A meta-analysis of 15 prospective studies suggests that elevated levels of circulating ferritin may predict the development of type 2 diabetes, with a stronger association observed for women vs. men, according to findings published in The Journal of Clinical Endocrinology & Metabolism.
“Previous observational studies conducted mainly in [the] U.S. have directly associated [type 2 diabetes] risk with higher iron stores characterized by higher circulating levels of ferritin,” Fudi Wang, PhD, director of the public health and preventive medicine at Zhejiang University School of Medicine in Hangzhou, China, and colleagues wrote in the study background. “However, controversies abound concerning the large heterogeneities and inconsistent findings across diverse populations. Recently, an increasing number of prospective studies from Asian and European countries have also reported significant relation between ferritin levels and [type 2 diabetes] risk, highlighting the important implications of iron for both individual and population health.”
In a meta-analysis, Wang and colleagues analyzed data from 15 prospective studies with 77,352 participants (52,723 men; 18,404 with type 2 diabetes), published between 2004 and 2017. Median follow-up time ranged from 2.8 to 16.8 years. Studies were published in Asia (n = 6), Europe (n = 5) and the United States (n = 4). Researchers used random-effects models to calculate the sex-specific association of circulating ferritin level with type 2 diabetes risk in men and women. Researchers also performed dose-response analyses to evaluate the association between ferritin level and type 2 diabetes risk due to a wide range of definitions across studies for the exposure categories.
Compared with participants in the lowest category of ferritin level, men and women in the highest category of ferritin level were 54% more likely to develop type 2 diabetes during follow-up (RR = 1.54; 95% CI, 1.32-1.79), according to researchers.
For each 100-g/L increment in ferritin levels, researchers found that the risk for developing type 2 diabetes increased by 22% (RR = 1.22; 95% CI, 1.14-1.31). However, in sex-specific sensitivity analyses excluding a study with high heterogeneity, the observed risk for each 100-g/L increment in ferritin levels was nearly twice as high for women (RR = 1.53; 95% CI, 1.29-1.82) vs. men (RR = 1.21; 95% CI, 1.15-1.27; (P for sex difference = .02), according to researchers. Results persisted after excluding a study that included only men.
In sex-specific analyses, geographic location modified the association between ferritin levels and type 2 diabetes risk in women only (P for interaction = .022), according to researchers, with positive associations observed only in Asian studies (RR = 1.29; 95% CI, 1.13-1.47) and European studies (RR = 1.61; 95% CI, 1.34-1.94).
“Sex-specific analysis showed that increased levels of ferritin appeared to have a greater impact on [type 2 diabetes] risk in women than in men,” the researchers wrote. “Our results suggest that circulating ferritin may offer a new realm for prediction of [type 2 diabetes] risk in a sex-specific manner. These findings highlight the importance of investigating the sex-specific etiologies of type 2 diabetes and its associated complications.” – by Regina Schaffer
Disclosures: The authors report no relevant financial disclosures.