Context: Published studies indicate marked variability in plasma leptin levels among persons with similar body mass index (BMI). We tested the hypothesis that such variations in leptin levels reflect differences in insulin sensitivity.
Subjects and methods: Using euglycemic clamp, we assessed insulin sensitivity (ISI) in 57 nondiabetic adults (36 women, 21 men), whose BMI ranged from 20 to 78 kg/m2. We identified 38 age-matched subjects, stratified by fasting leptin (normal, <15 ng/ml vs. high, >or=15 ng/ml) and BMI (nonobese, <27 kg/m2 vs. overweight/obese, BMI>or=27 kg/m2) and compared ISI across the four strata.
Results: Fasting leptin levels correlated with ISI (r=-0.66 in men and -0.60 in women). In a multivariate regression model, leptin emerged as a strong predictor of ISI (r=-0.41, P=0.0002) after controlling for adiposity, whereas insulin weakened as a predictor (r=-0.32, P=0.0116). From regression plots of ISI vs. BMI and leptin, a BMI greater than 27 kg/m2 and a leptin level greater than 15 ng/dl strongly predicted decreased ISI. A fasting leptin cutoff of 15 ng/ml for detection of insulin sensitivity has a sensitivity of 72.7%, specificity of 56.3%, and positive predictive value of 69.6%. Overweight/obese subjects with fasting leptin less than 15 ng/ml were 100% more insulin sensitive than control subjects with leptin greater than 15 ng/ml.
Conclusions: Insulin sensitivity explains about 40% of the variance in fasting leptin levels. Thus, fasting plasma leptin levels probably serve as an endogenous response to ambient insulin resistance and may provide a surrogate measure of insulin action.