Hyperinsulinemia and sex hormones in healthy premenopausal women: relative contribution of obesity, obesity type, and duration of obesity.

Insulin secretion in response to an oral glucose tolerance test (OGTT) and sex hormone levels (free testosterone, androstenedione, dehydroepiandrosterone sulfate [DHEAS], estradiol, and sex hormone-binding globulin [SHBG]) were evaluated in 49 healthy obese premenopausal women (body mass index [BMI], 30 to 50.6 kg/m2) and 21 control subjects (BMI, 17.8 to 24.0 kg/m2) with normal glucose tolerance and without signs of hyperandrogenism. Obese women were divided into two groups according to waist to hip ratio (WHR): 27 subjects with upper-body obesity (WHR > 0.85) and 22 subjects with lower-body obesity (WHR < 0.8). Both fasting and glucose-induced insulin levels were higher in women with upper-body obesity than in controls (P < .001) and those with lower-body obesity (P < .001). Hyperandrogenism was observed in women with upper-body obesity, as evident by significantly elevated free testosterone (P < .05 v controls and subjects with lower-body obesity) and decreased SHBG (P < .001 v controls). The most important independent determinants of fasting insulin levels were BMI (P < .01) and the ratio of DHEAS to free testosterone (P < .01). The most important determinants of cumulative insulin response were WHR (P < .0005), duration of obesity (P < .01), and androstenedione levels (P < .01). In conclusion, in healthy obese premenopausal women without clinical signs of hyperandrogenism, a high BMI and more pronounced upper-body fat localization resulted in hyperinsulinemia and hyperandrogenism. The duration of obesity exaggerated the glucose-induced insulin level and cumulative insulin response independently of the degree of obesity and obesity type. The ratio of DHEAS to free testosterone was an independent determinant of fasting insulin concentration. Furthermore, the ratio of DHEAS to free testosterone rather than either of these androgens alone may be important in the regulation of insulin action in women.