; Dexcom, Inc. Consultant; Roche Diabetes Care. Speaker's Bureau; Roche Diabetes Care, Sanofi, Eli Lilly and Company, Boehringer-Ingelheim. B. Kulzer: Advisory Panel; Abbott, Dexcom, Inc. Consultant; Becton, Dickinson and Company. Other Relationship; Insulet Corporation, AstraZeneca. Board Member; Sanofi-Aventis Deutschland GmbH. Advisory Panel; Roche Diabetes Care, Novo Nordisk. N. Hermanns: Advisory Panel; Dexcom, Inc., Abbott Diagnostics. Speaker's Bureau; Abbott Diagnostics. Advisory Panel; Roche Diabetes Care.FundingFunded by the European Innovation Council (EIC) under grant agreement No. 101115233. The EIC receives support from the European Union's Horizon Europe research and innovation programme.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-977-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 978-P: Dexcom G7 Accuracy and Reproducibility in the Intensive Care Unit
-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 978-P
Abstract: Introduction and Objective: To evaluate the accuracy and reproducibility of the Dexcom G7 sensor in a hospital ICU setting in persons with diabetes or stress hyperglycemia in the absence of diabetes.Methods: At a U.S. academic center, 30 adults hospitalized in the ICU with either diabetes (N=12) or stress hyperglycemia without diabetes (n=18) wore 2 Dexcom G7 sensors simultaneously that were blinded for the purpose of the study. CGM glucose values were paired with venous or capillary blood glucose (BG) measurements for accuracy analyses. Reproducibility of the 2 simultaneously worn sensors was assessed.Results: For 1515 CGM-BG pairs, the median relative absolute difference (RAD) was 12%, with 72% of CGM values either within 20% (when BG ≥100 mg/dL) or 20 mg/dL (when BG <100 mg/dL) of the corresponding BG value (Table). Median RAD was consistent across the first 8 days of sensor wear (insufficient data subsequently). Median difference (CGM minus BG) was -6 mg/dL. For 28,926 paired CGM values from 2 simultaneously worn sensors, median RAD was 11%.Conclusion: In the ICU setting, the accuracy and reproducibility of the G7 sensor were very good and close to the accuracy achieved in the outpatient setting. The G7 sensor may be a useful tool for monitoring BG levels in the ICU.DisclosureJ.D. Baran: None. C. Spanbauer: None. R. Bais: None. H. Chiang: None. J.H. Chao: Research Support; Dexcom, Inc. D. Khakpour: None. P. Panfil: None. F.J. Pasquel: Consultant; Insulet Corporation. Research Support; Novo Nordisk, Dexcom, Inc., Ideal Medical Technologies, Tandem Diabetes Care, Inc, Insulet Corporation. Consultant; Dexcom, Inc. J. Ullal: None. M.S. Jones: None. C.C. Low Wang: Research Support; Dexcom, Inc., Virta Health Corp. J.B. Buse: Other Relationship; Corcept Therapeutics, Dexcom, Inc., Novo Nordisk. Consultant; Altimmune Inc, Amgen Inc, ApStem, Aqua Medical, AstraZeneca, Boehringer-Ingelheim, CeQur, Eli Lilly and Company, embecta, GentiBio. Other Relationship; Glyscend Therapeutics. Consultant; Insulet Corporation, Medtronic. Other Relationship; Mellitus Health. Consultant; Metsera. Other Relationship; Pendulum Therapeutics, Praetego, Stability Health. Consultant; Tandem Diabetes Care, Inc, TERNS Pharmaceuticals, Vertex Pharmaceuticals Incorporated, Zealand Pharma A/S. B. Draznin: None. J. Sibayan: None. C. Kollman: Research Support; Dexcom, Inc., Insulet Corporation, MannKind Corporation, Breakthrough T1D (formerly JDRF), Capillary Biomedical, Inc, Hemsley Charitable Trust, National Institute of Diabetes and Digestive and Kidney Diseases, Tandem Diabetes Care, Inc. R.W. Beck: Research Support; Insulet Corporation. Consultant; Insulet Corporation. Research Support; Tandem Diabetes Care, Inc, Beta Bionics, Inc, Dexcom, Inc., Bigfoot Biomedical, Inc, Abbott, embecta, Sequel Med Tech, MannKind Corporation. Consultant; Novo Nordisk, Vertex Pharmaceuticals Incorporated, Hagar, Ypsomed AG, Zucara Therapeutics, Abata Therapeutics, Eli Lilly and Company. I.B. Hirsch: Research Support; Dexcom, Inc., Tandem Diabetes Care, Inc, MannKind Corporation. Consultant; Abbott, Roche Diabetes Care, Hagar.FundingDexcom; National Institutes of Diabetes and Digestive and Kidney Disease (P30DK124723 and 2P30DK111024-06); National Center for Advancing Translational Sciences (UM1TR004406 and 3UL1TR002378-05S2)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-978-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 979-P: Leveraging Machine Learning and Demographic Insights to Optimize
Blood Glucose Management on a Digital Health Platform-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 979-P
Abstract: Introduction and Objective: Digital health and machine learning (ML) are reshaping clinical care. This study leverages data from Dario Health platform to explore individual blood glucose (BG) patterns influenced by demographics. The insights aim to personalize interventions and potentially enhance an AI model.Methods: Retrospective analysis was conducted on high-risk T2D users (average BG >180 mg/dL at month 1) who measured their BG since 2020 for >2 months (m). A piecewise linear mixed-effects (LME) model analyzed time-related fluctuations in monthly average BG (AvgBG) with cutoff at 4m based on data visualization over a year. A machine-learning piecewise LME decision tree identified BG patterns by demographic subgroups (age, gender, BMI, ethnicity). Additional LME model tested if lifestyle activities (physical activity; meal tagging) moderated improvement.Results: A group of 22414 users was evaluated (Age 57.5 SD ±12.1; 46% females). AvgBG showed a significant decrease during the first 4m (B=-6.8, p<.001) followed by a milder decrease in the next 8m (B=-.3, p<.001). Gender, BMI and ethnicity did not moderate AvgBG fluctuations, underscoring the broad applicability of digital health interventions across demographics. The decision tree segmented users into three age groups (<35, 35-60, >60) showing significant AvgBG improvement in the first 4m (p<.001); greater in the oldest group. Over next 8m, <35 age group showed no change in AvgBG (p=.7), 35-60 had a slight reduction (B=-.3, p<.05) and >60 showed the most significant improvement (B=-4, p<.001). Those >60 demonstrated a greater increase in lifestyle activities during the first 4m compared to younger age groups.Conclusion: These results highlight the potential of ML to enhance understanding of the diabetes population and to personalize care on digital health platforms using demographic factors. Age-driven AvgBG fluctuations emphasize the value of demographic data in BG management.Disclosure Y. Fundoiano-Hershcovitz: Employee; DarioHealth Corp. I. Breuer Asher: None. O. Manejwala: Employee; DarioHealth Corp. Stock/Shareholder; DarioHealth Corp.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-979-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 980-P: Leveraging Machine Learning to Enhance Blood Glucose
Management—Insights from Digital Health Platform-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 980-P
Abstract: Introduction and Objective: Integrating digital health and machine learning (ML) is reforming clinical care by offering a personalized, data-driven approach to optimize interventions. This study utilizes Dario's digital health platform data to gain insights into blood glucose (BG) patterns influenced by clinical and engagement factors, for developing personalized interventions.Methods: Retrospective data analysis was performed on high-risk T2D users (BG >180 mg/dL at month 1, equivalent to eA1c 8.0) who measured their BG since 2020 for >2 months (m). A piecewise linear mixed-effects (LME) model defined time-related fluctuations in monthly average BG (AvgBG) with cutoff at 4m based on a year data visualization. An ML approach was adopted using a piecewise LME decision tree to identify factors moderating BG trajectories such as no. of comorbidities, any insulin usage, self-reported BMI, year of diagnosis, and monthly number of BG measurements.Results: A group of 22414 users was evaluated (Age 57.5 SD ±12.1; 46% females). Significant decrease in the AvgBG was observed in the first 4m (B=-6.8, p<.001) followed by a milder decrease in the next 8m (B=-.3, p<.001). The clinical tree first split based on insulin usage and then on the year since diagnosis, categorizing users into <5 and ≥5 years. In the first 4m, insulin users with <5 years since diagnosis had the strongest decrease in AvgBG (B=-14.3, p<.001). BG monitoring tree segmented into 2 subgroups: ≤12 and >12 monthly measurements. There was a significant decrease in the AvgBG in the first 4m for both groups (≤12: B=-6.4, p<.001; >12: B=-9.0, p<.001), with a stronger decrease for the >12 group. In the following 8m, >12 group demonstrated an additional decrease in the AvgBG (B=-1.3, p<.001) yet the ≤12 experienced no change (p=.5).Conclusion: These findings highlight the importance of using ML to understand clinical and engagement factors enabling the development of personalized interventions on digital health platforms.Disclosure Y. Fundoiano-Hershcovitz: Employee; DarioHealth Corp. I. Breuer Asher: None. O. Manejwala: Employee; DarioHealth Corp. Stock/Shareholder; DarioHealth Corp.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-980-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 981-P: Success of Online CME at Improving Clinical Knowledge, Competence,
and Confidence regarding CGM-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 981-P
Abstract: Introduction and Objective: We sought to determine if online continuing medical education (CME) could improve the clinical knowledge, competence and confidence of primary care physicians (PCPs) and diabetologists/endocrinologists (D/Es) related to CGM.Methods: Intervention was a 45-min online video expert interview series with downloadable slides. Education effect assessed with matched pre-/post-assessment design. A paired samples t-test was conducted for significance testing and a McNemar test was conducted at the question level (5% significance level, P <.05). Confidence was assessed in a Likert scale question. Data collection was May 15, 2024 to July 18, 2024.Results: 191 PCPs and 34 D/Es were included in the study, of which 41% of PCPs and 53% of D/Es improved their knowledge/competence. On a question-level: 15% of both PCPs and D/Es demonstrated improvements at patient selection for use of CGM (P<.05 for PCPs and P=NS for D/Es). 21% of PCPs and 29% of D/Es demonstrated improvements at overcoming barriers to CGM use in a practical scenario (P<.01 for both PCPs and D/Es). 14% of PCPs and 18% of D/Es demonstrated improvements at identifying benefits of CGM (P<.01 for PCPs and P=NS D/Es). 34% of PCPs and 21% of D/Es had a measurable improvement in confidence in initiating CGM (P<.01 for PCPs and P=NS for D/Es). Continued educational gaps include: 61% of PCPs and 56% of D/Es need education on patient selection for CGM use, 50% of PCPs and 56% of D/Es need additional education on overcoming barriers to CGM, and 35% of PCPs need additional education on benefits of CGM.Conclusion: This study demonstrates the success of online CME consisting of an expert interview series on improving clinical knowledge, competence and confidence of both PCPs and D/Es related to CGM use. Significant continued knowledge and competence gaps were identified in both groups, with the largest gaps in knowledge seen in PCPs and competence in D/Es.DisclosureA. Larkin: None. M. LaCouture: None. A. Le: None.FundingIndependent educational grant from Abbott Diabetes Care
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-981-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 982-P: Factors Associated with Discrepancy between A1C and GMI in Veteran
Population on Insulin Pump-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 982-P
Abstract: Introduction and Objective: Discrepancies between A1c and GMI larger than 0.5% are considered clinically significant differences (CSD). About 26-68% of published studies reported CSD. In this study from a real-life setting, we aim to assess factors associated with CSD between A1C and GMI in a Veteran population.Methods: A retrospective study from a specialized diabetes clinic, included 110 patients using Medtronic pumps and sensors (Guardian 3 or 4) in 2023 and 2024 (age: 64±14; BMI: 28 ± 4 kg/m2). Among them, 36 patients (26 with T1D and 10 with T2D) had paired A1C-90-day CGM data, resulting in 122 paired downloads, 86 for T1D and 36 for T2D. A1C was correlated with CGM data, and when available, hemoglobin levels and renal function tests were analyzed.Results: Among all paired A1C-CGM downloads (n=122) at the 90-day interval, 56% had a significant discrepancy between A1C and GMI. Any degree of discrepancy was negatively correlated with CGM wear percentage (R² = 0.153, F (1, 52) = 9.42, p = 0.0034). When A1c was higher than GMI by 0.5%, this correlation remained statistically significant (R² = 0.156, F(1, 47) = 8.66, p = 0.0050). Interestingly, when A1C was lower than GMI by 0.5%, the negative correlation was stronger (R² = 0.786, F(1, 3) = 11, p = 0.045). In participants with T2D (n=36), at the 90-day interval, the discrepancy between A1C and GMI was strongly correlated with CGM wear percentage (R² = 0.466, F(1, 11) = 9.59, p = 0.0102). Anemia or renal function did not affect CSD. However, most patients had normal or near normal renal function (median eGFR 85) and hemoglobin levels (median 13.8).Conclusion: In a real-world setting, discrepancy of A1C and GMI is associated to the percentage of CGM wear at the 90-day interval, more so in T2D. Anemia and renal function did not affect this discrepancy, likely due to the population's preserved renal function and hemoglobin levels. These findings underscore the importance of consistent CGM use and highlight the need for further research to understand these discrepancies.DisclosureT. Nguyen: None. J.A. Leey: None.FundingNational Institutes of Health (UL1TR001427)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-982-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 983-P: Continuous Glucose Monitoring in DKA and Acute
Hyperglycemia—Performance and Insights-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 983-P
