JournalTOCs

Diabetologia
Journal Prestige (SJR): 3.228

Citation Impact (citeScore): 5
Number of Followers: 116

Hybrid journal (It can contain Open Access articles)
ISSN (Print) 1432-0428 - ISSN (Online) 0012-186X
Published by Springer-Verlag

[2468 journals]

Diabetes and natural and man-made disasters: prevention, preparation,
response and recovery
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  Abstract: Both the global prevalence of diabetes and the frequency of natural and man-made disasters are increasing. Of all chronic diseases, the consequences of sudden loss of medical supplies are most serious for those with diabetes, with people living with type 1 diabetes being at risk of death within a few days without insulin. This review considers how to prepare for and respond to sudden reductions in medical supplies to those with diabetes. Recent experiences with the COVID-19 pandemic in India, the war in Ukraine and the war/blockade in the Tigray region of Ethiopia are described, and the importance of prevention, preparedness, response and recovery are discussed. It is hoped that lessons from these and other disasters and ongoing advocacy and other actions may help to mitigate the risks of significant morbidity and mortality for people with diabetes in disaster-impacted regions across the world. Graphical Abstract
  PubDate: 2025-04-15
Exercise-induced meteorin-like protein protects human pancreatic beta
cells from cytokine-induced apoptosis
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  Abstract: Aims/hypothesis Inflammation-driven pancreatic beta cell death is a hallmark of type 1 diabetes progression. We have previously shown that serum obtained from individuals after high-intensity interval training prevents cytokine-induced human beta cell apoptosis, but the mediators of this beneficial effect remain to be characterised. In this study we evaluated the role of exercise-induced meteorin-like protein (Metrnl) in human beta cell protection. Methods Human EndoC-βH1 cells and induced pluripotent stem cell (iPSC)-derived islets were exposed to proinflammatory cytokines and treated with serum collected before and after high-intensity interval training, with and without Metrnl-neutralising antibodies. The effects of Metrnl on apoptosis, insulin secretion and chemokine CXCL10 gene and protein expression were assessed. Results Post-exercise serum had an increased concentration of Metrnl compared with pre-exercise level serum, resulting in a 46% reduction in cytokine-induced beta cell death. Additionally, direct treatment with recombinant Metrnl at concentrations of 100 ng/ml and 200 ng/ml reduced cytokine-induced cell death by 24% and 41%, respectively, in EndoC-βH1 cells, with similar results obtained in iPSC-derived islets. Metrnl treatment also preserved insulin secretion under inflammatory stress. These effects were associated with a decrease in CXCL10 mRNA expression and protein release. Blocking Metrnl with a neutralising antibody eliminated the protective effects of serum from trained individuals on EndoC-βH1 cells exposure to proinflammatory cytokines. Conclusions/interpretation Our findings reveal that the exerkine Metrnl is a key mediator of the beneficial effects of exercise on pancreatic beta cells, suggesting that Metrnl is a potential therapeutic target for preserving human beta cell function and survival in type 1 diabetes. Graphical Abstract
  PubDate: 2025-04-12
The genetic architecture of type 1 diabetes over time: how well can we
rely on past data to predict the future'
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  PubDate: 2025-04-12
Alterations in cerebral perfusion and substrate metabolism in type 2
diabetes: interactions with APOE-ε4
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  Abstract: Aims/hypothesis Epidemiological studies indicate that type 2 diabetes increases the risk for Alzheimer’s disease. Alterations in cerebral metabolism have been proposed as a potential mechanism underlying this association. A better understanding of these metabolic changes may elucidate potential pathways linking type 2 diabetes to Alzheimer’s disease. The aim of the current exploratory study was to investigate whether cerebral metabolism, including glucose and fatty acid uptake as well as cerebral blood flow, is altered in individuals with type 2 diabetes compared with both overweight individuals and lean control individuals. Methods This exploratory study included 38 participants (ten with type 2 diabetes, 13 overweight individuals and 15 lean control individuals). Brain metabolism was assessed using multiple imaging techniques: [18F]fluorodeoxyglucose and [18F]fluoro-6-thiaheptadecanoic acid positron emission tomography for glucose and fatty acid uptake; arterial spin-labelling MRI for cerebral perfusion; and 1H-magnetic resonance spectroscopy for specific metabolites. Neurodegeneration markers were evaluated from lumbar puncture samples. Group comparisons were assessed using one-way ANOVA and unpaired t tests, and correlations were assessed with linear regression. Results Individuals with type 2 diabetes exhibited lower cerebral glucose uptake compared with both lean and overweight groups (p
