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dc.contributor.authorDe Silva, N Maneka Gen
dc.contributor.authorBorges, Maria Carolinaen
dc.contributor.authorHingorani, Aroon Den
dc.contributor.authorEngmann, Jorgenen
dc.contributor.authorShah, Tinaen
dc.contributor.authorZhang, Xiaoshuaien
dc.contributor.authorLuan, Jian'anen
dc.contributor.authorLangenberg, Claudiaen
dc.contributor.authorWong, Andrewen
dc.contributor.authorKuh, Dianaen
dc.contributor.authorChambers, John Cen
dc.contributor.authorZhang, Weihuaen
dc.contributor.authorJarvelin, Marjo-Rittaen
dc.contributor.authorSebert, Sylvainen
dc.contributor.authorAuvinen, Juhaen
dc.contributor.authorUCLEB consortium,en
dc.contributor.authorGaunt, Tom Ren
dc.contributor.authorLawlor, Deborah Aen
dc.date.accessioned2019-05-15T13:22:59Z
dc.date.available2019-05-15T13:22:59Z
dc.date.issued2019-08en
dc.identifier.issn0012-1797
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/292846
dc.description.abstractABSTRACT Liver dysfunction and type 2 diabetes (T2D) are consistently associated. However, it is currently unknown whether liver dysfunction contributes to, results from or is merely correlated with T2D due to confounding. We used Mendelian randomization (MR) to investigate the presence and direction of any causal relation between liver function and T2D risk including up to 64,094 T2D cases and 607,012 controls. Several biomarkers were used as proxies of liver function [i.e. alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and gamma-glutamyl transferase (GGT)]. Genetic variants strongly associated with each liver function marker were used to investigate the effect of liver function on T2D risk. In addition, genetic variants strongly associated with T2D risk and with fasting insulin were used to investigate the effect of predisposition to T2D and insulin resistance, respectively, on liver function. Genetically predicted higher circulating ALT and AST were related to increased risk of T2D. There was a modest negative association of genetically predicted ALP with T2D risk and no evidence of association between GGT and T2D risk. Genetically predisposition to higher fasting insulin, but not to T2D, was related to increased circulating ALT. Since circulating ALT and AST are markers of NAFLD, these findings provide some support for insulin resistance resulting in NAFLD, which in turn increases T2D risk.
dc.description.sponsorshipThe Fenland Study is funded by the Wellcome Trust and the Medical Research Council (Grant number: MC_U106179471 and MC_UU_12015/1).
dc.format.mediumPrint-Electronicen
dc.languageengen
dc.publisherAmerican Diabetes Association
dc.rightsAll rights reserved
dc.subjectUCLEB consortiumen
dc.subjectLiveren
dc.subjectHumansen
dc.subjectDiabetes Mellitus, Type 2en
dc.subjectInsulin Resistanceen
dc.subjectgamma-Glutamyltransferaseen
dc.subjectAlanine Transaminaseen
dc.subjectAspartate Aminotransferasesen
dc.subjectBlood Glucoseen
dc.subjectFastingen
dc.subjectRisk Factorsen
dc.subjectMendelian Randomization Analysisen
dc.titleLiver Function and Risk of Type 2 Diabetes: Bidirectional Mendelian Randomization Study.en
dc.typeArticle
prism.endingPage1691
prism.issueIdentifier8en
prism.publicationDate2019en
prism.publicationNameDiabetesen
prism.startingPage1681
prism.volume68en
dc.identifier.doi10.17863/CAM.39998
dcterms.dateAccepted2019-05-05en
rioxxterms.versionofrecord10.2337/db18-1048en
rioxxterms.versionAM
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2019-08en
dc.contributor.orcidBorges, Maria Carolina [0000-0001-7785-4547]
dc.contributor.orcidLuan, Jian'an [0000-0003-3137-6337]
dc.contributor.orcidLangenberg, Claudia [0000-0002-5017-7344]
dc.contributor.orcidWong, Andrew [0000-0003-2079-4779]
dc.contributor.orcidGaunt, Tom R [0000-0003-0924-3247]
dc.contributor.orcidLawlor, Deborah A [0000-0002-6793-2262]
dc.identifier.eissn1939-327X
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idMRC (MC_UU_12015/1)
pubs.funder-project-idMRC (MC_PC_13046)
pubs.funder-project-idMedical Research Council (MC_U106179471)
cam.orpheus.successTue Mar 31 10:41:00 BST 2020 - Embargo updated*
rioxxterms.freetoread.startdate2019-08-31


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