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

The incidence of diabetes mellitus was increased in patients with congenital rubella. Experimental congenital rubella infection in rabbits caused histological changes in the beta-cells of the pancreatic islets similar to those found in mice made diabetic by the M variant of the encephalomyocarditis virus. It is concluded that the diabetes seen in congenital rubella is due to viral infection of the pancreatic islet cells.
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PMID:Rubella infection and diabetes mellitus. 7 64

50 patients with congenital rubella, born in 1939-43, were reviewed in 1967. Here we report their outcome in 1991. Since 1967, there have been 7 deaths (3 cardiovascular, 3 malignant disease, 1 AIDS). 40 had full clinical assessment. The prevalence of diabetes mellitus is similar to that in 1967: 4 of the 5 reported diabetic then, remain so, and there is 1 new case. 1 subject has malignant melanoma and 3 have died from cancer. Although the incidence of malignant disease is not increased, the death rate is (standardised mortality rate 6.0, 95% CI 1.24-17.57). Longer follow-up will be required to confirm this observation.
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PMID:A fifty-year follow-up of congenital rubella. 135 68

A high incidence of insulin-dependent diabetes mellitus (IDDM) has been reported in children and young adults previously afflicted with congenital rubella syndrome (CRS). The authors have studied the effect of rubella virus infection on human pancreatic islet cells in tissue culture. These experiments were performed with the use of both monolayers and free-floating human fetal islets of Langerhans tissue. Levels of production of immunoreactive insulin by islet cells that had been infected by rubella virus were lower than those observed in control cultures, under conditions of high glucose concentration (11.1 mmol/L) in the medium. The presence of rubella viral antigens in human pancreatic beta and non-beta cells was demonstrated by double-label immunofluorescence. These results suggest that rubella virus can infect human pancreatic islet cells and that such infection may lead to significant reductions in levels of secreted insulin.
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PMID:Infection of cultured human fetal pancreatic islet cells by rubella virus. 264 1

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

The specific genes causing type 1 diabetes susceptibility in any species are unknown. Serological HLA studies have shown susceptibility to type 1 diabetes is linked to HLA DR3 and DR4 allels, whereas DR2 and DR5 alleles contain protective elements. DR4 chromosomes can be divided into diabetes prone or resistant by restriction fragment length polymorphism analyses with cDNA probes for DQ beta-gene. No type 1 diabetes-specific environmental factors have been revealed to be convincingly implicated in human type 1 diabetes. Congenital rubella, by its lasting influence on T cells creates susceptibility to many organ-specific autoimmune diseases. Certain dietary proteins shown in BB rats as well as hyperglycemia during the prenatal period increase the later incidence of type 1 diabetes. Human type 1 diabetes results from a progressive probably autoimmune loss of the pancreatic beta cells. The immunologic hallmarks of type 1 diabetes is the lymphocytic infiltration of pancreatic islets, the hyperexpression of class I MHC on all islet cells and the abarrent class II MHC expression on beta cells within inflamed islets, the increased frequency of activated T cells in islet and circulation. It is generally accepted that cellular immunity plays the major role in the pathogenesis of type 1 diabetes. The heightened autoimmune reactivity being detectable during the preclinical period, lasting months to years, has been proved by antibodies directed against cytoplasmic islet cell antigens (ICA), beta cell surface antigens (ICSA), insulin (IAA), and with a lower frequency against non-islet cell antigens. The presence of IgG insulin autoantibodies and complement fixing ICA confers increased risk for future type 1 diabetes development in genetically predisposed individuals than the presence of either marker alone. For ICSA a more specific and quantitative assay is needed. 90% of children developing type 1 diabetes were detected positive for ICA and/or IAA. By the time of clinical onset if type 1 diabetes some 90% of the insulin secretory beta cell mass has already been destroyed. For this reason, new approaches are needed to address the causes of diabetes and not just the consequences. The development of insulin-dependent diabetes may be reversible, or even preventable by early detection coupled with the judicious use of immunotherapy.
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PMID:Immunological disorders of type 1 diabetes mellitus. 268 94

The major goal of rubella immunization is the prevention of the congenital rubella syndrome. As many as 20 per cent of women in the reproductive age group in the United States continue to be susceptible to rubella despite the immunization programs currently in place. Intensified efforts are therefore needed to identify persons at risk for infection and to vaccinate them. Women who develop a rubella-like illness during pregnancy should have the diagnosis confirmed serologically because a diagnosis based on clinical criteria alone is unreliable and because of the serious implications of gestational rubella infection. The rubella virus can infect the fetus at any stage of pregnancy, but defects are rarely noted when this occurs after the 16th week of gestation. The most common abnormalities in the congenital rubella syndrome are hearing loss, mental retardation, cardiac malformations, and eye defects. Diabetes mellitus, thyroid disease, glaucoma, and other delayed manifestations of congenital rubella syndrome are common, thereby necessitating long-term followup of these patients. The detection of rubella-specific IgM antibodies in fetal blood is helpful in establishing the diagnosis prenatally and can aid in the management of pregnancies complicated by this infection. Susceptible women identified through screening during pregnancy should be immunized in the immediate postpartum or postabortion period. Although the live, attenuated rubella vaccine is contraindicated during pregnancy, pregnant women who are inadvertently immunized are not candidates for pregnancy termination because no defects consistent with congenital rubella have been reported to date in the offspring of other similarly vaccinated women.
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PMID:Maternal rubella and the congenital rubella syndrome. 328 22

