Autoimmune insulin-dependant diabetes

Blood sugar (blood glucose) in human beings is controlled by the secretion of (—>) insulin by the beta (B- or (3-) cells of the islands of Langerhans in the pancreas. Loss of insulin synthesis leads to (—>) diabetes. Type 1 diabetes (insulin dependent diabetes mellitus, EDDM) begins in juveniles as an organ-specific autoimmune reaction, the destructive insulitis. 

First trials with CD3 antibodies for therapy of autoimmune diseases (insulin-dependent diabetes mellitus psoriatic arthritis... 

Type 1 Autoimmune disease resulting in an absolute deficiency of insulin. Formerly referred to as juvenile onset diabetes, type I DM or insulin dependent diabetes mellitus (IDDM). Ketosis is common in poorly controlled subjects. 

Diabetes mellitus occurs when the human body does not produce enough insulin. This form of diabetes is called insulin-dependent diabetes mellitus (IDDM, or juvenile diabetes, or type I diabetes). IDDM is an autoimmune disease (see Exhibit 4.7) in which the j8 cells are targeted by the body s own immune system and progressively destroyed. Once destroyed, they are unable to produce insulin. 

Type 1 diabetes is an autoimmune disease in which antibodies are made to proteins of the P cells of the pancreas. These antibodies gradually destroy these cells and, with them, the body s source of insulin. Untreated, insulin-dependent diabetes is a fatal disease. 

Diabetes mellitus is a very common metabolic disease that is caused by absolute or relative insulin deficiency. The lack of this peptide hormone (see p. 76) mainly affects carbohydrate and lipid metabolism. Diabetes mellitus occurs in two forms. In type 1 diabetes (insulin-dependent diabetes mellitus, IDDM), the insulin-forming cells are destroyed in young individuals by an autoimmune reaction. The less severe type 2 diabetes (non-insulin-dependent diabetes mellitus, NIDDM) usually has its first onset in elderly individuals. The causes have not yet been explained in detail in this type. 

Cyclosporine appears to have promise in the treatment of autoimmune diseases. It has a beneficial effect on the course of rheumatoid arthritis, uveitis, insulin-dependent diabetes, systemic lupus erythematosus, and psoriatic arthropathies in some patients. Toxicity is more of a problem in these conditions than during use in transplantation, since higher doses of cyclosporine are often required to suppress autoimmune disorders. 

A. Autoimmune Nature of Insulin-Dependent Diabetes Mellitus... 

Kaufman, D. L., Erlander, M. G., Clare-Salzler, M., Atkinson, M. A., Maclaren, N. K., and Tobin, A. J. (1992). Autoimmunity to two forms of glutamate decarboxylase in insulin-dependent diabetes mellitus. J. Clin. Invest. 89, 283-292. 

Sigurdsson, E., and Baekkeskov, S. (1990). The 64-kDa beta cell membrane autoantigen and other target molecules of humoral autoimmunity in insulin-dependent diabetes mellitus. Curr. Top. Microbiol. Immunol. 164, 143-168. 

Examples of some conditions which are known,or are believed to be, to be autoimmune responses include myasthenia gravis (destruction of acetylcholine receptors), rheumatic fever (a streptococcal infection challenges the immune system and then the immune system mistakes heart tissue for another strep infection), Addison s disease (destruction of the adrenal glands), arthritis (an infection of unknown origin starts the immune response but somehow IgG becomes changed, enough so as to start another IgM response - this time to the body s own IgG), pernicious anemia (inability to process vitamin B12)- insulin-dependent diabetes mellitus (IDDM or type I diabetes), multiple sclerosis, aspermatogenesis, and photosensitivity. 

Classen JB, Classen DC. Clustering of cases of insulin dependent diabetes (IDDM) occurring three years after Hemophilus influenza B (HiB) immunization support causal relationship between immunization and IDDM. Autoimmunity 2002 35(4) 247-53. 

Models of autoimmune diabetes in nonobese diabetic mice (NOD) mice, insulin-dependent diabetes, and experimental allergic encephalyomyelitis (EAE) were also used to evaluate naked pDNA therapy. In the latter models, a predominant Thl cytokine response is thought to play a role in disease symptoms and etiology. Treatment of these mouse models with a TH2 type cytokine, such as IL-10 or IL-4, has been found to shift the immune response and lessen the severity of disease. Therefore, the efficacy of pDNA delivery of a Th2 cytokine was explored in these specific models. 

Bach, J.F. (1994) Insulin-dependent diabetes mellitus as an autoimmune disease. Endocr. Rev., 15, 516-542. 

