IMPAIRED ADAPTATION OF FIRST-PHASE INSULIN-SECRETION IN POSTMENOPAUSAL WOMEN WITH GLUCOSE-INTOLERANCE

This study examined whether insulin secretion, insulin sensitivity, gl ucose effectiveness, and hepatic extraction of insulin are altered in subjects with impaired glucose tolerance (IGT). The frequently sampled intravenous glucose tolerance test was performed in postmenopausal wo men (age 63 yr, body mass index range 21.6-28.9 kg/m(2)) with IGT (n = 10) or normal glucose tolerance (NGT; n = 10). Insulin sensitivity (S -I) was significantly lower in IGT than in NGT (P = 0.030). In contras t, insulin secretion was not significantly different between the two g roups as determined by area under the curve for insulin and C-peptide, acute insulin response to glucose (AIR(G)), and glucose sensitivity o f first-phase (phi(1)) or of second-phase (phi(2)) insulin secretion. In NGT (r = -0.68, P = 0.029) but not in IGT (r = -0.05, not significa nt), S-I correlated negatively with phi(1). The B-cell ''adaptation in dex'' (S-I x phi(1)) was lower in IGT than in NGT [83 +/- 25 vs. 171 /- 29 min(-2)/(mmol/l), P = 0.042]. Also, the B-cell ''disposition ind ex'' (S-I times AIR(G)) was lower in IGT (83 +/- 25 10(-4) min(-1)) th an in NGT (196 +/- 30 10(-4) min(-1), P = 0.011). In contrast, glucose effectiveness or hepatic extraction of insulin was not different betw een IGT and NGT. We conclude that postmenopausal women with IGT fail t o adequately adapt to lowered S-I by increasing first-phase insulin se cretion.