The Impact of Abnormalities in IGF and Inflammatory Systems on the Metabolic Syndrome

OBJECTIVE: Low plasma levels of IGF-I, particularly when coupled with low levels of the potentially inhibitory IGF binding protein (IGFBP)-1 and higher levels of C-reactive protein (CRP), have been implicated in the pathogenesis of metabolic syndrome X and cardiovascular disease. We report the relative contributions of IGFBP-1 and CRP to the occurrence of the metabolic syndrome in a healthy population cohort to establish the extent to which these factors may contribute to subsequent risk of cardiovascular disease. RESEARCH DESIGN AND METHODS: The volunteers in the study were all participants in the Ely study, a continuing population-based cohort in Ely, Cambridgeshire, U.K. Of 839 individuals studied, 154 (18.4%) fulfilled criteria for the metabolic syndrome. RESULTS: Subjects with the metabolic syndrome had lower IGFBP-1 (14.4 microg/l [95% CI 12.9-16.0] vs. 25.4 [24.1-26.7], P < 0.001) and higher CRP (1.9 mg/l [1.6-2.2] vs. 1.0 [0.9-1.1], P < 0.001). Logistic regression, adjusted for age, sex, fasting insulin, and IGF-I, demonstrated a striking 14-fold increased risk for the metabolic syndrome (odds ratio 14.1 [4.1-48.4], P < 0.001) in individuals with a CRP value in the highest tertile and IGFBP-1 levels below the median. CONCLUSIONS: The combination of a high CRP concentration coupled with a low IGFBP-1 results in a dramatic increase in an individual's risk of having the metabolic syndrome. Further elucidation of the biological processes linking the IGF and inflammatory systems may allow the identification of novel therapeutic targets for cardiovascular risk reduction.