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

¹ Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama
² Southern Iron Disorders Center, Birmingham, Alabama
³ Department of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, North Carolina
⁴ Department of Medicine, London Health Sciences Centre, London, Ontario, Canada
⁵ Department of Epidemiology and Biostatistics, University of Western Ontario, London, Ontario, Canada
⁶ Department of Medicine, Howard University, Washington, DC
⁷ Epidemiology and Biometry Program, National Heart, Lung, and Blood Institute, Bethesda, Maryland
⁸ Department of Medicine, University of California, Irvine, California
⁹ Veterans Affairs Long Beach Healthcare System, Long Beach, California
¹⁰ Kaiser Permanente Center for Health Research, Portland, Oregon, and Honolulu, Hawaii

Address correspondence and reprint requests to Ronald T. Acton, PhD, MCLM 265, 1530 3rd Ave. South, Birmingham, AL 35294-0005. E-mail: acton{at}uab.edu

OBJECTIVE—We evaluated the associations of self-reported diabetes with serum ferritin concentration, transferrin saturation (TfSat), and HFE C282Y and H63D mutations in six racial/ethnic groups recruited at five field centers in the Hemochromatosis and Iron Overload Screening (HEIRS) study.

RESEARCH DESIGN AND METHODS—Analyses were conducted on 97,470 participants. Participants who reported a previous diagnosis of diabetes and/or hemochromatosis or iron overload were compared with participants who did not report a previous diagnosis.

RESULTS—The overall prevalence of diabetes was 13.8%; the highest prevalence was in Pacific Islanders (20.1%). Of all participants with diabetes, 2.0% reported that they also had hemochromatosis or iron overload. The mean serum ferritin concentration was significantly greater in women with diabetes in all racial/ethnic groups and in Native-American men with diabetes than in those without diabetes. The mean serum ferritin concentration was significantly lower in Asian men with diabetes than in those without diabetes. Mean TfSat was lower in participants with diabetes from all racial/ethnic groups except Native-American women than in those without diabetes. There was no significant association of diabetes with HFE genotype. The mean serum ferritin concentration was greater (P < 0.0001) in women with diabetes than in those without diabetes for HFE genotypes except C282Y/C282Y and C282Y/H63D. Log serum ferritin concentration was significantly associated with diabetes in a logistic regression analysis after adjusting for age, sex, racial/ethnic group, HFE genotype, and field center.

CONCLUSIONS—Serum ferritin concentration is associated with diabetes, even at levels below those typically associated with hemochromatosis or iron overload.

Abbreviations: BRFSS, Behavioral Risk Factor Surveillance System • HEIRS, Hemochromatosis and Iron Overload Screening • NHANES III, National Health and Nutrition Examination Survey III • TfSat, transferrin saturation

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