Genetic risk factors for type 1 diabetes
(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
-
- scopus:84975920751
- pmid:27302272
- wos:000376969100036
- 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
- 2024-09-21 19:21:43
@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}}, }