RESTORED INSULIN SENSITIVITY BUT PERSISTENTLY INCREASED EARLY INSULIN-SECRETION AFTER WEIGHT-LOSS IN OBESE WOMEN WITH POLYCYSTIC-OVARY-SYNDROME

The impact of weight reduction on metabolic, endocrine, and anthropome tric variables was studied in 13 obese, insulin-resistant women with t he polycystic ovary syndrome (PCOS). Insulin sensitivity (euglycemic i nsulin clamp), insulin secretion and glucose tolerance (iv glucose tol erance test), basal sex steroid hormones, gonadotropins and free fatty acids (FFA), skin folds and waist hip ratio (WHR) were evaluated befo re (PCO-BD) and after (PCO-AD) diet-induced weight reduction to a weig ht stable level [mean (so) diet duration 14.9 (6.2) months]. Mean weig ht loss was 12.4 kg (4.7; P < 0.0001), equalling a reduction from a bo dy mass index (BMI) of 32.2 (3.7) kg/m(2) to 27.6 (3.7; P < 0.0001) kg /m(2). The results were compared with those of two groups of weight st able (no diet) women, 21 with PCOS (PCO-ND) and 23 normal control subj ects (C), who were matched to the BMI the diet group reached after wei ght loss. Insulin sensitivity index (M/I) improved on average 132% (P < 0.0001), levels of serum testosterone were reduced by 36% (P < 0.001 ) and plasma FFA by 32% (P < 0.01), serum sex hormone binding globulin levels increased by 35% (P < 0.01), and the sum of truncal-abdominal skinfolds (subscapular, umbilical, and suprailiacal) were reduced by 2 8% (P < 0.0001), whereas the early insulin response to iv glucose, the levels of gonadotropins and androstenedione, and the femoral sc fat d id not change significantly with weight loss. M/I, levels of SHBG and FFA. and truncal-abdominal fat reached levels similar to the controls, whereas PCO-ND had lower M/I (P < 0.01) and SHBG levels (P < 0.0001), greater concentrations of FFA (P < 0.01) and truncal-abdominal fat (P < 0.05) than C. Among women with normal glucose tolerance, the insuli n increment was higher in both PCO-AD (P < 0.05) and PCO-ND (P < 0.01) than in C. There was a strong correlation between Mil and sum of trun cal-abdominal skinfolds in all groups (PCO-BD: r = 0.82; P < 0.001, PC O-AD: r = 0.68; P < 0.05, PCO-ND: r = 0.81; P < 0.0001, C: r = 0.44; P < 0.05). The variation in M/I in PCO-AD and PCO-ND (pooled) was best explained by FFA and truncal-abdominal fat (model R(2) = 0.67). In con clusion, insulin resistance in obese women with PCOS was reduced by we ight loss to similar levels as BMI-matched control subjects, suggestin g that insulin resistance in PCOS is not a feature of PCOS per se. The results underline the strong association between insulin resistance a nd truncal-abdominal fat mass in PCOS. Concomitantly reduced levels of FFA and testosterone may be involved in the improved insulin sensitiv ity. A persistently increased early insulin response to glucose after weight reduction seems to be an abnormality of insulin secretion that is independent of obesity and could provide a stimulus to weight gain in women with PCOS.