Autoimmunity plays a role in the onset of diabetes after 40 years of age
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Published:2019-11-11
Issue:2
Volume:63
Page:266-277
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ISSN:0012-186X
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Container-title:Diabetologia
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language:en
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Short-container-title:Diabetologia
Author:
Rolandsson OlovORCID, Hampe Christiane S., Sharp Stephen J., Ardanaz Eva, Boeing Heiner, Fagherazzi Guy, Mancini Francesca Romana, Nilsson Peter M., Overvad Kim, Chirlaque Maria-Dolores, Dorronsoro Miren, Gunter Marc J., Kaaks Rudolf, Key Timothy J., Khaw Kay-Tee, Krogh Vittorio, Kühn Tilman, Palli Domenico, Panico Salvatore, Sacerdote Carlotta, Sánchez Maria-José, Severi Gianluca, Spijkerman Annemieke M. W., Tumino Rosario, van der Schouw Yvonne T., Riboli Elio, Forouhi Nita G., Langenberg Claudia, Wareham Nicholas J.
Abstract
Abstract
Aims/hypothesis
Type 1 and type 2 diabetes differ with respect to pathophysiological factors such as beta cell function, insulin resistance and phenotypic appearance, but there may be overlap between the two forms of diabetes. However, there are relatively few prospective studies that have characterised the relationship between autoimmunity and incident diabetes. We investigated associations of antibodies against the 65 kDa isoform of GAD (GAD65) with type 1 diabetes and type 2 diabetes genetic risk scores and incident diabetes in adults in European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct, a case-cohort study nested in the EPIC cohort.
Methods
GAD65 antibodies were analysed in EPIC participants (over 40 years of age and free of known diabetes at baseline) by radioligand binding assay in a random subcohort (n = 15,802) and in incident diabetes cases (n = 11,981). Type 1 diabetes and type 2 diabetes genetic risk scores were calculated. Associations between GAD65 antibodies and incident diabetes were estimated using Prentice-weighted Cox regression.
Results
GAD65 antibody positivity at baseline was associated with development of diabetes during a median follow-up time of 10.9 years (HR for GAD65 antibody positive vs negative 1.78; 95% CI 1.43, 2.20) after adjustment for sex, centre, physical activity, smoking status and education. The genetic risk score for type 1 diabetes but not type 2 diabetes was associated with GAD65 antibody positivity in both the subcohort (OR per SD genetic risk 1.24; 95% CI 1.03, 1.50) and incident cases (OR 1.97; 95% CI 1.72, 2.26) after adjusting for age and sex. The risk of incident diabetes in those in the top tertile of the type 1 diabetes genetic risk score who were also GAD65 antibody positive was 3.23 (95% CI 2.10, 4.97) compared with all other individuals, suggesting that 1.8% of incident diabetes in adults was attributable to this combination of risk factors.
Conclusions/interpretation
Our study indicates that incident diabetes in adults has an element of autoimmune aetiology. Thus, there might be a reason to re-evaluate the present subclassification of diabetes in adulthood.
Publisher
Springer Science and Business Media LLC
Subject
Endocrinology, Diabetes and Metabolism,Internal Medicine
Reference41 articles.
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