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

Type 1 diabetes and celiac disease are both immunologic disorders where specific HLA alleles are associated with disease risk. We have developed a radioassay for autoantibodies to tissue transglutaminase (tTG) following the report that this enzyme is 'the' endomysial autoantigen (EMA) of celiac disease. The radioassay for transglutaminase autoantibodies is similar to that utilized for detecting anti-islet autoantibodies. The 'cut-off' for the IgA autoantibody assay was established as 3 x 100th percentile of 184 healthy control subjects at an index of 0.05. Ninety-eight of 847 patients with type 1 diabetes (11.6%) had tissue transglutaminase autoantibodies (tTG). All EMA-positive patients were positive (49/49) for transglutaminase autoantibodies, as were 49/540 EMA-negative patients. Twenty transglutaminase-positive patients consented to intestinal biopsy and 15 biopsies were positive for celiac disease. All patients with a transglutaminase level greater than 0.70 (13/13) had a positive biopsy, while none (0/3) with a level <0.3 had a positive biopsy. The prevalence of transglutaminase autoantibodies was higher in diabetic patients with HLA DQ2 or DQ8. One third of DQ2 homozygous patients (22/68) expressed transglutaminase autoantibodies vs. less than 2% of patients lacking DQ2 or DQ8. A simple radioassay for IgA transglutaminase autoantibodies detects all endomysial antibody positive patients and detects transglutaminase autoantibodies in 5% of endomysial autoantibody negative patients. The prevalence of transglutaminase autoantibodies is associated with DQ2 and DQ8 and in particular DQ2 homozygosity. Autoimmunity to transglutaminase is remarkably prevalent amongst patients with type 1 diabetes expressing certain class II HLA alleles.
 ...
PMID:One third of HLA DQ2 homozygous patients with type 1 diabetes express celiac disease-associated transglutaminase autoantibodies. 1044 Nov 79

Calreticulin (CRT), a high-affintiy calcium binding protein and chaperone, was recently identified as one of the targets of autoantibodies in coeliac disease. We evaluated the level of IgA and IgG antibodies to CRT in sera from patients with coeliac disease and various autoimmune diseases. The level of antibodies to gliadin (shown previously to cross-react with CTR), isolated enterocytes and tissue transglutaminase were determined for comparison. The mean level of IgA antibodies to CRT was significantly higher (P< 0.001) in sera from coeliac patients with active disease (139.9+/-11.2 AU/+/-SE) than in healthy controls (20.9+/-1.7 AU). In sera of patients with systemic lupus erythematosus (SLE), insulin dependent diabetes mellitus (IDDM), multiple sclerosis (MS) and autoimmune thyroiditis (AT) or inflammatory bowel disease (IBD) the mean level (25.8+/-3.7 to 38.1+/-5.6 AU) did not exceed the cut-off value. A low level of these antibodies, however, was detected in some sera of patients with MS and IBD. The level of IgG anti-CRT antibodies was increased in coeliac patients (mean 125.4+/-8.0 AU, P< 0.001) when compared to that in healthy controls (33.9+/-2.3 AU). The IgG anti-CRT antibodies were also detected in about 30% of SLE patients sera (54.1+/-3.6 AU, P< 0.001), but the mean level reached only half that detected in coeliac patients.
 ...
PMID:Occurrence of IgA and IgG autoantibodies to calreticulin in coeliac disease and various autoimmune diseases. 1109 Feb 43

Celiac disease (CD) is a small intestinal disorder with overt malabsorption in the minority and with subclinical or atypical symptoms in the majority of patients. It is triggered by gluten and related cereal proteins in a unique genetic background (HLA-DQ2 or DQ8 and other unmapped genes). CD is characterized by a highly specific mucosal autoantibody response to tissue transglutaminase. In the intestine this enzyme creates antigenic neoepitopes in gluten peptides which are more efficiently presented to the immune system in the context of HLA-DQ2 or DQ8. Between 3% and 6% of patients with type 1 diabetes mellitus (DM) have (atypical) CD, and the prevalence of a variety of autoimmune diseases in patients with CD correlates with the time of gluten exposure, reaching 35% after 20 years. It is still unknown whether oligosymptomatic CD favors the development of type 1 DM and whether a gluten-free diet modifies the progression of DM in general. Apart from shared or adjacent HLA loci in both diseases, post-translational modification of potential autoantigens by enzymes such as tissue transglutaminase could play a role in the autoimmunity of type 1 DM.
 ...
PMID:Celiac disease and its link to type 1 diabetes mellitus. 1139 50

