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dc.contributor.authorPodmore, Claraen
dc.contributor.authorMeidtner, Karinaen
dc.contributor.authorSchulze, Matthias Ben
dc.contributor.authorScott, Roberten
dc.contributor.authorRamond, Annaen
dc.contributor.authorButterworth, Adamen
dc.contributor.authordi, Angelantonio Emanueleen
dc.contributor.authorDanesh, Johnen
dc.contributor.authorArriola, Larraitzen
dc.contributor.authorBarricarte, Aurelioen
dc.contributor.authorBoeing, Heineren
dc.contributor.authorClavel-Chapelon, Françoiseen
dc.contributor.authorCross, Amanda Jen
dc.contributor.authorDahm, Christina Cen
dc.contributor.authorFagherazzi, Guyen
dc.contributor.authorFranks, Paul Wen
dc.contributor.authorGavrila, Dianaen
dc.contributor.authorGrioni, Saraen
dc.contributor.authorGunter, Marc Jen
dc.contributor.authorGusto, Gaelleen
dc.contributor.authorJakszyn, Paulaen
dc.contributor.authorKatzke, Verenaen
dc.contributor.authorKey, Timothy Jen
dc.contributor.authorKühn, Tilmanen
dc.contributor.authorMattiello, Amaliaen
dc.contributor.authorNilsson, Peter Men
dc.contributor.authorOlsen, Anjaen
dc.contributor.authorOvervad, Kimen
dc.contributor.authorPalli, Domenicoen
dc.contributor.authorQuirós, J Ramónen
dc.contributor.authorRolandsson, Oloven
dc.contributor.authorSacerdote, Carlottaen
dc.contributor.authorSánchez-Cantalejo, Emilioen
dc.contributor.authorSlimani, Nadiaen
dc.contributor.authorSluijs, Ivonneen
dc.contributor.authorSpijkerman, Annemieke MWen
dc.contributor.authorTjonneland, Anneen
dc.contributor.authorTumino, Rosarioen
dc.contributor.authorvan, der A Daphne Len
dc.contributor.authorvan, der Schouw Yvonne Ten
dc.contributor.authorFeskens, Edith JMen
dc.contributor.authorForouhi, Nitaen
dc.contributor.authorSharp, Stephenen
dc.contributor.authorRiboli, Elioen
dc.contributor.authorLangenberg, Claudiaen
dc.contributor.authorWareham, Nicholasen
dc.date.accessioned2016-01-22T13:14:13Z
dc.date.available2016-01-22T13:14:13Z
dc.date.issued2016-02-09en
dc.identifier.citationDiabetes Care 2016. DOI: 10.2337/dc15-0257en
dc.identifier.issn0149-5992
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/253424
dc.description.abstractObjective: Observational studies show an association between ferritin and type 2 diabetes (T2D), suggesting a role of high iron stores for T2D development. However, ferritin is influenced by factors other than iron stores, which is less the case for other biomarkers of iron metabolism. We investigate 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 and Design Methods: The EPIC-InterAct study includes 12,403 incident T2D cases and a representative sub-cohort 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 sub-cohort 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 [HR in men and women, respectively: 1.07 (95% CI: 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, centre, BMI, physical activity, smoking status, education, hsCRP, ALT and GGT. Elevated TSAT (≥45% versus <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.
dc.description.sponsorshipWe thank all EPIC participants and staff for their contribution to the study. We thank Nicola Kerrison (MRC Epidemiology Unit, Cambridge) for managing the data for the InterAct Project. We thank Dr Felix Day (MRC Epidemiology Unit, Cambridge) for assistance with figures. Funding for the InterAct project was provided by the EU FP6 programme (grant number LSHM_CT_2006_037197). In addition, InterAct investigators acknowledge funding from the following agencies: IS, JWJB and YTvdS: Verification of diabetes cases was additionally funded by NL Agency grant IGE05012 and an Incentive Grant from the Board of the UMC Utrecht (The Netherlands); HBBdM, AMWS and DLvdA: Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands); FLC: Cancer Research UK; PWF: Swedish Research Council, Novo nordisk, Swedish Heart Lung Foundation, Swedish Diabetes Association; JH, KO and AT: Danish Cancer Society; RK: Deutsche Krebshilfe; SP: Associazione Italiana per la Ricerca sul Cancro; JRQ: Asturias Regional Government; MT: Health Research Fund (FIS) of the Spanish Ministry of Health; the CIBER en Epidemiología y Salud Pública (CIBERESP), Spain; Murcia Regional Government (Nº 6236); RT: AIRE-ONLUS Ragusa, AVIS-Ragusa, Sicilian Regional Government. Biomarker measurements in the EPIC-InterAct subcohort were partially funded by a grant from the UK Medical Research Council and British Heart Foundation (EPIC-Heart: G0800270). Clara Podmore is funded by the Wellcome Trust (097451/Z/11/Z).
dc.languageEnglishen
dc.language.isoenen
dc.publisherAmerican Diabetes Association
dc.titleThe Association of Multiple Biomarkers of Iron Metabolism and Type 2 Diabetes - the EPIC-InterAct Studyen
dc.title.alternativeIron Metabolism and Type 2 Diabetes Incidenceen
dc.typeArticle
dc.description.versionThis is the author accepted manuscript. The final version is available at http://care.diabetesjournals.org/content/early/2016/01/29/dc15-0257.abstract.en
prism.endingPage581
prism.publicationDate2016en
prism.publicationNameDiabetes Careen
prism.startingPage572
prism.volume39en
dc.rioxxterms.funderBHF
dc.rioxxterms.funderMRC
dc.rioxxterms.funderWellcome Trust
dc.rioxxterms.projectidG0800270
dc.rioxxterms.projectid097451/Z/11/Z
dcterms.dateAccepted2016-01-10en
rioxxterms.versionofrecord10.2337/dc15-0257en
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2016-02-09en
dc.contributor.orcidPodmore, Clara [0000-0002-2452-8067]
dc.contributor.orcidRamond, Anna [0000-0002-9958-3693]
dc.contributor.orcidButterworth, Adam [0000-0002-6915-9015]
dc.contributor.orcidDanesh, John [0000-0003-1158-6791]
dc.contributor.orcidForouhi, Nita [0000-0002-5041-248X]
dc.contributor.orcidSharp, Stephen [0000-0003-2375-1440]
dc.contributor.orcidLangenberg, Claudia [0000-0002-5017-7344]
dc.contributor.orcidWareham, Nicholas [0000-0003-1422-2993]
dc.identifier.eissn1935-5548
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idMRC (MC_UU_12015/1)
pubs.funder-project-idMRC (MC_UU_12015/5)
pubs.funder-project-idMRC (G0800270)
pubs.funder-project-idMRC (MC_PC_13046)
pubs.funder-project-idMRC (MR/L003120/1)
pubs.funder-project-idWellcome Trust (097451/Z/11/Z)
pubs.funder-project-idBritish Heart Foundation (RG/08/014/24067)


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