Autoimmune type 1 diabetes: Resolved and unresolved issues

Research output: Contribution to journalReview article


Based on the presence of autoantibodies and a strong HLA linkage, type 1 diabetes is now classified as a chronic autoimmune disease. Many issues, however, remain unresolved. Although autoantibodies to GAD65, IA-2, and insulin are clearly markers for this disease, it is not known whether they contribute to pathogenesis or are simply the response to an existing underlying destructive process. Based on extensive studies in animal models, it is thought that it is the cell-mediated immune response that is actually responsible for the destruction of β cells. However, this has not been unequivocally established in humans because of the lack of a reliable assay for measuring cell-mediated immunity to β cell antigens. What triggers the autoimmune response also is not known. The search for type 1 diabetes -specific genes so far has not been revealing, and environmental triggers, although widely viewed as important, have remained elusive. Despite enormous interest in the basis of the disease, type 1 diabetes pathogenesis remains understudied because of the difficulty and hazards in biopsying the pancreas. Nevertheless, the studies on autoimmunity have provided clinically useful information. In particular, the demonstration of the presence of autoantibodies years before the onset of clinical symptoms has made it possible to identify individuals at high risk of developing type 1 diabetes and to initiate therapeutic intervention trials on relatively small numbers of subjects. Thus, to a very large degree, type 1 diabetes is a predictable disease. In addition, the demonstration of autoantibodies in 5-10% of individuals who were classified with type 2 diabetes suggests either that some of these individuals have a combination of type 1 and type 2 diabetes or that the number of patients with type 1 diabetes may be nearly twice as great as previously thought.


External organisations
  • University of Washington
Original languageEnglish
Pages (from-to)1247-1252
Number of pages6
JournalJournal of Clinical Investigation
Issue number9
Publication statusPublished - 2001
Publication categoryResearch
Externally publishedYes