Elevated Interleukin-18 Levels Are Associated With the Metabolic Syndrome Independent of Obesity and Insulin Resistance

Abstract

Objective— Activated innate immunity is thought to be involved in the pathogenesis of metabolic syndrome and type 2 diabetes. Interleukin-18 (IL-18) is a pleiotropic proinflammatory cytokine with important regulatory functions in the innate immune response. We sought to determine whether an elevated IL-18 concentration was a risk predictor for metabolic syndrome in a community population independent of obesity and hyperinsulinemia. Methods and Results— A representative general population, aged 27 to 77 years, without clinical diabetes was studied for clinical and biochemical risk factors for metabolic syndrome. Serum IL-18 concentration measured in 955 subjects correlated with metabolic syndrome traits including body mass index (BMI), waist circumference, triglyceride, high-density lipoprotein (inversely), and fasting glucose and insulin levels (all PPP trend=0.007). The graded risk relation was even stronger in nonobese subjects and not attenuated when adjusted for C-reactive protein and IL-6 levels. Conclusion— Our findings support the hypothesis that activation of IL-18 is involved in the pathogenesis of the metabolic syndrome. We found in a cross-sectional community population that an elevated serum IL-18 level was associated with increased odds ratio for metabolic syndrome independently of obesity and insulin resistance. The risk relation was not attenuated when adjusted for C-reactive protein and IL-6 levels. Our findings support the hypothesis that activation of IL-18 is involved in the pathogenesis of metabolic syndrome.