UMLS:C0011860 - FACTA Search

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Query: UMLS:C0011860 (type 2 diabetes)
57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Glutamic acid decarboxylase (GAD) 65 antibodies were measured by a new quantitative immunoprecipitation followed by immunoblotting assay using Chinese hamster ovary cells to produce recombinant human islet GAD65 and were compared with islet cell antibodies (ICA), antibodies against 64,000-Mr islet cell proteins (64K antibodies) and antibodies against GAD purified from pig brain. This assay showed that sensitivity and specificity were 83.3% and 100%, respectively. GAD65 antibodies were assayed in 32 Japanese patients with insulin-dependent diabetes mellitus (IDDM), 25 patients with non-insulin-dependent diabetes mellitus (NIDDM and 25 healthy volunteers. GAD65 antibodies were found in 12 (80.0%) of 15 patients with newly-diagnosed IDDM and in 9 (52.9%) of 17 patients with long-term IDDM. GAD65 antibodies were detected in none of 25 patients with NIDDM or 25 healthy volunteers. The correlation between GAD65 antibodies and ICA, and 64K antibodies was observed to be significant (r = 0.60, P = 0.0003 and r = 0.47, P = 0.007, respectively). GAD65 antibodies and antibodies against GAD purified from pig brain correlated well (r = 0.70, P = 0.0001). The concordance between GAD65 antibodies and ICA, 64K antibodies, and antibodies against GAD purified from pig brain, including GAD65 and GAD67, were 87.5% (28/32), 75.0% (24/32) and 90.6% (29/32), respectively. We observed that a quantitative immunoprecipitation followed by immunoblotting assay had high sensitivity and specificity in detecting GAD65 antibodies, that the prevalence of GAD65 antibodies was as high as in Caucasians, and that GAD65 was also one of the major autoantigens in Japanese patients with IDDM.
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PMID:Autoantibodies against glutamic acid decarboxylase 65 in Japanese patients with insulin-dependent diabetes mellitus (IDDM). 773 39

Glutamic acid decarboxylase antibodies (GAD65Ab) are common in new onset Caucasian insulin-dependent diabetic (IDDM) patients but it is unclear if this marker is also prevalent in patients of other ethnic backgrounds. We determined antibodies against human recombinant GAD in Japanese diabetic patients using a radioimmunoassay with competition between in vitro translated 35S-GAD65 and non-labelled recombinant human GAD65 (rhGAD65). GAD67 antibodies (GAD67Ab) were similarly analyzed but without antigen competition. In 73 Japanese diabetic patients, GAD65Ab were found in 11/16 (69%) of patients with short-duration (less than 5 yrs) IDDM, 6/23 (26%) with long-duration (5 or more yrs) IDDM and 10/20 (50%) with slowly progressive diabetes. High GAD65Ab levels were associated with concomitant autoimmune diseases (p = 0.021). GAD67Ab were found in 4/16 (25%) of patients with short-duration IDDM, 3/23 (13%) with long-duration IDDM and 2/20 (10%) with slowly progressive diabetes. In 14 non-insulin dependent diabetic (NIDDM) patients, GAD65Ab and GAD67Ab were not found (0/14) and 1/50 (2%) healthy controls were positive in either assay. Among the GAD67Ab-positive samples, 8/9 (88%) were also high level GAD65Ab positive, 7/9 (77%) were displaced by an excess of rhGAD65 and the antibody levels correlated (r2 = 0.573; p = 0.003). Our data are consistent with a strong association of GAD65Ab also in Japanese IDDM, and suggest that, when present, GAD67Ab are frequently directed to epitope(s) common to GAD65 and GAD67.
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PMID:Radioimmunoassay detects the frequent occurrence of autoantibodies to the Mr 65,000 isoform of glutamic acid decarboxylase in Japanese insulin-dependent diabetes. 777 1

It was recently reported that antibodies against glutamic acid decarboxylase (GADAb) have a high positive predictive value for insulin-dependency in non-insulin-dependent diabetic (NIDDM) patients. We studied 289 patients classified at onset as having NIDDM. Patients positive for GAD65Ab had a disease onset at a younger age, lower body mass index (BMI) and lower serum C-peptide concentration, and were more often treated with insulin. Among 73 insulin-treated patients, patients with lower C-peptide level (n = 30, C-peptide < or = 0.9 ng/ml) showed a higher frequency of GAD65Ab (46.7%) than patients with normal C-peptide (n = 53, C-peptide > 0.9; 7.5%, P < 0.0001). The 206 remaining non-insulin-treated patients were divided into 48 short-duration (less than 5 years from diagnosis) and 158 long-duration patients. Frequency of GAD65Ab in short-duration patients (10.4%) was significantly higher than that in long-duration patients (3.2%, P < 0.05). Among short-duration patients, there was no significant difference in C-peptide levels between GAD65-positive and negative patients (2.175 and 2.226 ng/ml). In conclusion, GAD65Ab, a marker of insulin deficiency, may predict the development of insulin dependency in non-insulin-dependent Japanese diabetic patients before serum C-peptide concentration decreases.
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PMID:Antibody to the M(r) 65,000 isoform of glutamic acid decarboxylase are detected in non-insulin-dependent diabetes in Japanese. 884 47

