Genetic risk factors for type 1 diabetes
Research output: Contribution to journal › Review › Research › peer-review
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.
Original language | English |
---|---|
Journal | The Lancet |
Volume | 387 |
Issue number | 10035 |
Pages (from-to) | 2331-9 |
Number of pages | 9 |
ISSN | 0140-6736 |
DOIs | |
Publication status | Published - Jun 2016 |
- Adolescent, Adult, Aged, Autoantibodies, Child, Child, Preschool, Diabetes Complications, Diabetes Mellitus, Type 1, Gene-Environment Interaction, Genetic Predisposition to Disease, Genome, Human, HLA Antigens, Haplotypes, Humans, Infant, Infant, Newborn, Insulin-Secreting Cells, Middle Aged, RNA, Risk Factors, Young Adult, Journal Article, Review
Research areas
ID: 177058491