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Lancet. 2016 Jun 4;387(10035):2331-2339. doi: 10.1016/S0140-6736(16)30582-7.

Genetic risk factors for type 1 diabetes.

Author information

1
Department of Pediatrics, Herlev and Gentofte Hospital, DK-2730 Herlev, Denmark.
2
Department of Clinical Sciences, Lund University, Skåne University Hospital, SE-20502 Malmö, Sweden. Electronic address: ake.lernmark@med.lu.se.

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 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.

PMID:
27302272
DOI:
10.1016/S0140-6736(16)30582-7
[Indexed for MEDLINE]

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