278-OR: Higher Static Phase Insulin Secretory Rate Compensates for Lower Insulin Sensitivity in South Asian Youth—The Charisma Study

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Introduction and Objective: South Asian (SA) adult studies suggest insulin deficiency contributes to increased T2D risk. Our prior data found higher OGTT insulin in SA vs. White (W) and African American (AA) adolescents and young adults (AYA). Using mathematical modeling, we aim to investigate this finding by characterizing insulin sensitivity (Si), 1st pass hepatic extraction (HE), and the β-cell’s biphasic insulin secretory rates (ISR).Methods: SA, W, and AA AYA with BMI ≥80%ile (≥23kg/m2 if ≥18y) without diabetes underwent 180-min OGTT with derivation of Si by the oral minimal model, HE by the insulin clearance model, and ISR dynamic (1st phase) and static (2nd phase) by the beta-cell function model. ISR AUC for both phases at 180 min were calculated using the trapezoidal method. Disposition index (DI) for both phases: Si x ISR AUC. Ancestry differences were tested with age, sex, and BMIZ-adjusted robust linear regression.Results: AYA [49 SA of mean age: 19.8y, 52 W: 18.9y, 47 AA: 18.8y, p=0.02] did not differ by sex or BMIZ. SA had lower Si [marginal mean (SE): 5.14 (0.77) 104mu/L-1*min-1] vs W [8.25 (0.74); p=0.004] but not vs AA. SA had borderline higher dynamic ISR AUC vs W (p=0.051) but did not differ from AA. Static ISR AUC was 44.7% higher in SA [marginal mean (SE): 27984 (1267) pmol/l] vs W [19334 (1219), p=0.0001] and 66.0% higher in SA vs AA [16858 (1297), p=0.0001]. HE did not differ for SA vs W, but was 13.8% lower in AA vs SA (p=0.0001). DI for both insulin secretory phases did not differ between SA vs W or vs AA.Conclusion: Higher postprandial hyperinsulinemia in SA AYA is due to hypersecretion rather than lower HE. Static phase insulin hypersecretion in SA AYA may precede β-cell failure and T2D in SA adults. Dynamic phase insulin secretion, which typically compensates for lower Si to preserve DI, was unchanged in SA AYA. Future studies can interrogate the roles of alterations in each insulin secretion phase in the progression to β-cell failure and the emergence of T2D in SA.

Disclosure

T.A. Hitt: None. D. Stefanovski: None. B.S. Zemel: Consultant; Incyte. A. Kelly: None. S.N. Magge: None.

Funding

NIH NDDK (R01DK115648); CTSA NIH support (UL1TR001878, UL1TR00107)



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