In order to determine if congenital rubella infection is associated with persistent T cell abnormalities, T cell subsets were quantitated in 16 non-institutionalized subjects (ages nine to 21) with the clinical stigmata and history of congenital rubella. Flow cytometric analysis revealed a decreased T4/T8 ratio (mean +/- SEM in subjects with rubella, 1.57 +/- 0.15, p less than 0.01; in normal subjects, 2.3 +/- 0.4; in subjects with type I diabetes, 2.3 +/- 0.3), decreased percent of T4-positive "helper" cells (42.6 +/- 2.3) different from that in both normal subjects (52.6 +/- 2.4, p less than 0.01) and subjects with recent-onset diabetes (51.5 +/- 2.4), and increased percent of T8-positive "suppressor/cytotoxic" T cells (29.9 +/- 1.4, p less than 0.02) relative to that in normal subjects (24.2 +/- 1.5) and subjects with type I diabetes (23.9 +/- 1.4). Five of 16 subjects with congenital rubella had an elevation of la-positive T cells. Approximately 20 percent had antimicrosomal antibodies. One subject had diabetes mellitus and hypothyroidism, one had hypoglobulinemia, and one had previously undiagnosed hyperthyroidism. Glycosylated hemoglobin levels were normal in all except the diabetic subject, and none of the subjects was islet cell antibody-positive. The T cell abnormalities documented may predispose persons with congenital rubella to the development of organ-specific autoimmunity.
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PMID:Congenital rubella. Monoclonal antibody-defined T cell abnormalities in young adults. 349 Jul 85

Although target tissues or glands differ, several common threads have begun to emerge that link the diseases of the autoimmune endocrine syndromes. In the polyglandular syndrome type II, a defect resides in one of the genes of the major histocompatibility locus which, in concert with other gene(s), results in susceptibility. Genetic susceptibility is necessary but not sufficient to produce the disorder. This is illustrated by the lack of 100% concordance of disease in identical twins. This lack of concordance has led to the search for environmental influences or "triggers" of the autoimmune process. These "triggers" have not been well defined, but may include amiodarone or other iodine-containing medications for thyroid autoimmunity and congenital rubella for some patients with diabetes and thyroiditis. The autoimmune destruction of most target glands appears to be a slow process with a long preclinical prodrome that may last for years. During this period, autoantibodies, lymphocyte abnormalities, and subclinical endocrine defects are usually present. As knowledge of target antigens has progressed, it appears that despite polyendocrine disease, within each gland specific antigens are the targets of the autoimmune process. When the genetic defect(s) and environmental influences of organ specific autoimmunity are better understood, it may be possible to devise specific "replacement" or corrective therapies. In the absence of this knowledge, therapies directed at partial immunosuppression are currently being studied in Type I diabetes and Graves' ophthalmopathy. Given the similar features of many of the organ-specific autoimmune disorders, it is likely that if immunotherapeutic modalities are successful in one disease, they may be of benefit in related disorders.
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PMID:Polyglandular autoimmunity. 351 21

The congenital rubella syndrome provides the best documentation in humans that a viral infection is associated with the subsequent development of insulin-dependent diabetes mellitus. We have developed an animal model in neonatal golden Syrian hamsters infected with rubella virus passaged in beta-cells that closely parallels the diabetes observed with congenital rubella. The hamsters develop hyperglycemia and hypoinsulinemia, which are sustained throughout the 15-wk study period. A mononuclear infiltration of the islets, isolation of rubella virus from whole pancreas, the presence of viral antigen in beta-cells by immunofluorescent localization, and cytoplasmic islet cell antibodies (40%) are demonstrated. These data suggest that an autoimmune process and diabetes develop after rubella virus infection in neonatal hamsters. This model may uncover the precise mechanism by which rubella virus induces similar disease in humans.
Diabetes 1986 Nov
PMID:Rubella virus-induced diabetes in the hamster. 353 Aug 56

An increased incidence of insulin-dependent diabetes mellitus (IDDM) has been reported in patients with congenital rubella syndrome (CRS). Thus, studies of children with CRS would be of great importance in following the development of IDDM in a susceptible population. A total of 242 children with CRS, 30 of whom already have diabetes (mean age, 17.4 +/- 0.3 years) have been evaluated. In this latter group, the frequency of HLA DR3 is significantly increased and that of HLA DR2 significantly decreased. While pancreatic islet cell cytotoxic or surface antibodies (ICSA) are found in 20.2% of the total population of patients with CRS, they are present in 50%-80% of patients with glucose abnormalities. In all but five of the ICSA-positive patients, glucose abnormalities are currently present. In addition, glucose intolerance is found in greater than 50% of the DR3-positive nondiabetic patients with CRS evaluated to date. The data demonstrate that patients with CRS at risk for IDDM have the same genetic and immunologic features seen in classic IDDM, namely the presence of HLA DR3 and the absence of HLA DR2 and the high prevalence of ICSA before decompensation.
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PMID:Diabetes mellitus and autoimmunity in patients with the congenital rubella syndrome. 389 Jan 4


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