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

In 1814, George Maton, first recognized that a mild illness characterized by rash, adenopathy, and little or no fever was a discrete entity. Henry Veale, in 1866, named the disease rubella. The illness attracted little attention until 1942, when Norman Gregg noticed that first-trimester maternal rubella caused serious birth defects. The full spectrum and impact of rubella embryopathy remained unclarified until rubella virus was isolated in tissue culture in 1962 by two independent groups: Parkman, Buescher, and Artenstein; and Neva and Weller. Using the new tools of the virus laboratory, many investigators concentrated on the consequences of a severe rubella epidemic in 1964, which affected approximately 1% of pregnancies. Newly recognized transient manifestations of congenital rubella infection (CRI) include neonatal thrombocytopenic purpura, hepatitis, bone lesions, and meningoencephalitis and late-emerging sequelae such as diabetes mellitus and progressive rubella panencephalitis added to the cataract, heart disease, mental retardation, and deafness previously defined as due to CRI. Sharp contrasts were documented between the patterns of virus excretion and immune response of postnatal vs. congenital rubella. Licensure and widespread distribution of attenuated rubella virus vaccines in 1969 have prevented epidemic rubella. Pockets of illness remain, even in the United States. Continued effort will be required to eliminate the rubella problem.
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PMID:The history and medical consequences of rubella. 389 Jan 5

The manifestations of congenital rubella syndrome (CRS) can be grouped according to time of onset into newborn, extended, and delayed CRS. The delayed manifestations are not present in early life and include the following: endocrinopathies: diabetes, thyroid disease, and growth hormone deficiency; deafness; ocular damage: glaucoma, keratic precipitates, keratoconus, corneal hydrops, and absorption of the cataractous lens; vascular effects: fibromuscular proliferation of the intima, sclerosis of arteries, systemic hypertension secondary to renal disease, and subretinal neovascularization; and progressive rubella panencephalitis. Several mechanisms of pathogenesis of the damage have to be considered for the delayed manifestations, including growth of the virus in tissues, resulting in a reduced growth rate and shortened life-span of the cells; autoimmune responses, initially stimulated by the infection; genetic susceptibility; vascular damage by the viral infection with further stenosis or occlusion of the vessels later; reactive hypervascularization; and chronic persistence of the virus in the tissue with subsequent extension of the infection to other areas.
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PMID:Delayed manifestations of congenital rubella. 400 24

An increased prevalence of Type 1 (insulin-dependent) diabetes has been reported in patients with congenital rubella. Rubella virus multiplies in the pancreas, and we have hypothesized that studies of children with congenital rubella would be of great importance in following the development of Type 1 diabetes in a defined, susceptible population. Two hundred and forty-one children with congenital rubella (mean age 17.4 +/- 0.3 years; 65% black and hispanic) have been evaluated, 30 of whom already have diabetes and 17 of whom have borderline glucose tolerance. In these latter two groups, HLA-DR3 is significantly increased and HLA-DR2 significantly decreased. Pancreatic islet cell cytotoxic surface antibodies are found in 20% of the total congenital rubella population, including in more than 50% in the time period before they develop diabetes and are not related to any specific HLA type. In addition, anti-microsomal and anti-thyroglobulin antibodies are found in 34% of this population. The data demonstrate that Type 1 diabetes developing in congenital rubella patients has the genetic and immunological features of classical Type 1 diabetes, namely the presence of HLA-DR3, the absence of HLA-DR2, islet cell surface antibodies before decompensation and an increased prevalence of anti-thyroid antibodies. Patients with non-diabetic congenital rubella represent an easily identifiable group in whom other immunological factors associated with Type 1 diabetes can be elucidated and possibly modified.
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PMID:Congenital rubella syndrome as a model for type 1 (insulin-dependent) diabetes mellitus: increased prevalence of islet cell surface antibodies. 638 25

The HLA antigens of 173 patients with the congenital rubella syndrome (CR) are reported. Twenty-one of these patients are also clinically diabetic, and among them the frequencies of the HLA antigens DR2 and DR3 are significantly lower and higher, respectively, than in CR patients without diabetes or in controls. These data suggest that the genes that control susceptibility to type I or insulin-dependent diabetes mellitus are necessary for the development of glucose intolerance in CR patients.
Diabetes 1982 Dec
PMID:The HLA system in congenital rubella patients with and without diabetes. 695 35

A male patient born to a mother who developed rubella during the tenth week of gestation presented a typical congenital rubella syndrome with mental retardation, neuro-sensory deafness, hypoplasia of the dental enamel and chorioretinitis. Hyperthyroidism occurred at the age of 3 10/12 years and was treated successfully with propylthiouracil for 4 years. The course was complicated by premature craniosynostosis and a craniectomy was performed at the age of 7 years. Overt diabetes mellitus developed at 17 years and was well controlled by insulin therapy. Histocompatilibity (HLA) antigens were A2, B8, B40. Diabetes mellitus and thyroid disorders have previously been reported after congenital rubella, and recently after congenital cytomegalovirus infection. Our patient had both endocrinopaties. It is possible that HLA B8 antigens might be responsible for increased susceptibility to rubella infection.
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PMID:Hyperthyroidism, diabetes mellitus and the congenital rubella syndrome. 736 31

