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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It is now well known that insulin-dependent diabetes is a chronic progressive autoimmune disease. The prolonged prediabetic phase of progressive beta-cell dysfunction is associated with immunological abnormalities. A prediabetic period is suggested by the appearance of islet cell antibodies, anti-insulin antibodies, and anti-insulin receptor antibodies. The existence of activated T lymphocytes and abnormal T cell subsets are also other markers. There is still no concensus about the use of the immunosuppression superimposed upon conventional insulin therapy in early diagnosed IDDM and the follow-up of the relatives of IDDM patients who share the genetic predisposition and serological markers for the risk of future onset of IDDM. Treatment in the prodromal period cannot be justified because a link between the disease and early markers such as ICA has not been established with certainty (Diabetes Research Program NIH, 1983). Many immunopharmacological manipulations were reported to be effective in animal models. However, most of them are not readily applied to human subjects. Moreover, IDDM patients are now believed to be heterogeneous, with a complex genetic background. HLA-DR, and more recently DQ, are closely related to the genetic predisposition to IDDM but those genes are not themselves diabetogenic. The contribution of autoimmunity does not appear to be uniform, and in some cases, the contribution of virus is considered more important. There is a lack of a marker for the future onset of IDDM. ICA and ICSA were found after mumps infection, but the existence of those autoantibodies and even the co-existence of HLA-DR3 do not always indicate the future trend to insulin dependency. More precise markers will be disclosed through the biochemical analysis of the target antigens on pancreatic beta-cell for islet antibodies and effector T cells. Much safer and more effective immunopharmacological treatment will be developed through animal experimentation using rat and mouse models. The recent development and interest in this field will further facilitate the attainment of the goal for the complete prevention of IDDM.
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PMID:Immunological aspects of diabetes mellitus: prospects for pharmacological modification. 251 48

The in vitro production of interferon-alpha was studied in cultures of peripheral blood mononuclear cells from children with insulin-dependent diabetes. Significantly lower levels (p less than 0.01) of interferon (median 64 IU/ml) were found in mumps antigen stimulated cultures of IDDM patients compared to control children (median 256 IU/ml) whereas no differences between groups were found in the amount of interferon induced by Coxsackie B pool antigen or live Sendai virus.
Diabetes Res 1989 Oct
PMID:Low levels of mumps virus antigen induced interferon-alpha production in insulin-dependent diabetes. 256 52

In spite of the potential assay problems, a relatively clear general picture concerning islet cell antibodies has emerged. They are undoubtedly the most potent indicator of risk for insulin-dependent diabetes, at least among high-risk persons (that is, first-degree relatives of insulin-dependent diabetics). Islet cell antibodies have been the focus of intense research scrutiny over the last decade, yet their etiologic role remains unclear. In patients with insulin-dependent diabetes, there is no striking relation at onset between islet cell antibodies and determinants such as age and HLA type. Certain characteristics, however, may be related to islet cell autoimmunity in a more complex way. There appears to be some racial difference in onset-related islet cell antibody prevalence and other autoimmunity. The observation that autoimmune abnormalities are more frequent among women and among diabetics leads to the question of whether there is an interaction of sex and autoimmune diabetes. There may be a group of early-onset patients, distinguished by persistent islet cell antibodies or coexistent autoimmune phenomena, who are predominantly female. At present, there is only limited evidence for this in the literature: Bottazzo et al. found that juvenile diabetics with persistent islet cell antibodies were more often female. Female diabetics have been shown to have an increased prevalence of thyroid autoantibodies compared with male diabetics. Several observations of differences based on sex have emerged from recent studies of insulin-dependent diabetes: 1) the HLA-DR4 antigen is more frequent among female diabetic patients; 2) male HLA-identical siblings of diabetics have a lowered insulin response to glucose administered intravenously; 3) in areas of low insulin-dependent diabetes incidence, the patterns of onset by age differ markedly between the sexes. These sex-specific differences may help to clarify the relation between islet cell autoimmunity and sex. Among nondiabetic persons, those having the highest genetic "risk" for disease appear to have an increased prevalence of islet cell antibodies. There is also some indication that HLA-DR3 may be associated with islet cell autoimmunity. Other related diseases, notably gestational diabetes, non-insulin-dependent diabetes, and certain autoimmune endocrinopathies, are associated with an increased prevalence of islet cell antibodies. An increase in islet cell antibody prevalence occurs in certain viral infections, particularly mumps and congenital rubella. Islet cell antibodies have been noted in the sera of subjects many years before the onset of insulin-dependent diabetes, as well as in normoglycemic relatives.
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PMID:Epidemiology of islet cell antibodies. 268 May 55

