Elevated circulating ferritin levels are independently associated with increased risk for type 2 diabetes (T2D), with a greater association observed in women, according to results of a meta-analysis published in The Journal of Clinical Endocrinology & Metabolism.

To examine the sex-specific association between circulating ferritin and T2D risk, researchers conducted a meta-analysis of 15 prospective studies pertaining to circulating ferritin levels. These consisted of 77,352 participants (52,723 men and 24,629 women), including 18,404 cases of T2D (aged 20-80 years). Follow-up durations for the studies ranged from approximately 3 to 17 years.

Compared with participants who had the lowest ferritin levels, both men and women with the highest levels of circulating ferritin were 54% more likely to have T2D. In addition, for every 100 μg/L increase in ferritin, T2D risk increased by an additional 22%. Excluding 1 study with high heterogeneity, the researchers discovered that women were at significantly greater risk for T2D than men when they had increased ferritin levels (risk ratios per 100 μg/L increase in ferritin, 1.53 vs 1.21, respectively).

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Furthermore, using restricted cubic spline analysis, the researchers discovered a sex-dimorphic association between circulating ferritin and T2D risk. As such, risk for T2D was twice as strong in women who had the same ferritin levels as men.

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The researchers were unable to conclude any significant findings about the effects of menopause on the ferritin-T2D association, because few included studies considered menopause status.

“These findings highlight the importance of investigating the sex specific etiologies of type 2 diabetes and its associated complications,” said the researchers. “More attention should be taken on sex dependent relations in the design of future…trials to better understand the associations of circulating ferritin levels with future risk [for] T2D.”

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Jiang L, Wang K, Lo K, et al. Sex-specific association of circulating ferritin levels and risk of type 2 diabetes: a dose-response meta-analysis of prospective studies [published online May 10, 2019]. J Clin Endocrinol Metab. doi:10.1210/jc.2019-00495