Response of pancreatic beta-cells to improved insulin sensitivity in womenat high risk for type 2 diabetes

The purpose of this study was to examine the response of pancreatic beta-ce lls to changes in insulin sensitivity in women at high risk for type 2 diab etes. Oral glucose tolerance tests (OGTTs) and frequently sampled intraveno us glucose tolerance tests (FSIGTs) were conducted on Latino women with imp aired glucose tolerance and a history of gestational diabetes before and af ter 12 weeks of treatment with 400 mg/day troglitazone (n = 13) or placebo (n = 12), Insulin sensitivity was assessed by minimal model analysis, and b eta-cell insulin release was assessed as acute insulin responses to glucose (AIR(g)) and tolbutamide (AIR(t)) during FSIGTs and as the 30-min incremen tal insulin response (30-min dINS) during OGTTs. beta-Cell compensation for insulin resistance was assessed as the product (disposition index) of mini mal model insulin sensitivity and each of the 3 measures of beta-cell insul in release. In the placebo group, there was no significant change in insuli n sensitivity or in any measure of insulin release, beta-cell compensation for insulin resistance, or glucose tolerance. Troglitazone treatment result ed in a significant increase in insulin sensitivity, as reported previously . In response, AIR(g) did not change significantly so that the disposition index for AIR(g) increased significantly from baseline (P = 0.004) and comp ared with placebo (P = 0.02). AIR(t) (P = 0.001) and 30-min dINS (P = 0.02) fell with improved insulin sensitivity during troglitazone treatment, so t hat the disposition index for each of these measures of beta-cell function did not change significantly from baseline (P > 0.20) or compared with plac ebo (P > 0.3). Minimal model analysis revealed that 89% of the change from baseline in insulin sensitivity during troglitazone treatment was accounted for by lowered plasma insulin concentrations. Neither oral nor intravenous glucose tolerance changed significant ly from baseline or compared with pl acebo during troglitazone treatment, The predominant response of beta-cells to improved insulin sensitivity in women at high risk for type 2 diabetes was a reduction in insulin release to maintain nearly constant glucose tole rance.