Interleukin-1, pancreatic P cells, and insulin-dependent diabetes mellitus Insulin-dependent diabetes mellitus is an autoimmune disease that causes the gradual destruction of insulin-producing pancreatic P cells. It has been postulated that the infiltration of macrophages into the pancreatic islets plays a key role in the destruction of P cells and that cytokines, especially interleukin-1, which is released locally from macrophages, may be the toxic molecule causing this destruction. 

Serreze, D. V. and Leiter, E. H. (2001) Genes and pathways underlying autoimmune diabetes in NOD mice, in Molecular Pathology of Insulin Dependent Diabetes Mellitus (von Herrath, M. G., ed.). Karger Press, New York, pp. 31-67. 

Bach, J. F. (1995). Insulin-dependent diabetes mellitus as a beta-cell targeted disease of immunoregulation. J. Autoimmun. 8, 439 463. 

Palmer JP, Asplin CM, Raghu PK et al. (1986) Anti-insulin antibodies in insulin-dependent diabetics before insulin treatment - A new marker for autoimmune 6-cell damage Pe-diatr Adolesc Endocrinol 15 111-116... 

Transplantation of islets of Langerhans as a means of treating insulin-dependent diabetes mellitus has become an important field of interest [217-219]. However, tissue rejection and relapse of the initial autoimmune process have limited the success of this treatment. Immunoisolation of islets in semipermeable microcapsules has been proposed to prevent their immune destruction [220, 221]. Nevertheless, a pericapsular cellular reaction eventually develops around micro-encapsulated islets, inducing graft failure [222]. Since empty microcapsules elicit a similar reaction [223], the reaction is not related to the presence of islets within the capsule but is, at least partially, caused by the capsule itself. Consequently, microcapsule biocompatibility appears to constitute a major impediment to the successful microencapsulated islet transplantation. 

Diabetes mellitus ( sweet urine ) involves relative over-production of glucose by the liver and under-utilization by other organs. Diabetes is the most serious metabolic disease in terms of its social impact. Obesity and the indulgent Western diet correlates with mature age diabetes. Type 1 diabetes (juvenile diabetes) typically manifests at less than 20 years from autoimmune destruction of the insulin-producing pancreatic (3 cells. Type 1 diabetes is insulin-dependent diabetes mellitus (IDDM) and is fatal without exogenous insulin. Type 2 diabetes mellitus (mature age diabetes) occurs later in life and typically involves both deficient insulin production and insulin resistance , that is, the target cells are less responsive to insulin. Type 2 diabetes is initially non-insulin-dependent diabetes (NIDDM) but insulin therapy (in addition to oral antidiabetics) may eventually be required. Hyperglycaemia due... 

Diabetes mellitus (DM) is an increasingly common disease of sugar metabolism. Juvenile-onset diabetes, also known as Type I or insulin-dependent diabetes (IDDM), is an autoimmune disease that results in decreased release of insulin by the pancreas. Late-onset diabetes, also known as Type II or non-insulin-dependent diabetes (NIDDM), results from reduced sensitivity of cells to the insulin signal. A convenient animal model for studying diabetes and testing alternative therapies is the streptozotocin-freated diabetic rat. Streptozotocin (STZ) attacks the pancreas and decreases insulin production and release, thus, mimicking many aspects of the human disease. Since insulin is not orally absorbed, the oral administration of vanadium compounds that are insuhn-mimetic or insulin-enhancing would be a very attractive therapy ... 

In this case, which was marked by three autoimmune complications (insulin-dependent diabetes mellitus, myositis, and myasthenia gravis) in a single patient, a retrospective analysis of the patient s serum before aldesleukin therapy showed the presence of antibodies against glutamic acid decarboxylase, insulin, islet cell antigen, and striated muscle, but was negative for acetylcholine receptor antibodies. Immune stimulation by aldesleukin was... 

The exact mechanisms of tacrolimus-induced diabetes are unknown. In one renal transplant patient with genetic susceptibility, tacrolimus was associated with insulin-dependent diabetes mellitus and the simultaneous occurrence of anti-glutamic acid decarboxylase antibody (54). Within 2 months after conversion from tacrolimus to ciclosporin, the antibody was no longer detected and the patient s insulin requirements fell dramatically. Tacrolimus-induced direct beta cell toxicity, with subsequent development of beta cell autoimmunity, was therefore suggested as a possible mechanism in patients with genetic susceptibility for type I diabetes. 

Autoimmune diseases include autoimmune thrombocytopenia, Graves disease, hemolytic anemia, Hashimoto s thyroiditis, insulin-dependent diabetes mellitus (diabetes... 

Bach, J.-E (1994). Insulin-dependent diabetes melUtus as an autoimmune disease. Endocrine Rev. 15,516-542. 

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