Low-Grade Chronic Inflammation in the Relationship between Insulin Sensitivity and Cardiovascular Disease (RISC) Population: Associations with insulin resistance and cardiometabolic risk profile

OBJECTIVE: Low-grade chronic inflammation has been hypothesized to underlie the constellation of cardiometabolic risk factors, possibly by inducing insulin resistance. In the present study, we investigated associations between inflammation markers, insulin sensitivity (expressed as the ratio of the M value to the mean plasma insulin concentrations measured during the final 40 min of the clamp [M/I]), and a range of cardiometabolic risk factors in a large, healthy population. RESEARCH DESIGN AND METHODS: The Relationship between Insulin Sensitivity and Cardiovascular Disease (RISC) cohort includes 1,326 nondiabetic European men and women, aged between 30 and 60 years. We measured cardiometabolic risk factors and performed a hyperinsulinemic-euglycemic clamp. We determined total white blood cell count (WBC) and erythrocyte sedimentation rate (ESR) as markers of chronic inflammation. RESULTS: WBC and ESR were both strongly associated with M/I. WBC and ESR were further associated with a range of cardiometabolic risk factors. Associations between WBC and HDL cholesterol, triglycerides, heart rate, fasting C-peptide, and insulin and 2-h insulin in men and women and between WBC and 2-h glucose in women remained significant after adjustment for both M/I and waist circumference. Associations between ESR and HDL cholesterol, heart rate, fasting, and 2-h insulin in men and women and between ESR and fat mass in women remained significant after adjustment for M/I and waist circumference. CONCLUSIONS: This study showed that low-grade chronic inflammation is associated with the cardiometabolic risk profile of a healthy population. Insulin resistance, although strongly associated with inflammation, does not seem to play a large intermediary role.