New Perspectives in Studying Type 1 Diabetes Susceptibility Biomarkers

Type 1 diabetes (T1D) is generally viewed as an etiologic subtype of diabetes caused by the autoimmune destruction of the insulin-secreting β-cells. It has been known that autoreactive T cells unfortunately destroy healthy β-cells. However, there has been a notion of etiologic heterogeneity around the world implicating a varying incidence of a non-autoimmune subgroup of T1D related to insulin deficiency associated with decreased β cell mass, in which the β-cell is the key contributor to the disease. Beta cell dysfunction, reduced mass, and apoptosis may lead to insufficient insulin secretion and ultimately to the development of T1D. Interestingly, Korean as well as other ethnic genetic results have also suggested that genes related with insulin deficiency, let alone those of immune regulation, were associated with the risk of T1D in the young. Genes related with insulin secretion may influence the phenotype of diabetes differentially and different genes may be working on different steps of T1D development. Although we admit the consensus that islet autoimmunity is an essential component in the pathogenesis of T1D, however, dysfunction might occur not only in the immune system but also in the β-cells, the defect of which may induce further dysfunction of the immune system. These arguments stem from the fact that the β-cell might be the trigger of an autoimmune response. This emergent view has many parallels with the fact that by their nature and function, β-cells are prone to biosynthetic stress with limited measures for self-defense. Beta cell stress may induce an immune attack that has considerable negative effects on the production of a vital hormone, insulin. If then, both β-cell stress and islet autoimmunity can be harnessed as targets for intervention strategies. This also may explain why immunotherapy at best delays the progression of T1D and suggests the use of alternative therapies to expand β-cells, in combination with immune intervention strategies, to reverse the disease. Future research should extend to further investigate β-cell biology, in addition to studies of immunologic areas, to find appropriate biomarkers of T1D susceptibility. This will help to decipher β-cell characteristics and the factors regulating their function to develop novel therapeutic approaches.