RELATIONSHIP BETWEEN INSULIN SENSITIVITY AND CIRCULATING SEX HORMONE-BINDING GLOBULIN LEVELS IN HYPERANDROGENIC OBESE WOMEN

The aim of this work was to examine the effect of an insulin infusion on SHBG levels as well as the relationship between SHBG levels and ins ulin sensitivity. Acute insulin infusion was used with the insulin-glu cose clamp technique. The subjects were 14 consecutive well-characteri zed hyperandrogenic non-diabetic obese women without biological and ec hographic symptoms of polycystic ovary syndrome. Adiposity and fat dis tribution were assessed respectively by the body mass index (BMI: 38.7 +/- 1.6 kg/m(2)) and by the waist hip ratio (WHR: 0.91 +/- 0.01). Hyp erandrogenism was evidenced by hirsutism and serum testosterone greate r than 2.8 nM. Circulating SHBG levels were determined in the fasting state by RIA. Insulin sensitivity was assessed using the euglycemic hy perinsulinemic glucose clamp technique with three incremental doses of insulin. Seven non-obese non-hyperandrogenic subjects (BMI: 21.0 +/- 0.6 kg/m(2)) served as controls for the study of the insulin resistanc e state. Because of supraphysiological insulin infusion rates (40, 100 , and 350 mU/min.m(2), each dose for 2 h), insulin sensitivity was mai nly studied at peripheral level. We calculated the Km, i.e. the ED(50) of the dose-response curve, the glucose disposal rate, and the maxima l glucose disposal rate per U insulin (M/I). The hyperandrogenic obese subjects exhibited marked insulin resistance. SHBG levels, although a lready in the lower half of normal in the basal state, decreased from 34.8 +/- 3.4 nmol/l to 29.7 +/- 3.3 nmol/l (P = 0.001; normal values a re 18-83 nmol/l). Basal SHBG levels correlated negatively with plasma insulin levels of the last insulin infusion step (r = -0.55, P < 0.05) and positively with M/I (r = 0.64, P < 0.05). We demonstrate for the first time an in vivo inhibitory effect of insulin on SHBG levels in h yperandrogenic obese women. Taken together reported data, this finding reinforces the idea that insulin is an important determinant of SHBG levels.