C-reactive protein and the development of the metabolic syndrome and diabetes in middle-aged men

Aims/hypothesis. Low-grade inflammation has been implicated in the development of Type 2 diabetes and cardiovascular disease, but its role in the pathogenesis of the metabolic syndrome is unclear. We investigated the association between C-reactive protein (CRP) levels and the development of the metabolic syndrome and diabetes in men. Methods. Serum CRP concentrations and factors related to insulin resistance were determined in middle-aged Finnish men who participated in a population-based cohort study and were free of diabetes at baseline. Results. At the 11-year follow-up, 143 of 680 men had developed the metabolic syndrome as defined by the National Cholesterol Education Program (NCEP) and 103 of 598 men had developed the metabolic syndrome as defined by the World Health Organization (WHO). Our analyses excluded men with the metabolic syndrome by the respective definition at baseline. In all, 78 of 762 men developed diabetes over the same period. Men with CRP concentrations greater than or equal to3 mg/l had a several-fold higher age-adjusted risk of developing the metabolic syndrome (NCEP definition: odds ratio [OR]=3.2, 95% CI 1.9-5.5; WHO definition: OR=3.4, 95% CI 2.0-6.1) or diabetes (OR=4.1, 95% CI 2.1-8.0) than men whose CRP levels were <1.0 mg/l. Even after further adjustment for potentially confounding lifestyle factors and factors related to insulin resistance, the risk of diabetes (OR=2.3, 95% CI 1.0-5.1) was still increased in men with CRP concentrations greater than or equal to3 mg/l, but the association with the metabolic syndrome was no longer significant. Conclusions/interpretation. Low-grade inflammation may increase the risk of the metabolic syndrome and diabetes in middle-aged men, but some of the risk is mediated through obesity and factors related to insulin resistance.