Distinct beta-cell defects in impaired fasting glucose and impaired glucose tolerance

To characterize the defects in b-cell function in subjects with impaired fasting glucose (IFG) and compare the results to impaired glucose tolerance (IGT) and normal glucose tolerance (NGT) subjects, b-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 secondphase insulin secretion were quantitated. Compared with NGT, subjects with IFG and IGT manifested a decrease in b-cell glucose sensitivity; IFG subjects, but not IGT subjects, had decreased b-cell rate sensitivity. In IFG subjects, the defect in b-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 (?C-pep [AUC]0-12) was inversely related with the increase in FPG concentration (r = 236, r = 0.001), whereas ?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, firstphase 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 b-cell function in IFG and IGT