title: Association of Multiple Biomarkers of Iron Metabolism and Type 2 Diabetes: The EPIC-InterAct Study.
abstract: Observational studies show an association between ferritin and type 2 diabetes (T2D), suggesting a role of high iron stores in T2D development. However, ferritin is influenced by factors other than iron stores, which is less the case for other biomarkers of iron metabolism. We investigated associations of ferritin, transferrin saturation (TSAT), serum iron, and transferrin with T2D incidence to clarify the role of iron in the pathogenesis of T2D.
  
  
  
  The European Prospective Investigation into Cancer and Nutrition-InterAct study includes 12,403 incident T2D cases and a representative subcohort of 16,154 individuals from a European cohort with 3.99 million person-years of follow-up. We studied the prospective association of ferritin, TSAT, serum iron, and transferrin with incident T2D in 11,052 cases and a random subcohort of 15,182 individuals and assessed whether these associations differed by subgroups of the population.
  
  
  
  Higher levels of ferritin and transferrin were associated with a higher risk of T2D (hazard ratio [HR] [95% CI] in men and women, respectively: 1.07 [1.01-1.12] and 1.12 [1.05-1.19] per 100 μg/L higher ferritin level; 1.11 [1.00-1.24] and 1.22 [1.12-1.33] per 0.5 g/L higher transferrin level) after adjustment for age, center, BMI, physical activity, smoking status, education, hs-CRP, alanine aminotransferase, and γ-glutamyl transferase. Elevated TSAT (≥45% vs. <45%) was associated with a lower risk of T2D in women (0.68 [0.54-0.86]) but was not statistically significantly associated in men (0.90 [0.75-1.08]). Serum iron was not associated with T2D. The association of ferritin with T2D was stronger among leaner individuals (Pinteraction < 0.01).
  
  
  
