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Environmental Triggers and Determinants of Type 1 Diabetes

¹ Hospital for Children and Adolescents, University of Helsinki, Helsinki, Finland
² Department of Pediatrics, Tampere University Hospital, Tampere, Finland
³ Department of Pediatrics, University of Oulu, Oulu, Finland
⁴ Department of Epidemiology and Health Promotion, Nutrition Unit, National Public Health Institute, Helsinki, Finland
⁵ Tampere School of Public Health, University of Tampere, Tampere, Finland
⁶ Tampere University Hospital Research Unit, Tampere, Finland
⁷ Department of Virology, University of Tampere, Tampere, Finland
⁸ Department of Clinical Microbiology, Centre for Laboratory Medicine, Tampere University Hospital, Tampere, Finland
⁹ Department of Viral Diseases and Immunology, National Public Health Institute, Helsinki, Finland
¹⁰ Department of Molecular and Clinical Medicine, Linköping University, Linköping, Sweden

Type 1 diabetes is perceived as a chronic immune-mediated disease with a subclinical prodromal period characterized by selective loss of insulin-producing ß-cells in the pancreatic islets in genetically susceptible subjects. A series of evidence supports a critical role of exogenous factors in the development of type 1 diabetes, such as 1) the fact that <10% of individuals with HLA-conferred diabetes susceptibility do progress to clinical disease, 2) a pairwise concordance of type 1 diabetes of <40% among monozygotic twins, 3) a more than 10-fold difference in the disease incidence among Caucasians living in Europe, 4) a several-fold increase in the incidence over the last 50 years, and 5) migration studies indicating that the disease incidence has increased in population groups who have moved from a low-incidence to a high-incidence region. This article discusses the trigger-booster hypothesis claiming that the diabetic disease process is triggered by an exogenous factor with definite seasonal variation and driven by one or several other environmental determinants. In addition, there are a series of modifying factors affecting the fate and pace of the process. Accordingly, progression to clinical type 1 diabetes typically requires the unfortunate combination of genetic disease susceptibility, a diabetogenic trigger, and a high exposure to a driving antigen.

Abbreviations: DAISY, Diabetes Autoimmunity Study in the Young; DIPP, Finnish Diabetes Prediction and Prevention; IAA, insulin autoantibody

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