Early postprandial glucagon concentrations are higher in type 1 diabetes (T1D) than in individuals with no diabetes (ND). To determine the cause, we infused stable [13C9, 15N1]glucagon before, during, and after a mixed meal in 16 ND and 16 T1D individuals to measure glucagon turnover. In a subcohort of 9 ND and 12 T1D individuals, […]
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Urinary Branched-Chain Amino Acid Excretion and Chronic Kidney Disease Progression in Patients With Type 2 Diabetes
Preclinical studies suggest that activating branched-chain amino acid (BCAA) catabolism may improve chronic kidney disease (CKD). In this prospective clinical study, we sought to examine the association between urinary BCAA excretion and risk of CKD progression in patients with type 2 diabetes. Baseline urinary BCAAs were measured by mass spectrometry in 1,868 outpatients with type […]
Read MoreB Lymphocytes Impede Tregs to Erode Islet Tolerance in Type 1 Diabetes
B lymphocytes are thought to drive β-cell destruction in type 1 diabetes (T1D) by activating anti-islet T cells. However, the observation that autoreactive T-cell activation and disease progression can occur without B cells challenges this view. Still, preclinical and clinical studies have shown that B-cell depletion alleviates β-cell destruction, suggesting a critical role for B […]
Read MoreMODY Is Prevalent in Later-Onset Diabetes and Has Potential for Targeted Therapy but Is Challenging to Identify
Maturity-onset diabetes of the young (MODY) can present after the age of 40 years, but its prevalence and clinical characteristics, and the utility of simple clinical features for selecting cases in this age group, remain poorly defined. We analyzed whole-exome and clinical data from 51,619 individuals with diabetes diagnosed after age 40 years from one […]
Read MoreEffects of Marked Weight Loss Induced by Gastric Bypass Surgery or Low-Calorie Diet Alone on Postprandial Glucose Disposal in Type 2 Diabetes
We used a dual (intravenous and oral) glucose tracer protocol to evaluate rates of glucose appearance in the circulation, insulin-mediated glucose disposal (IMGD), and noninsulin-mediated glucose disposal (NIMGD) for 4 h after consumption of a mixed meal in people with obesity and type 2 diabetes before and after marked (∼20%) weight loss, induced by behavioral […]
Read MoreAdipose TGR5 Deletion Promotes Hepatic Steatosis Through Decreasing Adiponectin Secretion in Mice
Metabolic dysfunction–associated steatotic liver disease (MASLD) has emerged as a global epidemic, yet its underlying molecular mechanisms remain elusive, and therapeutic options are limited. The interorgan communication between liver and adipose tissue plays a crucial role in maintaining hepatic lipid homeostasis. This study investigates the role of G-protein–coupled bile acid receptor 1 (TGR5) in adipose […]
Read MoreMultiorgan Fibrosis and Risk of Type 2 Diabetes: Genetic and Observational Evidence Highlighting a Causal Role of Pancreatic Fibrosis
Pancreatic fibrosis has been proposed as a contributor to type 2 diabetes (T2D) by impairing islet function, but whether it plays a causal role remains unclear. We investigated this question using two complementary approaches. First, we performed a computed tomography–based retrospective case-control study (T2D case patients: n = 58; control participants: n = 58) assessing […]
Read MoreProlonged Semaglutide Treatment Reveals Stage-Dependent Changes to Feeding Behavior and Metabolic Adaptations in Male Mice
Glucagon-like peptide 1 receptor (GLP-1R) agonists have transformed obesity treatment, but weight loss responses to these drugs vary widely. Elucidating behavioral and metabolic phenotypes throughout GLP-1R agonist treatment could identify mechanisms underlying this response spectrum. We characterized food intake, meal patterns, energy expenditure (EE), and substrate oxidation during prolonged semaglutide treatment and posttreatment recovery in […]
Read MoreProfiling Associations Between IGHG-FCGR Ligand-Receptor Interactions and Disease Progression From Stage 1 and 2 to Stage 3 Type 1 Diabetes
The primary objective of this study was to investigate whether ligand-receptor interactions (LRIs) between IGHG and FCGR gene products are associated with progression to type 1 diabetes (T1D). Using two completed clinical trials (DPT-1 and TN07), we applied next-generation targeted sequencing to genotype IGHG and FCGR genes in a cohort of 1,214 individuals and assessed […]
Read MoreMaternal Obesity Leads to Muscle Dysfunction via H19 -Mediated Programming of Insulin-Like Growth Factor 2 Signaling
Forty-two percent of American women of childbearing age have obesity, impacting offspring muscle and metabolism. The insulin-like growth factor 2 (IGF2) pathway is vital for muscle growth, but its regulation by maternal obesity (MO) remains unclear. H19, a long noncoding RNA, is reciprocally regulated with Igf2, which has multiple promoters (P0–P3). H19 interacts with EZH2, […]
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