155 results on '"Glutamic acid decarboxylase antibody"'
Search Results
2. Stiff Person Syndrome and Brittle Type 1 Diabetes: Report of 2 Cases
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Ismael A. Quintal-Medina, MD, Francisco J. Gómez-Pérez, MD, and Paloma Almeda-Valdes, MD, PhD
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stiff person syndrome ,type 1 diabetes ,glutamic acid decarboxylase antibody ,Diseases of the endocrine glands. Clinical endocrinology ,RC648-665 - Abstract
Background/Objective: Stiff person syndrome (SPS) and type 1 diabetes (T1D) are heterogeneous disorders characterized by antibodies (Abs) against glutamic acid decarboxylase (GAD). Case Report: We describe 2 patients with T1D and autoimmune thyroid disease who presented with muscle rigidity and intermittent spasms that affected gait and with elevated circulating anti-GAD titers. Classic SPS and stiff limb syndrome were diagnosed, respectively. Muscle spasms resolved with immunotherapy and muscle relaxants in both patients, and the ability to ambulate without an assistive device was restored in 1 patient. Patients also had brittle diabetes with high glycemic variability, requiring the use of flash glucose monitoring with an insulin pump and a second-generation basal insulin analog, respectively. Discussion: GAD Ab–associated syndromes include SPS, T1D, and other endocrinopathies. The clinical heterogeneity implies variable susceptibility of γ-aminobutyric acid-ergic neurons and pancreatic beta cells to anti-GAD or other autoantibodies. Conclusion: Our case series represent the heterogeneity in natural history, clinical course, and response to therapy in patients with Abs against GAD-spectrum disorders.
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- 2024
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3. Case report: Strong GAD antibody positivity and type 1 diabetes-HLA-susceptible haplotype-DRB1*04:05- DQB1*04:01 in a Japanese patient with immune checkpoint inhibitor-induced type 1 diabetes.
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Shunya Yabuki, Hiroyuki Hirai, Chihiro Moriya, Yoshiro Kusano, and Takeo Hasegawa
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IMMUNE checkpoint proteins ,TYPE 1 diabetes ,JAPANESE people ,GLUTAMATE decarboxylase ,DIABETIC acidosis ,DRUG side effects - Abstract
Immune checkpoint inhibitors (ICIs) are widely used in cancer treatment; however, they can lead to immune-related adverse events, including immune checkpoint inhibitor-induced type 1 diabetes mellitus (ICI-T1DM). While fulminant T1DM is common in East Asia, ICI-T1DM has predominantly been reported in Western countries. In this report, we present the case of a 66-yearold Japanese man with type 2 diabetes mellitus undergoing dialysis for diabetic nephropathy. The patient was diagnosed with left upper lobe lung cancer, and treatment with nivolumab and ipilimumab was initiated. After 48 days, the patient experienced impaired consciousness and difficulty moving. His blood glucose levels were 815 mg/dL, and metabolic acidosis was detected, leading to a diagnosis of diabetic ketoacidosis. The patient was subsequently treated with continuous intravenous insulin. However, his C-peptide levels rapidly depleted, and new-onset ICI-T1DM was diagnosed. Although most Japanese patients with ICI-T1DM test negative for glutamic acid decarboxylase (GAD) antibodies, this case exhibited a strong positivity. Thus, we reviewed the literature on 15 similar Japanese cases, revealing a mean HbA1c level at onset of 8.7% and a mean time from ICI administration to onset of 9.7 weeks, which was shorter than that in GAD-negative cases. Moreover, human leukocyte antigen typing revealed five cases of DRB1*04:05-DQB1*04:01, including the present case, and one case of DRB1*09:01-DQB1*03:03, both of which were susceptible to T1DM haplotypes. These findings suggest that GAD antibody positivity may be associated with acute onset and disease progression in some cases of Japanese patients with ICI-Frontiers T1DM. Given that the prediction of new-onset ICI-T1DM is challenging, monitoring GAD antibody levels might be useful. However, further studies with large sample sizes and validation across different racial and ethnic populations are warranted. [ABSTRACT FROM AUTHOR]
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- 2024
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4. Az 1-es típusú diabetes mellitus immunterápiája.
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Arapovicsné Kiss, Krisztina, Tóth, Anna, Schandl, László, Kiss, Zsófia, Winkler, Gábor, and Kis, János Tibor
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Copyright of Hungarian Medical Journal / Orvosi Hetilap is the property of Akademiai Kiado and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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- 2024
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5. Imeglimin Improved Plasma Glucose Levels in Patients With Latent Autoimmune Diabetes of Adults: Report of 2 Cases.
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Okada, Shuichi, Okada, Kazuya, Okada, Junichi, and Yamada, Eijiro
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BLOOD sugar , *GLYCOSYLATED hemoglobin , *TYPE 1 diabetes , *TYPE 2 diabetes , *ADULTS - Abstract
Imeglimin has not been well studied as an oral agent for the treatment of latent autoimmune diabetes of adults (LADA). We treated 2 cases of LADA with imeglimin. The case 1 patient was originally diagnosed with type 2 diabetes (T2D) at age 50 years and was treated with sulfonylurea, biguanide, canagliflozin, imeglimin, and dulaglutide. Before imeglimin, his glycated hemoglobin A1c (HbA1c) change was 94.0 mmol/mol (8.6%) in November 2022, but it dropped to 71.0 mmol/mol (6.5%) in May 2023 after imeglimin was added. The case 2 patient was originally diagnosed with T2D when she was aged 48 years. She was treated with vildagliptin, biguanide, luseogliflozin, and imeglimin. Her HbA1c before imeglimin was 92.9 mmol/mol (8.5%) in January 2023, which decreased to 75.4 mmol/mol (6.9%) in July 2023 after imeglimin was added. Although imeglimin has not been approved for treating type 1 diabetes and LADA, adding imeglimin to the current medication was effective in improving and controlling the patients' plasma glucose. [ABSTRACT FROM AUTHOR]
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- 2024
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6. Effects of rosuvastatin on serum glucose and insulin in hyperuricemic rats
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Dilidaer Xilifu, Zumulaiti Tuerxun, Buweiayixiemu Nuermaimaiti, Ayinu Aili, Nijiati Rehemu, Huiping Sun, and Xiangyang Zhang
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Rosuvastatin ,Hyperuricaemic rat ,Fasting blood glucose ,Insulin ,Glutamic acid decarboxylase antibody ,Therapeutics. Pharmacology ,RM1-950 ,Toxicology. Poisons ,RA1190-1270 - Abstract
Abstract Background Hyperuricemia is a state in which the serum levels of uric acid (UA) are elevated. This study was to determine the roles of rosuvastatin in fasting blood glucose (FGB) and insulin levels in hyperuricemic rats. Methods Thirty-six Sprague-Dawley (SD) rats were randomized divided into the control, model and rosuvastatin groups: the control was given no intervention, the model group was established by administrating yeast extract powder and oxonic acid potassium salt, and the rosuvastatin group was given intravenous administration of rosuvastatin for 28 days in hyperuricemic rats. Serum uric acid (SUA), fasting blood glucose (FBG), fasting blood insulin (FBI), glutamic acid decarboxylase antibody (GADA), oral glucose tolerance test (OGTT) levels, and the ultrastructure of pancreatic β-cells were measured. Also, homeostasis model assessment of insulin resistance (HOMA-IR) scores was computed in three groups. Results Compared to the model group, SUA were decreased, while the FBG, GADA, OGTT and HOMA-IR at week 4 were significantly increased in rosuvastatin group. However, FBI was not significantly changed between three groups. It was also showed that the structure of pancreatic β-cells was damaged and the number of β-cells was changed in hyperuricemic rats while they were aggravated in rosuvastatin group. Conclusion Rosuvastatin has roles in inducing FGB, GADA, OGTT and pancreatic β-cells damage in hyperuricemic rats.
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- 2022
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7. The relationship between GAD65 autoantibody and the risk of T1DM onset.
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Keshavarzi, Elham, Noveiry, Behnoud Baradaran, and Rezaei, Nima
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ISLANDS of Langerhans , *GLUTAMATE decarboxylase , *TYPE 1 diabetes , *TYPE 2 diabetes , *GLYCEMIC control , *CELL physiology , *AUTOANTIBODIES , *HYPERGLYCEMIA - Abstract
Objectives: Type 1 diabetes mellitus (T1DM) is a well-known autoimmune disease, characterized by β-cell destruction in pancreas islet cells, which results insulin deficiency and subsequent hyperglycemic sequelae. While there is screening for type 2 DM that leads to better glycemic control and outcome, the majority of T1DM patients are diagnosed when much of the pancreatic cells and their function are disturbed. The aim of this article is to present an overview of the effective factors in the positivity of Glutamic acid decarboxylase antibody)GADA(and identifying the high-risk individuals for T1DM. Methods: We searched English literature available at National Library of Medicine via PubMed, and Google Scholar through December 2020. Finally, 79 papers have been included in the study. Studies were summarized based on the number of positive autoantibodies and onset of T1DM over time and GADA correlation with different variables. Conclusions: GADA is an easy marker to measure that can be detected many months prior to the clinical presentation and remains positive even after early childhood. [ABSTRACT FROM AUTHOR]
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- 2022
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8. Latent Autoimmune Diabetes in Adults (LADA) and its Metabolic Characteristics among Yemeni Type 2 Diabetes Mellitus Patients
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Al-Zubairi T, AL-Habori M, and Saif-Ali R
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latent autoimmune diabetes in adults ,type 2 dm ,metabolic syndrome ,insulin resistance ,glutamic acid decarboxylase antibody ,Specialties of internal medicine ,RC581-951 - Abstract
Thekra Al-Zubairi, Molham AL-Habori, Riyadh Saif-Ali Department of Biochemistry and Molecular Biology, Faculty of Medicine and Health Sciences, University of Sana`a, Sana`a, YemenCorrespondence: Molham AL-Habori Email malhabori@hotmail.comPurpose: Although there is ample data about the prevalence of diabetes in the Middle East, little is known about the prevalence and features of autoimmune diabetes in this region. The aim of this study was to investigate the prevalence and metabolic characteristics of latent autoimmune diabetes in adults (LADA) amongst Yemeni Type 2 DM patients.Patients and Methods: In this cross-section study, 270 Type 2 DM patients aged 30– 70 years were recruited from the National Diabetes Center, Al-Thowra Hospital, Sana’a city, during the period November 2015 to August 2016. All Type 2 DM patients were diagnosed within 5 years and who did not require insulin for a minimum of 6 months following diagnosis. Levels of glutamic acid decarboxylase autoantibodies (GADA) were measured in all patients, and LADA was diagnosed in patients testing positive for anti-GAD antibodies. Further, biochemical analysis was carried out including fasting blood glucose (FBG), glycated haemoglobin (HbA1c), insulin, and lipid profile. Insulin resistance (HOMA-IR) and β-cell function (HOMA-β) were calculated.Results: The prevalence of LADA, as defined by GADA-positive, amongst patient with Type 2 DM was 4.4%; with no significant difference in the prevalence between male (5.8%) and female (3.4%). LADA patients were younger than GADA-negative Type 2 DM. Body mass index, waist circumference, insulin and HOMA-β were significantly lower in LADA patients, whereas triglyceride, cholesterol, HDL-c and HOMA-IR were non-significantly lower with respect to Type 2 DM. In contrast, FBG and HbA1c were significantly higher in LADA patients. Moreover, the prevalence of metabolic syndrome was significantly lower in LADA as compared with Type 2 DM. Only 2 out of the 12 GADA-positive (16.7%) were on insulin treatment at the time of the study.Conclusion: The prevalence of LADA in Yemeni Type 2 DM is lower than many of those reported in the literature, with no gender preference. Metabolic syndrome was significantly lower in LADA patients. Patients with LADA share insulin resistance with Type 2 DM but display a more severe defect in β-cell function, thus highlighting the importance of an early diagnosis of LADA, to correctly treat LADA patients, allowing safe and effective therapies.Keywords: latent autoimmune diabetes in adults, Type 2 DM, metabolic syndrome, insulin resistance, glutamic acid decarboxylase antibody