Abstract: Introduction and Objective: This pilot study compared the accuracy of CGM (Dexcom G6 pro) in individuals hospitalized with diabetes ketoacidosis (DKA) compared to those with hyperglycemia in the critical care setting requiring IV insulin infusion.Methods: Individuals meeting criteria for DKA diagnosis were eligible for the DKA arm and those in a critical care setting with glucose > 250 mg/dL at time of enrollment were eligible for the control arm. All patients were on IV insulin at time of sensor placement. After consent was obtained, a Dexcom G6 pro was inserted and worn through hospitalization or until sensor expired. CGM glucose data was compared retrospectively to POC/serum BG measurements and analyzed using the Diabetes Technology Society (DTS) error grid software.Results: A total of 20 patients were enrolled, 10 in the DKA arm and 10 in the control arm. Average age 60 years old (27-84 years) and 60% male. Time on insulin infusion ranged from 11-77 hours with average 37 hours on IV insulin (DKA arm= 35 hours, control arm = 42 hours).Conclusion: Mean absolute relative difference (MARD) was higher in the DKA arm however, both are well above MARD values reported in the outpatient setting. Bias was positive and the absolute relative difference between CGM and comparator BG was frequently > 20%. Almost all values were within the no risk or mild risk zones on the DTS error grid. This pilot emphasizes the need for further investigation including the role of CGM calibration and patient selection.Disclosure R. Longo: Advisory Panel; Dexcom, Inc. G.M. Calderon: None. P. Aron: None. J. Upadhyay: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-983-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 984-P: Exploring the Impact of Dexcom CGM and Levels Metabolic Health
App’s Meal Logging Feature on Glycemic Outcomes and Behaviors across BMI
Categories in a Real-World Cohort without Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 984-P
Abstract: Introduction and Objective: CGM use is increasingly popular among those without diabetes. Levels Health (LH), a digital platform integrating Dexcom CGM data with its meal logging (ML) feature, provides personalized health insights. We examined the impact of CGM integration with ML on behaviors and glycemic outcomes during the first 30 days of use.Methods: We analyzed real-world data from LH users who reported no diabetes diagnosis and wore Dexcom G7 CGM for 30 days. Demographics, glycemic metrics, and meal logging content and engagement (days with ≥ 1 meal log/ days wearing CGM) were analyzed over 30 days. Changes from first to last 10 days were compared. Analyses were stratified by BMI and other subgroups.Results: Sample included 1304 people (53% 40-59 years; 60% female; BMI categories: 2% underweight, 41% normal, 33% overweight, 24% obesity). With higher BMI, mean glucose rose (30-day mean ± SD: 102 ± 7, 104 ± 10, 108 ± 13, 113 ± 16 mg/dL), while TIRs 70-140 mg/dL (94% ± 6, 94% ± 7, 92% ± 10, 89% ± 16) and 70-110 mg/dL (70% ± 16, 69% ± 18, 61% ± 22, 52% ± 26) declined; between-group differences for full 30 days and first and last 10 days, all p <0.001. Median ML engagement was 84% and only 2% of participants logged meals on days they were not wearing CGM. Participants with above-median ML engagement spent more TIR 70-140 mg/dL and 70-110 mg/dL, had lower maximum glucose values, and reported consuming a lower percentage of carbohydrates than those with below-median engagement (all p <0.05).Conclusion: These findings underscore the link between body weight, glycemic risk, and the value of CGM in helping individuals understand how behaviors affect glycemic outcomes. Leveraging CGM and digital tools presents a significant opportunity to improve metabolic health through behavioral insights and interventions.Disclosure M.A. Crawford: Employee; Dexcom, Inc. C. Hicks: Employee; Dexcom, Inc. S. Menon: Employee; Dexcom, Inc. D.S. Carey: Employee; Levels Health. H. Singh: Employee; Dexcom, Inc.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-984-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 985-P: Continuous Glucose Monitoring and Associated Outcomes in
Insulin-Using Older Adults with Diabetes and Alzheimer’s Disease and
Related Dementias Using Medicare 2016–2020 Data-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 985-P
Abstract: Introduction and Objective: The co-occurrence of dementia and diabetes significantly impacts quality of life, healthcare costs, and mortality rates. Effective management of both conditions using technology like continuous glucose monitoring (CGM) could improve outcomes.Methods: This retrospective study used 2016-2020 Medicare fee-for-service claims data (15% random sample) with continuous Part A, B, and D enrollment. We included patients with diabetes and cognitive impairment/ADRD, excluding those with 2020 CGM claims, non-users without SMBG at baseline, in hospice, or with Part C enrollment. Follow-up began at the first CGM claim and ended at death, disenrollment, or Dec 31, 2020. Propensity score matching (1:1) ensured balanced cohorts (SMD <0.1). Cox proportional hazards models compared outcomes between CGM and SMBG users, with significance set at 95% CI not crossing 1.Results: In our matched cohort of 1011 CGM and 1011 SMBG users, CGM use was associated with significant reductions in all-cause hospitalizations (HR: 0.86, 95% CI: 0.76-0.96) and all-cause mortality (HR: 0.57, 95% CI: 0.48-0.67) compared to SMBG users. There were no significant differences in hypoglycemia hospitalizations, hyperglycemia, or falls. Subgroup analyses showed lower hypoglycemia risk in male CGM users (HR: 0.35, 95% CI: 0.15-0.87) and higher hyperglycemia risk in CGM users with type 1 diabetes (HR: 1.78, 95% CI: 1.15-2.75). Other subgroup findings by race/ethnicity, sex, and diabetes type aligned with overall results.Conclusion: Our findings highlight CGM's benefit in reducing all-cause mortality, hospitalizations, and hypoglycemia risk in male users among older adults with diabetes and cognitive impairment. These results support including CGM in diabetes management guidelines for this population.Disclosure P. Kotecha: Employee; Takeda Pharmaceutical Company. W.T. Donahoo: None. S.M. Smith: None. J. Bian: None. J. Guo: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-985-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 986-P: A1C Benefits of Dexcom rtCGM Compared with SMBG among People with
Type 2 Diabetes on Less Intensive Therapies-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 986-P
Abstract: Introduction and Objective: This study evaluated the difference in A1c improvement between Dexcom rtCGM and SMBG among people with type 2 diabetes (PwT2D) using basal insulin (BI) or non-insulin therapy (NIT).Methods: This retrospective study used Optum’s Clinformatics® de-identified US health claims database (09/2016 to 06/2024). Cohorts consisted of CGM-naïve BI or NIT PwT2D who began using Dexcom G-series rtCGM (index = first rtCGM claim) or SMBG (index = random date). Cohorts were propensity score matched on baseline demographics, A1c and healthcare resource utilization. Changes in A1c were assessed 12 months pre- (baseline) and post-index (follow-up) as: (1) the mean change in A1c following CGM initiation and the difference-in-differences (DiD) between cohorts, (2) the proportion achieving A1c <7% or <8% during follow-up, and (3) the proportion with a baseline A1c ≥7% who achieved an A1c <7% after rtCGM initiation.Results: Across indications (BI n=2,866; NIT n=1,559), rtCGM use was associated with a greater A1c reduction compared to SMBG use (BI: -0.84 vs -0.30 [DiD= -0.53, p<0.01]; NIT: -0.79 vs -0.35 [DiD= -0.44, p<0.01]). In the BI cohort, a greater percentage of rtCGM users achieved A1c levels <7% or <8% at follow-up vs SMBG users (A1c <7%: 32.6% vs 24.1%, p<0.01; A1c <8%: 67.6% vs 53.6%, p<0.01). Likewise, a higher percentage of NIT rtCGM users achieved A1c <7% or <8% at follow-up compared to SMBG users (A1c <7%: 48.0% vs 41.0%, p<0.01; A1c <8%: 29.8% vs 18.05%, p<0.01). In addition, a greater percentage of rtCGM users with a baseline A1c ≥7% achieved an A1c <7% at follow-up vs SMBG users (BI: 21.3% vs 12.7%, p<0.01; NIT: 23.3% vs 14.9%, p<0.01).Conclusion: These findings indicate Dexcom rtCGM may be a valuable tool for glycemic management for PwT2D on less intensive therapies and may contribute to individuals reaching their glycemic goals. These results support rtCGM as a preferred monitoring strategy over SMBG in clinical practice for BI and NIT PwT2D.Disclosure B.C. Liu: Employee; Dexcom, Inc. K. Hannah: Employee; Dexcom, Inc. P. Nemlekar: Employee; Dexcom, Inc. G.J. Norman: Employee; Dexcom, Inc.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-986-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 987-P: Baseline Characteristics of Adults with Type 2 Diabetes in a Pilot
RCT of an Interactive Digital Food Diary App and CGM-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 987-P
Abstract: Introduction and Objective: Mobile health applications are increasingly popular, yet most function as glucose diaries, and few are evidence-based. Here we discuss baseline findings from an in-progress RCT to examine the effectiveness of a photo-based food diary smartphone app (Undermyfork, Hermosa Beach) and CGM (Dexcom, Inc., San Diego) for adults with type 2 diabetes (T2D).Methods: Descriptives statistics; bivariate Pearson correlations. Inclusion criteria: T2D, aged 18-80, A1c >7.7%, CGM naïve, and not on bolus insulin.Results: A total of N=215 patients were screened for the pilot trial. Of those approached (n=110), 32% (n=35) were eligible and interested, and 18% (n=20) were enrolled into the study (enrollment ongoing). Descriptive statistics of the enrolled patients (n = 20; 67% male) revealed an average age of 61 ± 12.6, average A1c of 8.75% ± 1.1, and an average T2D diagnosis length of 13.9 ± 9.6 years. Baseline findings revealed important trends in the use and comfortability of mobile applications as health resources. Over 1/3 of participants (35%) reported never using mobile applications as a health resource. Age was weakly, negatively correlated with both the use (r = -0.48, p<.05) and comfortability (r = -0.44, p<.05) of mobile health applications, suggesting older adults were less likely to engage with this technology. Additionally, sex also weakly correlated with diabetes distress (r=.44, p<.05), with women reporting higher levels of diabetes distress than men. Although baseline data included information on A1c and diabetes self-care activities (i.e., diet, exercise, blood glucose testing, and foot care), no other significant correlations were observed.Conclusion: These findings highlight the need to address age-related barriers to improve comfort with mobile applications and CGM use for managing T2D. Targeted education and user-friendly designs may enhance engagement for better self-management and outcomes.DisclosureK. Brown: None. M. Ushakov: Stock/Shareholder; Undermyfork, Inc. E. Molodkin: Stock/Shareholder; Undermyfork, Inc. N. Orendain: None. S.R. Spierling Bagsic: None. C.D. Bell: None. A. Philis-Tsimikas: Advisory Panel; Dexcom, Inc. Research Support; Dexcom, Inc. Advisory Panel; Lilly Diabetes. Research Support; Lilly Diabetes. Advisory Panel; Novo Nordisk. Research Support; Novo Nordisk. Advisory Panel; Medtronic, Sanofi.FundingDexcom, Inc.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-987-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 988-P: Understanding Glycemic Control in the Post-discharge Period through
Blinded Continuous Glucose Monitoring-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 988-P
Abstract: Introduction and Objective: Little is known about glycemic control in the immediate post-hospital discharge period.Methods: In this observational study, patients wore blinded Dexcom G6 Pro CGM during their hospital stays and for up to 10 days post-discharge. Clinical data were extracted from the electronic medical record. Percent time in range (70-180 mg/dl, %TIR), above range (>180 mg/dl, %TAR), below range (<70 mg/dl, %TBR), and episodes of hypoglycemia from the inpatient and post-discharge periods were calculated. The difference between inpatient and post-discharge glycemic control was analyzed with paired t-tests. Predictors of post-discharge glycemic control were evaluated with logistic regression.Results: This cohort of 24 adults (mean age 65.7 ± 13.6 years, 37.5% female) had post-discharge mean %TIR 43.9 ± 33.2%, mean %TAR 55.9 ± 33.3%, and median %TBR 0% (0, 0.04). Glycemic control was similar pre- and post-discharge (post-discharge vs inpatient %TIR -3.7 ± 22.5%, p=0.4). CGM detected 16 episodes of hypoglycemia <70 mg/dl post-discharge. Of the clinical factors assessed, only measures of inpatient glycemic control were associated with achieving post-discharge glycemic control (Table).Conclusion: Inpatient glycemic control may impact post-discharge glycemic control, though the mediators are unclear. CGM may be useful in identifying hypoglycemia after discharge.DisclosureR. Patel: None. M. O'Connor: None. A. Sabean: None. A. Ashley: None. H. Zheng: None. J. Yan: None. B. Steiner: None. N. Anandakugan: None. M.M. Calverley: None. R. Bartholomew: None. E. Greaux: None. L.E. Castellanos: None. M.E. Larkin: None. S.J. Russell: Employee; Beta Bionics, Inc. Stock/Shareholder; Beta Bionics, Inc. M.S. Putman: Consultant; Anagram Therapeutics. Research Support; Dexcom, Inc. Other Relationship; Vertex Pharmaceuticals Incorporated. K.L. Flint: None.FundingNational Institute of Diabetes and Digestive and Kidney Diseases (R01DK119699-S1 and T32DK007028); Dexcom Investigator Initiated Studies grant
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-988-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 989-P: Minimum Glucose of the Day in People with Type 2 Diabetes on
Long-Acting Insulin-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 989-P
Abstract: Introduction and Objective: When titrating long-acting insulin (LAI) for people living with Type 2 Diabetes (pwT2D), fasting blood glucose (FBG) in the morning is often used as a conservative measure to adjust the LAI dose as it is often the lowest glucose in a 24-hour period. However, the actual minimum glucose of the day (MGD) can occur at any time. De-identified real-world glucose data from FreeStyle Libre 2 (FSL2) flash glucose monitoring system users was examined to determine the timing when MGD occurred.Methods: MGD is defined as the lowest one-hour average of continuous glucose monitoring (CGM) data of each day. All users were on basal insulin +/- other oral diabetes medications. For each user, 15 consecutive days were randomly selected in which an MGD was identified. Subgroup analysis for hypoglycemia-inducing agents was also done for sulfonylurea (SU) and meglitinide (Meg) users to evaluate if there are differences in MGD in this group.Results: Data from 3,137 FSL2 users with T2D on LAI showed that 39% of the MGD values occurred during the day (between 10AM and 10PM). Less than 15% of the MGD values occurred between 6AM and 9AM, the typical timing of self-monitoring of FBG. The subgroup with SU and Meg had a similar distribution of MGD timings.Conclusion: A substantial number of MGDs occur during the day in pwT2D on LAI, including the SU/Meg subgroup. Using morning FBG may miss capturing the true MGD. CGM can provide a more conservative tool for identifying MGD which may be a safer measure to dose LAI.Disclosure A. Bhattacharya: Employee; Abbott. N. Singh: None. B.P. Olson: Employee; Abbott, Bigfoot Biomedical, Inc. A. Bindal: Employee; Abbott.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-989-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 990-P: Impact of Early Continuous Glucose Monitor Placement in Pediatric
