Leptin is involved in gender‐related differences in insulin sensitivity

BACKGROUND: Although the effects of insulin on leptin levels are relatively well characterized, the possible actions of leptin on insulin sensitivity are not so well studied. This study was undertaken to examine whether gender-related differences in insulin sensitivity could be explained partially by leptin levels. SUBJECTS: The study involved 22 women (13 obese) and 20 (11 obese) fat mass- and age-matched men. All participants were healthy. MEASUREMENTS: Several anthropometric measures of body fatness were quantified and the percentage of body fat was determined through bioelectric impedance. Oral glucose tolerance test and a frequently sampled intravenous glucose tolerance test was performed in all subjects. Serum leptin was measured by radioimmunoassay. RESULTS: Nine lean women (BMI 20.4 +/- 2 kg m2 mean +/- SD) showed increased leptin levels (7.8 +/- 2.7 vs. 4.3 +/- 1.3 micrograms/l, P = 0.003), increased insulin sensitivity (5.2 +/- 1.3 vs. 2.9 +/- 0.9 min-1/mU/l, P = 0.001) and similar fat mass (11.1 +/- 3.7 vs. 13.2 +/- 7.8 kg, P = NS) in comparison with 9 age-matched lean men (33.6 +/- 6 vs. 34.5 +/- 6.3 years, P = NS). Thirteen obese women (BMI 32.5 +/- 2.7) kg m2 also showed increased leptin levels (29.6 +/- 8.4 vs. 11.7 +/- 4.8 micrograms/l, P < 0.0001), increased insulin sensitivity (1.7 +/- 0.7 vs. 0.95 +/- 0.9 min-1 mU/l, P = 0.04) and similar fat mass (34.4 +/- 8.0 vs. 30.9 +/- 9.6 kg, P = NS) in comparison with 11 age-matched obese men (34.5 +/- 7.8 vs. 38.7 +/- 8.2 years, P = NS). A strong linear association between leptin levels and insulin sensitivity (Si) was found (r = -0.67, P = 0.001, in men; r = -0.82, P < 0.0001, in women). After controlling for percentage of body fat, this association remained significant only in men (r = -0.56, P = 0.01, in men; r = -0.30, P = NS in women). In stepwise regression analysis models, both gender (P = 0.00001) and leptin (P = 0.00001) contributed to 67% of the variance in Si independently of body fat. CONCLUSIONS: Leptin levels and gender contribute to the variance of insulin sensitivity, independently of body fat. These results suggest that leptin could affect insulin sensitivity.