  PubDate: 2025-04-11
Metabolic effects of 3-hydroxybutyrate infusion in individuals with type 1
diabetes compared with healthy control participants: a randomised
crossover trial showing intact feedback suppression of lipolysis
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  Abstract: Aims/hypothesis Diabetic ketoacidosis remains a severe complication in type 1 diabetes, arising from insufficient insulin levels and accelerated lipolytic rate, leading to increased β-oxidation of NEFA and ketone body production in the liver. The ketone body 3-hydroxybutyrate (3-OHB) inhibits lipolysis in healthy individuals. The current study aimed to test whether this feedback suppression of lipolysis by 3-OHB is disrupted in individuals with type 1 diabetes. Methods We used a single-blind, randomised, crossover design to study ten men diagnosed with type 1 diabetes and ten healthy control participants. Eligibility criteria were male sex, age ≥18 years, BMI of 19–26 kg/m2 and no severe comorbidities/diseases. Following an overnight fast, each participant received two 3 h i.v. infusions: (i) sodium-d/l-3-OHB and (ii) iso-osmolar saline (NaCl), separated by a 1 h washout period. The order of the two interventions was assigned by randomisation for each participant. Participants were blinded to the allocation throughout the study day, but investigators were aware of the assigned intervention order. We evaluated the lipolytic rate and glucose turnover using [9,10-3H]palmitate and [3-3H]glucose tracers. Additionally, adipose tissue signalling was quantified using western blotting techniques in subcutaneous abdominal adipose tissue biopsies. The primary endpoint measure was palmitate flux (lipolytic rate). Results During the infusion of 3-OHB, the d/l-3-OHB blood concentrations increased to 3.3 ± 0.7 mmol/l in participants with type 1 diabetes compared with 2.9 ± 0.5 mmol/l in control participants (p=0.03). The infusion effectively suppressed the lipolytic rates by more than 50% (p
  PubDate: 2025-04-10
The genetics of low and high birthweight and their relationship with
cardiometabolic disease
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  Abstract: Aims/hypothesis Low birthweight infants are at increased risk not only of mortality, but also of type 2 diabetes mellitus and CVD in later life. At the opposite end of the spectrum, high birthweight infants have increased risk of birth complications, such as shoulder dystocia, neonatal hypoglycaemia and obesity, and similarly increased risk of type 2 diabetes mellitus and CVD. However, previous genome-wide association studies (GWAS) of birthweight in the UK Biobank have primarily focused on individuals within the ‘normal’ range and have excluded individuals with high and low birthweight (4.5 kg). The aim of this study was to investigate genetic variation associated within the tail ends of the birthweight distribution, to: (1) see whether the genetic factors operating in these regions were different from those that explained variation in birthweight within the normal range; (2) explore the genetic correlation between extremes of birthweight and cardiometabolic disease; and (3) investigate whether analysing the full distribution of birthweight values, including the extremes, improved the ability to detect genuine loci in GWAS. Methods We performed case–control GWAS analysis of low (4.5 kg) birthweight in the UK Biobank using REGENIE software (Nlow=20,947; Nhigh=12,715; Ncontrols=207,506) and conducted three continuous GWAS of birthweight, one including the full range of birthweights, one involving a truncated GWAS including only individuals with birthweights between 2.5 and 4.5 kg and a third GWAS that winsorised birthweight values 4.5 kg. Additionally, we performed bivariate linkage disequilibrium (LD) score regression to estimate the genetic correlation between low/normal/high birthweight and cardiometabolic traits. Results Bivariate LD score regression analyses suggested that high birthweight had a mostly similar genetic aetiology to birthweight within the normal range (genetic correlation coefficient [rG]=0.91, 95% CI 0.83, 0.99), whereas there was more evidence for a separate set of genes underlying low birthweight (rG=−0.74, 95% CI 0.66, 0.82). Low birthweight was also significantly positively genetically correlated with most cardiometabolic traits and diseases we examined, whereas high birthweight was mostly positively genetically correlated with adiposity and anthropometric-related traits. The winsorisation strategy performed best in terms of locus detection, with the number of independent genome-wide significant associations (p
