Cases reported "Diabetes Mellitus, Type 1"

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1/61. Minimal-change nephrotic syndrome and acute renal failure in a patient with aged onset insulin-dependent diabetes mellitus and autoimmune thyroiditis.

    A 61-year-old woman with a 2-year history of insulin-dependent diabetes mellitus (IDDM) developed nephrotic syndrome. Renal biopsy showed minimal-change nephrotic syndrome (MCNS), and no evidence of diabetic glomerulosclerosis. Although steroid therapy was initiated, plasma urea and creatinine rose and hemodialysis was required. After 4 weeks, she responded to steroids and her renal function returned to normal. MCNS, which is not associated with diabetic glomerulosclerosis, has rarely been seen in IDDM patients with nephrotic syndrome. Her human leukocyte antigen typing was A24, BW52, BW61, DR2 and DR9. This typing has been reported to be associated with both IDDM and renal disease.
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2/61. Bilateral pulmonary aspergilloma caused by an atypical isolate of aspergillus terreus.

    A case of bilateral pulmonary aspergilloma caused by an atypical isolate of aspergillus terreus is described. The diagnosis was established by the presence of septate, dichotomously branched fungal elements in freshly collected bronchoalveolar lavage and sputum specimens and by repeated isolation of the fungus in culture. Specific precipitating antibodies against the A. terreus isolate were demonstrated in the patient's serum. The isolate was atypical as it failed to produce fruiting structures on routine mycological media, but it did so on extended incubation on potato flake agar and produced globose, relatively heavy-walled, hyaline accessory conidia (formerly termed aleurioconidia) on both vegetative and aerial mycelia. Also, it produced an intense yellow diffusing pigment in the medium. The report underscores the increasing importance of A. terreus in the etiology of pulmonary aspergillosis. It is suggested that A. terreus antigen be included in the battery of serodiagnostic reagents to facilitate the early diagnosis of infections caused by this species.
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3/61. Toxic shock syndrome associated with newly diagnosed type I diabetes.

    Studies of two post-mortem pancreata of children at the onset of type I diabetes have suggested activation and expansion of islet infiltrating T cells by a superantigen. We present the first reported case of a superantigen mediated disease, toxic shock syndrome (TSS), occurring at the diagnosis of type I diabetes. A 12-year-old girl presented with TSS and newly diagnosed diabetes with ketoacidosis. At presentation she was unconscious, febrile and hypotensive, with a desquamating erythematous rash and Kussmaul breathing. During resuscitation, her renal impairment, diarrhoea, thrombocytopaenia and ketoacidosis resolved. vaginal discharge and blood cultures grew staphylococcus aureus. T cell studies at 2 weeks after diagnosis detected a high level of spontaneous and islet antigen-specific proliferation with associated interleukin-10 production compared to human leucocyte antigen DR matched controls.
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4/61. Evidence of recurrent type I diabetes following HLA-mismatched pancreas transplantation.

    Type 1 diabetes mellitus is considered as an autoimmune disease against beta cells. Diabetes recurrence after pancreas transplantation is well known in HLA-identical twins while it is rarely reported in recipients of cadaveric pancreatic grafts. In the present case report, diabetes recurrence occurred in a recipient who underwent cadaveric combined pancreas kidney transplantation. Seven years after transplantation the patient exhibited progressive hyperglycemia needing insulin therapy while the renal graft was well functioning. The diagnosis of recurrent disease was obtained on the histological features such as selective loss of beta cells without clear signs of insulitis and on the presence of markers (GAD 65 and IA-2) for humoral autoimmunity. It is intriguing that, at the time of recurrence of type 1 diabetes, the patient had stopped steroids and azathioprine, while only cyclosporine was maintained as immunosuppressive treatment. Our case report underlines the relevance of studying the humoral autoimmune response directed to islet autoantigens in cadaveric pancreas allograft recipients. Furthermore, it suggests that an efficient immunosuppressive treatment after transplantation may be able to reduce the autoimmune response against the pancreatic allograft.
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5/61. Acute onset of type I diabetes mellitus after severe echovirus 9 infection: putative pathogenic pathways.

    enterovirus infections have been implicated in the development of type I diabetes mellitus. They may cause beta cell destruction either by cytolytic infection in the pancreas or indirectly by contributing to autoimmune reactivity. We sought evidence for these 2 mechanisms in a case of acute-onset diabetes mellitus that occurred during severe echovirus 9 infection. The virus was isolated and administered to cultured human beta cells. No viral proliferation was observed, and no beta cell death was induced, while parallel exposure to Coxsackie B virus serotype 3 resulted in viral proliferation and massive beta cell death. Although the viral protein 2C exhibited a sequence similar to that of the beta cell autoantigen glutamic acid decarboxylase (GAD(65)), no cross-reactive T cell responses were detected. The patient did not develop antibodies to GAD(65) either. Absence of evidence for direct cytolytic action or an indirect effect through molecular mimicry with GAD(65) in the present case raises the possibility of another indirect pathway through which enteroviruses can cause diabetes mellitus.
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6/61. Slowly progressive insulin-dependent diabetes mellitus in an elderly patient with Graves' disease.

