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000147615 0247_ $$2doi$$a10.1007/s00125-019-05016-3
000147615 0247_ $$2pmid$$apmid:31713011
000147615 0247_ $$2ISSN$$a0012-186X
000147615 0247_ $$2ISSN$$a1432-0428
000147615 0247_ $$2altmetric$$aaltmetric:70422944
000147615 037__ $$aDKFZ-2019-02606
000147615 041__ $$aeng
000147615 082__ $$a610
000147615 1001_ $$00000-0002-1341-6828$$aRolandsson, Olov$$b0
000147615 245__ $$aAutoimmunity plays a role in the onset of diabetes after 40 years of age.
000147615 260__ $$aHeidelberg$$bSpringer$$c2020
000147615 3367_ $$2DRIVER$$aarticle
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000147615 500__ $$a 2020 Feb;63(2):266-277
000147615 520__ $$aType 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.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.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.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.
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000147615 7001_ $$aHampe, Christiane S$$b1
000147615 7001_ $$aSharp, Stephen J$$b2
000147615 7001_ $$aArdanaz, Eva$$b3
000147615 7001_ $$aBoeing, Heiner$$b4
000147615 7001_ $$aFagherazzi, Guy$$b5
000147615 7001_ $$aMancini, Francesca Romana$$b6
000147615 7001_ $$aNilsson, Peter M$$b7
000147615 7001_ $$aOvervad, Kim$$b8
000147615 7001_ $$aChirlaque, Maria-Dolores$$b9
000147615 7001_ $$aDorronsoro, Miren$$b10
000147615 7001_ $$aGunter, Marc J$$b11
000147615 7001_ $$0P:(DE-He78)4b2dc91c9d1ac33a1c0e0777d0c1697a$$aKaaks, Rudolf$$b12$$udkfz
000147615 7001_ $$aKey, Timothy J$$b13
000147615 7001_ $$aKhaw, Kay-Tee$$b14
000147615 7001_ $$aKrogh, Vittorio$$b15
000147615 7001_ $$0P:(DE-He78)0907a10ba1dc8f53f04907f54f6fdcfe$$aKühn, Tilman$$b16$$udkfz
000147615 7001_ $$aPalli, Domenico$$b17
000147615 7001_ $$aPanico, Salvatore$$b18
000147615 7001_ $$aSacerdote, Carlotta$$b19
000147615 7001_ $$aSánchez, Maria-José$$b20
000147615 7001_ $$aSeveri, Gianluca$$b21
000147615 7001_ $$aSpijkerman, Annemieke M W$$b22
000147615 7001_ $$aTumino, Rosario$$b23
000147615 7001_ $$avan der Schouw, Yvonne T$$b24
000147615 7001_ $$aRiboli, Elio$$b25
000147615 7001_ $$aForouhi, Nita G$$b26
000147615 7001_ $$aLangenberg, Claudia$$b27
000147615 7001_ $$aWareham, Nicholas J$$b28
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