  PubDate: 2025-04-10
Clinical use of polygenic scores in type 2 diabetes: challenges and
possibilities
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  Abstract: Resulting from a combination of genetic and environmental factors, type 2 diabetes is highly heterogeneous in manifestation and disease progression, with the only common feature being chronic hyperglycaemia. In spite of vigorous efforts to elucidate the pathogenetic origins and natural course of the disease, there is still a lack of biomarkers and tools for prevention, disease stratification and treatment. Genome-wide association studies have reported over 1200 variants associated with type 2 diabetes, and the decreased cost of generating genetic data has facilitated the development of polygenic scores for estimating an individual’s genetic disease risk based on combining effects from most—or all—genetic variants. In this review, we summarise the current knowledge on type 2 diabetes-related polygenic scores in different ancestries and outline their possible clinical role. We explore the potential applicability of type 2 diabetes polygenic scores to quantify genetic liability for prediction, screening and risk stratification. Given that most genetic risk loci are determined from populations of European origin while other ancestries are under-represented, we also discuss the challenges around their global applicability. To date, the potential for clinical utility of polygenic scores for type 2 diabetes is limited, with such scores outperformed by clinical measures. In the future, rather than predicting risk of type 2 diabetes, the value of polygenic scores may be in stratification of the severity of disease (risk for comorbidities) and treatment response, in addition to aiding in dissecting the pathophysiological mechanisms involved. Graphical Abstract
  PubDate: 2025-04-05
Cardiac remodelling, recognition memory deficits and accelerated ageing in
a rat model of gestational diabetes
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  Abstract: Aims/hypothesis Women with prior gestational diabetes mellitus (GDM) have higher incidence of age-associated diseases, including type 2 diabetes, CVD and cognitive impairment. Human studies cannot readily determine whether GDM causes these conditions or the underlying mechanisms. Here we used a well-validated rat model of GDM to address these questions. Methods Rats with beta cell-specific expression of human amylin, a pancreatic hormone, were used as a GDM model. Five-month-old female rats were randomly assigned to no-pregnancy, one-pregnancy and two-pregnancies experimental groups. GTTs and transthoracic echocardiography were performed at baseline and during the postpartum period. At 18 months of age, the novel object recognition test was administered, followed by euthanasia and organ collection. Results All female rats developed glucose intolerance and showed cardiac remodelling and impaired left ventricular relaxation with ageing. Glucose intolerance was exacerbated in rats with prior GDM pregnancies compared with nulliparous rats, with significant differences starting at 9 months of age. However, blood glucose levels were comparable in the three groups during the course of the study. Rats with two GDM-complicated pregnancies had increased left ventricular mass compared with the other groups following the second pregnancy and until the end of the study. At 18 months of age, rats with prior GDM pregnancies presented aggravated demyelination, particularly in the hippocampus and mid-brain region, oxidative stress and neuroinflammation, and had a lower recognition index in the novel object recognition test compared with nulliparous rats. Higher parity exacerbated these effects. Shorter telomeres and reduced mitochondrial DNA content, two hallmarks of biological ageing, were found in the brain, heart and pancreas of rats with prior GDM. Conclusions/interpretation These findings support the concept that GDM is a sex-specific risk factor for ageing-related diseases, and point to accelerated cellular ageing as a contributing mechanism. Data availability Cardiac echocardiography and GTT data are available at Dataverse under the identifier https://doi.org/10.7910/DVN/R2HITG Graphical Abstract
  PubDate: 2025-04-05
The effect of once-weekly insulin icodec vs once-daily basal insulin on
physical activity-attributed hypoglycaemia in type 2 diabetes: a post hoc
analysis of ONWARDS 1–5