Alterations in T-lymphocyte subsets have been connected to the autoimmune pathogenesis of Type 1 (insulin-dependent) diabetes. In this study peripheral blood lymphocytes were analysed by flow cytometry using OKT3, OKT4, OKT8, anti-HLA-DR, anti-IL-2 receptor and anti-membrane immunoglobulin antibodies in newly diagnosed Type 1 diabetic children, their healthy siblings and healthy control children. The results were compared to the occurrence of serologically verified recent virus infections, some of which can induce lymphocyte subset alterations and have also been connected with the onset of diabetes. In most diabetic patients the amounts of OKT3, OKT4, OKT8 and membrane-Ig-positive cells were within the normal range. Exceptional helper/inducer and suppressor/cytotoxic T cell profiles were observed in a few patients, most of whom had serologically verified recent Epstein-Barr, rubella, mumps or Coxsackie B virus infection. In addition, increased numbers of activated IL-2 receptor-positive cells were observed in the patient group. These results suggest that significant lymphocyte subset alterations are not characteristic of Type 1 diabetes but can occasionally be induced by recent virus infections in newly diagnosed patients. However, the slight increase in activated lymphocytes could reflect the activation of cellular immune systems to the autoantigens in the pancreas.
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PMID:Flow-cytometric analysis of lymphocyte subsets in relation to virus infections at the onset of type 1 (insulin-dependent) diabetes. 284 9

Patients from England, Austria, and Australia with recently diagnosed juvenile-onset insulin-dependent diabetes (type 1) mellitus (IDDM) and matched controls were tested for specific IgM responses to Coxsackie B1-5 viruses. 37 of 122 (30%) patients aged less than 15, but only 15 of 204 (6%) controls, were positive (p less than 0.005). Differences in Coxsackie B virus specific IgM responses between patients and controls were statistically significant for patients in England and Austria (p less than 0.005). Coxsackie B virus specific IgM responses were detected in only 3 of 31 patients aged greater than 16. Virus-specific IgM responses were directed against a single serotype, usually Coxsackie B4 or 5, in 23 of 37 (62.5%) children aged less than 15; 10 of 13 (77%) of children aged less than 7 had monotypic responses. Among families of Austrian patients with IDDM, 8 of 79 (10%) siblings had Coxsackie B virus specific IgM responses, 1 of whom subsequently had IDDM, but none of the 80 parents was positive. In contrast, there was no evidence of recent infection by mumps, rubella, or cytomegalovirus (CMV), since mumps-virus specific IgM was present in only 2 of 100 children with IDDM and 5 of 139 controls; no rubella or CMV specific IgM responses were detected in 60 sera from patients with IDDM.
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PMID:Coxsackie B, mumps, rubella, and cytomegalovirus specific IgM responses in patients with juvenile-onset insulin-dependent diabetes mellitus in Britain, Austria, and Australia. 286 61

The proliferative T lymphocyte responses to Coxsackie B4-, mumps- and varicella-zoster viral antigens were characterized. No significant difference in responsiveness was found between healthy individuals and patients with Type 1 (insulin-dependent) diabetes mellitus. Theophyllamine and verapamil decreased antigen-stimulated proliferation, whereas indomethacin in physiologic concentrations (1 microgram/ml) slightly increased proliferation. A major part of the response seemed to be restricted by HLA-DR molecules. Furthermore, for the mumps antigen the DR3- and DR4-determinants which are associated with Type 1 diabetes, seemed to have a different regulatory function on the T lymphocyte response in that an increased frequency of low responders was found among DR3 positive individuals and an increased frequency of high responders among DR4 positives.
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PMID:T lymphocyte responses to Coxsackie B4 and mumps virus. I. Influence of HLA-DR restriction elements. 299 51