Patients-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 990-P
Abstract: Introduction and Objective: Continuous glucose monitors (CGM) improve diabetes control. Obtaining approval at diagnosis can be challenging. We evaluated the impact of CGM initiation at diabetes diagnosis on change in hemoglobin A1c (HbA1c) at follow up in pediatric patients.Methods: Patients with newly diagnosed diabetes were enrolled in a prospective cohort study at a pediatric hospital September 2023-March 2024. Patients starting CGM within several days of diagnosis were included in the ‘early CGM’ group. For the ‘late CGM’ comparison group, we used retrospective data (September 2022-March 2023); patients were not offered CGM at diagnosis but could start CGM later. All patients started injection basal bolus insulin therapy and had follow up scheduled per American Diabetes Association guidelines. Change in HbA1c from diagnosis to follow up was compared between groups.Results: 93 patients started a CGM at diagnosis, 105 patients did not start CGM at diagnosis. Mean age (early CGM: 10.9 years vs late CGM: 11.0 years) and HbA1c at diagnosis (early CGM: 11.4% vs late CGM: 11.7%) did not significantly differ between groups. There was no significant difference in change in HbA1c between groups (Figure 1).Conclusion: Starting a CGM at diabetes diagnosis did not significantly impact early changes in HbA1c. Further research is needed to assess the impact of early CGM initiation on other metrics, including hypoglycemia.DisclosureS. Giger: None. J.D. Courter: None. L. Hornung: None. A.L. Poetker: None. S. Lawson: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-990-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 992-P: A Retrospective Comparative Study of Glycemic Control Metrics at
Six Months in 133 Patients with Type 1 Diabetes after Switching from isCGM
to rtCGM with the Same Sensor Profile-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 992-P
Abstract: Introduction and Objective: In Japan, FreeStyle Libre 2 (Libre 2) was approved as real-time continuous glucose monitoring (rtCGM) only when used smartphone application since its initial release, December 2023. Because early approval as rtCGM like Japan is uncommon, the efficacy of switching from intermittently scanned CGM (isCGM) to rtCGM with identical accuracy and specifications remains unclear.Methods: This retrospective study included adults with type 1 diabetes. Changes in HbA1c and CGM metrics were assessed before and 6 months after switching from isCGM to rtCGM. In patients switched from isCGM to isCGM with low and high glucose alert functions (Libre 2 reader users), due to difference of release day between the reader and app, only 3-month data were analyzed.Results: Of 133 patients enrolled from January 2024 through June 2024. 67 (50.4%) were male; the mean (±SD) age of the patients was 45.6 ± 15.3 years and HbA1c was 7.51 ± 0.64%. At 6 months post-switching, significant improvements were observed in mean HbA1c (7.51 vs. 7.35, p < 0.01), TAR (37.5% vs. 35.3%, p < 0.01), TIR (58.7% vs. 61.4%, p < 0.01), TITR (37.6% vs. 39.0%, p = 0.04), CV (38.0% vs. 36.3%, p < 0.01) and MAGE (127.3mg/dL vs. 118.9mg/dL, p < 0.01). No significant differences were observed for TBR (3.72% vs. 3.33%, p = 0.13) or Level 2 TBR (0.51% vs. 0.38%, p = 0.16). Similar effects on HbA1c and CGM metrics were observed in a 3-month analysis. On the other hand, 35 patients switched from isCGM to isCGM with alert functions showed no significant differences in HbA1c, TIR, TAR, and TBR at 3 months.Conclusion: Switching from isCGM to rtCGM improved glycemic control at 6 months in patients with type 1 diabetes. The lack of improvement in HbA1c and CGM metrics in patients using isCGM with alert functions suggests monitoring real-time glucose levels, rather than alert functions, may play a crucial role in achieving better glucose outcomes.DisclosureD. Sekiguchi: None. Y. Maeda: None. M. Morita: None. Y. Kurogi: None. M. Minami: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-992-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 993-P: Performance of iCan CGM System in a Pediatric Population
-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 993-P
Abstract: Introduction and Objective: The iCan CGM system, developed by Sinocare Meditech Inc. is equipped with GDH-FAD based 3rd generation sensor technology. After receiving CE-mark for a wear-time of 15d in an adult population the next step was to conduct a regulatory performance study in a pediatric population. This study was conducted according to international standards in three leading hospitals in China.Methods: The study has a single arm, prospective multicenter design. The full analysis set includes 76 subjects, age 2-17 yrs. with 16 subjects aged 2-5 yrs. The majority of all subjects were people with T1D (86.8%). At days 1-2, 6-8 and 15 the performance of the device was assessed by comparison to laboratory reference device. The data were analyzed according to generally accepted procedures.Results: We report the per protocol analysis of a single sensor with an overall MARD of 8.30%, and a 20/20% performance of 96.40%. The MARD results at the 3 accuracy testing visits were estimated to 8.46% (1-2d), 7.52% (6-8d), and 8.98% (14-15d). The 20/20% performance for the same visits were estimated to 95.18%, 98.17% and 95.82% respectively. The Consensus error grid analysis shows 100.0% (95%CI: 99.8% - 100.0%) of the paired readings in Zones A+B. There were no device related and skin related adverse events reported in the safety data set.Conclusion: This first regulatory performance study of the iCan CGM System in a pediatric population demonstrates high overall accuracy and a single digit MARD below 9.0% at each accuracy testing visit together with a 20/20% performance consistently above a 95% threshold throughout the 15d wear-time. The overall performance of the iCan CGM System in this population confirms the consistent performance previously seen and reported in adults.Disclosure J. Zheng: Employee; Sinocare Inc. J. Fei: Employee; Sinocare Inc. Board Member; Trividia Health Inc. F. Gao: Employee; Sinocare Inc. Y. Yu: None. A. Gao: Employee; Sinocare Inc. Z. Qian: Employee; Sinocare Inc. F. Flacke: Consultant; Sinocare Inc, BOYDSense SAS, embecta, Sanofi-Aventis Deutschland GmbH. W. Haiying: None. D. Shuxia: None. O. Wenxian: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-993-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 994-P: Impact of Telemonitoring and Remote Care on Patients with Type 2
Diabetes Mellitus—Hospital De Calderon, Quito, Ecuador-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 994-P
Abstract: Introduction and Objective: Diabetes is the fourth chronic non-communicable disease (1) and one of the main causes of death and disability worldwide. Type 2 diabetes accounts for 96% of reported cases worldwide Objective: The following study aims to evaluate the impact of telemonitoring and remote care on glycemic control in patients with type 2 diabetes mellitus who are insulin users in the HGDC outpatient unit.Methods: A prospective case-control study with 100 patients: 50 controls (without telemonitoring) and 50 cases (telemonitoring). The information was obtained from the Accu Chek Care platform during telemonitoring, and the results of glycosylated hemoglobin from the institution's laboratory were taken at the beginning of the research, at the third and sixth month.Results: Glycosylated hemoglobin at the beginning of the study only varied by 0.4 points between both groups, being 9.8% in the study group and 10.2% in the control group. At the end of the 6 months of telemonitoring, the study group significantly decreased glycated hemoglobin by 25% (HbA1c 7.3%) compared to that seen in the control group, where the reduction was a little more stable at 13% (HbA1c 8.9%). A 66% reduction in the incidence of diabetes-related emergency admissions was observed in the follow-up group. It is predicted that with the implementation of this telemonitoring strategy projected to 5 years, 25% of the main complications could be prevented, including 48% of amputations, 43% of microvascular diseases and 42% of nephropathy cases.Conclusion: It is concluded that the implementation of telemonitoring for the follow-up of patients diagnosed with type 2 diabetes mellitus with insulin treatment has been shown to have a positive impact in the short and long term on the quality of life of patients. Likewise, remote monitoring reduces the use of hospital resources and identifies the progress of the disease in a timely manner.DisclosureA.B. Santillan: None.FundingROCHE
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-994-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 995-P: Current Gaps in CGM Data Tools and Methods
-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 995-P
Abstract: Introduction and Objective: Continuous glucose monitors (CGMs) are critical clinical tools whose use in research is rapidly expanding. We aim to understand the current state of knowledge around standard methods and tools for managing and analyzing CGM data.Methods: Literature review: We searched PubMed for articles that: 1) described a clinical trial, 2) were published in the last 5 years, 3) used CGMs to collect data, and 4) included a description of how CGM data was treated in the methods section. Surveys: We built an online survey to understand how researchers work with CGM data. A link to the survey was distributed via email and posted on social media platforms. Interviews: We recruited established diabetes researchers who either completed the survey, attended diabetes research meetings, or published recent articles about CGM data.Results: 89 out of 123 articles screened met inclusion criteria. Fewer than half of those described how their CGM data was extracted and cleaned, how missingness was handled, and which data tools were used. Our survey was completed by 43 researchers with a median of 8 years of experience with CGM research. Only 23 had ever used CGM-specific data tools; others reported using tools like Excel, R, and Python. Twenty-one content area experts from the United States and abroad who use CGM data in their research—averaging nine years of experience—were interviewed about the greatest benefits and challenges of using CGM data and their procedures for treating data. Twenty (over 95%) interviewees were not aware of standardized or universally accepted foundational texts containing information about CGM research methodologies. All 21 agreed that a repository of CGM data would improve diabetes research, increase connectivity, and advance innovation.Conclusion: Few if any standardized methods and tools are designed specifically to help researchers work with CGM data. It is vital to develop tools and resources to improve the quality of CGM-driven research by leveraging standardized practices and simplifying technical processes.Disclosure J.C. Espinoza: Consultant; Sanofi. Other Relationship; Big Health. Speaker's Bureau; Dexcom, Inc. E. Friedman: None. A. DuNova: None. C. Ho: None. A. Ayers: Consultant; Liom Health AG. E. Williams Jr.: None. L. Lett: None. S.N. Shah: None. D.C. Klonoff: Consultant; Synchneuro, Thirdwayv, Tingo, Afon, embecta, Glucotrack, Lifecare, Novo Nordisk, Samsung.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-995-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 996-P: Continuous Glucose Monitoring Reveals Predictors of Hyperglycemia
Duration in Diabetic Inpatient Care-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 996-P
Abstract: Introduction and Objective: Inpatient hyperglycemia is linked to a higher risk of complications and mortality. Limited research has examined the duration and outcomes of hyperglycemia events using CGM technology. This study explored factors contributing to individual differences in the length of hyperglycemia episodes and evaluated its implications for inpatient glycemic management.Methods: We conducted a post-hoc analysis of two prospective inpatient CGM studies that enrolled patients aged ≥18 with diabetes. Hyperglycemia episodes were defined as glucose levels ≥180 mg/dL, lasting ≥15 minutes. We considered individual factors, including gender, race, obesity, diabetes history, insulin dose in the past 24 hours, and number of previous hyperglycemia episodes. A novel quantile regression method was applied to identify predictors and characterize their outcome effects.Results: The analysis included 2,419 hyperglycemia episodes from 239 patients. On average, patients experienced 10.1 episodes (median: 8, range: 1-48) with a median episode length of 3.73 hours (median: 2.13, IQR: 1.33-3.71). A one-unit/kg increase in insulin dose was associated with a 2.01-hour decrease (95% CI: 0.45-4.71) in median episode length, while each additional prior episode or one additional year of diabetes history was linked to a 0.06-hour increase (95% CI: 0.02-0.11) or a 0.04-hour increase (95% CI: -0.01-0.09), respectively. The median episode length in obese patients was 0.96 hours (95% CI: 0.22-2.10) shorter than in non-obese patients. Gender and race showed minimal effects.Conclusion: This study highlights the interplay of factors influencing the duration of hyperglycemic events. Higher insulin dosage and obesity were associated with shorted events, while the longer duration of diabetes and prior episodes led to prolonged hyperglycemia. These findings enhance our understanding of hyperglycemia dynamics and improve strategies for optimizing inpatient glycemic management.DisclosureY. Liu: None. G. Umpierrez: Research Support; Abbott, Dexcom, Inc., Bayer Pharmaceuticals, Inc, Corcept Therapeutics. Advisory Panel; Dexcom, Inc., GlyCare Health. G.M. Davis: Research Support; Insulet Corporation. M. Fayfman: Research Support; Abbott, Dexcom, Inc. L. Peng: None.FundingNational Institutes of Health (R01DK136023)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-996-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 997-P: Effectiveness of Telemedicine in Improvements of Glycemic Control
in Patient with Diabetes Mellitus in Saudi Arabia-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 997-P
