title: Circulating ferritin concentrations and risk of type 2 diabetes in Japanese individuals.
abstract: OBJECTIVE
  Higher iron storage has been linked to an increased risk of type 2 diabetes, but little is known about the mediator of this association. Here, we prospectively investigated the association between circulating ferritin, a marker of iron storage, and the incidence of type 2 diabetes among Japanese individuals.
  
  
  METHODS
  The participants were 4,754 employees who attended a comprehensive health check-up in 2008-2009 and donated blood for the study. During 5 years of follow up, diabetes was identified based on plasma glucose, glycated hemoglobin and self-report. Two controls matched to each case on sex, age and date of check-up were randomly chosen using density sampling, giving 327 cases and 641 controls with ferritin measurement. Cox proportional hazards regression was used to estimate the hazard ratio while adjusting for a series of potential confounders or mediators.
  
  
  RESULTS
  Elevated serum ferritin levels were associated with a significantly increased risk of type 2 diabetes, with the hazard ratio adjusted for known risk factors in the highest vs lowest quartile of 1.42 (95% confidence interval: 1.03-1.96). This association was unchanged after adjustment for C-reactive protein and adiponectin, but attenuated after adjustment for liver enzyme and insulin resistance (hazard ratio 1.04). The ferritin-diabetes association was confined to non-obese participants.
  
  
  CONCLUSIONS
  These results suggest that elevated iron storage is associated with increased risk of type 2 diabetes in normal weight individuals, and that this association is partly mediated through liver dysfunction and resulting insulin resistance.
authors.affiliation: Department of Epidemiology and Prevention, Bureau of International Health Cooperation, National Center for Global Health and Medicine, Tokyo, Japan.
authors.forename: Shamima
authors.initials: S
authors.lastname: Akter
authors.affiliation: Department of Epidemiology and Prevention, Bureau of International Health Cooperation, National Center for Global Health and Medicine, Tokyo, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Nanri
authors.affiliation: Department of Epidemiology and Prevention, Bureau of International Health Cooperation, National Center for Global Health and Medicine, Tokyo, Japan.|Teikyo University Graduate School of Public Health, Tokyo, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Kuwahara
authors.affiliation: Department of Clinical Research Coordination, Center for Clinical Sciences, National Center for Global Health and Medicine, Tokyo, Japan.
authors.forename: Yumi
authors.initials: Y
authors.lastname: Matsushita
authors.affiliation: Hitachi Health Care Center, Hitachi, Ltd., Ibaraki, Japan.
authors.forename: Tohru
authors.initials: T
authors.lastname: Nakagawa
authors.affiliation: Department of Epidemiology and Prevention, Bureau of International Health Cooperation, National Center for Global Health and Medicine, Tokyo, Japan.
authors.forename: Maki
authors.initials: M
authors.lastname: Konishi
authors.affiliation: Hitachi Health Care Center, Hitachi, Ltd., Ibaraki, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Honda
authors.affiliation: Hitachi Health Care Center, Hitachi, Ltd., Ibaraki, Japan.
authors.forename: Shuichiro
authors.initials: S
authors.lastname: Yamamoto
authors.affiliation: Hitachi Health Care Center, Hitachi, Ltd., Ibaraki, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Hayashi
authors.affiliation: Department of Diabetes Research, Diabetes Research Center, National Center for Global Health and Medicine, Tokyo, Japan.|Department of Endocrinology and Diabetes, Saitama Medical University, Saitama, Japan.
authors.forename: Mitsuhiko
authors.initials: M
authors.lastname: Noda
authors.affiliation: Department of Epidemiology and Prevention, Bureau of International Health Cooperation, National Center for Global Health and Medicine, Tokyo, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Mizoue
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000208:ethnology; D005260:Female; D005293:Ferritins / Q000097:blood*; D006801:Humans; D015994:Incidence; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged
chemical_list: D005293:Ferritins
keywords: Ferritin; Japanese; Type 2 diabetes