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- 2021
9. Effects of rosuvastatin on serum glucose and insulin in hyperuricemic rats.
- Author
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Xilifu, Dilidaer, Tuerxun, Zumulaiti, Nuermaimaiti, Buweiayixiemu, Aili, Ayinu, Rehemu, Nijiati, Sun, Huiping, and Zhang, Xiangyang
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URIC acid ,GLUTAMATE decarboxylase ,ROSUVASTATIN ,GLUCOSE tolerance tests ,BLOOD sugar ,RATS ,INSULIN - Abstract
Background: Hyperuricemia is a state in which the serum levels of uric acid (UA) are elevated. This study was to determine the roles of rosuvastatin in fasting blood glucose (FGB) and insulin levels in hyperuricemic rats. Methods: Thirty-six Sprague-Dawley (SD) rats were randomized divided into the control, model and rosuvastatin groups: the control was given no intervention, the model group was established by administrating yeast extract powder and oxonic acid potassium salt, and the rosuvastatin group was given intravenous administration of rosuvastatin for 28 days in hyperuricemic rats. Serum uric acid (SUA), fasting blood glucose (FBG), fasting blood insulin (FBI), glutamic acid decarboxylase antibody (GADA), oral glucose tolerance test (OGTT) levels, and the ultrastructure of pancreatic β-cells were measured. Also, homeostasis model assessment of insulin resistance (HOMA-IR) scores was computed in three groups. Results: Compared to the model group, SUA were decreased, while the FBG, GADA, OGTT and HOMA-IR at week 4 were significantly increased in rosuvastatin group. However, FBI was not significantly changed between three groups. It was also showed that the structure of pancreatic β-cells was damaged and the number of β-cells was changed in hyperuricemic rats while they were aggravated in rosuvastatin group. Conclusion: Rosuvastatin has roles in inducing FGB, GADA, OGTT and pancreatic β-cells damage in hyperuricemic rats. [ABSTRACT FROM AUTHOR]
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- 2022
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10. Method Performance Verification of Anti-GAD65 and Anti-Insulin antibody Assays.
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Rihwa Choi, Sukjung Lee, Eunkyung Lee, Hyerim Kim, and Sang Gon Lee
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INSULIN antibodies ,CHEMILUMINESCENCE immunoassay ,GLUTAMATE decarboxylase - Abstract
Background: The aim of this study was to evaluate the performance of chemiluminescence immunoassays for anti-GAD65 and anti-insulin antibodies following user verification guidelines. Methods: The analytical performance of anti-GAD65 and anti-insulin antibodies using a MAGLUMI 2000 analyzer was verified following user verification guidelines by the Clinical and Laboratory Standards Institute. Results: Performance specifications including precision, linearity, carry-over, cutoffs for positive results, reference intervals, and comparability with pre-existing commercially available radioimmunoassays using patient specimens and certified reference material were verified (coefficients of variation for precision of anti-GAD65 and anti-insulin antibodies were 2.6% and 3.4%, respectively). Comparability assessed using clinical serum specimens showed overall agreement with radioimmunoassay of 87.2% (95% confidence interval 74.8% - 94.0%) for the anti-GAD65 antibody assay and 85.4% (95% confidence interval 71.6% - 93.1%) for the anti-insulin antibody assay. Conclusions: The results of this study verified the analytical performance of MAGLUMI anti-GAD65 and anti-insulin antibody assays for clinical use. [ABSTRACT FROM AUTHOR]
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- 2022
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11. Predictive Value of GAD Antibody for Diabetes in Normal Chinese Adults: A Retrospective Cohort Study in China
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Li J, Lin S, Deng C, and Xu T
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autoimmune diabetes ,glutamic acid decarboxylase antibody ,latent autoimmune diabetes in adults ,obesity ,prevention ,Specialties of internal medicine ,RC581-951 - Abstract
Jing Li,1 Songbai Lin,1 Chuiwen Deng,2 Tengda Xu1 1Department of Health Management, Peking Union Medical College Hospital, Beijing, People’s Republic of China; 2Rheumatology and Immunology Department, Peking Union Medical College Hospital, Beijing, People’s Republic of ChinaCorrespondence: Tengda XuDepartment of Health Management, Peking Union Medical College Hospital, 1# Shuaifuyuan, Dongcheng District, Beijing, 100730, People’s Republic of ChinaTel/Fax +86 10 6915 9866Email xutd@pumch.cnPurpose: To investigate the prevalence of GAD antibody (GADA) in the general adult population and to evaluate its predictive value for diabetes in China.Patients and Methods: We searched the PUMCH-HM database and identified 36,731 adult subjects with GADA test results from 2012 to 2015. We then established a retrospective cohort of 4835 nondiabetic subjects at baseline with complete annual health evaluation records through 2019. The median follow-up time was 4.8 (3.0– 7.3) years.Results: The overall prevalence of GADA was 0.53% and was higher in diabetic subjects (1.25%) than in nondiabetic subjects (0.47%). We found a decrease in baseline body mass index (BMI) from the GADA- to GADAhigh subgroups among baseline diabetic and prediabetic patients and also those who developed diabetes later in the cohort study. A total of 136 subjects (2.8%) developed diabetes after a median follow-up of 3.5 years. For GADA+ participants, BMI was not associated with the risk for diabetes. In the Cox regression model, the GADAlow and GADAhigh exhibited 2.63-fold and 4.16-fold increased risk for diabetes, respectively. This increased risk for diabetes by GADA-positivity is only found in male adults (HR 4.55, 95% CI 2.25– 9.23).Conclusion: GADA has a low prevalence in China but is associated with a 2.63– 4.16-fold increased risk for diabetes.Keywords: autoimmune diabetes, glutamic acid decarboxylase antibody, latent autoimmune diabetes in adults, obesity, prevention
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- 2021
12. rs3806265 and rs4612666 of the NLRP3 Gene Are Associated With the Titer of Glutamic Acid Decarboxylase Antibody in Type 1 Diabetes.
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Sun, Xiaoxiao, Xu, Linling, Xia, Ying, Luo, Shuoming, Lin, Jian, Xiao, Yang, Huang, Gan, Li, Xia, Xie, Zhiguo, and Zhou, Zhiguang
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GLUTAMATE decarboxylase ,TYPE 1 diabetes ,NLRP3 protein ,CHINESE people ,GENETIC models ,AUTOIMMUNE diseases - Abstract
Background and Aims: The NLRP3 gene is reportedly associated with several autoimmune diseases. However, in the Chinese Han population, whether NLRP3 polymorphisms are associated with type 1 diabetes (T1D) is unclear. Therefore, this study examined the associations of rs3806265 and rs4612666 of the NLRP3 gene with T1D susceptibility and the clinical characteristics of Chinese Han T1D patients. Methods: In total, 510 classic T1D patients and 531 healthy controls from the Chinese Han population were recruited for a case-control study. rs3806265 and rs4612666 of the NLRP3 gene were genotyped by MassARRAY. Logistic regression analysis and the chi-square test were used to compare the distributions of the alleles and genotypes of rs3806265 and rs4612666. The relationships between rs3806265 and rs4612666 and the clinical characteristics of T1D patients were analyzed by Kruskal-Wallis one-way ANOVA. Student's t test was used to analyze normally distributed data. Bonferroni correction was used for multiple comparisons. Results: 1) rs3806265 was associated with glutamic acid decarboxylase antibody (GADA) titers (P = 0.02), and patients with the CC genotype had higher GADA titers than patients with the TT genotype. 2) rs4612666 was also associated with GADA titers (P=0.041). Compared with patients with the CC genotype, patients with the TT genotype had higher GADA titers. 3) rs3806265 and rs4612666 of the NLRP3 gene were not significantly associated with T1D susceptibility under different genetic models. Conclusion: rs3806265 and rs4612666 of the NLRP3 gene were significantly associated with GADA titers in Chinese Han T1D patients. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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13. 血清 GAD、ICA 及 C-P 联合检测对 I 型糖尿病的诊断价值.