Abstract: Introduction and Objective: Diabetes mellitus is a significant global health burden, with rising prevalence worldwide and in Saudi Arabia. With the development of the technology, the telemedicine helps in improving the health outcomes by increasing access to diabetes care and medical information and using the diabetic technology to monitor the patient widely through different distances and times.Methods: It is a Retrospective cohort study conducted in KSA for a duration of 2 Years, between January 2022 to January 2024. Data on glycemic control, including HbA1c and Time in Range (TIR), were collected and analyzed using statistical tests to assess improvements and identify predictive factors. Data is analyzed via IBM SPSS 29.0.0.Results: Our study assessed the effectiveness of telemedicine in managing diabetes mellitus (T1DM) among 227 patients. The majority were female (n=131, 57.7%), with a mean age of 23.8 years (SD=6.2). Most participants were normotensive (n=211, 93.0%) and resided in Riyadh Province (n=213, 93.8%). Glycemic control improved modestly after telemedicine, with Time in Range (TIR) increasing significantly from 36.95% to 39.44% (p=0.004). However, the reduction in HbA1c (from 9.27% to 9.12%) was not statistically significant (p=0.514). Predictors of normal TIR included age, with a 16.8% increase in likelihood per additional year (Exp(B)=1.168, p=0.016). Married participants had lower odds of achieving normal TIR compared to single participants (Exp(B)=0.184, p=0.036). Gender, BMI, education, and insulin dosages did not significantly impact glycemic outcomes (p > 0.05).Conclusion: Telemedicine modestly improved glycemic control in T1DM, significantly increasing TIR but not HbA1c. Age predicted better TIR outcomes, while marital status influenced adherence. Telemedicine shows potential but requires combined interventions for substantial long-term impact and improved diabetes management strategies.DisclosureA.A. Alateyah: None. G.H. Adawi: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-997-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 998-P: GMI–A1C Concordance in Emerging Adults with T1D from the
iHERO Study-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 998-P
Abstract: Introduction and Objective: Glucose Management Indicator (GMI) can approximate A1C and may be valuable for those with barriers to clinic visits, including emerging adults (ages 18-30 years). Recent studies revealed less GMI-A1C concordance than expected, particularly in those with greater time above 180 mg/dL. Our objective was to assess GMI-A1C correlation and influence of time above range (TAR) on GMI-A1C concordance in emerging adults with T1D from the Insurance, Health, and Economic Resources Online (iHERO) study.Methods: We performed a cross-sectional comparison of baseline data from this national longitudinal remote study, in which participants perform home capillary A1C collection sent for lab analysis and CGM data upload. Correlation between 14-day GMI and A1C was run. Demographic and glycemic data were compared between those meeting and not meeting goal TAR (<25% above 180 mg/dL).Results: Of the 96 participants currently enrolled, 60 (62.5%) had usable CGM data and A1C results. Pearson's correlation between GMI and A1C was 0.875 (p<0.001). See table 1 for descriptives by TAR group.Conclusion: Irrespective of meeting goal TAR, GMI and A1C were highly concordant. These preliminary findings support the role of GMI as an accessible tool that can approximate A1C in emerging adults with T1D outside of the clinic setting. Further data collection will continue to enhance our understanding of factors influencing GMI-A1C concordance.DisclosureN.J. Rodgers: None. B.M. Petrovich: None. C. Lewis: Other Relationship; Dexcom, Inc. J. Rieke: None. D.A. Williams: None. J.E. Blanchette: Speaker's Bureau; Insulet Corporation. Research Support; Leona M. and Harry B. Helmsley Charitable Trust. Advisory Panel; Eli Lilly and Company, Cardinal Health/Edgepark. Consultant; embecta. Research Support; National Institute of Diabetes and Digestive and Kidney Diseases. Board Member; Juvenile Diabetes Research Foundation (JDRF). B. Hatipoglu: Research Support; Tandem Diabetes Care, Inc, Diasome Pharmaceuticals. E.L. Lundgrin: None.FundingThe Leona M. and Harry B. Helmsley Charitable Trust (G-2305- 05992)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-998-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 999-P: Continuous Glucose Monitoring Metrics Predict All-Cause Mortality
in Patients with Both Type 1 and Type 2 Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 999-P
Abstract: Introduction and Objective: To examine whether continuous glucose monitoring (CGM) metrics predict 5-year all-cause mortality in adults with type 1 or type 2 diabetes (T1D/T2D).Methods: 2,752 Veterans (age ≥21 years; 70% T2D) who initiated Dexcom CGM (2015-2020) had all CGM data merged with electronic health records data. Cox proportional hazard models assessed associations between mortality and CGM metrics, including estimated blood glucose (eBG), time in range (TIR), time above range (TAR), coefficient of variation (CV), and glycemic risk index (GRI).Results: Mean age was 64 years, with a median CGM use of 3 years, and 407 total deaths. After adjusting for mortality related variables, higher eBG, TAR, GRI, and CV, and lower TIR from 6 months of LM CGM were significantly linked with mortality (all p ≤ 0.01). After adjusting for average LM HbA1c, these associations remained, and shorter CGM windows (14 days or 3 months) showed similar but slightly weaker effects (Table). CV’s association was independent of other metrics and strongest among those with lower HbA1c.Conclusion: CGM-derived metrics predict all-cause mortality in patients with diabetes, independent of HbA1c, underscoring their importance for risk stratification.DisclosureT. Okuno: None. S. Macwan: None. G.J. Norman: Employee; Dexcom, Inc. D.R. Miller: None. P. Reaven: Research Support; Dexcom, Inc. J. Zhou: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-999-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 1000-P: Observed Glycemic and Psychosocial Benefits in the Prospective
Bigfoot Unity Real-World Study (BURST)—A Twelve-Month Analysis-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 1000-P
Abstract: Introduction and Objective: The Bigfoot Unity System integrates Abbott FreeStyle Libre 2 CGM data into a smart insulin pen cap and mobile app enabling clinician-directed insulin dose recommendations and real time alerts. The objective was to analyze real world, 12-month data for System users.Methods: We conducted a 12-month final analysis from the prospective BURST study (NCT05088265) and report the per-protocol results (N=125). Participants completed baseline, adverse event and patient-reported outcome surveys electronically. HbA1c data were from home kits or electronic medical records.Results: Median age was 58 years and 86% had T2D. Mean HbA1c decreased from 9.2±1.8% at baseline to 8.0±1.2% at 12 months (mean change -1.3%, 95%CI -1.6, -0.9; p<0.001). There were six severe hypoglycemia events in 4 participants (none System related), and no DKA. Diabetes Distress Scale scores decreased (mean change -0.8, 95%CI -1.0, -0.6; p<0.001) and Hypoglycemic Confidence Scale scores increased (mean change 0.5, 95%CI 0.4, 0.7; p<0.001) with System use (Table).Conclusion: Durable glycemic improvement with reduced diabetes distress and increased hypoglycemic confidence occurred using the System for 6 months and sustained through 12 months. The reduction in HbA1c occurred while meeting established hypoglycemia targets of <4 and <1% for percent time below 70 and 54 mg/dL, respectively.Disclosure J. Tillman: Employee; Abbott. R.W. Beck: Research Support; Insulet Corporation. Consultant; Insulet Corporation. Research Support; Tandem Diabetes Care, Inc, Beta Bionics, Inc, Dexcom, Inc., Bigfoot Biomedical, Inc, Abbott, embecta, Sequel Med Tech, MannKind Corporation. Consultant; Novo Nordisk, Vertex Pharmaceuticals Incorporated, Hagar, Ypsomed AG, Zucara Therapeutics, Abata Therapeutics, Eli Lilly and Company. W.H. Polonsky: Consultant; Abbott. Research Support; Abbott. Consultant; Dexcom, Inc. Research Support; Dexcom, Inc. Other Relationship; Ascensia Diabetes Care. P. Calhoun: None. T.J. Mouse: None. R. Bailey: None. R. Nandan: Employee; Abbott, Bigfoot Biomedical, Inc.FundingAbbott
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-1000-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 1001-P: Association between Continuous Glucose Monitoring (CGM) Adherence
and Diabetes-Related (DR) Hospitalizations in People with Type 2 Diabetes
(PwT2D) on Intensive Insulin Therapy (IIT)-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 1001-P
Abstract: Introduction and Objective: This study evaluated the relationship between CGM adherence and DR hospitalizations in PwT2D on IIT.Methods: Retrospective analysis using Merative MarketScan® US healthcare claims database was conducted. CGM naïve PwT2D on IIT who initiated a CGM sensor (Dexcom or Libre) between 01/2019 and 12/2022 (index date=CGM initiation) were included. Continuous health plan coverage was required 12 months pre-(baseline) and post-(follow-up) index date. The association between CGM adherence and DR hospitalizations (i.e., diabetic ketoacidosis, hyperglycemia and hypoglycemia induced ER and inpatient visits) during 12 months of follow-up was assessed using linear regression. The proportion of days covered (PDC), from pharmacy claims for CGM sensors, was used as a proxy for CGM adherence. PDC was calculated as ‘days of CGM coverage/total days in follow-up’ with values ranging from 0.0 to 1.0. Model covariates included age, gender, region, insurance type, Charlson comorbidity score, and baseline measures of total healthcare resource utilization, DR healthcare utilization, DR hospitalizations, total medical costs and DR medical costs.Results: A total of 14,555 PwT2D on IIT using a CGM (Dexcom users=6,745) were identified. Mean(SD) PDC for Dexcom users was 0.75(0.28) compared to Libre users 0.57(0.34), p<0.0001. Irrespective of CGM brand, adherence was associated with a 4% decrease in inpatient DR visits (β = -0.04, 95% CI = [-0.07 to -0.01], p=0.0037). Similarly, each unit increase in PDC was associated with 6% decrease in DR ER visits (β = -0.06, 95% CI = [-0.08 to -0.04], p<0.0001).Conclusion: These findings indicate for PwT2D using IIT, adherence was higher among Dexcom users compared to Libre users. The results suggest that maintaining adherence to CGM can contribute to reduced DR healthcare utilization.Disclosure P. Nemlekar: Employee; Dexcom, Inc. K. Hannah: Employee; Dexcom, Inc. B.C.L. Liu: Employee; Dexcom, Inc. G.J. Norman: Employee; Dexcom, Inc.FundingAll authors employees of Dexcom Inc.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-1001-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 1002-P: HbA1c Improvement with the Addition of Continuous Glucose
Monitoring to GLP-1 Agonist Therapy in People with Type 2 Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 1002-P
Abstract: Introduction and Objective: Benefits of GLP-1 agonist (GLP-1) use in people with type 2 diabetes (PwT2D) are documented, but the impact of adding continuous glucose monitoring (CGM) to GLP-1 therapy on glycemic outcomes is not well studied.Methods: We conducted a retrospective cohort study of electronic medical record data from 3 centers. Eligible patients were aged ≥18 years, had completed endocrinology/primary care visits between 2021-2024, and had HbA1c measured at 4 timepoints: 12 & 6 months before, and 6 & 12 months after starting GLP-1. Pre-post effects of GLP-1 on HbA1c were evaluated using paired t-tests and McNemar tests. GLP-1 users on CGM initiated ±2 months of GLP-1 (GLP-1+CGM; n=349) were compared to GLP-1 only users (propensity matched 1:3 ratio).Results: We identified 4,110 GLP-1 users (GLP-1+CGM: n=349, mean age=60 years; GLP-1 only: n=3761, mean age=61 years) and 44,087 non-users. GLP-1 use led to reduction in mean HbA1c (7.7% to 7.1%, p < 0.001), increased proportion with HbA1c <7.0% (35% to 51%, p < 0.001), and decreased proportion with HbA1c >9.0% (14% to 6%, p < 0.001) 12 months after GLP-1 initiation. GLP-1+CGM users compared to GLP-1 only users had lower 12-month mean HbA1c (7.2% vs 7.4%, p=0.03) and a greater decrease in HbA1c from baseline to 12 months (-0.9 vs -0.4, difference-in-difference=0.5, p=0.001, Figure).Conclusion: GLP-1 is associated with improved HbA1c outcomes in PwT2D; adding CGM further lowered HbA1c.DisclosureS. Thapa: None. D. Vora: None. N. Rioles: None. S. Tsai: None. R.S. Weinstock: Research Support; Amgen Inc, Eli Lilly and Company, Tandem Diabetes Care, Inc, Diasome Pharmaceuticals, Insulet Corporation, MannKind Corporation, Dexcom, Inc. M. Zupa: None. J. Haw: None. F.J. Pasquel: Consultant; Insulet Corporation. Research Support; Novo Nordisk, Dexcom, Inc., Ideal Medical Technologies, Tandem Diabetes Care, Inc, Insulet Corporation. Consultant; Dexcom, Inc. T. Idrees: Research Support; AbbVie Inc. O. Ebekozien: Research Support; Abbott. Advisory Panel; Sanofi. Research Support; Sanofi, Lilly Diabetes, Medtronic.FundingThe Leona M. and Harry B. Helmsley Charitable Trust
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-1002-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 1003-P: Ketone Profiles in Free-living People with Type 1 Diabetes Using
Continuous Ketone Monitoring-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 1003-P
Abstract: Introduction and Objective: We aim to profile ketone levels in free-living people with type 1 diabetes (T1D).Methods: In addition to demographic, anthropometric, HbA1c and CGM (Abbott Freestyle Libre 2) data, interstitial ketone profiles were assessed 5-minutely with a novel subcutaneously-inserted continuous ketone monitor (CKM, Abbott) during a 2 week run-in for the PARTNER Study (ACTRN12624000448549) where prior SGLT2 inhibitor use was an exclusion.Results: Twelve participants (4 female (33.3%); Age 49.4 (33.0 - 63.6) years; HbA1c 54.1 (48.6 - 58.5) mmol/mol) have been studied to date (16.7% MDI and 83.3% AID). The majority (n=10, 83.3%) had ketone profiles that were <0.6mmol/L throughout the 2 weeks. Two participants had ketones >0.6 mmol/L (0.4% and 2.7% time with ketones 0.6-0.9mmol/L; 0.0% and 0.3% time with ketones 1.0-1.5mmol/L respectively, highest ketone 1.1mmol/L for the latter). Both were males with T1D for at least 10 years and undetectable C-peptide levels, on automated insulin delivery systems with excellent glycemia (HbA1c<53 mmol/mol or <7%) and with total daily insulin doses 0.38 and 0.56 units/kg.Conclusion: Whilst the majority of T1D adults had stable normal ketone levels, a small proportion had acceptable/elevated baseline ketone levels. We aim to determine the factors that could help predict those with T1D who would be at higher risk of diabetic ketoacidosis.DisclosureJ. Ngan: None. Y.W. Kong: None. J.L. Goad: None. M.L. Huang: None. A. Jenkins: Advisory Panel; Abbott. Speaker's Bureau; GlaxoSmithKline plc. Research Support; Abbott, Metronics, Ypsomed AG, Insulet Corporation, Jaeb Center for Health Research, Endogenex, Hemsley Charitable Trust. Speaker's Bureau; CSL Seqirus. Research Support; AbbVie Inc, National Institutes of Health, Juvenile Diabetes Research Foundation (JDRF). S. Vogrin: None. S. Trawley: None. E.I. Ekinci: Research Support; Amgen Inc, Novo Nordisk, Lilly Diabetes, AstraZeneca, Endogenex, Versanis. Advisory Panel; Lilly Diabetes, Novo Nordisk. A. Kriketos: None. S. Fourlanos: Speaker's Bureau; Novo Nordisk, Boehringer-Ingelheim. Research Support; Dexcom, Inc. C.J. Nolan: None. P.V. Taylor: Research Support; Eli Lilly and Company, Novo Nordisk, Boehringer-Ingelheim. J. Fenn: Research Support; Eli Lilly and Company, Novo Nordisk, Boehringer-Ingelheim, Amgen Inc, ACADI. S. Stranks: None. D.N. O'Neal: None.FundingAustralian Centre for Accelerating Diabetes Innovations and Breakthrough T1D (2-SRA-2025-1614-M-B)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-1003-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 1004-P: Glycemic Outcomes by Age in Real-World Implantable 180-Day
