Subjects -> MEDICAL SCIENCES (Total: 8810 journals)
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INTERNAL MEDICINE (180 journals)                     

Showing 1 - 180 of 180 Journals sorted alphabetically
Abdomen     Open Access  
ACP Hospitalist     Full-text available via subscription   (Followers: 9)
ACP Internist     Full-text available via subscription   (Followers: 10)
ACP Journal Club     Full-text available via subscription   (Followers: 11)
Acta Clinica Belgica     Hybrid Journal   (Followers: 1)
Acute and Critical Care     Open Access   (Followers: 11)
Acute Medicine     Full-text available via subscription   (Followers: 9)
Advances in Hepatology     Open Access   (Followers: 4)
Advances in Integrative Medicine     Hybrid Journal   (Followers: 6)
African Journal of Primary Health Care & Family Medicine     Open Access   (Followers: 6)
African Journal of Thoracic and Critical Care Medicine     Open Access  
American Family Physician     Full-text available via subscription   (Followers: 38)
American Journal of Hypertension     Hybrid Journal   (Followers: 31)
Anales de Medicina Interna     Open Access   (Followers: 1)
Anatomy & Physiology : Current Research     Open Access   (Followers: 9)
Angiology     Hybrid Journal   (Followers: 5)
Annals of Colorectal Research     Open Access   (Followers: 1)
Annals of Internal Medicine     Full-text available via subscription   (Followers: 392)
AORN Journal     Hybrid Journal   (Followers: 27)
Apollo Medicine     Open Access  
Archives of Drug Information     Hybrid Journal   (Followers: 5)
Archivos de Medicina Interna     Open Access   (Followers: 1)
Asia Oceania Journal of Nuclear Medicine & Biology     Open Access   (Followers: 4)
Asian Pacific Journal of Tropical Disease     Full-text available via subscription   (Followers: 3)
Australasian Physical & Engineering Sciences in Medicine     Hybrid Journal   (Followers: 1)
BMI Journal : Bariátrica & Metabólica Iberoamericana     Open Access   (Followers: 1)
BMJ Open Diabetes Research & Care     Open Access   (Followers: 35)
BMJ Quality & Safety     Hybrid Journal   (Followers: 69)
Bone & Joint Journal     Hybrid Journal   (Followers: 138)
Brain Communications     Open Access   (Followers: 4)
Brain Science Advances     Open Access  
Canadian Journal of General Internal Medicine     Open Access   (Followers: 2)
Cardiovascular Medicine in General Practice     Full-text available via subscription   (Followers: 7)
Case Reports in Internal Medicine     Open Access   (Followers: 1)
Cell Death & Disease     Open Access   (Followers: 3)
Cellular and Molecular Gastroenterology and Hepatology     Open Access   (Followers: 3)
Cephalalgia     Hybrid Journal   (Followers: 8)
Cephalalgia Reports     Open Access   (Followers: 4)
Chronic Diseases and Injuries in Canada     Free   (Followers: 1)
Clinical Ethics     Hybrid Journal   (Followers: 13)
Clinical Liver Disease     Open Access   (Followers: 5)
Clinical Nutrition     Hybrid Journal   (Followers: 98)
Clinical Thyroidology     Full-text available via subscription   (Followers: 1)
CNE Pflegemanagement     Hybrid Journal  
Communication Law and Policy     Hybrid Journal   (Followers: 5)
Current Diabetes Reports     Hybrid Journal   (Followers: 30)
Current Hepatology Reports     Hybrid Journal  
Current Research: Integrative Medicine     Open Access  
CVIR Endovascular     Open Access   (Followers: 1)
Der Internist     Hybrid Journal   (Followers: 12)
Diabetes     Full-text available via subscription   (Followers: 603)
Diabetes Care     Full-text available via subscription   (Followers: 578)
Diabetes Internacional     Open Access  
Diabetes Spectrum     Full-text available via subscription   (Followers: 17)
Diagnosis     Hybrid Journal   (Followers: 1)
Egyptian Journal of Bronchology     Open Access  
Egyptian Journal of Internal Medicine     Open Access   (Followers: 1)
Egyptian Journal of Neurosurgery     Open Access  
Egyptian Liver Journal     Open Access   (Followers: 2)
Egyptian Spine Journal     Open Access  
EMC - Aparato Locomotor     Hybrid Journal  
Endovascular Neuroradiology / Ендоваскулярна нейрорентгенохірургія     Open Access   (Followers: 1)
eNeuro     Open Access   (Followers: 3)
Ergonomics     Hybrid Journal   (Followers: 24)
European Journal of Inflammation     Open Access   (Followers: 2)
European Journal of Internal Medicine     Full-text available via subscription   (Followers: 10)
European Journal of Translational Myology     Open Access  
European Radiology Experimental     Open Access   (Followers: 2)
Head and Neck Tumors     Open Access   (Followers: 1)
Health Sociology Review     Hybrid Journal   (Followers: 14)
HemaSphere     Open Access   (Followers: 2)
Hepatology Communications     Open Access  
Hepatoma Research     Open Access   (Followers: 3)
Human Physiology     Hybrid Journal   (Followers: 5)
ImmunoHorizons     Open Access  
Immunological Medicine     Open Access  
Infectious Diseases: Research and Treatment     Open Access   (Followers: 5)
Inflammation and Regeneration     Open Access   (Followers: 2)
Inflammatory Intestinal Diseases     Open Access  
Innere Medizin up2date     Hybrid Journal   (Followers: 1)
Internal and Emergency Medicine     Hybrid Journal   (Followers: 5)
Internal Medicine Journal     Hybrid Journal   (Followers: 9)
International Journal of Abdominal Wall and Hernia Surgery     Open Access   (Followers: 1)
International Journal of Anatomy and Research     Open Access   (Followers: 2)
International Journal of Angiology     Hybrid Journal  
International Journal of Artificial Organs     Hybrid Journal   (Followers: 3)
International Journal of Hyperthermia     Open Access  
International Journal of Internal Medicine     Open Access   (Followers: 3)
International Journal of Noncommunicable Diseases     Open Access  
International Journal of Psychiatry in Clinical Practice     Hybrid Journal   (Followers: 6)
Iranian Journal of Neurosurgery     Open Access   (Followers: 1)
Italian Journal of Anatomy and Embryology     Open Access   (Followers: 1)
JAC-Antimicrobial Resistance     Open Access   (Followers: 4)
JAMA Internal Medicine     Full-text available via subscription   (Followers: 364)
JCSM Clinical Reports     Open Access   (Followers: 3)
JHEP Reports     Open Access  
JIMD Reports     Open Access  
JMV - Journal de Médecine Vasculaire     Hybrid Journal   (Followers: 1)
Joint Commission Journal on Quality and Patient Safety     Hybrid Journal   (Followers: 41)
JOP. Journal of the Pancreas     Open Access   (Followers: 2)
Journal of Basic & Clinical Physiology & Pharmacology     Hybrid Journal   (Followers: 1)
Journal of Bone Oncology     Open Access   (Followers: 1)
Journal of Cancer & Allied Specialties     Open Access  
Journal of Clinical and Experimental Hepatology     Full-text available via subscription   (Followers: 3)
Journal of Clinical Movement Disorders     Open Access   (Followers: 3)
Journal of Community Hospital Internal Medicine Perspectives     Open Access  
Journal of Cutaneous Immunology and Allergy     Open Access  
Journal of Developmental Origins of Health and Disease     Hybrid Journal   (Followers: 2)
Journal of Endoluminal Endourology     Open Access  
Journal of Gastroenterology and Hepatology Research     Open Access   (Followers: 4)
Journal of General Internal Medicine     Hybrid Journal   (Followers: 23)
Journal of Hypertension     Hybrid Journal   (Followers: 14)
Journal of Infectious Diseases     Hybrid Journal   (Followers: 48)
Journal of Interdisciplinary Medicine     Open Access  
Journal of Internal Medicine     Hybrid Journal   (Followers: 11)
Journal of Liver : Disease & Transplantation     Hybrid Journal   (Followers: 7)
Journal of Medical Internet Research     Open Access   (Followers: 24)
Journal of Movement Disorders     Open Access   (Followers: 2)
Journal of Pain and Symptom Management     Hybrid Journal   (Followers: 46)
Journal of Pancreatic Cancer     Open Access  
Journal of Renal and Hepatic Disorders     Open Access  
Journal of Solid Tumors     Open Access   (Followers: 1)
Journal of Sports Medicine and Allied Health Sciences : Official Journal of the Ohio Athletic Trainers Association     Open Access   (Followers: 1)
Journal of the American Board of Family Medicine     Open Access   (Followers: 11)
Journal of the European Mosquito Control Association     Open Access  
Journal of Translational Internal Medicine     Open Access  
Jurnal Vektor Penyakit     Open Access  
La Revue de Medecine Interne     Full-text available via subscription   (Followers: 3)
Lege artis - Das Magazin zur ärztlichen Weiterbildung     Hybrid Journal   (Followers: 1)
Liver Cancer International     Open Access  
Liver Research     Open Access  
Molecular Diagnosis & Therapy     Hybrid Journal   (Followers: 3)
Molecular Therapy - Oncolytics     Open Access  
Multiple Sclerosis and Demyelinating Disorders     Open Access   (Followers: 7)
MYOPAIN. A journal of myofascial pain and fibromyalgia     Hybrid Journal   (Followers: 18)
Neuro-Oncology Advances     Open Access   (Followers: 1)
Neurobiology of Pain     Open Access   (Followers: 2)
Neurointervention     Open Access   (Followers: 6)
Neuromuscular Diseases     Open Access  
Nigerian Journal of Gastroenterology and Hepatology     Full-text available via subscription  
OA Alcohol     Open Access   (Followers: 5)
Oncological Coloproctology     Open Access  
Open Journal of Internal Medicine     Open Access  
Pleura and Peritoneum     Open Access  
Pneumo News     Full-text available via subscription  
Polish Archives of Internal Medicine     Full-text available via subscription   (Followers: 2)
Preventing Chronic Disease     Free   (Followers: 2)
Progress in Transplantation     Hybrid Journal   (Followers: 1)
Prostate International     Open Access   (Followers: 2)
Psychiatry and Clinical Psychopharmacology     Open Access   (Followers: 1)
Pulmonary Therapy     Open Access   (Followers: 2)
Quality of Life Research     Hybrid Journal   (Followers: 20)
Research and Practice in Thrombosis and Haemostasis     Open Access  
Revista Chilena de Fonoaudiología     Open Access   (Followers: 1)
Revista de la Sociedad Peruana de Medicina Interna     Open Access   (Followers: 4)
Revista del Instituto de Medicina Tropical     Open Access  
Revista Hispanoamericana de Hernia     Open Access   (Followers: 1)
Revista Médica Internacional sobre el Síndrome de Down     Full-text available via subscription   (Followers: 1)
Revista Virtual de la Sociedad Paraguaya de Medicina Interna     Open Access   (Followers: 1)
Romanian Journal of Diabetes Nutrition and Metabolic Diseases     Open Access   (Followers: 1)
Romanian Journal of Internal Medicine     Open Access  
Russian Journal of Child Neurology     Open Access   (Followers: 1)
Scandinavian Journal of Primary Health Care     Open Access   (Followers: 8)
Schlaf     Hybrid Journal  
Schmerzmedizin     Hybrid Journal  
Scientific Journal of the Foot & Ankle     Open Access   (Followers: 1)
SciMedicine Journal     Open Access   (Followers: 3)
SEMERGEN - Medicina de Familia     Full-text available via subscription   (Followers: 1)
The Journal of Critical Care Medicine     Open Access   (Followers: 9)
Therapeutic Advances in Chronic Disease     Open Access   (Followers: 8)
Therapeutic Advances in Musculoskeletal Disease     Hybrid Journal   (Followers: 6)
Thieme Case Report     Hybrid Journal   (Followers: 1)
Tijdschrift voor Urologie     Hybrid Journal  
Tissue Barriers     Hybrid Journal   (Followers: 1)
Transactions of the Royal Society of Tropical Medicine and Hygiene     Hybrid Journal   (Followers: 3)
Transgender Health     Open Access   (Followers: 3)
Trends in Anaesthesia and Critical Care     Full-text available via subscription   (Followers: 23)
US Cardiology Review     Open Access  
Vascular and Endovascular Review     Open Access   (Followers: 1)
Ожирение и метаболизм     Open Access  


Similar Journals
Journal Cover
BMJ Open Diabetes Research & Care
Journal Prestige (SJR): 1.128
Citation Impact (citeScore): 2
Number of Followers: 35  

  This is an Open Access Journal Open Access journal
ISSN (Online) 2052-4897
Published by BMJ Publishing Group Homepage  [68 journals]
  • Cost-effectiveness of empagliflozin versus canagliflozin, dapagliflozin,
           or standard of care in patients with type 2 diabetes and established
           cardiovascular disease

    • Authors: Reifsnider, O. S; Kansal, A. R, Gandhi, P. K, Cragin, L, Brand, S. B, Pfarr, E, Fahrbach, K, Ustyugova, A.
      Abstract: IntroductionEmpagliflozin, a sodium-glucose co-transporter-2 (SGLT-2) inhibitor, is approved in the USA to reduce risk of cardiovascular (CV) death in adults with type 2 diabetes mellitus (T2DM) and established CV disease, based on EMPA-REG OUTCOME (Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients) trial results. Empagliflozin reduced major adverse CV event (MACE) by 14%, CV death by 38%, and hospitalization for heart failure (HHF) by 35% vs placebo, each on top of standard of care (SoC). SGLT-2 inhibitors canagliflozin and dapagliflozin have also been compared with placebo, all on top of SoC, in CV outcome trials. In the CANVAS (Canagliflozin Cardiovascular Assessment Study) Program, canagliflozin reduced MACE by 14% and HHF by 33%. Dapagliflozin reduced HHF by 27% in the DECLARE-TIMI 58 trial (Multicenter Trial to Evaluate the Effect of Dapagliflozin on the Incidence of Cardiovascular Events). This analysis estimated the cost-effectiveness of empagliflozin versus canagliflozin, dapagliflozin, or SoC, in US adults with T2DM and established CV disease.Research design and methodsIndividual patient-level discrete-event simulation was conducted to predict time-to-event for CV and renal outcomes, and specific adverse events over patients’ lifetimes. Occurrence of events in EMPA-REG OUTCOME was estimated based on event-free survival curves with time-dependent covariates. An HR for canagliflozin or dapagliflozin versus empagliflozin on each clinical event was estimated from published CANVAS, DECLARE-TIMI 58, and EMPA-REG OUTCOME data using indirect treatment comparison. Public sources provided US costs and utilities.ResultsThe model predicted longer survival for empagliflozin versus canagliflozin, dapagliflozin, and SoC mainly due to direct reduction in CV death. Empagliflozin dominated canagliflozin, yielding more quality-adjusted life years (QALYs; 0.38) at a lower cost (–US$306). Compared with dapagliflozin and SoC, empagliflozin yielded 0.50 and 0.84 incremental QALYs at US$1517 and US$27 539 incremental costs, yielding incremental cost-effectiveness ratios of US$3054/QALY and US$32 848/QALY, respectively.ConclusionsEmpagliflozin was projected to dominate canagliflozin and be highly cost-effective compared with dapagliflozin and SoC using US healthcare costs.
      Keywords: Open access
      PubDate: 2021-05-03T08:00:35-07:00
      DOI: 10.1136/bmjdrc-2020-001313
      Issue No: Vol. 9, No. 1 (2021)
  • Inappropriate intensification of glucose-lowering treatment in older
           patients with type 2 diabetes: the global DISCOVER study

    • Authors: Bongaerts, B; Arnold, S. V, Charbonnel, B. H, Chen, H, Cooper, A, Fenici, P, Gomes, M, Ji, L, Khunti, K, Kosiborod, M, Medina, J, Nicolucci, A, Shestakova, M, Shimomura, I, Tang, F, Watada, H, Rathmann, W.
      Abstract: IntroductionAlthough individualized target glycated hemoglobin (HbA1c) levels are recommended in older people with type 2 diabetes, studies report high levels of potential overtreatment. We aimed to investigate the proportion of older patients (aged ≥65 years) who potentially received an inappropriately intensive treatment (HbA1c level
      Keywords: Open access, Epidemiology/health services research
      PubDate: 2021-05-03T08:00:35-07:00
      DOI: 10.1136/bmjdrc-2020-001585
      Issue No: Vol. 9, No. 1 (2021)
  • Insulin resistance and liver histopathology in metabolically unhealthy
           subjects do not correlate with the hepatic abundance of NLRP3 inflammasome
           nor circulating IL-1{beta} levels

    • Authors: Quezada, N; Valencia, I, Torres, J, Maturana, G, Cerda, J, Arab, J. P, Fuentes, J. J, Pinto, C, Turiel, D, Cortes, V.
      Abstract: IntroductionSystemic chronic low-grade inflammation has been linked to insulin resistance (IR) and non-alcoholic steatohepatitis (NASH). NOD-like receptor protein 3 (NLRP3) inflammasome and its final product, interleukin (IL)-1β, exert detrimental effects on insulin sensitivity and promote liver inflammation in murine models. Evidence linking hepatic NLRP3 inflammasome, systemic IR and NASH has been scarcely explored in humans. Herein, we correlated the hepatic abundance of NLRP3 inflammasome components and IR and NASH in humans.Research design and methodsMetabolically healthy (MH) (n=11) and metabolically unhealthy (MUH) (metabolic syndrome, n=21, and type 2 diabetes, n=14) subjects were recruited. Insulin sensitivity (homeostatic model assessment of IR (HOMA-IR) and Oral Glucose Sensitivity (OGIS120)), glycemic (glycated hemoglobin), and lipid parameters were determined by standard methods. Plasma cytokines were quantified by Magpix. Hepatic NLRP3 inflammasome components were determined at the mRNA and protein levels by reverse transcription–quantitative PCR and western blot, respectively. Liver damage was assessed by histological analysis (Non-alcoholic Fatty Liver Disease Activity Score (NAS) and Steatosis, Inflammatory Activity, and Fibrosis (SAF) scores). IR and liver histopathology were correlated with NLRP3 inflammasome components as well as with liver and plasma IL-1β levels.ResultsBody Mass Index, waist circumference, and arterial hypertension frequency were significantly higher in MUH subjects. These patients also had increased high-sensitivity C reactive protein levels compared with MH subjects. No differences in the plasma levels of IL-1β nor the hepatic content of Nlrp3, apoptosis-associated speck-like (Asc), Caspase-1, and IL-1β were detected between MUH and MH individuals. MUH subjects had significantly higher NAS and SAF scores, indicating more severe liver damage. However, histological severity did not correlate with the hepatic content of NLRP3 inflammasome components nor IL-1β levels.ConclusionOur results suggest that NLRP3 inflammasome activation is linked neither to IR nor to the inflammatory status of the liver in MUH patients.
      Keywords: Open access, Obesity studies
      PubDate: 2021-05-03T08:00:35-07:00
      DOI: 10.1136/bmjdrc-2020-001975
      Issue No: Vol. 9, No. 1 (2021)
  • Antidiabetic E4orf1 protein prevents hepatic steatosis and reduces markers
           of aging-related cellular damage in high fat fed older mice

    • Authors: Mostofinejad, Z; Akheruzzaman, M, Abu Bakkar Siddik, M, Patkar, P, Dhurandhar, N. V, Hegde, V.
      Abstract: IntroductionOlder age is associated with greater prevalence of hyperinsulinemia, type 2 diabetes, and fatty liver disease. These metabolic conditions and aging are bidirectionally linked to mitochondrial dysfunction and telomere attrition. Although effectively addressing these conditions is important for influencing the health and the lifespan, it is particularly challenging in older age. We reported that E4orf1, a protein derived from human adenovirus Ad36, reduces hyperinsulinemia, improves glucose clearance, and protects against hepatic steatosis in younger mice exposed to high fat diet (HFD). Here, we tested if E4orf1 will improve glycemic control, liver fat accumulation, mitochondrial integrity, and reduce telomere attrition in older mice.Research design and methodsWe used 9-month-old mice that inducibly expressed E4orf1 in adipose tissue and non-E4orf1 expressing control mice. Mice were maintained on a 60% (kcal) HFD for 20 weeks and glycemic control was determined by intraperitoneal glucose tolerance test at week 20. Following 20 weeks of HF-feeding, mice were sacrificed and liver tissues collected to determine the expression of aging genes using qRT-PCR based RT2 Profiler PCR array.ResultsCompared with the control mice, E4orf1 significantly improved glycemic control and reduced hepatic steatosis and fibrosis. Additionally, E4orf1 maintained markers of mitochondrial integrity and telomere attrition.ConclusionE4orf1 has the potential to improve glycemic control in older mice, and the improvement persists even after longer term exposure. E4orf1 expression also maintains mitochondrial integrity and telomere attrition, thus delaying age-associated diseases. This provides strong evidence for therapeutic utility of E4orf1 in improving age-associated metabolic and cellular changes that occur with aging in humans.
      Keywords: Open access, Obesity studies
      PubDate: 2021-05-03T08:00:35-07:00
      DOI: 10.1136/bmjdrc-2020-002096
      Issue No: Vol. 9, No. 1 (2021)
  • Amyloid-related protein changes associated with dementia differ according
           to severity of hypoglycemia

    • Authors: Moin, A. S. M; Kahal, H, Al-Qaissi, A, Kumar, N, Sathyapalan, T, Atkin, S. L, Butler, A. E.
      Abstract: IntroductionHypoglycemia in type 2 diabetes (T2D) may increase risk for Alzheimer’s disease (AD), but no data on changes in AD-related proteins with differing degrees of hypoglycemia exist. We hypothesized that milder prolonged hypoglycemia would cause greater AD-related protein changes versus severe transient hypoglycemia.Research design and methodsTwo prospective case-control induced hypoglycemia studies were compared: study 1, hypoglycemic clamp to 2.8 mmol/L (50 mg/dL) for 1 hour in 17 subjects (T2D (n=10), controls (n=7)); study 2, hypoglycemic clamp to 2.0 mmol/L (36 mg/dL) undertaken transiently and reversed in 46 subjects (T2D (n=23), controls (n=23)). Blood sampling at baseline, hypoglycemia and 24-hour post-hypoglycemia, with proteomic analysis of amyloid-related proteins performed.ResultsIn control subjects, the percentage change from baseline to hypoglycemia differed between study 1 and study 2 for 5 of 11 proteins in the AD-related panel: serum amyloid A1 (SAA1) (p=0.009), pappalysin (PAPPA) (p=0.002), apolipoprotein E2 (p=0.02), apolipoprotein E3 (p=0.03) and apolipoprotein E4 (p=0.02). In controls, the percentage change from baseline to 24 hours differed between studies for two proteins: SAA1 (p=0.003) and PAPPA (p=0.004); however, after Bonferroni correction only SAA1 and PAPPA remain significant. In T2D, there were no differential protein changes between the studies.ConclusionsThe differential changes in AD-related proteins were seen only in control subjects in response to iatrogenic induction of hypoglycemic insults of differing length and severity and may reflect a protective response that was absent in subjects with T2D. Milder prolonged hypoglycemia caused greater AD-related protein changes than severe acute hypoglycemia in control subjects.Trial registration numbersNCT02205996, NCT03102801.
      Keywords: Open access, Pathophysiology/complications
      PubDate: 2021-04-30T07:01:53-07:00
      DOI: 10.1136/bmjdrc-2021-002211
      Issue No: Vol. 9, No. 1 (2021)
  • Serum galectin-3BP as a novel marker of obesity and metabolic syndrome in
           Chinese adolescents