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江 岩, 赵正科, 王光彦, 许连刚, 李梦蝶, 王茂繁, 龙双梅, 刘 蛟, and 钱 晋
- Abstract
Objective To explore the diagnostic value of glutamic acid decarboxylase antibody (GAD), islet cell autoantibody (ICA) and C-Peptide (C-P) detection in Type I diabetes mellitus. Methods GAD, ICA and C-P values of 54 T1DM confirmed patients in People’s Hospital of Chuxiong Yi Autonomous Prefecture from January 2019 to August 2020 were analyzed retrospectively, and compared with 50 normal people who came to our hospital for physical examination during this period. Results GAD and ICA in observation group were significantly higher than those in control group. The C-P of observation group was significantly lower than that of control group, and the difference was statistically significant (P < 0.05). The AUC of GAD, ICA, C-P and three combined tests for T1DM diagnosis were 0.927, 0.840, 0.956 and 0.993, respectively. The area under ROC curve (AUC) of GAD, ICA and C-P combined detection was the largest, suggesting that the diagnostic efficiency of GAD, ICA and C-P combined detection was higher than that of GAD, ICA and C-P alone. Conclusion The combined detection of GAD, ICA and C-P can improve the sensitivity and specificity of T1DM diagnosis, and play an outstanding role in the early diagnosis, treatment, prevention and early warning evaluation of T1DM. [ABSTRACT FROM AUTHOR]
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- 2022
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14. RELATIONSHIP BETWEEN AGE AT DIAGNOSIS AND GLUTAMIC ACID DECARBOXYLASE ANTIBODY IN NON-OVERWEIGHT/OBESE DIABETIC PATIENTS: A CROSS-SECTIONAL COHORT STUDY
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Tran Thua Nguyen
- Subjects
glutamic acid decarboxylase antibody ,diabetes ,non-overweight/obese ,age ,Medicine (General) ,R5-920 - Abstract
To evaluate the association between age at diagnosis, duration of diabetes, and the positivity of glutamic acid decarboxylase antibody (GADA) in non-overweight/obese diabetic individuals. A cross-sectional study including 284 non-overweight/obese diabetic patients at Hue Central Hospital was carried out from August 2017 to August 2019. All patients underwent a blood test to measure the level of GADA. GADA positivity was determined when GADA concentration was higher than 5 IU/mL. Clinical data included age, sex, weight, and height. Age at diagnosis was obtained from the patients. Data were analyzed using SPSS version 16.0. Non-overweight/obese diabetic patients with positive GADA (n=22, 7.7%) were younger at the onset of diabetes (52.4±14.1 versus 59.8±12.8 years, p=0.0103) and had a similar disease duration (8.0±6.9 versus 7.1±6.0 years, p=0.5048), as compared with negative GADA patients. The cut-off of age at diagnosis for detecting the risk of GADA positivity in non-overweight/obese diabetic individuals was 57. The rate of GADA positivity was 2.7 times higher in the age group of under 57 years at diagnosis compared to that in the older group. GADA measurement is a useful tool in the diagnosis of diabetes in non-overweight/obese diabetic individuals.
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- 2020
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15. rs3806265 and rs4612666 of the NLRP3 Gene Are Associated With the Titer of Glutamic Acid Decarboxylase Antibody in Type 1 Diabetes
- Author
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Xiaoxiao Sun, Linling Xu, Ying Xia, Shuoming Luo, Jian Lin, Yang Xiao, Gan Huang, Xia Li, Zhiguo Xie, and Zhiguang Zhou
- Subjects
inflammasome ,single nucleotide polymorphism ,type 1 diabetes ,correlation analysis ,glutamic acid decarboxylase antibody ,Diseases of the endocrine glands. Clinical endocrinology ,RC648-665 - Abstract
Background and AimsThe NLRP3 gene is reportedly associated with several autoimmune diseases. However, in the Chinese Han population, whether NLRP3 polymorphisms are associated with type 1 diabetes (T1D) is unclear. Therefore, this study examined the associations of rs3806265 and rs4612666 of the NLRP3 gene with T1D susceptibility and the clinical characteristics of Chinese Han T1D patients.MethodsIn total, 510 classic T1D patients and 531 healthy controls from the Chinese Han population were recruited for a case-control study. rs3806265 and rs4612666 of the NLRP3 gene were genotyped by MassARRAY. Logistic regression analysis and the chi-square test were used to compare the distributions of the alleles and genotypes of rs3806265 and rs4612666. The relationships between rs3806265 and rs4612666 and the clinical characteristics of T1D patients were analyzed by Kruskal-Wallis one-way ANOVA. Student’s t test was used to analyze normally distributed data. Bonferroni correction was used for multiple comparisons.Results1) rs3806265 was associated with glutamic acid decarboxylase antibody (GADA) titers (P = 0.02), and patients with the CC genotype had higher GADA titers than patients with the TT genotype. 2) rs4612666 was also associated with GADA titers (P=0.041). Compared with patients with the CC genotype, patients with the TT genotype had higher GADA titers. 3) rs3806265 and rs4612666 of the NLRP3 gene were not significantly associated with T1D susceptibility under different genetic models.Conclusionrs3806265 and rs4612666 of the NLRP3 gene were significantly associated with GADA titers in Chinese Han T1D patients.
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- 2022
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16. IT-DEX and B cell depletion in a child with anti-GAD 65 autoimmune encephalitis presenting as NORSE: A case report.
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Yarimi JM, Sandweiss AJ, Salazar KP, Massrey C, Ankar A, Muscal E, Lai YC, Cokley JA, Davila-Williams D, Shukla NM, and Fisher KS
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- Humans, Female, Child, Glutamate Decarboxylase immunology, Rituximab therapeutic use, Injections, Spinal, Hashimoto Disease drug therapy, Hashimoto Disease diagnosis, Hashimoto Disease immunology, Lymphocyte Depletion methods, Autoantibodies blood, Encephalitis immunology, Encephalitis drug therapy, Dexamethasone therapeutic use, Dexamethasone administration & dosage, Status Epilepticus drug therapy, Status Epilepticus etiology, Status Epilepticus immunology, B-Lymphocytes immunology
- Abstract
New-onset refractory status epilepticus (NORSE) is a devastating clinical condition that often leads to severe disability. Intrathecal dexamethasone (IT-DEX) has been reported to improve refractory status epilepticus. We present an 11-year-old female with anti-GAD 65 encephalitis presenting as NORSE who had minimal response to standard anti-seizure medications and first-line immunotherapies. The patient received 6 doses of IT-DEX in conjunction with rituximab which correlated with subsequent decreased neuroinflammation, reduced seizure burden and aided in weaning anesthetic infusions. Our case with literature review suggests IT-DEX may be utilized as an early intervention in those with refractory status epilepticus from various etiologies., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)
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- 2024
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17. Adult-onset autoimmune diabetes identified by glutamic acid decarboxylase autoantibodies: a retrospective cohort study.
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Wada, Eri, Onoue, Takeshi, Kinoshita, Tamaki, Hayase, Ayaka, Handa, Tomoko, Ito, Masaaki, Furukawa, Mariko, Okuji, Takayuki, Kobayashi, Tomoko, Iwama, Shintaro, Sugiyama, Mariko, Takagi, Hiroshi, Hagiwara, Daisuke, Suga, Hidetaka, Banno, Ryoichi, Goto, Motomitsu, and Arima, Hiroshi
- Abstract
Aims/hypothesis: Patients with GAD antibodies (GADAb) showing clinical features of type 2 diabetes typically exhibit progression to an insulin-dependent state in several months or years. This condition is diagnosed as slowly progressive insulin-dependent (type 1) diabetes mellitus (SPIDDM) or latent autoimmune diabetes in adults, a subtype of adult-onset autoimmune diabetes. However, some patients diagnosed with adult-onset autoimmune diabetes do not progress to an insulin-dependent state. We conducted a retrospective cohort study to identify patients with non-insulin-dependent diabetes among those diagnosed with adult-onset autoimmune diabetes using measurable indicators in routine clinical practice. Methods: We surveyed data from the electronic medical records of all patients with GADAb from eight medical centres in Japan for selecting and analysing patients who matched the diagnostic criteria of SPIDDM. Results: Overall, 345 patients were analysed; of these, 162 initiated insulin therapy (insulin therapy group), whereas 183 did not (non-insulin therapy group) during the follow-up period (median 3.0 years). Patients in the non-insulin therapy group were more likely to be male and presented a later diabetes onset, shorter duration of diabetes, higher BMI, higher blood pressure levels, lower HbA
1c levels, lower GADAb levels and lesser antidiabetic agent use than those in the insulin therapy group when GADAb was first identified as positive. A Cox proportional hazards model showed that BMI, HbA1c levels and GADAb levels were independent factors for progression to insulin therapy. Kaplan–Meier analyses revealed that 86.0% of the patients with diabetes having GADAb who presented all three factors (BMI ≥ 22 kg/m2 , HbA1c < 75 mmol/mol [9.0%] and GADAb <10.0 U/ml) did not require insulin therapy for 4 years. Conclusions/interpretation: Higher BMI (≥22 kg/m2 ), lower HbA1c (<75 mmol/mol [9.0%]) and lower GADAb levels (<10.0 U/ml) can predict a non-insulin-dependent state for at least several years in Japanese patients with diabetes having GADAb. [ABSTRACT FROM AUTHOR]- Published
- 2021
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18. Stiff Person Syndrome Associated with Compartment Syndrome
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Kok Pin Yong and Yew Long Lo
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Stiff person syndrome ,Compartment syndrome ,Glutamic acid decarboxylase antibody ,Autoimmune disease ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Stiff person syndrome (SPS) is a rare and disabling neurological disorder of autoimmune origin, characterized by progressive stiffness and muscle spasms affecting the axial and limb muscles, most frequently associated with antibodies against glutamic acid decarboxylase. We describe a patient who presented initially with compartment syndrome and was later diagnosed with SPS.This is the first case report of SPS possibly presenting initially with compartment syndrome. This case illustrates the importance of recognizing that patients with SPS may present with varied manifestations, including compartment syndrome, which by itself is a medical emergency.
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- 2019
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19. Maturity‐onset diabetes of the young type 5 uncovered during pregnancy with a long‐term diagnosis of type 1 diabetes
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Mingqun Deng, Xiaojing Wang, Xinhua Xiao, and Fan Ping
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Abdominal ultrasound ,Glutamic acid decarboxylase antibody ,Maturity‐onset diabetes of the young type 5 during pregnancy ,Diseases of the endocrine glands. Clinical endocrinology ,RC648-665 - Abstract
Abstract We report a case of missed diagnosis of maturity‐onset diabetes of the young type 5 uncovered during pregnancy with a previous diagnosis of type 1 diabetes. Maturity‐onset diabetes of the young type 5 cannot be excluded in early‐onset diabetes with positive islet‐related autoantibodies and type 1 diabetes‐prone human leukocyte antigen subtypes. Abdominal ultrasound should be used in all patients with pre‐gestational diabetes, and maturity‐onset diabetes of the young type 5 should be considered when renal abnormality is presented.