Eversense E3 CGM System Users-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 1004-P
Abstract: Introduction and Objective: The 180-day Eversense E3 CGM System was marketed in the U.S. and Europe in 2022. The objective was to determine if glycemic outcomes varied by age in real-world open-loop insulin regimen users.Methods: Anonymized sensor glucose (SG) data from Eversense data management system (DMS) were analyzed for the first 2412 users through a 180‐day wear. Mean SG, glucose management indicator (GMI), median 24-hour transmitter wear time, and percent in glycemic ranges were calculated by age ranges.Results: Among 2412 users, 867 (35.9%) reported TID and 981 (40.7%) reported T2D (38.4% using insulin). Mean percent time in range (TIR, 70-180mg/dL), time <70mg/dL/<54mg/dL and meeting hypoglycemic targets, and time >180mg/dL/>250mg/dL showed the oldest users met >70%TIR (Table). CGM metrics were promising in those 18-24 years; a group often with the least favorable glucometrics. Percent users meeting hypoglycemic targets and wear time were high ranging from 66 to 89% and 87 to 94%, respectively.Conclusion: In Eversense E3 CGM system open-loop users, glycemic outcome targets were met in older adults and were encouraging in the young adults and the whole adult population.Disclosure S. Han: Employee; Senseonics. C. Mdingi: Employee; Senseonics. K.S. Tweden: Employee; Senseonics. F.R. Kaufman: Employee; Senseonics. Consultant; MannKind Corporation, Twin Health.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-1004-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 1005-P: Comparison of Raman-Based Noninvasive Glucose Monitoring Sensor
with Commercially Available Methods-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 1005-P
Abstract: Introduction and Objective: MIT Laser Biomedical Research Center has been developing noninvasive glucose monitoring sensor for the past decades. Based on Raman spectroscopy, we have recently demonstrated the first direct observation of glucose signal from in-vivo skin. Here, we compare its performance with commercially available methods using swine glucose clamping experiments.Methods: One Female Yorkshire swine was selected and used for the three glucose clamping experiments with two-week interval. The blood glucose level was modulated within the range from 75mg/dL to 350 mg/dL. Raman-based noninvasive glucose monitoring sensor was installed to the ear and Dexcom G6 were installed to the belly. YSI and Accuchek measurements were performed on IV blood draw samples. All four measurements were performed every five minutes.Results: Raman-based noninvasive glucose monitoring sensor demonstrated successful prospective prediction with no laser-induced damages to the skin. MARD from Raman-based sensor was 8.8% in comparison with 9.0% from Dexcom G6 and 5.0% from Accuchek. The Clarke Error Grid Analysis confirms the high correlation with the YSI measurement with 96.6% (144/149) in Zone A and all remaining measurements in Zone B.Conclusion: After decades of research, Raman-based noninvasive glucose monitoring may finally become a viable long-term solution for diabetic patients.DisclosureJ. Kang: None. H. Kim: None. H. Yoon: None. P.T.C. So: Research Support; Apollon. Bio.FundingNational Institutes of Health (NIBIB P41EB015871), Samsung Advanced Institute of Technology, Apollon
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-1005-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 1006-P: Developing CGMap—Characterizing Continuous Glucose Monitoring
Data in Patients with Type 2 Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 1006-P
Abstract: Introduction and Objective: To characterize continuous glucose monitoring (CGM) data in patients with type 2 diabetes (T2D), and to assess the relationship between CGM-derived indicators and diabetes-related clinical parameters.Methods: The data was collected from a randomized trial in China (ChiCTR2000039424), in which patients with T2D wore CGM and received acarbose or sitagliptin. Ordinary least square linear regression and the Spearman method were used to test the relationship between CGM-derived indicators and diabetes-related clinical parameters.Results: In all, 528 patients with T2D from a randomized controlled trial were analyzed. It was shown that CV, SD, and MAGE increased with the growing age and diabetes duration, but decreased with the increase of body mass index. Higher fasting plasma glucose, higher baseline HbA1c, and higher insulin resistance levels were associated with higher GRI, TAR, and eA1c, and they were associated with lower TIR. Besides, higher HOMA-2β was associated with higher TIR and TBR, with lower TAR and eA1c. Hemoglobin had positive correlations to SD, TAR, and eA1c.Conclusion: It was found that glucose variability increased with age and the duration of diabetes. However, glucose variability decreased with increased BMI. Meanwhile, greater glycemic variability was associated with worse islet function, higher baseline glucose level, and higher hemoglobin.DisclosureS. Bai: None. C. Lin: None. X. Cai: None. W. Yang: None. F. Lyu: None. L. Ji: None.FundingBeijing Natural Science Foundation (No.7202216); National Natural Science Foundation of China (No.81970698 and No.81970708)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-1006-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 1007-P: Development of Noninvasive Blood Glucose Measurement Using Visible
Light Photoplethysmography Signals in Subjects with Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 1007-P
Abstract: Introduction and Objective: The global diabetic population is expected to reach 800 million by 2035, increasing the need for continuous blood glucose monitoring. Conventional methods, like finger-prick glucometers and invasive continuous glucose monitors, are burdensome due to pain, infection risks, and consumable costs. Non-invasive devices measuring glucose via fingertip tissue have been developed but lack the required accuracy for commercialization.Methods: This study investigates a non-invasive optical glucose meter that accounts for fingertip thickness, skin condition, and body mass index. Blood glucose was measured by analyzing photoplethysmography signals from 660 nm light irradiated onto the fingertip, with venous blood glucose levels used for calibration. Individual characteristics were incorporated during calibration by determining baseline values and applying an appropriate feature extraction algorithm to derive the final formula. A total of 28 diabetic patients (13 males, 15 females; 3 with type 1 and 25 with type 2 diabetes) had their fasting and postprandial glucose levels measured using both the non-invasive device and venous blood sampling.Results: The device's accuracy was evaluated with the mean absolute relative deviation (MARD), which was 8.8%, showing superior accuracy compared to previous studies. Consensus Error Grid (Type 1) analysis revealed 100% of data in zones A and B, confirming clinical reliability. ISO 15197 requires 99% of glucose values to fall within these zones, and this clinical trial confirmed 100% compliance.Conclusion: These results demonstrate the feasibility of non-invasive glucose measurement with accuracy comparable to venous blood glucose levels in subjects with diabetes, supporting the potential for commercialization with further research needed.DisclosureC. Kim: None. J. Yun: None. I. Song: None. H. Park: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-1007-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 1008-P: Assessing Obstetrician’s Awareness of and Experience with
Continuous Glucose Monitoring-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 1008-P
Abstract: Introduction and Objective: Continuous Glucose Monitoring (CGM) recently obtained pregnancy indication and may be used by OB-Gyn providers. The objective is to understand OB-Gyn experience.Methods: An anonymous survey was given to 68 providers in Nassau/Suffolk County, NY between 11/21-12/21/2023.Results: Of the 45 respondents, 42 manage diabetes in pregnancy; all 42 reported awareness of CGM technology. 19% (8/42) manage diabetes independently, 24% (10/42) refer fully to a specialist and 57% (24/42) co-manage diabetes with an endocrinologist or maternal fetal medicine specialist. All (10/10) in the very frequently, frequently and sometimes CGM utilization groups reported "more comprehensive data for decision-making" as the main reason to use CGM. This was also reported by all 8 of the providers that manage their patient’s diabetes. Other main reasons for choosing CGM included “patient satisfaction” by 93% (39/42), and “data for telehealth visits” by 57% (24/42). 89% (8/9) providers that never use CGM still reported "patient satisfaction" as a benefit. 100% (9/9) in the frequent and sometimes CGM utilization groups identified that "knowledge of interpreting CGM data" was a main barrier. Other common barriers were “coverage issues” for 95% (40/42) and “prior authorization requirements” for 88% (37/42). Only 7% (3/42) reported “not feeling confident in the accuracy of the glucose values.”Conclusion: Most OB/Gyn’s surveyed are aware of CGM and chose “patient satisfaction” and “comprehensive data” as main benefits. Improving access and education on data interpretation are barriers to address.DisclosureM. Smith-Levitin: None. R. Casamassa: None. M. Frazzitta: Employee; Abbott. A. Bindal: Employee; Abbott.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-1008-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 1009-P: Complexity Separation among Diabetes Types Depends on Time, Not
Scale Size-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 1009-P
Abstract: Introduction and Objective: This study employs meta-analysis to examine the influence of temporal versus size scales on complexity derived from continuous glucose monitoring (CGM) data in individuals with non-diabetes (ND), type 1 diabetes (T1D), and type 2 diabetes (T2D).Methods: We analyzed existing studies that reported complexity based on multiscale sample entropy (MSE) across at least two scales, using CGM data sampled every three or five minutes. Complexity was plotted against both scale size and time in scale.Results: When MSE was plotted against scale size (Figure 1A), the complexity curves for ND (black) overlapped with those of T1D and/or T2D (red, green, or blue), indicating no clear separation. In contrast, plotting MSE against time in scale (Figure 1B) revealed a distinct pattern: ND curves (black) consistently appeared above T2D curves (red), which were above T1D curves (green) and additionally the curve for mixed T1D and T2D (blue) generally fell below the T2D curves but above the T1D curve, demonstrating clear complexity separation among the groups.Conclusion: Complexity separation among diabetes types is determined by time in scale rather than scale size. These findings emphasize the importance of plotting MSE against time in scale rather than the conventional approach of plotting MSE against scale size for CGM-based complexity analyses.DisclosureR.D. Wang: None. S.J. Fisher: None. X.D. Zhang: None.FundingNational Institutes of Health (U01DK135111 and UL1TR001998, P30DK020579)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-1009-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 1010-P: Glucometer Usability for Type 2 Diabetes Patients Aged
65+—Insights on Physical and Cognitive Challenges-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 1010-P
Abstract: Introduction and Objective:Self-monitoring of blood glucose (SMBG) is essential for effective diabetes management. However, older adults with type 2 diabetes mellitus (T2DM) may face physical and cognitive challenges that hinder glucometer usage. Enhancing glucometer usability is critical to improving adherence and outcomes in this population. To investigate the physical and cognitive barriers to glucometer usage among T2DM patients aged 65 and older and to identify potential improvements in device design and functionality.Methods: This study, conducted at PSH, Vadodara, from January 2022 to April 2024, included interviews with 100 T2DM patients aged 65+, along with consultations with three physicians and senior residents. The study evaluated the usability of various glucometer models, explored patient satisfaction, and identified barriers. Focus group discussions provided additional insights for future enhancements.Results: Both patients and physicians reported general satisfaction with the basic functionalities of current glucometers. However, physical limitations (e.g., dexterity issues, poor vision) and cognitive impairments posed significant barriers to usage. Digital features, including connectivity and advanced interfaces, were often underutilized or deemed unnecessary by older patients but valued by healthcare professionals for monitoring and customizing treatment plans. Divergent responses highlighted the need for simpler designs tailored to geriatric users while maintaining advanced features for healthcare provider access.Conclusion: This study underscores the importance of designing glucometers that address the specific needs of older adults with T2DM. While advanced features may not always benefit patients directly, they can facilitate better healthcare delivery. Future glucometer models should balance simplicity for users with enhanced connectivity for healthcare providers to improve care and adherence.DisclosureV.M. Rathod: None. D. Raval: None. N.J. Patel: None. R.S. Shah: None. M. Subhan: None. A. Bhattacharya: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-1010-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 1011-P: Refined Time-in-Range Analysis for Continuous Glucose
Monitoring—Mitigating Bias from Missing Data in Inpatient Glycemic
Control-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 1011-P
