Association of Serum Leptin Levels With Homeostasis Model Assessment-Estimated Insulin Resistance and Metabolic Syndrome: The Key Role of Central Obesity

Background: Leptin is correlated with several features of metabolic syndrome; however, possible confounders (eg, obesity) of this association are not known. This study evaluated the relationship between leptin, metabolic syndrome, and insulin resistance in an Iranian population and further investigated whether this relationship is confounded by obesity or central obesity. Methods: A total of 387 participants (18-65 years old) who referred to a large university general hospital for routine health examinations were categorized into 2 groups with (n = 130) and without (n = 257) metabolic syndrome. Fasting plasma glucose, insulin, lipids, and leptin levels were measured and the homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. Metabolic syndrome was defined according to the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criteria. Results: Age-and sex-adjusted leptin levels were significantly higher in patients with than those without metabolic syndrome (29.62 +/- 1.67 vs. 18.50 +/- 1.21 ng/mL, P < 0.001). After adjustment for age, sex, and body mass index (BMI), leptin values were significantly correlated with HOMA-IR (P < 0.001), metabolic syndrome, and its components (P < 0.05). After adjustment for waist circumference, however, these associations were no longer statistically significant. Conclusions: We demonstrated that high leptin levels are associated with insulin resistance and metabolic syndrome independent of BMI but these associations are significantly mediated through the effects of central obesity.