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Am J Physiol Endocrinol Metab 273: E701-E707, 1997;
0193-1849/97 $5.00
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Vol. 273, Issue 4, E701-E707, October 1997

Impaired adaptation of first-phase insulin secretion in postmenopausal women with glucose intolerance

Bo Ahrén1 and Giovanni Pacini2

1 Department of Medicine, Lund University, S-205 02 Malmö, Sweden; and 2 Institute of Systems Science and Biomedical Engineering (LADSEB-Consiglio Nazionale delle Ricerca), I-35127 Padua, Italy

This study examined whether insulin secretion, insulin sensitivity, glucose 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 women (age 63 yr, body mass index range 21.6-28.9 kg/m2) with IGT (n = 10) or normal glucose tolerance (NGT; n = 10). Insulin sensitivity (SI) was significantly lower in IGT than in NGT (P = 0.030). In contrast, insulin secretion was not significantly different between the two groups as determined by area under the curve for insulin and C-peptide, acute insulin response to glucose (AIRG), and glucose sensitivity of 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 significant), SI correlated negatively with phi 1. The B-cell "adaptation index" (SI × 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 index" (SI times AIRG) was lower in IGT (83 ± 25 10-4 min-1) than in NGT (196 ± 30 10-4 min-1, P = 0.011). In contrast, glucose effectiveness or hepatic extraction of insulin was not different between IGT and NGT. We conclude that postmenopausal women with IGT fail to adequately adapt to lowered SI by increasing first-phase insulin secretion.

insulin sensitivity; glucose effectiveness; C-peptide; mathematical modeling; minimal model


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