Abstract: Introduction and Objective: Continuous glucose monitoring (CGM) is increasingly used in US hospitals for diabetes management, with Time in Range (TIR) as a key glycemic control metric. However, routine TIR analyses overlook missing data in inpatient CGM studies, such as insufficient CGM sampling due to short hospital stays. To address this, a refined TIR analysis approach was developed to mitigate biases from missing data.Methods: We applied the new method to data from 249 subjects in two prospective inpatient CGM studies. We compared TIR outcomes between patients undergoing CGM-guided insulin adjustment and those with capillary point-of-care glucose monitoring.Results: The analyses revealed differences between the new refined mean TIR analysis, which accounts for missing data, and the standard method, which does not (see Table 1). Group comparisons based on the refined analysis showed a notable reduction in the percent time spent in hypoglycemia of <70 mg/dL (0.34 ± 0.14% vs. 0.84 ± 0.15%, p=0.01) while maintaining comparable mean TIR in the target range of 70-180 mg/dL (60.43 ± 3.92% vs. 61.06 ± 2.12%, p=0.89).Conclusion: The refined TIR analyses confirmed significant reductions in hypoglycemia with CGM-guided insulin adjustments. This supports the ongoing integration of CGM into clinical practice to enhance glycemic control while minimizing the risk of hypoglycemia.DisclosureQ. Yu: None. G. Umpierrez: Research Support; Abbott, Dexcom, Inc., Bayer Pharmaceuticals, Inc, Corcept Therapeutics. Advisory Panel; Dexcom, Inc., GlyCare Health. G.M. Davis: Research Support; Insulet Corporation. M. Fayfman: Research Support; Abbott, Dexcom, Inc.FundingNational Institutes of Health (R01DK136023)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-1011-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 1012-P: Codesigning Solutions for CGM Use in Community Health Centers
-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 1012-P
Abstract: Introduction and Objective: Co-design is a research method to help develop solutions for complex healthcare problems. Continuous glucose monitoring (CGM) helps optimize diabetes mellitus (DM) care, yet uptake in community health centers (CHCs) is low. This study aimed to identify barriers to CGM use and propose user-centered solutions to increase CGM use in CHCs.Methods: DM team members involved in implementation or delivery of DM care in CHCs in the US were recruited to participate in 1-2 sessions via videoconferencing, which were audio recorded and transcribed. Session 1 elicited barriers and facilitators, guided by the Consolidated Framework for Implementation Research (CFIR) and System Engineering Initiative for Patient Safety (SEIPS) model. Session 2 (design) focused on ideating, categorizing, and prioritizing solutions. Transcripts were coded deductively using these constructs, and inductive codes were generated from data. A code matrix was used to organize coded data and develop themes. Solutions were categorized at the individual, clinic, or external level.Results: Twenty-two participants spanning roles (quality, clinical), across 5 states, participated. Analyses identified barriers, facilitators, and solutions to CGM initiation and data monitoring. CGM initiation was hindered by insurance requirements, inadequate staffing, and low confidence in managing patients with CGM. Remote monitoring of CGM data was limited by a perceived lack of patient access to necessary technologies (cell phones, internet) and limited integration of data into the EHR and workflows. Facilitators (dedicated expertise in CGM, utilization of CGM samples) and solutions were largely focused on initiation. Solutions were at the individual (trainings), clinic (partnerships with CGM companies, utilization of diabetes prevention program infrastructure), and external levels (broader coverage, receiver redesign).Conclusion: Multilevel solutions are needed to ensure that healthcare teams and patients benefit from DM technologies.DisclosureE.L. Lam: None. M.E. Wolter: None. A. Pack: Consultant; Gilead Sciences, Inc. J. Gacki-Smith: None. S.E. DeLacey: None. S. Agarwal: Research Support; Dexcom, Inc. B. Ankenman: None. D.W. Gatchell: None. A. Berry: None. C.T. Schaefer: None. M.J. O'Brien: None. A. Wallia: Research Support; UnitedHealth Group.FundingNIH NIDDK (P30DK020541-4751); Chicago Center for Diabetes Translation Research (P30 DK092949)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-1012-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 1013-P: Estimates of Mean Red Blood Cell Age (M RBC ) Obtained with
Continuous Glucose Monitoring (CGM)-Based Computational Methods Are
Comparable to Those Obtained with Stable Isotope (SI) In Vivo Measurements
-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 1013-P
Abstract: Introduction and Objective: HbA1c reflects average blood glucose over a period determined by individuals’ MRBC. Adjusting HbA1c for MRBC variation could enable personalized diabetes management. Computational methods that estimate MRBC using CGM and HbA1c (CGM-MRBC) offer a cost-effective and time-efficient alternative to in-vivo measurements (SI-MRBC). However, the accuracy of CGM-MRBC compared to SI-MRBC has yet to be evaluated.Methods: We analyzed 63 individuals without hematological abnormalities who exhibited a discrepancy >±0.5% between HbA1c-based and CGM-based glycemic estimates. Individuals had multiple HbA1c measurements preceded by at least 2 weeks of CGM data. CGM-MRBC was inferred at each HbA1c measurement using the model in Malka et al. (2016) and averaged to minimize noise. SI-MRBC was obtained using oral15N-glycine heme labeling for all 63 subjects, and was repeated for 7 subjects whose average was considered.Results: Individuals had an average of 6±2 estimates of CGM-MRBC with a mean (SD) intra-patient coefficient of variation of 7 (3) % corresponding on average to ~3 days. In the population, CGM-MRBC was lower than SI-MRBC, with means (SD) of 47.4 (7.3) and 59.9 (6.5) days respectively (two-sided one-sample t-test p<0.0001). CGM-MRBC and SI-MRBC were correlated with an R2 [95% CI] of 0.52 [0.38, 0.68] (p<0.0001).Conclusion: Initial analysis suggests CGM-MRBC explains more than half of the variance in SI-MRBC and might provide an efficient means to personalize HbA1c interpretation in patient care. Further work on the computational model used to estimate CGM-MRBC is needed to improve its accuracy.DisclosureV. Tozzo: None. J. Craig: None. S.O. Omololu: None. M. Genco: None. E.P. Smith: None. D. Thibault: None. S. Arbabi: None. W. Abplanalp: None. C.T. Quinn: Advisory Panel; Disc Medicine. Consultant; NovoNordisk. Research Support; Emmaus Medical. C.J. Lindsell: Research Support; Biomeme, biomerieux. Other Relationship; Rocket Phrmaceuticals, Regeneron Pharmaceuticals. Stock/Shareholder; Bioscape Digital. Research Support; Cytokinetics. Consultant; PersistenceBio. Advisory Panel; AstraZeneca, Novo Nordisk, Novartis Pharmaceuticals Corporation. R.M. Bergenstal: Advisory Panel; Abbott. Research Support; Abbott. Consultant; Abbott. Research Support; Dexcom, Inc. Consultant; Dexcom, Inc., Eli Lilly and Company. Research Support; Eli Lilly and Company. Consultant; Novo Nordisk. Research Support; Novo Nordisk. Consultant; Roche Diabetes Care, Sanofi, Medtronic. Research Support; Medtronic, Insulet Corporation, Hemsley Charitable Trust. Other Relationship; MannKind Corporation. Consultant; Medscape. Research Support; National Institute of Diabetes and Digestive and Kidney Diseases, Tandem Diabetes Care, Inc, UnitedHealth Group. Consultant; Vertex Pharmaceuticals Incorporated, Ascensia Diabetes Care, American Diabetes Association, Hygieia, embecta, Senseonics, Zealand Pharma A/S. R.S. Franco: None. J. Higgins: None. R.M. Cohen: Research Support; Dexcom, Inc. Stock/Shareholder; Abbott. Research Support; National Institute of Diabetes and Digestive and Kidney Diseases.FundingNational Institutes of Health R01 DK123330 (rmc); National Institutes of Health UL1 TR001425 (Center for Clinical & Translational Science & Training); Dexcom Corporation
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-1013-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 1014-P: The Cut Diabetes Trial—A Randomized Study of Culturally Tailored
Diabetes Self-Care and Management Education Support (DSMES) for Type 2
Diabetes with and without Real-time Continuous Glucose Monitoring and Its
Effect on Lifestyle-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 1014-P
Abstract: Introduction and Objective: Culturally tailored DSMES and RT-CGM support patients with T2DM. Our objective was to assess how culturally tailored DSMES influenced nutrition and activity and if RT-CGM use enhanced DSMES's effects in Latino populations.Methods: Latino adults with T2DM on no insulin or basal insulin only, were randomized 1:1 to receive virtually delivered education only (blinded CGM) or with cyclic RT-CGM. The primary outcome was HbA1c at 12-weeks; secondary outcomes included lifestyle modifications assessed by questionnaires.Results: Eighty one participants (41 RT-CGM and 40 blinded) completed lifestyle questionnaires at baseline and 12-weeks. The nutrition short summary score showed overall improvement (-1.76 (2.43) RT-CGM, -1.33 (3.58) blinded, (p=0.5)). RT-CGM reduced fast food or snack consumption by 34% vs. 19% for blinded. Sugared beverages decreased by 23% for RT-CGM vs. 26% for blinded. Vegetable and fruit consumption increased by 36% and 20% for RT-CGM and 23% and 26% for blinded, respectively. Physical activity days for vigorous and moderate exercise increased by 1.00 (3.18) and 0.86 (2.27) for RT-CGM vs. 0.14 (1.45) and 0.67 (2.40) for blinded. Walking for 10 minutes/day increased 0.3 (3.1) for RT-CGM and 1.0 (3.7) for blinded. Among RT-CGM users, 81% felt CGM made them read labels more, 83% limited or excluded rice, and 78% were more likely to go for a walk. 97% of RT-CGM participants felt that CGM led to a healthier lifestyle.Conclusion: Culturally tailored DSMES facilitates healthy lifestyle changes. CGM appeared to promote increased physical activity and it may improve lifestyle modifications when combined with DSMES.DisclosureJ. Vidovic: None. D. Gil Menchaca: None. E. Jones: None. P. Berberian: None. L. Wright: Advisory Panel; Genentech, Inc. A. Vasconcelos: None. B.A. Comstock: None. N.M. Ehrhardt: Advisory Panel; Novo Nordisk. Research Support; Dexcom, Inc. Advisory Panel; Bayer Pharmaceuticals, Inc. Research Support; Novo Nordisk. Advisory Panel; Dexcom, Inc. Research Support; Boehringer-Ingelheim.FundingAmerican Diabetes Association (11-21-ICTSHD-51)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-1014-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 1015-P: Improving CGM Implementation and Glycemia in Primary
Care—Primary Care Education and Practice Adoption Resource Evaluation
for Continuous Glucose Monitoring (PREPARE 4 CGM) Study-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 1015-P
Abstract: Introduction and Objective: Continuous glucose monitoring (CGM) improves glycemia and is in ADA Standards of Care, but uptake is limited in primary care, where most diabetes care occurs. We compared 3 CGM implementation strategies in 76 Colorado primary care clinics.Methods: Hybrid type 3 effectiveness-implementation study of 3 CGM implementation strategies: online education using American Academy of Family Physicians Transformation in Practice Series (TIPS), TIPS + practice facilitation (PF), and a virtual CGM initiation service (virCIS). Relationships between outcomes (CGM prescriptions, A1C) and independent variables (time, clinic characteristics, participant demographics) were assessed via generalized linear mixed models.Results: Table 1 shows baseline characteristics. All strategies increased CGM prescribing (F(2,110)=48.2, p<.001); TIPS+PF and virCIS had greater increases than TIPS (F(4,110)=4.0, p=.005). All strategies decreased A1C (F(1,155)=32.3, p<.001), with no difference between strategies (p>.05).Conclusion: All 3 strategies increased CGM implementation and decreased A1C in primary care settings. These strategies could be applied in other primary care clinics. Wider uptake would increase CGM access beyond endocrinology and may improve outcomes for primary care patients with diabetes.Disclosure S.M. Oser: Research Support; Abbott. Other Relationship; American Diabetes Association, Association of Diabetes Care & Education Specialists. Advisory Panel; Ascensia Diabetes Care. Research Support; Dexcom, Inc., Insulet Corporation, Leona M. and Harry B. Helmsley Charitable Trust. Advisory Panel; National Committee for Quality Assurance. Consultant; Sequel Med Tech. L. Dickinson: None. K.T. Wiggins: None. B. Jortberg: None. M. Gritz: None. S. Kirchner: None. T. Hall: None. W.P. Dickinson: None. T. Oser: Consultant; Dexcom, Inc. Research Support; Abbott, Insulet Corporation, Dexcom, Inc. Advisory Panel; Medscape.FundingHelmsley Charitable Trust (G-2204-05191)
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-1015-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 1016-P: Identification of Clinically Significant Automatically Detected
Meal-Like Glucose Excursion in People with Type 1 Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 1016-P
Abstract: Introduction and Objective: The clinical use of automatic meal detection algorithms is increasing, along with interest in the significance of missed bolus doses. This study aims to identify and validate characteristics of automatically detected meal-like glucose excursions that provide clinically significant information in adults with type 1 diabetes.Methods: This prospective cohort study enrolled 134 adults with type 1 diabetes who initiated personal continuous glucose monitoring (CGM) at Samsung Medical Center from April 2019 to January 2023. Participants wore either Dexcom G5/G6 or Freestyle Libre for at least 450 days, with a sensor wear time of 70%. Meal-like glucose excursions were detected by the Glucose Rate Increase Detector algorithm (GRID), which was modified to determine premeal and peak glucose as well.Results: At baseline, the inverse correlation between the number of GRID-detected meal-like glucose excursions (GRID-excursions) and time in range (70-180 mg/dL, TIR) increased with higher peak glucose thresholds (all excursions, R2= 0.125; ≥ 180 mg/dL, R2= 0.208; ≥ 250 mg/dL, R2= 0.459). There was a significant inverse correlation between the mean time-to-peak in minute for GRID-excursions and TIR (R2= 0.329). The inverse correlation between the number of GRID-excursions and TIR increased with longer time-to-peak time thresholds (≥ 60 min, R2= 0.262; ≥ 90min, R2= 0.319). An increase of 4 GRID-excursions with peak glucose ≥ 250 mg/dL per 14 days linked to a > 5% decrease in TIR, without baseline time-to-peak thresholds. Participants with 4 such excursions at baseline had higher odds for >10% points improvement in TIR over one year, adjusted for multiple covariates including baseline HbA1c.Conclusion: The number of GRID-excursions, where peak glucose levels were ≥ 250 mg/dL with any time-to-peak glucose, was identified as a correlate with baseline TIR and a predictor of greater improvement in TIR at one year.DisclosureS. Park: None. S. Kim: None. L. Jina: None. J. Kim: None. R. Oh: None. S. Cho: None. S. Park: None. G. Kim: None. J. Kim: None. S. Jin: None.FundingThe National Research Foundation (NRF) funded by the Korean government (MSIT) (No. RS-2023-00262002).
