title: Inadequate hepcidin serum concentrations predict incident type 2 diabetes mellitus.
abstract: BACKGROUND
  Type 2 diabetes mellitus (T2DM) is closely associated with elevated body iron stores. The hormone hepcidin is the key regulator of iron homeostasis. Inadequately low hepcidin levels were recently reported in subjects with manifest T2DM. We investigated whether alterations of hepcidin levels precede the manifestation of T2DM and predict T2DM development independently of established risk conditions.
  
  
  METHODS
  This prospective population-based study included 675 subjects aged 50-89 years, 51.9% of whom were female. Hepcidin levels were measured by gold standard tandem mass spectrometry. Diabetes was diagnosed according to American Diabetes Association criteria, and incident diabetes was recorded between baseline in 2000 and 2010.
  
  
  RESULTS
  The baseline hepcidin-to-ferritin ratio in subjects that subsequently developed diabetes during follow-up was reduced on average by 29.8% as compared with subjects with normal glucose tolerance (95% confidence interval, -50.7% to -0.2%; p = 0.049). After adjustment for age, sex, and serum ferritin, higher hepcidin levels were associated with reduced risk of incident diabetes (hazard ratio per 1-unit higher log2 hepcidin, 0.80; 95% confidence interval, 0.64-0.98; p = 0.035; 33 events). Additional adjustment for established diabetes risk factors and determinants of hepcidin concentration did not appreciably change these results (HR, 0.81; 95% CI, 0.66-0.99). Likewise, inadequately low hepcidin levels were also detected in subjects with prevalent T2DM (n = 76).
  
  
  CONCLUSIONS
  Hepcidin levels that are inadequately low in relation to body iron stores are an independent predictor for incident T2DM and may contribute to diabetes-related tissue iron overload. Copyright © 2015 John Wiley & Sons, Ltd.
authors.affiliation: Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Raimund
authors.initials: R
authors.lastname: Pechlaner
authors.affiliation: Department of Internal Medicine VI, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Günter
authors.initials: G
authors.lastname: Weiss
authors.affiliation: Institute of Pharmaceutical Science, King's College London, London, UK.
authors.forename: Sukhvinder
authors.initials: S
authors.lastname: Bansal
authors.affiliation: King's British Heart Foundation Centre, King's College London, London, UK.
authors.forename: Manuel
authors.initials: M
authors.lastname: Mayr
authors.affiliation: Department of Laboratory Medicine, Hospital of Bruneck, Bruneck, Italy.
authors.forename: Peter
authors.initials: P
authors.lastname: Santer
authors.affiliation: Department of Internal Medicine, Hospital of Bruneck, Bruneck, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Pallhuber
authors.affiliation: Department of Internal Medicine, Hospital of Bruneck, Bruneck, Italy.
authors.forename: Marlene
authors.initials: M
authors.lastname: Notdurfter
authors.affiliation: Division of Endocrinology, Diabetes and Metabolic Diseases, University and Hospital Trust of Verona, Verona, Italy.
authors.forename: Enzo
authors.initials: E
authors.lastname: Bonora
authors.affiliation: Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Johann
authors.initials: J
authors.lastname: Willeit
authors.affiliation: Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Stefan
authors.initials: S
authors.lastname: Kiechl
mesh_terms: D000368:Aged; D000890:Anti-Infective Agents / Q000097:blood; D015415:Biomarkers / Q000097:blood*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000175:diagnosis* / Q000453:epidemiology; D005060:Europe / Q000453:epidemiology; D005260:Female; D005293:Ferritins / Q000097:blood*; D005500:Follow-Up Studies; D064451:Hepcidins / Q000097:blood*; D006801:Humans; D015994:Incidence; D008297:Male; D011379:Prognosis; D011446:Prospective Studies; D012307:Risk Factors
chemical_list: D000890:Anti-Infective Agents; D015415:Biomarkers; D064451:Hepcidins; D005293:Ferritins
keywords: hepcidin; iron; iron overload; risk factors; type 2 diabetes mellitus