Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Autoantibodies to glutamic acid decarboxylase (GAD65) have been reported in sera from the Cln3(-/-) mouse model of juvenile neuronal ceroid lipofuscinosis (JNCL), and in individuals with this fatal paediatric neurodegenerative disorder. To investigate the existence of other circulating autoreactive antibodies, we used sera from patients with JNCL and other forms of neuronal ceroid lipofuscinosis (NCL) as primary antisera to stain rat and human central nervous system sections. JNCL sera displayed characteristic patterns of IgG, but not IgA, IgE or IgM immunoreactivity that was distinct from the other forms of NCL. Immunoreactivity of JNCL sera was not confined to GAD65-positive (GABAergic) neurons, but also stained multiple other cell populations. Preadsorption of JNCL sera with recombinant GAD65 reduced the intensity of the immunoreactivity, but did not significantly change its staining pattern. Moreover, sera from Stiff Person Syndrome and Type I Diabetes, disorders in which GAD65 autoantibodies are present, stained with profiles that were markedly different from JNCL sera. Collectively, these studies provide evidence of the presence of autoreactive antibodies within multiple forms of NCL, and are not exclusively directed towards GAD65.
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PMID:Distinct patterns of serum immunoreactivity as evidence for multiple brain-directed autoantibodies in juvenile neuronal ceroid lipofuscinosis. 1697 81

Incomplete intrinsic penetrance is the failure of some genetically susceptible individuals (e.g., monozygotic twins of those who have a trait) to exhibit that trait. For the first time, we examine penetrance of susceptibility genes for multiple MHC gene-determined traits in the same subjects. Serum levels of IgA, IgD, IgG3, but not IgG4, in 50 pairs of monozygotic twins discordant for type 1 diabetes (T1D) correlated more closely in the twins than in random paired controls. The frequencies of subjects deficient in IgA (6%), IgD (33%) and IgG4 (12%), but not in IgG3, were higher in the twins than in controls. We postulate that this was because the MHC haplotypes (and possible non-MHC genes) that predispose to T1D also carry susceptibility genes for certain immunoglobulin deficiencies. Immunoglobulin deficiencies were not associated with T1D. Pairwise concordance for the deficiencies in the twins was 50% for IgA, 57% for IgD and 50% for IgG4. There were no significant associations among the specific immunoglobulin deficiencies except that all IgA-deficient subjects had IgD deficiency. Thus, intrinsic penetrance is a random process independently affecting different MHC susceptibility genes. Because multiple different external triggers would be required to explain the results, differential environmental determinants appear unlikely.
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PMID:Incomplete penetrance of susceptibility genes for MHC-determined immunoglobulin deficiencies in monozygotic twins discordant for type 1 diabetes. 1702 85

In humans the primary trigger of insulin-specific immunity is a modified self-antigen, that is, dietary bovine insulin, which breaks neonatal tolerance to self-insulin. The immune response induced by bovine insulin spreads to react with human insulin. This primary immune response induced in the gut immune system is regulated by the mechanisms of oral tolerance. Genetic factors and environmental factors, such as the gut microflora, breast milk-derived factors, and enteral infections, control the development of oral tolerance. The age of host modifies the immune response to oral antigens because the permeability of the gut decreases with age and mucosal immune response, such as IgA response, develops with age. The factors that control the function of the gut immune system may either be protective from autoimmunity by supporting tolerance, or they may induce autoimmunity by abating tolerance to dietary insulin. There is accumulating evidence that the intestinal immune system is aberrant in children with type 1 diabetes (T1D). Intestinal immune activation and increased gut permeability are associated with T1D. These aberrancies may be responsible for the impaired control of tolerance to dietary insulin. Later in life, factors that activate insulin-specific immune cells derived from the gut may switch the response toward cytotoxic immunity. Viruses, which infect beta cells, may release autoantigens and potentiate their presentation by an infection-associated "danger signal." This kind of secondary immunization may cause functional changes in the dietary insulin primed immune cells, and lead to the infiltration of insulin-reactive T cells to the pancreatic islets.
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PMID:Is it dietary insulin? 1713 May 78

