Distinct β-Cell Defects in Impaired Fasting Glucose and Impaired Glucose Tolerance

To characterize the defects in beta-cell function in subjects with impaired fasting glucose (IFG) and compare the results to impaired glucose tolerance (IGT) and normal glucose tolerance (NGT) subjects, beta-cell glucose sensitivity and rate sensitivity during the oral glucose tolerance test were measured with the model by Mari in 172 Mexican Americans. A subgroup (n = 70) received a 2-h hyperglycemic clamp (+125 mg/dL), and first- and second-phase insulin secretion were quantitated. Compared with NGT, subjects with IFG and IGT manifested a decrease in beta-cell glucose sensitivity; IFG subjects, but not IGT subjects, had decreased beta-cell rate sensitivity. In IFG subjects, the defect in beta-cell glucose sensitivity was time dependent, began to improve after 60 min, and was comparable to NGT after 90 min. The incremental area under the plasma C-peptide concentration curve during the first 12 min of the hyperglycemic clamp (Delta C-pep [AUC](0-12)) was inversely related with the increase in FPG concentration (r = 36, r < 0.001), whereas Delta C-pep[AUC](15-120) positively correlated with FPG concentration (r = 0.29, r < 0.05). When adjusted for the prevailing level of insulin resistance, first-phase insulin secretion was markedly decreased in both IFG and IGT, whereas second-phase insulin secretion was decreased only in IGT. These results demonstrate distinct defects in beta-cell function in IFG and IGT. Diabetes 61:447-453, 2012