Glycotoxin and Autoantibodies Are Additive Environmentally Determined Predictors of Type 1 Diabetes
| العنوان: | Glycotoxin and Autoantibodies Are Additive Environmentally Determined Predictors of Type 1 Diabetes |
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| المؤلفون: | Harriëtte Riese, John C. Hutton, Harold Snieder, Howard W. Davidson, G. Beretta, Huibert Burger, Bernhard O. Boehm, Michael Schlosser, Mohammed I. Hawa, Richard David Leslie, Huriya Beyan |
| المصدر: | Diabetes |
| بيانات النشر: | American Diabetes Association, 2012. |
| سنة النشر: | 2012 |
| مصطلحات موضوعية: | Adult, Glycation End Products, Advanced, Male, Radioimmunoprecipitation Assay, Diabetes risk, Adolescent, Endocrinology, Diabetes and Metabolism, Enzyme-Linked Immunosorbent Assay, 030209 endocrinology & metabolism, Human leukocyte antigen, medicine.disease_cause, Autoimmunity, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Antibody Specificity, hemic and lymphatic diseases, Diabetes mellitus, Twins, Dizygotic, Internal Medicine, medicine, Humans, Child, Autoantibodies, 030304 developmental biology, 0303 health sciences, Type 1 diabetes, SLC30A8, biology, Lysine, Autoantibody, Twins, Monozygotic, medicine.disease, Twin study, 3. Good health, Diabetes Mellitus, Type 1, Population Surveillance, Immunology, biology.protein, Female, Immunology and Transplantation |
| الوصف: | In type 1 diabetes, diabetes-associated autoantibodies, including islet cell antibodies (ICAs), reflect adaptive immunity, while increased serum Nε-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. |
| تدمد: | 1939-327X 0012-1797 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1e0447479d817aa5fc8398520da9f732Test https://doi.org/10.2337/db11-0971Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....1e0447479d817aa5fc8398520da9f732 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 1939327X 00121797 |
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