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

Abstract

Aims/hypothesis: The chemokines monocyte chemoattractant protein-1 (MCP-1), IL-8 and interferon-γ-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. Subjects and methods: 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. Results: 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). Conclusions/interpretation: 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.

Genetic variants in the USF1 gene are associated with low-density lipoprotein cholesterol levels and incident type 2 diabetes mellitus in women: results from the MONICA/KORA Augsburg case–cohort study, 1984–2002

“…On this source population, we applied a case-cohort study consisting of a random sample (called subcohort; nZ1885) of the source population stratified by sex and survey, and all incident T2DM cases (nZ555) in the source population diagnosed up to December 31, 2002 as it was described more detailed previously (31,(35)(36)(37).…”

Inflammation as a link between obesity, metabolic syndrome and type 2 diabetes

“…Indeed, high levels of many inflammatory factors at baseline in diverse human populations are correlated with incident T2DM, regardless of the initial degree of insulin resistance and obesity. Prospective studies have identified white blood cell count [12,15], pro-inflammatory cytokines [16], chemokines [17], and other several indirect markers of inflammation such as fibrinogen, sialic acid and PAI-1 [15,18] as predictors of T2DM. In contrast to all these inflammatory biomarkers, CRP measurement is less expensive, standardized and widely available.…”

Effect of macrophage migration inhibitory factor (MIF) gene variants and MIF serum concentrations on the risk of type 2 diabetes: results from the MONICA/KORA Augsburg Case–Cohort Study, 1984–2002

“…The design of this prospective casecohort study [22], conducted within the population-based MONICA/KORA cohort, has recently been described in detail [23][24][25][26][27][28]. For detailed information on the study population see the Electronic supplementary material (ESM).…”