Specific Aim 2

Specific Aim 2 

Investigate molecular mechanisms of T2D in normal-weight Asian individuals, focusing on genetic and metabolic pathways.

Lead Postdoctoral Researcher: Debarun Patra, PhD

Goals: 

  • Exploring mitochondrial function and metabolism in NWA-T2D.
  • Analyzing comparative metabolic phenotypes between NWAT-T2D and European-T2D
  • Evaluating effects of common anti-diabetic medications on NWA and other ethnic groups.
  • Developing tailored therapeutic strategies for NWA-T2D.

Investigating mitochondrial function in Normal Weight Asian (NWA)-T2D utilizing patient iPSCs

Led by: Debarun Patra, PhD

Objectives: 

  • To investigate the role of mitochondrial function in NWA-T2D patients, we will utilize patient-derived iPSCs to preserve genetic integrity and differentiate them into hepatocytes and pancreatic islets.
  • Assess mitochondrial metabolism, function, and biogenesis in these cell types under T2D stress conditions.

Metabolic Profile of Normal Weight Diabetes (NWD) in Asians

Principal Investigator: Tracey McLaughlin, MD, MS

Objectives:

  • To characterize the heterogeneity of NWD with regard to underlying physiology and metabolism.
  • Some individuals are very insulin resistant and some have beta-cell dysfunction and some have both. The reasons for these metabolic profiles also may be impacted by sarcopenia, lipotoxicity (including fatty pancreas), impaired adipocyte fat storage, and genetics.
  • We specifically want to compare the physiologic profiles of NWD vs OWD and Asian vs Caucasian subgroups within the overall cohort.

Beta cell dysfunction disproportionately affects Asian populations and drives susceptibility to T2D

Principal Investigator and Collaborators: Joshua Knowles, MD, PhD; Themistocles (Tim) Assimes, MD, PhD, MS; Justin Annes, MD, PhD

Objectives: 

  • To simultaneously assess insulin resistance and insulin secretion in Asian individuals at risk of diabetes.
  • To determine that the polygenic risk score cluster for beta cell failure (insulin deficiency) is more prevalent in individuals of East and South Asian descent compared to those of European descent.
  • To identify proteomic (Olink platform) biomarkers and morphological measures of beta cell function in individuals of Asian descent.

Validation of NOURISH Project's Culturally Tailored Meals on Postprandial Glycemic Response Using Continuous Glucose Monitoring: A Quantitative and Qualitative Study

Principal Investigator: Minal Moharir, MD

Objectives:

  • Examine whether prescribing and delivering culturally-modified meals is feasible and improves diet quality, food access, food security, and glucose levels of 15 Asian Indians and 15 Filipinos with T2D.
  • By tracking adherence to medically tailored meals and glucose responses, we can better gain insight into reducing diabetes morbidity and improving glycemic control in Asian Indian and Filipino Americans.