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6 "GAD antibody"
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Case Reports
Clinical Courses of Two Women with Gestational Diabetes Mellitus Who are GAD Antibody Positive.
Sung Hoon Yu, Min Jun Song, Sung Hoon Kim, Chang Hoon Yim, Ki Ok Han, Won Kun Park, Hyun Koo Yoon, Ho Yeon Chung
Korean Diabetes J. 2006;30(5):398-402.   Published online September 1, 2006
DOI: https://doi.org/10.4093/jkda.2006.30.5.398
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AbstractAbstract PDF
Gestational diabetes mellitus (GDM) is defined as glucose intolerance of various degrees with onset or first recognition during pregnancy. Women with GDM are at high risk of developing type 2 diabetes later in life, but the risk of developing type 1 diabetes is also increased. Positivity for glutamic acid decarboxylase (GAD) antibodies during pregnancy confers a high risk for subsequent progression to type 1 diabetes. Here, we reported the two cases with GDM who were GAD antibody positive and progressed to type 1 diabetes with different time-courses. One woman with GDM progressed rapidly to classical type 1 diabetes while the other became slowly progressive IDDM (SPIDDM) [or latent autoimmune diabetes in adults (LADA)].
A Case of Diabetic Ketoacidosis in a GAD Antibody-positive Diabetes Patients who Recently Experienced Hyperglycemic Hyperosmolar State.
Jang Won Son, Seok Hong Lee, Jung Ahn Lee, Jaetaek Kim, Yeon Sahng Oh, Soon Hyun Shinn
Korean Diabetes J. 2005;29(3):267-270.   Published online May 1, 2005
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The term latent autoimmune diabetes in adults(LADA) was introduced to define adult diabetic patients who initially do not require insulin, but they have the immune markers of type 1 diabetes and in a number of cases, these patients progress to insulin dependency. LADA patients have several features of classic type 1 diabetes in addition to islet cell antibody positivity, including high rates of HLA-DR3 and DR4. We describe here a case of a patient with a diagnosis of LADA who, having been diagnosed with type 2 diabetes, was affected with diabetic ketoacidosis. In April 2000, a 65-year-old man was admitted to Chung-Ang University Hospital due to his decreased cognitive ability. The patient was diagnosed with type 2 diabetes 30-years ago and he was diagnosed 6-month ago as being in a hyperglycemic hyperosmolar state. He was positive for antibodies against GAD(anti-GAD, 31U/mL). His weight was 70kg, height 167cm, BMI 25 kg/m2 and the blood pressure was 86/52mmHg. No abnormalities on the physical examination were found. His acid-base balance was pH 6.937, serum bicarbonate 2.2mmol/L and the anion gap 38; he also had a strong positive reaction for ketones in his urine and serum. During half a year, the fasting C-peptide level decreased from 0.65nmol/L to 0.13nmol/L, which means the rapid progression of beta-cell destruction. Intensive treatment of LADA with insulin may improve this type of patients' quality of life, and so potentially save the beta-cell function and perhaps lessening the risk of a hyperglycemic crisis
Original Articles
The Prevalence of Islet Cell Cytoplasmic Antibody in Korean Type 1 Diabetes: Possible Replacement with Combined Measurement of Anti-GAD, Anti-ICA512, and Anti-phogrin Antibodies.
