A Mathematical Model-Derived Disposition Index Without Insulin Validated in Youth With Obesity.

Abstract

The gold-standard clamp measurements for insulin sensitivity (cSI), β-cell function (cBCF), and disposition index (cDI = cSI × cBCF) are not practical in large-scale studies. We sought to 1) validate a mathematical model-derived DI from oral glucose tolerance tests (OGTT) with insulin (mDI) and without (mDI-woI) against cDI and oral disposition index (oDI) and 2) evaluate the ability of the novel indices to detect prediabetes and type 2 diabetes (T2D). We carried out a secondary analysis of previously reported cross-sectional observational studies. The Insulin Sensitivity and Secretion mathematical model for glucose-insulin dynamics was applied to 5-point and 3-point OGTTs synchronized with hyperinsulinemic-euglycemic and hyperglycemic clamps from 130 youth with obesity (68 normal glucose tolerance [NGT], 33 impaired glucose tolerance [IGT], 29 T2D). Model-derived DI correlated well with clamp DI (R = 0.76 [logged]). Between NGT and IGT, mDI and mDI-woI decreased more than oDI and cDI, (60% and 59% vs 29% and 27%), and by receiver operating characteristic analysis were superior at detecting IGT compared with oDI and cDI (area under the curve [AUC] 0.88-0.87 vs 0.68-0.65), as was mean glucose (AUC 0.87). mDI-woI is better than oDI or the labor-intensive cDI for detecting dysglycemia in obese youth. Bypassing insulin measurements with mDI-woI from the OGTT provides a cost-effective approach for large-scale epidemiological studies of dysglycemia in youth.