As noted in the section on classification of diabetes, type 1 diabetes may be immune-mediated (type 1A) or idiopathic (type 1B). In either case, complete (or almost complete) loss of pancreatic beta cell function results in an absolute need for insulin therapy.
The pathogenesis of immune-mediated destruction of the pancreatic beta cells has received the most attention, and is better understood than idiopathic loss of beta cell function. Pathologically, it is characterized by degranulated beta cells, an inflammatory infiltrate, and preservation of the other pancreatic islet cells, such as the glucagon-secreting alpha cells or the somatostatin-producing delta cells. The inflammatory infiltrate is composed of lymphocytes (CD4 and CD8 cells), natural killer cells, and macrophages.
Islet involvement may be variable, and the clinical course of islet destruction may be slow or rapid.
Autoantibodies in the plasma are predictive and diagnostic for type 1A diabetes. Autoantibodies to the pancreatic islets were the first to be described. Subsequently, other autoantibodies have been found, including antibodies to glutamic acid decarboxylase (GAD), insulin, and other islet cell antigens. Type 1 diabetes-associated autoantibodies have been recognized before the onset of clinical disease, and their presence indicates a high risk of developing type 1 diabetes.
First-phase insulin release is often reduced, and hyperglycemia eventually occurs. Islet cell autoantibodies are present in at least 70-80% of people with newly diagnosed type 1 diabetes, and insulin autoantibodies are present in about 50%. As the disease progresses, titers of autoantibodies fall and may be undetectable with long-standing autoimmune type 1 diabetes. A relatively high incidence of other autoimmune diseases (thyroiditis, celiac disease, pernicious anemia,or Addison’s disease) in people with type 1 diabetes supports the role of autoimmunity in the pathogenesis of the disease.
The components of the immune system that are primarily responsible for cell destruction are under study. Elaboration of the cytokine interleukin-1 (IL-1) is thought to be of pathogenetic importance. IL-inhibits insulin secretion and may be cytotoxic to the islets. Another cytokine, IL-6, is produced by beta cells and can stimulate the immune response, enhance insulitis, and result in beta cell destruction. In one m it is hypothesized that viral infection of a beta cell increases release cytokines and adhesion of leukocytes. The infected beta cell is susceptible to attack by antiviral cytotoxic CD8 lymphocytes. Macrophages in the islets are stimulated to produce cytokines and free radicals, increasing the cytoxicity to the beta cells.
Macrophages offer viral antigens to CD4 lymphocytes, which activate B lymphocytes to produce antiviral and anti-beta-cell antibodies. The process is obviously a complicated one with evolving concepts. The end product of virtually complete beta cell destruction leads to an absolute need for insulin therapy.
Islet involvement may be variable, and the clinical course of islet destruction may be slow or rapid.
Autoantibodies in the plasma are predictive and diagnostic for type 1A diabetes. Autoantibodies to the pancreatic islets were the first to be described. Subsequently, other autoantibodies have been found, including antibodies to glutamic acid decarboxylase (GAD), insulin, and other islet cell antigens. Type 1 diabetes-associated autoantibodies have been recognized before the onset of clinical disease, and their presence indicates a high risk of developing type 1 diabetes.
First-phase insulin release is often reduced, and hyperglycemia eventually occurs. Islet cell autoantibodies are present in at least 70-80% of people with newly diagnosed type 1 diabetes, and insulin autoantibodies are present in about 50%. As the disease progresses, titers of autoantibodies fall and may be undetectable with long-standing autoimmune type 1 diabetes. A relatively high incidence of other autoimmune diseases (thyroiditis, celiac disease, pernicious anemia,or Addison’s disease) in people with type 1 diabetes supports the role of autoimmunity in the pathogenesis of the disease.
The components of the immune system that are primarily responsible for cell destruction are under study. Elaboration of the cytokine interleukin-1 (IL-1) is thought to be of pathogenetic importance. IL-inhibits insulin secretion and may be cytotoxic to the islets. Another cytokine, IL-6, is produced by beta cells and can stimulate the immune response, enhance insulitis, and result in beta cell destruction. In one m it is hypothesized that viral infection of a beta cell increases release cytokines and adhesion of leukocytes. The infected beta cell is susceptible to attack by antiviral cytotoxic CD8 lymphocytes. Macrophages in the islets are stimulated to produce cytokines and free radicals, increasing the cytoxicity to the beta cells.
Macrophages offer viral antigens to CD4 lymphocytes, which activate B lymphocytes to produce antiviral and anti-beta-cell antibodies. The process is obviously a complicated one with evolving concepts. The end product of virtually complete beta cell destruction leads to an absolute need for insulin therapy.
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