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)

Coeliac disease (CD), caused by an inappropriate T-cell-mediated immune response to the ingestion of cereal proteins in genetically susceptible individuals, is a common disorder with a prevalence of about 1% in Caucasian populations. It has a strong association with other autoimmune disorders, particularly type 1 diabetes and autoimmune thyroid disease. Although primarily affecting the small bowel, CD is a multisystem disorder and the adult or child patient may initially present to a wide range of clinical specialties. The concept of the 'coeliac iceberg' has been used to emphasize that many cases currently remain undiagnosed. The identification of tissue transglutaminase (TGA)-2 as the antigen against which the autoantibodies are directed has led to a greater understanding of the pathogenesis of CD and to the development of improved serological tests. Enzyme-linked immunoassays using human tissue TGA as antigen have high diagnostic sensitivity and specificity for the detection of CD. This review examines the evidence for adopting IgA anti-tissue TGA as the first-line diagnostic test for CD. It recommends a laboratory algorithm for the use and interpretation of TGA to enable the clinical laboratory to play a full part in detecting and monitoring a disorder that is eminently treatable once the diagnosis has been considered and confirmed.
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PMID:Anti-tissue transglutaminase antibodies and their role in the investigation of coeliac disease. 1653 12

Gluten sensitivity is an autoimmune disease that usually causes intestinal atrophy resulting in a malabsorption syndrome known as celiac disease. However, gluten sensitivity may involve several organs and is often associated with extraintestinal manifestations. Typically, patients with celiac disease have circulating anti-tissue transglutaminase and anti-gliadin antibodies. When patients with gluten sensitivity are affected by other autoimmune diseases, other autoantibodies may arise like anti-epidermal transglutaminase in dermatitis herpetiformis, anti-thyroid peroxidase antibodies in thyroiditis, and anti-islet cells antibodies in type 1 diabetes. The most common neurological manifestation of gluten sensitivity is ataxia, the so-called gluten ataxia (GA). In patients with GA we have demonstrated that anti-gliadin and anti-tissue transglutaminase antibodies cross-react with neurons but that additional anti-neural antibodies are present. The aim of the present article is to review the knowledge on animal models of gluten sensitivity, as well as reviewing the role of anti-neural antibodies in GA.
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PMID:Gluten ataxia: passive transfer in a mouse model. 1780 60

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

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

A reduced bone mineral density has been reported in patients with untreated celiac disease (CD) as well as in patients with poorly controlled type 1 diabetes mellitus (T1DM). The aim of this study was to evaluate the bone mineral status by phalangeal quantitative ultrasound in 52 children and adolescents with both diseases (mean age 13.3+/-4.9 years). As a control group 50 patients with T1DM and no CD (age 12.2+/-4.0 years) were studied. The following bone parameters, amplitude-dependent speed of sound (AD-SoS) and bone transmission time (BTT) were considered and expressed as z score. Compliance to gluten free diet and long term glycemic control (mean of four determinations of HbA1c in the last year) were also assessed. The lowest mean AD-SoS z score values were found in patients with T1DM and CD, who reported transgressions to gluten free diet and exhibited positivity for serum anti-tissue transglutaminase antibodies (tTG) and/or endomysial antibodies (EmA), compared with patients with occasional transgressions but negative for anti-tTG and/or -EmA, patients strictly adherent to the diet, and patients who suffered only from diabetes (ANOVA p=0.021). No difference was found between patients with diabetes alone and patients with both diseases strictly adherent to gluten free diet. Prevalence of osteopenia (z AD-SoS values <-2 SD) was higher in patients with T1DM and CD and poor compliance to the diet (45.5%) compared with patients with T1DM (8%) or patients with both diseases strictly compliant to diet (12.9%) (p=0.015). A negative correlation between Ad-SoS z score and HbA1c (r -0.236, p=0.036) was found when patients with T1DM and patients with T1DM and CD, who strictly adhere to the diet, were pooled. In conclusion the quality of bone as assessed by phalangeal ultrasound in patients with T1DM and CD, who strictly adhere to gluten free diet, is similar to that found in T1DM patients. A higher prevalence of osteopenia is present in patients with both diseases who reported habitual transgressions to gluten free diet. The gluten free diet, as well as the optimization of glycemic control, plays an important role in preventing the osteopenic status caused by the clustering of these two chronic diseases.
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PMID:The influence of gluten free diet on quantitative ultrasound of proximal phalanxes in children and adolescents with type 1 diabetes mellitus and celiac disease. 1849 52

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

There are no studies that compare the prevalence of organ-specific autoantibodies (OSAs) between adult (>or= 16 years) and childhood-onset type 1 diabetes (T1D). We evaluated the prevalence of the following OSAs: thyroid peroxidase, thyroid receptor, parietal cell, intrinsic factor, tissue transglutaminase, adrenal cortex, mitochondrial, smooth muscle, liver kidney microsomal, and ovarian autoantibodies. Three hundred twenty-seven (327) adults were screened for one or more of these OSAs. The prevalence of all the OSAs studied was similar in both groups. The most prevalent OSA observed was tissue transglutaminase (childhood-onset disease = 14.3%; adult-onset disease = 13.6%). This study did not demonstrate a distinct difference in the prevalence of OSAs between adult- and childhood-onset T1D patients.
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PMID:Prevalence of organ-specific autoantibodies in childhood- and adult-onset type 1 diabetes. 1912 Mar 8