The association between celiac disease (CD) and diabetes mellitus type 1 is well known. Only about one-third of all patients with CD are diagnosed in childhood as a result of typical gastrointestinal symptoms or growth retardation. To evaluate the feasibility of CD screening in diabetic children, we tested autoantibodies to tissue transglutaminase (tTGA) in all children with type 1 diabetes from our pediatric department during a 12-month period. In antibody-positive cases, we analyzed the clinical presentation and offered a duodenal biopsy to confirm the diagnosis and grade the severity of the inflammatory process. Of 205 children, 13 (6.3 %) were tTGA-positive. In seven of eight children who agreed to perform a biopsy, CD typical histological signs were detected (Marsh 1: n = 1, Marsh 3: n = 6). In three patients with confirmed disease, symptoms (iron deficiency, recurrent abdominal pain) remained undiscovered up to time of screening (latent form); in four, the disease was asymptomatic (silent form). Since clinical symptoms are mostly mild or absent in spite of severe signs of duodenal inflammation, we recommend tTGA screening in all diabetic children. This strategy may allow the identification of patients in an early stage in respect of prevention of long-term complications.
 ...
PMID:General screening for celiac disease is advisable in children with type 1 diabetes. 1198 28

MMDM patients are typically young at onset with low body mass index, require insulin treatment for glycemic control, have insulin resistance, and do not develop ketosis on withdrawal of insulin. WHO's revised classification in 1999, based on the etiopathogenesis of the disease, identifies only two categories: type 1 diabetes and type 2 diabetes. MMDM could be considered as type 1b diabetes. Genetic and immunological studies were done on MDDM patients (n = 72) from Cuttack and healthy controls to understand and to justify its inclusion in the category of type 1b diabetes. Antibodies (Abs) to tyrosine pyrophosphatase (IA2-Abs), glutamate decarboxylase 65 (GAD65-Abs), and other minor markers like ICA12 Abs and tissue transglutaminase Abs (TTG-Abs) were studied. HLA-DR and DQ were studied for the genetic markers. Of the MMDM patients 30% were positive for either GAD65 or IA-2 antibodies, and 14% were positive for ICA12 antibodies. All three antibody markers together accounted for 39% of PDDM patients, as some patients were positive for more than one autoantibody. TTG antibodies (specific for Celiac disease) were present in 14/71 (20%) of MMDM patients compared to 3/122 (2%) controls. All four autoantibodies accounted for 53% of PDDM patients, leaving 47% of patients free of known autoantibodies. The autoantibody-negative PDDM patients were analyzed for HLA and MICA markers, showing that DR7-DQ9 and MICA allele 9 are increased in this group compared to healthy controls, which suggests an autoimmune response to an unknown dietary autoantigen. We conclude from our data that an autoimmune mechanism is involved in the etiology of MMDM. In addition, the presence of silent celiac disease seen with MMDM patients, which has not yet been reported, is significant. It is important to note that subclinical celiac disease exists with diabetes mellitus and must be considered in the diagnosis of MMDM.
 ...
PMID:Molecular mechanisms involved in the etiopathogenesis of malnutrition-modulated diabetes mellitus. 1202 Oct 93

This study attempts to assess the prevalence of various autoantibodies in early-onset diabetics in northern India, with emphasis on antibodies against glutamic acid decarboxylase (GAD65), IA-2, ICA-12, 21-hydroxylase (21-OH), and tissue transglutaminase (TTG). GAD65 and IA-2 antibodies were found to be present in approximately 26% of cases of type 1 diabetes. A subset of patients clinically diagnosed to have MMDM appears to have an autoimmune etiology, with more than 20% showing serpositivity for IA-2 antibodies. Antibodies against ICA-12 were prevalent in both type 1 diabetes and MMDM. Approximately one of seven patients with type 1 diabetes showed erological evidence of celiac disease.
 ...
PMID:Prevalence of ICA-12 and other autoantibodies in north Indian patients with early-onset diabetes. 1202 Nov 9

In Latvia diabetes mellitus is diagnosed using the WHO's clinical criteria; assays for the detection of autoantibodies are not available, and hence slowly progressive autoimmune diabetes is likely to be missed. Autoantibodies against glutamic acid decarboxylase (GAD65) and protein tyrosine phosphatase (IA-2) among patients with clinically diagnosed NIDDM identify group of patients with slow-onset type 1 diabetes or LADA. The aim of this study was to estimate the risk of polyendocrine autoimmunity among clinically diagnosed NIDDM patients from Latvia. One hundred NIDDM patients and 100 healthy controls were tested for GAD65 and IA-2 autoantibodies as well as 21-hydroxylase (21-OH) and tissue transglutaminase (TTG) antibodies by RIA assay. Age at onset was >or= 30 years, and duration of disease less than 5 years. Of 100 patients, 85 were on oral hypoglycemic agents and 15 were on insulin. Body mass index (BMI) under 19 was recorded in 1% (1 of 100 cases), while overweight (BMI > 25.5 in females and 27 in males) was documented in 45% (45 of 100 cases). GAD65 antibodies were found in 30 of 100 (30%) and IA-2 antibodies in 40 of 100 (40%) patients. Either GAD65 or IA-2 antibodies were found in 55 of 100 (55%). None of the patients carried antibodies against 21-OH and only 1 of 100 (1%) carried antibodies against TTG. From the results obtained in our study we conclude that in Latvian adult NIDDM subjects, islet autoantibodies identify groups of slow-onset type 1 diabetes but not polyendocrine autoimmunity.
 ...
PMID:Islet autoantibodies in Latvian subjects with non-insulin-dependent diabetes mellitus: slow-onset type 1 diabetes or polyendocrine autoimmunity? 1202 Nov 19

