Fasting plasma leptin level is a surrogate measure of insulin sensitivity

Abstract

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.

Figure 1

Regression of fasting plasma leptin levels vs. BMI (A) and fasting insulin levels (B) and of ISI vs. fasting insulin (C) or leptin levels (D). The logarithmic regression equation was Y = 0.134 * e^(−0.055 * X) for ISI vs. fasting insulin and Y = 0.138 * e^(−0.03 * X) for ISI vs. fasting leptin levels. To convert insulin from microunits per milliliter to picomoles per liter, multiply by 6.0.

Figure 2

Logarithmic regression plots of ISI vs. fasting plasma leptin to BMI ratio for all subjects (A), men (B), and women (C). The regression equations are indicated in parentheses.

Figure 3

A and B, Linear regression analyses of ISI vs. BMI indicating BMI cutoff points associated with a normal ISI (≥0.1 μmol/kg · min⁻¹ per picomole per liter) in men (A) and women (B). C and D, Linear regression analyses of ISI vs. fasting leptin levels indicating cutoff points for leptin that are associated with a normal insulin sensitivity (ISI ≥ 0.1 μmol/kg · min⁻¹ per picomole per liter) in men (C) and women (D).

Figure 4

Comparison of ISI in four groups of subjects stratified by BMI and fasting leptin levels. Within each BMI stratum, subjects with fasting leptin less than 15 ng/ml were compared with age-matched subjects with fasting leptin levels of 15 ng/ml or greater. Within the overweight/obese group (BMI ≥ 27 kg/m²), subjects in the two leptin strata were further matched by gender. The rarity of subjects with low BMI and elevated fasting leptin did not permit matching by gender among subjects with BMI less than 27 kg/m². *, Significantly lower than group 1 (P = 0.0001), group 2 (P = 0.0025), and group 3 (P = 0.041); **, significantly lower than group 1 (P = 0.0028) and group 2 (P = 0.04).