    • Authors: Zhen, S; Ma, Y, Han, Y, Zhao, Z, Yang, X, Wen, D.
      Abstract: IntroductionChildhood obesity (OB) and metabolic syndrome (MetS) have become a worldwide health problem. Comparative proteomic approaches are widely used in human OB to analyze protein changes in blood plasma. The present study determined the galectin-3 binding protein (galectin-3BP) expression level in different weight categories and assessed the associations between galectin-3BP and OB and MetS.Research design and methodsThe current study included 932 Chinese adolescents 13–18 years of age. The biochemical and anthropometric variables of all the subjects were evaluated using standardized procedures. The differentially expressed proteins (DEPs) were investigated among 60 adolescents (20 normal weight, 20 overweight and 20 obese) using tandem mass tag (TMT) quantitative proteomics. The serum galectin-3BP level was measured using ELISA. The associations between galectin-3BP and OB and MetS were analyzed in 932 adolescents using multiple logistic regression analyses.ResultsA significant DEP, galectin-3BP, can effectively separate the obese from the normal weight group using TMT. Adolescents in tertile 3 of galectin-3BP, when compared with adolescents in the tertile 1, were positively associated with OB (OR=3.32, 95% CI 1.79 to 6.16) and MetS (OR=3.28, 95% CI 1.30 to 8.26). The receiver operating characteristic curve for galectin-3BP in subjects with MetS indicated that the area under the curve was 0.85 (95% CI 0.79 to 0.91).ConclusionsThis study confirmed an association between galectin-3BP and OB in Chinese adolescents, and galectin-3BP was also positively associated with MetS, and thus might be useful for identifying adolescents with MetS.
      Keywords: Open access, Genetics/genomes/proteomics/metabolomics
      PubDate: 2021-04-28T08:30:14-07:00
      DOI: 10.1136/bmjdrc-2020-001894
      Issue No: Vol. 9, No. 1 (2021)
  • Association between varying cut-points of intermediate hyperglycemia and
           risk of mortality, cardiovascular events and chronic kidney disease: a
           systematic review and meta-analysis

    • Authors: Gujral, U. P; Jagannathan, R, He, S, Huang, M, Staimez, L. R, Wei, J, Singh, N, Narayan, K. M. V.
      Abstract: IntroductionWe conducted a systematic review and meta-analysis to evaluate the updated evidence regarding prediabetes for predicting mortality, macrovascular and microvascular outcomes.Research design and methodsWe identified English language studies from MEDLINE, PubMed, OVID and Cochrane database indexed from inception to January 31, 2020. Paired reviewers independently identified 106 prospective studies, comprising nearly 1.85 million people, from 27 countries. Primary outcomes were all-cause mortality (ACM), cardiovascular mortality (CVDM), cardiovascular disease (CVD), coronary heart disease (CHD) and stroke. Secondary outcomes were heart failure, chronic kidney disease (CKD) and retinopathy.ResultsImpaired glucose tolerance was associated with ACM; HR 1.19, 95% CI (1.15 to 1.24), CVDM; HR 1.21, 95% CI (1.10 to 1.32), CVD; HR 1.18, 95% CI (1.11 to 1.26), CHD; HR; 1.13, 95% CI (1.05 to 1.21) and stroke; HR 1.24, 95% CI (1.06 to 1.45). Impaired fasting glucose (IFG) 110–125 mg/dL was associated with ACM; HR 1.17, 95% CI (1.13 to 1.22), CVDM; HR 1.20, 95% CI (1.09 to 1.33), CVD; HR 1.21, 95% CI (1.09 to 1.33), CHD; HR; 1.14, 95% CI (1.06 to 1.22) and stroke; HR 1.22, 95% CI (1.07 to 1.40). IFG 100–125 mg/dL was associated with ACM; HR 1.11, 95% CI (1.04 to 1.19), CVDM; HR 1.14, 95% CI (1.03 to 1.25), CVD; HR 1.15, 95% CI (1.05 to 1.25), CHD HR; 1.10, 95% CI (1.02 to 1.19) and CKD; HR; 1.09, 95% CI (1.01 to 1.18). Glycosylated hemoglobin A1c (HbA1c) 6.0%–6.4% was associated with ACM; HR 1.30, 95% CI (1.03 to 1.66), CVD; HR 1.32, 95% CI (1.00 to 1.73) and CKD; HR 1.50, 95% CI (1.32 to 1.70). HbA1c 5.7%–6.4% was associated with CVD HR 1.15, 95% CI (1.02 to 1.30), CHD; HR 1.28, 95% CI (1.13 to 1.46), stroke; HR 1.23, 95% CI (1.04 to 1.46) and CKD; HR 1.32, 95% CI (1.16 to 1.50).ConclusionPrediabetes is an elevated risk state for macrovascular and microvascular outcomes. The prevention and management of prediabetes should be considered.
      Keywords: Open access, Cardiovascular and metabolic risk
      PubDate: 2021-04-26T23:13:27-07:00
      DOI: 10.1136/bmjdrc-2020-001776
      Issue No: Vol. 9, No. 1 (2021)
  • Associations between attainment of incentivized primary care indicators
           and incident lower limb amputation among those with type 2 diabetes: a
           population-based historical cohort study

    • Authors: Gunn, L. H; Vamos, E. P, Majeed, A, Normahani, P, Jaffer, U, Molina, G, Valabhji, J, McKay, A. J.
      Abstract: IntroductionEngland has invested considerably in diabetes care through such programs as the Quality and Outcomes Framework (QOF) and National Diabetes Audit (NDA). Associations between program indicators and clinical endpoints, such as amputation, remain unclear. We examined associations between primary care indicators and incident lower limb amputation.Research design and methodsThis population-based retrospective cohort study, spanning 2010–2017, was comprised of adults in England with type 2 diabetes and no history of lower limb amputation. Exposures at baseline (2010–2011) were attainment of QOF glycated hemoglobin (HbA1c), blood pressure and total cholesterol indicators, and number of NDA processes completed. Propensity score matching was performed and multivariable Cox proportional hazards models, adjusting for disease-related, comorbidity, lifestyle, and sociodemographic factors, were fitted using matched samples for each exposure.Results83 688 individuals from 330 English primary care practices were included. Mean follow-up was 3.9 (SD 2.0) years, and 521 (0.6%) minor or major amputations were observed (1.62 per 1000 person-years). HbA1c and cholesterol indicator attainment were associated with considerably lower risks of minor or major amputation (adjusted HRs; 95% CIs) 0.61 (0.49 to 0.74; p
      Keywords: Open access, Pathophysiology/complications
      PubDate: 2021-04-26T06:55:51-07:00
      DOI: 10.1136/bmjdrc-2020-002069
      Issue No: Vol. 9, No. 1 (2021)
  • Exploring the GLP-1-GLP-1R axis in porcine pancreas and gastrointestinal
           tract in vivo by ex vivo autoradiography

    • Authors: Manell, E; Puuvuori, E, Svensson, A, Velikyan, I, Hulsart-Billström, G, Hedenqvist, P, Holst, J. J, Jensen Waern, M, Eriksson, O.
      Abstract: IntroductionGlucagon-like peptide-1 (GLP-1) increases insulin secretion from pancreatic beta-cells and GLP-1 receptor (GLP-1R) agonists are widely used as treatment for type 2 diabetes mellitus. Studying occupancy of the GLP-1R in various tissues is challenging due to lack of quantitative, repeatable assessments of GLP-1R density. The present study aimed to describe the quantitative distribution of GLP-1Rs and occupancy by endogenous GLP-1 during oral glucose tolerance test (OGTT) in pigs, a species that is used in biomedical research to model humans.Research design and methodsGLP-1R distribution and occupancy were measured in pancreas and gastrointestinal tract by ex vivo autoradiography using the GLP-1R-specific radioligand 177Lu-exendin-4 in two groups of pigs, control or bottle-fed an oral glucose load. Positron emission tomography (PET) data from pigs injected with 68Ga-exendin-4 in a previous study were used to retrieve data on biodistribution of GLP-1R in the gastrointestinal tract.ResultsHigh homogenous uptake of 177Lu-exendin-4 was found in pancreas, and even higher uptake in areas of duodenum. Low uptake of 177Lu-exendin-4 was found in stomach, jejunum, ileum and colon. During OGTT, there was no increase in plasma GLP-1 concentrations and occupancy of GLP-1Rs was low. The ex vivo autoradiography results were highly consistent with to the biodistribution of 68Ga-exendin-4 in pigs scanned by PET.ConclusionWe identified areas with similarities as well as important differences regarding GLP-1R distribution and occupancy in pigs compared with humans. First, there was strong ligand binding in the exocrine pancreas in islets. Second, GLP-1 secretion during OGTT is minimal and GLP-1 might not be an important incretin in pigs under physiological conditions. These findings offer new insights on the relevance of porcine diabetes models.
      Keywords: Open access, Metabolism
      PubDate: 2021-04-26T06:55:51-07:00
      DOI: 10.1136/bmjdrc-2020-002083
      Issue No: Vol. 9, No. 1 (2021)
  • Glycation by glyoxal leads to profound changes in the behavior of dermal

    • Authors: Guillon, C; Ferraro, S, Clement, S, Bouschbacher, M, Sigaudo-Roussel, D, Bonod, C.
      Abstract: IntroductionDiabetes is a worldwide health problem that is associated with severe complications. Advanced Glycation End products (AGEs) such as N-(carboxymethyl)lysine, which result from chronic hyperglycemia, accumulate in the skin of patients with diabetes. The effect of AGEs on fibroblast functionality and their impact on wound healing are still poorly understood.Research design and methodsTo investigate this, we treated cultured human fibroblasts with 0.6 mM glyoxal to induce acute glycation. The behavior of fibroblasts was analyzed by time-lapse monolayer wounding healing assay, seahorse technology and atomic force microscopy. Production of extracellular matrix was studied by transmission electronic microscopy and western blot. Lipid metabolism was investigated by staining of lipid droplets (LDs) with BODIPY 493/503.ResultsWe found that the proliferative and migratory capacities of the cells were greatly reduced by glycation, which could be explained by an increase in fibroblast tensile strength. Measurement of the cellular energy balance did not indicate that there was a change in the rate of oxygen consumption of the fibroblasts. Assessment of collagen I revealed that glyoxal did not influence type I collagen secretion although it did disrupt collagen I maturation and it prevented its deposition in the extracellular matrix. We noted a pronounced increase in the number of LDs after glyoxal treatment. AMPK phosphorylation was reduced by glyoxal treatment but it was not responsible for the accumulation of LDs.ConclusionGlyoxal promotes a change in fibroblast behavior in favor of lipogenic activity that could be involved in delaying wound healing.
      Keywords: Open access, Pathophysiology/complications
      PubDate: 2021-04-26T06:55:51-07:00
      DOI: 10.1136/bmjdrc-2020-002091
      Issue No: Vol. 9, No. 1 (2021)
  • Metabolites in the association between early-life famine exposure and type
           2 diabetes in adulthood over a 5-year follow-up period

    • Authors: Wang, Y; Xia, F, Wan, H, Chen, C, Chen, Y, Zhang, W, Wang, N, Lu, Y.
      Abstract: IntroductionExposure to malnutrition in early life has been found to significantly elevate type 2 diabetes risk in adulthood. However, the changes in metabolites resulting from malnutrition in early life have not been studied. The aim of this study was to identify metabolites with levels associated with type 2 diabetes resulting from exposure to China’s Great Famine (1959–1962).Research design and methodsParticipants were from SPECT-China 2014 and SPECT-China2 2019, two cross-sectional studies performed at the same site. In total, 2171 subjects participated in SPECT-China and SPECT-China2 simultaneously. The sample size of fetal-exposed (1959–1962) versus non-exposed (1963–1974) individuals was 82 vs 79 in 2014 and 97 vs 94 in 2019. Metabolomic profiling was performed between famine-exposed and non-exposed groups.ResultsAmong the different famine exposure groups, the fetal-exposed group (1959–1962) had the greatest incidence rate (12.5%), with an OR of 2.11 (95% CI 1.01 to 4.44), compared with the non-exposed group (1963–1974). Moreover, compared with those in the non-exposed group (1963–1974), four metabolites (indole-3-carbinol (I3C), phosphatidylcholine (PC) (22:6(4Z,7Z,10Z,13Z,16Z,19Z)/16:1(9Z)), pyrimidine, and PC(16:1(9Z)/22:5(4Z,7Z,10Z,13Z,16Z))) showed significantly lower relative intensities in the famine and diabetes groups both in 2014 and 2019. Pyrimidine significantly mediated the association of famine exposure with diabetes, and I3C marginally mediated this association.ConclusionsFamine exposure in the fetal period could increase type 2 diabetes risk in adults, even those in their 60s. I3C and pyrimidine are potential mediators of the effects of famine exposure on diabetes development.
      Keywords: Open access, Genetics/genomes/proteomics/metabolomics
      PubDate: 2021-04-22T06:56:49-07:00
      DOI: 10.1136/bmjdrc-2020-001935
      Issue No: Vol. 9, No. 1 (2021)
  • Periconception glycemic control and congenital anomalies in women with
           pregestational diabetes

    • Authors: Dude, A. M; Badreldin, N, Schieler, A, Yee, L. M.
      Abstract: IntroductionTo assess the relationship between periconception glycemic control and congenital anomalies in a contemporary, diverse population of women with pregestational diabetes.Research design and methodsThis is a retrospective cohort study of all pregnant women with pregestational diabetes at a single institution (2003–2017) in the USA. The primary outcome was frequency of major or minor congenital anomalies. Glycemic control was assessed by periconception glycosylated hemoglobin (HbA1c). The association of periconception HbA1c with pregnancy outcomes was assessed using bivariable and multivariable analyses.ResultsOur sample included 351 women, of which 63.8% had type 2 diabetes. Our study cohort is racially and ethnically diverse, with approximately equal numbers of women identifying as white non-Hispanic, black non-Hispanic and Hispanic, with 3.4% identifying as Asian. Of these 351 women, 52 (14.8%) had a fetus with a congenital anomaly, of whom the majority (n=43) had a major anomaly. Over half (51.1%) of all major anomalies were cardiovascular. Compared with the group with the best glycemic control (HbA1c ≤7.4%), which had an anomaly frequency of 10.2%, the frequency of congenital anomalies increased significantly with each category of worsening glycemic control (HbA1c 7.5%–9.4%: 20.6%, adjusted OR (aOR) 2.35, 95% confidence interval (CI) 1.08 to 5.13; HbA1c 9.5% to 11.4%: 25.8%, aOR 2.86, 95% CI 1.08 to 7.59; HbA1c ≥11.5%: 37.5%, aOR 7.66, 95% CI 2.27 to 25.9).ConclusionIn a diverse cohort of women with pregestational diabetes, higher periconception HbA1c, especially HbA1c >9.5, was significantly associated with major congenital fetal anomalies. Our study sample is reflective of the current population of pregnant women with diabetes, including women with type 2 diabetes and from racial and ethnic minorities.
      Keywords: Open access, Pathophysiology/complications
      PubDate: 2021-04-22T06:56:49-07:00
      DOI: 10.1136/bmjdrc-2020-001966
      Issue No: Vol. 9, No. 1 (2021)
  • Orai-vascular endothelial-cadherin signaling complex regulates
           high-glucose exposure-induced increased permeability of mouse aortic
           endothelial cells

    • Authors: Wei, Y; Bai, S, Yao, Y, Hou, W, Zhu, J, Fang, H, Du, Y, He, W, Shen, B, Du, J.
      Abstract: IntroductionDiabetes-associated endothelial barrier function impairment might be linked to disturbances in Ca2+ homeostasis. To study the role and molecular mechanism of Orais–vascular endothelial (VE)-cadherin signaling complex and its downstream signaling pathway in diabetic endothelial injury using mouse aortic endothelial cells (MAECs).Research design and methodsThe activity of store-operated Ca2+ entry (SOCE) was detected by calcium imaging after 7 days of high-glucose (HG) or normal-glucose (NG) exposure, the expression levels of Orais after HG treatment was detected by western blot analysis. The effect of HG exposure on the expression of phosphorylated (p)-VE-cadherin and VE-cadherin on cell membrane was observed by immunofluorescence assay. HG-induced transendothelial electrical resistance was examined in vitro after MAECs were cultured in HG medium. FD-20 permeability was tested in monolayer aortic endothelial cells through transwell permeability assay. The interactions between Orais and VE-cadherin were detected by co-immunoprecipitation and immunofluorescence technologies. Immunohistochemical experiment was used to detect the expression changes of Orais, VE-cadherin and p-VE-cadherin in aortic endothelium of mice with diabetes.Results(1) The expression levels of Orais and activity of SOCE were significantly increased in MAECs cultured in HG for 7 days. (2) In MAECs cultured in HG for 7 days, the ratio of p-VE-cadherin to VE-cadherin expressed on the cell membrane and the FD-20 permeability in monolayer endothelial cells increased, indicating that intercellular permeability increased. (3) Orais and VE-cadherin can interact and enhance the interaction ratio through HG stimulation. (4) In MAECs cultured with HG, the SOCE activator ATP enhanced the expression level of p-VE-cadherin, and the SOCE inhibitor BTP2 decreased the expression level of p-VE-cadherin. (5) Significantly increased expression of p-VE-cadherin and Orais in the aortic endothelium of mice with diabetes.ConclusionHG exposure stimulated increased expression of Orais in endothelial cells, and increased VE-cadherin phosphorylation through Orais–VE-cadherin complex and a series of downstream signaling pathways, resulting in disruption of endothelial cell junctions and initiation of atherosclerosis.
      Keywords: Open access, Pathophysiology/complications
      PubDate: 2021-04-22T06:56:49-07:00
      DOI: 10.1136/bmjdrc-2020-002085
      Issue No: Vol. 9, No. 1 (2021)
  • Prevalence of bone fracture and its association with severe hypoglycemia
           in Japanese patients with type 1 diabetes

    • Authors: Komorita, Y; Minami, M, Maeda, Y, Yoshioka, R, Ohkuma, T, Kitazono, T.
      Abstract: IntroductionType 1 diabetes (T1D) is associated with higher fracture risk. However, few studies have investigated the relationship between severe hypoglycemia and fracture risk in patients with T1D, and the results are controversial. Besides, none has investigated the risk factors for fracture in Asian patients with T1D. The aim of the present study was to investigate the prevalence of bone fracture and its relationship between severe hypoglycemia and other risk factors in Japanese patients with T1D.Research design and methodsThe single-center cross-sectional study enrolled 388 Japanese patients with T1D (mean age, 45.2 years; women, 60.4%; mean duration of diabetes, 16.6 years) between October 2019 and April 2020. The occurrence and circumstances of any fracture after the diagnosis of T1D were identified using a self-administered questionnaire. The main outcomes were any anatomic site of fracture and fall-related fracture. Severe hypoglycemia was defined as an episode of hypoglycemia that required the assistance of others to achieve recovery.ResultsA total of 92 fractures occurred in 64 patients, and 59 fractures (64%) were fall-related. Only one participant experienced fracture within the 10 years following their diagnosis of diabetes. In logistic regression analysis, the multivariate-adjusted ORs (95% CIs) of a history of severe hypoglycemia were 2.11 (1.11 to 4.09) for any fracture and 1.91 (0.93 to 4.02) for fall-related fracture. Fourteen of 18 participants with multiple episodes of any type of fracture had a history of severe hypoglycemia (p
      Keywords: Open access, Epidemiology/health services research
      PubDate: 2021-04-22T06:56:49-07:00
      DOI: 10.1136/bmjdrc-2020-002099
      Issue No: Vol. 9, No. 1 (2021)
  • Identifying sustainable lifestyle strategies for maintaining good glycemic
           control: a validation of qualitative findings

    • Authors: Weller, S. C; Vickers, B. N.
      Abstract: IntroductionDiabetes self-care practices are less effective outside of controlled research settings, and almost half of patients do not achieve good glycemic control. Qualitative studies suggest some lifestyle strategies may be linked to good control, but those strategies have not been validated. This study provides population-based evidence that dietary strategies identified in qualitative studies are associated with glycemic control in US patients with diabetes.Research design and methodsIn a cross-sectional sample of the National Health and Nutrition Examination Survey (NHANES), qualitative self-management themes were matched to survey questions and used to predict good glycemic control (hemoglobin A1c
      Keywords: Open access, Epidemiology/health services research
      PubDate: 2021-04-22T06:56:49-07:00
      DOI: 10.1136/bmjdrc-2020-002103
      Issue No: Vol. 9, No. 1 (2021)
  • Association between variability in body mass index and development of type
           2 diabetes: Panasonic cohort study

    • Authors: Okada, H; Hamaguchi, M, Habu, M, Kurogi, K, Murata, H, Ito, M, Fukui, M.
      Abstract: IntroductionContrasting results have been reported for the association between the variability in body weight and development of diabetes. In the present study, we evaluated the association between the variability in body mass index (BMI) and development of type 2 diabetes in 19 412 Japanese participants without obesity and without body weight gain or loss during the study period.Research design and methodsWe recorded body weight of the participants consecutively each year in Panasonic Corporation, Osaka, Japan from 2008 to 2014 to evaluate the variability of BMI. The participants with obesity (BMI ≥25 kg/m2) at baseline and body weight gain or loss from 2008 to 2014 (delta BMI ≥±1 kg/m2) were excluded from the study. In total, 416 participants developed type 2 diabetes from 2015 to 2018. We used coefficient of variation (CV) to represent the variability in BMI during 6 years of the study period.ResultsCox regression analyses revealed that the risk of developing type 2 diabetes was higher in the fourth quartile (HR 1.33; 95% CI 1.01 to 1.75) of CV of BMI than that in the first quartile (lowest quartile) of CV of BMI after adjusting for multiple confounding factors. The risk for developing diabetes increased by 11.1% per 1% increase in CV of BMI.ConclusionsIn conclusion, the variability in BMI is a risk factor for the development of diabetes in the Japanese population without obesity and without body weight gain or loss.
      Keywords: Open access, Epidemiology/health services research
      PubDate: 2021-04-22T06:56:49-07:00
      DOI: 10.1136/bmjdrc-2021-002123
      Issue No: Vol. 9, No. 1 (2021)
  • Neonatal amygdala microstructure mediates the relationship between
           gestational glycemia and offspring adiposity

    • Authors: Cai, S; Aris, I. M, Yuan, W. L, Tan, K. H, Godfrey, K. M, Gluckman, P. D, Shek, L. P.-C, Chong, Y.-S, Yap, F, Fortier, M. V, Meaney, M. J, Lee, Y. S, Qiu, A.
      Abstract: IntroductionTo determine if variations in the neonatal amygdala mediate the association between maternal antenatal glycemia and offspring adiposity in early childhood.Research design and methods123 non-obese pregnant women with no pregnancy complications aside from gestational diabetes underwent a 75 g 2-hour oral glucose tolerance test at 26–28 weeks’ gestation. Volume and fractional anisotropy (FA) of the neonatal amygdala (5–17 days old) were measured by MRI. The Body Mass Index (BMI) z-scores and sum of skinfold thickness (subscapular and triceps) of these children were tracked up to 60 months of age (18, 24, 36, 48, 54 and 60 months).ResultsMaternal fasting glucose levels were positively associated with the offspring’s sum of skinfold thickness at age 48 months (β=3.12, 95% CI 0.18 to 6.06 mm) and 60 months (β=4.14, 95% CI 0.46 to 7.82 mm) and BMI z-scores at 48 months (β=0.94, 95% CI 0.03 to 1.85), 54 months (β=0.74, 95% CI 0.12 to 1.36) and 60 months (β=0.74, 95% CI 0.08 to 1.39). Maternal fasting glucose was negatively associated with the offspring’s FA of the right amygdala (β=–0.019, 95% CI –0.036 to –0.003). Right amygdala FA was negatively associated with the sum of skinfold thickness in the offspring at age 48 months (β=–56.95, 95% CI –98.43 to –15.47 mm), 54 months (β=–46.18, 95% CI –88.57 to –3.78 mm), and 60 months (β=–53.69, 95% CI –105.74 to –1.64 mm). The effect sizes mediated by right amygdala FA between fasting glucose and sum of skinfolds were estimated at β=5.14 (95% CI 0.74 to 9.53) mm (p=0.022), β=4.40 (95% CI 0.08 to 8.72) (p=0.049) mm and β=4.56 (95% CI –0.17 to 9.29) mm (p=0.059) at 48, 54 and 60 months, respectively.ConclusionsIn the offspring of non-obese mothers, gestational fasting glucose concentration is negatively associated with neonatal right amygdala FA and positively associated with childhood adiposity. Neonatal right amygdala FA may be a potential mediator between maternal glycemia and childhood adiposity.
      Keywords: Open access, Epidemiology/health services research
      PubDate: 2021-04-22T06:56:48-07:00
      DOI: 10.1136/bmjdrc-2020-001396
      Issue No: Vol. 9, No. 1 (2021)
  • Nicorandil attenuates high glucose-induced insulin resistance by
           suppressing oxidative stress-mediated ER stress PERK signaling pathway

