Autoimmune Type 1 Diabetes
Alshiekh, Shehab LU ; Larsson, Helena Elding LU
; Ivarsson, Sten A.
LU
and Lernmark, Åke
LU
(2017)
p.143-153
- Abstract
The last several years of research, including children followed from birth and extensive genetic studies, have resulted in a paradigm shift of the etiology and pathogenesis of type 1 diabetes mellitus (T1DM). Autoimmune T1DM is characterized by the appearance in early childhood of a first β-cell autoantibody against either insulin (IAA) or GAD65 (GADA), or both. The genetic etiology is strongly associated with HLA-DR4-DQ8 for IAA and DR3-DQ2 for GADA. The trigger(s) of the first β-cell autoantibody is not yet known but enterovirus is implicated. The presence of one autoantibody is associated with a lifetime risk of about 10%. The appearance of a second or more β-cell autoantibody, including IAA, GADA, IA-2A, or ZnT8A, is associated with... (More)
The last several years of research, including children followed from birth and extensive genetic studies, have resulted in a paradigm shift of the etiology and pathogenesis of type 1 diabetes mellitus (T1DM). Autoimmune T1DM is characterized by the appearance in early childhood of a first β-cell autoantibody against either insulin (IAA) or GAD65 (GADA), or both. The genetic etiology is strongly associated with HLA-DR4-DQ8 for IAA and DR3-DQ2 for GADA. The trigger(s) of the first β-cell autoantibody is not yet known but enterovirus is implicated. The presence of one autoantibody is associated with a lifetime risk of about 10%. The appearance of a second or more β-cell autoantibody, including IAA, GADA, IA-2A, or ZnT8A, is associated with a lifetime risk of 100%. T1DM is thought to progress in three stages: (1) Triggering of β-cell autoimmunity resulting in one or multiple β-cell autoantibodies associated with gradual β-cell destruction but no dysglycemia or symptoms of diabetes; (2) loss of β-cell function in autoantibody-positive subjects with impaired glucose tolerance but no symptoms; (3) loss of β-cell capacity and appearance of diabetes symptoms. The pancreatic islets do not seem to be affected by mononuclear cells during stages 1 and 2 but are actually infiltrated by CD4+ and CD8+ T lymphocytes and macrophages during stage 3, eventually leading to insulitis. The progress in understanding the etiology and pathogenesis of T1DM and the approach to stage the disease should prove useful for clinical trials of primary (in children at genetic risk) and secondary (children with multiple autoantibodies) prevention and also intervention to save residual β cells.
(Less)
- author
- Alshiekh, Shehab
LU
; Larsson, Helena Elding
LU
; Ivarsson, Sten A.
LU
and Lernmark, Åke
LU
- publishing date
- 2017
- type
- Chapter in Book/Report/Conference proceeding
- publication status
- published
- subject
- keywords
- antigen-presenting cells, autoimmunity, CD4+ T cells, CD8+ T cells, GAD65 autoantibodies, human leukocyte antigen, IA-2 autoantibodies, insulin autoantibodies, insulin release, insulitis, ZnT8 autoantibodies, β-cell autoantibodies, β-cell function
- host publication
- Textbook of Diabetes
- editor
- Hold, R ; Cockram, CS ; Flyvbjerg, A and Goldstein, BJ
- edition
- 5th
- pages
- 143 - 153
- publisher
- Wiley
- external identifiers
-
- scopus:105000604632
- ISBN
- 9781118912027
- 9781118924853
- DOI
- 10.1002/9781118924853.ch10
- language
- English
- LU publication?
- no
- additional info
- Publisher Copyright: © 2017 John Wiley & Sons, Ltd. All rights reserved.
- id
- 0bc58b8e-a193-4368-bdf9-5a8e1a1535c7
- date added to LUP
- 2025-04-03 12:24:44
- date last changed
- 2025-07-10 20:07:59
@inbook{0bc58b8e-a193-4368-bdf9-5a8e1a1535c7,
abstract = {{<p>The last several years of research, including children followed from birth and extensive genetic studies, have resulted in a paradigm shift of the etiology and pathogenesis of type 1 diabetes mellitus (T1DM). Autoimmune T1DM is characterized by the appearance in early childhood of a first β-cell autoantibody against either insulin (IAA) or GAD65 (GADA), or both. The genetic etiology is strongly associated with HLA-DR4-DQ8 for IAA and DR3-DQ2 for GADA. The trigger(s) of the first β-cell autoantibody is not yet known but enterovirus is implicated. The presence of one autoantibody is associated with a lifetime risk of about 10%. The appearance of a second or more β-cell autoantibody, including IAA, GADA, IA-2A, or ZnT8A, is associated with a lifetime risk of 100%. T1DM is thought to progress in three stages: (1) Triggering of β-cell autoimmunity resulting in one or multiple β-cell autoantibodies associated with gradual β-cell destruction but no dysglycemia or symptoms of diabetes; (2) loss of β-cell function in autoantibody-positive subjects with impaired glucose tolerance but no symptoms; (3) loss of β-cell capacity and appearance of diabetes symptoms. The pancreatic islets do not seem to be affected by mononuclear cells during stages 1 and 2 but are actually infiltrated by CD4<sup>+</sup> and CD8<sup>+</sup> T lymphocytes and macrophages during stage 3, eventually leading to insulitis. The progress in understanding the etiology and pathogenesis of T1DM and the approach to stage the disease should prove useful for clinical trials of primary (in children at genetic risk) and secondary (children with multiple autoantibodies) prevention and also intervention to save residual β cells.</p>}},
author = {{Alshiekh, Shehab and Larsson, Helena Elding and Ivarsson, Sten A. and Lernmark, Åke}},
booktitle = {{Textbook of Diabetes}},
editor = {{Hold, R and Cockram, CS and Flyvbjerg, A and Goldstein, BJ}},
isbn = {{9781118912027}},
keywords = {{antigen-presenting cells; autoimmunity; CD4+ T cells; CD8+ T cells; GAD65 autoantibodies; human leukocyte antigen; IA-2 autoantibodies; insulin autoantibodies; insulin release; insulitis; ZnT8 autoantibodies; β-cell autoantibodies; β-cell function}},
language = {{eng}},
pages = {{143--153}},
publisher = {{Wiley}},
title = {{Autoimmune Type 1 Diabetes}},
url = {{http://dx.doi.org/10.1002/9781118924853.ch10}},
doi = {{10.1002/9781118924853.ch10}},
year = {{2017}},
}