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dc.contributor.authorBeyan, Hen_US
dc.contributor.authorRiese, Hen_US
dc.contributor.authorHawa, MIen_US
dc.contributor.authorBeretta, Gen_US
dc.contributor.authorDavidson, HWen_US
dc.contributor.authorHutton, JCen_US
dc.contributor.authorBurger, Hen_US
dc.contributor.authorSchlosser, Men_US
dc.contributor.authorSnieder, Hen_US
dc.contributor.authorBoehm, BOen_US
dc.contributor.authorLeslie, RDen_US
dc.date.accessioned2017-03-09T10:20:00Z
dc.date.issued2012-05en_US
dc.date.submitted2016-10-26T12:08:31.817Z
dc.identifier.urihttp://qmro.qmul.ac.uk/xmlui/handle/123456789/19765
dc.description.abstractIn type 1 diabetes, diabetes-associated autoantibodies, including islet cell antibodies (ICAs), reflect adaptive immunity, while increased serum N(ε)-carboxymethyl-lysine (CML), an advanced glycation end product, is associated with proinflammation. We assessed whether serum CML and autoantibodies predicted type 1 diabetes and to what extent they were determined by genetic or environmental factors. Of 7,287 unselected schoolchildren screened, 115 were ICA(+) and were tested for baseline CML and diabetes autoantibodies and followed (for median 7 years), whereas a random selection (n = 2,102) had CML tested. CML and diabetes autoantibodies were determined in a classic twin study of twin pairs discordant for type 1 diabetes (32 monozygotic, 32 dizygotic pairs). CML was determined by enzyme-linked immunosorbent assay, autoantibodies were determined by radioimmunoprecipitation, ICA was determined by indirect immunofluorescence, and HLA class II genotyping was determined by sequence-specific oligonucleotides. CML was increased in ICA(+) and prediabetic schoolchildren and in diabetic and nondiabetic twins (all P < 0.001). Elevated levels of CML in ICA(+) children were a persistent, independent predictor of diabetes progression, in addition to autoantibodies and HLA risk. In twins model fitting, familial environment explained 75% of CML variance, and nonshared environment explained all autoantibody variance. Serum CML, a glycotoxin, emerged as an environmentally determined diabetes risk factor, in addition to autoimmunity and HLA genetic risk, and a potential therapeutic target.en_US
dc.description.sponsorshipJ.C.H. was supported by the Children’s Diabetes Foundation in Denver, the University of Colorado Denver Diabetes and Endocrinology Research Center (National Institutes of Health [NIH] Grant P30-DK-57516), NIH Grant R01-DK-052068, and the Juvenile Diabetes Research Foundation International Autoimmunity Center Consortium; B.O.B. was supported by Deutsche Forschungsgemeinschaft (DFG SFB 518/ GRK 1041) and State Baden-Wuerttemberg Centre of Excellence “Metabolic Disorders”; and R.D.L. was supported by grants from the British Diabetic Twin Research Trust and the Juvenile Diabetes Research Foundation International. H.Be. was in receipt of an Eli Lilly award.en_US
dc.format.extent1192 - 1198en_US
dc.languageengen_US
dc.relation.ispartofDiabetesen_US
dc.rightsReaders may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.
dc.subjectAdolescenten_US
dc.subjectAdulten_US
dc.subjectAntibody Specificityen_US
dc.subjectAutoantibodiesen_US
dc.subjectChilden_US
dc.subjectDiabetes Mellitus, Type 1en_US
dc.subjectEnzyme-Linked Immunosorbent Assayen_US
dc.subjectFemaleen_US
dc.subjectGlycation End Products, Advanceden_US
dc.subjectHumansen_US
dc.subjectLysineen_US
dc.subjectMaleen_US
dc.subjectPopulation Surveillanceen_US
dc.subjectRadioimmunoprecipitation Assayen_US
dc.subjectTwins, Dizygoticen_US
dc.subjectTwins, Monozygoticen_US
dc.subjectYoung Adulten_US
dc.titleGlycotoxin and autoantibodies are additive environmentally determined predictors of type 1 diabetes: a twin and population study.en_US
dc.typeArticle
dc.rights.holder© 2012 by the American Diabetes Association.
dc.identifier.doi10.2337/db11-0971en_US
pubs.author-urlhttps://www.ncbi.nlm.nih.gov/pubmed/22396204en_US
pubs.issue5en_US
pubs.notesNot knownen_US
pubs.organisational-group/Queen Mary University of London
pubs.organisational-group/Queen Mary University of London/Faculty of Medicine & Dentistry
pubs.organisational-group/Queen Mary University of London/Faculty of Medicine & Dentistry/Blizard Institute
pubs.organisational-group/Queen Mary University of London/Faculty of Medicine & Dentistry/Blizard Institute/Immunobiology
pubs.organisational-group/Queen Mary University of London/REF
pubs.organisational-group/Queen Mary University of London/REF/REF - Blizard
pubs.publication-statusPublisheden_US
pubs.volume61en_US


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