American Journal of Epidemiology Advance Access originally published online on February 6, 2007
American Journal of Epidemiology 2007 165(9):1047-1054; doi:10.1093/aje/kwk093
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ORIGINAL CONTRIBUTIONS |
A Prospective Study of Plasma Ferritin Level and Incident Diabetes
The Atherosclerosis Risk in Communities (ARIC) Study
1 Department of Epidemiology and Welch Center for Prevention, Epidemiology, and Clinical Research, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD
2 School of Health Management and Policy, W. P. Carey School of Business, Arizona State University, Tempe, AZ
3 Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD
4 Department of Biostatistics, School of Public Health, University of North Carolina, Chapel Hill, NC
5 Graduate Studies Program in Epidemiology, School of Medicine, Federal University of Rio Grande do Sul, Porto Alegre, Brazil
6 Department of Medicine, Center for Cardiovascular Disease Prevention, Baylor College of Medicine, Houston, TX
7 Department of Anesthesiology, Johns Hopkins Medical Institutions, Baltimore, MD
8 Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN
Correspondence to Dr. Eliseo Guallar, Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins Medical Institutions, 2024 East Monument Street, Room 2-639, Baltimore, MD 21205 (e-mail: eguallar{at}jhsph.edu).
Received for publication June 12, 2006. Accepted for publication October 11, 2006.
The authors performed a case-cohort study nested within the Atherosclerosis Risk in Communities (ARIC) Study to determine the association between plasma ferritin level and risk of type 2 diabetes mellitus. Persons with incident cases of type 2 diabetes diagnosed over an average follow-up period of 7.9 years (n = 599) were compared with a random sample of the cohort (n = 690). After adjustment for age, gender, menopausal status, ethnicity, center, smoking, and alcohol intake, the hazard ratio for diabetes, comparing the fifth quintile of ferritin with the first quintile, was 1.74 (95% confidence interval: 1.14, 2.65; p-trend < 0.001). After further adjustment for body mass index and components of the metabolic syndrome, the hazard ratio was 0.81 (95% confidence interval: 0.49, 1.34; p-trend = 0.87). From a causal perspective, there are two alternative interpretations of these findings. Elevated iron stores, reflected in elevated plasma ferritin levels, may induce baseline metabolic abnormalities that ultimately result in diabetes. Alternatively, elevated ferritin may be just one of several metabolic abnormalities related to the underlying process that ultimately results in diabetes, rather than a causal factor for diabetes. Longitudinal studies with repeated measurements of glucose and iron metabolism parameters are needed to establish the role of iron stores and plasma ferritin in diabetes development.
cohort studies; diabetes mellitus, type 2; ferritins; incidence; iron
Abbreviations: ARIC, Atherosclerosis Risk in Communities; CI, confidence interval
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