  The pattern of association of TSAT and transferrin with T2D suggests that the underlying relationship between iron stores and T2D is more complex than the simple link suggested by the association of ferritin with T2D.
authors: MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge School of Clinical Medicine, Cambridge, U.K. clara.podmore@mrc-epid.cam.ac.uk.
authors: Clara
authors: 0000-0002-2452-8067
authors: C
authors: Podmore
authors: Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany.
authors: Karina
authors: K
authors: Meidtner
authors: Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany.
authors: Matthias B
authors: MB
authors: Schulze
authors: MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge School of Clinical Medicine, Cambridge, U.K.
authors: Robert A
authors: RA
authors: Scott
authors: Department of Public Health and Primary Care, University of Cambridge, Cambridge, U.K.
authors: Anna
authors: A
authors: Ramond
authors: Department of Public Health and Primary Care, University of Cambridge, Cambridge, U.K.
authors: Adam S
authors: AS
authors: Butterworth
authors: Department of Public Health and Primary Care, University of Cambridge, Cambridge, U.K.
authors: Emanuele
authors: E
authors: Di Angelantonio
authors: Department of Public Health and Primary Care, University of Cambridge, Cambridge, U.K.
authors: John
authors: J
authors: Danesh
authors: Public Health Division of Gipuzkoa, Basque Government, San Sebastian, Spain Instituto BIO-Donostia, Basque Government, San Sebastian, Spain Consortium for Biomedical Research in Epidemiology and Public Health (CIBER Epidemiología y Salud Pública), Madrid, Spain.
authors: Larraitz
authors: L
authors: Arriola
authors: Consortium for Biomedical Research in Epidemiology and Public Health (CIBER Epidemiología y Salud Pública), Madrid, Spain Navarre Public Health Institute, Pamplona, Navarra, Spain.
authors: Aurelio
authors: A
authors: Barricarte
authors: Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany.
authors: Heiner
authors: H
authors: Boeing
authors: INSERM, CESP Centre for Research in Epidemiology and Population Health, Villejuif, France University Paris-Sud, Villejuif, France.
authors: Françoise
authors: F
authors: Clavel-Chapelon
authors: Department of Epidemiology & Biostatistics, School of Public Health, Imperial College London, London, U.K.
authors: Amanda J
authors: AJ
authors: Cross
authors: Department of Public Health, Section for Epidemiology, Aarhus University, Aarhus, Denmark.
authors: Christina C
authors: CC
authors: Dahm
authors: INSERM, CESP Centre for Research in Epidemiology and Population Health, Villejuif, France University Paris-Sud, Villejuif, France.
authors: Guy
authors: G
authors: Fagherazzi
authors: Department of Clinical Sciences, Clinical Research Center, Skåne University Hospital, Lund University, Malmö, Sweden Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden.
authors: Paul W
authors: PW
authors: Franks
authors: Consortium for Biomedical Research in Epidemiology and Public Health (CIBER Epidemiología y Salud Pública), Madrid, Spain Department of Epidemiology, Murcia Regional Health Council, Murcia, Spain.
authors: Diana
authors: D
authors: Gavrila
authors: Fondazione IRCCS Istituto Nazionale dei Tumori Milan, Milan, Italy.
authors: Sara
authors: S
authors: Grioni
authors: Department of Epidemiology & Biostatistics, School of Public Health, Imperial College London, London, U.K.
authors: Marc J
authors: MJ
authors: Gunter
authors: INSERM, CESP Centre for Research in Epidemiology and Population Health, Villejuif, France University Paris-Sud, Villejuif, France.
authors: Gaelle
authors: G
authors: Gusto
authors: Nutrition, Environment and Cancer Unit, Department of Epidemiology, Catalan Institute of Oncology (ICO), Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain.
authors: Paula
authors: P
authors: Jakszyn
authors: Division of Cancer Epidemiology, German Cancer Research Centre (DKFZ), Heidelberg, Germany.
authors: Verena
authors: V
authors: Katzke
authors: Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, U.K.
authors: Timothy J
authors: TJ
authors: Key
authors: Division of Cancer Epidemiology, German Cancer Research Centre (DKFZ), Heidelberg, Germany.
authors: Tilman
authors: T
authors: Kühn
authors: Dipartimento di Medicina Clinica e Chirurgia, Federico II University, Naples, Italy.
authors: Amalia
authors: A
authors: Mattiello
authors: Department of Clinical Sciences, Clinical Research Center, Skåne University Hospital, Lund University, Malmö, Sweden.
authors: Peter M
authors: PM
authors: Nilsson
authors: Danish Cancer Society Research Center, Copenhagen, Denmark.
authors: Anja
authors: A
authors: Olsen
authors: Department of Public Health, Section for Epidemiology, Aarhus University, Aarhus, Denmark Department of Cardiology, Aalborg University Hospital, Aalborg, Denmark.
authors: Kim
authors: K
authors: Overvad
authors: Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute (ISPO), Florence, Italy.
authors: Domenico
authors: D
authors: Palli
authors: Consejería de Sanidad, Public Health Directorate, Oviedo-Asturias, Spain.
authors: J Ramón
authors: JR
authors: Quirós
authors: Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden.
authors: Olov
authors: O
authors: Rolandsson
authors: Unit of Cancer Epidemiology, AO Citta' della Salute e della Scienza Hospital-University of Turin and Center for Cancer Prevention (CPO), Turin, Italy Human Genetics Foundation (HuGeF), Turin, Italy.
authors: Carlotta
authors: C
authors: Sacerdote
authors: Consortium for Biomedical Research in Epidemiology and Public Health (CIBER Epidemiología y Salud Pública), Madrid, Spain Escuela Andaluza de Salud Pública, Instituto de Investigación Biosanitaria ibs.Granada, Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain.
authors: Emilio
authors: E
authors: Sánchez-Cantalejo
authors: International Agency for Research on Cancer, Dietary Exposure Assessment Group (DEX), Lyon, France.
authors: Nadia
authors: N
authors: Slimani
authors: Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands.
authors: Ivonne
authors: I
authors: Sluijs
authors: National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands.
authors: Annemieke M W
authors: AM
authors: Spijkerman
authors: Danish Cancer Society Research Center, Copenhagen, Denmark.
authors: Anne
authors: A
authors: Tjonneland
authors: Cancer Registry and Histopathology Unit, "Civile - M.P. Arezzo" Hospital, Ragusa, Italy Associazone Iblea per la Ricerca Epidemiologica - Onlus, Ragusa, Italy.
authors: Rosario
authors: R
authors: Tumino
authors: National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands.
authors: Daphne L
authors: DL
authors: van der A
authors: Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands.
authors: Yvonne T
authors: YT
authors: van der Schouw
authors: Division of Human Nutrition, Section of Nutrition and Epidemiology, Wageningen University, Wageningen, the Netherlands.
authors: Edith J M
authors: EJ
authors: Feskens
authors: MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge School of Clinical Medicine, Cambridge, U.K.
authors: Nita G
authors: NG
authors: Forouhi
authors: MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge School of Clinical Medicine, Cambridge, U.K.
authors: Stephen J
authors: SJ
authors: Sharp
authors: Department of Epidemiology & Biostatistics, School of Public Health, Imperial College London, London, U.K.
authors: Elio
authors: E
authors: Riboli
authors: MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge School of Clinical Medicine, Cambridge, U.K.
authors: Claudia
authors: C
authors: Langenberg
authors: MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge School of Clinical Medicine, Cambridge, U.K.
authors: Nicholas J
authors: NJ
authors: Wareham
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000410:Alanine Transaminase / Q000097:blood; D015415:Biomarkers / Q000097:blood*; D002097:C-Reactive Protein / Q000378:metabolism; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000453:epidemiology*; D005260:Female; D005293:Ferritins / Q000097:blood / Q000378:metabolism; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D007501:Iron / Q000097:blood* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D014168:Transferrin / Q000378:metabolism; D055815:Young Adult; D005723:gamma-Glutamyltransferase / Q000097:blood
chemical_list: D015415:Biomarkers; D014168:Transferrin; D002097:C-Reactive Protein; D005293:Ferritins; D007501:Iron; D005723:gamma-Glutamyltransferase; D000410:Alanine Transaminase