The aim of this study was to evaluate the correlation between changes in the concentration of serum magnesium and serum immunoglobulin concentrations in type 1 diabetes mellitus. In this study were included 110 patients with type 1 diabetes mellitus (64 men and 46 women) with ages ranging from 19 to 54 years (mean age 41.6+/-6.8 years). The mean duration of the disease was 8.7+/-7.5 years. Thirty-six healthy subjects served as a control group. The serum magnesium concentrations were evaluated by VITROS 750 XRC, Johnson & Johnson kit, (Ortho Clinical Diagnostics). Total serum IgA, IgG and IgM were determined by laser nephelometry (MININEPH The Binding Site kit). Values are means (x) + standard deviations (SD). Serum magnesium concentrations confirmed the magnesium deficit in patients with type 1 diabetes mellitus (1.8+/-0.11 mg/dL, range 1.73-2.47 mg/dL vs 2.2+/-0.2 mg/dL, range 1.6-2.4 mg/dL). In patients with type 1 diabetes mellitus, IgA levels are mildly elevated (4.03+/-0.51 g/L vs 3.43+/-0.48 g/L; p<0.05), while IgG levels are decreased (7.38+/-0.76 g/L vs 9.92+/-1.32 g/L; p<0.001) and IgM levels are almost constantly normal (1.18+/-0.16 g/L vs 1.22+/-0.15 g/L; p>0.05). Therefore, magnesium deficit has profound immunosuppressive capabilities in patients with type 1 diabetes mellitus by significantly reducing the number of IgG synthesizing cells and serum IgG concentrations.
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PMID:The effect of magnesium deficit on serum immunoglobulin concentrations in type 1 diabetes mellitus. 1723 88

Insulin autoantibodies (IAA) precede clinical type 1 diabetes in children. Immunization events leading to IAA are unknown. The aim of this study was to determine whether some IAA result from mucosal immunization. IgA-IAA and binding of IAA to non-human insulin were examined in selected high and low affinity IAA-positive samples and in first IAA-positive samples from children aged <2 years. High affinity IAA (>10(9)L/mol) bound strongly to human insulin and poorly to chicken insulin. In contrast, 12/13 lower affinity IAA were chicken insulin-reactive, binding equally to human and chicken insulin (n=4), or preferentially binding chicken insulin (n=8). IgA-IAA were found in association with chicken insulin-reactive IAA, and included cases where IgA-IAA predominated over IgG-IAA. Among 20 IAA-positive children aged <2 years, one had early IgA-chicken insulin-reactive IAA that were replaced by high affinity IgG-IAA. The findings suggest that some IAA can result from immunization against molecules other than human insulin at mucosal sites.
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PMID:Identification of insulin autoantibodies of IgA isotype that preferentially target non-human insulin. 1752 9

The aims of this study were to evaluate bone mineral density (BMD) and bone turnover markers in patients with type 1 diabetes and screening-identified evidence of celiac disease, i.e., celiac autoimmunity. We screened 50 consecutive type 1 diabetic patients for IgA antitissue transglutaminase to identify those with celiac autoimmunity. Eight seropositive patients were identified on this screening, and 12 patients matched for gender and age range were selected as a control group from among the type 1 diabetic patients without celiac autoimmunity. Patients and controls underwent dual-energy X-ray absorptiometry (DEXA) for measurement of bone mineral status and had their blood levels of osteocalcin, carboxy-terminal telopeptide of type I collagen (CTX), calcium, and phosphorus determined. BMD was further adjusted for height, weight, and pubertal stage. Radiographic and blood markers of bone mineralization were compared between patients and controls. BMD (Z-score) at the lumbar spine was -1.44 +/- 0.5 SD for patients and 0.04 +/- 0.2 SD for controls (P = 0.02). Bone mineral content was 37.9 +/- 4.5 g for patients and 49.4 +/- 2.6 g for controls (P = 0.049). Adjusted BMD was -0.62 +/- 0.5 SD for patients and 0.81 +/- 0.09 SD for controls (P = 0.04). After adjustment, four patients and none of the controls presented BMD < -1 SD (P = 0.01). Osteocalcin, CTX, calcium, and phosphorus blood levels were not significantly different between patients and controls. Celiac autoimmunity is associated with reduced bone mineralization in type 1 diabetic patients. The pathophysiological mechanisms and clinical relevance of this finding remain to be further investigated.
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PMID:Bone mineralization in young patients with type 1 diabetes mellitus and screening-identified evidence of celiac disease. 1793 41

Improving the status of elderly patients with diabetes mellitus is an important issue of gerontology and geriatrics. This work was aimed at the study of the effect of thymomimetic Vilon on the immune status and coagulation hemostasis in elderly patients with type I diabetes mellitus. It was found that the administration of Vilon as an addition to the complex therapy for this cohort of patients resulted in optimization of coagulation hemostasis, which was manifested in the increased content of natural anticoagulants: antithrombin III and protein C, as well as in the stimulation of fibrinolysis. In most cases Vilon reduced the dose of insulin necessary for the stabilization of carbohydrate metabolism. The content of T-helpers, T-dependent and non-T-dependent NK cells was reduced, and the level of active T-lymphocytes, B-lymphocytes and IgA was normalized, which points out the stabilizing effect of Vilon on the immune system and hemostasis.
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PMID:[Effect of vilon on the immunity status and coagulation hemostasis in patients of different age with diabetes mellitus]. 1830 98