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  Abstract: Aims/hypothesis Physical activity increases the risk of hypoglycaemia in individuals with type 2 diabetes when basal or basal-bolus insulin therapy is administered. Once-weekly basal insulins may elevate the risk of physical activity-attributed hypoglycaemia compared with other basal insulins because the administered levels cannot be reduced in anticipation of increased physical activity. This post hoc analysis of five separate randomised trials (ONWARDS 1–5) aimed to examine physical activity-attributed hypoglycaemic episodes in adults with type 2 diabetes receiving either once-weekly basal insulin icodec (herein referred to as ‘icodec’) or once-daily basal insulins. Methods The ONWARDS 1–5 Phase 3a randomised controlled trials compared the efficacy and safety of once-weekly basal icodec vs once-daily basal insulin in insulin-naive (ONWARDS 1, 3 and 5) and insulin-experienced (ONWARDS 2 and 4) adults with type 2 diabetes. Participants self-monitored their blood glucose levels using a blood glucose meter and a digital diary. In each trial, suspected hypoglycaemia symptoms triggered additional self-measured blood glucose readings, and values indicative of hypoglycaemia were recorded in the participants’ digital diary. Participants who experienced hypoglycaemic episodes were instructed to note any relation of each episode to physical activity. Hypoglycaemic episodes were classified as alert value (level 1: blood glucose
  PubDate: 2025-04-05
Parent-of-origin effects in the life-course evolution of cardiometabolic
traits
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  Abstract: Aims/hypothesis Cardiometabolic traits are heritable, and some display parent-of-origin effects, which indicates preferential inheritance from one parent or parental bias. Most studies of these phenomena have focused on adult populations. We aimed to investigate the heritability and parent-of-origin effects on cardiometabolic traits in a birth cohort with serial measurements to determine whether these patterns emerged early in life. Methods The Pune Maternal Nutrition Study comprises a birth cohort in which offspring and parents were studied from birth and followed up for 24 years. We investigated parent-of-origin effects on cardiometabolic traits cross-sectionally at available timepoints using linear regression, and longitudinally across the life course using mixed-effect regression. Maternal and paternal effects on offspring phenotype were modelled after adjusting for age, sex and BMI. Parent-of-origin effects were calculated based on the difference between maternal and paternal effects. We also investigated these effects in another birth cohort, that of the Pune Children’s Study. Genetic parent-of-origin effects were assessed using generalised estimating equations after taking the parental origin of the alleles into account. Results Birthweight showed a maternal parent-of-origin effect. At 24 years, maternal bias was seen for some obesity-related traits for daughters, while paternal bias was seen for WHR in sons. A shift from paternal bias at 6 years to maternal bias at 24 years for the skinfold thickness was observed in daughters. Fasting glucose and lipids showed maternal bias at 6, 12 and 24 years. For fasting insulin and HOMA2-S, a negative maternal effect at 6 years transitioned to a positive one at 12 years. For HOMA2-B, a paternal effect at 6 years transitioned to a maternal one at 12 years, and this remained so at 24 years. Some of these findings were also observed in the cohort from the Pune Children’s Study. Longitudinal modelling revealed stronger paternal effects over time for fasting insulin and HOMA indices but maternal effects for glucose and lipids, reflecting their cumulative effect over time. Genetic variants at the KCNQ1 locus showed a maternal parent-of-origin effect on birthweight, on HOMA2-B at 12 years, and on lipids at 6 and 12 years. Conclusions/interpretation Our study provides proof of concept of the existence of parent-of-origin effects on cardiometabolic traits from birth, through childhood and puberty, until adult age. Our results indicate a predominantly maternal influence on intrauterine, pubertal and reproductive-age metabolism in the offspring. While the longitudinal analysis indicated a maternal bias for the macronutrients (glucose and lipids), and a paternal bias for glucose–insulin metabolism, the cross-sectional analysis revealed a transition between parental influence across physiological stages. This dynamic relationship may have its origins in the life-history theory of evolution, and could inform strategies for primordial prevention aimed at curbing the rising burden of cardiometabolic disease. Further studies are needed to determine the mechanisms underlying such effects. Graphical Abstract
  PubDate: 2025-04-02