Women with gestational diabetes mellitus (GDM) have considerable risk for developing both type 1 and type 2 diabetes in life. Autoantibodies against glutamic acid decarboxylase (GAD65) and tyrosine phosphatase (IA-2) are strongly associated with autoimmune diabetes and can be useful in early identification of the development of type 1 diabetes in women with GDM. On the other hand antibodies against minor islet antigens in adults can be predictors for autoimmune polyendocrine syndrome. The aim of our study was to estimate the prevalence of autoantibodies against minor antigens-tissue transglutaminase (TTG), ICA12, and 21-hydroxylase (21-0H)-in GDM patients from southern India. Eighty-six serum samples from GDM subjects and 114 samples from healthy controls were tested for the presence of GAD65 and IA-2Ab as well as for the presence of 21-OH, TTG, and ICA12Ab by radiobinding assay with in vitro translated recombinant human 35S-GAD65, IA-2, TTG, ICA12, and 21-OH antigens. We observed the presence of GAD65 or IA-2 autoantibodies in 41% (35/86) of GDM patients, while none of the patients tested positive for any of the minor autoantibodies. Our results demonstrate that there is a high prevalence of autoantibodies in GDM subjects that are at higher risk of developing autoimmune diabetes later, but none of the patients carries antibodies against minor antigens, which could predict autoimmune polyendocrine syndrome in adults.
 ...
PMID:Women diagnosed with gestational diabetes mellitus do not carry antibodies against minor islet cell antigens. 1202 Nov 24

Autoimmune diabetes is one of the most common chronic diseases in the world. Autoantibodies against major antigens GAD65 and IA-2 as well as some minor antibodies are markers for autoimmune diabetes already several years before clinical onset in most populations. Screening the population for these autoantibodies can help identify subjects at risk for developing type 1 diabetes. In our study we screened 20,903 inhabitants in 26 villages outside Madras for diabetes. Among them 3.64% were detected to be diabetic. The aim of our study was to detect the presence of glutamic acid decarboxylase (GAD65), tyrosine phosphates (IA-2) and tissue transglutaminase (TTG) antibodies. We studied 169 individuals from this population, 75 of them were diagnosed as diabetics, based on presence of sugar in the urine and an elevated blood sugar, 58 had hypertension, and 36 were healthy subjects. We used radioimmunoassay with in vitro translated and transcribed human recombinant 35S-GAD65, IA-2 and TTG antigens. We observed presence of GAD65Ab in 10%, IA-2Ab in 5%, and TTGAb in 5% in diabetic subjects, while the healthy subjects and people with hypertension didn't carry any of these antibodies. We conclude that prevalence of autoimmune diabetes mellitus based on antibody screening in this population is significantly high.
 ...
PMID:Autoimmune diabetes in 26 villages outside Madras. 1202 Nov 25

Serology markers of coeliac disease (CD) - antigliadin IgA/IgG antibodies (AGA/AGG) with purified alpha-gliadin, antiendomysium IgA antibodies (EmA) and anti-tissue transglutaminase (atTG) IgA/IgG antibodies--determined in 1451 serum samples, were analysed with respect to different screening algorithms. Determination of atTG using five ELISA methods was compared taking into account the impact of human recombinant antigen and IgG class of atTG. A subgroup of 119 patients undergoing small intestinal biopsy was used to calculate sensitivity and specificity of CD markers. The highest sensitivity (94%) was obtained for AGG, and the highest specificity (93.5%) was obtained for EmA. All coeliac disease patients were detected using the combination of all four CD markers, resulting in 100% sensitivity. CD and type 1 diabetes mellitus autoantigens were determined in 139 diabetic patients. The atTG IgA mean value (16.7 IU/ml) was higher in the antiglutamate dehydrogenase antibody (GAD)-positive subgroup, where at least one CD marker was positive in 83.6% subjects. In the GAD-negative subgroup atTG IgA was 8.73 lU/ml and at least one CD marker was positive in 57.4% subjects. atTG in IgA and IgG classes could be recommended as valuable serological markers of CD in the differential diagnosis of malabsorption as well as in various screening algorithms. ELISA determination of atTG with human antigen could increase the specificity, especially in patients with other autoimmune diseases.
 ...
PMID:Tissue transglutaminase-serology markers for coeliac disease. 1211 93


1 2 3 4 5 6 7 8 Next >>