    • Authors: Liu, Z; Zhu, H, He, C, He, T, Pan, S, Zhao, N, Zhu, L, Guan, G, Liu, P, Zhang, Y, Wang, J.
      Abstract: IntroductionGlucose-induced insulin resistance is a typical character of diabetes. Nicorandil is now widely used in ischemic heart disease. Nicorandil shows protective effects against oxidative and endoplasmic reticulum (ER) stress, which are involved in insulin resistance. Here, we investigated mechanisms of nicorandil’s novel pharmacological activity on insulin resistance in diabetes.Research design and methodsNicorandil was administrated to streptozotocin-induced animals with diabetes and high glucose exposed skeletal muscle cells. Insulin resistance and glucose tolerance were evaluated. Molecular mechanisms concerning oxidative stress, ER stress signaling activation and glucose uptake were assessed.ResultsNicorandil attenuated high glucose-induced insulin resistance without affecting fasting blood glucose and glucose tolerance in whole body and skeletal muscle in rats with diabetes. Nicorandil treatment suppressed protein kinase C/nicotinamide adenine dinucleotide phosphate oxidases system activities by reducing cytoplasmic free calcium level in skeletal muscle cells exposed to high glucose. As a result, the oxidative stress-mediated ER stress protein kinase RNA-like endoplasmic reticulum kinase (PERK)/eukaryotic initiation factor 2α/activating transcription factor 4/CEBP homologous protein/tribbles homolog (TRB)3 signaling pathway activation was inhibited. Nicorandil downregulated expression of TRB3 and thus facilitated Akt phosphorylation in response to insulin stimulation, leading to glucose transporter4 plasma membrane translocation which promoted glucose uptake capability of skeletal muscle cells.ConclusionsBy reducing cytoplasmic calcium, nicorandil alleviated high glucose-induced insulin resistance by inhibiting oxidative stress-mediated ER stress PERK pathway.
      Keywords: Open access, Signal transduction
      PubDate: 2021-04-22T06:56:48-07:00
      DOI: 10.1136/bmjdrc-2020-001884
      Issue No: Vol. 9, No. 1 (2021)
  • Variation in hypoglycemia ascertainment and report in type 2 diabetes
           observational studies: a meta-epidemiological study

    • Authors: Rodriguez-Gutierrez, R; Salcido-Montenegro, A, Gonzalez-Gonzalez, J. G, McCoy, R. G.
      Abstract: IntroductionObservational studies constitute an important evidence base for hypoglycemia in diabetes management. This requires consistent and reliable ascertainment and reporting methodology, particularly in studies of type 2 diabetes where hypoglycemia risk is heterogeneous. Therefore, we aimed to examine the definitions of hypoglycemia used by observational studies of patients with type 2 diabetes.Research design and methodsWe conducted a meta-epidemiological review of observational studies reporting on hypoglycemia or evaluating glucose-lowering medications in adults with type 2 diabetes. MEDLINE and Google Scholar were searched from January 1970 to May 2018. The definitions of non-severe, severe and nocturnal hypoglycemia were examined.ResultsWe reviewed 243 studies: 47.7% reported on non-severe hypoglycemia, 77.8% on severe hypoglycemia and 16.9% on nocturnal hypoglycemia; 5.8% did not specify. Among 116 studies reporting non-severe hypoglycemia, 18.1% provided no definition, 23.3% used glucose values, 38.8% relied on patient-reported symptoms, 17.2% accepted either glucose values or patient-reported symptoms and 2.6% relied on International Classification of Disease (ICD) codes. Among 189 studies reporting severe hypoglycemia, 11.1% provided no definition, 53.4% required symptoms needing assistance, 3.7% relied on glucose values, 14.8% relied on ICD codes, 2.6% relied on ICD codes or glucose values and 15.9% required both symptoms needing assistance and glucose values. Overall, 38.2% of non-severe and 67.7% of severe hypoglycemia definitions were consistent with the International Hypoglycemia Study Group.ConclusionsThe marked heterogeneity in how hypoglycemia is defined in observational studies may contribute to the inadequate understanding and correction of hypoglycemia risk factors among patients with type 2 diabetes.
      Keywords: Open access, Epidemiology/health services research
      PubDate: 2021-04-22T06:56:48-07:00
      DOI: 10.1136/bmjdrc-2020-001906
      Issue No: Vol. 9, No. 1 (2021)
  • Associations between continuous glucose monitoring-derived metrics and
           diabetic retinopathy and albuminuria in patients with type 2 diabetes

    • Authors: Wakasugi, S; Mita, T, Katakami, N, Okada, Y, Yoshii, H, Osonoi, T, Nishida, K, Shiraiwa, T, Torimoto, K, Kurozumi, A, Gosho, M, Shimomura, I, Watada, H.
      Abstract: IntroductionPreventing the development and progression of diabetic microvascular complications through optimal blood glucose control remains an important challenge. Whether metrics based on continuous glucose monitoring are useful for the management of diabetic microvascular complications is not entirely clear.Research design and methodsThis is an exploratory analysis of an ongoing prospective, multicenter, 5-year follow-up observational study. Study participants included 999 outpatients with type 2 diabetes who underwent continuous glucose monitoring at baseline. Associations between continuous glucose monitoring-derived metrics and the severity of diabetic retinopathy or albuminuria were investigated using multivariable proportional odds models.ResultsThe overall prevalence of diabetic retinopathy was 22.2%. Multivariate analysis with proportional odds models demonstrated that continuous glucose monitoring-derived metrics related to intraday and interday glucose variability are significantly associated with the severity of diabetic retinopathy, even after adjusting for various possible risk factors. However, significant relationships were not observed after adjusting for hemoglobin A1c (HbA1c) levels. The prevalence of microalbuminuria and macroalbuminuria was 20.3% and 6.7%, respectively. Similarly, multivariate analysis demonstrated that those metrics are significantly associated with the severity of albuminuria. These relationships remained significant even after further adjusting for HbA1c levels.ConclusionsContinuous glucose monitoring-derived metrics related to intraday and interday glucose variability are significantly associated with the severity of diabetic retinopathy or albuminuria in patients with type 2 diabetes. Thus, evaluating these metrics might possibly be useful for risk assessment of diabetic microvascular complications.Trial registration number UMIN000032325.
      Keywords: Open access, Pathophysiology/complications
      PubDate: 2021-04-20T08:13:40-07:00
      DOI: 10.1136/bmjdrc-2020-001923
      Issue No: Vol. 9, No. 1 (2021)
  • Lifestyle interventions for type 2 diabetes management among migrants and
           ethnic minorities living in industrialized countries: a systematic review
           and meta-analyses

    • Authors: Rawal, L; Sahle, B. W, Smith, B. J, Kanda, K, Owusu-Addo, E, Renzaho, A. M. N.
      Abstract: The objective of this systematic review was to determine the effectiveness of lifestyle interventions to improve the management of type 2 diabetes mellitus (T2DM) among migrants and ethnic minorities. Major searched databases included MEDLINE (via PubMed), EMBASE (via Ovid) and CINAHL. The selection of studies and data extraction followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. In the meta-analysis, significant heterogeneity was detected among the studies (I2 >50%), and hence a random effects model was used. Subgroup analyses were performed to compare the effect of lifestyle interventions according to intervention approaches (peer-led vs community health workers (CHWs)-led). A total of 17 studies were included in this review which used interventions delivered by CHWs or peer supporters or combination of both. The majority of the studies assessed effectiveness of key primary (hemoglobin (HbA1c), lipids, fasting plasma glucose) and secondary outcomes (weight, body mass index, blood pressure, physical activity, alcohol consumption, tobacco smoking, food habits and healthcare utilization). Meta-analyses showed lifestyle interventions were associated with a small but statistically significant reduction in HbA1c level (–0.18%; 95% CI –0.32% to –0.04%, p=0.031). In subgroup analyses, the peer-led interventions showed relatively better HbA1c improvement than CHW-led interventions, but the difference was not statistically significant (p=0.379). Seven studies presented intervention costs, which ranged from US$131 to US$461 per participant per year. We conclude that lifestyle interventions using either CHWs or peer supporters or a combination of both have shown modest effectiveness for T2DM management among migrants of different background and origin and ethnic minorities. The evidence base is promising in terms of developing culturally appropriate, clinically sound and cost-effective intervention approaches to respond to the growing and diverse migrants and ethnic minorities affected by diabetes worldwide.
      Keywords: Open access, Epidemiology/health services research
      PubDate: 2021-04-20T08:13:40-07:00
      DOI: 10.1136/bmjdrc-2020-001924
      Issue No: Vol. 9, No. 1 (2021)
  • Plasma heat shock protein response to euglycemia in type 2 diabetes

    • Authors: Atkin, A. S; Moin, A. S. M, Al-Qaissi, A, Sathyapalan, T, Atkin, S. L, Butler, A. E.
      Abstract: IntroductionGlucose variability is associated with mortality and macrovascular diabetes complications. The mechanisms through which glucose variability mediates tissue damage are not well understood, although cellular oxidative stress is likely involved. As heat shock proteins (HSPs) play a role in the pathogenesis of type 2 diabetes (T2D) complications and are rapidly responsive, we hypothesized that HSP-related proteins (HSPRPs) would differ in diabetes and may respond to glucose normalization.Research design and methodsA prospective, parallel study in T2D (n=23) and controls (n=23) was undertaken. T2D subjects underwent insulin-induced blood glucose normalization from baseline 7.6±0.4 mmol/L (136.8±7.2 mg/dL) to 4.5±0.07 mmol/L (81±1.2 mg/dL) for 1 hour. Control subjects were maintained at 4.9±0.1 mmol/L (88.2±1.8 mg/dL). Slow Off-rate Modified Aptamer-scan plasma protein measurement determined a panel of HSPRPs.ResultsAt baseline, E3-ubiquitin-protein ligase (carboxyl-terminus of Hsc70 interacting protein (CHIP) or HSPABP2) was lower (p=0.03) and ubiquitin-conjugating enzyme E2G2 higher (p=0.003) in T2D versus controls. Following glucose normalization, DnaJ homolog subfamily B member 1 (DNAJB1 or HSP40) was reduced (p=0.02) in T2D, with HSP beta-1 (HSPB1) and HSP-70-1A (HSP70-1A) (p=0.07 and p=0.09, respectively) also approaching significance relative to T2D baseline levels.ConclusionsKey HSPRPs involved in critical protein interactions, CHIP and UBE2G2, were altered in diabetes at baseline. DNAJB1 fell in response to euglycemia, suggesting that HSPs are reacting to basal stress that could be mitigated by tight glucose control with reduction of glucose variability.
      Keywords: Open access, Pathophysiology/complications
      PubDate: 2021-04-20T08:13:40-07:00
      DOI: 10.1136/bmjdrc-2020-002057
      Issue No: Vol. 9, No. 1 (2021)
  • Central administration of sodium-glucose cotransporter-2 inhibitors
           increases food intake involving adenosine monophosphate-activated protein
           kinase phosphorylation in the lateral hypothalamus in healthy rats

    • Authors: Takeda, K; Ono, H, Ishikawa, K, Ohno, T, Kumagai, J, Ochiai, H, Matumoto, A, Yokoh, H, Maezawa, Y, Yokote, K.
      Abstract: IntroductionSodium glucose cotransporter-2 (SGLT2) inhibitors are widely used for diabetes treatment. Although SGLT2 inhibitors have been clinically observed to increase food intake, roles or even the presence of SGLT2 in the central nervous system (CNS) has not been established. We aimed to elucidate potential functions of SGLT2 in the CNS, and the effects of CNS-targeted SGLT2 inhibitors on food intake.Research design and methodsWe administered three kinds of SGLT2 inhibitors, tofogliflozin, dapagliflozin, and empagliflozin, into the lateral ventricle (LV) in rats and evaluated their effects on food intake. We also evaluated the effects of tofogliflozin administration in the third (3V) and fourth ventricle (4V). Intraperitoneal administration of liraglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist known to suppress food intake, was combined with central tofogliflozin to elucidate whether GLP-1 signaling antagonizes the effect of central SGLT2 inhibitors on food intake. To elucidate potential molecular mechanisms mediating changes in feeding, hypothalamic areas associated with food intake regulation were harvested and analyzed after intracerebroventricular administration (ICV) of tofogliflozin.ResultsBolus ICV injection of tofogliflozin induced a robust increase in food intake starting at 1.5 hours postinjection, and lasting for 5 days. No effect was observed when the same dose of tofogliflozin was administered intraperitoneally. ICV dapagliflozin and empagliflozin significantly enhanced food intake, although the strength of these effects varied among drugs. Food intake was most markedly enhanced when tofogliflozin was infused into the LV. Fewer or no effects were observed with infusion into the 3V or 4V, respectively. Systemic administration of liraglutide suppressed the effect of ICV tofogliflozin on food intake. ICV tofogliflozin increased phosphorylation of AMPK and c-fos expression in the lateral hypothalamus.ConclusionsSGLT2 inhibitors in the CNS increase food intake. SGLT2 activity in the CNS may regulate food intake through AMPK phosphorylation in the lateral hypothalamic area.
      Keywords: Open access, Metabolism
      PubDate: 2021-04-20T08:13:40-07:00
      DOI: 10.1136/bmjdrc-2020-002104
      Issue No: Vol. 9, No. 1 (2021)
  • Association of periodontal pocket area with type 2 diabetes and obesity: a
           cross-sectional study

    • Authors: Takeda, K; Mizutani, K, Minami, I, Kido, D, Mikami, R, Konuma, K, Saito, N, Kominato, H, Takemura, S, Nakagawa, K, Izumi, Y, Ogawa, Y, Iwata, T.
      Abstract: IntroductionThe aim was to investigate the relationship of full-mouth inflammatory parameters of periodontal disease with diabetes and obesity.Research design and methodsThis cross-sectional study conducted diabetes-related examinations and calculated periodontal inflamed and epithelial surface area (PISA and PESA) of 71 Japanese patients with type 2 diabetes. Multiple linear regression analyses were performed to evaluate associations between PISA or PESA and diabetes and obesity parameters.ResultsMedian value of body mass index (BMI), hemoglobin A1c (HbA1c) level, fasting plasma glucose (FPG) level, and visceral fat area (VFA) were 25.7 kg/m2, 9.1%, 151 mg/L, and 93.3 cm2, respectively. PISA and PESA were significantly associated with HbA1c after adjusting for age, sex, BMI, smoking status, and full-mouth plaque control level (PISA: coefficient=38.1, 95% CI 8.85 to 67.29, p=0.001; PESA: coefficient=66.89, 95% CI 21.44 to 112.34, p=0.005). PISA was also significantly associated with the highest FPG tertile (>175 mg/dL) after adjusting for confounders (coefficient=167.0, 95% CI 48.60 to 285.4, p=0.006). PISA and PESA were not significantly associated with BMI or VFA.ConclusionPISA was associated with FPG and HbA1c, but not with obesity parameters, independent from confounders such as full-mouth plaque control level in patients with type 2 diabetes.
      Keywords: Open access, Epidemiology/health services research
      PubDate: 2021-04-20T08:13:40-07:00
      DOI: 10.1136/bmjdrc-2021-002139
      Issue No: Vol. 9, No. 1 (2021)
  • Therapy adjustments in people with type 1 diabetes with impaired
           hypoglycemia awareness on multiple daily injections using real-time

    • Authors: Waldenmaier, D; Freckmann, G, Pleus, S, Hermanns, N, Ehrmann, D, Heinemann, L, Haug, C.
      Abstract: IntroductionStudies have shown beneficial effects of real-time continuous glucose monitoring (rtCGM) usage on clinical outcomes. The objective of this analysis was to identify which therapy adjustments were made by people with type 1 diabetes with impaired hypoglycemia awareness during rtCGM usage enabling reductions in the number of low glucose events observed in the HypoDE (Hypoglycemia in Deutschland) study.Research design and methodsIn the multicenter randomized controlled trial in people with type 1 diabetes on multiple daily injections with impaired hypoglycemia awareness, participants recorded their diabetes therapy in 7-day logbooks at baseline and at 6-month follow-up. They used rtCGM or self-monitoring of blood glucose for therapy adjustments. This mechanistic analysis looked at changes in various aspects of therapy.ResultsLogbooks were completed by 70 participants in the rtCGM group and 65 participants in the control group. Participants in the rtCGM group kept their total carbohydrate consumption, daily insulin doses and distribution constant during the study. However, they reported an increased intake of rescue carbohydrates (0.8±0.6 (mean±SD) vs 1.0±0.8 intake/day; baseline-adjusted between-group difference 0.3 intake (0.1–0.5), p=0.031). The glucose threshold at which rescue carbohydrate intake was initiated was elevated from 71±13 mg/dL (3.9±0.7 mmol/L) to 79±14 mg/dL (4.4±0.8 mmol/L) (adjusted between-group difference +7.6 mg/dL (2.4–12.8) (+0.4 mmol/L (0.1–0.7)); p=0.005) in the rtCGM group. Regression analysis showed that follow-up low glucose events were associated with group allocation (p
      Keywords: Open access, Clinical care/education/nutrition/psychosocial research
      PubDate: 2021-04-16T08:08:50-07:00
      DOI: 10.1136/bmjdrc-2020-001848
      Issue No: Vol. 9, No. 1 (2021)
  • Importance of applying treatment data to ascertain type 1 diabetes cases
           in health registries

    • Authors: Mosslemi, M; Wong, N. D.
      Keywords: Open access
      PubDate: 2021-04-16T08:08:50-07:00
      DOI: 10.1136/bmjdrc-2021-002280
      Issue No: Vol. 9, No. 1 (2021)
  • Interleukin-6 mediated exercise-induced alleviation of adiposity and
           hepatic steatosis in mice

    • Authors: Li, L; Huang, C, Yin, H, Zhang, X, Wang, D, Ma, C, Li, J, Zhao, Y, Li, X.
      Abstract: IntroductionExercise training has been shown to be the most effective strategy to combat obesity and non-alcoholic fatty liver disease. However, exercise promotes loss of adipose tissue mass and improves obesity-related hepatic steatosis through mechanisms that remain obscure.Research design and methodsTo study the role of interleukin-6 (IL-6) in high-fat diet (HFD)-induced adiposity and hepatic steatosis during treadmill running, IL-6 knockout (IL-6 KO) mice and wild-type (WT) mice were randomly divided into lean, obese (fed a HFD) and trained obese groups (fed a HFD and exercise trained).ResultsAfter 20 weeks of HFD feeding and 8 weeks of treadmill running, we found that exercise obviously reduced HFD-induced body weight gain, inhibited visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) expansion and almost completely reversed obesity-related intrahepatic fat accumulation in WT mice. However, IL-6 knockout (IL-6 KO) mice are refractory to the benefits of treadmill training on body weight, VAT and SAT mass elevation, and hepatic steatosis. Moreover, a panel of lipolytic-related and thermogenic-related genes, including ATGL, HSL and PGC-1α, was upregulated in the VAT and SAT of WT mice that received exercise training compared with untrained mice, which was not observed in IL-6 KO mice. In addition, exercise training resulted in a significant inhibition of hepatic peroxisome proliferator-activated receptor gamma (PPAR-) expression in WT mice, and these effects were not noted in IL-6 KO mice.ConclusionThese results revealed that IL-6 is involved in the prevention of obesity and hepatic fat accumulation during exercise training. The mechanisms underlying these antiobesity effects may be associated with enhanced lipolysis and thermogenesis in white adipose tissue. The improvement in hepatic steatosis by exercise training may benefit from the marked inhibition of PPAR- expression by IL-6.
      Keywords: Open access, Obesity studies
      PubDate: 2021-04-14T09:20:36-07:00
      DOI: 10.1136/bmjdrc-2020-001431
      Issue No: Vol. 9, No. 1 (2021)
  • Reducing weight and BMI following gestational diabetes: a systematic
           review and meta-analysis of digital and telemedicine interventions

    • Authors: Halligan, J; Whelan, M. E, Roberts, N, Farmer, A. J.
      Abstract: Women with past gestational diabetes mellitus (GDM) are at risk of subsequent type 2 diabetes and adverse cardiovascular events. Digital and telemedicine interventions targeting weight loss and reductions in body mass index (BMI) may help reduce risk for women with GDM. The aim was to compare the effectiveness of digital or telemedicine intervention with usual care. Randomized controlled trials (RCTs) were identified in Embase, Medline, CINAHL, PsycINFO and the Cochrane Library. Included trials recruited women with prior GDM but without pre-existing diabetes, and tested a digital or telemedicine intervention with or without an in-person component. Data extraction was carried out independently by two authors. The search yielded 898 citations. Eighteen articles reporting 15 trials were included, of which 8 tested digital interventions. Reported outcomes included weight, BMI, fasting plasma glucose and waist circumference. None of the included trials reported type 2 diabetes incidence or cardiovascular risk. Data were pooled using a random-effects model. The point estimate favored the intervention but was non-significant for both BMI (–0.90 kg/m2, 95% CI –1.89 to 0.09; p=0.08) and weight (–1.83 kg, 95% CI –4.08 to 0.42, p=0.11). Trials evaluating digital and telemedicine interventions identified clinically relevant, but non-significant improvements in BMI and weight compared with control. No trials assessed type 2 diabetes occurrence as an outcome. More well-designed RCTs with adequate power and long-term follow-up are needed to identify the impact of these interventions on type 2 diabetes occurrence.
      Keywords: Open access
      PubDate: 2021-04-14T09:20:36-07:00
      DOI: 10.1136/bmjdrc-2020-002077
      Issue No: Vol. 9, No. 1 (2021)
  • Trigger finger is associated with risk of incident cardiovascular disease
           in individuals with type 2 diabetes: a retrospective cohort study

    • Authors: Mineoka, Y; Ishii, M, Hashimoto, Y, Yuge, H, Toyoda, M, Nakamura, N, Katsumi, Y, Fukui, M.
      Abstract: IntroductionTrigger finger is one of the complications affecting the upper extremity in patients with diabetes. Diabetes is also a well-known risk factor that predisposes individuals to cardiovascular diseases (CVDs). This retrospective cohort study aimed to establish the association between trigger finger and the patients with incident CVD with type 2 diabetes.Materials and methodsTrigger finger was diagnosed by palpating a thickened tendon during flexion or on the manifestation of a locking phenomenon during extension or flexion of either finger. The relationship between trigger finger and other clinical parameters or complications of diabetes was examined by a comparative analysis. Cox regression analysis was used to evaluate the association between trigger finger and incidence of CVD. We calculated the propensity scores using sex, body mass index, age, smoking status, duration of diabetes, estimated glomerular filtration rate, hypertension, dyslipidemia, and hemoglobin A1c as the number of patients with incident CVD during the follow-up period was low.ResultsAmong the 399 patients with type 2 diabetes, 54 patients had trigger finger. Patients with trigger finger were significantly older in age and had been suffering from diabetes for a longer duration. They also displayed worse renal function and glycemic control, along with a higher incidence of hypertension, neuropathy and nephropathy. During the average 5.66±1.12 years of follow-up, a total of 18 incidents occurred. According to the Cox regression analysis, trigger finger was shown to be associated with enhanced risk of the incidence of CVD after adjustment for the covariates (adjusted HR=3.33 (95% CI 1.25 to 8.66), p=0.017).ConclusionsTrigger finger is associated with the risk of incident CVD in patients with type 2 diabetes. Thus, clinicians must consider these factors at the time of diagnosis of such patients.
      Keywords: Open access, Cardiovascular and metabolic risk
      PubDate: 2021-04-08T08:00:03-07:00
      DOI: 10.1136/bmjdrc-2020-002070
      Issue No: Vol. 9, No. 1 (2021)
  • Predictive utilities of lipid traits, lipoprotein subfractions and other
           risk factors for incident diabetes: a machine learning approach in the
           Diabetes Prevention Program

