Question

Include in the appropriate figure,

describe the etiology of insulin-dependent diabetes mellitus (Dm Type I) autoimmune disease.

Next, describe the infection with the etiology of Dm type I disease.

Answer 1

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Insulin-dependent diabetes mellitus (IDDM) is called type 1 diabetes (T1D). The major discovery of the autoimmune origin of T1D is derived in large part from the availability of two spontaneous animal models of the disease—namely, the non-obese diabetic (NOD) mouse and the Bio-Breeding (BB) rat. The immunologic, genetic, and clinical studies, which provide a comprehensive description of disease pathogenesis and to a lesser extent its etiology. Moreover, it can be clearly stated that T1D is a T-cell-mediated autoimmune disease. Its evolution involves a slow progression of insulitis with both inflammation and destruction of β-cells. The two timely questions concern triggering mechanisms—that is, the event that stimulates the differentiation of β-cell-specific T cells, and the nature of the maneuvers that could arrest or reverse the otherwise inevitable progression that ultimately leads to the complete and selective destruction of β-cells. Furthermore, several strategies are being investigated, with those aimed at stimulating regulatory T cells using either β-cell antigen peptides or anti-CD3 monoclonal antibodies seeming particularly attractive.

Type 1 diabetes mellitus (T1DM) comprises several diseases of the pancreatic ß cells which lead to an absolute insulin deficiency. This is usually considered to be the result of an autoimmune destruction of the pancreatic ß cells (type 1A). Some patients with T1DM with no evidence of ß cell autoimmunity have underlying defects in insulin secretion often from inherited defects in pancreatic ß cell glucose sensing and from other genetic or acquired diseases.

T1DM is one of the most common chronic diseases of childhood and is classified as an autoimmune disease. Most common autoimmune disorders predominantly affect females, but,T1DM equally affects males and females with a slight male predominance in younger children. This and other inconsistencies have raised questions as to whether T1DM is a “pure” auto-immune disease or whether the auto-immune component is a marker of a separate primary trigger.T1DM has been associated with other viral infections including rubella, mumps, Epstein–Barr and cytomegalovirus. The viral infection usually precedes the clinical presentation of T1DM. The causality between enterovirus infections and the diabetogenic proocess are still unclear.

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Several epidemiological and clinical studies have supported the role of enterovirus, especially Coxsackie B4 and B3 virus, in the development of T1DM in genetically predisposed individuals.[6] Such association is supported by the description of a temporal relationship between the occurrence of T1DM and peaks of enterovirus infections and by the detection of anti-enterovius antibodies, enterovirus RNA, and capsid protein VP1 in blood, small intestine biopsies, and autopsy pancreas specimens of individuals with T1DM.

Various mechanisms can explain the role of enterovirus in the pathogenesis of T1DM: (1) persistent infection of pancreatic beta cells provoking cell damage and release of sequestered antigens inducing an autoimmune response; (2) molecular mimicry (partial sequence homology) between the 2C viral protease and the GAD65 (Glutamic Acid Descarboxilase) and between the VP1 viral capsid protein and the IA2 protein; (3) bystander activation of autoreactive T cells; (4) thymus infection; and (5) loss of regulatory T cells. However, a causative correlation still needs to be established.