Ferritin levels and risk of type 2 diabetes mellitus: an updated systematic review and meta-analysis of prospective evidence.

BACKGROUND: Emerging evidence suggests that a strong link that exists between elevated baseline body iron stores and high risk of incident type 2 diabetes mellitus (T2DM) in general populations, but the precise magnitude of the associations remains uncertain.
METHODS: We conducted a systematic review and meta-analysis of published prospective studies evaluating the associations of baseline ferritin (a biomarker of body iron stores) levels with risk of T2DM in general populations. A subsidiary review of dietary heme iron status and T2DM risk associations was also conducted. Studies were identified in a literature search of PubMed, EMBASE, and Web of Science up to October 2012.
RESULTS: Of the 730 studies reviewed for eligibility, 12 published studies involving 185 462 participants and 11 079 incident T2DM events were included in the analyses. Nine studies assessed associations between ferritin levels and T2DM with heterogeneous findings (I(2)  = 58%, 12-80%, p = 0.014). The pooled fully adjusted relative risk (RR) with (95% confidence interval) for T2DM was 1.73 (1.35-2.22) in a comparison of extreme fifths of baseline ferritin levels. Three studies evaluated associations between dietary heme iron status and T2DM with a corresponding RR for T2DM of 1.28 (1.16-1.41). In dose-response analyses, the pooled RRs for an increment of 5 ng/mL in ferritin levels and 5 mg/day in dietary heme iron were, respectively, 1.01 (0.99-1.02) and 3.24 (2.05-5.10).
CONCLUSION: Elevated levels of ferritin may help identify individuals at high risk of T2DM. Further research is warranted to establish causality of these associations and to ascertain which patients are likely to benefit from lifestyle or therapeutic interventions.