Kyoung Ah Kim, Dong Jun Kim, Jae Hoon Chung, Yong Ki Min, Moon Kyu Lee, Kwang Won Kim, Dong Kyu Jin, Kyung Soo Ko, Sang Jin Kim, Myung Shik Lee
Korean Diabetes J. 2001;25(6):430-445.   Published online December 1, 2001
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AbstractAbstract PDF
BACKGROUND
Type 1 diabetes includes all forms of autoimmune-mediated and idiopathic beta-cell destruction leading to an absolute insulin deficiency. Evidence of an autoimmune pathogenesis was assessed by studying cytoplasmic islet cell antibodies (ICA), antibodies to glutamic acid decarboxylase (GADA), antibodies reacting with an islet tyrosine phosphatase-related molecule referred to as ICA512 (ICA512A), or its homologue phogrin (phogrin-A). In comparison with ICA, the best validation to assess the risk of type 1 diabetes, shows that a combination of antibodies to GADA with ICA512A has the power to detect a majority of ICA and 97~100% of subjects who progressed to overt diabetes. These findings suggest the possibility of replacing the laborious ICA test in the screening programs to identify subjects at risk of progressing to type 1 diabetes or forclassifying the stage of diabetes at the time of diagnosis. Up to now, it is unclear whether these results are applicable to the slowly progressive type 1 diabetes that appears to be more prevalent in Asian than in western countries. The prevalence of combined autoantibody testing (1 of GADA, ICA512A, or phogrin-A) was investigated in the patients with type 1 diabetes (typical and slowly progressive) and type 2 diabetes, and compared with that of ICA which is a more laborious and insensitive test. METHODS: The ICA assay was performed using immunoenzymatic staining of frozen human (blood group O) pancreatic sections with serial dilutions of serum samples with peroxidase-labeled protein A. For the GADA determination, commercially available GADA radioimmunoassay kits utilizing the 125I-labeled recombinant GAD65 (RSR , United Kingdom) as an antigen was used. Either ICA512A or phogrin-A were detected by a radioligand-binding assay after in vitro transcription and translation using the clone ICA512bdc or phogrin cDNA. Serum was obtainedfrom 76 patients with type 1 diabetes (mean age 22.8+/-14.0 years), 22 patients with slowly progressive type 1 diabetes (mean age 37.9+/-13.9 years) and 39 patients with type 2 diabetes (mean age 45.3+/-12.3 years). Typical and slowly progressive type 1 diabetes patients had the disease for between 4.0+/-4.6 and 10.1+/-9.5 years, respectively at the earliest serum sampling. RESULTS: 1) In typical type 1 diabetes, 30% of patients tested positive for ICA and 57% for the combined autoantibody test (1 of GADA, ICA512A, or phogrin-A). In the slowly progressive type 1 diabetes group, 18% of patients tested positive for ICA and 50% for the combined autoantibody test. In type 2 diabetes, 7.7% and 5.1% tested positive, respectively. 2) Ninety-six percent of ICA-positive patients expressed one or more of the 3 auto-antibody specificities in typical type 1 diabetes. Among the 53 ICA-negative patients with typical type 1 diabetes, 40% had one or more of these auto-antibodies. In the slowly progressive type 1 diabetes, 100% of the ICA-positive and 39% of the ICA- negative patients expressed one or more of the 3 autoantibody specificities. 3) Of the 23 patients with ICA-positive typical type 1 diabetes patients, 87% had a positive result for GADA, 48% for ICA512A, 44% for phogrin-A, and 96% for GADA or ICA512A. Of the 4 patients with ICA-positive slowly progressive type 1 diabetes, three had a positive result for GADA, and 1 for ICA512A. 4) When the prevalence of combined autoantibody testing was analyzed according to the duration of diabetes, the prevalence in patients tested within 4 years after the diagnosis and more than 4 years after the diagnosis was 61% and 52%, respectively in typical type 1 diabetes. Furthermore, that for the ICA was 37% and 21%, respectively. In the slowly progressive type 1 diabetes, the prevalence of combined auto-antibody testing was 88% and 25%, respectively (p<0.05), while that of ICA was 25% and 13%, respectively. 5) In typical type 1 diabetes, ICA were detected more frequently in patients younger than 15 years of age (48%) than in older patients (23%) (p<0.05), while the prevalence of combined auto-antibody testing -was not different according to the onset age (65% vs 53%). CONCLUSION: Combined autoantibody testing for GADA and ICA512A is more sensitive that ICA in type 1 diabetes. Therefore, it could replace the laborious ICA measurement and may be useful for discriminating the etiology of adult onset atypical diabetes.
Measurement of Anti-Phogrin Antibody in Korean Autoimmune Deabetes; Comparison to Anti-IA-2 Antibody.
