This study compares novel type 1 diabetes–related autoantibody assays developed to improve upon the standard radiobinding assay (RBA). Samples from 1,505 individuals, followed for 5 years or to clinical type 1 diabetes, originally tested by RBA were aliquoted and sent blindly to five laboratories (Barbara Davis Diabetes Center [BDC], Institute of Diabetes Research [IDR], Diabetes […]
Read MoreMonth: August 2025
GLP-1–Mediated Targeting of Inflammation Corrects Obesogenic Memory in Male Mice
Obesity-induced biologic changes often persist after weight loss and are difficult to reverse, a phenomenon known as obesogenic memory. This enduring effect is associated with metabolic inflammation, particularly in adipose tissue. In this study, we characterized a mouse model of obesogenic memory and evaluated the efficacy of the unimolecular conjugate glucagon-like peptide 1 (GLP-1)/dexamethasone (GLP-1/Dexa), […]
Read MoreAutoreactive T Cells and Cytokine Stress Drive β-Cell Senescence Entry and Accumulation in Type 1 Diabetes
Type 1 diabetes (T1D) results from a complex dialogue between the immune system and islets characterized by T cell–mediated autoimmune destruction of pancreatic β-cells. In this dialogue, β-cell stress responses have emerged as drug targets for slowing T1D progression, including a subpopulation of senescent β-cells that accumulate during T1D in humans and nonobese diabetic (NOD) […]
Read MoreCannabinoid Receptor 2 Agonism Demonstrates Therapeutic Potential in Experimental Models of Relevance to Diabetic Retinopathy
Evidence of retinal vascular inflammation accompanies diabetic retinopathy (DR) progression, and inflammatory cytokines tumor necrosis factor-α (TNFα) and interleukin-1β (IL-1β) are experimentally linked to several hallmark DR features, including retinal leukostasis. Cannabinoid receptor 2 (CB2) agonism has been shown to decrease inflammatory cytokine production and leukocyte recruitment and adhesion in nonocular inflammation models, suggesting CB2 […]
Read MoreThe Cardiac and Hemodynamic Effects of Ketone Bodies Are Abnormal in Patients With Type 1 Diabetes: A Randomized Controlled Trial
Impaired cardiac ketone oxidative capacity is a possible disease mechanism in the development of diabetic cardiomyopathy. We examined whether the cardiovascular effects of ketone bodies are different in patients with type 1 diabetes (T1D) compared with healthy control individuals. In a single-blind study with a crossover design, nine patients with T1D and eight age-matched, healthy […]
Read MoreDynamic Ca 2+ -Dependent Transcription Links Metabolic Stress to Impaired β-Cell Identity
By augmenting ATP-sensitive K+ channel–induced membrane depolarization, chronic metabolic stress in prediabetes may increase intracellular Ca2+ concentrations in pancreatic β-cells and cause a loss of cell identity and function. Here, we describe studies of the temporal transcriptomic dynamics induced by sulfonylurea-induced membrane depolarization. Gene expression in isolated islets is highly dynamic, with changes occurring within […]
Read MoreMacrophage-Expressed Micropeptide Smim30 Maintains Adipose Tissue Insulin Sensitivity and Safeguards Systemic Metabolic Homeostasis
A growing number of micropeptides (miPs) have been identified in recent years, but their biological roles remain largely unexplored. We identified a conserved 6-kDa miP, named small integral membrane protein 30 (SMIM30), as a potential metabolic regulator. To study the physiological function of Smim30, we generated a loss-of-function mouse strain using the CRISPR/Cas9-mediated knock-in strategy. […]
Read MoreSubclasses of Glucose Trajectories in Early Childhood Stratified the Risk of Abnormal Glucose Tolerance in Adolescence and Young Adulthood
Early-life exposures may shape long-term effects on glucose regulation. This study aimed to stratify long-term abnormal glucose tolerance (AGT) risk from early childhood. A total of 906 children were enrolled at baseline and reevaluated in adolescence and young adulthood. By using the latent class trajectory analysis, glucose trajectories of children were measured via five–time point […]
Read MoreT Cell–Mediated Immunity to Gliadin Is Elicited in the Gut Mucosa of Type 1 Diabetes Patients Only in Presence of Celiac Disease Comorbidity
Type 1 diabetes (T1D) and celiac disease (CeD) are two strongly associated autoimmune disorders, as they share genetic risk factors and immunopathogenic mechanisms. Several studies suggest an implication of gluten proteins, the causative antigen of CeD, in T1D pathogenesis. We investigated whether a gliadin-specific T-cell reactivity is present in the gut mucosa of children with […]
Read MoreFasting Lowers Glucagon Levels Under Basal Conditions and During Insulin-Induced Hypoglycemia in Individuals With Type 1 Diabetes
Short-term fasting (<24 h) is common in individuals with type 1 diabetes (T1D), but it is associated with increased risk of hypoglycemia. Current strategies to mitigate this risk include changing the timing and/or dose of insulin; however, it is unclear whether counterregulatory hormone secretion is diminished, which would also contribute to this elevated risk. The […]
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