    • Authors: Varga, T. V; Liu, J, Goldberg, R. B, Chen, G, Dagogo-Jack, S, Lorenzo, C, Mather, K. J, Pi-Sunyer, X, Brunak, S, Temprosa, M, On behalf of the Diabetes Prevention Program Research Group
      Abstract: IntroductionAlthough various lipid and non-lipid analytes measured by nuclear magnetic resonance (NMR) spectroscopy have been associated with type 2 diabetes, a structured comparison of the ability of NMR-derived biomarkers and standard lipids to predict individual diabetes risk has not been undertaken in larger studies nor among individuals at high risk of diabetes.Research design and methodsCumulative discriminative utilities of various groups of biomarkers including NMR lipoproteins, related non-lipid biomarkers, standard lipids, and demographic and glycemic traits were compared for short-term (3.2 years) and long-term (15 years) diabetes development in the Diabetes Prevention Program, a multiethnic, placebo-controlled, randomized controlled trial of individuals with pre-diabetes in the USA (N=2590). Logistic regression, Cox proportional hazards model and six different hyperparameter-tuned machine learning algorithms were compared. The Matthews Correlation Coefficient (MCC) was used as the primary measure of discriminative utility.ResultsModels with baseline NMR analytes and their changes did not improve the discriminative utility of simpler models including standard lipids or demographic and glycemic traits. Across all algorithms, models with baseline 2-hour glucose performed the best (max MCC=0.36). Sophisticated machine learning algorithms performed similarly to logistic regression in this study.ConclusionsNMR lipoproteins and related non-lipid biomarkers were associated but did not augment discrimination of diabetes risk beyond traditional diabetes risk factors except for 2-hour glucose. Machine learning algorithms provided no meaningful improvement for discrimination compared with logistic regression, which suggests a lack of influential latent interactions among the analytes assessed in this study.Trial registration numberDiabetes Prevention Program: NCT00004992; Diabetes Prevention Program Outcomes Study: NCT00038727.
      Keywords: Open access, Epidemiology/health services research
      PubDate: 2021-03-31T07:54:31-07:00
      DOI: 10.1136/bmjdrc-2020-001953
      Issue No: Vol. 9, No. 1 (2021)
  • Effects of nutrition education using a food-based approach, carbohydrate
           counting or routine care in type 1 diabetes: 12 months prospective
           randomized trial

    • Authors: Sterner Isaksson, S; Bensow Bacos, M, Eliasson, B, Thors Adolfsson, E, Rawshani, A, Lindblad, U, Jendle, J, Berglund, A, Lind, M, Axelsen, M.
      Abstract: IntroductionEvidence on the effects of structured nutrition education is weak in adults with type 1 diabetes mellitus (T1D) with moderately impaired glycemic control. Objective was to compare the effects of different types of nutrition education programs on glycemic control, cardiovascular risk factors, quality of life, diet quality and food choices in T1D.Research design and methodsA 12 months randomized controlled study conducted at nine diabetes specialist centers with three parallel arms: (i) a food-based approach (FBA) including foods with low glycemic index or (ii) carbohydrate counting (CC) according to today’s standard practice or (iii) individual sessions according to routine care (RC). The primary end point was difference in glycated hemoglobin A1c (HbA1c) between groups at 12 months.Results159 patients were randomized (FBA: 51; CC: 52; RC: 55). Mean (SD) age 48.6 (12.0) years, 57.9% females and mean (SD) HbA1c level 63.9 (7.9) mmol/mol, 8% (0.7%). After 3 months, HbA1c improved in both FBA and CC compared with RC. However, there were no significant differences at 12 months in HbA1c; FBA versus RC (–0.4 mmol/mol (1.3), 0.04% (0.1%)), CC versus RC (–0.8 mmol/mol (1.2), 0.1% (0.1%)), FBA versus CC (0.4 mmol/mol (0.3), 0.04% (0.01%)). At 12 months, intake of legumes, nuts and vegetables was improved in FBA versus CC and RC. FBA also reported higher intake of monounsaturated and polyunsaturated fats compared with RC, and dietary fiber, monounsaturated and polyunsaturated fats compared with CC (all p values
      Keywords: Open access, Clinical care/education/nutrition/psychosocial research
      PubDate: 2021-03-31T07:54:31-07:00
      DOI: 10.1136/bmjdrc-2020-001971
      Issue No: Vol. 9, No. 1 (2021)
  • Association between serum fibroblast growth factor 21 level and
           sight-threatening diabetic retinopathy in Chinese patients with type 2

    • Authors: Jin, S; Xia, N, Han, L.
      Abstract: IntroductionWe conducted this cross-sectional study to explore the relationship between serum fibroblast growth factor 21 (FGF21) level and sight-threatening diabetic retinopathy (STDR).Research design and methodsA total of 654 patients with type 2 diabetes were recruited. Diabetic retinopathy (DR) was evaluated by the bilateral retinal photography, and patients were assigned into groups of no DR (NDR) (n=345, 52.75%), non-sight-threatening diabetic retinopathy (NSTDR) (n=207, 31.65%), involving patients with mild or moderate non-proliferative retinopathy (NPDR) and STDR (n=102, 15.60%), including those with severe NPDR or proliferative diabetic retinopathy (PDR). Serum FGF21 levels were quantified by a sandwich ELISA. Patients were divided into quartiles according to their serum FGF21 level.ResultsThere was a significant difference in serum FGF21 level among the three groups of patients (p
      Keywords: Open access, Pathophysiology/complications
      PubDate: 2021-03-31T07:54:31-07:00
      DOI: 10.1136/bmjdrc-2021-002126
      Issue No: Vol. 9, No. 1 (2021)
  • Lack of effect of Lactobacillus rhamnosus GG and Bifidobacterium lactis
           Bb12 on beta-cell function in children with newly diagnosed type 1
           diabetes: a randomised controlled trial

    • Authors: Groele, L; Szajewska, H, Szalecki, M, Swiderska, J, Wysocka-Mincewicz, M, Ochocinska, A, Stelmaszczyk-Emmel, A, Demkow, U, Szypowska, A.
      Abstract: IntroductionThe gut microbiota may be relevant in the development of type 1 diabetes (T1D). We examined the effects of Lactobacillus rhamnosus GG and Bifidobacterium lactis Bb12 on beta-cell function in children with newly diagnosed T1D.Research design and methodsChildren aged 8–17 years with newly (within 60 days) diagnosed T1D were enrolled in a double-blind, randomised controlled trial in which they received L. rhamnosus GG and B. lactis Bb12 at a dose of 109 colony-forming units or placebo, orally, once daily, for 6 months. The follow-up was for 12 months. The primary outcome measure was the area under the curve (AUC) of the C-peptide level during 2-hour responses to a mixed meal.ResultsNinety-six children were randomised (probiotics, n=48; placebo n=48; median age 12.3 years). Eighty-eight (92%) completed the 6-month intervention, and 87 (91%) completed the follow-up at 12 months. There was no significant difference between the study groups for the AUC of the C-peptide level. For the secondary outcomes at 6 months, there were no differences between the study groups. At 12 months, with one exception, there also were no significant differences between the groups. Compared with the placebo group, there was a significantly increased number of subjects with thyroid autoimmunity in the probiotic group. However, at baseline, there was also a higher frequency of thyroid autoimmunity in the probiotic group. There were no cases of severe hypoglycemia or ketoacidosis in any of the groups. No adverse events related to the study products were reported.ConclusionsL. rhamnosus GG and B. lactis Bb12, as administered in this study, had no significant effect in maintaining the residual pancreatic beta-cell function in children with newly diagnosed T1D. It remains unclear which probiotics, if any, alone or in combination, are potentially the most useful for management of T1D.Trial registration numberNCT03032354.
      Keywords: Open access, Clinical care/education/nutrition/psychosocial research
      PubDate: 2021-03-26T09:15:27-07:00
      DOI: 10.1136/bmjdrc-2020-001523
      Issue No: Vol. 9, No. 1 (2021)
  • Incidence and pathophysiology of diabetes in South Asian adults living in
           India and Pakistan compared with US blacks and whites

    • Authors: Narayan, K. M. V; Kondal, D, Daya, N, Gujral, U. P, Mohan, D, Patel, S. A, Shivashankar, R, Anjana, R. M, Staimez, L. R, Ali, M. K, Chang, H. H, Kadir, M, Prabhakaran, D, Selvin, E, Mohan, V, Tandon, N.
      Abstract: IntroductionWe compared diabetes incidence in South Asians aged ≥45 years in urban India (Chennai and Delhi) and Pakistan (Karachi), two low-income and middle-income countries undergoing rapid transition, with blacks and whites in the US, a high-income country.Research design and methodsWe computed age-specific, sex-specific and body mass index (BMI)-specific diabetes incidence from the prospective Center for Cardiometabolic Risk Reduction in South Asia Study (n=3136) and the Atherosclerosis Risk in Communities Study (blacks, n=3059; whites, n=9924). We assessed factors associated with incident diabetes using Cox proportional hazards regression.ResultsSouth Asians have lower BMI and waist circumference than blacks and whites (median BMI, kg/m2: 24.9 vs 28.2 vs 26.0; median waist circumference, cm 87.5 vs 96.0 vs 95.0). South Asians were less insulin resistant than blacks and whites (age-BMI-adjusted homeostatic model assessment of insulin resistance, µIU/mL/mmol/L: 2.30 vs 3.45 vs 2.59), and more insulin deficient than blacks but not whites (age-BMI-adjusted homeostasis model assessment of β-cell dysfunction, µIU/mL/mmol/L: 103.7 vs 140.6 vs 103.9). Age-standardized diabetes incidence (cases/1000 person-years (95% CI)) in South Asian men was similar to black men and 1.6 times higher (1.37 to 1.92) than white men (26.0 (22.2 to 29.8) vs 26.2 (22.7 to 29.7) vs 16.1 (14.8 to 17.4)). In South Asian women, incidence was slightly higher than black women and 3 times (2.61 to 3.66) the rate in white women (31.9 (27.5 to 36.2) vs 28.6 (25.7 to 31.6) vs 11.3 (10.2 to 12.3)). In normal weight (BMI
      Keywords: Open access, Epidemiology/health services research
      PubDate: 2021-03-26T09:15:27-07:00
      DOI: 10.1136/bmjdrc-2020-001927
      Issue No: Vol. 9, No. 1 (2021)
  • Incidence of diabetes in South Asian young adults compared to Pima Indians

    • Authors: Narayan, K. M. V; Kondal, D, Kobes, S, Staimez, L. R, Mohan, D, Gujral, U. P, Patel, S. A, Anjana, R. M, Shivashankar, R, Ali, M. K, Chang, H. H, Kadir, M, Prabhakaran, D, Daya, N, Selvin, E, Tandon, N, Hanson, R, Mohan, V.
      Abstract: IntroductionSouth Asians (SA) and Pima Indians have high prevalence of diabetes but differ markedly in body size. We hypothesize that young SA will have higher diabetes incidence than Pima Indians at comparable body mass index (BMI) levels.Research design and methodsWe used prospective cohort data to estimate age-specific, sex, and BMI-specific diabetes incidence in SA aged 20–44 years living in India and Pakistan from the Center for Cardiometabolic Risk Reduction in South Asia Study (n=6676), and compared with Pima Indians, from Pima Indian Study (n=1852).ResultsAt baseline, SA were considerably less obese than Pima Indians (BMI (kg/m2): 24.4 vs 33.8; waist circumference (cm): 82.5 vs 107.0). Age-standardized diabetes incidence (cases/1000 person-years, 95% CI) was lower in SA than in Pima Indians (men: 14.2, 12.2–16.2 vs 37.3, 31.8–42.8; women: 14.8, 13.0–16.5 vs 46.1, 41.2–51.1). Risk of incident diabetes among 20–24-year-old Pima men and women was six times (relative risk (RR), 95% CI: 6.04, 3.30 to 12.0) and seven times (RR, 95% CI: 7.64, 3.73 to 18.2) higher as compared with SA men and women, respectively. In those with BMI
      Keywords: Open access, Epidemiology/health services research
      PubDate: 2021-03-26T09:15:27-07:00
      DOI: 10.1136/bmjdrc-2020-001988
      Issue No: Vol. 9, No. 1 (2021)
  • Pharmacologically treated diabetes and hospitalization among older
           Norwegians receiving homecare services from 2009 to 2014: a nationwide
           register study

    • Authors: Fismen, A.-S; Igland, J, Teigland, T, Tell, G. S, Ostbye, T, Haltbakk, J, Graue, M, Birkeland, K. I, Peyrot, M, Iversen, M. M.
      Abstract: IntroductionThe aim was to assess whether annual hospitalization (admissions, length of stay and total days hospitalized) among persons >65 years receiving home care services in Norway were higher for persons with diabetes than those without diabetes. Given the growing prevalence of diabetes, this issue has great importance for policy makers who must plan for meeting these needs.Research design and methodsData were obtained from national Norwegian registries, and the study population varied from 112 487 to 125 593 per calendar year during 2009–2014. Diabetes was defined as having been registered with at least one prescription for blood glucose lowering medication. Overall and cause-specific hospitalization were compared, as well as temporal trends in hospitalization. Hospitalization outcomes for persons with and without diabetes were compared using log-binomial regression or quantile regression, adjusting for age and gender. Results are reported as incidence rate ratios (IRRs).ResultsHigher total hospitalization rates (IRR 1.17; 95% CI 1.12 to 1.22) were found among persons with, versus without, diabetes, and this difference remained stable throughout the study period. Similar reductions over time in hospital length of stay were observed among persons with and without diabetes, but total annual days hospitalized decreased significantly (p=0.001) more among those with diabetes than among those without diabetes.ConclusionsAmong older recipients of home care services in Norway, diabetes was associated with a higher overall risk of hospitalization and increased days in the hospital. Given the growing prevalence of diabetes, it is important for policy makers to plan for meeting these needs.
      Keywords: Open access, Epidemiology/health services research
      PubDate: 2021-03-26T09:15:27-07:00
      DOI: 10.1136/bmjdrc-2020-002000
      Issue No: Vol. 9, No. 1 (2021)
  • Insulin resistance versus insulin deficiency: evidence of racial
           differences in the pathogenesis of type 2 diabetes

    • Authors: Garg R.
      Keywords: Open access
      PubDate: 2021-03-26T09:15:27-07:00
      DOI: 10.1136/bmjdrc-2021-002261
      Issue No: Vol. 9, No. 1 (2021)
  • Skin autofluorescence predicts cancer in subjects with type 2 diabetes

    • Authors: Foussard, N; Larroumet, A, Rigo, M, Mohammedi, K, Baillet-Blanco, L, Poupon, P, Monlun, M, Lecocq, M, Devouge, A.-C, Ducos, C, Liebart, M, Battaglini, Q, Rigalleau, V.
      Abstract: IntroductionSubjects with type 2 diabetes have an excess risk of cancer. The potential role of advanced glycation end products (AGEs) accumulated during long-term hyperglycemia in cancer development has been suggested by biological studies but clinical data are missing. AGEs can be estimated by measuring the skin autofluorescence. We searched whether the skin autofluorescence could predict new cancers in persons with type 2 diabetes.Research design and methodsFrom 2009 to 2015, we measured the skin autofluorescence of 413 subjects hospitalized for uncontrolled or complicated type 2 diabetes, without any history of cancer. The participants were followed for at least 1 year and the occurrences of new cancers were compared according to their initial skin autofluorescences.ResultsThe participants were mainly men (57.9%), with poorly controlled (HbA1c 72±14 mmol/mol or 8.7%±1.8%) and/or complicated type 2 diabetes. Their median skin autofluorescence was 2.6 (2.2–3.0) arbitrary units. Forty-five new cancer cases (10.9%) were registered during 4.8±2.3 years of follow-up: 75.6% of these subjects had skin autofluorescence higher than the median (2: p=0.001). By Cox regression analysis adjusted for age, gender, body mass index, history of smoking and renal parameters, skin autofluorescence >2.6 predicted a 2.57-fold higher risk of cancer (95% CI 1.28 to 5.19, p=0.008). This association remained significant after excluding the eight cancers that occurred in the 4 years after inclusion (OR 2.95, 95% CI 1.36 to 6.38, p=0.006). As a continuous variable, skin autofluorescence was also related to new cancers (OR 1.05, 95% CI 1.01 to 1.10, p=0.045).ConclusionsSkin autofluorescence, a potential marker of glycemic memory, predicts the occurrence of cancer in subjects with type 2 diabetes. This relation provides a new clinical argument for the role of AGEs in cancer. Their estimation by measuring the skin autofluorescence may help select subjects with diabetes in cancer screening programs.
      Keywords: Open access, Pathophysiology/complications
      PubDate: 2021-03-24T08:20:17-07:00
      DOI: 10.1136/bmjdrc-2020-001312
      Issue No: Vol. 9, No. 1 (2021)
  • Glycemic variability and cardiovascular disease in patients with type 2

    • Authors: Martinez, M; Santamarina, J, Pavesi, A, Musso, C, Umpierrez, G. E.
      Abstract: Glycated hemoglobin is currently the gold standard for assessment of long-term glycemic control and response to medical treatment in patients with diabetes. Glycated hemoglobin, however, does not address fluctuations in blood glucose. Glycemic variability (GV) refers to fluctuations in blood glucose levels. Recent clinical data indicate that GV is associated with increased risk of hypoglycemia, microvascular and macrovascular complications, and mortality in patients with diabetes, independently of glycated hemoglobin level. The use of continuous glucose monitoring devices has markedly improved the assessment of GV in clinical practice and facilitated the assessment of GV as well as hypoglycemia and hyperglycemia events in patients with diabetes. We review current concepts on the definition and assessment of GV and its association with cardiovascular complications in patients with type 2 diabetes.
      Keywords: Open access, Cardiovascular and metabolic risk
      PubDate: 2021-03-24T08:20:17-07:00
      DOI: 10.1136/bmjdrc-2020-002032
      Issue No: Vol. 9, No. 1 (2021)
  • Ethnic differences in beta cell function occur independently of insulin
           sensitivity and pancreatic fat in black and white men

    • Authors: Ladwa, M; Bello, O, Hakim, O, Shojaee-Moradie, F, Boselli, M. L, Charles-Edwards, G, Peacock, J, Umpleby, A. M, Amiel, S. A, Bonadonna, R. C, Goff, L. M.
      Abstract: IntroductionIt is increasingly recognized that type 2 diabetes (T2D) is a heterogenous disease with ethnic variations. Differences in insulin secretion, insulin resistance and ectopic fat are thought to contribute to these variations. Therefore, we aimed to compare postprandial insulin secretion and the relationships between insulin secretion, insulin sensitivity and pancreatic fat in men of black West African (BA) and white European (WE) ancestry.Research design and methodsA cross-sectional, observational study in which 23 WE and 23 BA men with normal glucose tolerance, matched for body mass index, underwent a mixed meal tolerance test with C peptide modeling to measure beta cell insulin secretion, an MRI to quantify intrapancreatic lipid (IPL), and a hyperinsulinemic-euglycemic clamp to measure whole-body insulin sensitivity.ResultsPostprandial insulin secretion was lower in BA versus WE men following adjustment for insulin sensitivity (estimated marginal means, BA vs WE: 40.5 (95% CI 31.8 to 49.2) x 103 vs 56.4 (95% CI 48.9 to 63.8) x 103 pmol/m2 body surface area x 180 min, p=0.008). There was a significantly different relationship by ethnicity between IPL and insulin secretion, with a stronger relationship in WE than in BA (r=0.59 vs r=0.39, interaction p=0.036); however, IPL was not a predictor of insulin secretion in either ethnic group following adjustment for insulin sensitivity.ConclusionsEthnicity is an independent determinant of beta cell function in black and white men. In response to a meal, healthy BA men exhibit lower insulin secretion compared with their WE counterparts for their given insulin sensitivity. Ethnic differences in beta cell function may contribute to the greater risk of T2D in populations of African ancestry.
      Keywords: Open access, Metabolism
      PubDate: 2021-03-24T08:20:17-07:00
      DOI: 10.1136/bmjdrc-2020-002034
      Issue No: Vol. 9, No. 1 (2021)
  • Are depressive symptoms associated with quality of care in diabetes'
           Findings from a nationwide population-based study

    • Authors: Jung, A; Du, Y, Nübel, J, Busch, M. A, Heidemann, C, Scheidt-Nave, C, Baumert, J.
      Abstract: IntroductionWe investigated whether the presence of depressive symptoms among adults with diagnosed diabetes is associated with adverse quality of diabetes care.Research design and methodsThe study population was drawn from the German national health survey ‘German Health Update’ 2014/2015-European Health Interview Survey and included 1712 participants aged ≥18 years with self-reported diabetes during the past 12 months. Depressive symptoms in the past 2 weeks were assessed by the eight-item depression module of the Patient Health Questionnaire (PHQ-8), with PHQ-8 sum score values ≥10 indicating current depressive symptoms. We selected 12 care indicators in diabetes based on self-reported information on care processes and outcomes. Associations of depressive symptoms with those indicators were examined in multivariable logistic regression models with stepwise adjustments.ResultsOverall, 15.6% of adults with diagnosed diabetes reported depressive symptoms, which were higher in women than in men (18.7% vs 12.9%). Adjusted for age, sex, education, social support, health-related behaviors, and diabetes duration, adults with depressive symptoms were more likely to report acute hypoglycemia (OR 1.81, 95% CI 1.13 to 2.88) or hyperglycemia (OR 2.10, 95% CI 1.30 to 3.37) in the past 12 months, long-term diabetes complications (OR 2.30, 95% CI 1.55 to 3.39) as well as currently having a diet plan (OR 2.14, 95% CI 1.39 to 3.29) than adults without depressive symptoms. Significant associations between depressive symptoms and other care indicators were not observed.ConclusionsThe present population-based study of adults with diagnosed diabetes indicates an association between depressive symptoms and adverse diabetes-specific care with respect to outcome but largely not to process indicators. Our findings underline the need for intensified care for persons with diabetes and depressive symptoms. Future research needs to identify underlying mechanisms with a focus on the inter-relationship between diabetes, depression and diabetes-related distress.
      Keywords: Open access, Epidemiology/health services research
      PubDate: 2021-03-22T08:46:28-07:00
      DOI: 10.1136/bmjdrc-2020-001804
      Issue No: Vol. 9, No. 1 (2021)
  • Time trends in the incidence of clinically diagnosed type 2 diabetes and
           pre-diabetes in the UK 2009-2018: a retrospective cohort study

    • Authors: Pal, K; Horsfall, L, Sharma, M, Nazareth, I, Petersen, I.
      Abstract: IntroductionTo describe recent trends in the incidence of clinically diagnosed type 2 diabetes and pre-diabetes in people seen in UK general practice.Research design and methodsA retrospective cohort study using IQVIA Medical Research Data looking at people newly diagnosed with type 2 diabetes and pre-diabetes through primary care registers in the UK between 1 January 2009 and 31 December 2018.ResultsA cohort of 426 717 people were clinically diagnosed with type 2 diabetes and 418 656 people met the criteria for a diagnosis of pre-diabetes in that time period. The incidence of clinically diagnosed type 2 diabetes per 1000 person years at risk (PYAR) in men decreased from a peak of 5.06 per 1000 PYAR (95% CI 4.97 to 5.15) in 2013 to 3.56 per 1000 PYAR (95% CI 3.46 to 3.66) by 2018. For women, the incidence of clinically diagnosed type 2 diabetes per 1000 PYAR decreased from 4.45 (95% CI 4.37 to 4.54) in 2013 to 2.85 (2.76 to 2.93) in 2018. The incidence rate of pre-diabetes tripled by the end of the same study period in men and women.ConclusionsBetween 2009 and 2018, the incidence rate of new clinical diagnoses of type 2 diabetes recorded in a UK primary care database decreased by a third from its peak in 2013–2014, while the incidence of pre-diabetes has tripled. The implications of this on timely treatment, complication rates and mortality need further longer term exploration.
      Keywords: Open access, Epidemiology/health services research
      PubDate: 2021-03-19T07:55:23-07:00
      DOI: 10.1136/bmjdrc-2020-001989
      Issue No: Vol. 9, No. 1 (2021)
  • Effect of tap dance on plantar pressure, postural stability and lower body
           function in older patients at risk of diabetic foot: a randomized
           controlled trial

