148-OR: Increased Insulin Secretion and Decreased Insulin Sensitivity in South Asian Youth without Diabetes

Introduction & Objective: The mechanisms underlying increased T2DM risk at lower BMI in South Asians (SA) compared to other ancestries are not known, but greater visceral fat (VFAT) for given BMI has been implicated. We examined the relationships of VFAT with insulin sensitivity (Si) and insulin secretory rate (ISR) in SA vs White (W) and African American (AA) adolescents and young adults (AYA).

Methods: SA, W, and AA aged 12-21y, BMI ≥ 80%ile for age and sex or BMI ≥ 23 kg/m², without diabetes, underwent DXA for VFAT area and a 3-hr, 10-sample OGTT with Si by Minimal Model, and ISR by parametric deconvolution of C-peptide kinetics (2-compartment model). ISR incremental AUC was calculated. Ancestry groups were compared using Kruskal Wallis or chi2; Spearman correlations tested associations between VFAT and metabolic indices. Linear regression with adjustment for age, sex and inclusion of a VFAT-by-ancestry interaction term examined ancestry differences in Si and ISR.

Results: AYA (n= 51 SA, 39 W, 25 AA) were of similar age (median (IQR); SA 20.3y (18.9, 21.5); W 19.3y (18.3, 21.1); AA 19.0y (18.0, 20.4)), BMIZ (mean ± SD; SA 1.21 ± 0.53; W 1.14 ± 0.57; AA 1.38 ± 0.60), and BMI (SA 27.9 kg/m² (25.1, 29.4); W 25.9 (24.6, 29.7); AA 27.3 (25.3, 35.5)), but differed by female sex: SA 52.9%; W 56.4%; AA 88.0% (p=0.009). SA had higher VFAT (97.5 cm² (82.0,121.0)) than W (87.2 (64.1,108.0) and AA (75.0 (51.2,102), p= 0.029. One cm² increase in VFAT associated with 41% lower Si (p=0.03) and 82% greater increase in ISR (p<0.001) in SA compared to W. Compared to AA, for 1cm² VFAT increase, SA had similar Si decrease, but 82% greater ISR increase (p=0.004).

Conclusion: Among AYA of similar BMI, SA had higher VFAT than W and AA. However, for similar increase in VFAT, SA had a greater reduction in Si and higher ISR increase compared to W. SA had a similar reduction in Si compared to AA, but again a greater increase in ISR. Thus, the higher T2DM risk in SA may be due to greater hyperinsulinemic compensation, resulting in beta cell exhaustion.