Since the 1990's, the widespread use of very sensitive and specific serological tests has completely changed the conditions of the diagnosis of celiac disease (CD). The active form of the disease is now only the tip of the iceberg representing it. Currently, CD is evoked either in front of mild digestive symptoms at the usual age or in the course of screening in siblings of an index case or in patients at risk (insulin dependent diabetes for example) at a later age using IgA anti-endomysium or anti-tissue transglutaminase antibodies, the sensitivities and specificities of which exceed 90%. In some cases, HLA typing is helpful in allowing to exclude a patient who is neither DQ2 nor DQ8. The intestinal biopsy remains the "gold standard" of the diagnosis showing villous atrophy; the latter, however, is less and less often severe as the disease is milder and milder. The diagnosis of CD then rests on the confrontation of the clinical, biological and histological data. Once CD has been diagnosed, it can be classified either as active or silent (positive serology with isolated villous atrophy), or latent (positive serology with a normal mucosa) and the appropriate therapeutic decision can be taken.
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PMID:[Celiac disease diagnosis in 2008]. 1840 Apr 80

Patients with autoimmune type 1 diabetes mellitus have often, besides immune diabetic markers, also other organ-specific antibodies. In many diabetic patients autoimmune thyroid diseases, i.e. Hashimoto thyroiditis and Grave's disease, with silent clinical course can be diagnosed. Because 50% of children with diabetes and significant titres of thyroid autoantibodies (ATA) develop thyroid problems within 3-4 years, examinations of thyroid antibodies should be performed yearly. In cases of significant antibody titres, thyroid function tests and ultrasound assessment are recommended in order to minimize the risk of undiagnosed hypothyroidism in these patients. Coeliac is an other disease commonly coexisting with type 1 diabetes mellitus and autoimmune thyroid diseases. It is recommended that screening for coeliac disease should be part of the routine investigation for all patients. Potential benefits of treatment coeliac disease is more prevalent in individuals with type 1 diabetes mellitus, and when untreated is associated with a number of medical complications, including poor glycaemic control. Identification of patients with coeliac has been facilitated in recent years by serological screening. Initial normal screening does not exclude coeliac and repeated screening is indicated, a positive IgA antibody test to tTG is a more sensitive parameter than EmA for silent coeliac disease in patients with diabetes. Confirmatory small bowel biopsy, however, remains necessary for diagnosis as some patients with positive antibodies may be without histological changes.
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PMID:[Coexistance of autoimmunological diseases with type 1 diabetes mellitus in young patients based on literature and own experience]. 1862 23

The objective of the study was to investigate whether immunologic and biochemical events occurring in the course of type 1 diabetes mellitus might play a role in the development of the celiac disease. The study was carried out on 223 children with long-standing diabetes mellitus type 1 (DM1). All the patients had TSH, fT4, fT3, urinary albumin secretion rate, IgA, level of antigliadin antibodies (AGA) IgA and IgG, antitissue transglutaminase IgA antibodies, antiendomysium (EmA) IgA and IgG antibodies and antitireoglobulin antibodies, antithyroid peroxidase antibodies evaluated. Serum TNF-alpha, IL-6, and IL-10 levels were also measured. The group of children with coincident DM1 and celiac disease and without autoimmune thyroiditis was characterized by significantly higher glycosylated hemoglobin, higher serum TNF-alpha, IL-6 but lower serum IL-10 in relation to the remaining diabetic patients. A statistically significant positive correlation was observed between IgA-anti-tTG and serum TNF-alpha (R = 0.28, p = 0.026); between IgG AGA and serum IL-6 (R = 0.31, p = 0.023); and between glycosylated hemoglobin and IgA-anti-tTG (R = 0.21, p = 0.001) and IgA antiendomysium (R = 0.22, p = 0.001). Poor metabolic control, persistent elevated levels of proinflammatory cytokines, and decreased level of antiinflammatory cytokines occurring in the course of type 1 diabetes mellitus might influence the incidence of celiac disease.
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PMID:Immunologic and biochemical factors of coincident celiac disease and type 1 diabetes mellitus in children. 1867 58


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