HYPERLEPTINEMIA AS A COMPONENT OF A METABOLIC SYNDROME OF CARDIOVASCULAR RISK

In humans, production of the adipocyte-derived peptide leptin has been linked to adiposity, insulin, and insulin sensitivity. We therefore c onsidered that alterations in plasma leptin concentrations could const itute an additional component of a metabolic syndrome of cardiovascula r risk. To explore this hypothesis, we employed factor analysis, a mul tivariate statistical technique that allows reduction of large numbers of highly intercorrelated variables to composite, biologically meanin gful factors. Seventy-four men [age, 48.4+/-1.3 years (mean+/-SEM); bo dy mass index (BMI), 25.6+/-0.3 kg/m(2)] who were free of coronary hea rt disease and diabetes underwent anthropometric measurements (subscap ular-to-triceps [S:T] and subscapular-to-biceps [S:B] skinfold thickne ss ratios, measurement of fasting plasma leptin, and an intravenous gl ucose tolerance test (IVGTT) for assessment of insulin sensitivity. Pl asma leptin concentrations were correlated with BMI (r=0.57, P<0.001), S:T (r=0.34, P=0.003), S:B (r=0.37, P<0.001), systolic and diastolic blood pressures (both r=0.24, P=0.044), fasting triglycerides (r=0.31, P=0.007), serum uric acid (r=0.35, P=0.003), fasting glucose (r=0.32, P=0.003) and insulin (r=0.33, P=0.003), and IVGTT insulin (r=0.63, P< 0.001). A negative correlation was observed between leptin and insulin sensitivity (r=-0.32, P=0.006). No significant correlations emerged b etween plasma leptin concentrations and age, high density lipoprotein cholesterol, or IVGTT glucose. In multivariate regression analyses, BM I (standardized coefficient [SC] =0.40, P=0.001), fasting insulin (SC= 0.23, P=0.036), and IVGTT insulin (SC=0.51, P<0.001) emerged as indepe ndent predictors of plasma leptin concentrations (R-2=0.56, P<0.001). After adjustment for BMI, only IVGTT insulin emerged as a significant predictor of plasma leptin concentrations (SC=0.56, P<0.001, R-2=0.45, P<0.001). Factor analysis of plasma leptin concentrations and the var iables that are considered relevant to the insulin resistance syndrome revealed a clustering of plasma leptin concentrations with a factor d ominated by insulin resistance and high IVGTT insulin, separate from a high IVGTT glucose/central obesity factor and a high triglyceride/low high density lipoprotein cholesterol factor. Together, these factors accounted for 55.9% of the total variance in the dataset. In conclusio n, interindividual variations in plasma leptin concentrations are stro ngly related to the principal components of the insulin resistance syn drome. Further studies are needed to determine whether the insulin-lep tin axis plays a coordinating role in this syndrome and whether plasma leptin concentrations could provide an additional measure of cardiova scular risk.