Prevalence Of Glutamic Acid Decarboxylase Antibodies Research Articles

Comparative characteristics of newly diagnosed adult diabetic patients: a pilot study.

Diabetes is one of the most common chronic diseases. Early and improved classification of the type of diabetes, whether autoimmune (type 1 diabetes mellitus, T1DM, and latent autoimmune diabetes, LADA) or type 2 diabetes mellitus (T2DM), is essential to determine appropriate therapy. We aimed to present the biochemical and immunological characteristics of adult patients with newly diagnosed diabetes without prior drug treatment. This pilot, a cross-sectional study assessed major phenotypic characteristics and antibody titers, including islet cell antibodies (ICA), insulin autoantibodies (IAA), tyrosine phosphatase antibodies (IA-2A), glutamic acid decarboxylase antibodies (GADA), zinc antibodies (ZnT8A), but also selected sphingolipids belongs to ceramides (Cer) and sphingomyelin (SM). A total of 59 participants were included: 21 with T1DM, 15 with T2DM, and 23 with LADA. Saturated fatty acids chain Cer such as Cer-C22:0 and Cer-C24:0 positively correlates with total cholesterol (TC), triglycerides (TC), and low-density lipoprotein cholesterol (LDL), particularly in autoimmune diabetes (LADA, T1DM) while in T2DM group we found a higher frequency of positive correlation only between Cer-C24:0 and TC. In LADA patients, SM-C18:1 and -C:20:4 values rise with increasing fasting and glucagon-stimulated C-peptide values. The prevalence of GADA in patients diagnosed with T1DM is higher in younger patients versus older ones. While patients with LADA were more likely to test positive for multiple (>4) antibodies. In this relatively small cross-sectional study adult patients with newly diagnosed diabetes have fluctuating clinical and metabolic features with variable severity of immune dysfunction, making it easier to diagnose patients.

Saudi children with celiac disease: are they at risk of developing type-1 diabetes mellitus?

Objectives Patients with type-1 diabetes mellitus (T1DM) and celiac disease (CeD) share the same genetic susceptibility alleles. The diabetes-associated autoantibodies (DAA) may be detected in CeD patients. The aim of this study is to describe the prevalence of DAA in children with CeD. Methods This is a cross-sectional study of children with CeD. The CeD patients were divided into two groups; group 1 (n=23) included patients with isolated CeD and group 2 included patients with combined T1DM and CeD. The study was conducted at King Abdulaziz University Hospital (KAUH) in 2012-2014. DAA, including glutamic acid decarboxylase antibodies (GADA) and protein tyrosine phosphatase-2 antibodies (IA-2), were measured by enzyme-linked immunosorbent assay (ELISA) in both groups. Clinical, demographic, and laboratory data were collected from the patients' medical charts. Results DAA were determined in 23 patients in group-1 and 18 patients in group-2. Group-1 comprised 43.5% males and 56.5% females; the mean age was 15±3.7 years (with a range of 5-18 years). The prevalence of GADA and IA-2 was 69.6 and 4%, respectively. Group-2 comprised 55.6% males and 44.4% females; the mean age was 15.1±2.8 years (with a range of 7-18 years). The prevalence of GADA and IA-2 was 66.7 and 22.2%, respectively. No significant differences were found between both groups in the prevalence of GADA (p=1.0) or IA-2 (p=0.15). Conclusions Saudi children with CeD have higher prevalence of GADA than reported in a number of other Western studies. Long-term follow-up data is required before recommending routine screening for DAA.

Organ-specific autoantibodies in Chinese patients newly diagnosed with type 1 diabetes mellitus.