Imbalance between different types of T lymphocytes, such as T helper (Th) and regulatory T cells (Tregs), has been reported to play a part in the pathogenesis behind such autoimmune diseases as type 1 diabetes (T1D) and celiac disease (CD). Defects in Tregs are proposed to at least partly explain the imbalance of Th cells found in children with immunologic diseases. Peripheral blood mononuclear cells from 24 children with T1D and/or CD, and reference children (that is, those without any of these diseases) were stimulated with disease-associated antigens (insulin, gluten, transglutaminase [tTG]), and phytohemagglutinin (PHA). The mRNA expression of the Treg-associated marker FOXP3 was analyzed with multiplex real-time RT-PCR. Children with T1D showed both a low spontaneous (P < 0.05) and PHA-induced (P < 0.01) expression of FOXP3 mRNA compared to children with CD. Children with T1D also had a low PHA-induced FOXP3 mRNA expression compared to the group of children diagnosed with both T1D and CD (P < 0.05). Spontaneous (P < 0.05) and PHA-induced (P < 0.05) FOXP3 mRNA expression was high in children with CD compared to reference children. In contrast, stimulation with insulin tended to induce high FOXP3 mRNA expression in T1D children compared to reference children (P= 0.057). In conclusion, children with only T1D generally showed a lower FOXP3 mRNA expression than did children with CD, or with T1D in combination with CD, which suggests impaired regulation of the immune system in children with T1D.
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PMID:Diverse foxp3 expression in children with type 1 diabetes and celiac disease. 1912 Mar 12

Public anxiety over gluten has fuelled widespread demand for gluten-free food, yet coeliac disease remains significantly underdiagnosed and some confusion remains regarding optimal diagnostic practices. Small bowel histology is the gold standard for diagnosis. High-quality commercial enzyme-linked immunosorbent assays for transglutaminase immunoglobulin A and deamidated gliadin immunoglobulin A and G are sensitive tools for screening, but almost 10% of coeliac disease is seronegative and serological testing is unreliable in the very young, in people already following a gluten-reduced diet, and those using immunosuppressive medications. HLA DQA and DQB genotyping to show that alleles encoding HLA DQ2 and DQ8 are absent virtually excludes coeliac disease. Confirming histological remission reduces the risks of later complications, such as osteoporosis and cancer. Monitoring remission by serology is unreliable. Because gluten is an exogenous antigen and the small intestine is readily accessible, the immunopathogenesis of coeliac disease is better understood than other strongly major histocompatibility complex class II-associated diseases, such as type 1 diabetes mellitus. Therapeutic targets have been identified and drugs are under development to supplement or even replace gluten-free diet. With greater awareness and non-dietary therapeutics, diagnosis and treatment of coeliac disease will be increasingly prominent in medical practice.
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PMID:Coeliac disease: current approach and future prospects. 1950 13

Individuals with Turner syndrome (TS) are prone to develop autoimmune conditions such as coeliac disease (CD), thyroiditis and type 1 diabetes (T1DM). The objective of the present study was to examine TS of various karyotypes for autoantibodies and corresponding diseases. This was investigated in a prospective cross-sectional study of Danish TS patients (n = 107, median age 36.7 years, range: 6-60 years). A medical history was recorded and a blood sample was analysed for autoantibodies against gliadin, transglutaminase, adrenal cortex, intrinsic factor, anti-thyroid peroxidase (anti-TPO) and glutamic-acid-decarboxylase 65 (GAD-65). Autoantibodies were present in 58% (n = 61) of all patients, whereof 18% (11) had autoantibodies targeting more than one organ. Patients with autoantibodies were significantly older than those without (P = 0.001). Anti-TPO was present in 45% (48) of patients, of whom 33% (16) were hypothyroid. Overall, 18% (19) presented with CD autoantibodies, of whom 26% (five) had CD. Anti-TPO and CD autoantibodies co-existed in 9% (10). Immunoglobulin A deficiency was found in 3% (three) of patients, who all had CD autoantibodies without disease. Among four patients with anti-GAD-65 none had T1DM, but two were classified as having T2DM. One patient had adrenocortical autoantibodies but not adrenal failure. Autoantibodies against intrinsic factor were absent. Anti-GAD-65 was increased in isochromosomal karyotypes (3/23 versus 1/84, P = 0.008) with no other association found between autoantibodies and karyotype. In conclusion, TS girls and women face a high prevalence of autoimmunity and associated disease with a preponderance towards hypothyroidism and CD. Thus, health care providers dealing with this patient group should be observant and test liberally for these conditions even before clinical symptoms emerge.
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PMID:Increased prevalence of autoimmunity in Turner syndrome--influence of age. 1929 6


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