Environmental Triggers and Determinants of Type 1 Diabetes

  1. Mikael Knip12,
  2. Riitta Veijola3,
  3. Suvi M. Virtanen456,
  4. Heikki Hyöty78,
  5. Outi Vaarala910 and
  6. Hans K. Åkerblom1
  1. 1Hospital for Children and Adolescents, University of Helsinki, Helsinki, Finland
  2. 2Department of Pediatrics, Tampere University Hospital, Tampere, Finland
  3. 3Department of Pediatrics, University of Oulu, Oulu, Finland
  4. 4Department of Epidemiology and Health Promotion, Nutrition Unit, National Public Health Institute, Helsinki, Finland
  5. 5Tampere School of Public Health, University of Tampere, Tampere, Finland
  6. 6Tampere University Hospital Research Unit, Tampere, Finland
  7. 7Department of Virology, University of Tampere, Tampere, Finland
  8. 8Department of Clinical Microbiology, Centre for Laboratory Medicine, Tampere University Hospital, Tampere, Finland
  9. 9Department of Viral Diseases and Immunology, National Public Health Institute, Helsinki, Finland
  10. 10Department of Molecular and Clinical Medicine, Linköping University, Linköping, Sweden
  1. Address correspondence and reprint requests to Mikael Knip, MD, Hospital for Children and Adolescents, University of Helsinki, P.O. Box 281, FI-00029 HUCH, Helsinki, Finland. E-mail: mikael.knip{at}hus.fi

Abstract

Type 1 diabetes is perceived as a chronic immune-mediated disease with a subclinical prodromal period characterized by selective loss of insulin-producing β-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.

Footnotes

  • This article is based on a presentation at a symposium. The symposium and the publication of this article were made possible by an unrestricted educational grant from Servier.

    • Accepted June 2, 2005.
    • Received March 7, 2005.
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