Insulin Resistance and β-Cell Function in South vs. East Asians and Caucasians

Introduction and Objective: Asians have high rates of type 2 diabetes, particularly at normal body weights. The mechanism is unclear but may involve insulin resistance (IR) or impaired β-cell function at lower BMI. We evaluated metabolic function using physiologic tests in a cohort of nondiabetic Asians vs Caucasians stratified by BMI. Methods: 371 adult volunteers without diabetes in metabolic research studies at Stanford University were included. Testing included a 3hr oral glucose tolerance test (OGTT) with glucose and insulin measurements and steady-state plasma glucose (SSPG) testing to quantify IR. Insulin secretion and β-cell function were assessed using the insulinogenic and disposition indexes, respectively. Race comparisons utilized ANOVA adjusted for age, sex, and BMI. Results: Among BMI-matched Asians (67) and Caucasians (304), differences were greatest at BMI <27 kg/m². Asians had higher glucose at all OGTT time points and greater IR without differences in insulin secretion or beta-cell function. South Asians exhibited greater IR, whereas East Asians were more hyperglycemic, not explained by impaired β-cell function. At BMI >27 kg/m², racial differences were minimal except slightly higher glucoses in Asians vs Caucasians. Conclusion: Metabolic differences in Asians vs Caucasians are most pronounced at lower BMI and include greater IR, which is worse in South vs East Asians. The metabolic basis for increased hyperglycemia in East Asians may be due to factors not measured in this study. Disclosure: E. Yandle: None. M. Luzuriaga: None. T. McLaughlin: Research Support; Ended; Lilly. Advisory Panel; Ended; Regeneron Pharmaceuticals Inc. Research Support; Current; Recordati S.p.A. Stock/Shareholder; Current; January, Inc. Research Support; Current; WW International, Inc. Consultant; Ended; Eiger BioPharmaceuticals. Advisory Panel; Current; Amylyx. Consultant; Current; Oura. Research Support; Current; Dexcom, Inc. Funding: American Diabetes Association (9-24-ICTSWH-02)