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type I (insulin-dependent) diabetes mellitusWhat is type I diabetes?
Type 1 Insulin-dependent Diabetes Mellitus (IDDM) is the result of a sudden intolerance for pancreatic islet cells. In this pathology the body responds with an immune response against the β-pancreatic cells; cells responsible for producing insulin. The immune response launched against the β-pancreatic cells leads to phagocytising of these cells, and as a result the patient becomes diabetic as their body can no longer appropriately respond to fluctuating blood glucose levels.
Insulin Dependent Diabetes Mellitus Pathology.
Like many other autoimmune diseases, IDDM has been attributed to a mutation of the Major Histocompatibility Complexes (MHC), containing genetic information which encodes the Human Lymphocyte Antigens (HLA), classes I and II, and many other non-HLA proteins.
Islet Cell Cytoplasmic Antibodies (ICCA) are also produced by the body during IDDM. These ICCAs appear to attack other types of cells in the Islets of Langerhan, including α-pancreatic and β-pancreatic cells. One immediate effect of this autoimmune response against the β-pancreatic cells is a decrease in insulin production, though other types of cells are also affected. In addition to the loss of insulin production, α-pancreatic cells, which normally produce glucagon in response to decreased blood sugar levels, are also modified. This alteration leads to an excessive increase in the production of glucagon as the α-pancreatic cells become desensitized to increased blood sugar levels. Perhaps the most damaging effect of IDDM is ketoacidosis, a build up of toxic ketone bodies in the blood, which in severe cases can lead to a diabetic coma and consequently fatal hypoglycemia.
Genomic analyses of families with two or more siblings diagnosed with IDDM, have shown genetic correlations for IDDM within related family members. Also suggesting a mutation in the MHC complex and mutations in other non-MHC proteins are correlated with the onset of IDDM[12,13] familial clusters.
Treatment for IDDM
Much of the research on the treatment for IDDM to date, has focused on relieving the symptoms rather than resolving the problem. Many of these proposed solutions include finding novel ways of controlling blood sugar levels. As an autoimmune disease, IDDM and the possible therapies can have significant effects on a patient's quality of life, and continual monitoring of blood sugar levels and subsequent injections of insulin can be costly. Further research in the area of immunotherapy, is critical if we are to provide a better standard of life for patients suffering from IDDM.
references10) Becker KG: Comparative Genetics of Type I Diabetes and Autoimmune Disease: Common loci, common pathways. Diabetes 1999, 48:1353-1358.
11) Komulainen J, Lounamaa R, Knip M, Kaprio EA, Akerblom HK. Ketoacidosis at the diagnosis of type 1 (insulin dependent) diabetes mellitus is related to poor residual beta cell function. Childhood Diabetes in Finland Study Group. Archives of Disease in Childhood 1996, 75: 410-415.
12) Hashimoto L, Habita C, Beressi J, Delepine M, Besse C, Cambon-Thomsen A, Deschamps I, Rooter J, Djoulah S, James M, Froguel P, Weissenbach J, Lathrop G, Julier C. Genetic Mapping of Susceptibility locus for Insulin-Dependent Daibetes Mellitus on Chromosome 11q. Nature 1994, 371: 161-164.
13) Davies JL, Kawaguchi Y, Bennett S.T. Coperman JB, Cordell HJ, Pritchard LE, Reed PW Gough SCL, Jenkins SC, Palmer SM, Balfour KM, Rowe B Farrall M, Barnett AH, Bain SC, Todd JA. A genome-wide search for human type 1 Diabetes susceptibility genes. Nature 1994, 371: 130-136.