Biobehavioral Studies of Obesity, Weight loss and Recidivism

National Institute Of Diabetes And Digestive And Kidney Diseases

Investigators

Linked publications, trials & patents

Abstract

In the last year, we have focused our study on 1) the phenotype of rare obesity variants; 2) the beta cell and alpha cell function and 3) the incretin response in healthy volunteers and insulin resistant subjects. Primary Insulin Hypersecretion: Enhanced β-cell glucose responsivity contributes to primary insulin hypersecretion, potentially playing a causal role in type 2 diabetes independent of insulin resistance. Our studies reveal that vulnerable populations may exhibit increased first-phase insulin secretion, driven by heightened sensitivity to metabolic pathways rather than differences in readily releasable insulin pools, suggesting targeted therapeutic approaches to modulate β-cell metabolic sensitivity may help prevent β-cell exhaustion. α-cell Function: Glucagon secretion from pancreatic α-cells stimulates β-cell insulin secretion via paracrine mechanisms, and increased glucagon release observed in vitro among individuals at risk of diabetes may not translate to differences in vivo, indicating the influence of additional regulatory factors in the physiological environment and the need for further investigation into the clinical significance of these findings. β-cell Carrying Capacity: The maximal insulin secretion potential, or β-cell carrying capacity, defines the threshold for glycemic compensation and is critical in the progression from prediabetes to diabetes. Higher carrying capacity is generally protective, but its effectiveness in reducing diabetes risk may be diminished in certain at-risk groups, potentially due to genetic, metabolic, and environmental factors, underscoring the need to clarify its role in disease disparities. Pancreatic and Metabolic Function in South Asians: Research highlights significant insulin resistance, altered adipocyte insulin sensitivity, diminished β-cell compensation, and increased cardiometabolic risk in some vulnerable groups. Novel biomarkers such as GlycA and LP-IR provide reliable metrics for assessing inflammation and insulin resistance, and incretin and glucagon dynamics offer insight into metabolic regulation in these populations. Pharmacogenetics of GLP-1R Agonists: Genetic factors may modulate individual responses to GLP-1 receptor agonists; however, recent pilot studies using minimal model analysis validate FSIGT as a method for pharmacodynamic assessment, while also demonstrating that observed genetic variants did not significantly influence outcomes, supporting ongoing pharmacogenomic research for tailored diabetes therapeutics.