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- 2019
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20. Predicting non-insulin-dependent state in patients with slowly progressive insulin-dependent (type 1) diabetes mellitus or latent autoimmune diabetes in adults. Reply to Sugiyama K and Saisho Y [letter]
- Author
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Wada, Eri, Onoue, Takeshi, Kinoshita, Tamaki, Hayase, Ayaka, Handa, Tomoko, Ito, Masaaki, Furukawa, Mariko, Okuji, Takayuki, Kobayashi, Tomoko, Iwama, Shintaro, Sugiyama, Mariko, Takagi, Hiroshi, Hagiwara, Daisuke, Suga, Hidetaka, Banno, Ryoichi, Goto, Motomitsu, Arima, Hiroshi, Wada, Eri, Onoue, Takeshi, Kinoshita, Tamaki, Hayase, Ayaka, Handa, Tomoko, Ito, Masaaki, Furukawa, Mariko, Okuji, Takayuki, Kobayashi, Tomoko, Iwama, Shintaro, Sugiyama, Mariko, Takagi, Hiroshi, Hagiwara, Daisuke, Suga, Hidetaka, Banno, Ryoichi, Goto, Motomitsu, and Arima, Hiroshi
- Published
- 2023
21. A convenient diagnostic tool for discriminating adult-onset glutamic acid decarboxylase antibody-positive autoimmune diabetes from type 2 diabetes: a retrospective study
- Author
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Hon-Ke Sia, Shih-Te Tu, Pei-Yung Liao, Kuan-Han Lin, Chew-Teng Kor, and Ling-Ling Yeh
- Subjects
GAD antibody ,Diagnosis ,Autoimmune diabetes ,Type 1 ,Type 2 ,Glutamic acid decarboxylase antibody ,Medicine ,Biology (General) ,QH301-705.5 - Abstract
Background The glutamic acid decarboxylase antibody (GADA) test, commonly used to diagnose autoimmune diabetes, is not cost-effective in areas of low prevalence. The aim of this study was to develop a convenient tool to discriminate adult-onset GADA-positive autoimmune diabetes from type 2 diabetes (T2DM) in patients with newly diagnosed diabetes. Methods This retrospective cross-sectional study, conducted at Changhua Christian Hospital in Taiwan, collected electronic medical record data from January 2009 to December 2018. Patients were divided into a case group (GADA+, n = 152) and a reference group (T2DM, n = 358). Variables that differed significantly between the groups were subjected to receiver operator characteristic analysis to establish cutoff values. Discriminant function analysis was then employed to discriminate the two groups. Results At the onset of diabetes, the GADA+ group was younger, with lower body mass index (BMI), higher hemoglobin A1c (HbA1c), higher high-density lipoprotein cholesterol (HDL-C), and lower total cholesterol and triglycerides (TG). Five major factors were identified to form the linear discriminant functions: BMI, age at onset, TG, HDL-C, and HbA1c. BMI < 23 kg/m2 was the most important factor, followed by TG < 98 mg/dL, HDL-C ≥ 46 mg/dL, age at onset < 30 years, and HbA1c ≥ 8.6%. The overall accuracy of the linear discriminant functions was 87.1%, with 84.2% sensitivity and 88.3% specificity. Conclusions Routine tests in diabetes care were used to establish a convenient, low-cost tool that may assist in the early identification of adult-onset GAD+ autoimmune diabetes in clinical practice.
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- 2020
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22. Downregulation of T-Cell Transcription Factors in Adult Latent Autoimmune Diabetes with High-Titer Glutamic Acid Decaroxylase Antibody.
- Author
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Wang, Xia, Yang, Lin, Cheng, Ying, Liang, Huiying, Hu, Jingping, Zheng, Peilin, Huang, Gan, and Zhou, Zhiguang
- Subjects
- *
TRANSCRIPTION factors , *GLUTAMIC acid , *FORKHEAD transcription factors , *TYPE 2 diabetes , *GLUTAMATE decarboxylase - Abstract
Introduction: Latent autoimmune diabetes in adults (LADA) shows a heterogeneous clinical profile that is dependent on the glutamic acid decaroxylase antibody (GADA) titer. We speculated that LADA patients with a high or low GADA titer may have distinct T-lymphocyte subset profiles and distinct expression patterns of transcription factors involved in T-cell immunomodulation. Methods: Patients with LADA (n = 40) and type 2 diabetes (T2DM; n = 14) were recruited to the study, and peripheral blood mononuclear cells were isolated. The proportions of T-lymphocyte subsets (Th1 [T helper type 1], Th2 [T helper type 2], Treg [regulatory T], and Th17 [T helper type 17] cells) were determined by flow cytometry. Real-time polymerase chain reaction (PCR) was performed to estimate mRNA expression levels of the T-cell subtype-enriched transcription factors T-bet (Th1), GATA3 (Th2), transcription factor forkhead box protein 3 (FOXP3) (Treg), and RORC (Th17). Results: The frequency of Th1 (as a percentage of total CD4+T cells) was greater in the LADA patients with high-titer GADA than in the LADA patients with low-titer GADA (11.06 ± 1.62 vs. 7.05 ± 0.86, P = 0.030). Compared to the T2DM group, in the low-titer GADA group the frequency of Th1 was significantly reduced (7.05 ± 0.86 vs. 16.75 ± 3.73, P = 0.017) and the frequency of Th17 frequency was signficantly increased (1.11 ± 0.09 vs. 0.74 ± 0.16, P = 0.017). Compared to T2DM patients, in the high-titer GADA group there was a significantly reduced expression of FOXP3 (0.35 ± 0.13 vs. 1.75 ± 0.54, P = 0.002), RORC (0.53 ± 0.19 vs. 2.00 ± 0.77, P = 0.046), and GATA3 (0.74 ± 0.17 vs. 2.31 ± 0.91, P = 0.046). Similarly, the high-titer GADA group expressed reduced levels of FOXP3 and RORC compared to the low-titer GADA group (0.35 ± 0.13 vs. 1.50 ± 0.41, P = 0.027; 0.53 ± 0.19 vs. 1.35 ± 0.21, P = 0.027, respectively). There was a negative correlation between FOXP3 expression level and GADA titer for the entire cohort (r = − 0.0433, P = 0.015) and a stronger negative correlation in LADA patients (r = − 0.606, P = 0.008). Conclusion: LADA patients with high-titer GADA express lower levels of T-cell transcription factors, including the Treg transcription factor FOXP3, which may contribute to differences in the clinical profile compared to LADA patients with low-titer GADA. Trial Registration: ClinicalTrials.gov identifier, NCT01159847. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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23. The preliminary clinical application of electrochemiluminescence assays for islet β cell autoantibodies.
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Qian Li, Zhu Yuxiao, Zou Jing, Chen Rourou, Liu Qing, He Rongbo, Peng Li, Yu Liping, and Liu Yu
- Abstract
Objective To establish a new standard for measurement islet autoantibodies by electrochemiluminescence (ECL) assay and to discuss its applications for type 1 diabetes mellitus (T1DM) prediction and diagnosis. Methods ECL assay was used to measure serum levels of glutamic acid decarboxylase antibody (GADA65), insulin autoantibody (IAA) and protein tyrosine phosphatase antibody (IA-2A) in 124 healthy volunteers, 180 T1DM patients, and 180 type 2 diabetes mellitus (T2DM) patients. Patients admitted in Sir Run Run Hospital, Nanjing Medical University from December 2016 to June 2018 with diagnosis of T1DM or T2DM were enrolled in the study. Healthy volunteers were recruited from students in Nanjing Medical University. The serum antibody level was represented as antibody index. The positive cut-off limit for each antibody was defined as 99% of the indicated antibody index from healthy volunteers. The chi-square test was used to analyze the positivity of GADA65, IAA, IA-2A of T1DM and T2DM patients detected by ECL method. Results The cut-off points for GADA65, IAA and IA-2A were 0.047, 0.009 and 0.0029 respectively by ECL methods. The intra-assay coefficients of variation (CV) for GADA65, IAA and IA-2A were 1.88% - 8.30%, 1.39% - 3.40%, 1.23% - 3.17% respectively, and the inter-assay CV were 3.9%-7.3%, 2.7%-9.8%, 2.2%-7.4% respectively. The repeatability of the result was 99.8%. The positivity of GADA65, IAA, IA-2A were 52% (94/180), 45% (81/180), 21% (39/180) respectively in T1DM patients and were 2.2% (4/180), 2.2% (4/180), 2.2% (4/180) respectively in T2DM patients. There were statistic significances in positivity between T1DM and T2DM for all three antibodies (χ²=113.57, 32.35, 91.31, all P<0.001). The positive ratio of GADA65 and IA-2A detected by ECL or radio-binding assay shows no difference. Conclusion The ECL assay has high sensitivity, specificity and repeatability and could be used for the prediction and diagnosis of T1DM. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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24. Stiff Person Syndrome Associated with Compartment Syndrome.