To study the relationships between the responses to viral antigens and the HLA-DR3 and -DR4 associations in Type 1 (insulin-dependent) diabetes mellitus, the frequency of T-lymphocyte proliferating in response to mumps, Coxsackie B4 and varicella-zoster antigens was determined. A decreased frequency was found in T lymphocytes able to respond to mumps or Coxsackie B4 when presented together with DR3, as compared with the frequency of T lymphocytes able to respond to these viruses together with other DR determinants. This was not found for varicella-zoster or purified protein derivative of tuberculin. In contrast, an increased frequency was found in T lymphocytes responding to mumps or Coxsackie B4 together with DR4, compared with other DR determinants. The results were similar in Type 1 diabetic and healthy individuals. The results suggest that elements on the DR3 and DR4 molecules may control T-lymphocyte responses to mumps and Coxsackie B4 viruses.
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PMID:HLA-DR3 and -DR4 control T-lymphocyte responses to mumps and Coxsackie B4 virus: studies on patients with type 1 (insulin-dependent) diabetes and healthy subjects. 299 83

Insulin-dependent diabetes mellitus (IDDM) results from the destruction of pancreatic beta cells. Viruses have been suggested as one of the possible causes. The evidence for viruses comes largely from experiments in animals, but several studies in humans also point to viruses as a trigger of this disease in some cases. Encephalomyocarditis (EMC) virus, Mengovirus (2T), and Coxsackie B4 virus infect and destroy pancreatic beta cells when inoculated into mice. This results in hypoinsulinemia and hyperglycemia. The development of EMC virus-induced diabetes is dependent on the genetic background of the host and genetic makeup of the virus. Animals with diabetes for several months show some long-term complications, including glomerulosclerosis, ocular changes, and decreased bone formation and mineralization in addition to acute metabolic changes. EMC virus-induced diabetes can be prevented by a live-attenuated vaccine. The capacity of Coxsackie B4 virus to induce diabetes is also influenced by the genetic background of the host. However, Mengovirus-induced diabetes is not dependent on the genetic background of the host. In contrast to the EMC, Mengo, and Coxsackie B4 viruses, reovirus type 1 seems to be somehow associated with an autoimmune response producing a diabetes-like syndrome in suckling mice. This virus produces an autoimmune polyendocrinopathy that results in very mild and transient glucose intolerance. Several common human viruses including mumps, Coxsackie B3 and B4 viruses, and reovirus type 3 can infect human beta cells in culture and destroy them. A variant of Coxsackie B4 virus has been isolated from the pancreas of a child who died of acute-onset IDDM.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes Care
PMID:Perspectives on the role of viruses in insulin-dependent diabetes. 299 65

Type 1 diabetes mellitus is thought to derive from organ-specific autoimmune reactions, probably triggered by environmental factors. In view of the possible involvement of mumps virus and reoviruses in the pathogenesis of autoimmune endocrine disease, serum antibody levels to these viruses were measured in newly-diagnosed diabetic patients aged 5 to 25 years and in matched control subjects. Diabetic patients showed a significantly lower prevalence and reduced titers of antibodies to mumps and reoviruses. By contrast, the antibody response to measles virus (a non-diabetogenic agent) was remarkably similar in the two groups. It is suggested that individuals with an impaired humoral response to some viral agents are at increased risk of developing diabetes when exposed to pancreotropic viruses.
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PMID:Role of antecedent mumps and reovirus infections on the development of type 1 (insulin-dependent) diabetes. 302 16

The conditions are critically reviewed under which diseases might be aetiologically related to infection by a certain virus. Such a causal correlation has to obey Koch's postulates, but may be very difficult to prove in the case of a "hit and run" process. This will be exemplified in the case of insulin-dependent diabetes mellitus (IDDM). Observations in humans and the results of experiments on laboratory animals are reported, whereby the Coxsackie B and mumps viruses are of particular interest. Furthermore, the mechanisms by which viruses may produce autoimmune diseases are discussed, including virological and immunological aspects. The hypothesis of "molecular mimicry" by Oldstone is quoted as a unifying one, allowing the combination of both aspects. His main assumption is oligopeptide homology between certain virus proteins and some cell proteins and some examples are given. In the presence of such homologies the immune system is first stimulated by the parasitic virus protein, but somewhat later this reaction switches against the host structures, causing continuing cellular damage with the development of autoimmune disease. It is concluded that Koch's postulates in such cases have to be supplemented by assaying for amino acid homologies in viruses and certain cell types.
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PMID:[Is type I diabetes a virus-induced disease?]. 304 11


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