Leptin concentrations and insulin sensitivity in normoglycemic men

Objective: Leptin is a hormone regulating weight in the mouse. Leptin regulates food intake and appetite. Leptin concentrations are increased in obese individuals suggesting resistance to its effect. However, there is considerable variability in leptin levels at each level of adiposity suggesting that environmental and genetic factors may regulate leptin concentrations. We examined whether subjects with decreased insulin sensitivity have increased leptin levels. Methods: We used a radioimmunoassay to measure serum leptin levels and the hyperinsulinemic euglycemic clamp (with indirect calorimetry) to measure insulin sensitivity in 87 normoglycemic relatively lean men. Results: Leptin levels were significantly correlated with fasting insulin (r = 0.58), insulin area (r = 0.45), overall (r = -0.57), non-oxidative (r = -0.51) and oxidative (r = -0.51) whole body glucose disposal (all P-values < 0.001). After adjustment for body mass index, leptin levels remained significantly correlated with fasting insulin (r = 0.44), insulin area (r = 0.40), overall (r = -0.40), non-oxidative (r = -0.28) and oxidative (r = -0.33) whole body glucose disposal although the magnitude of the associations was considerably decreased. Leptin levels were significantly related to insulin sensitivity in both less obese and more obese subjects. Conclusions: We conclude that leptin concentrations are related to insulin resistance and insulin concentrations in relatively lean normoglycemic men and these associations are to some extent independent of body mass index. Thus, subjects with insulin resistance may be relatively resistant to the effects of leptin.