Moon kyu Lee, Yong Ki Min, Myung Shik Lee, Sung Hoon Kim, Byoung Joon Kim, Dong Jun Kim, Jong Ryeal Hahm, Dong Kyu Jin, Kyoung Ah Kim, Kwang Won Kim
Korean Diabetes J. 1999;23(3):269-277.   Published online January 1, 2001
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AbstractAbstract PDF
BACKGROUND
Since the discovery of IA-2 as a major autoantigen in type 1 diabetes, the question arose as to whether other PTPs (protein tyrosine phosphatases) could act as diabetic autoantigens as well. A novel PTP, designated IA-2 B (phogrin; phosphatase homologue in granules of insulinoma) was isolated that has a high sequence similarity to IA-2. Since some studies suggested that auto- immunity to phogrin, rather than IA-2 may be more closely associated with the development of type 1 diabetes, we measured the frequency of anti-phogrin antibody in Korean patients with type 1 diabetes and compared it with that of anti-IA-2 antibody/ anti-GAD antibody. METHODS: The anti-phogrin antibody and the anti-IA-2 antibody were measured by radioligand binding assays using in vitro transcribed and translated S-labeled phogrin and IA-2, respectively. Anti-GAD antibody was measured using a commercial radioimmunoassay kit (RSR, Cardiff, U.K.). The subjects in this study consisted of 41 patients with classical type 1 diabetes, 22 with slowly progressive type 1 diabetes, and 39 with type 2 diabetes. Their average mean age was 16.9 years, 37.9 years and 45.3 years respectively. RESULTS: The prevalence of anti-phogrin antibody, anti-IA-2 antibody and anti-GAD antibody in classical type 1 diabetes was 24.4%, 26.8% and 51.2% respectively. That, in slowly progressive type 1 diabetes was 0%, 9.1% and 40.9% respectively. When the anti-GAD antibody assay and the anti-IA-2 antibody assay were combined, the prevalence of autoantibodies was 58.5% in classical type 1 diabetes and 50% in slowly progressive type I diabetes. However, the addition of the anti-phogrin antibody to the anti-GAD antibody/anti-IA-2 antibody measurement did not significantly increase the prevalence of autoantibody. The level of the antiphogrin antibody was positively correlated with that of the anti-IA-2 antibody. The presence of the anti-phogrin antibody and the anti-IA-2 antibody was negatively correlated with the age at diagnosis. One patient with type 1 diabetes had the anti-phogrin antibody without the anti-IA-2 antibody. CONCLUSION: Combined measurement of the anti-phogrin antibody with the anti-IA-2 antibody/ anti-GAD antibody did not significantly increase the prevalence of autoantibodies in Korean patients with type 1 diabetes. In the majority of Korean type 1 diabetes patients, the anti-phogrin antibody appears to share epitopes with the anti-IA-2 antibody. However, a small proportion of type 1 diabetes patients may have a specific autoimmune response to phogrin.
The Frequency of ICA and anti-GAD Antibody in Korean IDDM and NIDDM Patients.
Kyung Soo Ko, Sung Kwan Hong, Ki Up Lee, Nan Hee Kim, Dong Seop Choi, Sung Hee Ihm, Sung Woo Park, Chul Hee Kim, Dong Won Byun, Kyo Il Suh, Hak Chul Chang, Byoung Doo Rhee
Korean Diabetes J. 1998;22(3):312-319.   Published online January 1, 2001
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AbstractAbstract PDF
BACKGROUND
It has been suggested that the clinical and immunological characteristics of diabetes mellitus in Koreans are different from those of Caucasians. This study was undertaken to investigate the prevalence of autoimmune markers in Korean adults with IDDM and recent-onset NIDDM. METHODS: Seventy-seven Korean adults with IDDM and 245 recently(within 2 years) diagnosed NIDDM were included in the study. Islet cell cytoplasmic antibody was measured by immunohistochemical method, and anti-glutamic acid decarboxylase (anti-GAD) antibody was measured by radioimmunoassay. RESULTS: 1) The prevalence of ICA, anti-GAD antibody positivity was 27% and 40% in IDDM patients, and 5% and 4% in recent-onset NIDDM patients, respectively. 2) The prevalence of ICA positivity in IDDM patients decreased from 42% within one year to 21% over one year after clinical onset of disease. On the other hand, the positivity of anti-GAD antibody did not change according to the duration of diabetes. 3) The prevalence of ICA tends to be lower in IDDW patients with low serum C-peptide concentrations. In contrast, the prevalence of anti-GAD antibody was not different according to sernm C-peptide levels. CONCLUSION: These results suggested that the prevalence of ICA and antii-GAD antibody was lower in Korean adult IDDM and recent-onset NIDDM patients than that in Caucasians.