This study aims to investigate the prevalence of islet autoantibodies and other organ-specific autoantibodies in type 1 diabetes mellitus (T1DM) patients and characterize their clinical features. Glutamic acid decarboxylase antibody (GADA), insulinoma antigen 2 antibody (IA-2A), zinc transporter 8 antibody (ZnT8A) and tetraspanin7 antibody (TSPAN7A) were assayed by radioligand or luciferase immunoprecipitation system assays in 205 newly diagnosed acute-onset T1DM patients and 170 healthy controls. Other organ-specific autoantibodies, including thyroid peroxidase antibody (TPOA), thyroglobulin antibody (TGA), tissue transglutaminase antibody (tTGA) and 21-hydroxylase antibody (21-OHA), were also measured. The prevalence of GADA, IA-2A, ZnT8A, TSPAN7A, TPOA, TGA and 21-OHA was higher in T1DM patients than in healthy controls. The combinational assay of various islet autoantibodies could increase the frequency of autoantibody positivity in T1DM to 85.4%. GADA+ IA-2A+ T1DM patients preferentially had TPOA and TGA, while IA-2A+ patients often had tTGA. Patients positive for two or more islet autoantibodies often had TPOA and TGA. BMI of multiple islet autoantibody-positive patients was lower than that of patients with single or no islet autoantibodies, and there were no significant differences in C-peptide and glycated hemoglobin between patients positive for islet autoantibodies combined with other organ-specific antibodies and noncombined patients. Younger female patients who were islet autoantibody positive were more likely to have TPOA and TGA. The frequency of Graves' disease was much higher in T1DM patients than in healthy controls. T1DM usually occurs together with other organ-specific autoantibodies. Measuring of other organ-specific autoantibodies will be beneficial for T1DM patients.

The Incidence of Glutamic Acid Decarboxylase Autoantibodies and its Association With Clinical Features in Pregnant Women With Gestational Diabetes Mellitus

Introduction: The association between the incidence of glutamic acid decarboxylase antibodies(GADAs) and risk of diabetes in pregnant women is controversial. Here, our aim was to investigate the incidence and clinical relevance of GADA and its association with development of post-delivery diabetes in women with gestational diabetes mellitus (GDM).Methods: This cohort study was conducted in Torbat–e Heydarieh (Khorasan Razavi, Iran) from October 2015 to March 2017. A total of 147 pregnant women with GDM were included in case group. The control group consisted of 147 healthy controls. A GAD diagnostic kit (Diametra Co.,Italy) was used for diagnosis of GADA. The history of insulin therapy and the development of diabetes one year after delivery were investigated.Results: Of 147 pregnant women with GDM, 9 (6.1%) had GADA in their sera. 14.3% (21 out of 147) of women with GDM had history of insulin therapy. 33.3% (7 of 21) of women who had received insulin developed diabetes one year after delivery. Type 1 and type 2 diabetes were observed in, respectively, 1 (0.7%) and 7 (4.8%) of women with GDM at one year after delivery.At one year after delivery, no women in GADA negative women was diagnosed with type 1 diabetes. However, type 2 diabetes was observed in 2.9% of GADA negative pregnant women.Type 1 and type 2 diabetes were also noticed in, respectively, 11.1% and 33.3% of GADA positive mothers at one year after delivery.Conclusion: The prevalence of GADA was 6.1% in diabetic pregnant women. The GADA positivity and history of insulin therapy during pregnancy were significant risk factors for diabetes at one year after delivery. In addition, development of type 1 diabetes was higher in GADA positive pregnant women with GDM than GADA negative women.

Low prevalence of latent autoimmune diabetes in adults in northern India.

To study the frequency of islet antibodies in a large cohort of clinic- and community-based patients with Type 2 diabetes in northern India. We measured glutamic acid decarboxylase (GAD) antibodies in 618 adults with Type 2 diabetes (378 patients with diabetes attending a hospital clinic, 240 patients diagnosed in a community survey) and in 192 healthy subjects residing in north India. Islet antigen 2 (IA2) antibodies were also studied in a proportion of the patients with diabetes (n = 492) and in a control population (n = 191). GAD and IA2 antibodies were measured by immunoprecipitation of the respective (35) S-labelled recombinant antigen. We found that GAD antibodies were present in nine (1.5%) patients with diabetes (clinic population: 0.8%, community study: 2.5%), a prevalence similar to that among the subjects without diabetes (n = 2; 1%). IA2 antibodies were detected in seven patients with Type 2 diabetes (1.4%) and in two healthy control subjects (1.0%). The frequency of either GAD or IA2 antibodies was similar in people with and without diabetes (3.2 vs 2.1%). No subject was found to have both antibodies. Insulin requirement was higher among antibody-positive than among antibody-negative patients (GAD antibody: 33 vs 6.3%; P = 0.001; GAD or IA2 antibody: 23.1 vs 6.4%; P = 0.02); however, other clinical features were similar in the two groups. In the present north-Indian population with Type 2 diabetes, the overall prevalence of GAD antibodies and the prevalence of either GAD or IA2 antibodies were considerably lower than those reported in white European populations.