    • Authors: Zhao, Y; Cai, K, Wang, Q, Hu, Y, Wei, L, Gao, H.
      Abstract: IntroductionTo examine the effects of tap dance (TD) on dynamic plantar pressure, static postural stability, ankle range of motion (ROM), and lower extremity functional strength in patients at risk of diabetic foot (DF).Research design and methodsA randomised, single-blinded, two-arm prospective study of 40 patients at risk of DF was conducted. The intervention group (n=20) received 16 weeks of TD training (60 min/sessionx3 sessions/week). The control group attended four educational workshops (1 hour/sessionx1 session/month). Plantar pressure, represented by the primary outcomes of peak pressure (PP) and pressure-time integral (PTI) over 10 areas on each foot, was measured using the Footscan platform system. Secondary outcomes comprised static postural stability, ankle ROM and lower extremity functional strength.ResultsReductions in intervention group PP (right foot: mean differences=4.50~27.1, decrease%=25.6~72.0; left foot: mean differences=–5.90~6.33, decrease%=–22.6~53.2) and PTI at 10 areas of each foot (right foot: mean differences=1.00~12.5, decrease%=10.4~63.6; left foot: mean differences=0.590~25.3, decrease%=21.9~72.6) were observed. Substantial PP and PTI differences were noted at the second through fourth metatarsals, medial heel and lateral heel in the right foot. Substantial PP and PTI differences were detected at metatarsals 1 and 2 and metatarsal 2 in the left foot, respectively. Moderate training effects were found in plantar flexion ROM of both feet, lower extremity functional strength, and length of center-of-pressure trajectory with eyes closed and open (r=0.321–0.376, p
      Keywords: Open access, Clinical care/education/nutrition/psychosocial research
      PubDate: 2021-03-18T08:46:26-07:00
      DOI: 10.1136/bmjdrc-2020-001909
      Issue No: Vol. 9, No. 1 (2021)
  • Years of potential life lost in pre-diabetes and diabetes mellitus: data
           from a 40-year follow-up of the Israel study on Glucose intolerance,
           Obesity and Hypertension

    • Authors: Rapoport, M; Chetrit, A, Cantrell, D, Novikov, I, Roth, J, Dankner, R.
      Abstract: IntroductionWe examined years of potential life lost (YPLL) associated with pre-diabetes as compared with either normoglycemia or diabetes, using data of the Israel cohort of Glucose intolerance, Obesity and Hypertension 40-year follow-up.Research design and methodsMen and women (N=2844, mean age 52.0±8.2 years) who underwent oral glucose tolerance test and anthropometric measurements, during 1976–1982, were followed for mortality until May 2019. Multiple imputation procedures for missing mortality dates and multivariable regression mixed models were applied.ResultsAt baseline, 35.8%, 48.8% and 15.4% individuals were found with normoglycemia, pre-diabetes, and diabetes, respectively. The average difference in YPLL associated with pre-diabetes as compared with normoglycemia was 4.3 years (95% CI 3.3 to 5.2; p
      Keywords: Open access, Epidemiology/health services research
      PubDate: 2021-03-10T07:28:34-08:00
      DOI: 10.1136/bmjdrc-2020-001981
      Issue No: Vol. 9, No. 1 (2021)
  • Oxidized LDL, insulin sensitivity and beta-cell function in newborns

    • Authors: Fang, F; Nuyt, A. M, Garofalo, C, Zhang, J, Julien, P, Fraser, W, Levy, E, Luo, Z.-C.
      Abstract: IntroductionOxidized low-density lipoprotein (OxLDL), a biomarker of oxidative stress, itself possesses proatherogenic and proinflammatory effects. Elevated circulating OxLDL levels have been consistently associated with insulin resistance and diabetes in adults. We sought to assess whether OxLDL may be associated with insulin sensitivity and beta-cell function in early life.Research design and methodsIn a birth cohort study, we assessed cord plasma OxLDL concentration and OxLDL to total LDL ratio in relation to glucose to insulin ratio (an indicator of fetal insulin sensitivity), proinsulin to insulin ratio (an indicator of fetal beta-cell function), and leptin and adiponectin concentrations in 248 singleton newborns.ResultsCord plasma OxLDL concentration was positively correlated with glucose to insulin ratio (r=0.24, p
      Keywords: Open access, Metabolism
      PubDate: 2021-03-09T06:28:05-08:00
      DOI: 10.1136/bmjdrc-2020-001435
      Issue No: Vol. 9, No. 1 (2021)
  • Methylation status of vault RNA 2-1 promoter is a predictor of glycemic
           response to glucagon-like peptide-1 analog therapy in type 2 diabetes

    • Authors: Lin, C.-H; Lee, Y.-S, Huang, Y.-Y, Tsai, C.-N.
      Abstract: IntroductionTherapeutic efficiency of glucagon-like peptide-1 (GLP-1) analog is about 50%–70% in type 2 diabetes mellitus (T2DM). Discovery of potential genetic biomarkers for prediction of treatment efficiency of GLP-1 analog before therapy is still necessary. We assess whether DNA methylation was associated with glycemic response to GLP-1 analog therapy in patients with poorly controlled T2DM.Research design and methodsGenomic DNA was extracted from the peripheral blood of training (n=10) and validation (n=128) groups of patients with T2DM receiving GLP-1 analogs. DNA methylome was analyzed using Infinium Human Methylation EPIC Bead Chip in the training group. The candidate genes were examined using a pyrosequencing platform in the validation group. The association between DNA methylation status and glycemic response to GLP-1 was analyzed in these patients.ResultsThe most differential methylation region between those with a good (responsive) and poor (unresponsive) glycemic response to GLP-1 analog therapy was located on chromosome 5q31.1 (135415693 to 135416613), the promoter of VTRNA2-1 in the training group. The methylation status of the VTRNA2-1 promoter was examined in the validation group via pyrosequencing reaction, and the hypomethylation of VTRNA2-1 (
      Keywords: Open access, Genetics/genomes/proteomics/metabolomics
      PubDate: 2021-03-05T06:38:25-08:00
      DOI: 10.1136/bmjdrc-2020-001416
      Issue No: Vol. 9, No. 1 (2021)
  • Plasma lipidomics profile in pregnancy and gestational diabetes risk: a
           prospective study in a multiracial/ethnic cohort

    • Authors: Rahman, M. L; Feng, Y.-C. A, Fiehn, O, Albert, P. S, Tsai, M. Y, Zhu, Y, Wang, X, Tekola-Ayele, F, Liang, L, Zhang, C.
      Abstract: IntroductionDisruption of lipid metabolism is implicated in gestational diabetes (GDM). However, prospective studies on lipidomics and GDM risk in race/ethnically diverse populations are sparse. Here, we aimed to (1) identify lipid networks in early pregnancy to mid-pregnancy that are associated with subsequent GDM risk and (2) examine the associations of lipid networks with glycemic biomarkers to understand the underlying mechanisms.Research design and methodsThis study included 107 GDM cases confirmed using the Carpenter and Coustan criteria and 214 non-GDM matched controls from the National Institute of Child Health and Human Development Fetal Growth Studies-Singleton cohort, untargeted lipidomics data of 420 metabolites (328 annotated and 92 unannotated), and information on glycemic biomarkers in maternal plasma at visit 0 (10–14 weeks) and visit 1 (15–26 weeks). We constructed lipid networks using weighted correlation network analysis technique. We examined prospective associations of lipid networks and individual lipids with GDM risk using linear mixed effect models. Furthermore, we calculated Pearson’s partial correlation for GDM-related lipid networks and individual lipids with plasma glucose, insulin, C-peptide and glycated hemoglobin at both study visits.ResultsLipid networks primarily characterized by elevated plasma diglycerides and short, saturated/low unsaturated triglycerides and lower plasma cholesteryl esters, sphingomyelins and phosphatidylcholines were associated with higher risk of developing GDM (false discovery rate (FDR)
      Keywords: Open access, Epidemiology/health services research
      PubDate: 2021-03-05T06:38:25-08:00
      DOI: 10.1136/bmjdrc-2020-001551
      Issue No: Vol. 9, No. 1 (2021)
  • Factors associated with missed appointments by adults with type 2 diabetes
           mellitus: a systematic review

    • Authors: Sun, C.-A; Taylor, K, Levin, S, Renda, S. M, Han, H.-R.
      Abstract: Keeping regular medical appointments is a key indicator of patient engagement in diabetes care. Nevertheless, a significant proportion of adults with type 2 diabetes mellitus (T2DM) miss their regular medical appointments. In order to prevent and delay diabetes-related complications, it is essential to understand the factors associated with missed appointments among adults with T2DM. We synthesized evidence concerning factors associated with missed appointments among adults with T2DM. Using five electronic databases, including PubMed, Embase, Cumulative Index to Nursing and Allied Health Literature, PsycINFO and Web of Science, a systematic literature search was done to identify studies that describe factors related to missed appointments by adults with T2DM. A total of 18 articles met the inclusion criteria. The majority of studies included in this review were cohort studies using medical records. While more than half of the studies were of high quality, the operational definitions of missed appointments varied greatly across studies. Factors associated with missed appointments were categorized as patient characteristics, healthcare system and provider factors and interpersonal factors with inconsistent findings. Patient characteristics was the most commonly addressed category, followed by health system and provider factors. Only three studies addressed interpersonal factors, two of which were qualitative. An increasing number of people live with one or more chronic conditions which require more careful attention to patient-centered care and support. Future research is warranted to address interpersonal factors from patient perspectives to better understand the underlying causes of missed appointments among adults with T2DM.
      Keywords: Open access, Epidemiology/health services research
      PubDate: 2021-03-05T06:38:25-08:00
      DOI: 10.1136/bmjdrc-2020-001819
      Issue No: Vol. 9, No. 1 (2021)
  • apoA2 correlates to gestational age with decreased apolipoproteins A2, C1,
           C3 and E in gestational diabetes

    • Authors: Ramanjaneya, M; Butler, A. E, Bashir, M, Bettahi, I, Moin, A. S. M, Ahmed, L, Elrayess, M. A, Hunt, S. C, Atkin, S. L, Abou-Samra, A. B.
      Abstract: IntroductionPregnant women with gestational diabetes mellitus (GDM) are at risk of adverse outcomes, including gestational hypertension, pre-eclampsia, and preterm delivery. This study was undertaken to determine if apolipoprotein (apo) levels differed between pregnant women with and without GDM and if they were associated with adverse pregnancy outcome.Research design and methodsPregnant women (46 women with GDM and 26 women without diabetes (ND)) in their second trimester were enrolled in the study. Plasma apos were measured and correlated to demographic, biochemical, and pregnancy outcome data.ResultsapoA2, apoC1, apoC3 and apoE were lower in women with GDM compared with control women (p=0.0019, p=0.0031, p=0.0002 and p=0.015, respectively). apoA1, apoB, apoD, apoH, and apoJ levels did not differ between control women and women with GDM. Pearson bivariate analysis revealed significant correlations between gestational age at delivery and apoA2 for women with GDM and control women, and between apoA2 and apoC3 concentrations and C reactive protein (CRP) as a measure of inflammation for the whole group.ConclusionsApoproteins apoA2, apoC1, apoC3 and apoE are decreased in women with GDM and may have a role in inflammation, as apoA2 and C3 correlated with CRP. The fact that apoA2 correlated with gestational age at delivery in both control women and women with GDM raises the hypothesis that apoA2 may be used as a biomarker of premature delivery, and this warrants further investigation.
      Keywords: Open access, Metabolism
      PubDate: 2021-03-05T06:38:25-08:00
      DOI: 10.1136/bmjdrc-2020-001925
      Issue No: Vol. 9, No. 1 (2021)
  • What factors explain the much higher diabetes prevalence in Russia
           compared with Norway' Major sex differences in the contribution of

    • Authors: Iakunchykova, O; Averina, M, Wilsgaard, T, Malyutina, S, Kudryavtsev, A. V, Cook, S, Wild, S, Eggen, A. E, Hopstock, L. A, Leon, D. A.
      Abstract: IntroductionCompared with many other countries Russia has a high prevalence of diabetes in men and women. However, contrary to what is found in most other populations, the risk is greater among women than men. The reasons for this are unclear.Research design and methodsPrevalence and risk factors for diabetes at ages 40–69 years were compared in two population-based studies: Know Your Heart (KYH) (Russia, 2015–2018, n=4121) and the seventh wave of the Tromsø Study (Tromsø 7) (Norway, 2015–2016, n=17 649). Diabetes was defined by the level of glycated hemoglobin and/or self-reported diabetes and/or diabetes medication use. Marginal structural models were used to estimate the role of key risk factors for diabetes in differences between the studies.ResultsAge-standardized prevalence of diabetes was higher in KYH compared with Tromsø 7 in men (11.6% vs 6.2%) and in women (13.2% vs 4.3%). Age-adjusted ORs for diabetes in KYH compared with Tromsø 7 were 2.01 (95% CI 1.68 to 2.40) for men and 3.66 (95% CI 3.13 to 4.26) for women. Adiposity (body mass index and waist circumference) explained none of this effect for men but explained 46.0% (39.6, 53.8) for women. Addition of smoking and C reactive protein, as further mediators, slightly increased the percentage explained of the difference between studies to 55.5% (46.5, 66.0) for women but only to 9.9% (–0.6, 20.8) for men.ConclusionsAdiposity is a key modifiable risk factor that appears to explain half of the almost threefold higher female prevalence of diabetes in Russia compared with Norway, but none of the twofold male difference.
      Keywords: Open access, Epidemiology/health services research
      PubDate: 2021-03-04T07:08:17-08:00
      DOI: 10.1136/bmjdrc-2020-002021
      Issue No: Vol. 9, No. 1 (2021)
  • Lifetime risk and years lost to type 1 and type 2 diabetes in Denmark,

    • Authors: Carstensen, B; Ronn, P. F, Jorgensen, M. E.
      Abstract: IntroductionLifetime risk and lifetime lost to diabetes are measures of current diabetes burden in a population. We aimed at quantifying these measures in the Danish population.Research design and methodsWe modeled incidence and mortality of type 1 diabetes (T1D) and type 2 diabetes (T2D) and non-diabetes mortality based on complete follow-up of the entire population of Denmark in 1996–2016. A multistate model with these transition rates was used to assess the lifetime risk of diabetes, as well as the difference in expected lifetime between persons with type 1 and T2D and persons without.ResultsIn 2016, the lifetime risk of T1D was 1.1% and that for T2D 24%, the latter a 50% increase from 1996. For 50-year-old persons, the lifetime lost was 6.6 years for T1D and 4.8 years for T2D. These figures have been declining over the study period.At 2016, the total foreseeable lives lost in Denmark among patients with T1D were 182 000 years, and those among patients with T2D were 766 000 years, corresponding to 6.6 and 3.0 years per person, respectively.ConclusionAt the individual level, improvements in the disease burden for both T1D and T2D have occurred. At the population level, the increasing number of patients with T2D has contributed to a large increase in the total loss of lifetime.
      Keywords: Open access, Epidemiology/health services research
      PubDate: 2021-03-02T06:33:14-08:00
      DOI: 10.1136/bmjdrc-2019-001065
      Issue No: Vol. 9, No. 1 (2021)
  • Birth weight modifies the relation between adulthood levels of
           insulin-like growth factor-1 and type 2 diabetes: a prospective cohort

    • Authors: Geng, T; Wang, M, Li, X, Zhou, T, Ma, H, Fonseca, V. A, Koh, W.-P, Huang, T, Heianza, Y, Qi, L.
      Abstract: IntroductionInsulin-like growth factor-1 (IGF-1) has been implicated in fetal and early-life growth and development of type 2 diabetes (T2D). We aimed to examine the interaction between circulating IGF-1 and birth weight in relation to risk of T2D.Research design and methodsWe included 181 090 adults, aged 39–70 years in the UK Biobank Study, who were free of diabetes or major cardiovascular diseases at baseline. Serum IGF-1 levels were determined using chemiluminescent immunoassay method. Birth weight was self-reported; a Genetic Risk Score (GRS) was calculated to define the genetically determined birth weight. The outcome was the incidence of T2D.ResultsWe identified 3299 incident T2D cases over an average of 9.9 years of follow-up. Among the participants with birth weight of ≥2.5 kg, IGF-1 levels were inversely associated with T2D risk in a dose-dependent manner (p-trend
      Keywords: Open access, Press releases, Cardiovascular and metabolic risk
      PubDate: 2021-03-01T15:30:22-08:00
      DOI: 10.1136/bmjdrc-2020-001885
      Issue No: Vol. 9, No. 1 (2021)
  • Effects of D-allulose on glucose tolerance and insulin response to a
           standard oral sucrose load: results of a prospective, randomized,
           crossover study

    • Authors: Franchi, F; Yaranov, D. M, Rollini, F, Rivas, A, Rivas Rios, J, Been, L, Tani, Y, Tokuda, M, Iida, T, Hayashi, N, Angiolillo, D. J, Mooradian, A. D.
      Abstract: IntroductionCurrent dietary guidelines recommend limiting sugar intake for the prevention of diabetes mellitus (DM). Reduction in sugar intake may require sugar substitutes. Among these, D-allulose is a non-calorie rare monosaccharide with 70% sweetness of sucrose, which has shown anti-DM effects in Asian populations. However, there is limited data on the effects of D-allulose in other populations, including Westerners.Research design and methodsThis was a prospective, randomized, double-blind, placebo-controlled, crossover study conducted in 30 subjects without DM. Study participants were given a standard oral (50 g) sucrose load and randomized to placebo or escalating doses of D-allulose (2.5, 5.0, 7.5, 10.0 g). Subjects crossed-over to the alternate study treatment after 7–14 days of wash out. Plasma glucose and insulin levels were measured at five time points: before and at 30, 60, 90 and 120 min after ingestion.ResultsD-allulose was associated with a dose-dependent reduction of plasma glucose at 30 min compared with placebo. In particular, glucose was significantly lower with the 7.5 g (mean difference: 11; 95% CI 3 to 19; p=0.005) and 10 g (mean difference: 12; 95% CI 4 to 20; p=0.002) doses. Although glucose was not reduced at the other time points, there was a dose-dependent reduction in glucose excursion compared with placebo, which was significant with the 10 g dose (p=0.023). Accordingly, at 30 min D-allulose was associated with a trend towards lower insulin levels compared with placebo, which was significant with the 10 g dose (mean difference: 14; 95% CI 4 to 25; p=0.006). D-allulose did not reduce insulin at any other time point, but there was a significant dose-dependent reduction in insulin excursion compared with placebo (p=0.028), which was significant with the 10 g dose (p=0.002).ConclusionsThis is the largest study assessing the effects of D-allulose in Westerners demonstrating an early dose-dependent reduction in plasma glucose and insulin levels as well as decreased postprandial glucose and insulin excursion in subjects without DM. These pilot observations set the basis for large-scale investigations to support the anti-DM effects of D-allulose.Trial registration numberNCT02714413.
      Keywords: Open access, Clinical care/education/nutrition/psychosocial research
      PubDate: 2021-02-26T06:25:13-08:00
      DOI: 10.1136/bmjdrc-2020-001939
      Issue No: Vol. 9, No. 1 (2021)
  • Bidirectional temporal relationship between obesity and hyperinsulinemia:
           longitudinal observation from a Chinese cohort

    • Authors: Xu, C; Zhou, G, Zhao, M, Zhang, X, Fang, L, Guan, Q, Zhang, H, Gao, L, Zhang, T, Zhao, J.
      Abstract: IntroductionAlthough obesity and hyperinsulinemia are closely intercorrelated, their temporal sequence is still uncertain. This study aims to investigate the temporal relationship patterns between obesity measures and hyperinsulinemia in Chinese adults.Research design and methodsThe longitudinal cohort consisted of 2493 participants (860 males and 1633 female, mean age 56.71 years at follow-up) for whom measurements of obesity and hyperinsulinemia measures were collected twice between 2011 and 2014, with an average follow-up time of 3 years. Cross-lagged panel analysis was used to examine the temporal relationship between obesity measures (body mass index (BMI); waist circumference (WC); hip circumference (HC); waist-to-hip ratio (WHR)) and hyperinsulinemia (insulin, homeostasis model assessment of insulin resistance (HOMA-IR), or homeostasis model assessment of beta cell function (HOMA-%β)).ResultsAfter the adjustment of age, sex, smoking, drinking and follow-up years, in the BMI-insulin model, the path coefficient (β2=0.229; p
      Keywords: Open access, Epidemiology/health services research
      PubDate: 2021-02-25T07:26:33-08:00
      DOI: 10.1136/bmjdrc-2020-002059
      Issue No: Vol. 9, No. 1 (2021)
  • Multilevel clustering approach driven by continuous glucose monitoring
           data for further classification of type 2 diabetes

    • Authors: Tao, R; Yu, X, Lu, J, Shen, Y, Lu, W, Zhu, W, Bao, Y, Li, H, Zhou, J.
      Abstract: IntroductionMining knowledge from continuous glucose monitoring (CGM) data to classify highly heterogeneous patients with type 2 diabetes according to their characteristics remains unaddressed. A refined clustering method that retrieves hidden information from CGM data could provide a viable method to identify patients with different degrees of dysglycemia and clinical phenotypes.Research design and methodsFrom Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, we selected 908 patients with type 2 diabetes (18–83 years) who wore blinded CGM sensors (iPro2, Medtronic, California, USA). Participants were clustered based on CGM data during a 24-hour period by our method. The first level extracted the knowledge-based and statistics-based features to describe CGM signals from multiple perspectives. The Fisher score and variables cluster analysis were applied to fuse features into low dimensions at the second level. The third level divided subjects into subgroups with different clinical phenotypes. The four subgroups of patients were determined by clinical phenotypes.ResultsFour subgroups of patients with type 2 diabetes with significantly different statistical features and clinical phenotypes were identified by our method. In particular, individuals in cluster 1 were characterized by the lowest glucose level factor and glucose fluctuation factor, and the highest negative glucose factor and C peptide index. By contrast, cluster 2 had the highest glucose level factor and the lowest C peptide index. Cluster 4 was characterized by the greatest degree of glucose fluctuation factor, was the most insulin-sensitive, and had the lowest insulin resistance. Cluster 3 ranked in the middle concerning the CGM-derived metrics and clinical phenotypes compared with those of the other three groups.ConclusionA novel multilevel clustering approach for knowledge mining from CGM data in type 2 diabetes is presented. The results demonstrate that subgroups are adequately distinguished with notable statistical and clinical differences.
      Keywords: Open access
      PubDate: 2021-02-24T06:49:59-08:00
      DOI: 10.1136/bmjdrc-2020-001869
      Issue No: Vol. 9, No. 1 (2021)
  • Glucolipotoxicity and GLP-1 secretion

    • Authors: Hong, J.-H; Kim, D.-H, Lee, M.-K.
      Abstract: IntroductionThe concept of glucolipotoxicity refers to the combined, deleterious effects of elevated glucose and/or fatty acid levels.Research design and methodsTo investigate the effects of chronic glucolipotoxicity on glucagon-like peptide-1-(7-36) amide (GLP-1) secretion, we generated glucolipotoxic conditions in human NCI-H716 enteroendocrine cells using either 5 or 25 mM glucose with or without 500 µM palmitate for 72 hours. For in vivo study, we have established a chronic nutrient infusion model in the rat. Serial blood samples were collected for 2 hours after the consumption of a mixed meal to evaluate insulin sensitivity and β-cell function.ResultsChronic glucolipotoxic conditions decreased GLP-1 secretion and the expressions of pCREB, pGSK3β, β-catenin, and TCF7L2 in NCI-H716 cells. Glucolipotoxicity conditions reduced glucose transporter expression, glucose uptake, and nicotinamide-adenine dinucleotide phosphate (NADPH) levels in L-cells, and increased triglyceride accumulation. In contrast, PPARα and ATP levels were reduced, which correlated well with decreased levels of SUR1 and Kir6.2, cAMP contents and expressions of pCAMK2, EPAC and PKA. We also observed an increase in reactive oxygen species production, UCP2 expression and Complex I activity. Simultaneous treatment with insulin restored the GLP-1 secretion. Glucolipotoxic conditions decreased insulin secretion in a time-dependent manner in INS-1 cells, which was recovered with exendin-4 cotreatment. Glucose and SMOFlipid infusion for 6 hours decreased GLP-1 secretion and proglucagon mRNA levels as well as impaired the glucose tolerance, insulin and C-peptide secretion in rats.ConclusionThese results provide evidence for the first time that glucolipotoxicity could affect GLP-1 secretion through changes in glucose and lipid metabolism, gene expressions, and proglucagon biosynthesis and suggest the interrelationship between glucolipotoxicities of L-cells and β-cells which develops earlier than that of L-cells.
      Keywords: Open access, Metabolism
      PubDate: 2021-02-24T06:49:59-08:00
      DOI: 10.1136/bmjdrc-2020-001905
      Issue No: Vol. 9, No. 1 (2021)
  • Serum calcification propensity is associated with HbA1c in type 2 diabetes

