1600-P: One Hour OGTT Plasma Glucose as a Biomarker of ß-Cell Function

Progression of hyperglycemia is mediated by loss of β-cell function, but we lack a marker which would be sufficiently accurate and convenient to use in large prospective trials. To determine if the 1 hour OGTT plasma glucose (1hrOGTT) could serve such a purpose, we compared it to standard measures of the disposition index (DI, insulin secretion*insulin action) in 584 European adults without known diabetes in the Relationship between Insulin Sensitivity and Cardiovascular Disease Risk (RISC) study dataset, to predict progression over 3 years. Measures included DImodeling (OGTT modeling β-cell glucose sensitivity*insulin sensitivity), DI-ISI ([0-30min ΔC-peptide/Δglucose]*[1/fasting insulin]), DIclamp (acute C-peptide response to glucose*euglycemic clamp glucose disposal [M/I]), and DIhybrid (OGTT modeling β-cell glucose sensitivity*M/I). Using ADA OGTT criteria, for predicting progression from normal glucose to any dysglycemia (diabetes [DM, FPG >126 or 2hrPG >200 mg/dl] or prediabetes [IFG, FPG 100-125, or IGT, 2hrPG 140-199 mg/dl], n=115), the area under receiver operating characteristic curves (ROC) for the 1hrOGTT was 0.637 vs. 0.607, 0.602, 0.565, and 0.582 for DImodeling, DI-ISI, DIclamp, and DIhybrid, respectively. For non-high risk progressing to high risk dysglycemia ([DM] or [IFG + IGT], n=40), the 1hrOGTT ROC was 0.790 vs. 0.738, 0.737, 0.647, and 0.729 for the DI indices, respectively, and for non-DM progressing to DM (n=6), the 1hrOGTT ROC was 0.910, vs. 0.899, 0.822, 0.741, and 0.837 for the DI indices, respectively. Conclusions: The 1hrOGTT plasma glucose level appears to be comparable or superior to the DI based on more labor-intensive and costly direct assessments of insulin secretion and action in predicting progression of hyperglycemia over 3 years. Consideration should be given to use of the 1hrOGTT glucose as both an accurate and convenient indirect measure of β-cell function in clinical trials, and possibly also of the risk of development and progression of hyperglycemia in clinical practice.