C-peptide and insulin, but not C19-steroids, support the predictive value of body mass index on leptin in serum of premenopausal women

Hyperleptinaemia is known to be positively associated with obesity in females. Therefore, circulating leptin concentrations are predicted by body mass index (BMI). Additional effects of endogenous C19-steroids, sex hormone binding globulin (SHBG), luteinizing hormone (LH), follicle stimulating hormone (FSH), C-peptide and insulin on the predictive value of BMI on serum leptin were investigated in 56 hyperandrogenaemic and/or hyperinsulinaemic and/or obese premenopausal women. Serum concentrations (after an overnight 12 h fast) of leptin, total testosterone, free testosterone, SHBG, dehydroepiandrosterone sulphate (DHEAS), LH, FSH, and oestradiol as well as serum concentrations of C- peptide and insulin prior to, and 1 h after, an oral 100 mg glucose load (1 h values) were determined by immunoassays. Subjects with regular menstrual cycles were studied in the mid-follicular phase while the remainder were studied at random. Nineteen normotestosteronaemic, normoinsulinaemic, lean and ovulatory volunteers served as controls; in order to determine the effect of different stages of the menstrual cylce, serum concentrations of leptin (and of oestradiol in 12 out of the 19 individuals) were determined at the preovulatory, the mid-luteal and the following mid-follicular phase. Significant differences between the patients versus control were not found possibly because of the heterogeneity in the patient group. Multiple regression indicated a hyperbolic correlation between BMI and leptin concentrations. As expected, BMI was the major determinant responsible for >50% (R2=0.51) of the elevation of leptin concentrations. The combination of BMI with fasting C-peptide or fasting insulin enhanced the R2 up to 0.59. The multiple regression with two explaining parameters showed a significant regression coefficient for BMI at the 0.001 level, and for fasting C- peptide and fasting insulin at the 0.01 level, which was as statistically significant as the combination of BMI with the 1 h values of C-peptide and of insulin. In contrast, total testosterone, free testosterone, SHBG, free testosterone/SHBG ratio, DHEAS and LH/FSH ratio had no effect. Similarly, models with more than two variables did not measurably improve the explained variation. In the control group, leptin concentrations were significantly higher in preovulatory and mid- luteal phases than the two mid-follicular phases (P < or = 0.05) and must be considered when determining sampling time. In conclusion, hyperandrogenaemia does not have a predictive value on leptin concentrations in premenopausal subjects but hyperinsulinaemia exerts an effect independent of obesity that is the strongest predictor for elevation of leptin concentrations. Hyperinsulinaemia might contribute to the hyperbolic correlation of circulating leptin in obese patients.