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Yong, Kok Pin and Lo, Yew Long
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COMPARTMENT syndrome ,GLUTAMATE decarboxylase ,SPASMS ,NEUROLOGICAL disorders ,FIBRODYSPLASIA ossificans progressiva ,EMERGENCY medicine - Abstract
Stiff person syndrome (SPS) is a rare and disabling neurological disorder of autoimmune origin, characterized by progressive stiffness and muscle spasms affecting the axial and limb muscles, most frequently associated with antibodies against glutamic acid decarboxylase. We describe a patient who presented initially with compartment syndrome and was later diagnosed with SPS.This is the first case report of SPS possibly presenting initially with compartment syndrome. This case illustrates the importance of recognizing that patients with SPS may present with varied manifestations, including compartment syndrome, which by itself is a medical emergency. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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25. Diagnostic value of islet autoantibody assays practised in Russia. 1. Classic immunofluorescence islet cell antibody assay, immunoradiometric glutamic acid decarboxylase antibody assay, and ELISA tyrosine phosphatase antibody and insulin antibody assays
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Alexei V. Timofeev, Ksenia A. Gorst, Valentin Y. Uvarov, Ekaterina A. Pronina, Alisa V. Vitebskaya, Anastasiya V. Popovich, Anatoliy N. Tiulpakov, Natalia A. Zubkova, Olesya A. Gioeva, Yulia V. Tikhonovich, Alexander V. Ilin, Oleg Y. Latyshev, Goar F. Okminjan, Ksenia L. Kabolova, Julianna A. Kanokova, Leokadia Y. Zhuleva, Igor E. Koltunov, Elena E. Petriaikina, Irina G. Rybkina, Irina V. Garyaeva, Salome L. Guguchia, Angelina B. Shimarova, Artiom V. Bullikh, Irina G. Kolomina, Evgenia A. Evsyukova, Sergei S. Bukin, Natalia N. Egarmina, Natalia Y. Arbatskaya, Elina Y. Yanovskaya, Vladimir I. Popenko, and Alexander A. Arkhipkin
- Subjects
diabetes mellitus ,diabetes mellitus type 1 ,differential diagnosis ,autoantibodies ,islet cell antibody ,glutamic acid decarboxylase antibody ,tyrosine phosphatase antibody ,insulin antibody ,immunofluorescence assay ,radioimmune assay ,immunoenzyme assa ,Nutritional diseases. Deficiency diseases ,RC620-627 - Abstract
Objective. To estimate performance characteristics and diagnostic value of immunofluorescent islet cell antibody (ICA) assay, immunoradiometric glutamic acid decarboxylase antibody (GADA) assay, and ELISA tyrosine phosphatase IA-2 antibody (IA-2A) and insulin antibody (IA) assays.Research Design and Methods. Antibodies were tested in 438 children and adolescents with newly diagnosed diabetes mellitus (DM) type 1, and in 891 subjects without DM type 1. ICA were determined by the classic indirect immunofluorescent method recommended by the Juvenile Diabetes Foundation International, GADA were determined with the Immunotech IRMA Anti-GAD kit, and IA-2A and IA were determined with Medizym Anti-IA2 and Orgentec Anti-Insulin ELISA kits, respectively. Sensitivity (Se), specificity (Sp), positive predictive value (PPV) and negative predictive value (NPV) of the tests were estimated with contingency tables. Diagnostic accuracy was estimated from areas under receiver operating curves (AUC).Results. ICA test was of the greatest diagnostic value (Se=88%, Sp=96%, PPV=96%, NPV=94%, AUC=0,94), followed by IA-2A (Se=66%, Sp=98%, PPV=98%, NPV=59%, AUC=0,82) and GADA (Se=73%, Sp=84%, PPV=75%, NPV=83%, AUC=0,79). IA test exhibited a very low Se (4,3%) and lacked diagnostic accuracy (AUC=0,5).Conclusions. We recommend to use ICA, IA-2A and GADA tests surveyed in our study for diagnosis of DM type 1 and differential diagnosis of DM. We don’t recommend IA testing with an Orgentec Anti-Insulin ELISA kit for usage in clinical practice.
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- 2016
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26. Clinical Management of Epilepsy With Glutamic Acid Decarboxylase Antibody Positivity: The Interplay Between Immunotherapy and Anti-epileptic Drugs
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Kari-Matti Mäkelä, Aki Hietaharju, Antti Brander, and Jukka Peltola
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clinical management ,glutamic acid decarboxylase antibody ,limbic encephalitis ,autoimmune epilepsy ,case series ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Background: There is scanty guidance in the literature on the management of patients with glutamic acid decarboxylase (GAD65) antibody associated autoimmune epilepsy (GAD-epilepsy). GAD-epilepsy is a rare distinct neurological syndrome with a wide clinical spectrum. We describe six GAD-epilepsy patients with special emphasis on the treatment timing and the relationship between immunologic and anti-epileptic therapy.Methods: Six patients diagnosed with GAD-epilepsy in Tampere University Hospital who had received immunotherapy from 2013 to 2017 were retrospectively analyzed from patient records. Data about symptom onset, including antibody levels, magnetic resonance imaging (MRI), electroencephalograms, immunotherapy and anti-epileptic treatment timing and treatment responses were collected and analyzed. Kruskall-Wallis test was used in the statistical evaluation.Results: All patients were female aged 9–54 at symptom onset. Three had hypothyroidism, none had diabetes, two had migraine. Five patients had very high (>2,000 IU/ml) and one had high (52–251 IU/ml) GAD65 antibody titers. All patients presented with seizure disorders. Patients who received early initiation of immunotherapy (3–10 months) responded well to treatment; patients in whom the immunotherapy was started later (15–87 months) did not respond (p = 0.0495). The first patient was seizure-free after 1 year of regular intravenous immunoglobulin and one antiepileptic drug (AED). The second patient developed unilateral temporal lobe T2 signal changes in MRI; she responded well to immunotherapy, experiencing a significant reduction in seizure frequency and resolution of MRI abnormalities. However, seizures continued despite trials with several AEDs. The third patient responded well to immunoadsorption and rituximab with one AED, with lowering of GAD65 titers (from >2,000 to 300). There was a long delay in the diagnosis of GAD-epilepsy in the three patients who had developed refractory epilepsy, one with hippocampal sclerosis. They all received immunotherapy but none responded. However, AED modification or vagus nerve stimulation reduced the seizure frequency in two patients. Epilepsy surgery was ineffective.Conclusions: These results highlight the importance of early detection of GAD65 antibodies in refractory epilepsy as immunotherapy can be effective if administered in the early stages of the disease when it can prevent permanent brain tissue damage.
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- 2018
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27. Limbic Encephalitis
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Urbach, Horst, Bien, Christian G., and Urbach, Horst, editor
- Published
- 2013
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28. Prediabetes Genes in Pima and Amish
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Baier, Leslie J. and LeRoith, Derek, editor
- Published
- 2012
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29. [Immunotherapy of type 1 diabetes mellitus].
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Arapovicsné Kiss K, Tóth A, Schandl L, Kiss Z, Winkler G, and Kis JT
- Subjects
- Humans, Autoantibodies, Immunotherapy, Diabetes Mellitus, Type 1 therapy
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- 2024
- Full Text
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30. Zinc transporter 8 autoantibody (ZnT8A) by ELISA for diagnosing type 1 diabetes among Chinese people.
- Author
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Qiu, Xuan, Liu, Kuanzhi, Ning, Cuili, Xiao, Lin, Jing, Jianmin, and Mu, Zhenyun
- Subjects
- *
TYPE 1 diabetes , *ACETONEMIA , *ZINC transporters , *GLUTAMATE decarboxylase , *GLYCOSYLATED hemoglobin , *TYPE 2 diabetes - Abstract
This study aimed to evaluate the utility of enzyme-linked immunosorbent assay (ELISA) to measure ZnT8A for diagnosing type 1 diabetes among Chinese people. We recruited a group of 95 patients with type 1 diabetes, 130 patients with type 2 diabetes, and 110 subjects without diabetes. We measured ZnT8A level by ELISA and glutamic acid decarboxylase antibody (GADA) level by radioimmunoassay. We collected data on their history-based variables, body mass index (BMI), fasting blood glucose, glycosylated hemoglobin, and lipid levels. 24.2% were positive for ZnT8A in type 1 diabetics, compared to 0.0% in type 2 diabetics and 0.9% in the participants without diabetes (both p < 0.001). And the type 1 diabetics had higher ZnT8A level compared with the latter two groups (both p < 0.001). The frequency of ZnT8A in the "classical" type 1 diabetics was higher than that in patients with latent autoimmune diabetes in adults (45.0 vs. 18.7%, p < 0.05). The frequency/level of ZnT8A was higher in the youngest group (all p < 0.05). The ROC curve area was 0.892. The combination of ZnT8A and GADA increased the diagnostic sensitivity. The ZnT8A level was correlated with the GADA level. ZnT8A-positive type 1 diabetics had younger age at diagnosis (p = 0.022), lower BMI scores (p = 0.016), and more frequent ketosis (p = 0.034) and needed more insulin (p = 0.041) than ZnT8A-negative type 1 diabetics. This study demonstrated the value of ZnT8A in addition to GADA for the diagnosis of type 1 diabetes. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
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31. Clinical Management of Epilepsy With Glutamic Acid Decarboxylase Antibody Positivity: The Interplay Between Immunotherapy and Anti-epileptic Drugs.