Thyroid autoimmunity in 72 children with type 1 diabetes mellitus: relationship with pancreatic autoimmunity and child growth

The aim of this study was to assess the association between pancreatic and thyroid autoimmunity (TA) and determine impact of thyroid antibodies on statural growth. Seventy-two children with type 1 diabetes mellitus (TIDM) and no clinical evidence of thyroid disorders were evaluated: glycated haemoglobin (A1c), thyroid peroxidase antibodies (TPOAb), glutamic acid decarboxylase antibody (GADA), tyrosine phosphatase antibodies (IA2A), and thyroid-stimulating hormone (TSH). The score of standard deviation for height (SDS) was calculated. There were 72 patients, 38 (52.7%) boys and 34 (47.2%) girls, with a mean age of 10.89 +/- 4.26 years and a mean duration of T1DM of 3.41 +/- 2.56 years. TPOAb were present in 23.6% of patients; 12.5% of subjects were positive for GADA and 41.6% for IA2A. Patients with TA had more prevalent GADA and IA2A (23.5% vs. 9%, p < 0.001, and 58.8% vs. 36.3%, p < 0.001, respectively). A1c was higher in patients with TA (9.7% +/- 2.05% vs. 8.6% +/- 2.11%, p = 0.05). TA was associated with lower SDS (0.26 vs. 0.98, p = 0.043). TSH was higher in patients with TA (3.39 vs. 2.15 microU/mL, p < 0.05). Logistic regression analysis revealed that a negative SDS for height was independently associated with duration of diabetes (p = 0.049) and TSH (p = 0.027) but not with birth weight, A1c, and TPOAb. In conclusion, TA was found in 23.6% TIDM children. Patients with TA had significantly higher prevalence of GADA and IA2A and significantly higher A1c vs. patients without TA. Our data suggest significant association between TA and height in children with T1DM. SDS was independently associated with diabetes duration and TSH.

Occurrence of Type 1 Diabetes in Graves' Disease Patients Who Are Positive for Antiglutamic Acid Decarboxylase Antibodies: An 8-Year Followup Study

Glutamic acid decarboxylase antibodies (GADAs) are one of the markers of islet cell autoimmunity and are sometimes present before the onset of type 1 diabetes (T1D). GADA can be present in Graves' patients without diabetes; however, the outcome of GADA-positive Graves' patients is not fully understood, and the predictive value of GADA for the development of T1D in Graves' patients remains to be clarified. We investigated the prevalence of GADA in 158 patients with Graves' disease and detected GADA in 10 patients. They were followed up to discover whether or not T1D developed. In the course of eight years, 2 patients with high titers of GADA developed T1D, both had long-standing antithyroid drug-resistant Graves' disease. Thus, Graves' disease with high GADA titer seems to be at high risk for T1D.

The prevalence of GAD antibodies in Korean women with gestational diabetes mellitus and their clinical characteristics during and after pregnancy

We conducted this research in order to evaluate the prevalence of glutamic acid decarboxylase antibodies (GADA) in Korean women with gestational diabetes mellitus (GDM), to identify the clinical characteristics of these women, and to gauge the prevalence of diabetes among them after childbirth. We studied 887 Korean women with GDM who were screened for GADA, and assessed their antepartum clinical characteristics and the outcomes of their pregnancies. At 6 weeks' postpartum, 75 g oral glucose tolerance tests were performed to determine the diabetic status of GDM women with GADA. The prevalence of GADA in Korean women with GDM was 1.7%. Plasma glucose levels at 0- and 3-h during oral glucose tolerance tests were significantly different between GADA-positive and GADA-negative women with GDM. There were no significant differences between them in terms of age, body mass index, family history of diabetes, fasting insulin, and lipid profiles. However, GADA-positive women with GDM required insulin treatment during pregnancy more frequently than GADA-negative patients. The development of diabetes at early postpartum was significantly higher in GADA-positive women with GDM than those who were GADA negative. The prevalence of GADA in Korean women with GDM was low. However, GADA-positive women with GDM are more susceptible to subsequently developing type 1 diabetes, even in the early postpartum period. Long-term follow up studies and intervention to prevent type 1 diabetes among GADA-positive GDM women are needed.

