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Autoimmune type 1 diabetes : Resolved and unresolved issues

Notkins, Abner Louis and Lernmark, Åke LU (2001) In Journal of Clinical Investigation 108(9). p.1247-1252
Abstract

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... (More)

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.

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author
publishing date
type
Contribution to journal
publication status
published
in
Journal of Clinical Investigation
volume
108
issue
9
pages
6 pages
publisher
The Journal of Clinical Investigation
external identifiers
  • scopus:0035197969
ISSN
0021-9738
DOI
10.1172/JCI200114257
language
English
LU publication?
no
id
9ba661cf-18ef-433a-b441-d36bb0751d98
date added to LUP
2017-09-07 09:37:39
date last changed
2018-01-07 12:18:20
@article{9ba661cf-18ef-433a-b441-d36bb0751d98,
  abstract     = {<p>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.</p>},
  author       = {Notkins, Abner Louis and Lernmark, Åke},
  issn         = {0021-9738},
  language     = {eng},
  number       = {9},
  pages        = {1247--1252},
  publisher    = {The Journal of Clinical Investigation},
  series       = {Journal of Clinical Investigation},
  title        = {Autoimmune type 1 diabetes : Resolved and unresolved issues},
  url          = {http://dx.doi.org/10.1172/JCI200114257},
  volume       = {108},
  year         = {2001},
}