Association of Multiple Biomarkers of Iron Metabolism and Type 2 Diabetes: The EPIC-InterAct Study-Reference-Cited by-同舟云学术

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

Published:2016-02-09 Issue:4 Volume:39 Page:572-581
ISSN:0149-5992
Container-title:Diabetes Care
language:en
Short-container-title:

Author:

Podmore Clara¹^ORCID,Meidtner Karina²,Schulze Matthias B.²,Scott Robert A.¹,Ramond Anna³,Butterworth Adam S.³,Di Angelantonio Emanuele³,Danesh John³,Arriola Larraitz⁴⁵⁶,Barricarte Aurelio⁶⁷,Boeing Heiner⁸,Clavel-Chapelon Françoise⁹¹⁰,Cross Amanda J.¹¹,Dahm Christina C.¹²,Fagherazzi Guy⁹¹⁰,Franks Paul W.¹³¹⁴,Gavrila Diana⁶¹⁵,Grioni Sara¹⁶,Gunter Marc J.¹¹,Gusto Gaelle⁹¹⁰,Jakszyn Paula¹⁷,Katzke Verena¹⁸,Key Timothy J.¹⁹,Kühn Tilman¹⁸,Mattiello Amalia²⁰,Nilsson Peter M.¹³,Olsen Anja²¹,Overvad Kim¹²²²,Palli Domenico²³,Quirós J. Ramón²⁴,Rolandsson Olov¹⁴,Sacerdote Carlotta²⁵²⁶,Sánchez-Cantalejo Emilio⁶²⁷,Slimani Nadia²⁸,Sluijs Ivonne²⁹,Spijkerman Annemieke M.W.³⁰,Tjonneland Anne²¹,Tumino Rosario³¹³²,van der A Daphne L.³⁰,van der Schouw Yvonne T.²⁹,Feskens Edith J.M.³³,Forouhi Nita G.¹,Sharp Stephen J.¹,Riboli Elio¹¹,Langenberg Claudia¹,Wareham Nicholas J.¹

Affiliation:

1. MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge School of Clinical Medicine, Cambridge, U.K.

2. Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany

3. Department of Public Health and Primary Care, University of Cambridge, Cambridge, U.K.

4. Public Health Division of Gipuzkoa, Basque Government, San Sebastian, Spain

5. Instituto BIO-Donostia, Basque Government, San Sebastian, Spain

6. Consortium for Biomedical Research in Epidemiology and Public Health (CIBER Epidemiología y Salud Pública), Madrid, Spain

7. Navarre Public Health Institute, Pamplona, Navarra, Spain

8. Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany

9. INSERM, CESP Centre for Research in Epidemiology and Population Health, Villejuif, France

10. University Paris-Sud, Villejuif, France

11. Department of Epidemiology & Biostatistics, School of Public Health, Imperial College London, London, U.K.

12. Department of Public Health, Section for Epidemiology, Aarhus University, Aarhus, Denmark

13. Department of Clinical Sciences, Clinical Research Center, Skåne University Hospital, Lund University, Malmö, Sweden

14. Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden

15. Department of Epidemiology, Murcia Regional Health Council, Murcia, Spain

16. Fondazione IRCCS Istituto Nazionale dei Tumori Milan, Milan, Italy

17. Nutrition, Environment and Cancer Unit, Department of Epidemiology, Catalan Institute of Oncology (ICO), Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain

18. Division of Cancer Epidemiology, German Cancer Research Centre (DKFZ), Heidelberg, Germany

19. Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, U.K.

20. Dipartimento di Medicina Clinica e Chirurgia, Federico II University, Naples, Italy

21. Danish Cancer Society Research Center, Copenhagen, Denmark

22. Department of Cardiology, Aalborg University Hospital, Aalborg, Denmark

23. Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute (ISPO), Florence, Italy

24. Consejería de Sanidad, Public Health Directorate, Oviedo-Asturias, Spain

25. Unit of Cancer Epidemiology, AO Citta' della Salute e della Scienza Hospital—University of Turin and Center for Cancer Prevention (CPO), Turin, Italy

26. Human Genetics Foundation (HuGeF), Turin, Italy

27. Escuela Andaluza de Salud Pública, Instituto de Investigación Biosanitaria ibs.Granada, Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain

28. International Agency for Research on Cancer, Dietary Exposure Assessment Group (DEX), Lyon, France

29. Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands

30. National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands

31. Cancer Registry and Histopathology Unit, “Civile - M.P. Arezzo” Hospital, Ragusa, Italy

32. Associazone Iblea per la Ricerca Epidemiologica - Onlus, Ragusa, Italy

33. 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.

Funder

EU FP6 programme

Wellcome Trust

Swedish Research Council

Novo Nordisk

Swedish Heart Lung Foundation

Swedish Diabetes Association

NL Agency

Incentive Grant from the Board of the UMC Utrecht

Dutch Ministry of Public Health

Netherlands Cancer Registry

LK Research Funds