Antibodies to GAD and ICA in Type 2 DM with Secondary Failure of Oral Hypoglycemic Therapy

Background: Secondary failure of oral hypoglycemic agents is defined as tha t blood glucose is no longer controlled with sulfonylurea after a proven period of good glycemic control. There are many causes of secondary failure, including that drug problem, acute illnesses, inappropriate drug dosages, oxidative stress & glucose toxicity of β-cell, etc. And many studies have suggested role of immunologic process such as islet cell antibody (ICA) and/or glutamic acid decarboxylase antibody (GADA) for the causes of secondary failure. So we evaluated the prevalence of ICA & GADA in type 2 diabetes with secondary failure of oral hypoglycemic agents and the pathogenesis of the secondary failure. Methods: We studied 267 patients with type 2 diabetes. We regarded 84 pa tients who could not control HbA1c less than 8% after good glycemic control for at least 1 y ear as secondary failure group (group 1) and regarded the other 183 patients as group 2. We measured GADA in both group, and measured the prevalence of GADA and ICA in secondary failure group who were especially divided into obese group and nonobese group according to BMI and were divided into insulin deficiency group and noninsulin deficiency group according to fasting C-peptide level. Results: The prevalence of GADA in all subjects was 4.1%, which was 9.5 % in group 1 and 1.6% in group 2 (P < 0.05). Among 35 patients of the group 1 who could be checked ICA, the prevalence of GADA & ICA were 33% & 25% in insulin deficiency group and 4.3% & 0% in non-insulin deficiency group, respectively (P < 0.05). The prevalence of GADA & ICA were none in obese group and 33.3% & 20% in nonobese group, respectively (P < 0.05). The prevalence of GADA & ICA were 36.4% & 27.3% in nonobese and insulin deficiency, 4.2% & 0% in obese and non-insulin deficiency. Conclusion: We suggest that autoimmune mechanism is associated with increased risk for secondary failure of oral hypoglycemic agents in type 2 diabetes, so the measurement of GADA and ICA could help to predict the potential risk and insulin treatment. (J Kor Diabetes Assoc 31:402~409, 2007)

GAD antibodies in probands and their relatives in a cohort clinically selected for Type 2 diabetes

A subset of patients who present as if they have Type 2 diabetes have positive pancreatic autoantibodies, and have been referred to as having latent autoimmune diabetes in adults (LADA). We assessed the prevalence and clinical characteristics of patients with glutamic acid decarboxylase antibodies (GADA) in a cohort clinically selected for Type 2 diabetes and determined the presence of diabetes and GADA in their first-degree relatives. GADA were measured in 2059 subjects, not known to be related, and clinically selected as having Type 2 diabetes for genetic studies. Clinical characteristics were compared in GADA positive and GADA negative subjects. Diabetes and GAD antibody status were compared in 208 first-degree relatives of GADA positive and GADA negative probands. Of the subjects, 136 (7%) were GADA positive. Compared with the GADA negative subjects, they were slimmer (P < 0.001), diagnosed at a younger age (P = 0.011) and progressed to insulin faster (P < 0.001). Thirty-three per cent of GADA positive subjects had a first-degree relative with diabetes compared with 42% of GADA negative subjects (P = 0.034). The overall prevalence of GADA was similar in the first-degree relatives of GADA positive and GADA negative probands (4 v 5%), and 19 of 22 (86%) diabetic relatives of GADA positive probands were GADA negative. Despite clinically selecting a Type 2 diabetes cohort, 7% were GADA positive with an altered phenotype. These GADA positive patients had a strong family history of non-autoimmune diabetes. This suggests that, in this subgroup of patients, autoimmune pancreatic beta-cell destruction occurs on a background of Type 2 diabetes genetic susceptibility.

