(1) family history: Type 1 diabetes has certain familial aggregation. It has been reported that the incidence of type 1 diabetes is 4% ~ 11% in the children of parents with a history of diabetes, 6% ~ 11% in the family with type 1 diabetes among siblings, and less than 50% in the identical twins.
(2) HLA and Type 1 diabetes: the Human leukocyte antigen gene is located on the short arm of chromosome 6 and is a closely linked group of genes. HLA is encoded by Class I, II and III genes. Class I regions include HLA-A, HLA-B, HLA-C and other genes and pseudogenes that encode antigen molecules on the surface of all nucleated cells and are responsible for presenting foreign antigens to the T lymphocyte of CD8 The Class II gene region consists of three subdomains, namely HLA-DR, HLA-DQ and HLA-DP3, which encode DR, DQ and DP antigens, and are present on the surface of mature B lymphocyte and antigen presenting cells, responsible for presenting antigens to CD4 cells Class III regions encode soluble proteins, including certain complement components, such as C2C4A, C4B, Tumor necrosis factors, and Heat shock protein. HLA is restricted by major histocompatibility complex (MHC) , participates in the interaction of T lymphocyte recognition antigens and other immune cells, and the formation and maintenance of self tolerance, it plays an important role in the recognition of self and alien, induction and regulation of immune response. Thus, HLA plays an important role in the occurrence and development of many autoimmune diseases including Type 1 diabetes.
Some HIA has been strongly associated with the development of type 1 diabetes. In a family with type 1 diabetes, siblings with the same HLA antigen had a 5% to 10% chance of developing diabetes, while siblings with non HLA counterparts had less than a 1% chance. In the Caucasian population, 95% of people with type 1 diabetes have HLA-DR3 or HLA-DR4, compared with 45% to 50% of those without diabetes; hla-dr2 has a protective effect against type 1 diabetes. HLA-DQ gene is a more specific marker of susceptibility to type 1 diabetes, which determines the susceptibility and resistance of B cells to autoimmune destruction. HLA-DQw3.2 has been reported in almost 70% of patients with type 1 diabetes and HLA-DQw3.1 in DR4 controls. The study found that if the 57th position of both DQ β alleles was occupied by L-Aspartic Acid, autoimmune diabetes would not occur, but if both alleles were aspartic acid, type 1 diabetes would be highly susceptible, the 52nd Arginine of HLA-DQA1 chain is also a susceptibility gene for type 1 diabetes. Individuals with non-aspartic acid homozygotes at DQ β1 and arginine homozygotes at HLA-DQA1 have the highest relative risk of type 1 diabetes. The 45 amino acids in the DQ β chain are recognized by the Epitope as DQW3.2 rather than DQW3.1. These findings may explain why the Association of HIA-DQ and HLA-DR alleles is associated with a higher risk of type 1 diabetes than the association alone.
HLA and type 1 diabetes subtype: according to the HLA phenotype of type 1 diabetes subtype, the clinical and etiological differences are meaningful. It is generally believed that HLA expressed as HLA-DR3/DR3 will lead to primary autoimmune disease, and HLA-DR4/DR4 represents primary environmental factors as the main inducement, the result is secondary autoimmune reaction. Type 1 diabetes with HLA-DR3 is often accompanied by other autoimmune diseases (such as adrenal cortex dysfunction, Hashimoto’s thyroiditis, etc.) and is more common in women. Type 1 diabetes, which is associated with HLA-DR4, is rarely associated with other endocrine disease, and is more common in men, with a lower onset age. According to HLA typing, 745 cases of type 1 diabetes with onset from 1 to 19 years old have been reported. HLA-DR3 patients have milder onset than HLA-dr4 patients, milder ketosuria and greater tendency of partial remission.
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