- Author
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Mäkelä, Kari-Matti, Hietaharju, Aki, Brander, Antti, and Peltola, Jukka
- Subjects
EPILEPSY ,GLUTAMATE decarboxylase ,IMMUNOTHERAPY - Abstract
Background: There is scanty guidance in the literature on the management of patients with glutamic acid decarboxylase (GAD65) antibody associated autoimmune epilepsy (GAD-epilepsy). GAD-epilepsy is a rare distinct neurological syndrome with a wide clinical spectrum.We describe six GAD-epilepsy patients with special emphasis on the treatment timing and the relationship between immunologic and anti-epileptic therapy. Methods: Six patients diagnosed with GAD-epilepsy in Tampere University Hospital who had received immunotherapy from 2013 to 2017 were retrospectively analyzed from patient records. Data about symptom onset, including antibody levels, magnetic resonance imaging (MRI), electroencephalograms, immunotherapy and anti-epileptic treatment timing and treatment responses were collected and analyzed. Kruskall-Wallis test was used in the statistical evaluation. Results: All patients were female aged 9-54 at symptom onset. Three had hypothyroidism, none had diabetes, two had migraine. Five patients had very high (>2,000 IU/ml) and one had high (52-251 IU/ml) GAD65 antibody titers. All patients presented with seizure disorders. Patients who received early initiation of immunotherapy (3-10 months) responded well to treatment; patients in whom the immunotherapy was started later (15-87 months) did not respond (p = 0.0495). The first patient was seizure-free after 1 year of regular intravenous immunoglobulin and one antiepileptic drug (AED). The second patient developed unilateral temporal lobe T2 signal changes in MRI; she responded well to immunotherapy, experiencing a significant reduction in seizure frequency and resolution of MRI abnormalities. However, seizures continued despite trials with several AEDs. The third patient responded well to immunoadsorption and rituximab with one AED, with lowering of GAD65 titers (from >2,000 to 300). There was a long delay in the diagnosis of GAD-epilepsy in the three patients who had developed refractory epilepsy, one with hippocampal sclerosis. They all received immunotherapy but none responded. However, AED modification or vagus nerve stimulation reduced the seizure frequency in two patients. Epilepsy surgery was ineffective. Conclusions: These results highlight the importance of early detection of GAD65 antibodies in refractory epilepsy as immunotherapy can be effective if administered in the early stages of the disease when it can prevent permanent brain tissue damage. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
32. Latent Autoimmune Diabetes in Adults (LADA) and its Metabolic Characteristics among Yemeni Type 2 Diabetes Mellitus Patients
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Thekra Al-Zubairi, Molham Al-Habori, and Riyadh Saif-Ali
- Subjects
Pharmacology ,medicine.medical_specialty ,medicine.diagnostic_test ,business.industry ,glutamic acid decarboxylase antibody ,Insulin ,medicine.medical_treatment ,Autoantibody ,Type 2 Diabetes Mellitus ,medicine.disease ,metabolic syndrome ,Insulin resistance ,insulin resistance ,Internal medicine ,Diabetes mellitus ,Type 2 DM ,Internal Medicine ,medicine ,latent autoimmune diabetes in adults ,Metabolic syndrome ,business ,Lipid profile ,Targets and Therapy [Diabetes, Metabolic Syndrome and Obesity] ,Body mass index ,Original Research - Abstract
Thekra Al-Zubairi, Molham AL-Habori, Riyadh Saif-Ali Department of Biochemistry and Molecular Biology, Faculty of Medicine and Health Sciences, University of Sana`a, Sana`a, YemenCorrespondence: Molham AL-Habori Email malhabori@hotmail.comPurpose: Although there is ample data about the prevalence of diabetes in the Middle East, little is known about the prevalence and features of autoimmune diabetes in this region. The aim of this study was to investigate the prevalence and metabolic characteristics of latent autoimmune diabetes in adults (LADA) amongst Yemeni Type 2 DM patients.Patients and Methods: In this cross-section study, 270 Type 2 DM patients aged 30â 70 years were recruited from the National Diabetes Center, Al-Thowra Hospital, Sanaâa city, during the period November 2015 to August 2016. All Type 2 DM patients were diagnosed within 5 years and who did not require insulin for a minimum of 6 months following diagnosis. Levels of glutamic acid decarboxylase autoantibodies (GADA) were measured in all patients, and LADA was diagnosed in patients testing positive for anti-GAD antibodies. Further, biochemical analysis was carried out including fasting blood glucose (FBG), glycated haemoglobin (HbA1c), insulin, and lipid profile. Insulin resistance (HOMA-IR) and β-cell function (HOMA-β) were calculated.Results: The prevalence of LADA, as defined by GADA-positive, amongst patient with Type 2 DM was 4.4%; with no significant difference in the prevalence between male (5.8%) and female (3.4%). LADA patients were younger than GADA-negative Type 2 DM. Body mass index, waist circumference, insulin and HOMA-β were significantly lower in LADA patients, whereas triglyceride, cholesterol, HDL-c and HOMA-IR were non-significantly lower with respect to Type 2 DM. In contrast, FBG and HbA1c were significantly higher in LADA patients. Moreover, the prevalence of metabolic syndrome was significantly lower in LADA as compared with Type 2 DM. Only 2 out of the 12 GADA-positive (16.7%) were on insulin treatment at the time of the study.Conclusion: The prevalence of LADA in Yemeni Type 2 DM is lower than many of those reported in the literature, with no gender preference. Metabolic syndrome was significantly lower in LADA patients. Patients with LADA share insulin resistance with Type 2 DM but display a more severe defect in β-cell function, thus highlighting the importance of an early diagnosis of LADA, to correctly treat LADA patients, allowing safe and effective therapies.Keywords: latent autoimmune diabetes in adults, Type 2 DM, metabolic syndrome, insulin resistance, glutamic acid decarboxylase antibody
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- 2021
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33. Maturity-Onset Diabetes of the Young: Molecular Genetics, Clinical Manifestations and Therapy
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Stoffel, Markus and Poretsky, Leonid, editor
- Published
- 2004
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34. Brain FDG‐PET findings in glutamic acid decarboxylase antibody‐associated epilepsy
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Gabriel Reynés-Llompart, Sònia Jaraba, Laura Rodriguez-Bel, Francisco Morandeira, Jacint Sala-Padró, Neus Mongay-Ochoa, and Mercè Falip
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endocrine system ,Pathology ,medicine.medical_specialty ,Glutamate decarboxylase ,Glutamic acid decarboxylase antibody ,computer.software_genre ,Hippocampus ,030218 nuclear medicine & medical imaging ,Temporal lobe ,03 medical and health sciences ,Epilepsy ,0302 clinical medicine ,Fluorodeoxyglucose F18 ,Voxel ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Cerebral Cortex ,Hippocampal sclerosis ,Glutamate Decarboxylase ,business.industry ,medicine.disease ,Magnetic Resonance Imaging ,nervous system diseases ,Epilepsy, Temporal Lobe ,nervous system ,Positron-Emission Tomography ,Neurology (clinical) ,business ,computer ,Insula ,030217 neurology & neurosurgery ,Mesial temporal lobe epilepsy - Abstract
BACKGROUND AND PURPOSE Glutamic acid decarboxylase antibodies (GAD-Ab) are sometimes associated with chronic drug-resistant focal epilepsy. Clinically, it may manifest as mesial temporal lobe epilepsy (mTLE), with GAD-Ab patients difficult to distinguish. Therefore, the aim of this study is to compare brain metabolism of patients with mTLE and high serum titers of GAD-Ab (>2000 UI/ml) to those with mTLE and hippocampal sclerosis (HS) and confirmed GAD-ab negativity. METHODS Images from PET studies were normalized to an SPM 12 template. Voxel to voxel comparisons were made using a two-sample one-tailed t-test. RESULTS In both patients with GAD-Ab and controls (mTLE-HS), hypometabolism in mesial temporal lobe areas was observed. When comparing the two groups, GAD-Ab patients had statistically significant reduced metabolism in both insulae and medial inferior frontal-hypothalamus area (p < 0.001). CONCLUSIONS Hypometabolism in mesial temporal lobe areas together with hypometabolism in insulae and medial inferior frontal-hypothalamus may be characteristic of patients with epilepsy and GAD-ab. This PET pattern could be a useful diagnostic tool to identify GAD-Ab patients.
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- 2021
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35. Maturity‐onset diabetes of the young type 5 uncovered during pregnancy with a long‐term diagnosis of type 1 diabetes.
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Deng, Mingqun, Wang, Xiaojing, Xiao, Xinhua, and Ping, Fan
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TYPE 1 diabetes ,HLA histocompatibility antigens ,DIABETES ,GLUTAMATE decarboxylase ,PREGNANCY - Abstract
We report a case of missed diagnosis of maturity‐onset diabetes of the young type 5 uncovered during pregnancy with a previous diagnosis of type 1 diabetes. Maturity‐onset diabetes of the young type 5 cannot be excluded in early‐onset diabetes with positive islet‐related autoantibodies and type 1 diabetes‐prone human leukocyte antigen subtypes. Abdominal ultrasound should be used in all patients with pre‐gestational diabetes, and maturity‐onset diabetes of the young type 5 should be considered when renal abnormality is presented. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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36. Predictive Value of GAD Antibody for Diabetes in Normal Chinese Adults: A Retrospective Cohort Study in China
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Jing Li, Chuiwen Deng, Tengda Xu, and Songbai Lin
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obesity ,medicine.medical_specialty ,Glutamate decarboxylase ,030209 endocrinology & metabolism ,030204 cardiovascular system & hematology ,autoimmune diabetes ,03 medical and health sciences ,0302 clinical medicine ,prevention ,Diabetes mellitus ,Internal medicine ,Internal Medicine ,medicine ,latent autoimmune diabetes in adults ,Targets and Therapy [Diabetes, Metabolic Syndrome and Obesity] ,Original Research ,Pharmacology ,Proportional hazards model ,business.industry ,glutamic acid decarboxylase antibody ,Retrospective cohort study ,medicine.disease ,Predictive value ,Obesity ,business ,Body mass index ,Cohort study - Abstract
Jing Li,1 Songbai Lin,1 Chuiwen Deng,2 Tengda Xu1 1Department of Health Management, Peking Union Medical College Hospital, Beijing, People’s Republic of China; 2Rheumatology and Immunology Department, Peking Union Medical College Hospital, Beijing, People’s Republic of ChinaCorrespondence: Tengda XuDepartment of Health Management, Peking Union Medical College Hospital, 1# Shuaifuyuan, Dongcheng District, Beijing, 100730, People’s Republic of ChinaTel/Fax +86 10 6915 9866Email xutd@pumch.cnPurpose: To investigate the prevalence of GAD antibody (GADA) in the general adult population and to evaluate its predictive value for diabetes in China.Patients and Methods: We searched the PUMCH-HM database and identified 36,731 adult subjects with GADA test results from 2012 to 2015. We then established a retrospective cohort of 4835 nondiabetic subjects at baseline with complete annual health evaluation records through 2019. The median follow-up time was 4.8 (3.0– 7.3) years.Results: The overall prevalence of GADA was 0.53% and was higher in diabetic subjects (1.25%) than in nondiabetic subjects (0.47%). We found a decrease in baseline body mass index (BMI) from the GADA- to GADAhigh subgroups among baseline diabetic and prediabetic patients and also those who developed diabetes later in the cohort study. A total of 136 subjects (2.8%) developed diabetes after a median follow-up of 3.5 years. For GADA+ participants, BMI was not associated with the risk for diabetes. In the Cox regression model, the GADAlow and GADAhigh exhibited 2.63-fold and 4.16-fold increased risk for diabetes, respectively. This increased risk for diabetes by GADA-positivity is only found in male adults (HR 4.55, 95% CI 2.25– 9.23).Conclusion: GADA has a low prevalence in China but is associated with a 2.63– 4.16-fold increased risk for diabetes.Keywords: autoimmune diabetes, glutamic acid decarboxylase antibody, latent autoimmune diabetes in adults, obesity, prevention
- Published
- 2021
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37. Stiff-Person Syndrome: Case Series
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Yu Jin Jung, Han G. Jeong, Ryul Kim, Han-Joon Kim, and Beom S. Jeon
- Subjects
Stiff-person syndrome ,Glutamic acid decarboxylase antibody ,Autoimmune disease ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Stiff-person syndrome (SPS) is a rare disorder, characterized by progressive fluctuating muscular rigidity and spasms. Glutamic acid decarboxylase (GAD) antibody is primarily involved in the pathogenesis of SPS and SPS is strongly associated with other autoimmune disease. Here we report three cases of patients with classical SPS finally confirmed by high serum level of GAD antibodies. All of our patients respond favorably to gamma amino butyric acid-enhancing drugs and immunotherapies.
