dc.contributor.author | Beyan, H | en_US |
dc.contributor.author | Riese, H | en_US |
dc.contributor.author | Hawa, MI | en_US |
dc.contributor.author | Beretta, G | en_US |
dc.contributor.author | Davidson, HW | en_US |
dc.contributor.author | Hutton, JC | en_US |
dc.contributor.author | Burger, H | en_US |
dc.contributor.author | Schlosser, M | en_US |
dc.contributor.author | Snieder, H | en_US |
dc.contributor.author | Boehm, BO | en_US |
dc.contributor.author | Leslie, RD | en_US |
dc.date.accessioned | 2017-03-09T10:20:00Z | |
dc.date.issued | 2012-05 | en_US |
dc.date.submitted | 2016-10-26T12:08:31.817Z | |
dc.identifier.uri | http://qmro.qmul.ac.uk/xmlui/handle/123456789/19765 | |
dc.description.abstract | In 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.sponsorship | J.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.extent | 1192 - 1198 | en_US |
dc.language | eng | en_US |
dc.relation.ispartof | Diabetes | en_US |
dc.rights | Readers 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.subject | Adolescent | en_US |
dc.subject | Adult | en_US |
dc.subject | Antibody Specificity | en_US |
dc.subject | Autoantibodies | en_US |
dc.subject | Child | en_US |
dc.subject | Diabetes Mellitus, Type 1 | en_US |
dc.subject | Enzyme-Linked Immunosorbent Assay | en_US |
dc.subject | Female | en_US |
dc.subject | Glycation End Products, Advanced | en_US |
dc.subject | Humans | en_US |
dc.subject | Lysine | en_US |
dc.subject | Male | en_US |
dc.subject | Population Surveillance | en_US |
dc.subject | Radioimmunoprecipitation Assay | en_US |
dc.subject | Twins, Dizygotic | en_US |
dc.subject | Twins, Monozygotic | en_US |
dc.subject | Young Adult | en_US |
dc.title | Glycotoxin and autoantibodies are additive environmentally determined predictors of type 1 diabetes: a twin and population study. | en_US |
dc.type | Article | |
dc.rights.holder | © 2012 by the American Diabetes Association. | |
dc.identifier.doi | 10.2337/db11-0971 | en_US |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/22396204 | en_US |
pubs.issue | 5 | en_US |
pubs.notes | Not known | en_US |
pubs.publication-status | Published | en_US |
pubs.volume | 61 | en_US |