Two large population-based case-control studies are reviewed. The aim is to determine the effects of HLA, other genetic factors and immune markers (ICA, IAA and GAD65Ab) on the age at onset of insulin-dependent diabetes mellitus (IDDM) in 0-34 year olds. The primary HLA risk gene sequence for IDDM was difficult to identify because of the low recombination frequency within the HLA region. The frequency of the DR3-DQA1*0501-DQB1*0201 haplotype and the DR3-DQA1*0501-DQB1*0201 (DQ2)/DR4-DQA1*0301-DQB1*0302 (DQ8) genotype were higher among patients diagnosed before the age of 10 compared with those diagnosed after the age of 30. The negatively associated haplotype, DR15-DQA1*0102-DQB1*0602 was absent before the age of 10, but the frequency increased with increasing age at onset. The IDDM2 gene representing the variable number of tandem repeat (VNTR) sequences and 5' of the insulin gene on chromosome 11 were associated with IDDM since homozygous short VNTR was positive but not homozygous, and heterozygous long VNTR was negatively associated with the disease. The diagnostic sensitivity and specificity of GAD65 (GA65Ab) and insulin (IAA) autoantibodies varied with the age at onset and gender. GAD65Ab had the highest sensitivity (> 80%) in patients older than 20 years of age with no difference in gender. The lowest sensitivity (54%) was in 0-10 year old boys, while age did not affect the sensitivity in girls. In contrast, the sensitivity of IAA was highest (46%) before the age of 15 but decreased thereafter as did the sensitivity for ICA. Classification of patients who develop IDDM above 20-25 years of age was inadequate since many patients classified with NIDDM either had GAD65Ab or ICA or developed these antibodies after 1-2 years of NIDDM. We conclude that not only age but also gender affect the risk for IDDM associated with HLA, other IDDM genes as well as commonly used immunological markers for IDDM.
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PMID:Genetic and immunological findings in patients with newly diagnosed insulin-dependent diabetes mellitus. The Swedish Childhood Diabetes Study Group and The Diabetes Incidence in Sweden Study (DISS) Group. 885 82

To clarify whether glutamic acid decarboxylase65 antibodies (GAD65 Ab) and insulin autoantibodies (IAA) are good predictive markers for insulin-dependency in NIDDM, we studied GAD65 Ab and IAA in NIDDM patients treated with diet alone or in combination with oral hypoglycemic agents. GAD65 Ab were found in 12 or 29 (5.2%, P = 0.079 vs. control) NIDDM patients and IAA in 8 of 229 (3.5%). The frequency of GAD65 Ab and IAA positivity in NIDDM did not differ significantly from those of healthy controls (2/150, 1.3%, 2/150, 1.3%, respectively), but the frequency of patients who were positive for either GAD65 Ab or IAA, or both, was significantly higher than that of normal controls (17/229, 7.4% and 4/150, 2.7%, respectively, P < 0.05). In addition, the prevalences of GAD65 Ab and of IAA in those patients whose disease durations, since the diagnosis of diabetes, were less than one year were significantly higher than those of controls (4/30, 13.3%, P < 0.05, 4/30, 13.3%, P < 0.05, respectively). We found no differences between GAD65 Ab positive- and negative-patients in either BMI or serum C-peptide levels. Over a one to five year follow-up period (mean 2.0 yrs), serum C-peptide levels gradually decreased necessitating insulin treatment in three of the patients positive for GAD65 Ab and/or IAA (3/17, 17.6%; two were positive for both GAD65 Ab and IAA and one was positive for GAD65 Ab only). In contrast, only five patients negative for the two antibodies developed insulin requirement (5/212, 2.4%, P < 0.01). These results suggest that GAD65 Ab and IAA are good markers for predicting the development of insulin dependency in NIDDM patients and that the predictive value for insulin-dependency in NIDDM is enhanced by measuring both antibodies.
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PMID:Glutamic acid decarboxylase65 (GAD65) antibodies and insulin auto-antibodies in Japanese patients with non-insulin-dependent diabetes mellitus. 915 13