Macular perfusion alterations in people with recent-onset diabetes and
novel diabetes subtypes
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  Abstract: Aims/hypothesis Our aim was to detect early structural and functional changes in the macular capillaries using optical coherence tomography angiography during the course of type 1 or 2 diabetes mellitus. Methods In this cross-sectional study, individuals with type 1 diabetes (n=143) or type 2 diabetes (n=197) from the German Diabetes Study (ClinicalTrials.gov registration no. NCT01055093) underwent clinical examination and cluster analysis to identify phenotype-based diabetes subtypes, using BMI, age, HbA1c, homoeostasis model estimates and islet autoantibodies. Colour fundus photography, optical coherence tomography and optical coherence tomography angiography were performed within the first year of diabetes diagnosis (baseline) and at 5 year intervals up to year 10. Age- and sex-adjusted participants served as control participants (n=105). Perfusion density, vessel density, presence of retinal microaneurysms in superficial, intermediate and deep capillary plexus (SCP, ICP, DCP), choriocapillaris flow deficit density (CC FD) and the foveal avascular zone (FAZ) of the macula as well as retinal layer thickness, visual acuity and contrast sensitivity were analysed. Results Perfusion density and vessel density of SCP were already reduced at baseline in type 2 diabetes (expected difference compared with control participants: −0.0071, p=0.0276, expected difference: −0.0034, p=0.0184, respectively), especially in participants with severe insulin-deficient and mild obesity-related diabetes. At year 10 only perfusion density of the SCP and DCP was reduced in both type 1 and 2 diabetes (p=0.0365, p=0.0062, respectively). The FAZ was enlarged and the CC FD within the first year increased in type 1 (p=0.0327, p=0.0474, respectively) and more markedly in type 2 diabetes (p=0.0006, p
  PubDate: 2025-03-31
HEXA-FC protein therapy increases skeletal muscle glucose uptake and
improves glycaemic control in mice with insulin resistance and in a mouse
model of type 2 diabetes
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  Abstract: Aims/hypothesis Type 2 diabetes is a chronic metabolic disorder characterised by insulin resistance and sustained hyperglycaemia, and is a major cause of blindness, kidney failure, heart attacks and stroke. Our team has recently identified hexosaminidase A (HEXA) as an endocrine factor secreted by the liver that regulates sphingolipid metabolism in skeletal muscle. Specifically, HEXA converts GM2 to GM3 gangliosides within cell-surface lipid rafts. Remodelling of ganglioside composition by HEXA enhances IGF1 signalling in skeletal muscle, increasing muscle glucose uptake and improving blood glucose control. Methods We produced a long-acting HEXA-FC fusion protein (murine HEXA and the fragment crystallisable [FC] region from IgG1) and evaluated the effects of chronic bi-weekly HEXA-FC administration (1 mg/kg body weight) on glycaemic control in C57BL/6 mice with diet-induced obesity and insulin resistance and the db/db mouse model of severe type 2 diabetes. Outcome measures included glucose and insulin tolerance, including a stable isotope-labelled GTT and assessment of tissue-specific glucose disposal, as well as proteomics analysis to define changes in skeletal muscle metabolism. Results Chronic administration of a long-acting recombinant HEXA-FC fusion protein led to improvements in random blood glucose, fasting blood glucose and glucose tolerance, driven by increased glucose disposal into skeletal muscle, effects that were associated with enhancement of IGF1 signalling in muscle. Conclusions/interpretation Given that skeletal muscle is a primary site of insulin resistance in individuals with type 2 diabetes, HEXA-FC protein therapy may open new avenues for therapeutic advancement in type 2 diabetes. Graphical Abstract
  PubDate: 2025-03-29
TMEM55A-mediated PI5P signalling regulates alpha cell actin
depolymerisation and glucagon secretion
