Genetic risk factors for type 1 diabetes
Pociot, Flemming LU and Lernmark, Åke LU
(2016)
In The Lancet
387(10035).
p.2331-2339
- Abstract
Type 1 diabetes is diagnosed at the end of a prodrome of β-cell autoimmunity. The disease is most likely triggered at an early age by autoantibodies primarily directed against insulin or glutamic acid decarboxylase, or both, but rarely against islet antigen-2. After the initial appearance of one of these autoantibody biomarkers, a second, third, or fourth autoantibody against either islet antigen-2 or the ZnT8 transporter might also appear. The larger the number of β-cell autoantibody types, the greater the risk of rapid progression to clinical onset of diabetes. This association does not necessarily mean that the β-cell autoantibodies are pathogenic, but rather that they represent reproducible biomarkers of the pathogenesis. The... (More)
Type 1 diabetes is diagnosed at the end of a prodrome of β-cell autoimmunity. The disease is most likely triggered at an early age by autoantibodies primarily directed against insulin or glutamic acid decarboxylase, or both, but rarely against islet antigen-2. After the initial appearance of one of these autoantibody biomarkers, a second, third, or fourth autoantibody against either islet antigen-2 or the ZnT8 transporter might also appear. The larger the number of β-cell autoantibody types, the greater the risk of rapid progression to clinical onset of diabetes. This association does not necessarily mean that the β-cell autoantibodies are pathogenic, but rather that they represent reproducible biomarkers of the pathogenesis. The primary risk factor for β-cell autoimmunity is genetic, mainly occurring in individuals with either HLA-DR3-DQ2 or HLA-DR4-DQ8 haplotypes, or both, but a trigger from the environment is generally needed. The pathogenesis can be divided into three stages: 1, appearance of β-cell autoimmunity, normoglycaemia, and no symptoms; 2, β-cell autoimmunity, dysglycaemia, and no symptoms; and 3, β-cell autoimmunity, dysglycaemia, and symptoms of diabetes. The genetic association with each one of the three stages can differ. Type 1 diabetes could serve as a disease model for organ-specific autoimmune disorders such as coeliac disease, thyroiditis, and Addison's disease, which show similar early markers of a prolonged disease process before clinical diagnosis.
(Less)
- author
- Pociot, Flemming
LU
and Lernmark, Åke
LU
- organization
- publishing date
- 2016-06-04
- type
- Contribution to journal
- publication status
- published
- subject
- in
- The Lancet
- volume
- 387
- issue
- 10035
- pages
- 9 pages
- publisher
- Elsevier
- external identifiers
-
- pmid:27302272
- wos:000376969100036
- scopus:84975920751
- ISSN
- 0140-6736
- DOI
- 10.1016/S0140-6736(16)30582-7
- language
- English
- LU publication?
- yes
- id
- 9e87e0e2-093a-46aa-921c-255386079e36
- date added to LUP
- 2016-07-19 09:00:44
- date last changed
- 2024-04-05 03:28:24
@article{9e87e0e2-093a-46aa-921c-255386079e36,
abstract = {{<p>Type 1 diabetes is diagnosed at the end of a prodrome of β-cell autoimmunity. The disease is most likely triggered at an early age by autoantibodies primarily directed against insulin or glutamic acid decarboxylase, or both, but rarely against islet antigen-2. After the initial appearance of one of these autoantibody biomarkers, a second, third, or fourth autoantibody against either islet antigen-2 or the ZnT8 transporter might also appear. The larger the number of β-cell autoantibody types, the greater the risk of rapid progression to clinical onset of diabetes. This association does not necessarily mean that the β-cell autoantibodies are pathogenic, but rather that they represent reproducible biomarkers of the pathogenesis. The primary risk factor for β-cell autoimmunity is genetic, mainly occurring in individuals with either HLA-DR3-DQ2 or HLA-DR4-DQ8 haplotypes, or both, but a trigger from the environment is generally needed. The pathogenesis can be divided into three stages: 1, appearance of β-cell autoimmunity, normoglycaemia, and no symptoms; 2, β-cell autoimmunity, dysglycaemia, and no symptoms; and 3, β-cell autoimmunity, dysglycaemia, and symptoms of diabetes. The genetic association with each one of the three stages can differ. Type 1 diabetes could serve as a disease model for organ-specific autoimmune disorders such as coeliac disease, thyroiditis, and Addison's disease, which show similar early markers of a prolonged disease process before clinical diagnosis.</p>}},
author = {{Pociot, Flemming and Lernmark, Åke}},
issn = {{0140-6736}},
language = {{eng}},
month = {{06}},
number = {{10035}},
pages = {{2331--2339}},
publisher = {{Elsevier}},
series = {{The Lancet}},
title = {{Genetic risk factors for type 1 diabetes}},
url = {{http://dx.doi.org/10.1016/S0140-6736(16)30582-7}},
doi = {{10.1016/S0140-6736(16)30582-7}},
volume = {{387}},
year = {{2016}},
}