RT Journal Article
T1 Autoimmunity plays a role in the onset of diabetes after 40 years of age.
A1 Rolandsson, Olov
A1 Hampe, Christiane S
A1 Sharp, Stephen J
A1 Ardanaz, Eva
A1 Boeing, Heiner
A1 Fagherazzi, Guy
A1 Mancini, Francesca Romana
A1 Nilsson, Peter M
A1 Overvad, Kim
A1 Chirlaque, Maria-Dolores
A1 Dorronsoro, Miren
A1 Gunter, Marc J
A1 Kaaks, Rudolf
A1 Key, Timothy J
A1 Khaw, Kay-Tee
A1 Krogh, Vittorio
A1 Kühn, Tilman
A1 Palli, Domenico
A1 Panico, Salvatore
A1 Sacerdote, Carlotta
A1 Sanchez-Perez, Maria-Jose
A1 Severi, Gianluca
A1 Spijkerman, Annemieke M W
A1 Tumino, Rosario
A1 van der Schouw, Yvonne T
A1 Riboli, Elio
A1 Forouhi, Nita G
A1 Langenberg, Claudia
A1 Wareham, Nicholas J
K1 Autoantibody
K1 Autoimmunity
K1 Genetic risk score
K1 Incident diabetes
K1 Type 1 diabetes
K1 Type 2 diabetes
AB 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.
PB Springer
YR 2019
FD 2019-08-22
LK http://hdl.handle.net/10668/14672
UL http://hdl.handle.net/10668/14672
LA en
NO Rolandsson O, Hampe CS, Sharp SJ, Ardanaz E, Boeing H, Fagherazzi G, et al. Autoimmunity plays a role in the onset of diabetes after 40 years of age. Diabetologia. 2020 Feb;63(2):266-277.
NO Open access funding provided by Umea University. Funding for the InterAct project was provided by the EU FP6 Programme (grant number LSHM_CT_2006_037197). The autoantibody measurement was funded by Västerbotten County Council and Umeå University, Sweden (OR), the National Institutes of Health (DK26190) (CSH) and the Medical Research Council (MC_UU_12015/1) (NJW). OR: the Västerbotten County Council, Umeå University; MDC: Health Research Fund (FIS) of the Spanish Ministry of Health; Murcia Regional Government (N∫ 6236); EA: the Health Research Fund (FIS) of the Spanish Ministry of Health and Navarre Regional Government; RK: German Cancer Aid, the German Ministry of Research (BMBF); TJK: Cancer Research UK; KTK: the Medical Research Council UK, Cancer Research UK; PMN: the Swedish Research Council; KO: the Danish Cancer Society; SP: Compagnia di San Paolo; AMWS: the Dutch Ministry of Public Health, Welfare and Sports (VWS), the Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands; RT: AIRE-ONLUS Ragusa, AVIS-Ragusa, Sicilian Regional Government; AMWS: LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF); YTvdS: verification of diabetes cases was additionally funded by NL Agency grant IGE05012 and an Incentive Grant from the Board of the UMC Utrecht, LK Research Funds, Dutch Prevention Funds; NGF: MRC core support (MC_UU_12015/5); NIHR Cambridge Biomedical Research Centre (IS-BRC-1215-20014). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.
DS RISalud
RD Apr 6, 2025