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-1016-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 1018-P: GluVue: Revolutionizing Continuous Glucose Monitoring Data
Interpretation in Clinical Practice-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 1018-P
Abstract: Introduction and Objective: GluVue is a free application designed to enhance the efficiency of continuous glucose monitoring (CGM) data analysis for healthcare providers. Its primary goal is to improve clinical workflows and patient care in diabetes management.Methods: GluVue is designed to integrate seamlessly with electronic health records (EHR) and provide real-time analysis of continuous glucose monitoring (CGM) data. The application initiates its workflow when a healthcare provider places an order in the patient's EHR, which triggers a connection request in the MyChart patient portal app. Upon patient or proxy acceptance, connectivity is established, allowing CGM data to be shared with Apple Health or the Health Connect app via HealthKit and subsequently integrated into the Epic EHR through MyChart. The system pulls raw glucose data from Epic and transforms it into intuitive visual formats i.e. modal-day reports, daily/weekly trend graphs, and an Ambulatory Glucose Profile display without storing data in Epic, thereby addressing potential security concerns.Results: GluVue significantly reduces the time required for CGM data interpretation, allowing clinicians to access real-time insights without the need for multiple portal logins. Users report enhanced ability to identify glucose management opportunities, leading to more informed, data-driven conversations with patients. This automated handling of CGM data increases the efficiency of reviewing patient data.Conclusion: GluVue represents a significant advancement in diabetes care by streamlining CGM data interpretation and integrating seamlessly within EHR systems. GluVue empowers healthcare providers to make more informed and timely decisions, ultimately improving patient outcomes. The implementation process can be initiated through GluVue's Showroom webpage by submitting a request to the institution's informatics Systems department, enabling widespread adoption of this innovative clinical tool.Disclosure K. Cefalu: Stock/Shareholder; Abbott, Dexcom, Inc.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-1018-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 1019-P: Artificial Intelligence (AI)-Driven HbA1c Estimation from Retinal
Images and Its Correlation with Lab-Measured HbA1c-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 1019-P
Abstract: Introduction and Objective: Retina provides a window to systemic diseases, including Type 2 Diabetes(T2D). We evaluated an AI model for estimating HbA1c using retinal biomarkers.Methods: We evaluated retinal fundus camera images & HbA1c (measured on same day in lab with HPLC method) from routine evaluations (12 normal; 158 T2D per ADA criteria) at a tertiary center in India. We extracted 226 vascular features (e.g., tortuosity, branching) & pruned correlated features. Linear Discriminant Analysis with 3 fold cross validation identified top 10 features via Wilcoxan Rank-Sum test to distinguish T2D from normal. A Random Forrest Regressor was trained (St,n=85) on these features to estimate HbA1c & evaluated on test set (Sv,n=85). Model performance was tested using Pearson's Correlation Coefficient (PCC) & Bland-Altman analysis (BA) for linearity & agreement with lab-based HbA1c.Results: The venous feature-based model exhibited a strong linear correlation [PCC=0.98 (95%CI:0.67,0.99), R2=0.84 (95%CI:0.61,0.99), mean absolute error=0.8]. BA revealed minimal bias (mean difference=0.09) & acceptable agreement (-0.83 to +1.0), confirming good agreement between estimated and lab-based HbA1c (Fig).Conclusion: This proof-of-principle study shows AI-based HbA1c estimation, using retinal biomarkers on routine fundus images, is possible & correlates well with lab-based HbA1c.DisclosureS. Kaup: None. S. Sil Kar: None. R. Rajalakshmi: None. R.M. Carrillo-Larco: None. R. Dhamdhere: None. A. Madabhushi: Stock/Shareholder; Picture Health. Consultant; AbbVie Inc, SimbioSys, Aiforia. Stock/Shareholder; Inspirata. Research Support; Bristol-Myers Squibb Company, AstraZeneca. Stock/Shareholder; Elucid Bioimaging. R. Anjana: None. R. Jagannathan: None. M.K. Ali: Advisory Panel; Eli Lilly and Company. V. Mohan: Speaker's Bureau; Novo Nordisk. Advisory Panel; Abbott. Research Support; Servier Laboratories. Speaker's Bureau; USV Private Limited, Sanofi, Medtronic, Eli Lilly and Company. K. Narayan: None.FundingCOALESCE program, which is a project funded by Fogarty International Center of the National Institutes of Health under Award Number D43 TW011404
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-1019-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 1020-P: Evaluating Glycemic Benefits of an AI-Driven Glucose Prediction
App via Digital Twin Technology-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 1020-P
Abstract: Introduction and Objective: AI-driven glucose predictions help CGM users manage glucose levels more proactively. The Accu-Chek® SmartGuide Predict app notifies of low glucose levels within 30 minutes (LGP), nighttime hypoglycemia risk (NLP), and provides a continuous 2-hour glucose forecast (GP). This study evaluates the potential glycemic benefits of the app via in-silico analysis.Methods: Using UVa's digital twin methodology, 2458 days from 20 individuals in the REPLACE-BG dataset were simulated. Interventions: 15g fast-acting carbs after LGP notifications, 30g slow-absorbing carbs for high NLP risk at 22:30, and advancing/adding correction boli if GP forecast >220 mg/dL. Baseline intervention used a GP-like hyperglycemia mitigation strategy, substituting predictions with current CGM data. All hypoglycemia interventions are aligned with ADA guidelines. Nighttime meals/boli were omitted to better assess NLP.Results: LGP reduced %time <70mg/dL (4.2±1.5 vs 0.46±0.28 p<1e-4). GP reduced %time >180mg/dL (25.3±10.2 vs 22.0±8.6 p<1e-4). NLP decreased overnight %time <70mg/dL (5.6±2.2 vs 3.8±1.2 p<1e-4). Combining all features significantly reduced time outside range.Conclusion: The Accu-Chek® SmartGuide Predict app has the potential to enhance glycemic control in T1D. Limitations include the in-silico nature of the study and assumptions made in the user behaviour models.Disclosure P. Herrero: Employee; Roche Diabetes Care. M. Andorrà: Employee; Roche Diagnostics. Stock/Shareholder; Roche Diagnostics. M.D. Breton: Speaker's Bureau; Sinocare Inc, Tandem Diabetes Care, Inc. Consultant; Roche Diabetes Care, Boydsense. Y. Klopfenstein: Consultant; Roche Diagnostics. T. Glatzer: Employee; Roche Diabetes Care. Stock/Shareholder; Roche Diabetes Care, Abbott, Dexcom, Inc.FundingThe research has been funded by Roche Diabetes Care GmbH
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-1020-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 1021-P: Analysis of Self-Management Actions Taken by Level2 Participants
with T2DM to Improve Long-Term Glycemic Control-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 1021-P
Abstract: Introduction and Objective: Level2 Specialty Care combines providers, coaches, an app, and CGM devices to help people with T2DM improve their glucose management. Participants can work with a care team to understand factors impacting glucose levels then implement behavioral changes to improve glycemic control. A component is the use of planned actions in the Level2 app. The objective of this research is to analyze the type, frequency, and pattern of actions taken by participants based on their glucose data.Methods: The analysis cohort comprised participants joining Specialty Care between Jan 1, 2023 and Jun 15, 2024 with a CGM utilization window of at least 180 days between their first recorded CGM data and their end date (the earliest of the last recorded CGM data, leaving Specialty Care, or the analysis end date of Dec 15, 2024) together with CGM data for at least 50% of days and at least 5 of every 6 months during the utilization window. All logged actions were manually categorized into themes.Results: A total of 3,773 participants were included, with a mean (SD) CGM utilization window of 479 (182) days and a mean daily CGM utilization rate of 83.6% (13.8%). The cohort was 45% male, with a mean age of 53 (9) years, mean first recorded GMI of 7.2% (1.1%), and mean first recorded time in range of 70% (28%). Overall, 30,772 actions were logged by 3,092 people (82% of the cohort), a mean of 8.1 per participant. Actions were categorized as Nutrition (36%), Movement (33%), Tracking (19%), Mindfulness (9%), Treatment (actions related to medications, seeing a physician, coaching, etc.; 1%), and Other (2%). Movement was the action category logged by the most participants (54%). Treatment was the least common action category, logged by 4% of participants.Conclusion: The Level2 app, in conjunction with CGM data, was well utilized by participants with T2DM, who typically logged multiple actions. Changes to Nutrition and Movement were the most recorded categories of self-management actions.Disclosure S. Bacon: Employee; UnitedHealth Group. Stock/Shareholder; UnitedHealth Group. C. Simmer: Employee; UnitedHealth Group.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-1021-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 1023-P: Noninvasive Detection of Hyperglycemic Events in Persons with
Diabetes through Development of a Breath-Based Sensor Array-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 1023-P
Abstract: Introduction and Objective: Breath-based approaches in medical diagnostics is an expanding field that has great potential to make clinical impact in the 21st century. Exhaled breath analysis in biomedicine has significant advantages since it is highly noninvasive, virtually limitless by nature, and most importantly a rich source of volatile organic compound (VOC) biomarkers.Methods: VOCs in breath are not only clinically relevant biomarkers for diabetes, but also hyper- and hypoglycemic events. Therefore, this study seeks to develop and test a wearable prototype device, in the form of a breathalyzer, that can be used to alert diabetic patients of hypo- or hyperglycemia onset. The watch-sized device is designed to be worn around the patient’s neck and houses a chip of four gas sensors coated with a proprietary layer of tin oxide which uniquely responds to different biomarkers of hypo-/hyperglycemia. The prototype is also equipped with a heater which activates the metal oxide sensing layers, as well as humidity and temperature sensors which can be used to normalize the resulting data. Finally, the device leverages a Bluetooth communication module to transmit data seamlessly to a smart phone device through the cloud.Results: Experiments were undertaken to qualify the device through testing acetone standards in the gas phase at concentrations and flow rates relative to exhaled breath analysis. The results showed that the sensors responded to acetone at concentrations as low as 800 parts per billion with a dynamic linear range that spanned at least 4 parts per million. The calibration curve displayed a strong linear correlation across these ranges as demonstrated through the high coefficient of determination (R2 > 0.95).Conclusion: We anticipate performing further studies to consider additional factors including VOC selectivity and inter-device variability. The next step will be clinical trials to observe how the device performs for persons with diabetes in real world settings.DisclosureM.D. Woollam: None. S.S. Heranjal: None. Y. Kasa: None. A.P. Siegel: Consultant; Scosche Industries. M. Agarwal: Consultant; Scosche Industries.FundingThis work in partial was supported by Scosche Industries.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-1023-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 1024-P: An Innovative Approach to Durable and Accurate Glucose Sensing
Technology-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 1024-P
