Chemokines as risk factors for type 2 diabetes: results from the MONICA/KORA Augsburg study, 1984-2002

The chemokines monocyte chemoattractant protein-1 (MCP-1), IL-8 and interferon-gamma-inducible protein-10 (IP-10) are released by adipocytes and appear to be involved in atherosclerosis. We hypothesised that these chemokines may be risk factors for the development of type 2 diabetes. Using a case-cohort design based on data from the population-based Monitoring of Trends and Determinants in Cardiovascular Disease (MONICA)/Kooperative Gesundheitsforschung in der Region Augsburg/Cooperative Health Research in the Region of Augsburg (KORA Augsburg) study, chemokine levels at baseline were analysed in 526 individuals with and 1,695 individuals without incident type 2 diabetes. The mean follow-up time was 10.8 years. MCP-1 was associated with type 2 diabetes, largely independently of classic risk factors, whereas various clinical and metabolic parameters as well as lifestyle factors were major confounders of the association of IL-8 and IP-10 with type 2 diabetes. Further adjustment for C-reactive protein (CRP) and IL-6 had no impact on the observed associations. The hazard ratio (HR) for subjects with systemic concentrations of all three chemokines (MCP-1, IL-8 and IP-10) above the respective median compared with those with all chemokines below or equal to the median was 1.79 (95% CI 1.18-2.72) and was comparable with the HR for elevated CRP and IL-6 together (adjusted for age, sex, survey, BMI, systolic blood pressure, total cholesterol:HDL cholesterol ratio, physical activity, alcohol intake, smoking and parental history of diabetes). Elevated concentrations of MCP-1, IL-8 and IP-10 are associated with incident type 2 diabetes. Whereas the association of IL-8 and IP-10 with diabetes was attenuated by multivariable adjustment, high MCP-1 levels contributed to diabetes risk independently of previously described clinical, metabolic and immunological risk factors.