New Study Reveals Iron's Impact on Sex Differences in Diabetes

Sex-specific prevalence and incidence of T2D have been widely reported, but the biological mechanisms driving these differences remain uncertain. In a new study published in the Journal of Endocrine Society, led by Dr. Farnaz Khatami and a team of scientists from University of Lausanne, Bern, Groningen and Epistudia, new insights were provided on whether iron biomarkers—such as ferritin, transferrin saturation (TSAT), hepcidin, and soluble transferrin receptor (sTfR)—mediate the the difference between men and women in glucose metabolism, as well as the development of T2D.

The study used data from 5,312 individuals (51.3% female) from the general population in Groningen, Netherlands, part of the prospective Prevention of REnal and Vascular ENd-stage Disease (PREVEND) study. The researchers measured levels of ferritin, TSAT, hepcidin, sTfR, fasting plasma glucose (FPG), fasting plasma insulin (FPI), and the incidence of T2D.

The study found that women had lower FPG and FPI levels compared to men, as well as a reduced risk of developing T2D. Specifically, ferritin, hepcidin, and sTfR were shown to mediate the relationship between sex and FPG by 21%, 5%, and 7.1%, respectively. These biomarkers also influenced the association between sex and FPI by 48.6%, 5.7%, and 3.1%, respectively. Interestingly, TSAT played a suppressive role in the connection between sex and both FPG and FPI. Additionally, ferritin accounted for 19.2% of the difference in T2D risk between men and women.

The findings suggest that iron biomarkers are not just passive players but could be actively mediating the differences in glucose metabolism and T2D incidence between men and women. Ferritin stands out as a significant mediator.

While these results are promising, further research is needed to establish causality and explore the mechanisms by which iron influences glucose homeostasis and T2D risk. Understanding these pathways could lead to more personalized and effective strategies for preventing and treating T2D, taking into account the unique biological differences between sexes.

This study represents a significant step forward in our understanding of the complex interplay between sex, iron metabolism, and type 2 diabetes. By shedding light on the potential mediating role of iron biomarkers, the research opens new avenues for investigation and underscores the importance of considering biological sex in diabetes research and treatment.

For those who want to dive deeper into the details, the full study is accessible here.