    • Authors: Mencke, R; van der Vaart, A, Pasch, A, Harms, G, Waanders, F, Bilo, H. J. G, van Goor, H, Hillebrands, J.-L, van Dijk, P. R.
      Abstract: IntroductionSerum calcification propensity is emerging as an independent predictor for cardiovascular outcomes in high-risk populations. Calcification propensity can be monitored by the maturation time of calciprotein particles in serum (T50 test). A low T50 value is an independent determinant of cardiovascular morbidity and mortality in various populations. Aim was to investigate the T50 and its relationship to type 2 diabetes mellitus.Research design and methodsUsing nephelometry, serum T50 was cross-sectionally measured in 932 stable patients with type 2 diabetes mellitus (55% male) with a median age of 66 (62–75) years, diabetes duration of 6.5 (3.0–10.2) years and hemoglobin A1c (HbA1c) of 49 (44–54) mmol/mol.ResultsSerum T50 was normally distributed with a mean value of 261±66 min. In linear regression, serum T50 was lower in women and current smokers. A lower T50 value was found in patients with a higher HbA1c or higher systolic blood pressure, insulin users and patients with a longer history of diabetes. The association with HbA1c was independent of other determinants in multivariable analysis. There was no association between T50 and previous macrovascular events or the presence of microvascular disease.ConclusionsSerum calcification propensity is independently associated with glycemic control, suggesting that a lower HbA1c may be associated with better cardiovascular outcomes. Retrospective analysis could not establish an association between a history of macrovascular events and T50, and prospective studies will have to be performed to address this hypothesis.Trial registration numberNCT01570140.
      Keywords: Open access, Cardiovascular and metabolic risk
      PubDate: 2021-02-24T06:49:59-08:00
      DOI: 10.1136/bmjdrc-2020-002016
      Issue No: Vol. 9, No. 1 (2021)
  • Casual blood glucose and subsequent cardiovascular disease and all-cause
           mortality among 159 731 participants in Cohort of Norway (CONOR)

    • Authors: Riise, H. K. R; Igland, J, Sulo, G, Graue, M, Haltbakk, J, Tell, G. S, Iversen, M. M.
      Abstract: IntroductionOur aim was to assess the association between casual blood glucose level and subsequent cardiovascular disease (CVD) and mortality among community-dwelling adults without a diagnosis of diabetes.Research design and methodsIn this community-based cohort study, 159 731 individuals with a measurement of casual blood glucose were followed from their participation date in Cohort of Norway (CONOR) (1994–2003) until a CVD episode, death or 31 December 2009. All analyses were done using Cox proportional hazard regression, and the results are reported as multivariable-adjusted HRs with 95% CI.ResultsCompared with those with normal glucose levels (11.0 mmol/L) had an even more increased risk. One mmol/L increase in glucose level was associated with an increased risk of all four endpoints among participants with borderline as well as within normal glucose levels. In analyses stratified by sex and age group, the CVD risk estimates tended to be higher in women than in men and in those
      Keywords: Open access, Cardiovascular and metabolic risk
      PubDate: 2021-02-23T06:30:07-08:00
      DOI: 10.1136/bmjdrc-2020-001928
      Issue No: Vol. 9, No. 1 (2021)
  • Spousal concordance in pathophysiological markers and risk factors for
           type 2 diabetes: a cross-sectional analysis of The Maastricht Study

    • Authors: Silverman-Retana, O; Brinkhues, S, Hulman, A, Stehouwer, C. D. A, Dukers-Muijrers, N. H. T. M, Simmons, R. K, Bosma, H, Eussen, S, Koster, A, Dagnelie, P, Savelberg, H. H. C. M, Schaper, N. C, van Dongen, M. C. J. M, Witte, D. R, Schram, M. T.
      Abstract: IntroductionWe compared the degree of spousal concordance in a set of detailed pathophysiological markers and risk factors for type 2 diabetes to understand where in the causal cascade spousal similarities are most relevant.Research design and methodsThis is a cross-sectional analysis of couples who participated in The Maastricht Study (n=172). We used quantile regression models to assess spousal concordance in risk factors for type 2 diabetes, including four adiposity measures, two dimensions of physical activity, sedentary time and two diet indicators. We additionally assessed beta cell function and insulin sensitivity and glucose metabolism status with fasting and 2-hour plasma glucose and hemoglobin A1c.ResultsThe strongest spousal concordance (beta estimates) was observed for the Dutch Healthy Diet Index (DHDI) in men. A one-unit increase in wives’ DHDI was associated with a 0.53 (95% CI 0.22 to 0.67) unit difference in men’s DHDI. In women, the strongest concordance was for the time spent in high-intensity physical activity (HPA); thus, a one-unit increase in husbands’ time spent in HPA was associated with a 0.36 (95% CI 0.17 to 0.64) unit difference in women’s time spent in HPA. The weakest spousal concordance was observed in beta cell function indices.ConclusionsSpousal concordance was strongest in behavioral risk factors. Concordance weakened when moving downstream in the causal cascade leading to type 2 diabetes. Public health prevention strategies to mitigate diabetes risk may benefit from targeting spousal similarities in health-related behaviors and diabetes risk factors to design innovative and potentially more effective couple-based interventions.
      Keywords: Open access, Epidemiology/health services research
      PubDate: 2021-02-17T06:28:19-08:00
      DOI: 10.1136/bmjdrc-2020-001879
      Issue No: Vol. 9, No. 1 (2021)
  • Incidence and determinants of hypophosphatemia in diabetic ketoacidosis:
           an observational study

    • Authors: van der Vaart, A; Waanders, F, van Beek, A. P, Vriesendorp, T. M, Wolffenbuttel, B. H. R, van Dijk, P. R.
      Abstract: IntroductionDiabetic ketoacidosis (DKA) is a life-threatening complication of type 1 diabetes mellitus (T1DM) characterized by hyperglycemia and metabolic acidosis. Hypophosphatemia in DKA often occurs during hospital admittance for DKA. Literature on the magnitude, determinants and consequences of hypophosphatemia in DKA is scarce. Primary aim of this study was to investigate the incidence and consequences of hypophosphatemia during hospitalisation for DKA.Research design and methodsCohort study among individuals with T1DM who were admitted for DKA between 2005 and 2020 in an academic and a non-academic hospital. Multivariate regression models were performed to investigate determinants of the lowest phosphate during the treatment of DKA.ResultsA total of 127 episodes of DKA among 80 individuals were identified. Age at DKA presentation was 28 (22–46) years, 45% of the cases was female, diabetes duration was 13.2 (8.9–25.5) years with glycosylated hemoglobin levels of 91.9±26.2 mmol/mol. In 9% of all cases, DKA was the first presentation of T1DM. Lowest phosphate levelss reported during the treatment phase were 0.54 (0.32–0.83) mmol/L and hypophosphatemia was present in 74% (62/84). The time to lowest phosphate was 16 (8–23) hours. In multivariate analysis, baseline bicarbonate and hemoglobin at admission were significantly associated with the lowest phosphate level reported. No adverse effects of hypophosphatemia on hospital stay duration, morbidity or mortality were found, even if left untreated.ConclusionsHypophosphatemia during DKA is common and increases with severe acidosis. However, in this study it was not related to adverse outcomes. Although limitations of this retrospective study should be taken into account, the routine and repeated measurement of phosphate levels in DKA could be reconsidered, provided that possible symptoms related to hypophosphatemia are monitored.
      Keywords: Open access, Cardiovascular and metabolic risk
      PubDate: 2021-02-17T06:28:19-08:00
      DOI: 10.1136/bmjdrc-2020-002018
      Issue No: Vol. 9, No. 1 (2021)
  • Metabolomics-based multidimensional network biomarkers for diabetic
           retinopathy identification in patients with type 2 diabetes mellitus

    • Authors: Zuo, J; Lan, Y, Hu, H, Hou, X, Li, J, Wang, T, Zhang, H, Zhang, N, Guo, C, Peng, F, Zhao, S, Wei, Y, Jia, C, Zheng, C, Mao, G.
      Abstract: IntroductionDespite advances in diabetic retinopathy (DR) medications, early identification is vitally important for DR administration and remains a major challenge. This study aims to develop a novel system of multidimensional network biomarkers (MDNBs) based on a widely targeted metabolomics approach to detect DR among patients with type 2 diabetes mellitus (T2DM) efficiently.Research design and methodsIn this propensity score matching-based case-control study, we used ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry system for serum metabolites assessment of 69 pairs of patients with T2DM with DR (cases) and without DR (controls). Comprehensive analysis, including principal component analysis, orthogonal partial least squares discriminant analysis, generalized linear regression models and a 1000-times permutation test on metabolomics characteristics were conducted to detect candidate MDNBs depending on the discovery set. Receiver operating characteristic analysis was applied for the validation of capability and feasibility of MDNBs based on a separate validation set.ResultsWe detected 613 features (318 in positive and 295 in negative ESI modes) in which 63 metabolites were highly relevant to the presence of DR. A panel of MDNBs containing linoleic acid, nicotinuric acid, ornithine and phenylacetylglutamine was determined based on the discovery set. Depending on the separate validation set, the area under the curve (95% CI), sensitivity and specificity of this MDNBs system were 0.92 (0.84 to 1.0), 96% and 78%, respectively.ConclusionsThis study demonstrates that metabolomics-based MDNBs are associated with the presence of DR and capable of distinguishing DR from T2DM efficiently. Our data also provide new insights into the mechanisms of DR and the potential value for new treatment targets development. Additional studies are needed to confirm our findings.
      Keywords: Open access, Genetics/genomes/proteomics/metabolomics
      PubDate: 2021-02-16T06:55:05-08:00
      DOI: 10.1136/bmjdrc-2020-001443
      Issue No: Vol. 9, No. 1 (2021)
  • Comparing the effects of tofogliflozin and pioglitazone in non-alcoholic
           fatty liver disease patients with type 2 diabetes mellitus (ToPiND study):
           a randomized prospective open-label controlled trial

    • Authors: Yoneda, M; Honda, Y, Ogawa, Y, Kessoku, T, Kobayashi, T, Imajo, K, Ozaki, A, Nogami, A, Taguri, M, Yamanaka, T, Kirikoshi, H, Iwasaki, T, Kurihashi, T, Saito, S, Nakajima, A.
      Abstract: IntroductionThe treatment of diabetes has a significant impact on the pathogenesis of non-alcoholic fatty liver disease (NAFLD). We compared the effectiveness of tofogliflozin, a selective sodium-glucose cotransporter 2 inhibitor, and pioglitazone for the treatment of NAFLD patients with type 2 diabetes mellitus.Research design and methodsThis open-label, prospective, single-center, randomized clinical trial recruited NAFLD patients with type 2 diabetes mellitus and a hepatic fat fraction of at least 10% as assessed based on the MRI-proton density fat fraction (MRI-PDFF). Eligible patients were stratified according to hemoglobin A1c (HbA1c), alanine transaminase, and MRI-PDFF levels and randomly assigned (1:1) to receive either 20 mg tofogliflozin or 15–30 mg pioglitazone, orally, once daily for 24 weeks. The primary endpoint was an absolute change in MRI-PDFF at 24 weeks. Efficacy and safety was assessed in all treated patients. This trial was registered in the Japan Registry of Clinical Trials.ResultsOverall, 40 eligible patients were randomly assigned to receive tofogliflozin (n=21) or pioglitazone (n=19). Changes in hepatic steatosis after 24 weeks of treatment were evaluated by MRI-PDFF, which showed a significant decrease in both groups (–7.54% (p
      Keywords: Open access, Metabolism
      PubDate: 2021-02-16T06:55:05-08:00
      DOI: 10.1136/bmjdrc-2020-001990
      Issue No: Vol. 9, No. 1 (2021)
  • Impact of undiagnosed type 2 diabetes and pre-diabetes on severity and
           mortality for SARS-CoV-2 infection

    • Authors: Vargas-Vazquez, A; Bello-Chavolla, O. Y, Ortiz-Brizuela, E, Campos-Munoz, A, Mehta, R, Villanueva-Reza, M, Bahena-Lopez, J. P, Antonio-Villa, N. E, Gonzalez-Lara, M. F, Ponce de Leon, A, Sifuentes-Osornio, J, Aguilar-Salinas, C. A.
      Abstract: IntroductionDiabetes and hyperglycemia are risk factors for critical COVID-19 outcomes; however, the impact of pre-diabetes and previously unidentified cases of diabetes remains undefined. Here, we profiled hospitalized patients with undiagnosed type 2 diabetes and pre-diabetes to evaluate its impact on adverse COVID-19 outcomes. We also explored the role of de novo and intrahospital hyperglycemia in mediating critical COVID-19 outcomes.Research design and methodsProspective cohort of 317 hospitalized COVID-19 cases from a Mexico City reference center. Type 2 diabetes was defined as previous diagnosis or treatment with diabetes medication, undiagnosed diabetes and pre-diabetes using glycosylated hemoglobin (HbA1c) American Diabetes Association (ADA) criteria and de novo or intrahospital hyperglycemia as fasting plasma glucose (FPG) ≥140 mg/dL. Logistic and Cox proportional regression models were used to model risk for COVID-19 outcomes.ResultsOverall, 159 cases (50.2%) had type 2 diabetes and 125 had pre-diabetes (39.4%), while 31.4% of patients with type 2 diabetes were previously undiagnosed. Among 20.0% of pre-diabetes cases and 6.1% of normal-range HbA1c had de novo hyperglycemia. FPG was the better predictor for critical COVID-19 compared with HbA1c. Undiagnosed type 2 diabetes (OR: 5.76, 95% CI 1.46 to 27.11) and pre-diabetes (OR: 4.15, 95% CI 1.29 to 16.75) conferred increased risk of severe COVID-19. De novo/intrahospital hyperglycemia predicted critical COVID-19 outcomes independent of diabetes status.ConclusionsUndiagnosed type 2 diabetes, pre-diabetes and de novo hyperglycemia are risk factors for critical COVID-19. HbA1c must be measured early to adequately assess individual risk considering the large rates of undiagnosed type 2 diabetes in Mexico.
      Keywords: Open access, Pathophysiology/complications, COVID-19
      PubDate: 2021-02-16T06:55:05-08:00
      DOI: 10.1136/bmjdrc-2020-002026
      Issue No: Vol. 9, No. 1 (2021)
  • Impaired exocrine pancreatic function in different stages of type 1

    • Authors: Dozio, N; Indirli, R, Giamporcaro, G. M, Frosio, L, Mandelli, A, Laurenzi, A, Bolla, A. M, Stabilini, A, Valle, A, Locatelli, M, Cavestro, G. M, Scavini, M, Battaglia, M, Bosi, E.
      Abstract: IntroductionAim of this study was to investigate the pancreatic exocrine function in patients with type 1 diabetes (T1D) by multiple non-invasive tests.Research design and methodsThe study is a single-center, cross-sectional study of pancreatic exocrine function in adult patients with new-onset or long-standing T1D and healthy controls.ResultsHealthy controls, new-onset T1D, and long-standing T1D were similar for age at the time of the study, gender and body mass index (BMI) categories. Age of onset of T1D patients with long-standing disease was younger than that of patients with new-onset T1D (p
      Keywords: Open access, Pathophysiology/complications
      PubDate: 2021-02-15T06:56:08-08:00
      DOI: 10.1136/bmjdrc-2019-001158
      Issue No: Vol. 9, No. 1 (2021)
  • Cross-sectional and prospective relationships of endogenous progestogens
           and estrogens with glucose metabolism in men and women: a KORA F4/FF4

    • Authors: Lau, L. H. Y; Nano, J, Cecil, A, Schederecker, F, Rathmann, W, Prehn, C, Zeller, T, Lechner, A, Adamski, J, Peters, A, Thorand, B.
      Abstract: IntroductionRelationships between endogenous female sex hormones and glycemic traits remain understudied, especially in men. We examined whether endogenous 17α-hydroxyprogesterone (17-OHP), progesterone, estradiol (E2), and free estradiol (fE2) were associated with glycemic traits and glycemic deterioration.Research design and methods921 mainly middle-aged and elderly men and 390 perimenopausal/postmenopausal women from the German population-based Cooperative Health Research in the Region of Augsburg (KORA) F4/FF4 cohort study were followed up for a median of 6.4 years. Sex hormones were measured at baseline using mass spectrometry. We calculated regression coefficients (β) and ORs with 95% CIs using multivariable-adjusted linear and logistic regression models for Z-standardized hormones and glycemic traits or glycemic deterioration (ie, worsening of categorized glucose tolerance status), respectively.ResultsIn the cross-sectional analysis (n=1222 men and n=594 women), in men, 17-OHP was inversely associated with 2h-glucose (2hG) (β=–0.067, 95% CI –0.120 to –0.013) and fasting insulin (β=–0.074, 95% CI –0.118 to –0.030), and positively associated with Quantitative Insulin Sensitivity Check Index (QUICKI) (β=0.061, 95% CI 0.018 to 0.105). Progesterone was inversely associated with fasting insulin (β=–0.047, 95% CI –0.088 to –0.006) and positively associated with QUICKI (β=0.041, 95% CI 0.001 to 0.082). E2 was inversely associated with fasting insulin (β=–0.068, 95% CI –0.116 to –0.020) and positively associated with QUICKI (β=0.059, 95% CI 0.012 to 0.107). fE2 was positively associated with glycated hemoglobin (HbA1c) (β=0.079, 95% CI 0.027 to 0.132). In women, 17-OHP was positively associated with fasting glucose (FG) (β=0.068, 95% CI 0.014 to 0.123). fE2 was positively associated with FG (β=0.080, 95% CI 0.020 to 0.141) and HbA1c (β=0.121, 95% CI 0.062 to 0.180). In the sensitivity analyses restricted to postmenopausal women, we observed a positive association between 17-OHP and glycemic deterioration (OR=1.518, 95% CI 1.033 to 2.264).ConclusionsInter-relations exist between female sex hormones and glucose-related traits among perimenopausal/postmenopausal women and insulin-related traits among men. Endogenous progestogens and estrogens appear to be involved in glucose homeostasis not only in women but in men as well. Further well-powered studies assessing causal associations between endogenous female sex hormones and glycemic traits are warranted.
      Keywords: Open access, Epidemiology/health services research
      PubDate: 2021-02-11T07:05:09-08:00
      DOI: 10.1136/bmjdrc-2020-001951
      Issue No: Vol. 9, No. 1 (2021)
  • Impaired brain fractalkine-CX3CR1 signaling is implicated in cognitive
           dysfunction in diet-induced obese mice

    • Authors: Kawamura, N; Katsuura, G, Yamada-Goto, N, Novianti, E, Inui, A, Asakawa, A.
      Abstract: IntroductionA diet high in saturated fat is well known to affect neuronal function and contribute to cognitive decline in experimental animals and humans. Fractalkine released from neurons acts on its receptor, CX3C chemokine receptor 1 (CX3CR1), in the microglia to regulate several brain functions. The present study addressed whether fractalkine-CX3CR1 signaling in the brain, especially the hippocampus, contributes to the cognitive deficits observed in diet-induced obese (DIO) mice.Research design and methodsMice were given 60% high-fat diet for 16 weeks. The expression of fractalkine and CX3CR1 in the hippocampus, amygdala and prefrontal cortex of DIO mice was analyzed. Cognitive ability in the Y-maze test and hippocampal glutamate receptors and synaptic markers were observed in DIO and CX3CR1 antagonist-treated mice. Regulation of fractalkine and CX3CR1 expression in the hippocampus was examined following administration of a selective insulin-like growth factor-1 (IGF-1) receptor inhibitor and a tyrosine receptor kinase B (TrkB) antagonist in normal mice.ResultsDIO mice exhibited significant cognitive deficits in the Y-maze test and decrease in fractalkine and CX3CR1 in the hippocampus and amygdala compared with mice fed a control diet (CD mice). Administration of the CX3CR1 antagonist 18a in normal mice induced significant cognitive deficits in the Y-maze test. DIO mice and CX3CR1 antagonist-treated mice exhibited significant decreases in protein levels of NMDA (N-methyl-D-aspartate) receptor subunit (NR2A), AMPA (α-amino-5-methyl-3-hydroxy-4-isoxazole propionate) receptor subunit (GluR1) and postsynaptic density protein 95 in the hippocampus compared with their respective controls. Furthermore, plasma IGF-1 and hippocampal brain-derived neurotrophic factor were significantly decreased in DIO mice compared with CD mice. Administration of a selective IGF-1 receptor inhibitor and a TrkB antagonist in normal mice significantly decreased fractalkine and CX3CR1 in the hippocampus.ConclusionsThese findings indicate that the cognitive decline observed in DIO mice is due, in part, to reduced fractalkine-CX3CR1 signaling in the corticolimbic system.
      Keywords: Open access, Obesity studies
      PubDate: 2021-02-10T07:11:40-08:00
      DOI: 10.1136/bmjdrc-2020-001492
      Issue No: Vol. 9, No. 1 (2021)
  • Associations of pre-pregnancy impaired fasting glucose and body mass index
           among pregnant women without pre-existing diabetes with offspring being
           large for gestational age and preterm birth: a cohort study in China

    • Authors: Tang, J; Chen, R, Yu, Y, Bao, W, Tiemeier, H, Rodney, A, Zhu, X, Li, M, Huang, D, Zhao, Q.
      Abstract: IntroductionAssociations of pre-pregnancy impaired fasting glucose (IFG) and body mass index (BMI) with large for gestational age (LGA) and preterm birth (PTB) have been poorly understood. We aimed to investigate the associations of maternal BMI, separately and together with pre-pregnancy IFG, with LGA and PTB in Chinese population. We also aimed to quantify these associations by maternal age.Research design and methodsThis was a retrospective cohort study of women from the National Free Preconception Health Examination Project with singleton birth from 121 counties/districts in 21 cities of Guangdong Province, China, from January 1, 2013 to December 31, 2017. Women were included if they did not have pre-existing chronic diseases (diabetes, hypertension, etc). Participants were divided into eight groups according to their BMI (underweight (BMI
      Keywords: Open access, Epidemiology/health services research
      PubDate: 2021-02-10T07:11:40-08:00
      DOI: 10.1136/bmjdrc-2020-001641
      Issue No: Vol. 9, No. 1 (2021)
  • Clinician prescription of lipid-lowering drugs and achievement of

    • Authors: Garcia-Ulloa, A. C; Lechuga-Fonseca, C, Del Razo-Olvera, F. M, Aguilar-Salinas, C. A, Galaviz, K. I, Narayan, K. M. V, Hernandez-Jimenez, S, On behalf of Group of Study CAIPaDi
      Abstract: IntroductionLipid control is essential in type 2 diabetes mellitus (T2DM). The aim of this study is to investigate factors associated with lipid therapy adherence and achievement of goals in real-life setting among patients with recently diagnosed T2DM.Research design and methodsThis is a longitudinal analysis in a center of comprehensive care for patients with diabetes. We include patients with T2DM,
      Keywords: Open access, Epidemiology/health services research
      PubDate: 2021-02-10T07:11:40-08:00
      DOI: 10.1136/bmjdrc-2020-001891
      Issue No: Vol. 9, No. 1 (2021)
  • Time in range-A1c hemoglobin relationship in continuous glucose monitoring
           of type 1 diabetes: a real-world study

    • Authors: Valenzano, M; Cibrario Bertolotti, I, Valenzano, A, Grassi, G.
      Abstract: IntroductionThe availability of easily accessible continuous glucose monitoring (CGM) metrics can improve glycemic control in diabetes, and they may even become a viable alternative to hemoglobin A1c (HbA1c) laboratory tests in the next years. The REALISM-T1D study (REAl-Life glucoSe Monitoring in Type 1 Diabetes) was aimed at contributing, with real-world data, to a deeper understanding of these metrics, including the time in range (TIR)–HbA1c relationship, to facilitate their adoption by diabetologists in everyday practice.Research design and methods70 adults affected by type 1 diabetes were monitored for 1 year by means of either flash (FGM) or real-time (rtCGM) glucose monitoring devices. Follow-up visits were performed after 90, 180 and 365 days from baseline and percentage TIR70–180 evaluated for the 90-day time period preceding each visit. HbA1c tests were also carried out in the same occasions and measured values paired with the corresponding TIR data.ResultsA monovariate linear regression analysis confirms a strong correlation between TIR and HbA1c as found in previous studies, but leveraging more homogeneous data (n=146) collected in real-life conditions. Differences were determined between FGM and rtCGM devices in Pearson’s correlation (rFGM=0.703, rrtCGM=0.739), slope (β1,FGM=–11.77, β1,rtCGM=–10.74) and intercept (β0,FGM=141.19, β0,rtCGM=140.77) coefficients. Normality of residuals and homoscedasticity were successfully verified in both cases.ConclusionsRegression lines for two patient groups monitored through FGM and rtCGM devices, respectively, while confirming a linear relationship between TIR and A1c hemoglobin (A1C) in good accordance with previous studies, also show a statistically significant difference in the regression intercept, thus suggesting the need for different models tailored to device characteristics. The predictive power of A1C as a TIR estimator also deserves further investigations.
      Keywords: Open access
      PubDate: 2021-01-29T06:50:30-08:00
      DOI: 10.1136/bmjdrc-2019-001045
      Issue No: Vol. 9, No. 1 (2021)
  • Clusters of people with type 2 diabetes in the general population:
           unsupervised machine learning approach using national surveys in Latin
           America and the Caribbean

