Month: January 2026

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 […]

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 […]

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 […]

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 […]

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 […]

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 […]

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, […]

White adipose tissue (WAT) insulin resistance (IR) is a central feature of metabolic syndrome; however, data regarding defects in WAT insulin signaling in humans with IR is limited. To determine which defects in WAT insulin signaling are associated with human IR, WAT was obtained from three cohorts of patients with obesity. In a bariatric surgery […]

Type 2 diabetes and obesity are commonly accompanied by metabolic dysfunction–associated steatotic liver disease (MASLD), increasing the risk of developing metabolic dysfunction–associated steatohepatitis (MASH) and fibrosis. The early stages of MASLD are characterized by dysfunctional lipid metabolism, including remodeling of the hepatic lipidome. In this context, reductions in hepatic phosphatidylserine (PS) have been associated with […]

Insulin secretion varies widely in preclinical type 1 diabetes. To understand the pathogenesis of this metabolic heterogeneity, we asked whether genetic predisposition to type 2 diabetes, quantified by a type 2 diabetes genetic risk score (T2D-GRS), modulates β-cell function and disease progression in individuals at risk of type 1 diabetes. We analyzed 4,324 islet autoantibody–positive […]