Type 1 Diabetes Mellitus

Type 1 diabetes (T1D) is a chronic autoimmune disease characterized by selective autoimmune- mediated destruction of pancreatic islet beta- cells leading gradually to absolute insulin deficiency. T1D is under polygenic control. The HLA complex attributes 50% of the genetic risk for T1D while as many as 20 genes influence susceptibility to T1D. The autoimmune beta-cell destruction could be triggered by environmental factors. While the exact trigger of anti-islet autoimmunity remains elusive, it can lead to an imbalance between regulatory T cells and autoimmune effector T cells. During the initiation of insulitis, emerging evidences suggest that the infiltrating macrophages via toll-like receptor 2 (TLR2) activation lead to induction and amplification of insulitis. Following the priming of diabetogenic T-cells, autoreactive T effector cells destroy the beta cells by direct contact- dependent cytolysis or by soluble mediators secreted from macrophages or CD4 T effector cells. The hyperglycemia occurs late in its course after 80% of the beta cells have been destroyed. Although no current cure exists, refinement of genetic studies and islet autoantibodies has improved the ability to predict the risk of T1D and aid the establishment of rationally designed preventive therapies. Other strategies involve beta-cell replacement by islet transplantation. Extensive and long-term research on the efficacy of islet transplantation and preservation of beta-cell function is keenly needed.

Type 1 Diabetes Mellitus

Type 1 diabetes (T1D) is a chronic autoimmune disease characterized by selective autoimmune- mediated destruction of pancreatic islet beta- cells leading gradually to absolute insulin deficiency. T1D is under polygenic control. The HLA complex attributes 50% of the genetic risk for T1D while as many as 20 genes influence susceptibility to T1D. The autoimmune beta-cell destruction could be triggered by environmental factors. While the exact trigger of anti-islet autoimmunity remains elusive, it can lead to an imbalance between regulatory T cells and autoimmune effector T cells. During the initiation of insulitis, emerging evidences suggest that the infiltrating macrophages via toll-like receptor 2 (TLR2) activation lead to induction and amplification of insulitis. Following the priming of diabetogenic T-cells, autoreactive T effector cells destroy the beta cells by direct contact- dependent cytolysis or by soluble mediators secreted from macrophages or CD4 T effector cells. The hyperglycemia occurs late in its course after 80% of the beta cells have been destroyed. Although no current cure exists, refinement of genetic studies and islet autoantibodies has improved the ability to predict the risk of T1D and aid the establishment of rationally designed preventive therapies. Other strategies involve beta-cell replacement by islet transplantation. Extensive and long-term research on the efficacy of islet transplantation and preservation of beta-cell function is keenly needed.

Pathogenesis of Type 1 Diabetes / 한양의대학술지

Type 1 diabetes mellitus (T1D) is a chronic autoimmune disease characterized by selective destruction of pancreatic islet betacells causing insulin deficiency. T1D has been shown to be a polygenic trait, associated with several loci, among which the human leukocyte antigen (HLA) region accounts for 40% of the genetic risk to develop T1D. The betacell autoimmune response is triggered by environmental or unknown events in the predisposing genetic background. The triggers of autoimmunity can lead to a localized imbalance between regulatory T cells and autoimmune effector T cells. The macrophages and autoreactive lymphocytes infiltrate the islets and the interaction of betacells and immune cells leads to inductionamplification of insulitis and loss of betacells. T cells destroy betacells in a direct cytotoxic manner or influence the induction of betacell apoptosis through the release of cytotoxic molecules, such as cytokines. The autoimmune process progresses subclinically for many years in the majority of patients, and clinical symptom do not appear until more than 80% of betacells have been destroyed. Although no current "cure" exists, there is a major effort to develop immunotherapies to prevent or halt the disorder that still requires much research to fully understand exact triggering events leading toautoimmune activation. Other strategies involve beta- cell replacement by islet transplantation, but researchs to enhance the islet mass transplanted and preserve beta-cell function are necessary.