    • Authors: Carrillo-Larco, R. M; Castillo-Cara, M, Anza-Ramirez, C, Bernabe-Ortiz, A.
      Abstract: IntroductionWe aimed to identify clusters of people with type 2 diabetes mellitus (T2DM) and to assess whether the frequency of these clusters was consistent across selected countries in Latin America and the Caribbean (LAC).Research design and methodsWe analyzed 13 population-based national surveys in nine countries (n=8361). We used k-means to develop a clustering model; predictors were age, sex, body mass index (BMI), waist circumference (WC), systolic/diastolic blood pressure (SBP/DBP), and T2DM family history. The training data set included all surveys, and the clusters were then predicted in each country-year data set. We used Euclidean distance, elbow and silhouette plots to select the optimal number of clusters and described each cluster according to the underlying predictors (mean and proportions).ResultsThe optimal number of clusters was 4. Cluster 0 grouped more men and those with the highest mean SBP/DBP. Cluster 1 had the highest mean BMI and WC, as well as the largest proportion of T2DM family history. We observed the smallest values of all predictors in cluster 2. Cluster 3 had the highest mean age. When we reflected the four clusters in each country-year data set, a different distribution was observed. For example, cluster 3 was the most frequent in the training data set, and so it was in 7 out of 13 other country-year data sets.ConclusionsUsing unsupervised machine learning algorithms, it was possible to cluster people with T2DM from the general population in LAC; clusters showed unique profiles that could be used to identify the underlying characteristics of the T2DM population in LAC.
      Keywords: Open access, Epidemiology/health services research
      PubDate: 2021-01-29T06:50:30-08:00
      DOI: 10.1136/bmjdrc-2020-001889
      Issue No: Vol. 9, No. 1 (2021)
  • Sex, diabetes status and cognition: findings from the study of longevity
           in diabetes

    • Authors: Moran, C; Gilsanz, P, Beeri, M. S, Whitmer, R. A, Lacy, M. E.
      Abstract: IntroductionWomen comprise two-thirds of people with dementia, making female sex a significant dementia risk factor. Both type 1 diabetes (T1D) and type 2 diabetes (T2D) are known dementia risk factors with an increasing global incidence. Understanding whether subtle sex differences persist in cognitive function prior to dementia in the context of diabetes may help elucidate the magnitude of sex effects on dementia risk.Research design and methodsWe examined cross-sectional data from the Study of Longevity in Diabetes (SOLID), a prospective cohort study of members of Kaiser Permanente Northern California aged 60 years and older with T1D (n=758), T2D (n=232) and without either T1D or T2D (n=247). We used factor analysis to generate summary scores of cognitive domains and used regression analyses to examine the associations between sex and cognition adjusting for sociodemographic and cardiovascular confounders.ResultsWe included 1237 participants (630 women and 607 men) with mean age 68 years. By design, the distribution of men and women in T1D, T2D and no diabetes was similar. Women had better cognitive performance than men in global cognition (β=0.21, 95% CI 0.16 to 0.26), language (β=0.08, 95% CI 0.004 to 0.15), executive function (β=0.13, 95% CI 0.05 to 0.20), episodic verbal memory (β=0.68, 95% CI 0.59 to 0.77) and attention (β=0.20, 95% CI 0.11 to 0.28) but not in episodic visual memory (β=0.006, 95% CI –0.07 to 0.09) adjusting for age and education independent of diabetes status. We did not find an interaction between sex and diabetes status for any of the cognitive outcomes.ConclusionsWomen in late mid-life have better cognitive performance than men in many cognitive domains independent of the presence of T1D or T2D. Further work is required to understand whether these differences change over time or in older cohorts and to understand their relationship to subsequent dementia.
      Keywords: Open access, Epidemiology/health services research
      PubDate: 2021-01-28T07:12:23-08:00
      DOI: 10.1136/bmjdrc-2020-001646
      Issue No: Vol. 9, No. 1 (2021)
  • Time spent in hypoglycemia is comparable when the same amount of exercise
           is performed 5 or 2 days weekly: a randomized crossover study in people
           with type 1 diabetes

    • Authors: Steineck, I. I. K; Ranjan, A. G, Schmidt, S, Norgaard, K.
      Abstract: IntroductionPeople with type 1 diabetes are recommended to exercise regularly. However, limited evidence exists on how frequency and duration of exercise affect the risk of hypoglycemia. The study aimed to compare the percentage of time spent in hypoglycemia between two 5-day periods with different frequency and duration of physical activity.Research design and methodsIn this outpatient randomized crossover study, 26 participants aged 18–65 years with type 1 diabetes for ≥2 years and insulin pump use for ≥1 year were included. After a 7-day observation period, participants completed two 5-day intervention periods separated by a washout period of at least 14 days. One period included five exercise sessions on 5 consecutive days (5S), each consisting of 4 min of resistance training and 30 min of aerobic exercise. Another period included two exercise sessions on 2 days with at least 2 days in between (2S), each consisting of 10 min of resistance training and 75 min of aerobic exercise. During each period, participants performed in total 150 min of aerobic exercise and 20 min of resistance training and wore continuous glucose monitors (Dexcom G6) and accelerometers (ActiGraph wGT3X-BT).ResultsTwenty insulin pump-treated adults (10 women) with type 1 diabetes completed the study. The baseline median (range) age was 48 (24–64) years, glycated hemoglobin 55 (44–66) mmol/mol, diabetes duration 24 (8–57) years, and body mass index 28.4 (22.3–35.8) kg/m2. No differences were observed between 5S and 2S in the percentage (mean±SD) of time spent below 3.9 mmol/L (3.5%±2.8% vs 4.5%±4.2%, p=0.28), time spent in 3.9–10.0 mmol/L (65.3%±15.0% vs 68.5%±13.6%, p=0.31), time spent above 10.0 mmol/L (31.2%±16.4% vs 27.3%±14.5%, p=0.15), mean glucose (8.7±1.3 mmol/L vs 8.5±1.2 mmol/L, p=0.33) and glycemic variability (35.8%±5.3% vs 35.8%±6.6%, p=0.97).ConclusionsTime spent in hypoglycemia was comparable between the two 5-day periods with different duration and frequency of physical activity.Trial registration numberNCT04089462.
      Keywords: Open access, Clinical care/education/nutrition/psychosocial research
      PubDate: 2021-01-28T07:12:23-08:00
      DOI: 10.1136/bmjdrc-2020-001919
      Issue No: Vol. 9, No. 1 (2021)
  • Effects of modified lipoproteins on human trophoblast cells: a role in
           pre-eclampsia in pregnancies complicated by diabetes

    • Authors: McLeese, R. H; Zhao, J, Fu, D, Yu, J. Y, Brazil, D. P, Lyons, T. J.
      Abstract: IntroductionPre-eclampsia (PE) is increased ~4-fold by maternal diabetes. Elevated plasma antiangiogenic factors, soluble fms-like tyrosine kinase (sFLT-1) and soluble endoglin (sENG), precede PE onset. We investigated whether diabetes-related stresses, modified lipoproteins and elevated glucose enhance trophoblast sFLT-1 and sENG release and/or alter placental barrier function and whether oxidized low-density lipoprotein (Ox-LDL) is in placental tissue.Research design and methodsHTR8/SVneo cells were exposed to ‘heavily-oxidized, glycated’ LDL (HOG-LDL) versus native LDL (N-LDL) (10–200 mg protein/L) for 24 hours ±pretreatment with glucose (30 mmol/L, 72 hours). Concentrations of sFLT-1 and sENG in supernatants (by ELISA) and expressions of sFLT-1-I13 and sFLT-1-E15A isoforms, endoglin (ENG) and matrix metalloproteinase-14 (MMP-14; by RT-PCR) were quantified. For barrier studies, JAR cells were cultured in Transwell plates (12–14 days), then exposed to LDL. Transepithelial electrical resistance (TEER) was measured after 6, 12 and 24 hours. In placental sections from women with and without type 1 diabetes, immunostaining of apolipoprotein B100 (ApoB, a marker of LDL), Ox-LDL and lipoxidation product 4-hydroxynonenal was performed.ResultsHOG-LDL (50 mg/L) increased sFLT-1 (2.7-fold, p
      Keywords: Open access, Pathophysiology/complications
      PubDate: 2021-01-27T07:42:46-08:00
      DOI: 10.1136/bmjdrc-2020-001696
      Issue No: Vol. 9, No. 1 (2021)
  • Risk of morbidity and mortality in patients with type 2 diabetes treated
           with sodium-glucose cotransporter-2 inhibitor and/or dipeptidyl
           peptidase-4 inhibitor: a nationwide study

    • Authors: Süto, G; Molnar, G. A, Rokszin, G, Fabian, I, Kiss, Z, Szekanecz, Z, Poor, G, Jermendy, G, Kempler, P, Wittmann, I.
      Abstract: IntroductionMortality and disability in diabetes mellitus are determined mostly by cardiovascular complications and cancer. The impact of dipeptidyl peptidase-4 inhibitor (DPP-4i) and sodium-glucose cotransporter-2 inhibitor (SGLT2i) monotherapy or combination on long-term complications of type 2 diabetes mellitus was studied.Research design and methodsPatients with type 2 diabetes treated with DPP-4i or SGLT2i during a 3-year period were identified in the database of the National Institute of Health Insurance Fund in Hungary. All-cause mortality, acute myocardial infarction, stroke, hospitalization for heart failure (HHF), lower limb amputation (LLA) and cancer were assessed. Outcomes of add-on SGLT2i to DPP-4i treatment in comparison with switching DPP-4i therapy to SGLT2i were also evaluated. After propensity score matching, survival analysis was performed with a Cox proportional hazards model.ResultsAfter propensity score matching, both SGLT2i and DPP-4i groups included 18 583 patients. All-cause mortality (HR, 0.80; 95% CI 0.68 to 0.94; p=0.0057), HHF (HR, 0.81; 95% CI 0.71 to 0.92; p=0.0018), and risk of cancer (HR, 0.75; 95% CI 0.66 to 0.86; p
      Keywords: Open access, Epidemiology/health services research
      PubDate: 2021-01-20T07:42:54-08:00
      DOI: 10.1136/bmjdrc-2020-001765
      Issue No: Vol. 9, No. 1 (2021)
  • Variability in preventive care practices among US adults with diabetes

    • Authors: Baccaglini, L; Kusi Appiah, A, Ray, M, Yu, F.
      Abstract: IntroductionPatients with diabetes are advised to follow standard medical care including daily blood glucose and foot checks, eye examinations with pupil dilation, and cholesterol checks to prevent diabetes-related complications. It is unclear how these practices currently vary across different US population subgroups. The objective of this study was to assess variation in overall and individual diabetes care practices and identify specific factors associated with differences in these practices in a representative sample of US diabetic adults.Research design and methodsCross-sectional data were from the 2017 Behavioral Risk Factor Surveillance System. Survey logistic regression was used to account for the complex sampling design.ResultsAmong 30 780 eligible participants, 8957 (equivalent to 28% of the target population) followed all four diabetes care practices. Insulin-dependent participants had higher adjusted odds (adjusted OR=2.95; 95% CI 2.62 to 3.31) of following all four diabetic care practices compared with those who did not. Cost-related variables (having healthcare coverage and/or a personal doctor) were positively associated with diabetes care practices, with the strongest association observed for adherence to more costly practices (annual eye examination and cholesterol check) versus less costly ones (daily blood glucose check, daily foot check).ConclusionsOur findings suggest the need for diabetes care practice-specific and population subgroup-specific public health interventions to encourage early adherence to diabetic care practices and reduce complications.
      Keywords: Open access, Epidemiology/health services research
      PubDate: 2021-01-19T08:05:43-08:00
      DOI: 10.1136/bmjdrc-2020-001861
      Issue No: Vol. 9, No. 1 (2021)
  • Neurovascular coupling alterations in type 2 diabetes: a 5-year
           longitudinal MRI study

    • Authors: Zhang, Y; Zhang, X, Ma, G, Qin, W, Yang, J, Lin, J, Zhang, Q.
      Abstract: IntroductionRespective alterations in resting-state brain neural activity and cerebral blood flow (CBF) in type 2 diabetes mellitus (T2DM) have been reported. However, their coupling alteration in T2DM remains largely unknown.Research design and methodsTwenty-seven patients with T2DM aged 40–67 years and 36 well-matched healthy controls (HCs) underwent resting-state functional MRI (rs-fMRI) and arterial spin labeling (ASL) scans at two time points with a 5-year interval. Regional homogeneity (ReHo) and CBF were calculated from rs-fMRI and ASL, respectively. The standardized ReHo:CBF ratio (mReHo:mCBF ratio), the spontaneous neuronal activity per unit CBF supply, was compared between the two time points. Relationships between the mReHo:mCBF ratio and memory performance were analyzed.ResultsOver 5 years, decreased mReHo:mCBF ratios in patients with T2DM were mainly distributed in four regions, among which the left insula exhibited more severely decreased mReHo:mCBF ratio in patients with T2DM than in HCs, while the left postcentral gyrus, the right Rolandic operculum, and the right precentral gyrus showed no significant intergroup difference. Correlations between the mReHo:mCBF ratio and memory performance were also found in patients with T2DM.ConclusionsThis study suggests that T2DM may accelerate neurovascular coupling impairment in specific brain regions (the left insula), contributing to memory decline. This study implies that the mReHo:mCBF ratio is a potential imaging marker for detecting neurovascular changes.
      Keywords: Open access, Pathophysiology/complications
      PubDate: 2021-01-18T07:10:41-08:00
      DOI: 10.1136/bmjdrc-2020-001433
      Issue No: Vol. 9, No. 1 (2021)
  • Clinical decision support to improve management of diabetes and
           dysglycemia in the hospital: a path to optimizing practice and outcomes

    • Authors: Pichardo-Lowden, A; Umpierrez, G, Lehman, E. B, Bolton, M. D, DeFlitch, C. J, Chinchilli, V. M, Haidet, P. M.
      Abstract: IntroductionInnovative approaches are needed to design robust clinical decision support (CDS) to optimize hospital glycemic management. We piloted an electronic medical record (EMR), evidence-based algorithmic CDS tool in an academic center to alert clinicians in real time about gaps in care related to inpatient glucose control and insulin utilization, and to provide management recommendations.Research design and methodsThe tool was designed to identify clinical situations in need for action: (1) severe or recurrent hyperglycemia in patients with diabetes: blood glucose (BG) ≥13.88 mmol/L (250 mg/dL) at least once or BG ≥10.0 mmol/L (180 mg/dL) at least twice, respectively; (2) recurrent hyperglycemia in patients with stress hyperglycemia: BG ≥10.0 mmol/L (180 mg/dL) at least twice; (3) impending or established hypoglycemia: BG 3.9–4.4 mmol/L (70–80 mg/dL) or ≤3.9 mmol/L (70 mg/dL); and (4) inappropriate sliding scale insulin (SSI) monotherapy in recurrent hyperglycemia, or anytime in patients with type 1 diabetes. The EMR CDS was active (ON) for 6 months for all adult hospital patients and inactive (OFF) for 6 months. We prospectively identified and compared gaps in care between ON and OFF periods.ResultsWhen active, the hospital CDS tool significantly reduced events of recurrent hyperglycemia in patients with type 1 and type 2 diabetes (3342 vs 3701, OR=0.88, p=0.050) and in patients with stress hyperglycemia (288 vs 506, OR=0.60, p
      Keywords: Open access
      PubDate: 2021-01-18T07:10:41-08:00
      DOI: 10.1136/bmjdrc-2020-001557
      Issue No: Vol. 9, No. 1 (2021)
  • Estimating the impact of tax policy interventions on the projected number
           and prevalence of adults with type 2 diabetes in Germany between 2020 and

    • Authors: Tönnies, T; Heidemann, C, Paprott, R, Seidel-Jacobs, E, Scheidt-Nave, C, Brinks, R, Hoyer, A.
      Abstract: IntroductionAs a population-wide intervention, it has been proposed to raise taxes on unhealthy products to prevent diseases such as type 2 diabetes. In this study, we aimed to estimate the effect of tax policy interventions in 2020 on the projected prevalence and number of people with type 2 diabetes in the German adult population in 2040.Research design and methodsWe applied an illness-death model and the German Diabetes Risk Score (GDRS) to project the prevalence and number of adults with type 2 diabetes in Germany under a base case scenario and under a tax policy intervention scenario. For the base case scenario, we assumed constant age-specific incidence rates between 2020 and 2040. For the intervention scenario, we assumed a 50% price increase for sugar-sweetened beverages, tobacco and red meat products in the year 2020. Based on price elasticities, we estimated the impact on these risk factors alone and in combination, and calculated subsequent reductions in the age-specific and sex-specific GDRS. These reductions were used to determine reductions in the incidence rate and prevalence using a partial differential equation.ResultsCompared with the base case scenario, combined tax interventions in 2020 resulted in a 0.95 percentage point decrease in the prevalence of type 2 diabetes (16.2% vs 17.1%), which corresponds to 640 000 fewer prevalent cases of type 2 diabetes and a relative reduction by 6%.ConclusionsTaxation of sugar-sweetened beverages, tobacco products and red meat by 50% modestly lowered the projected number and prevalence of adults with type 2 diabetes in Germany in 2040. Raising taxes on unhealthy products as a stand-alone measure may not be enough to attenuate the future rise of type 2 diabetes.
      Keywords: Open access, Epidemiology/health services research
      PubDate: 2021-01-17T07:34:45-08:00
      DOI: 10.1136/bmjdrc-2020-001813
      Issue No: Vol. 9, No. 1 (2021)
  • Intraperitoneal insulin administration in pigs: effect on circulating
           insulin and glucose levels

    • Authors: Dirnena-Fusini, I; Am, M. K, Fougner, A. L, Carlsen, S. M, Christiansen, S. C.
      Abstract: IntroductionThe effect of intraperitoneal insulin infusion has limited evidence in the literature. Therefore, the aim of the study was to investigate the pharmacokinetics and pharmacodynamics of different intraperitoneal insulin boluses. There is a lack of studies comparing the insulin appearance in the systemic circulation after intraperitoneal compared with subcutaneous insulin delivery. Thus, we also aimed for a comparison with the subcutaneous route.Research design and methodsEight anesthetized, non-diabetic pigs were given three different intraperitoneal insulin boluses (2, 5 and 10 U). The order of boluses for the last six pigs was randomized. Endogenous insulin and glucagon release were suppressed by repeated somatostatin analog injections. The first pig was used to identify the infusion rate of glucose to maintain stable glucose values throughout the experiment. The estimated difference between insulin boluses was compared using two-way analysis of variance (GraphPad Prism V.8).In addition, a trial of three pigs which received subcutaneous insulin boluses was included for comparison with intraperitoneal insulin boluses.ResultsDecreased mean blood glucose levels were observed after 5 and 10 U intraperitoneal insulin boluses compared with the 2 U boluses. No changes in circulating insulin levels were observed after the 2 and 5 U intraperitoneal boluses, while increased circulating insulin levels were observed after the 10 U intraperitoneal boluses. Subcutaneously injected insulin resulted in higher values of circulating insulin compared with the corresponding intraperitoneal boluses.ConclusionsSmaller intraperitoneal boluses of insulin have an effect on circulating glucose levels without increasing insulin levels in the systemic circulation. By increasing the insulin bolus, a major increase in circulating insulin was observed, with a minor additive effect on circulating glucose levels. This is compatible with a close to 100% first-pass effect in the liver after smaller intraperitoneal boluses. Subcutaneous insulin boluses markedly increased circulating insulin levels.
      Keywords: Open access, Metabolism
      PubDate: 2021-01-15T07:18:19-08:00
      DOI: 10.1136/bmjdrc-2020-001929
      Issue No: Vol. 9, No. 1 (2021)
  • Feasibility study of real-time online text-based CBT to support
           self-management for people with type 1 diabetes: the Diabetes On-line
           Therapy (DOT) Study

    • Authors: Doherty, A. M; Herrmann-Werner, A, Rowe, A, Brown, J, Weich, S, Ismail, K.
      Abstract: IntroductionThis study examines the feasibility of conducting diabetes-focused cognitive–behavioral therapy (CBT) via a secure online real-time instant messaging system intervention to support self-management and improve glycemic control in people with type 1 diabetes.Research design and methodsWe used a pre–post uncontrolled intervention design over 12 months. We recruited adults with type 1 diabetes and suboptimal glycemic control (HbA1c ≥69 mmol/mol (DCCT 8.5%) for 12 months) across four hospitals in London. The intervention comprised 10 sessions of diabetes-focused CBT delivered by diabetes specialist nurses. The primary outcomes were number of eligible patients, rates of recruitment and follow-up, number of sessions completed and SD of the main outcome measure, change in HbA1c over 12 months. We measured the feasibility of collecting secondary outcomes, that is, depression measured using Patient Health Questionnaire-9 (PHQ-9), anxiety measured Generalised Anxiety Disorder (GAD) and the Diabetes Distress Scale (DDS).ResultsWe screened 3177 patients, of whom 638 were potentially eligible, from whom 71 (11.1%) were recruited. The mean age was 28.1 (13.1) years, and the mean HbA1c was 84.6 mmol/mol (17.8), DCCT 9.9%. Forty-six (65%) patients had at least 1 session and 29 (41%) completed all sessions. There was a significant reduction in HbA1c over 12 months (mean difference –6.2 (2.3) mmol/mol, DCCT 0.6%, p=0.038). The change scores in PHQ-9, GAD and DDS also improved.ConclusionsIt would be feasible to conduct a full-scale text-based synchronized real-time diabetes-focused CBT as an efficacy randomized controlled trial.
      Keywords: Open access, Clinical care/education/nutrition/psychosocial research
      PubDate: 2021-01-15T07:18:19-08:00
      DOI: 10.1136/bmjdrc-2020-001934
      Issue No: Vol. 9, No. 1 (2021)
  • Long-term safety and efficacy of alogliptin, a DPP-4 inhibitor, in
           patients with type 2 diabetes: a 3-year prospective, controlled,
           observational study (J-BRAND Registry)

    • Authors: Ueki, K; Tanizawa, Y, Nakamura, J, Yamada, Y, Inagaki, N, Watada, H, Shimomura, I, Nishimura, R, Miyoshi, H, Abiko, A, Katagiri, H, Hayashi, M, Shimada, A, Naruse, K, Fujimoto, S, Fujiwara, M, Shikata, K, Okada, Y, Araki, E, Yamazaki, T, Kadowaki, T, J-BRAND Registry Group
      Abstract: IntroductionGiven an increasing use of dipeptidyl peptidase-4 (DPP-4) inhibitors to treat patients with type 2 diabetes mellitus in the real-world setting, we conducted a prospective observational study (Japan-based Clinical Research Network for Diabetes Registry: J-BRAND Registry) to elucidate the safety and efficacy profile of long-term usage of alogliptin.Research design and methodsWe registered 5969 patients from April 2012 through September 2014, who started receiving alogliptin (group A) or other classes of oral hypoglycemic agents (OHAs; group B), and were followed for 3 years at 239 sites nationwide. Safety was the primary outcome. Symptomatic hypoglycemia, pancreatitis, skin disorders of non-extrinsic origin, severe infections, and cancer were collected as major adverse events (AEs). Efficacy assessment was the secondary outcome and included changes in hemoglobin A1c (HbA1c), fasting blood glucose, fasting insulin and urinary albumin.ResultsOf the registered, 5150 (group A: 3395 and group B: 1755) and 5096 (3358 and 1738) were included for safety and efficacy analysis, respectively. Group A patients mostly (>90%) continued to use alogliptin. In group B, biguanides were the primary agents, while DPP-4 inhibitors were added in up to ~36% of patients. The overall incidence of AEs was similar between the two groups (42.7% vs 42.2%). Kaplan-Meier analysis revealed the incidence of cancer was significantly higher in group A than in group B (7.4% vs 4.8%, p=0.040), while no significant incidence difference was observed in the individual cancer. Multivariate Cox regression analysis revealed that the imbalanced patient distribution (more elderly patients in group A than in group B), but not alogliptin usage per se, contributed to cancer development. The incidence of other major AE categories was with no between-group difference. Between-group difference was not detected, either, in the incidence of microvascular and macrovascular complications. HbA1c and fasting glucose decreased significantly at the 0.5-year visit and nearly plateaued thereafter in both groups.ConclusionsAlogliptin as a representative of DPP-4 inhibitors was safe and durably efficacious when used alone or with other OHAs for patients with type 2 diabetes in the real world setting.
      Keywords: Open access, Clinical care/education/nutrition/psychosocial research
      PubDate: 2021-01-13T06:45:14-08:00
      DOI: 10.1136/bmjdrc-2020-001787
      Issue No: Vol. 9, No. 1 (2021)
  • One-year intensive lifestyle intervention and improvements in
           health-related quality of life and mental health in persons with type 2
           diabetes: a secondary analysis of the U-TURN randomized controlled trial