Autoantibodies to 65 kD glutamic acid decarboxylase (GADAA) and ICA512 (ICA512AA) were measured by radioimmunoassays using as antigens in vitro transcribed and translated [35S]-methionine-labeled human GAD65 and ICA512 (IA-2). The prevalence of GADAA and ICA512AA in sera from 87 patients with IDDM was 39 and 23%, respectively. The frequency and titer of ICA512AA declined sharply within 5 years after the onset of IDDM. Among patients tested within 4 years after diagnosis, the prevalence of ICA512AA was significantly higher in acute onset IDDM than in slowly progressive IDDM (37 versus 6%, P < 0.025) irrespective of age, while there was no difference in GADAA frequency between acute onset and slowly progressive subtypes (51 versus 63%). A total of two patients out of 121 patients with NIDDM were positive for GADAA, and two other NIDDM patients, who were suffering from sarcoidosis, were positive for ICA512AA. Neither of the antibodies were positive in sera from four atypical NIDDM patients, aged < 20 years, who showed ketosis at onset and required insulin followed by excellent metabolic control with diet restriction alone. These observations suggest that ICA512AA are associated with rapid progression of beta cell damage in IDDM. ICA512 radioassay, in combination with GAD assay may provide a useful diagnostic marker for IDDM especially in youth.
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PMID:Combined measurements of GAD65 and ICA512 antibodies in acute onset and slowly progressive IDDM. 917 63

Glutamic acid decarboxylase (GAD) catalyzes the formation of gamma-aminobutyric acid (GABA), which is a major transmitter in the central nervous system. Two forms of GAD (GAD65 and GAD67) are known to be expressed in human tissues and GAD65 is predominantly expressed in pancreatic beta-cells. Recent findings revealed that GAD functions as an autoantigen in human autoimmunity, especially in insulin-dependent diabetes mellitus (IDDM). GAD is a key antigen for the development of autoimmunity against beta-cells and the production of GADAb precedes other autoantibodies such as IAA and ICA512/IA-2Ab prior to the clinical onset of IDDM. At onset, GADAb is detected in 50-80% of patients using RIA or RBA method. Factors that influence the positivities and titers of GADAb at onset, such as onset age, sex, presence of autoimmunity against thyroid, HLA type, have been reported. After onset, GADAb titer decreased more slowly than that of ICA512/IA-2Ab. These findings suggest that autoantibodies against beta-cells, such as GADAb, may develop independently. The presence of GADAb in relatives of IDDM patients and NIDDM patients predicts the development of beta-cell destruction in combination with other anti-islet autoantibodies.
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PMID:[GAD antibody in IDDM]. 959 23

To compare the clinical usefulness of commercial radioimmunoassay (RIA) kits based on recombinant and pig brain GAD, we measured glutamic acid decarboxylase autoantibody (GADAb) titers in 125 non-obese (body mass index < 24) Japanese diabetics without insulin therapy using two commercial RIA kits based on recombinant human (rh) GAD65 (GADAb Cosmic) and purified pig brain native GAD (RIP Anti-GAD Hoechst). The frequencies of GADAb positivity using these two RIA kits (normal ranges; < 1.3 and < 4.0 U/ml, respectively) were about 4.8 (6/125) and 3.2% (4/125), respectively. The six patients found to be positive with RIA using GADAb Cosmic demonstrated significantly higher prevalence of NIDDM in their parents (P = 0.04), lower beta-cell function estimated by intravenous glucagon loading tests (P = 0.03) and higher prevalence of progression to insulin therapy (P = 0.0001). Five of these six patients slowly progressed to insulin-requiring status within 34 +/- 11 months of follow-up evaluation, and one of these five patients progressed to a completely insulin-dependent status within 30 months from the onset of diabetes. Of these six patients, two demonstrated chronic pancreatitis, three had chronic thyroiditis, and five showed HLA DR4. Interestingly, two of the six patients demonstrated very low GADAb titers (2.3 and 2.9 U/ml), while RIP Anti-GAD Hoechst showed no positivity with the same sera. Based on the binding study after pre-incubation of unlabeled GADs, these low titrated GADAb were elucidated to be true specific reactions to rh GAD65 alone. Moreover, one of the two patients with chronic thyroiditis and HLA DR4 slowly progressed to insulin-requiring status over a period of 45 months. These findings suggest that the measurement of GADAb using a commercial assay kit with rh GAD65 may be more useful to detect non-insulin-dependent type I diabetics among non-obese patients than using a commercial kit with purified pig brain native GAD, especially among those with low GADAb titers.
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PMID:Antibodies to glutamic acid decarboxylase (GAD) in non-obese Japanese diabetics without insulin therapy: a comparison of two commercial RIA kits based on recombinant and pig brain GAD. 976 69