Analysis of the Persistence of Islet Cell Cytoplasmic Antibodies and Glutamic Acid Decarboxylase ( GAD ) 65 Antibodies in Type 1 Diabetic Children.
Hyoung Woo Lee, Kyu Chang Won
Korean Diabetes J. 1998;22(2):145-154.   Published online January 1, 2001
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AbstractAbstract PDF
BACKGROUND
Type 1 diabetes mellitus is attributable to progressive autoimmune destruction of insulin-producing pancreatic islet cells, which result in absolute deficiency of insulin. Serum antibodies against islet antigens in patients with type 1 diabetes mellitus have been recognized. These include insulin autoantibodies, islet cell cytoplasmic antibodies(ICA) and glutamic acid decarboxylase(GAD) antibodies. Although, indirect immunofluorescence assay for measuring ICA have been studied as a marker for the loss of beta cell function and for monitoring the effects of immunosuppressive treatment at onset of type 1 diabetes mellitus, problem with reproducibility and standardization between laboratories still exist. Further, because the classic assays of glutamic acid decarboxylase(GAD) are still rather time-cansuming, a more simple and reproducible radioligand assay is widely used currently. Thus, this study was performed to evaluate the prevalence of cytoplasmic islet cell antibodies and glutamic acid decarboxylase antibodies in Korean patients with type 1 diabetes mellitus and to observe the associations of glutamic acid decarboxylase antibodies with islet cell cytoplasmic antibodies. METHODS: Patients with type 1 diabetes(n=26) and control(n=20) sera were used to develop quantitative antibody assays with in vitro synthesized recombinant S-methionine-labelled GAD, and protein A-sepharose to separate free from antibody-bound ligand. Also the sera were screened for conventional ICA-IgG by means of indirect immunotluorescence on section of blood group 0 human pancreas. Then, Positive sample were titered by doubling dilution. RESULTS: The overall prevalences of islet cell cytoplasmic antibodies and glutamic acid decarboxylase (GAD) antibodies in Korean patients with type 1 diabetes mellitus were 46%(12 of 26) and 39%(10 of 26) respectively. In a subset of these patients with recent onset type 1 diabetes mellitus(<1 year), the prevalence of islet cell cytoplasmic antibodies(ICA) and glutamic acid decarboxylase (GAD) antibodies were all 75%(3 of 4). The prevelances of islet cell cytoplasmic antibodies(ICA) and glutamic acid decarboxylase(GAD) antibodies were dereased in patients with long standing diabetes at 41%(9 of 22) and 32%(7 of 22) respectively. The frequency of glutamic acid decarboxylase(GAD) antibodies increased as the JDF units of islet cell cytoplasmic antibodies(ICA) increased. The frequency of islet cell cytoplasmic antibodies(ICA) increased as the GAD index increased. CONCLUSION: These results suggest that islet cell cytoplasmic antibodies(ICA) test by standard indirect immunofluorescence technique and glutamic acid decarboxylase(GAD) antibodies test by radioligand binding assay is useful for screening and diagnosis of Korean patient with type 1 diabetic children, But, long-term prospective studies on large cohorts of patients should be done to evaluate the predictive power and the prevalence of islet cell cytoplasmic antibodies and glutamic acid decarboxylase antibodies in Korean patients with type 1 diabetic children.

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