    We report a case of slowly progressive insulin-dependent diabetes mellitus in an elderly patient with Graves' disease. A 69-year-old man presented with apathetic thyrotoxicosis and weight loss. Laboratory findings indicated insulin-dependent diabetes mellitus (IDDM) with Graves' disease. Human leukocyte antigens DR4 and DR9, which are recognized as markers for IDDM with autoimmune thyroid disease, were detected. The clinical course of the IDDM was compatible with the slowly progressive type. Onset of this disease during old age is rare, and such cases should be analyzed with a thyroid function test because the symptom of thyrotoxicosis may be masked in the elderly.
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7/61. Neonatal Type I diabetes associated with maternal echovirus 6 infection: a case report.

    AIMS/HYPOTHESIS: Neonatal diabetes mellitus is rare, and it has not been associated with beta-cell autoimmunity. Enteroviral infections during pregnancy have been implicated as a risk factor for the later development of Type I (insulin-dependent) diabetes mellitus. We now report of a baby girl who was born severely growth-retarded with neonatal insulin-deficient diabetes, and look for evidence of intrauterine enteroviral infections and beta-cell targeted autoimmunity. methods: Diabetes-associated autoimmunity was studied by measurement of several types of islet cell reactive autoantibodies. The infant's T-cell responses to insulin and enterovirus antigens were recorded and enterovirus antibodies were measured both from the mother and the child. RESULTS: Several types of diabetes-associated autoantibodies were detected postnatally, including insulin autoantibodies, conventional islet cell autoantibodies and glutamic acid decarboxylase antibodies, whereas no autoantibodies were observed in the mother. The infant's T-cells showed reactivity to insulin and purified enterovirus particles. Based on serological studies, the pathogenetic process could have been triggered by an echovirus 6 infection during pregnancy. The patient's diabetes has been permanent, although there were signs of endogenous insulin production for several months. exocrine pancreatic insufficiency was diagnosed at the age of 1 year. CONCLUSION/INTERPRETATION: These observations suggests that enteroviral infections may induce beta-cell autoimmunity even in utero.
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8/61. A case of insulin dependent diabetes mellitus following systemic treatment for Vogt-Koyanagi-Harada syndrome.

    A 29-year-old man developed acute visual impairment, cough, and headache. Both eyes showed serous retinal detachment in the posterior fundus. fluorescein angiography showed subretinal pooling of fluorescein in the late phase. A diagnosis of Vogt-Koyanagi-Harada (VKH) syndrome was made based on clinical features. Treatment with systemic corticosteroids resulted in improvement of uveitis and both eyes showed "sunset glow" fundus 11 months later. insulin-dependent diabetes mellitus (IDDM) developed 13 months later (3 months after systemic corticosteroid therapy). Despite treatment with insulin, glycemic control was poor. Human leukocyte antigen (HLA) typing showed HLADR9 and DQB 1*0303 related to IDDM. We postulated that treatment with corticosteroids precipitated IDDM, a yet unknown common autoimmune mechanism might have caused IDDM and VKH, or both conditions occurred coincidentally.
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9/61. HLA-DR53 molecules restrict glutamic acid decarboxylase peptide presentation to T cells of a Type I diabetes patient: specification of the trimolecular HLA-peptide/T-cell receptor complex.

    AIMS/HYPOTHESIS: Our aim was to define the molecular specificity of glutamic acid decarboxylase-specific T-cells isolated from a patient (patient 40) with recent onset Type I (insulin-depent) diabetes mellitus. methods: The peptide epitope was defined using synthetic peptides to identify the minimal sequence required for T-cell activation and to determine the amino acids that contribute either to MHC binding or T-cell receptor signaling. The MHC class II-restricted peptide presentation was determined using a panel of allogeneic antigen-presenting cells and murine fibroblast-cell lines transfected to express individual human class II alleles and by blocking studies with monoclonal antibodies. The T-cell receptor was also molecularly characterized. RESULTS: Despite that patient 40 carries high-risk alleles of the DRB1 and DQB1 loci, his T-cells recognize a glutamic acid decarboxylase-derived peptide in association with class II, DR53, molecules. Although anchor residues for DR53 molecules have not yet been determined, it was possible to model epitope binding based on sequence comparisons with other class II molecules associated with susceptibility or protection for Type I diabetes. CONCLUSION/INTERPRETATION: The complete molecular specification of the MHC-peptide ligand and the T-cell receptor complex of glutamic acid decarboxylase-specific T-cells will enable analysis of strategies designed to alter T-cell function. For example, the role of altered peptide ligands or T-cell receptor-specific peptides can be studied using a model whose components reflect the natural affinities of MHC-peptide and T-cell receptor-ligand interactions selected in response to this important autoantigen.
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10/61. common variable immunodeficiency, insulin-dependent diabetes mellitus and celiac disease.

    common variable immunodeficiency is a disorder characterised by hypogammaglobulinemia with b-lymphocytes in peripheral blood and repeated infections. We report a child with a diagnosis of diabetes mellitus and celiac disease during lactation, and in whom common variable immunodeficiency was diagnosed at the age of 5. During evolution of the disease he presented multiple respiratory infections in spite of substitution therapy with gamma globulins. He presented pulmonary fibrosis with a pulmonary volume reduced, and a spirometric restrictive patron. Immunologically, he presents reduction in CD4 lymphoid population. He expresses the alleles DQ2 A1 0501 and B1 which are strongly associated with susceptibility to insulin-dependent diabetes mellitus and celiac disease, but don't express antigens HLA class II DR3 and DR4 that are more frequent in these entities. The main disease and all the complications had affected his curve pondostatural.
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