Glutamic Acid Decarboxylase Autoantibody Prevalence and Association with HLA Genotype in Patients with Younger-Onset Type 1 Diabetes and Proliferative Diabetic Retinopathy

To investigate the relationship of HLA status and autoantibodies to glutamic acid decarboxylase (GAD) in proliferative diabetic retinopathy (PDR) to assess the role of autoimmunity and genetic markers in retinopathy. Retrospective, nonrandomized, comparative study. Patients who had suffered from type 1 diabetes for >10 years and who had been first diagnosed as diabetic under 30 years of age were studied. They were classified into 3 groups: 20 patients with diabetes and PDR (PDR group), 22 patients who had diabetes and severe nonproliferative diabetic retinopathy (SNPDR group), and 25 patients who had diabetes with no diabetic retinopathy (non-DR group). Blood was collected, and the relationship between HLA status and GAD autoantibody positivity in diabetic retinopathy was investigated in a cross-sectional study. Human leukocyte antigen status and GAD autoantibody positivity. The highest positive rate of GAD autoantibody was 56.0% in the non-DR group, followed by the SNPDR group (40.1%) and the PDR group (15.0%). The frequencies of the HLA-DQ4 and -DR4/-DQ4 haplotypes were significantly higher in the PDR group (75.0% and 65%, respectively) than in the SNPDR group (40.9% and 31.8%) or the non-DR group (40.0% and 28.0%) (P = 0.035 and P = 0.026, respectively). The prevalence of GAD antibodies was lower in patients with the HLA-DR4 and HLA-DQ4 alleles and -DR4/-DQ4 haplotype frequencies in the PDR group (P = 0.018, P = 0.0088, and P = 0.0031, respectively). We found that the existence of GAD antibodies is inversely related and HLA status is directly related to the stage or severity of retinopathy.

Prevalence of latent autoimmune diabetes of adults (LADA) in Southern Spain

Objective: To study the prevalence of diabetes mellitus and islet autoantibodies in an adult population from Southern Spain. Research design and methods: A cross-sectional study in Southern Spain of 1226 people, age 18–65 years. Clinical data were obtained and a blood sample taken to measure autoantibodies (glutamic acid decarboxylase antibodies (GADAb), tyrosine phosphatase antibodies (IA2Ab), and insulin antibodies (IAA)). An oral glucose tolerance test (OGTT) was also given to 982 of the subjects. Results: The overall prevalence of diabetes mellitus according to the WHO 1979 criteria was 10.9% and according to the ADA 1997 criteria it was 14.7% (8.8% were unaware of their diabetes). The prevalence of impaired fasting glucose (IFG) was 12.4% and of impaired glucose tolerance (IGT) 11.5%. The prevalence of GADAb+ in the general population was 0.9% and in the diabetic population 3.7%. There were no significant differences between groups in the prevalence of IA2Ab or IAA (both were 0.8% in the general population). Of the three autoantibodies studied, only GADAb were significantly different in the diabetic population ( P=0.0006). Conclusions: The prevalence of Type 2 diabetes and LADA are high in the south of Spain

Antibodies to pancreatic islet cell antigens in diabetes seen in Southern India with particular reference to fibrocalculous pancreatic diabetes.

Fibrocalculous pancreatic diabetes (FCPD) is a type of diabetes secondary to tropical chronic non-alcoholic pancreatitis. Little is known about the aetiopathogenesis of FCPD. We studied glutamic acid decarboxylase antibodies (GAD-Ab) and islet cell antibodies (ICA) in patients with FCPD and compared the results with Type 1 (insulin dependent) diabetes mellitus, Type 2 (non-insulin-dependent) diabetes mellitus and non-diabetic subjects in Southern India. The prevalence of GAD-Ab was 7.0% (95% Confidence Interval (CI) 1.9-17.2) in FCPD, 47.5% (CI 31.4-64.0) in Type 1 (p < 0.001 compared to FCPD), 5.6% (CI 1.5-13.9) in Type 2 (non-significant (NS) compared to FCPD) and 0% in controls. The prevalence of ICA was 6.3% (CI 1.2-17.4) in FCPD, 53.8% (CI 37.1-70.0) in Type 1 (p < 0.001 compared to FCPD), 9.9% (CI 4.0-19.4) in Type 2 (NS compared to FCPD) and 4.7% (CI 0.4-16.1) in controls. The data suggest that in FCPD, the frequency of auto-antibodies is low and its aetiology is probably not linked to autoimmunity in the majority of the patients.

