The stages of type 1A diabetes: 2005

Immunol Rev. 2005 Apr;204:232-49. doi: 10.1111/j.0105-2896.2005.00248.x.


Type 1A diabetes is a chronic autoimmune disease usually preceded by a long prodrome during which autoantibodies to islet autoantigens are present. These antibodies are directed to a variety of antigens, but the best characterized are glutamic acid decarboxylase-65, insulinoma-associated antigen-2, and insulin. We hypothesize that the natural history of type 1A diabetes can be represented by several stages, starting from genetic susceptibility and ending in complete beta-cell destruction and overt diabetes. Type 1A diabetes probably results from a balance between genetic susceptibility and environmental influences. In both humans and animal models, the major determinants of the disease are genes within the major histocompatibility complex. The next best-characterized susceptibility locus is the insulin gene, the variable nucleotide tandem repeat locus. This gene affects the expression of insulin in the thymus and thus may play a role in the modulation of tolerance to this molecule. In a subset of genetically susceptible individuals, the activation of autoimmunity may be triggered by environmental factors such as viruses and/or diet. However, no conclusive association has been established between type 1A diabetes and specific environmental triggers. In this review, we provide evidence that insulin has a fundamental role in anti-islet autoimmunity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Autoantibodies / immunology
  • Autoantigens / immunology
  • Diabetes Mellitus, Type 1 / genetics
  • Diabetes Mellitus, Type 1 / immunology*
  • Diabetes Mellitus, Type 1 / physiopathology*
  • Diabetes Mellitus, Type 1 / therapy
  • Humans
  • Insulin / metabolism
  • Insulin Secretion
  • Islets of Langerhans / immunology
  • Islets of Langerhans / metabolism
  • Islets of Langerhans / pathology


  • Autoantibodies
  • Autoantigens
  • Insulin