Abstract: Introduction and Objective: Continuous glucose monitoring (CGM) faces significant challenges in achieving long-term stability and precision, particularly in hypoglycemic ranges. To address these limitations, Carbometrics has developed a novel CGM based on a synthetic Glucose Binding Molecule (GBM) that is both robust and accurate. This study aims to evaluate the performance of this innovative CGM sensor through extensive in vivo and in vitro testing.Methods: Prototype percutaneous filament-type CGM sensors were prepared by immobilizing the sensor chemistry within a durable and biocompatible polymer and coating it onto a fibre optic filament using a simple and highly reproducible process. The sensors were sterilized using ethylene oxide and randomized into three groups: <ol> <li>In vivo testing: Sensors implanted subcutaneously into a pig.</li> <li>In vitro testing: Sensors cycled daily between 2-20 mM glucose at 37°C in phosphate-buffered saline (PBS) in a custom-built in vitro setup.</li> <li>Dry aging: Sensors aged dry at ambient temperature.</li> </ol>Results:In vivo and in vitro testing demonstrated: <ul> <li>Exceptional stability and accuracy, particularly in hypoglycemic ranges, sustained over six weeks of in vivo testing.</li> <li>No statistically significant differences were observed between the in vivo, in vitro, or dry-aged sensors.</li> <li>No significant interference from potential interfering substances during in vitro testing.</li> <li>Longevity exceeding one year (based on extrapolated in vitro data), with performance unaffected by ethylene oxide sterilization.</li> </ul>Conclusion: The novel CGM technology developed in this study represents a transformative advancement in continuous glucose monitoring solutions. Its unparalleled stability and precision, particularly in challenging hypoglycemic ranges, make it an ideal candidate for long-term implantable CGMs and critical care applications. This platform addresses key limitations of current CGM technologies, paving the way for more reliable and impactful glucose monitoring solutions.DisclosureA. Chapman: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-1024-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 1025-P: Effect of Intermittently Scanned Continuous Glucose Monitoring in
Older Adults with Type 2 Diabetes on Noninsulin Therapy—A Post Hoc
Analysis of a Randomized Clinical Trial-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 1025-P
Abstract: Introduction and Objective: CGM decreases A1C and glycemic variability and reduces the risk of hypo- and hyperglycemia in insulin-using older adults with T2D. Limited data document CGM efficacy in older adults not using insulin. In this post-hoc analysis of data from the IMMEDIATE study, we compared differences in mean percentage TIR with intermittent subcutaneous CGM (isCGM) + DSME vs DSME alone in participants with T2D aged <65 and ≥65 years.Methods: The isCGM metrics were analyzed using a linear mixed-effects model, with fixed effects for treatment and age group and random effect for study site.Results: See tablesConclusion: Our findings support the use of isCGM + DSME to increase TIR in non-insulin using persons with T2D aged <65 and ≥65 years.DisclosureC. DeCara: None. A.M. Marney: None. S. Gholam: None. J. Skelly: None. M.P. Gilbert: Advisory Panel; Novo Nordisk.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-1025-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 1026-P: Sustained Benefits of Continuous Glucose Monitoring Combined with
Geriatric Principles in Reducing Hypoglycemia at 12 Months in Older Adults
with Type 1 Diabetes-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 1026-P
Abstract: Introduction and Objective: In our previous study entitled “Technological Advances in Glucose Management in Older Adults [TANGO]” (NCT03078491), we have shown that CGM use enhanced by geriatric principles (eCGM) in older adults with type 1 diabetes (T1D) lowers hypoglycemia (<70 mg/dL) without worsening glycemic control, compared to control group receiving usual care, at 6-months (PMID: 39325586). The aim of this study is to evaluate whether the benefits of eCGM are sustained during the observational extension phase.Methods: Older adults with T1D (≥65 years old) with hypoglycemia, either CGM naïve or CGM users, who completed the 6 month intervention phase, were assessed at 12 months. The primary endpoint was change in duration <70 mg/dL. Secondary outcomes included changes in other CGM metrics and HbA1c from 6 to 12 months.Results: Out of 48 participants in the intervention arm at 6 months, 90% (n=43) completed the 12 month assessment. Between 6 and 12 months, there was no change in median duration of hypoglycemia (<70 mg/dL) (1.34 (IQR 1.6) vs 1.1 (IQR 2.2) %; p=0.4), mean glucose (171 ± 22 vs 168 ± 26 mg/dL; p=0.1), coefficient of variation (0.35 ± 0.06 vs 0.35 ± 0.07%; p=0.5) and HbA1c (7.5 ± 0.8% vs 7.5 ± 0.9%; p=0.7), while time-in-range improved (57% vs 62%; p <0.001). There were no differences in these measures when the group was stratified by CGM use at baseline (naïve vs. user).Conclusion: In older adults with T1D and hypoglycemia, benefits of CGM use, combined with geriatric principles, were sustained after observational extension phase, independent of the status of CGM use at baseline.Disclosure E. Toschi: Consultant; Vertex Pharmaceuticals Incorporated, Sequel Med Tech. Research Support; Dexcom, Inc. C. Slyne: None. M. Savory: None. S. Kasetti: None. H. Brabant: None. N. Krakoff: None. A. Adam: None. M. Munshi: Advisory Panel; Abbott, Medtronic. Research Support; Dexcom, Inc. Advisory Panel; Sanofi.FundingThis study was supported by theNational Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health (grant DP3DK112214 to M.N.M. and E.T.). CGM materials were partially suppliedby Dexcom.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-1026-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 1027-P: Evaluating the Accuracy of a Novel AI-powered Optical Device for
Noninvasive Glucose Monitoring—Results from a Prospective Clinical Study
-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 1027-P
Abstract: Introduction and Objective: Diabetes management requires frequent glucose monitoring. While self-monitoring using finger-stick tests is common, it is invasive and painful, leading to poor adherence. Non-invasive glucose monitoring technologies offer a promising alternative by providing a more convenient option. The objective of this prospective clinical study was to evaluate the accuracy and performance of a novel prototype device combining optical sensors with artificial intelligence (AI) algorithms for non-invasive glucose measurement in individuals with and without diabetes.Methods: For this study 805 individuals (mean age 50.99 ± 15.97 years; 57.27% female) were recruited to undergo blood glucose measurement using both the prototype device and conventional finger stick method. The measurement agreement between the two methods was evaluated using modified Bland-Altman analysis and mean absolute relative difference (MARD). Factors influencing measurement discrepancies were identified through generalized linear regression. Laboratory parameters were compared between glucose level subgroups.Results: For glucose levels ≤100 mg/dL, 89.8% of prototype measurements were within ±15 mg/dL or 83.5% within ±15% of reference values. For levels >100 mg/dL, 63.8% were within ±15 mg/dL or 74.0% within ±15%. Overall, MARD was 9.84 ± 8.33%. HbA1c and estimated average glucose showed significant associations with measurement discrepancies (p < 0.0199). Participants with glucose levels >100 mg/dL exhibited significantly higher levels of HbA1c and estimated average glucose compared to those with glucose levels ≤100 mg/dL (p < 0.0001).Conclusion: The novel device demonstrated promising results for non-invasive glucose monitoring, particularly in the lower glucose range. This technology shows potential for convenient, pain-free glucose monitoring in diabetes management, though additional research is required to validate its performance in larger, more diverse populations.DisclosureD. Avtanski: None. E. Karami: None. P.K. Karla: None. T. Leung: None. J. Isenberg: None. B. Salehian: None. M. Kochakzade: None.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-1027-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 1028-P: How Stable Is the Discrepancy between HbA1c and Glucose Management
Index' The Multicenter Franco–Belgian Concordance Study over 2 Years-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 1028-P
Abstract: Introduction and Objective: Discrepancy between HbA1c and glucose management index (GMI) is usual but its stability over time is unknown.Methods: We analyzed 386 patients with diabetes (83% type 1) in 10 centers. They had continuous glucose monitoring (CGM) with FreeStyleLibre® 1 or 2 (FSL). For each participant, we specifically collected CGM data over 90 days and concomitant HbA1c level at Month 0 (M0), 12 (M12) and 24 (M24). We calculated the HbA1c/GMI ratio and considered three groups: ratio≤0.95 (G-), 0.96-1.05 (G=) and >1.05 (G+).Results: At M0, mean age was 51±17 years, HbA1c 7.6±1.0%, GMI 7.4±0.8%. The mean HbA1c/GMI ratio changed over time (1.031 at M0, 1.015 at M12 and 0.999 at M24; p<0.05 even after adjustment for FSL type). At M0, the repartition in G-, G= and G+ was 12.2%, 44.0% and 43.8%, respectively (X-axis). Many individuals switched to other groups at M12 (Y-axis) and further at M24 (G- in green, G= in orange and G+ in red). The 13.2% of patients consistently G+ at M0-M12-M24 were associated to high age (by 10 years: aOR 1.45 (95%CI 1.15-1.84, p=0.002), but not complications.Conclusion: The high instability of the HbA1c/GMI ratio over time can be explained by time-varying unmeasured individual and collective factors and measurement errors, suggesting that both indicators should be considered per se during follow-up of patients.Disclosure E. Cosson: Board Member; Abbott Diagnostics, Amgen Inc, Bayer Pharmaceuticals, Inc, Boehringer-Ingelheim, Dexcom, Inc., Lilly Diabetes, Medtronic, Novartis AG, Novo Nordisk, Roche Diagnostics, Sanofi. G. Prevost: None. P. Oriot: Research Support; Abbott. A. Andrieu: None. A. Vandelaer: None. M. Joubert: Board Member; Abbott, Medtronic, Insulet Corporation, Dexcom, Inc., Ypsomed AG, Lilly Diabetes, Novo Nordisk, Sanofi. R. Leroy: Consultant; Elivie -home health provider. Research Support; Medtronic, MEDTRUM. P.A. Monguillon: Consultant; Abbott Diagnostics, Novo Nordisk, Sanofi, Eli Lilly and Company, AstraZeneca. A. Penfornis: Speaker's Bureau; Abbott, AstraZeneca. Board Member; Abbott. Speaker's Bureau; Boehringer-Ingelheim, Dexcom, Inc., Eli Lilly and Company. Board Member; Insulet Corporation. Speaker's Bureau; Insulet Corporation. Board Member; Medtronic. Speaker's Bureau; Menarini. J. Philips: None. J. Julla: Other Relationship; Lilly Diabetes. Board Member; Sanofi. Other Relationship; Novo Nordisk. A. Gillibert: None. M. Vannier: None. J. Riveline: Consultant; Abbott, Lilly Diabetes, Novo Nordisk, Sanofi, Dexcom, Inc., Air Liquide, Insulet Corporation. Research Support; Tandem Diabetes Care, Inc, Juvenile Diabetes Research Foundation (JDRF).
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-1028-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 1029-P: Periodic Use of Intermittently Scanned CGM with AI Food Camera in
Non-insulin-Treated Type 2 Diabetes—A Randomized Clinical Trial-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
First page: 1029-P
Abstract: Introduction and Objective: To evaluate the efficacy of periodic use of intermittently scanned continuous glucose monitoring (isCGM) with an artificial intelligence (AI)-Food Camera in non-insulin-treated type 2 diabetes (T2D) patients.Methods: In this randomized clinical trial, participants were randomly assigned in a 1:1:1 ratio: group 1 (isCGM + AI Camera once), group 2 (isCGM + AI Camera twice with a 3-month interval), and a control group (finger stick + food diary twice with a 3-month interval). All participants received diet education once based on their data. The primary outcome was a change in HbA1c at 6 months.Results: Among 120 participants (HbA1c 7.5±0.7%), 40 participants were allocated to each group. Ninety-nine subjects were included in the primary analysis. At 3 months, no significant HbA1c reduction was observed in group 1 and 2 compared to the control group. At 6 months, compared to the control group, group 2 achieved significant HbA1c reduction (difference -0.34% [95% CI -0.66 to -0.01], P=0.041), but group 1 did not (0.19% [95% CI -0.11 to 0.49], P=0.216). Time in tight range of 70-140 mg/dL tended to be better in group 2 compared to the control group (9.1% [95% CI -1.3 to 19.6], p=0.086).Conclusion: In non-insulin-treated T2D patients, periodic short-term use of isCGM with AI-Camera was an effective method for glucose control when repeated after three months.Disclosure S. Moon: Research Support; Dexcom, Inc., Abbott. Consultant; Medtronic. Research Support; iSense, Kakao Health. Stock/Shareholder; Novo Nordisk, Lilly Diabetes. Consultant; Curestream. E. Rhee: None. J. Park: None. D. Lee: None. W. Lee: None. C. Park: None.FundingThis study was supported by DaeWoong.
PubDate: Fri, 20 Jun 2025 00:00:00 GMT
DOI: 10.2337/db25-1029-P
Issue No: Vol. 74, No. Supplement_1 (2025)
-
- 1030-P: Device Pathways following CGM Discontinuation in Adults with Type
1 Diabetes (T1D)-
Free pre-print version: Loading...Rate this result: What is this?Please help us test our new pre-print finding feature by giving the pre-print link a rating.
</
A 5 star rating indicates the linked pre-print has the exact same content as the published article.
-