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  Abstract: Aims/hypothesis Diabetes is associated with the dysfunction of glucagon-producing pancreatic islet alpha cells, although the underlying mechanisms regulating glucagon secretion and alpha cell dysfunction remain unclear. While insulin secretion from pancreatic beta cells has long been known to be controlled partly by intracellular phospholipid signalling, very little is known about the role of phospholipids in glucagon secretion. Using patch-clamp electrophysiology and single-cell RNA sequencing, we previously found that expression of PIP4P2 (encoding TMEM55A, a lipid phosphatase that dephosphorylates phosphatidylinositol-4,5-bisphosphate [PIP2] to phosphatidylinositol-5-phosphate [PI5P]) correlates with alpha cell function. We hypothesise that TMEM55A is involved in glucagon secretion and aim to validate the role of TMEM55A and its potential signalling molecules in alpha cell function and glucagon secretion. Methods Correlation analysis was generated from the data in www.humanislets.com. Human islets were isolated at the Alberta Diabetes Institute IsletCore. Electrical recordings were performed on dispersed human or mouse islets with scrambled siRNA or si-PIP4P2 (si-Pip4p2 for mouse) transfection. Glucagon secretion was measured using an islet perfusion system with intact mouse islets. TMEM55A activity was measured using an in vitro on-beads phosphatase assay and live-cell imaging. GTPase activity was measured using an active GTPase pull-down assay. Confocal microscopy was used to quantify F-actin intensity using primary alpha cells and alphaTC1–9 cell lines after chemical treatment. Results TMEM55A regulated alpha cell exocytosis and glucagon secretion. TMEM55A knockdown in both human and mouse alpha cells reduced exocytosis at low glucose levels and this was rescued by the direct reintroduction of PI5P. PI5P, instead of PIP2 increased the glucagon secretion using intact mouse islets. This did not occur through an effect on Ca2+ channel activity but through a remodelling of cortical F-actin dependent on TMEM55A lipid phosphatase activity, which occurred in response to oxidative stress. TMEM55A- and PI5P-induced F-actin remodelling depends on the inactivation of GTPase and RhoA, instead of Ras-related C3 botulinum toxin substrate 1 or CDC42. Conclusions/interpretation We reveal a novel pathway by which TMEM55A regulates alpha cell exocytosis by controlling intracellular PI5P and the F-actin network. Graphical Abstract
  PubDate: 2025-03-26
Quinine: rediscovery of an old glucose-lowering drug
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  PubDate: 2025-03-25
Regulating islet stress responses through CD47 activation
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  Abstract: Aims/hypothesis Diabetes is a global health burden characterised by incremental beta cell loss. Islet transplantation is a recognised treatment for individuals with type 1 diabetes and hypoglycaemia unawareness but broader application is constrained by limited islet survival and function post-transplantation. The underlying molecular mechanisms that induce beta cell dysfunction and demise remain unclear, and therapeutic agents that protect against cellular loss and maintain insulin secretion are in demand as potential treatment options. CD47 is a cell surface protein implicated in cellular stress responses but its role in beta cell function remains relatively unexplored. We hypothesised that modulating CD47 expression would demonstrate a cytoprotective effect in beta cells. Methods We used primary murine islets with/without genetic deletion of CD47, as well as human islets and MIN6 cells subjected to pharmacological disruption of CD47 signalling (siRNA or blocking antibody). Metabolic stress was induced in cells by exposure to hypoxia, hyperglycaemia or thapsigargin, and markers of the unfolded protein response, cell survival and insulin secretory function were assessed. Human pancreases from individuals with and without diabetes were examined for evidence of CD47 signalling. Results Expression of CD47 and its high affinity ligand thrombospondin-1 (TSP1) was robustly upregulated by exogenous stressors. Limiting CD47 signalling improved markers of senescence, apoptosis, endoplasmic reticulum stress, unfolded protein response, self-renewal and autophagy, and maintained insulin secretory responses. We also found concurrent upregulated expression of CD47 and senescence markers in the endocrine pancreas of aged donors and those with type 2 diabetes. Both CD47 and TSP1 expression were increased in pancreases of humans with type 1 diabetes, as were plasma levels of TSP1. Conclusions/interpretation Our study provides key insights into the essential role of CD47 as a novel regulator of islet dysfunction, regulating cytoprotective responses to stress. CD47 may contribute to beta cell damage during the development of diabetes and failure of islet transplant function. Therefore, limiting CD47 activation may be a potential therapeutic tool in conditions where islet function is inadequate. Graphical Abstract
  PubDate: 2025-03-25
Immunotherapy with low-dose IL-2 attenuates vascular injury in mice with
diabetic and neovascular retinopathy by restoring the balance between
Foxp3+ Tregs and CD8+ T cells
