Author: sugaradmin

Introduction and Objective: Despite advances in the development of new insulin formulations and the use of diabetes technologies, severe hypoglycemia remains a major problem for people with type 1 diabetes on intensive insulin therapy due in part to defective counterregulatory hormone responses and a lack of symptomatic awareness of hypoglycemia. Elevated brain lactate levels in […]

Introduction and Objective: To achieve adipose mass reduction while maintaining or improving insulin sensitivity involves an integration of multiple neuroendocrine and paracrine inputs that requires an in vivo setting to be adequately studied. We therefore performed in vivo Perturb-Seq of visceral adipocytes to identify novel targets for the treatment of obesity.Methods: An AAV library encoding […]

Introduction and Objective: Type I (IFNα) and Type II (IFNγ) interferons have been shown to play a critical role in T1D pathogenesis. Studies on pancreatic biopsies from individuals with recent-onset T1D suggest an upregulation of IFN-stimulated gene signatures. However, their impact on the β-cell epitranscriptome and translatome remains untested.Methods: Human islets from 12 cadaveric donors […]

Introduction and Objective: T2D is a heterogeneous disease involving defects in multiple metabolic processes, which could be assessed by partitioned pathway-specific polygenic scores (pPS) developed from clustering T2D GWAS lead variants based on associations with related cardiometabolic traits. Here, we demonstrate the use of T2D pPS to identify T2D patient subgroups with distinct clinical features […]

Introduction and Objective: In GO MOMs, early pregnancy OGTT did not sufficiently improve prediction of gestational diabetes (GDM) or large-for-gestational age birthweight (LGA) beyond clinical factors to warrant universal first-trimester screening. This secondary analysis evaluated if early metabolic or lipid measures improved predictions of these outcomes.Methods: Singleton gravidas without preexisting diabetes from 9 US centers […]

Introduction and Objective: Translating genetic and molecular biomarkers into clinically actionable T2D risk prediction models is challenged by uncertain incremental value beyond standard clinical factors in real-world populations. We assessed metabolomic risk score (MRS) and a polygenic risk score (PRS) for incident T2D prediction in a diverse healthcare system.Methods: We studied 36,352 adults free of […]

Introduction and Objective: Weight loss is associated with a significant reduction of lean mass (LM). The effects of GLP-1 therapy in patients with pre-existing low LM (LLM) are not well characterized. Here, we analyze the effects of trevogrumab (trevo) with and without garetosmab (garet) in people living with obesity with and without LLM at baseline […]

Introduction and Objective: Type 1 diabetes (T1D) is driven by loss of immune tolerance and immune-mediated destruction of functional β cells. Effective therapies should preserve and regenerate β cells while reducing immunogenicity and restoring immune regulation. Harmine (H) plus exendin-4 (E) robustly expands human β cells, but its impact on β cell survival and immunogenicity […]

Introduction and Objective: Inflammatory cytokine signaling contributes to beta-cell autoimmunity in type 1 diabetes (T1D), but the contribution of interferon-gamma (IFNγ) versus other inflammatory pathways remains unclear. We hypothesized that beta-cells from donors with T1D display elevated IFNγ response relevant to autoimmunity.Methods: We identified differentially expressed genes from two publicly available human islet bulk RNA-seq […]