    • Authors: MacDonald, C. S; Nielsen, S. M, Bjorner, J, Johansen, M. Y, Christensen, R, Vaag, A, Lieberman, D. E, Pedersen, B. K, Langberg, H, Ried-Larsen, M, Midtgaard, J.
      Abstract: IntroductionThe effects of lifestyle interventions in persons with type 2 diabetes (T2D) on health-related quality of life (HRQoL) and subjective well-being are ambiguous, and no studies have explored the effect of exercise interventions that meet or exceed current recommended exercise levels. We investigated whether a 1-year intensive lifestyle intervention is superior in improving HRQoL compared with standard care in T2D persons.Research design and methodsWe performed secondary analyses of a previously conducted randomized controlled trial (April 2015 to August 2016). Persons with non-insulin-dependent T2D (duration ≤10 years) were randomized to 1-year supervised exercise and individualized dietary counseling (ie, ‘U-TURN’), or standard care. The primary HRQoL outcome was change in the 36-item Short Form Health Survey (SF-36) physical component score (PCS) from baseline to 12 months of follow-up, and a key secondary outcome was changes in the SF-36 mental component score (MCS).ResultsWe included 98 participants (U-TURN group=64, standard care group=34) with a mean age of 54.6 years (SD 8.9). Between-group analyses at 12-month follow-up showed SF-36 PCS change of 0.8 (95% CI –0.7 to 2.3) in the U-TURN group and deterioration of 2.4 (95% CI –4.6 to –0.1) in the standard care group (difference of 3.2, 95% CI 0.5 to 5.9, p=0.02) while no changes were detected in SF-36 MCS. At 12 months, 19 participants (30%) in the U-TURN group and 6 participants (18%) in the standard care group achieved clinically significant improvement in SF-36 PCS score (adjusted risk ratio 2.6, 95% CI 1.0 to 4.5 corresponding to number needed to treat of 4, 95% CI 1.6 to infinite).ConclusionIn persons with T2D diagnosed for less than 10 years, intensive lifestyle intervention improved the physical component of HRQoL, but not the mental component of HRQoL after 1 year, compared with standard care.Trial registration numberNCT02417012.
      Keywords: Open access, Clinical care/education/nutrition/psychosocial research
      PubDate: 2021-01-13T06:45:14-08:00
      DOI: 10.1136/bmjdrc-2020-001840
      Issue No: Vol. 9, No. 1 (2021)
  • Circulating long non-coding RNAs NKILA, NEAT1, MALAT1, and MIAT expression
           and their association in type 2 diabetes mellitus

    • Authors: Alfaifi, M; Ali Beg, M. M, Alshahrani, M. Y, Ahmad, I, Alkhathami, A. G, Joshi, P. C, Alshehri, O. M, Alamri, A. M, Verma, A. K.
      Abstract: BackgroundType 2 diabetes mellitus (T2DM) is a multifactorial disorder that leads to alterations in gene regulation. Long non-coding RNAs (lncRNAs) have become a major research topic as they are involved in metabolic disorders.MethodsThis study included a total of 400 study subjects; 200 were subjects with T2DM and 200 were healthy subjects. Extracted RNA was used to synthesize cDNA by quantitative real time. Serum analysis was carried out to determine differences in biochemical parameters. Recorded data were used to evaluate associations with expression of lncRNAs NF-kappaB interacting lncRNA (NKILA), nuclear enriched abundant transcript 1 (NEAT1), metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), and myocardial infarction-associated transcript (MIAT) in T2DM cases.ResultsCompared with healthy controls, patients with T2DM showed an overall increase in expression of lncRNAs NKILA, NEAT, MALAT1, and MIAT by 3.94-fold, 5.28-fold, 4.46-fold, and 6.35-fold, respectively. Among patients with T2DM, higher expression of lncRNA NKILA was associated with hypertension (p=0.001), smoking (p
      Keywords: Open access, Genetics/genomes/proteomics/metabolomics
      PubDate: 2021-01-12T07:17:32-08:00
      DOI: 10.1136/bmjdrc-2020-001821
      Issue No: Vol. 9, No. 1 (2021)
  • Service user and community clinician design of a partially virtual
           diabetic service improves access to care and education and reduces
           amputation incidence

    • Authors: Watt, A; Beacham, A, Palmer-Mann, L, Williams, A, White, J, Brown, R, Williams, E, Richards, G, White, L, Budge, P, Darvall, K, Bond, E, Paisey, R.
      Abstract: IntroductionDesign of an integrated diabetes service based on needs of service users (persons living with diabetes) and community clinicians in a semirural low-income health district of the UK.Research design and methodsOne hundred and eighty-five service users engaged through public meetings, questionnaires and focus groups. General practice staff contributed views through workshops and questionnaires. Analysis of feedback indicated service user needs for better access to education, dietary advice and foot care. General practice staff endorsed these views and requested regular access to secondary care in the community. Seven hundred persons registered with diabetes attended eight well-being events in the community. From 2017 virtual practice multidisciplinary patient reviews, virtual referral of foot cases and non-face-to-face helplines were developed. A National Health Service (NHS) approved ‘App’ and web-based personalized education support for those recently diagnosed with diabetes was introduced.ResultsEngagement in education for those recently diagnosed with diabetes increased from 5% to 71%. Weight and hemoglobin A1c (HbA1c) levels before and 6 months after starting the program were 99.4±25 and 95.5±24.2 kg and 59.3±16 and 54.8±12.9 mmol/mol, respectively, p=0.00003 and 0.003. Of those engaging at well-being events, 44 had missed regular follow-up. One hundred and seventy-five cases were reviewed virtually with practice staff by the secondary care team avoiding referral to the hospital diabetic clinic. One hundred and seventy-six referrals were made to the virtual multidisciplinary diabetic foot team clinic. Major amputation incidence declined from 13 to 3 major procedures/10 000 per annum and minor amputation from 26 to 18/10 000. Percentage bed day occupancy by persons with diabetes fell significantly in the district general hospital.ConclusionsIntegrated community-based diabetes care delivery has been achieved with partially virtual reviews. Patient education, secondary care in the community, access to dietetic advice and foot care outcomes have all improved.
      Keywords: Open access, Clinical care/education/nutrition/psychosocial research
      PubDate: 2021-01-11T07:44:47-08:00
      DOI: 10.1136/bmjdrc-2020-001657
      Issue No: Vol. 9, No. 1 (2021)
  • Associations of cells from both innate and adaptive immunity with lower
           nerve conduction velocity: the Maastricht Study

    • Authors: Maalmi, H; Wouters, K, Savelberg, H. H. C. M, van der Velde, J. H. P. M, Reulen, J. P. H, Mess, W, Schalkwijk, C. G, Stehouwer, C. D. A, Roden, M, Ziegler, D, Herder, C, Schaper, N. C.
      Abstract: IntroductionDistal sensorimotor polyneuropathy (DSPN) is common in people with diabetes but is also found in pre-diabetes. Peripheral nerve myelin damage, which can be assessed by reduced nerve conduction velocity (NCV), is an essential feature of DSPN. Emerging evidence indicates that the development of DSPN may involve the activation of the immune system. However, available studies have mainly investigated circulating immune mediators, whereas the role of immune cells remains unclear. Therefore, we aimed to test whether leukocyte subsets are associated with NCV.Research design and methodsThis cross-sectional study analyzed data from 850 individuals (of whom 252 and 118 had type 2 diabetes and pre-diabetes, respectively) of the Maastricht Study. NCV was measured in the peroneal and tibial motor nerves and the sural sensory nerve and summed to calculate a standardized NCV sum score. Associations between percentages of leukocyte subsets and NCV sum scores were estimated using linear regression models adjusted for demographic, lifestyle, metabolic and clinical covariates.ResultsAfter adjustment for covariates, higher percentages of basophils and CD4+ T cells were associated with lower NCV (p=0.014 and p=0.005, respectively). The percentage of CD8+ T cells was positively associated with NCV (p=0.022). These associations were not modified by glucose metabolism status (all pinteraction >0.05). No associations were found for monocytes, eosinophils, neutrophils, lymphocytes, total T cells, Treg cells and B cells.ConclusionsThe associations of basophils, CD4+ and CD8+ T cells with NCV suggest that cell types from both innate and adaptive immunity may be implicated in the development of DSPN.
      Keywords: Open access, Pathophysiology/complications
      PubDate: 2021-01-11T07:44:47-08:00
      DOI: 10.1136/bmjdrc-2020-001698
      Issue No: Vol. 9, No. 1 (2021)
  • Association between hemoglobin A1c variability and hypoglycemia-related
           hospitalizations in veterans with diabetes mellitus

    • Authors: Zhao, M. J. Y; Prentice, J. C, Mohr, D. C, Conlin, P. R.
      Abstract: IntroductionTo study the impact of hemoglobin A1c (A1c) variability on the risk of hypoglycemia-related hospitalization (HRH) in veterans with diabetes mellitus.Research design and methods342 059 veterans with diabetes aged 65 years or older were identified for a retrospective cohort study. All participants had a 3-year baseline period from January 1, 2005 to December 31, 2016, during which they had at least four A1c tests. A1c variability measures included coefficient of variation (A1c CV), A1c SD, and adjusted A1c SD. HRH was identified during a 2-year follow-up period from Medicare and the Veterans Health Administration through validated algorithms of International Classification of Diseases (ICD)-9 and ICD-10 codes. Logistic regression modeling was used to evaluate the relationship between A1c variability and HRH risk while controlling for relevant clinical covariates.Results2871 patients had one or more HRH in the 2-year follow-up period. HRH risk increased with greater A1c variability, and this was consistent across A1c CV, A1c SD, and adjusted A1c SD. Average A1c levels were also independently associated with HRH, with levels 9% (75 mmol/mol) with greater risk. The relationships between A1c variability remained significant after controlling for average A1c levels and prior HRH during the baseline period.ConclusionIncreasing A1c variability and elevated A1c levels are associated with a greater risk of HRH in older adults with diabetes. Clinicians should consider A1c variability when assessing patients for risk of severe hypoglycemia.
      Keywords: Open access, Cardiovascular and metabolic risk
      PubDate: 2021-01-11T07:44:47-08:00
      DOI: 10.1136/bmjdrc-2020-001797
      Issue No: Vol. 9, No. 1 (2021)
  • Association of the Diabetes Health Plan with emergency room and inpatient
           hospital utilization: a Natural Experiment for Translation in Diabetes
           (NEXT-D) Study

    • Authors: Moin, T; Steers, N, Ettner, S. L, Duru, K, Turk, N, Chan, C, Keckhafer, A. M, Luchs, R. H, Ho, S, Mangione, C. M.
      Abstract: IntroductionTo examine the association of a novel disease-specific health plan, known as the Diabetes Health Plan (DHP), with emergency room (ER) and hospital utilization among patients with diabetes and pre-diabetes.Research design and methodsQuasi-experimental design, with employer group as the unit of analysis, comparing changes in any ER and inpatient hospital utilization over a 3-year period. Inverse probability weighting was used to control for differences between employers purchasing DHP versus standard plans. Estimated differences in utilization are calculated as average treatment effects on the treated. We used employees and dependents from employer groups contracting with a large, national private insurer between 2009 and 2012. Eligibility and claims data from continuously covered employees and dependents with diabetes and pre-diabetes (n=74 058) were aggregated to the employer level. The analysis included 9 DHP employers (n=7004) and 183 control employers (n=67 054).ResultsDHP purchase was associated with 2.4 and 1.8 percentage points absolute reduction in mean rates of any ER utilization, representing 13% and 10% relative reductions at 1 and 2 years post-DHP (p=0.012 and p=0.046, respectively). There was no significant association between DHP purchase and hospital utilization.ConclusionEmployers purchasing diabetes-specific health benefit designs may experience lower rates of resource-intensive services such as ER utilization.
      Keywords: Open access, Epidemiology/health services research
      PubDate: 2021-01-11T07:44:47-08:00
      DOI: 10.1136/bmjdrc-2020-001802
      Issue No: Vol. 9, No. 1 (2021)
  • Increased stress, weight gain and less exercise in relation to glycemic
           control in people with type 1 and type 2 diabetes during the COVID-19

    • Authors: Ruissen, M. M; Regeer, H, Landstra, C. P, Schroijen, M, Jazet, I, Nijhoff, M. F, Pijl, H, Ballieux, B. E. P. B, Dekkers, O, Huisman, S. D, de Koning, E. J. P.
      Abstract: IntroductionLockdown measures have a profound effect on many aspects of daily life relevant for diabetes self-management. We assessed whether lockdown measures, in the context of the COVID-19 pandemic, differentially affect perceived stress, body weight, exercise and related this to glycemic control in people with type 1 and type 2 diabetes.Research design and methodsWe performed a short-term observational cohort study at the Leiden University Medical Center. People with type 1 and type 2 diabetes ≥18 years were eligible to participate. Participants filled out online questionnaires, sent in blood for hemoglobin A1c (HbA1c) analysis and shared data of their flash or continuous glucose sensors. HbA1c during the lockdown was compared with the last known HbA1c before the lockdown.ResultsIn total, 435 people were included (type 1 diabetes n=280, type 2 diabetes n=155). An increase in perceived stress and anxiety, weight gain and less exercise was observed in both groups. There was improvement in glycemic control in the group with the highest HbA1c tertile (type 1 diabetes: –0.39% (–4.3 mmol/mol) (p
      Keywords: Open access, Clinical care/education/nutrition/psychosocial research, COVID-19
      PubDate: 2021-01-11T07:44:47-08:00
      DOI: 10.1136/bmjdrc-2020-002035
      Issue No: Vol. 9, No. 1 (2021)
  • Peripheral artery disease, lower limb revascularization, and amputation in
           diabetes patients with and without coronary artery disease: a cohort study
           from the Western Denmark Heart Registry

    • Authors: Olesen, K. K. W; Gyldenkerne, C, Thim, T, Thomsen, R. W, Maeng, M.
      Abstract: IntroductionPatients with diabetes have increased risk of lower limb revascularization and amputation due to higher risk of peripheral artery disease (PAD) and peripheral neuropathy. The additive effect of coronary artery disease (CAD) is less clear. We examined the risk of PAD, lower limb revascularization, and amputation in diabetes and non-diabetes patients with and without CAD in patients examined by coronary angiography (CAG).Research design and methodsWe included all patients undergoing CAG between 2003 and 2016 in Western Denmark. Patients with previous CAD, PAD, lower limb revascularization, or amputation were excluded. Patients were stratified by diabetes and CAD status and followed for a maximum of 10 years. Outcomes were PAD, lower limb revascularization, and amputation. We estimated 10-year cumulative incidences and adjusted HRs (aHRs) using patients neither diabetes nor CAD as reference.ResultsA total of 118 787 patients were included, of whom 41 878 (35%) had neither diabetes nor CAD, 5735 (5%) had diabetes alone, 59 427 (50%) had CAD alone, and 11 747 (10%) had both diabetes and CAD. Median follow-up was 6.9 years. Diabetes patients without CAD had higher risk of PAD (3.5%, aHR 1.73, 95% CI 1.51 to 1.97), lower limb revascularization (1.6%, aHR 1.55, 95% CI 1.16 to 2.05), and lower limb amputation (2.4%, aHR 5.51, 95% CI 4.09 to 7.43) compared with patients with neither diabetes nor CAD. CAD was associated with 2.5-fold and 1.8-fold higher risk of PAD and amputation, respectively, among patients without diabetes, and associated with 3.9-fold and 9.5-fold higher risk of PAD and lower limb amputation among patients with diabetes.ConclusionsDespite absence of obstructive CAD, patients with diabetes remained at higher risk of PAD, lower limb revascularization, and lower limb amputation. Diabetes was more strongly associated with amputation than CAD, but CAD exacerbated the risks of PAD, revascularization, and amputation in patients with diabetes.
      Keywords: Open access, Cardiovascular and metabolic risk
      PubDate: 2021-01-07T08:09:00-08:00
      DOI: 10.1136/bmjdrc-2020-001803
      Issue No: Vol. 9, No. 1 (2021)
  • Adverse outcomes in COVID-19 and diabetes: a retrospective cohort study
           from three London teaching hospitals

    • Authors: Izzi-Engbeaya, C; Distaso, W, Amin, A, Yang, W, Idowu, O, Kenkre, J. S, Shah, R. J, Woin, E, Shi, C, Alavi, N, Bedri, H, Brady, N, Blackburn, S, Leczycka, M, Patel, S, Sokol, E, Toke-Bjolgerud, E, Qayum, A, Abdel-Malek, M, Hope, D. C. D, Oliver, N. S, Bravis, V, Misra, S, Tan, T. M, Hill, N. E, Salem, V.
      Abstract: IntroductionPatients with diabetes mellitus admitted to hospital with COVID-19 have poorer outcomes. However, the drivers of poorer outcomes are not fully elucidated. We performed detailed characterization of patients with COVID-19 to determine the clinical and biochemical factors that may be drivers of poorer outcomes.Research design and methodsThis is a retrospective cohort study of 889 consecutive inpatients diagnosed with COVID-19 between March 9 and April 22, 2020 in a large London National Health Service Trust. Unbiased multivariate logistic regression analysis was performed to determine variables that were independently and significantly associated with increased risk of death and/or intensive care unit (ICU) admission within 30 days of COVID-19 diagnosis.Results62% of patients in our cohort were of non-white ethnic background and the prevalence of diabetes was 38%. 323 (36%) patients met the primary outcome of death/admission to the ICU within 30 days of COVID-19 diagnosis. Male gender, lower platelet count, advancing age and higher Clinical Frailty Scale (CFS) score (but not diabetes) independently predicted poor outcomes on multivariate analysis. Antiplatelet medication was associated with a lower risk of death/ICU admission. Factors that were significantly and independently associated with poorer outcomes in patients with diabetes were coexisting ischemic heart disease, increasing age and lower platelet count.ConclusionsIn this large study of a diverse patient population, comorbidity (ie, diabetes with ischemic heart disease; increasing CFS score in older patients) was a major determinant of poor outcomes with COVID-19. Antiplatelet medication should be evaluated in randomized clinical trials among high-risk patient groups.
      Keywords: Open access, Clinical care/education/nutrition/psychosocial research, COVID-19
      PubDate: 2021-01-06T07:53:52-08:00
      DOI: 10.1136/bmjdrc-2020-001858
      Issue No: Vol. 9, No. 1 (2021)
  • Vitamin D status and risk of type 2 diabetes in the Norwegian HUNT cohort
           study: does family history or genetic predisposition modify the

    • Authors: Denos, M; Mai, X.-M, Asvold, B. O, Sorgjerd, E. P, Chen, Y, Sun, Y.-Q.
      Abstract: IntroductionWe sought to investigate the relationship between serum 25-hydroxyvitamin D (25(OH)D) level and the risk of type 2 diabetes mellitus (T2DM) in adults who participated in the Trøndelag Health Study (HUNT), and the possible effect modification by family history and genetic predisposition.Research design and methodsThis prospective study included 3574 diabetes-free adults at baseline who participated in the HUNT2 (1995–1997) and HUNT3 (2006–2008) surveys. Serum 25(OH)D levels were determined at baseline and classified as
      Keywords: Open access, Epidemiology/health services research
      PubDate: 2021-01-05T07:33:14-08:00
      DOI: 10.1136/bmjdrc-2020-001948
      Issue No: Vol. 9, No. 1 (2021)
  • Geographical clustering and socioeconomic factors associated with
           hypoglycemic events requiring emergency assistance in Andalusia (Spain)

    • Authors: Gomez-Peralta, F; Abreu, C, Benito, M, Barranco, R. J.
      Abstract: IntroductionThe geographical distribution of hypoglycemic events requiring emergency assistance was explored in Andalusia (Spain), and potentially associated societal factors were determined.Research design and methodsThis was a database analysis of hypoglycemia requiring prehospital emergency assistance from the Public Company for Health Emergencies (Empresa Pública de Emergencias Sanitarias (EPES)) in Andalusia during 2012, which served 8 393 159 people. Databases of the National Statistics Institute, Basic Spatial Data of Andalusia and System of Multiterritorial Information of Andalusia were used to retrieve spatial data and population characteristics. Geographic Information System software (QGIS and GeoDA) was used for analysis and linkage across databases. Spatial analyses of geographical location influence in hypoglycemic events were assessed using Moran’s I statistics, and linear regressions were used to determine their association with population characteristics.ResultsThe EPES attended 1 137 738 calls requesting medical assistance, with a mean hypoglycemia incidence of 95.0±61.6 cases per 100 000 inhabitants. There were significant differences in hypoglycemia incidence between basic healthcare zones attributable to their geographical location in the overall population (Moran’s I index 0.122, z-score 7.870, p=0.001), women (Moran’s I index 0.088, z-score 6.285, p=0.001), men (Moran’s I index 0.076, z-score 4.914, p=0.001) and aged >64 years (Moran’s I index 0.147, z-score 9.753, p=0.001). Hypoglycemia incidence was higher within unemployed individuals (β=0.003, p=0.001) and unemployed women (β=0.005, p=0.001), while lower within individuals aged 64 years, which was affected by societal factors such as unemployment, literacy/education, housing and sports facilities. These data can be useful to design specific prevention programs.
      Keywords: Open access, Epidemiology/health services research
      PubDate: 2021-01-04T06:57:58-08:00
      DOI: 10.1136/bmjdrc-2020-001731
      Issue No: Vol. 9, No. 1 (2021)
  • Prevalence and incidence of microvascular and macrovascular complications
           over 15 years among patients with incident type 2 diabetes

    • Authors: An, J; Nichols, G. A, Qian, L, Munis, M. A, Harrison, T. N, Li, Z, Wei, R, Weiss, T, Rajpathak, S, Reynolds, K.
      Abstract: IntroductionType 2 diabetes (T2D) is a common condition that, if left untreated or poorly managed, can lead to adverse microvascular and macrovascular complications. We estimated the prevalence and incidence of microvascular and macrovascular complications among patients newly diagnosed with T2D within a US integrated healthcare system.Research design and methodsWe conducted a retrospective cohort study among patients newly diagnosed with T2D between 2003 and 2014. We evaluated 13 complications, including chronic kidney disease (CKD), cardiovascular disease (CVD), and all-cause mortality through 2018. Multivariable Cox proportional hazards models were used to study factors associated with complications.ResultsWe identified 135 199 patients with incident T2D. The mean age was 58 years, and 48% were women. The prevalence of CKD was the highest of the complications at the time of T2D diagnosis (prevalence=12.3%, 95% CI 12.2% to 12.5%), while the prevalence of CVD was among the lowest at 3.3% (95% CI 3.2% to 3.3%). The median time to incidence of a T2D complication ranged from 3.0 to 5.2 years. High incidence rates (95% CI) of T2D complications included peripheral neuropathy (26.9, 95% CI 26.5 to 27.3 per 1000 person-years (PY)), CKD (21.2, 95% CI 20.9 to 21.6 per 1000 PY), and CVD (11.9, 95% CI 11.7 to 12.2 per 1000 PY). The trend of 5-year incidence rates of T2D complications by diagnosis year decreased over time (p value
      Keywords: Open access, Epidemiology/health services research
      PubDate: 2021-01-04T06:57:58-08:00
      DOI: 10.1136/bmjdrc-2020-001847
      Issue No: Vol. 9, No. 1 (2021)
School of Mathematical and Computer Sciences
Heriot-Watt University
Edinburgh, EH14 4AS, UK
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