Autoimmunity plays a role in the onset of diabetes after 40 years of age

Year: 2019

Type: article

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.

Source: Diabetologia

DOI: 10.1007/s00125-019-05016-3

Institutions: Umeå University, University of Washington, University of Cambridge, MRC Epidemiology Unit, Navarre Institute of Health Research, Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública, German Institute of Human Nutrition, Inserm, Université Paris-Saclay, Centre de recherche en Epidémiologie et Santé des Populations, Lund University, Skåne University Hospital, Aarhus University, Aalborg University Hospital, Instituto Murciano de Investigación Biosanitaria, Basque Government, Centre international de recherche sur le cancer, German Cancer Research Center, University of Oxford, Addenbrooke's Hospital, Fondazione IRCCS Istituto Nazionale dei Tumori, Federico II University Hospital, University of Naples Federico II, Azienda Ospedaliera Citta' della Salute e della Scienza di Torino, Piedmont Reference Center for Epidemiology and Cancer Prevention, University of Turin, Universidad de Granada, Instituto de Investigación Biosanitaria de Granada, Andalusian School of Public Health, Université Paris-Sud, Université de Versailles Saint-Quentin-en-Yvelines, National Institute for Public Health and the Environment, Azienda Usl 8 Arezzo, Associazione Iblea per la Ricerca Epidemiologica E.T.S., University Medical Center Utrecht, Imperial College London

Language: English

Topic: Diabetes and associated disorders

Subfield: Genetics

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $4,390

OpenAlex ID: W2986133512