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  Abstract: Aims/hypothesis Diabetic retinopathy features damage to the retinal microvasculature that causes vessels to leak and proliferate and can lead to vision loss and blindness. Inflammation contributes to the development of diabetic retinopathy, but little is known about the role of the adaptive immune system, including the benefits of augmenting the Forkhead box protein P3 (Foxp3) regulatory T cell (Treg) compartment. We aimed to determine whether treatment with low-dose IL-2 expands and activates Tregs and reduces CD8+ T cells in the retina, and attenuates retinal inflammation and vasculopathy in murine models of diabetic retinopathy and neovascular retinopathy. Methods Mouse models of streptozocin-induced diabetes and oxygen-induced retinopathy (OIR) were administered low-dose IL-2 (25,000 U) or vehicle (sterile water) by i.p. injection. Reporter mice expressing Foxp3 as a red fluorescent protein (RFP) conjugate or CD8 as a green fluorescent protein (GFP) conjugate were used to evaluate Foxp3+ Tregs and CD8+ T cells, respectively, in blood, lymphoid organs and retina using flow cytometry or confocal microscopy. Vasculopathy and the expression of angiogenic and inflammatory factors were assessed in the retina. Results Low-dose IL-2 significantly expanded CD4+CD25+Foxp3+ Tregs in the blood and spleen of mouse models of OIR and diabetes (1.4- to 1.9-fold increase, p
  PubDate: 2025-03-25
Quinine: rediscovery of an old glucose-lowering drug. Reply to Henquin J-C
[letter]
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  PubDate: 2025-03-25
Early weight loss, diabetes remission and long-term trajectory after
diagnosis of type 2 diabetes: a retrospective study
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  Abstract: Aims/hypothesis Weight loss can improve glycaemic management in individuals with type 2 diabetes, but its long-term effects on remission, cardiovascular risk factors and complications remain unclear. We investigated clinical outcomes following non-interventional ≥10% body weight loss in people with newly diagnosed type 2 diabetes in a routine care setting. Methods We retrospectively analysed two cohorts of people with newly diagnosed type 2 diabetes. After exclusions, cohort 1 included 1934 individuals followed for up to 25 years; cohort 2 comprised 13,277 individuals followed for up to 10 years. Participants were categorised into two groups based on whether or not they lost at least 10% body weight. In a sensitivity analysis, a group of participants with intermediate weight loss (5% to
  PubDate: 2025-03-22
Up Front
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  PubDate: 2025-03-21
The efficacy of islet autoantibody screening with or without genetic
pre-screening strategies for the identification of presymptomatic type 1
diabetes
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  Abstract: Early detection of type 1 diabetes, in its presymptomatic stage, offers significant clinical advantages, including treatment that can delay disease onset. Current screening focuses on identifying islet autoantibody positivity, with proposed optimal testing at ages 2, 6 and 10 years potentially achieving up to 80% sensitivity. However, challenges arise from participation rates and costs associated with multiple screenings. Genetic pre-screening has been suggested as a complementary strategy to target high-risk individuals prior to autoantibody testing, but its real-world benefits remain uncertain. Broad genetic selection strategies, based on family history, HLA typing or polygenic risk scores, can identify subsets of the population at elevated risk. However, these approaches face issues like low recall rates, socioeconomic biases and limited applicability across diverse ancestries. Additionally, the cost-effectiveness and infrastructure requirements of integrating genetic testing into routine healthcare remain significant hurdles. The combined use of genetic and autoantibody testing could improve predictive value, especially with innovations like point-of-care genetic testing. Yet, the ultimate success of any screening programme depends less on specific strategies and more on maximising public and healthcare-provider engagement, ensuring high participation, and addressing socioeconomic and demographic disparities. Digital-health infrastructure may play a crucial role in improving recall rates and maintaining follow-up adherence. In conclusion, while repeated islet autoantibody screening remains the most effective standalone approach, conducting genetic screening prior to islet autoantibody testing may be practical in certain contexts, provided that sufficient resources and equitable strategies are employed. Public engagement and robust infrastructure are essential to realising the full potential of early type 1 diabetes detection programmes. Graphical Abstract
  PubDate: 2025-03-19

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