Sex-specific Association of Circulating Ferritin Levels and Risk of Type 2 Diabetes: A Dose-response Meta-analysis of Prospective Studies.

Abstract

CONTEXT\nAlthough the role of iron in the development of type 2 Diabetes (T2D) has long been concerned, prospective studies directly linking body iron stores to T2D risk in sex-dependent context still inconsistent.\n\n\nOBJECTIVE\nA systematic meta-analysis was conducted to explore the sex-specific association of circulating ferritin with T2D risk among men and women.\n\n\nDATA SOURCES\nWe searched PubMed, Web of Science, and EMBASE databases to identify available prospective studies through 1 August 2018.\n\n\nRESULTS\nFifteen prospective studies comprising a total of 77,352 participants and 18,404 T2D cases aged 20 to 80 years with approximately 3 to 17 years follow-up durations was identified. In highest vs lowest category, combined participants had a 54% increased risk of T2D associated with ferritin levels (RR=1.54, 95% CI 1.32-1.79). For each 100 μg/L increment in ferritin levels, T2D risk increased by 22% (RR=1.22, 95% CI, 1.14-1.31). Notably, significant heterogeneities by sex were identified in that increased ferritin levels appeared to have a greater impact on T2D risk in women (RR=1.53, 95% CI, 1.29-1.82) than in men (RR=1.21, 95% CI 1.15-1.27) after excluding a study with high heterogeneity (41,512 men and 6,974 women for sex-specific analyses, P = 0.020 for sex difference). Further restricted cubic spline analysis between circulating ferritin and T2D risk also showed sex- dimorphic association in that T2D risk for women were twice as strong in magnitude than that of men at the same ferritin level.\n\n\nCONCLUSIONS\nGreater circulating ferritin levels were independently associated with increased T2D risk, which appeared stronger among women than men. Our findings provide prospective evidence for further testing the utility of circulating ferritin levels as a predicator for T2D risk in a sex-specific manner.