Risk of progression to type 2 diabetes based on relationship between postload plasma glucose and fasting plasma glucose

OBJECTIVE - We sought to assess the risk of progression to type 2 diabetes in normal glucose tolerance (NGT) subjects based on the relationship between the plasma glucose concentration during oral glucose tolerance tests (OGTTs) and the fasting plasma glucose (FPG) concentration. RESEARCH DESIGN AND METHODS - Subjects with NGT (n = 1,282) from the San Antonio Heart Study received an OGTT with measurement of the plasma glucose concentration at 0, 30, 60, and 120 min at baseline and after 7-8 years of follow-up. Subjects were divided into four groups based on the relationship between the plasma glucose concentration during the OGTT and the FPG concentration on the same day as the OGTT. Insulin resistance was calculated by the homeostasis model assessment of insulin resistance (HOMA-IR) and Matsuda index. Early-phase insulin secretion was calculated as the ratio between the incremental plasma insulin and glucose concentrations during the first 30 min of the OGTT (ΔI_0-30/ ΔG_0-30). Total insulin secretion was calculated as the ratio between the incremental areas under the insulin and glucose curves during the OGTT [ΔG(AUC)/ΔI(AUC)]. RESULTS - In 23 subjects (group I), the plasma glucose concentration during the OGTT returned to levels below the FPG concentration at 30 min; in 111 subjects (group II) and in 313 subjects (group III), the plasma glucose concentration during the OGTT returned to levels below the FPG concentration at 60 and 120 min, respectively. In the remaining 835 subjects (group IV), the plasma glucose concentration during the OGTT never fell below the FPG concentration. Insulin resistance, measured by HOMA-IR and the Matsuda index, increased progressively from group I through group IV, while insulin secretion measured by ΔI_0-30/ΔG_0-30 and ΔG(AUC)/ΔI(AUC) decreased progressively from group I through group IV. The incidence of type 2 diabetes was 0% in group I and progressively increased to 0.9% in group II, 3.2% in group III, and 6.4% in group IV. CONCLUSIONS - Subjects whose postload plasma glucose concentration returned to baseline (i.e., FPG level) more quickly had greater insulin sensitivity, a higher insulinogenic index, and a lower risk of developing type 2 diabetes after 8 years of follow-up compared with subjects whose postload glucose concentration returned to baseline more slowly.