South Asian vs. White Adolescents Have Lower Insulin Sensitivity and Higher Insulin AUC

Background: T2D occurs at higher rates in South Asian (SA) adults, even at non-overweight/obese BMI. OGTT metrics were compared in SA vs White (W) adolescents to identify early contributors to increased T2D risk. Methods: Healthy SA and W adolescents, ages 12-21y, with BMI ≥80%ile (or ≥23kg/m2 if ≥18y) underwent 10-sample 180-min OGTT to determine incremental insulin AUC (iAUC), Oral Minimal Model insulin sensitivity (Si), and disposition index (DI: Si x insulin iAUC at 180min). Ancestry differences in OGTT outcomes were compared using linear regression adjusted for age, sex, and BMI. Results: For n=21, age [median (IQR) W: 20.1y (16.1, 21.3), SA: 21.0 (20.3, 21.6)], sex [W: 6F, SA: 4F], and BMI [W: 25.2kg/m2 (24.7, 31.4), SA: 24.6 (24.1, 27.9)] were not different for SA vs W. Fasting glucose [β=7.1, p=0.01; SA: 98.0mg/dL (92.0, 102.5), W: 89.0mg/dL (87.0, 93.5)], fasting insulin [β=7.0, p=0.005], insulin iAUC at 30min [β=1192, p=0.02], and log-transformed insulin iAUC at 180min [β=0.98, p=0.002] were higher, and log-transformed Si [β=-1.07, p=0.008] lower in SA than W. HbA1c, OGTT 1h and 2h glucose, and DI did not differ. Conclusions: Higher OGTT insulin in overweight SA adolescents contrast with reduced insulin found in SA adults and suggests reduced Si and insulin hyper-secretion are precursors to β-cell failure and T2D in SA adults. Understanding T2D mechanistic differences by ancestry may lead to improved T2D treatments. Disclosure T.A.Hitt: None. D.Stefanovski: None. S.Malina: None. C.X.D.Wang: None. B.S.Zemel: None. A.Kelly: None. S.N.Magge: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases (R01DK115648); National Institutes of Health (UL1TR001878, UL1TR001079)