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@ARTICLE{Rolandsson:147615,
author = {O. Rolandsson and C. S. Hampe and S. J. Sharp and E.
Ardanaz and H. Boeing and G. Fagherazzi and F. R. Mancini
and P. M. Nilsson and K. Overvad and M.-D. Chirlaque and M.
Dorronsoro and M. J. Gunter and R. Kaaks$^*$ and T. J. Key
and K.-T. Khaw and V. Krogh and T. Kühn$^*$ and D. Palli
and S. Panico and C. Sacerdote and M.-J. Sánchez and G.
Severi and A. M. W. Spijkerman and R. Tumino and Y. T. van
der Schouw and E. Riboli and N. G. Forouhi and C. Langenberg
and N. J. Wareham},
title = {{A}utoimmunity plays a role in the onset of diabetes after
40 years of age.},
journal = {Diabetologia},
volume = {63},
number = {2},
issn = {1432-0428},
address = {Heidelberg},
publisher = {Springer},
reportid = {DKFZ-2019-02606},
pages = {266-277},
year = {2020},
note = {2020 Feb;63(2):266-277},
abstract = {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.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.},
cin = {C020},
ddc = {610},
cid = {I:(DE-He78)C020-20160331},
pnm = {313 - Cancer risk factors and prevention (POF3-313)},
pid = {G:(DE-HGF)POF3-313},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:31713011},
doi = {10.1007/s00125-019-05016-3},
url = {https://inrepo02.dkfz.de/record/147615},
}