Etiology of diabetes
1. Genetic factors
(1) Family history: Type 1 diabetes has certain family aggregation. It has been reported that both parents have diabetes history, and the incidence of type 1 diabetes in their children is 4%~11%; The incidence of familial aggregation of type 1 diabetes among siblings was 6%~11%; The consistency of type 1 diabetes in identical twins is less than 50%.
(2) HLA and type 1 diabetes: Human leukocyte antigen (HLA) gene is located on the short arm of the sixth chromosome, which is a closely linked gene group. HLA is encoded by class I, II and III genes. Class I gene regions include HLA-A, HLA-B, HLA-C and other genes and pseudogenes with unknown functions. The antigen molecules encoded by these genes exist on the surface of all nucleated cells and are responsible for presenting foreign antigens to CD8 T lymphocytes; Class II gene region mainly includes three sub regions of HLA-DR, HLA-DQ and HLA-DP, encoding DR, DQ and DP antigens respectively, which exist on the surface of mature B lymphocytes and antigen presenting cells and are responsible for presenting antigens to CD4 cells; Class III gene regions encode some soluble proteins including some complement components, such as C2C4A, C4B, tumor necrosis factor (TNF) and heat shock protein (HSP). HLA participates in the interaction of T lymphocytes to recognize antigens and other immune cells, as well as the formation and maintenance of self tolerance through the restriction of major histocompatibility complex (MHC), and plays an important role in many aspects, such as self recognition and dissimilarity, induction and regulation of immune response. It can be seen that HLA is associated with many autoimmune diseases, including type 1 diabetes.
2. The occurrence of environmental factor type 1 diabetes is often related to some infections or occurs after infection. It is common to infect the original mumps virus, rubella virus, cytomegalovirus, measles virus, influenza virus, encephalitis virus, poliovirus, coxsackie virus and Epstein Barr virus, but after virus infection, the susceptibility or resistance to diabetes may be determined by previous days. If two people (like cell brothers or sisters) are exposed to the same virus infection, they may show the same increase of virus antibody, but diabetes may only occur in one person, which may be due to the difference of internal genetic susceptibility factors. Susceptibility may mean that B cells are sensitive to a specific dose of a virus; Or the tendency of autoimmunity to an autoantigen expressed in the process of B cell virus antigen or slight B cell damage.
3. Interaction between genetic and environmental factors Genetic and environmental factors have different effects on the onset of type 1 diabetes in an individual. How environmental factors initiate the autoimmune reaction process of pancreatic islet B cells is still not completely clear. Generally, human type l diabetes needs the genetic background of susceptibility, that is, some environmental substances induce the autoimmune reaction of B cells in individuals with genetic susceptibility. Hypothesis: Type 1 diabetes occurs once the damage of environmental factors to B cells exceeds the tolerance of individual genetic determination of B cell damage.