In light of an occurring growth of elderly people affected by type 2 diabetes and recent observations indicating that type 2 diabetes may be a disease of the innate immune system, we evaluated whether signs of islet cell autoimmunity are associated with an abnormal glucose control, the presence of insulin requirement, or an activation of the acute-phase response in older individuals with type 2 diabetes. GAD65 and IA-2 autoantibodies along with the acute-phase response markers fibrinogen and C-reactive protein were tested in 196 serum samples from patients with type 2 diabetes and in 94 nondiabetic control subjects over the age of 65 years from the Pittsburgh cohort of the Cardiovascular Health Study. Of the diabetic patients, 12% (24 of 196) had autoantibodies against GAD65 and/or IA-2, a prevalence significantly higher than that found in nondiabetic individuals (1 of 94, 1.1%; P = 0.001). Type 2 diabetic patients who were positive for GAD65 and/or IA-2 autoantibodies (Ab+), as compared with those negative for these autoantibodies (Ab-), had an abnormal oral glucose tolerance test (OGTT) (P = 0.03) before and a higher frequency of oral hypoglycemic treatment (P = 0.003) at the time of autoantibody testing. No differences were seen in the percentage of insulin requirement in the two groups. Moreover, a statistically significant increase in fibrinogen (P = 0.005) and C-reactive protein levels (P = 0.025) was found in type 2 diabetic patients with high levels of GAD65 and/or IA-2 autoantibodies as compared with Ab-patients and control subjects. In conclusion, in type 2 diabetic subjects > or =65 years old, the presence of islet cell autoimmunity is associated with an impairment of the acute-phase insulin secretion, as revealed by an OGTT. A pronounced activation of the acute-phase response, found to be associated with islet cell autoimmunity, may in part explain this defect in insulin secretion. These findings not only have direct implications for adequate classification and treatment of diabetes in the elderly, but also for understanding the autoimmune/inflammatory mechanisms involved in the pathogenesis of hyperglycemia.
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PMID:Evidence of islet cell autoimmunity in elderly patients with type 2 diabetes. 1061 47

Some type 2 diabetic subjects develop secondary failure to sulphonylurea treatment and require insulin therapy. To test the diagnostic sensitivity and specificity of epitopes of GAD65 autoantibodies (GAD65Ab) for insulin requirement, in patients with latent autoimmune diabetes of the adult, we studied 569 adult subjects with a clinical diagnosis of type 2 diabetes mellitus. All the patients had been initially treated with hypoglycemic agents and/or diet for at least 1 yr. The presence of GAD65Ab (61/569, 10.7%) depended on insulin therapy (P<0.0001), low BMI (P<0.0001), and low basal C-peptide (P = 0.01). The majority of GAD65Ab-positive subjects (47/61, 77%) had antibodies directed to both middle (GAD65-MAb) and COOH-terminal (GAD65-CAb) epitopes. However, GAD65-CAb were more frequent in insulin-treated subjects (92% of GAD65Ab+ individuals) than in subjects treated with hypoglycemic agents and/or diet (18.2% of GAD65Ab+ individuals), while the exclusive presence of GAD65-MAb was more frequent in subjects treated with hypoglycemic agents and/or diet (81.8% vs. 8%) (P<0.0001). The presence of GAD65-CAb had a diagnostic specificity for insulin requirement as high as 99.4% (compared with 96.9% of GAD65Ab as measured in the traditional radiobinding assay) and identified a subgroup of patients with low BMI, low basal C-peptide values, and a need for insulin therapy. Subjects carrying only GAD65-MAb were phenotypically indistinguishable from GAD65Ab-negative patients. Patients positive for GAD65-M+CAb, but not those positive for GAD65-MAb only, showed an increased risk for thyroid autoimmunity, as revealed by the presence of thyroid peroxidase autoantibodies. Our study demonstrates that the use of epitope-specific antibody assays improves the diagnostic specificity of GAD65Ab, and that the presence of GAD65Ab binding to COOH-terminal epitopes is strongly associated with a need for insulin requirement.
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PMID:Autoantibody recognition of COOH-terminal epitopes of GAD65 marks the risk for insulin requirement in adult-onset diabetes mellitus. 1063 4

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