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Diabetes Care. 2016 Apr;39(4):572-81. doi: 10.2337/dc15-0257. Epub 2016 Feb 9.

Association of Multiple Biomarkers of Iron Metabolism and Type 2 Diabetes: The EPIC-InterAct Study.

Author information

1
MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge School of Clinical Medicine, Cambridge, U.K. clara.podmore@mrc-epid.cam.ac.uk.
2
Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany.
3
MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge School of Clinical Medicine, Cambridge, U.K.
4
Department of Public Health and Primary Care, University of Cambridge, Cambridge, U.K.
5
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.
6
Consortium for Biomedical Research in Epidemiology and Public Health (CIBER Epidemiología y Salud Pública), Madrid, Spain Navarre Public Health Institute, Pamplona, Navarra, Spain.
7
Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany.
8
INSERM, CESP Centre for Research in Epidemiology and Population Health, Villejuif, France University Paris-Sud, Villejuif, France.
9
Department of Epidemiology & Biostatistics, School of Public Health, Imperial College London, London, U.K.
10
Department of Public Health, Section for Epidemiology, Aarhus University, Aarhus, Denmark.
11
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.
12
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.
13
Fondazione IRCCS Istituto Nazionale dei Tumori Milan, Milan, Italy.
14
Nutrition, Environment and Cancer Unit, Department of Epidemiology, Catalan Institute of Oncology (ICO), Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain.
15
Division of Cancer Epidemiology, German Cancer Research Centre (DKFZ), Heidelberg, Germany.
16
Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, U.K.
17
Dipartimento di Medicina Clinica e Chirurgia, Federico II University, Naples, Italy.
18
Department of Clinical Sciences, Clinical Research Center, Skåne University Hospital, Lund University, Malmö, Sweden.
19
Danish Cancer Society Research Center, Copenhagen, Denmark.
20
Department of Public Health, Section for Epidemiology, Aarhus University, Aarhus, Denmark Department of Cardiology, Aalborg University Hospital, Aalborg, Denmark.
21
Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute (ISPO), Florence, Italy.
22
Consejería de Sanidad, Public Health Directorate, Oviedo-Asturias, Spain.
23
Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden.
24
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.
25
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.
26
International Agency for Research on Cancer, Dietary Exposure Assessment Group (DEX), Lyon, France.
27
Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands.
28
National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands.
29
Cancer Registry and Histopathology Unit, "Civile - M.P. Arezzo" Hospital, Ragusa, Italy Associazone Iblea per la Ricerca Epidemiologica - Onlus, Ragusa, Italy.
30
Division of Human Nutrition, Section of Nutrition and Epidemiology, Wageningen University, Wageningen, the Netherlands.

Abstract

OBJECTIVE:

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.

RESEARCH DESIGN AND METHODS:

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.

RESULTS:

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).

CONCLUSIONS:

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.

PMID:
26861925
PMCID:
PMC5058436
DOI:
10.2337/dc15-0257
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

Duality of Interest. P.W.F. has received funding from Novo Nordisk. No other potential conflicts of interest relevant to this article were reported.

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