Relationships of Serum Ferritin, Transferrin Saturation, and HFE Mutations and Self-Reported Diabetes Mellitus in the Hemochromatosis and Iron Overload Screening (HEIRS) Study.

Mean serum ferritin concentration (SF) has been positively associated with diabetes mellitus in some racial/ethnic groups. We evaluated the associations of self-reported diabetes mellitus with SF, serum transferrin saturation (TfSat), and HFE C282Y and H63D mutations in six racial/ethnic groups recruited at five Field Centers in the multi-center, primary care-based HEIRS Study. Analyses were conducted on the 97,470 participants for whom pertinent data were available. Participants who reported that they had been previously diagnosed with diabetes mellitus and/or hemochromatosis or iron overload were compared to participants who did not report a previous diagnosis. The overall prevalence of diabetes mellitus was 13.8%; the highest prevalence was observed in Native Hawaiian/Pacific Islanders (20.1%). 2.0% of all participants with diabetes mellitus and 2.2% of whites with diabetes mellitus reported that they also had hemochromatosis or iron overload. Mean SF was elevated in women with diabetes mellitus in all racial/ethnic groups and in American Indian/Alaska Native men with diabetes mellitus. Mean SF was significantly lower in Asian men with diabetes mellitus. Mean TfSat was lower (or not increased) in participants with diabetes mellitus than in those without diabetes mellitus. There was no significant association of diabetes mellitus with HFE genotype. Mean SF was greater (p <0.0001) in women with diabetes mellitus than in those without diabetes mellitus for HFE genotypes except C282Y/C282Y and C282Y/H63D. There was a significant positive association of log SF and diabetes mellitus in a logistic regression analysis after adjusting for age, gender, racial/ethnic group, HFE genotype, and Field Center. We conclude that SF is significantly associated with diabetes mellitus, even at levels of SF below those typically associated with hemochromatosis or iron overload.