The high frequency of insulin-dependent diabetes (IDDM) in children with congenital rubella suggests that the infectious agent may trigger the autoimmune process. To explore the immunologic relationship between rubella virus and IDDM, we examined a panel of mAb that recognizes rubella virus capsid and envelope glycoproteins for reactivity with islet cell Ag. One mAb, C9, which recognizes a defined domain within the capsid protein of rubella virus, was found to react with extracts from a rat beta-cell tumor and normal rat and human islets. Using one and two dimensional immunoblot analysis of rat beta-cell tumor extracts, the C9-like epitope was found to reside on a 52 kDa protein that is also the target of autoantibodies from human IDDM and nonobese diabetic mice. To confirm this cross-reactivity, antibodies in diabetic sera were absorbed to the recombinant rubella virus capsid protein, eluted, and then shown to react with the 52 kDa insulinoma protein. These data show that an immunogenic epitope on the rubella virus capsid protein is mimicked by a similar structure on a beta-cell protein. These findings suggest that rubella virus has the potential to sensitize susceptible individuals for an autoimmune response to beta-cell Ag and identify one mechanism that may contribute to beta destruction in IDDM.
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PMID:Monoclonal antibody to rubella virus capsid protein recognizes a beta-cell antigen. 845 75

Despite recent progress in immunology and genetics, the causes of type 1 diabetes remain unknown. Prevention of autoimmune diseases through immunomodulation or gene therapy has not yet been successful in humans. In contrast, some autoimmune diseases such as celiac disease, rheumatic fever, and congenital rubella induced diabetes can be avoided through modification of environmental factors. Candidate environmental causes of type 1 diabetes are now being characterized in cohort studies and clinical trials. An alternative approach to prevention of type 1 diabetes may include a "vaccination" in early childhood to induce tolerance to critical autoantigen(s). This paper reviews the status of current diabetes prevention trials in humans and selected new interventions that are being tested in animal models. We estimate the cost of public health implementation of selected screening and intervention scenarios. The ethical, logistic, and funding issues underlying these scenarios are discussed.
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PMID:Prevention of type 1 diabetes from laboratory to public health. 1043 2

To fully characterize human glutamic acid decarboxylase (GAD)65 protein T-cell epitopes associated with insulin-dependent diabetes mellitus (IDDM), CTL clones specific to GAD65 protein antigens were isolated from two congenital rubella syndrome (CRS)-associated IDDM patients. Overlapping nonamer T-cell epitopes recognized by both CD4+ or CD8+ CTL clones within peptides GAD65(252-266) and GAD65(274-286) were identified as sequences bounded by GAD65(255-266) with 6/9 overlapping residues, and GAD65(276-285) with 8/9 overlapping residues, respectively, using two panels of overlapping peptide analogs in cytotoxicity assays. HLA restrictive elements of the T-cell clones were also identified using a panel of B cell lines with different HLA phenotypes as targets in cytotoxicity assays. The antigenic GAD65 peptides elicited cytotoxic responses of peptide-specific CD4+ T-cell clones in the context of HLA DRB1*0404. The CD8+ T-cell clone specific to GAD65(255-263) was found to be restricted by HLA A3 and A11. Similarly, the CD8+ T-cell clone specific to GAD65(277-285) killed peptide-sensitized target cells expressing HLA B35 and B15. The observed HLA restriction of these overlapping epitopes implies that a tandem of [DRB1*0404-A11(3)] and/or a tandem of [DRB1*0404-B35(15)] might predispose CRS patients to development of IDDM.
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PMID:CD4+ and CD8+ T-cell clones from congenital rubella syndrome patients with IDDM recognize overlapping GAD65 protein epitopes. Implications for HLA class I and II allelic linkage to disease susceptibility. 1043 11

Type 1A diabetes is an immune mediated disorder that results from progressive destruction of the islet beta-cells in the setting of genetic susceptibility. Both MHC and non-MHC genes contribute to disease with class II HLA molecules major determinants of susceptibility or protection. The presence of multiple anti-islet autoantibodies is associated with a high risk of disease progression, and the first anti-islet autoantibodies may appear as early as the first year of life. Congenital rubella is the only infection clearly associated with the development of type 1A diabetes. With the ability to detect children in the first year of life activating autoimmunity, prospective studies may in the future document additional environmental factors either increasing or decreasing diabetes risk.
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PMID:Type 1A diabetes induced by infection and immunization. 1133 4

The clinical characteristics, autoantibody profiles and seroprevalence of human T lymphotropic virus Type 1 (HTLV-1) were assessed in 30 Jamaican patients with Type 1 diabetes mellitus. Two hundred and fifty-two blood donors and 108 patients with Graves' disease were included as controls for the HTLV-1 component of the study. The mean age of onset of diabetes mellitus was 20.5 +/- 9.2 years and the mean duration of diabetes mellitus was 10.5 +/- 6.1 years. The remarkable clinical data included an absence of other associated organ-specific autoimmune diseases, and clinical evidence and history of congenital rubella in one patient. Islet cell cytoplasmic antibodies (ICA) were absent but 17% (5/30) of the diabetic patients tested positive for glutamic acid decarboxylase (GAD) antibodies. No other organ-specific autoantibodies were detected but non-organ-specific autoantibodies were present in 9 (30%) of the sera of diabetic patients. The seroprevalence of HTLV-1 in the patients with diabetes mellitus was significantly higher than that in the healthy controls (17% (5/30) versus 4% (11/252), p = 0.05). Autoantibodies were found in the sera of 4/5 (80%) of the diabetic patients who were positive for HTLV-1. None of the patients with onset of diabetes mellitus below age 15 years was HTLV-1 positive. The likely polyaetiological nature of Type 1 diabetes mellitus in Jamaicans is being further investigated at the molecular level.
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PMID:Autoantibodies, human T lymphotropic virus type 1 and type 1 diabetes mellitus in Jamaicans. 1250 40


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