GAD Antibodies in NIDDM: Ten-year follow-up from the diagnosis

To study the frequency of antibodies to glutamic acid decarboxylase (GAD) and islet cell antibodies (ICAs) and their predictive value with respect to the development of insulin deficiency in 133 newly diagnosed middle-aged patients with non-insulin-dependent diabetes mellitus (NIDDM) and in 126 control subjects and to study the persistence of GAD antibodies in diabetic patients during the follow-up. The study participants consisted of a well-characterized group of 133 middle-aged newly diagnosed patients with NIDDM and 126 control subjects. The follow-up examinations were performed 5 and 10 years after the baseline. The development of absolute and relative insulin deficiency was based on a stimulated C-peptide level that was undetectable or < 0.70 nmol/l, respectively. GAD antibodies were measured retrospectively from stored samples. The overall prevalence of GAD antibody and ICA positivity at the time of diagnosis was 9.0 and 3.8% in diabetic patients and 1.6 and 0% in the control population, respectively. During the 10-year follow-up, 3 (2.3%) and 10 (7.5%) of the diabetic patients developed absolute and relative insulin deficiency, respectively. Of these, two (67%) and six (60%) had been GAD antibody-positive at the time of diagnosis. The sensitivity and specificity of the GAD antibody to predict absolute or relative insulin deficiency were 67 vs. 94% and 60 vs. 95%, while corresponding figures for ICA were 33 vs. 97% and 20 vs. 98%, respectively. The negative predictive value of GAD antibody testing was higher than positive predictive value (97 vs. 50%). During the follow-up, low-grade GAD antibody positivity showed an evanescent nature, whereas the high levels were quite persistent. In an unselected population of newly diagnosed NIDDM patients, the prevalence of latent autoimmune diabetes in adults was < 10%. While GAD antibody and ICA measured at the time of diagnosis of NIDDM are equally specific predictors of subsequent insulin dependency, the GAD antibody may have a higher sensitivity. Therefore, measurements of GAD antibody may aid the clinician in the choice of treatment of these patients.

Autoantibodies to glutamic acid decarboxylase (GAD), 64000-Mr islet cell protein (64K) antibodies and islet cell antibodies (ICA) in insulin-dependent diabetes mellitus with and without autoimmune diseases in Japan

IDDM is known to be a heterogeneous disease which is frequently complicated with other autoimmune diseases (AID). We previously reported that IDDM patients with AID were characterized by late onset of diabetes, persistent ICA-positivity and increased association with DR9, while those without AID were characterized by rapid decline of ICA with duration of diabetes and increased association with DR4. The present study was performed to investigate the prevalence of autoantibodies to glutamic acid decarboxylase (GAD), autoantibodies to 64KDa islet cell protein (64K antibodies) and islet cell antibodies (ICA) in Japanese IDDM patients with and without AID. In short-duration diabetes (< 1 year), the prevalence of GAD antibodies, 64K antibodies and ICA were 100%, 100%, and 100%, respectively, in IDDM patients with AID, and 82%, 64% and 82%, respectively, in patients without AID. In long-standing diabetes (3–28 years), the prevalence of GAD antibodies were 76%, 48% and 33%, respectively, in IDDM patients with AID, and 48%, 28% and 16%, respectively, in patients without AID. The mean levels of GAD antibodies, 64K antibodies and ICA in IDDM patients with AID was significantly higher than in those without AID. Furthermore, the prevalence of GAD antibodies were detected more frequently than ICA and 64K antibodies in long standing IDDM patients. Our results demonstrate that the prevalence of GAD antibodies in IDDM patients were as high as those reported in Caucasians, and high levels of GAD antibodies were observed in IDDM patients with AID.