Inflammatory Markers and Risk of Type 2 Diabetes: A systematic review and meta-analysis

OBJECTIVE: There has been growing evidence that inflammatory markers play a role in the development of type 2 diabetes. We aimed to systematically review prospective studies on the associations of elevated levels of interleukin-6 (IL-6) and C-reactive protein (CRP) with increased risk of type 2 diabetes by conducting a meta-analysis. RESEARCH DESIGN AND METHODS: A systematic search of the PubMed, EMBASE, ISI Web of Knowledge, and Cochrane Library databases up until 10 February 2012 was conducted to retrieve prospective studies matched to search terms. We used generalized least-squares trend estimation to assess dose-response relationships. The summary risk estimates were pooled using either fixed-effects or random-effects models to incorporate between-study variation. RESULTS: The meta-analysis, including 10 prospective studies, with a total of 19,709 participants and 4,480 cases, detected a significant dose-response association of IL-6 levels with type 2 diabetes risk (relative risk [RR] 1.31 [95% CI 1.17–1.46]). For CRP, the meta-analysis involving 22 cohorts, with a total of 40,735 participants and 5,753 cases, showed that elevated CRP levels were significantly associated with increased risk of type 2 diabetes (1.26 [1.16–1.37]), with the absence of publication bias. Sensitivity and subgroup analyses further supported the associations. CONCLUSIONS: This meta-analysis provides further evidence that elevated levels of IL-6 and CRP are significantly associated with increased risk of type 2 diabetes.