- Published
- 2014
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38. Predicting non-insulin-dependent state in patients with slowly progressive insulin-dependent (type 1) diabetes mellitus or latent autoimmune diabetes in adults. Reply to Sugiyama K and Saisho Y [letter]
- Author
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Wada, Eri, Onoue, Takeshi, Kinoshita, Tamaki, Hayase, Ayaka, Handa, Tomoko, Ito, Masaaki, Furukawa, Mariko, Okuji, Takayuki, Kobayashi, Tomoko, Iwama, Shintaro, Sugiyama, Mariko, Takagi, Hiroshi, Hagiwara, Daisuke, Suga, Hidetaka, Banno, Ryoichi, Goto, Motomitsu, and Arima, Hiroshi
- Published
- 2022
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39. Predicting non-insulin-dependent state in patients with slowly progressive insulin-dependent (type 1) diabetes mellitus or latent autoimmune diabetes in adults
- Author
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Sugiyama, Kazutoshi and Saisho, Yoshifumi
- Published
- 2022
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40. Anti-glutamic Acid Decarboxylase Antibody-associated Cerebellar Ataxia: A Case Report
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Miray Atacan Yaşgüçlükal, Cansu Tunç, Muhammet Duran Bayar, Birgül Baştan, Sefer Günaydın, Belgin Petek Balcı, and Özlem Çokar
- Subjects
endocrine system diseases ,Cerebellar ataxia ,business.industry ,autoimmunity ,glutamic acid decarboxylase ,Glutamic acid decarboxylase antibody ,Molecular biology ,Medicine ,cerebellar ataxia ,Neurology. Diseases of the nervous system ,Neurology (clinical) ,medicine.symptom ,RC346-429 ,business - Abstract
Anti-glutamic acid decarboxylase antibodies (anti-GAD-ab) are associated with various neurologic conditions. High titers of anti-GAD-abs are observed in stiff person syndrome and subacute cerebellar degeneration. Type 1 diabetes mellitus (T1DM) and other autoimmune endocrinopathies may coexist in patients who are anti-GAD-ab positive. Herein, we describe a 62-year-old female patient with a past medical history of diabetes mellitus (DM) and smoking, presenting with gradual progression of gait ataxia, dizziness, and vertigo for 6 weeks. A neurologic examination revealed gaze-evoked nystagmus and left-sided dysmetria. She could stand up only with double-sided support. Laboratory examinations showed remarkably increased serum and cerebrospinal fluid anti-GAD-ab levels. Cerebral magnetic resonance imaging was unremarkable. Coexisting autoimmune endocrine diseases were also investigated and the patient was also diagnosed as having T1DM and Hashimoto thyroiditis. Paraneoplastic etiologies were excluded. Treatment was started with intravenous methylprednisolone. Due to a lack of significant clinical improvement, intravenous immunoglobulin (IVIG) was administered. With minimal improvement of gait ataxia, the patient was followed with prednisone 1 g/day for 1 day and then IVIG 400 mg/kg/day for 1 day once per month. Although it is a rare disease, anti-GAD-ab-associated cerebellar ataxia should be considered, especially in female patients with coexisting autoimmune disorders, for prompt initiation of immunotherapy.
- Published
- 2021
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41. 僵人综合征合并成人隐匿性自身免疫糖尿病一例及文献回顾.
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李萍, 梁琳琅, 陈若然, 张景华, 夏程, and 陈会生
- Abstract
Objective To summarize the clinical features in a case of stiffman syndrome combined with latent autoimmune diabetes in adults (LADA). Methods A 61-year old male patient who presented with progressive trunk muscle stiffness, ankylosis and paroxysmal painful spasm for 3 years was admitted to hospital in April 2016. He was diagnosed with type 2 diabetes 2 years prior and initially stabilized by oral medicine of metformin and acarbose. His fasting plasma glucose (FPG) was 15.29 mmol/L, glycosylated hemoglobin (HbA1c) was 10.60%, glutamic acid decarboxylase antibody (GADA) was 39.0 mU/L, thyroid globulin (TG) antibody was 1 044 mU/L and he presented with absolute insulin deficiency. Results Clonazepam and baclofen were used to relieve muscle stiffness. After insulin treatment for 3 months, the patient's HbA1c was 7.4%, GADA was 36.4 mU/L, TG antibody was 1 068 mU/L and insulin deficiency was persistant. Literature review revealed that GADA was involved in the pathogenesis of LADA, stiffman syndrome, thyroiditis and other autoimmune diseases. Conclusion The result shows extremely high titers of GADA can trigger multiple autoimmune antigen and result in stiffman syndrome, LADA concomitant with other autoimmune diseases. It is recommended that diabetic patients with neurological symptoms should be screened for islet autoantibodies to identify the types of the disease and guide treatment. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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42. 中国胰岛自身抗体检测标准化计划报告: 检测方法调查及准确性评估.
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黄干, 杨涛, 刘煜, 郑沛林, and 周智广
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Objective To investigate the current situation of islet autoantibodies detection in China, and to evaluate assay proficiency to improve the diagnosis and classification of autoimmune diabetes. Methods Islet autoantibodies questionnaire was sent to 20 members of National Clinical Research Center for Metabolic Diseases in April 2015. In accordance with international standardization of islet autoantibodies program, sera of 50 patients with newly diagnosed type 1 diabetes, 100 healthy controls were blindly numbered and assayed in three core units using radioligand assay. The area under the receiver operating characteristic curve (ROC) (AUC) was applied to evaluate the sensitivity and specificity, as well as the consistency of the results. Mann-Whitney U test was used to compare the WHO values of type 1 diabetes mellitus and healthy volunteers autoantibodies. Linear correlation analysis was applied to evaluate the correlation of 3-lab results after converting into WHO standard unit. Results (1) All of 20 hospitals carried out the detection of glutamic acid decarboxyase antibody(GADA), and 7 hospitals detect GADA+protein tyrosinephosphate antibody(IA-2A) paralelly (35%); The detection methods included immunoblotting (30%), chemiluminescence (20%), enzyme-linked immunosorbent assay (20%), radioimmunoassay (15%) and radioligand assay (15%). (2) Among three core units, sensitivity for GADA detection ranged from 72% to 80%, while specificity ranged from 95% to 100%; sensitivity for IA-2A detection ranged from 38% to 58% with the specificity from 98% to 100%. The ROC analysis showed that the AUC of GADA was 0.897-0.935, of IA-2A was 0.716-0.749. The consistency of GADA detection among three units was 92.7%, of IA-2A was 92%. Conclusion Islet autoantibodies detection in Chinese hospitals need to be standardized. Radioligand assay is recommended for centralized detection of islet autoantibodies in China. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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43. The prevalence and characteristics of latent autoimmune diabetes in adults subset among type two diabetes mellitus patients in Northern Nigeria.
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Muazu, Salisu Babura, Okpe, Innocent, and Anumah, Felicia
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- *
AUTOIMMUNE diseases , *DIABETES in old age , *GLUTAMATE decarboxylase , *PANCREATIC beta cells , *GLUTAMIC acid - Abstract
Introduction: Latent autoimmune diabetes in adult (LADA) is a form of Type 1 diabetes mellitus (T1DM) that occurs in adult or with advancing age. It commonly occurs in people aged ≥30 years and is characterized by initial response to oral hypoglycemic agents, lean body mass, and presence of glutamic acid decarboxylase autoantibody (GAD-Ab). It exhibits rapid deterioration of the pancreatic β-cells secretory function due to the destructive action of the autoantibodies. The prevalence of LADA among T2DM patients varies among population due to different diagnostic criteria, patients' characteristics, the assay used, and genetic predisposition. In this study, we intend to document prevalence and clinical characteristics of LADA subset patients in Northern Nigeria. Methods: Two-hundred noninsulin-requiring T2DM patients were recruited from the diabetes clinic based on the selection criteria. Their clinical characteristics were documented, and we measured their serum GAD-Ab, glycated hemoglobin (HbA1c), fasting C-peptide, fasting plasma glucose, and fasting serum lipids. The mean (standard deviation) of these clinical and biochemical parameters was compared between GAD-Ab+ and GAD-Ab-groups. The data were analyzed using SPSS version 20 with P < 0.05 as statistically significant. Results: The prevalence of LADA among the T2DM patients studied was found to be 10.5% (21/200); there were more males than females (15 [71%]:6 [29%], c2 = 4.2, P < 0.05). The mean age of the GAD-Ab+ was 52.0 (11.0), and there was no statistical difference with GAD-Ab-group. GAD-Ab+ was found more common in the age group of 40-49 years 10/21 (48%). The body mass index, waist circumference, and serum C-peptide were found to be significantly lower in GAD-Ab+ than in GAD-Ab-group (22.1 [51], 80.1 [12.4], 0.84 [0.05] vs. 27.3 [4.9], 93.2 [10.9], 1.72 [0.43]), P < 0.05. The HbA1c was found to be significantly higher in GAD-Ab+ than in GAD-Ab-(8.3 [1.4] vs. 7.0 [2.1]). Other clinical and metabolic parameters were found not to be significantly different between the two groups. Conclusion: We conclude that the prevalence of LADA among T2DM patients in Northern Nigeria is 10.5%. It is more common among males aged 40-49 years and lean subjects. The male sex and decreasing central adiposity are predictors of GAD-Ab+ among T2DM subjects. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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44. Evaluation of Glutamic Acid Decarboxylase Antibody Levels in Patients with Juvenile Myoclonic Epilepsy and Mesial Temporal Lobe Epilepsy with Hippocampal Sclerosis.
