Increased circulating leptin concentrations in insulin-resistant first-degree relatives of patients with non-insulin-dependent diabetes mellitus: Relationship to body composition and insulin sensitivity but not to family history of non-insulin-dependent diabetes mellitus

Objective: To explore a possible association between serum concentration of leptin, insulin sensitivity and non-insulin-dependent diabetes mellitus (NIDDM), Design: Forty first-degree relatives of NIDDM patients and 35 control subjects matched for age, gender and body mass index underwent a hyperinsulinaemic (insulin infusion rate 0.6 mU/kg per min) euglycaemic clamp combined with indirect calorimetry. Serum leptin was measured in fasting blood samples obtained before the clamp, Results: All subjects had a normal oral glucose tolerance test. Insulin-stimulated glucose uptake (M) was decreased in the relatives compared with the control subjects (4.58+/-0.27 versus 6.06+/-0.25 mg/kg per min, P<0.001). Conversely, serum leptin was increased in the relatives (9.6 ./divided by 1.1 versus 6.1 ./divided by 1.2 ng/ml (geometric mean ./divided by antilog S.E.M.), P<0.05) A positive correlation was observed between circulating levels of leptin and percentage body fat (P<0.001) and inverse correlations were found between leptin, M (P<0.01), mardmal aerobic capacity (VO2 max) (P<0.01), and energy expenditure (P less than or equal to 0.01) in both groups. In multiple linear regression analysis, percentage body fat, gender and M significantly detennined the level of leptin (r(2)=0.71, P<0.001) whereas family history of NIDDM and VO2 max did not. Conclusion: Serum leptin is increased in insulin-resistant offspring of MDDM patients. The association behveen leptin, anthropometric measures and insulin sensitivity is, however, comparable with that of a control group. The increased concentrations of serum leptin in the relatives appear to be associated with the insulin resistance, but not with a family history of NIDDM.