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

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  • Olov Rolandsson, Department of Public Health and Clinical Medicine, Family Medicine, Umeå University, 901 87, Umeå, Sweden. olov.rolandsson@umu.se., Sverige
  • Christiane S Hampe, Department of Medicine, Division of Metabolism, Endocrinology and Nutrition, University of Washington, Seattle, WA, USA., USA
  • Stephen J Sharp, MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge School of Clinical Medicine, Cambridge, Storbritannien
  • Eva Ardanaz, Navarre Public Health Institute, Pamplona, Navarra Institute for Health Research (IdiSNA), Pamplona, Spain.
  • ,
  • Heiner Boeing, Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany., Tyskland
  • Guy Fagherazzi, CESP, Faculty of Medicine, University Paris-South, Faculty of Medicine, University Versailles-St Quentin, Inserm U1018, University Paris-Saclay, Villejuif, France., Frankrig
  • Francesca Romana Mancini, CESP, Faculty of Medicine, University Paris-South, Faculty of Medicine, University Versailles-St Quentin, Inserm U1018, University Paris-Saclay, Villejuif, France., Frankrig
  • Peter M Nilsson, Lund University, Sverige
  • Kim Overvad
  • Maria-Dolores Chirlaque, Department of Epidemiology, Regional Health Council, IMIB-Arrixaca, Murcia, Spain., Spanien
  • Miren Dorronsoro, CIBER Epidemiología y Salud Pública (CIBERESP), Murcia, Spain; Public Health Division of Gipuzkoa, San Sebastian, Spain; Instituto BIO-Donostia, Basque Government, San Sebastian, Spain., Spanien
  • Marc J Gunter, Biostatistics Group, International Agency for Research on Cancer, Lyon, France.
  • ,
  • Rudolf Kaaks, Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany. r.kaaks@dkfz-heidelberg.de., Tyskland
  • Timothy J Key, Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK., Storbritannien
  • Kay-Tee Khaw, Department of Public Health and Primary Care, School of Clinical Medicine, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom, Storbritannien
  • Vittorio Krogh, 12 Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy., Italien
  • Tilman Kühn, Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany. r.kaaks@dkfz-heidelberg.de., Tyskland
  • Domenico Palli, Cancer Risk Factors and Lifestyle Epidemiology Unit, Institute for cancer research, prevention and clinical network (ISPRO), Florence, Italy., Italien
  • Salvatore Panico, EPIC Centre of Naples. Dipartimento di Medicina Clinica e Chirurgia Federico II University, Naples, Italy., Italien
  • Carlotta Sacerdote, Unit of Cancer Epidemiology, Azienda Ospedaliera Universitaria (AOU) Citta' della Salute e della Scienza Hospital-University of Turin and Center for Cancer Prevention (CPO), Torino, Italy., Italien
  • Maria-José Sánchez, Escuela Andaluza de Salud Pública. Instituto de Investigación Biosanitaria ibs.GRANADA, Hospitales Universitarios de Granada/Universidad de Granada, 18014 Granada, Spain., Spanien
  • Gianluca Severi, Facultés de Medicine, Université Paris-Sud, Université Paris-Saclay, University of Versailles Saint-Quentin-en-Yvelines (UVSQ) Gustave Roussy, Villejuif, France., Frankrig
  • Annemieke M W Spijkerman, Centre for Health Protection, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands., Holland
  • Rosario Tumino, Associazone Iblea per la Ricerca Epidemiologica - Organizazione Non Lucrativa di Utilità Sociale, Ragusa, Italy., Italien
  • Yvonne T van der Schouw, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands., Holland
  • Elio Riboli, School of Public Health, Imperial College London, London, UK., Storbritannien
  • Nita G Forouhi, MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge School of Clinical Medicine, Cambridge, Storbritannien
  • Claudia Langenberg, MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge School of Clinical Medicine, Cambridge, Storbritannien
  • Nicholas J Wareham, MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge School of Clinical Medicine, Cambridge, Storbritannien

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.

OriginalsprogEngelsk
TidsskriftDiabetologia
Vol/bind63
Nummer2
Sider (fra-til)266-277
Antal sider12
ISSN0012-186X
DOI
StatusUdgivet - feb. 2020

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