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CEYHAN DİRİCAN, Ayten, ELİBİRLİK, Sevilay, KÖKSAL, Ayhan, ÖZTÜRK, Musa, ALTUNKAYNAK, Yavuz, BAYBAŞ, Sevim, and DİRİCAN, Ahmet
- Subjects
- *
AUTOANTIBODIES , *DRUG resistance , *HIPPOCAMPUS (Brain) , *LYASES , *RADIOIMMUNOASSAY , *INFANTILE spasms , *TEMPORAL lobe epilepsy , *CROSS-sectional method - Abstract
Introduction: Several clinical studies have been conducted to investigate the role of autoantibodies and immunological mechanisms in the etiology of treatment-resistant epilepsy in recent years. Some immunological treatments have been suggested as a result of these studies. In this study, we aimed to investigate the role of autoimmunity in partial and idiopathic generalized epilepsy and determine the relationship between drug resistance and autoimmune antibodies. Methods: Twenty-eight patients (24 treatment-responsive and 4 treatment-resistant) with juvenile myoclonic epilepsy (JME), 26 patients with mesial temporal lobe epilepsy with hippocampal sclerosis (MTLEHS) resistant to antiepileptic drug treatment, and 26 age-matched healthy control subjects were included in a two-year cross sectional study Glutamic acid decarboxylase antibody (GADA) levels were measured with a radioimmunoassay method in the serum of the included subjects. Results: High GADA titers were detected in 2 patients with JME (7.1%), 1 patient with MTLEHS (3.8%), and 1 healthy subject (3.8%). There was no statistically significant difference among the groups regarding the serum GADA level. Although a limited number of drug-resistant patients with JME our study did not show relationships among anti-GADAs, both epileptic syndromes and drug resistance. Conclusion: Because we did not determine any significant relationship between GADA levels and JME or MTLEHS, we do not recommend analysis of serum GADA levels in routine examinations where there is no evidence to suggest risk factors for autoimmunity. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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45. Persistence of glutamic acid decarboxylase antibody (GADA) is associated with clinical characteristics of latent autoimmune diabetes in adults: a prospective study with 3-year follow-up.
- Author
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Huang, Gan, Yin, Min, Xiang, Yufei, Li, Xia, Shen, Wei, Luo, Shuoming, Lin, Jian, Xie, Zhiguo, Zheng, Peilin, and Zhou, Zhiguang
- Subjects
AUTOANTIBODIES ,COMPARATIVE studies ,ENZYMES ,LONGITUDINAL method ,RESEARCH methodology ,MEDICAL cooperation ,PROGNOSIS ,RESEARCH ,EVALUATION research ,CASE-control method ,GLUCOSE intolerance - Abstract
Background: Latent autoimmune diabetes in adults (LADA) is a form of autoimmune diabetes with heterogeneous features. This study aimed to investigate the persistent status of glutamic acid decarboxylase antibody (GADA) in patients with LADA and its association with clinical characteristics.Methods: This 3-year follow-up study enrolled 107 LADA and 40 type 2 diabetes mellitus (T2DM) patients from October 2005 to December 2013. GADA titer, epitopes, and clinical characteristics (including fasting C-peptide and HbA1c ) in LADA patients were assayed annually. The human leukocyte antigen DQ (HLA-DQ) genotypes were also analysed. The relationship between the persistence of GADA and the clinical characteristics was investigated in LADA patients.Results: After 3-year follow-up, 36.5% (39/107) LADA patients remained GADA positive (persistently positive group), 19.6% (21/107) patients fluctuated positively and negatively (fluctuating group), and 43.9% (47/107) patients became GADA negative, among which 61.7% (29/47) seroconversions occurred within 6 months of follow-up (transiently positive group). The GADA persistently positive group possessed higher titer of GADA than transiently positive group and fluctuant group (all p = 0.000), higher reactivities to middle and C-terminal regions of GAD65 than those in transiently positive group (p = 0.001 and p = 0.000, respectively), and lower baseline fasting C-peptide level than T2DM patients and transiently positive group [415(31-1862) vs 620(220-1658) pmol/L, p = 0.014; and 415(31-1862) vs 705(64-1541) pmol/L, p = 0.017, respectively]. The GADA transiently positive group retained a higher HbA1c level when compared with T2DM patients (p = 0.023). In addition, the three LADA groups shared similar frequencies of HLA-DQ susceptible haplotypes that were higher as compared with T2DM. The GADA persistently positive group had a higher annual declining rate in fasting C-peptide than T2DM patients [-14%(-174-33%) vs -1%(-27-28%), p = 0.007].Conclusion: The LADA patients with GADA transient positivity account for a large proportion, whose clinical characteristics and HLA-DQ haplotypes are different from those of T2DM. The patients with high titer GADA and reactivities to GADA65 middle and C-terminal regions showed a persistent GADA positivity, in which a worse baseline and accelerated decline of β-cell function need early intervention in the practice. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]- Published
- 2016
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46. Stiff Person Syndrome Associated with Compartment Syndrome
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Yew Long Lo and Kok Pin Yong
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Pathology ,medicine.medical_specialty ,Glutamate decarboxylase ,education ,Glutamic acid decarboxylase antibody ,Case Report ,Neurological disorder ,lcsh:RC346-429 ,03 medical and health sciences ,0302 clinical medicine ,fluids and secretions ,Stiff person syndrome ,Autoimmune disease ,medicine ,030212 general & internal medicine ,lcsh:Neurology. Diseases of the nervous system ,biology ,business.industry ,fungi ,Compartment (chemistry) ,medicine.disease ,equipment and supplies ,Compartment syndrome ,biology.protein ,Neurology (clinical) ,Antibody ,business ,030217 neurology & neurosurgery - Abstract
Stiff person syndrome (SPS) is a rare and disabling neurological disorder of autoimmune origin, characterized by progressive stiffness and muscle spasms affecting the axial and limb muscles, most frequently associated with antibodies against glutamic acid decarboxylase. We describe a patient who presented initially with compartment syndrome and was later diagnosed with SPS.This is the first case report of SPS possibly presenting initially with compartment syndrome. This case illustrates the importance of recognizing that patients with SPS may present with varied manifestations, including compartment syndrome, which by itself is a medical emergency.
- Published
- 2019
47. Predicting non-insulin-dependent state in patients with slowly progressive insulin-dependent (type 1) diabetes mellitus or latent autoimmune diabetes in adults
- Author
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Yoshifumi Saisho and Kazutoshi Sugiyama
- Subjects
Adult ,Type 1 diabetes ,medicine.medical_specialty ,business.industry ,Glutamate Decarboxylase ,Endocrinology, Diabetes and Metabolism ,Non insulin dependent diabetes mellitus ,Glutamic acid decarboxylase antibody ,Human physiology ,medicine.disease ,Endocrinology ,Diabetes Mellitus, Type 1 ,Autoimmune diabetes ,Internal medicine ,Internal Medicine ,medicine ,Humans ,Insulin ,In patient ,Insulin dependent ,business ,Latent Autoimmune Diabetes in Adults - Published
- 2021
48. Saxagliptin improves glycaemic control and C-peptide secretion in latent autoimmune diabetes in adults (LADA).
- Author
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Buzzetti, R., Pozzilli, P., Frederich, R., Iqbal, N., and Hirshberg, B.
- Abstract
Background: To assess the efficacy and tolerability of saxagliptin and C-peptide secretion in patients with diagnosed type 2 diabetes classified as glutamic acid decarboxylase antibody (GADA)-positive or GADA-negative.Methods: Post hoc analysis of data pooled from five randomized, placebo-controlled, 24-week phase 3 studies (n = 2709) was conducted. We evaluated mean change from baseline at week 24 in HbA1c , fasting plasma glucose, postprandial plasma glucose, fasting and postprandial C-peptide, and HOMA2-%β and the proportion of patients achieving HbA1c < 7% (53 mmol/mol) at week 24.Results: Saxagliptin produced greater adjusted mean reductions from baseline in HbA1c versus placebo for GADA-negative [difference vs placebo (95% CI), -0.62% (-0.71% to -0.54%); -6.8 mmol/mol (-7.8, -5.9)] and GADA-positive patients [-0.64% (-1.01% to -0.27%); -7.0 mmol/mol (-11.0, -3.0)]. Consistently, saxagliptin produced a greater reduction from baseline in fasting plasma glucose and postprandial plasma glucose versus placebo in GADA-positive versus GADA-negative patients, and more patients achieved HbA1c < 7% (53 mmol/mol) with saxagliptin versus placebo in both GADA-negative and GADA-positive patients. Saxagliptin increased β-cell function as assessed by HOMA2-%β and postprandial C-peptide area under the curve from baseline in patients in both GADA-positive and GADA-negative patients. Adverse events and hypoglycaemic events were similar across treatment groups and GADA categories.Conclusion: Saxagliptin was effective in lowering blood glucose levels and generally well tolerated in GADA-positive patients. Interestingly, saxagliptin appears to improve β-cell function in these patients, although a longer treatment duration may be needed to confirm this finding. [ABSTRACT FROM AUTHOR]- Published
- 2016
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49. Latent autoimmune diabetes amongst adults with type 2 diabetes in a Nigerian tertiary hospital.
- Author
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Ipadeola, Arinola, Adeleye, Jokotade O., and Akinlade, Kehinde S.
- Abstract
Aims The aim was to investigate the frequency and characteristics of persons with latent autoimmune diabetes in adults (LADA) amongst patients who had been clinically diagnosed as type 2 diabetes mellitus (CT2DM) in a tertiary care centre. Methodology One hundred and sixty patients with CT2DM participated in this cross-sectional study following selection by systematic random sampling. Demographic data, relevant clinical history and anthropometric measurements (weight, height, waist circumference and hip circumference) were taken and blood samples were obtained for analysis of fasting blood glucose, glycated haemoglobin (HbA1c) and glutamic acid decarboxylase antibodies (GADA). The results were analysed using SPSS version 16. Results Nineteen (11.9%) out of 160 persons with CT2DM were positive for GADA. 95(59.4%) of the total study population were females. The mean (SD) age, BMI, waist circumference, were 60.49 (10.37) years, 26.47 (4.80) kg/m 2 , 92.16 (11.50) cm respectively. Subjects with CT2DM who were GADA positive had trend towards lower mean BMI (25.64 kg/m 2 vs. 26.59 kg/m 2 ) and waist circumference (89.80 kg/m 2 vs. 92.47 kg/m 2 ) than GADA negative subjects. GADA positive subjects also had a trend showing higher mean fasting blood glucose (144 mg/dl vs. 125 mg/dl, t = 2.20, p = 0.14), higher mean HbA1c (7% vs. 6.1%, t = 3.19, p = 0.077) and a higher proportion on insulin (31.6% vs. 22%, χ 2 = 0.07, p = 0.25) when compared with GADA negative patients. Conclusion The prevalence of LADA amongst a subset of Nigerians with CT2DM was 11.9%. There were no distinguishing clinical features to help characterize persons with LADA. The above finding emphasizes the importance of GADA testing for appropriate classification of persons with CT2DM. Early diagnosis of LADA would help direct appropriate therapy to optimize glycaemic control. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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50. Autoimmune encephalitis associated with glutamic acid decarboxylase antibodies: a case series
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Incecik, Faruk, Herguner, Ozlem M., Besen, Seyda, and Yılmaz, Mustafa
- Published
- 2018
- Full Text
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