Androgen Response to Endogenous Insulin Secretion during the Frequently Sampled Intravenous Glucose Tolerance Test in Normal and Hyperandrogenic Women*

Publisher Website
Google Scholar
Abstract
Women with ovarian hyperandrogenism frequently have insulin resistance, whose underlying mechanism remains to be determined. In the present study we have investigated the relationship between insulin sensitivity and the acute effect of endogenous insulin secretion on circulating androgen levels. Insulin sensitivity, glucose-mediated insulin release, and glucose/insulin-stimulated androgen responses were determined during a frequently sampled iv glucose tolerance test in a group of 19 women with clinical evidence of polycystic ovary syndrome (PCOS) and 9 age- and weight-matched controls. Insulin (I), glucose, androstenedione, testosterone (T), free T, and dehydroepiandrosterone (DHEA) levels were measured before and during the 3 h following iv administration of glucose (300 mg/kg). Intravenous tolbutamide (300-500 mg) was injected 20 min after the glucose injection. Insulin sensitivity (SI) was calculated by application of the minimal model of glucose kinetics. Fasting androstenedione, T, free T, and I concentrations were significantly higher in the women with PCOS than in controls (P < 0.02). In PCOS subjects, fasting I was correlated with both T (r = 0.51; P < 0.05) and DHEA (r = -0.706; P < 0.01). SI was significantly lower in PCOS subjects [SI, 68.35 .+-. 8.34 min-1/(nmol/mL)) than in control subjects (SI, 133.36 .+-. 21.7 min-1/ (nmol/mL)]. A significant decline in DHEA levels was observed in control subjects 3 h after glucose administration (from 28.4 .+-. 3.0; final, 16.2 .+-. 2.4; P < 0.02). PCOS women with normal insulin sensitivity [SI,>75.0 min-1/(nmol/mL)] showed a similar fall in DHEA (from 20.3 .+-. 2.5 to 12.8 .+-. 1.8 nmol/L; P < 0.02). No significant change occurred in insulin-resistant PCOS subjects [SI, <75.0 min-1/(nmol/mL)]. Other androgen levels showed a modest nonsignificant decline during the study in PCOS and control groups. These findings confirm the weight-independent insulin resistance of some hyperandrogenic women. The failure of glucose stimulated endogenous insulin secretion to significantly depress DHEA levels in insulin-resistant women with PCOS may account in part for their androgen excess.

This publication has 0 references indexed in Scilit: