Glutamic Acid Decarboxylase Antibody Positivity Research Articles

Glutamic acid decarboxylase antibody-related stiff person syndrome: Two case reports of a child and an adult

Stiff person syndrome (SPS) is a disease characterized by rigidity in the extremities, axial muscles, and abdominal muscles, severe and painful spasms, and accompanying gait disturbances. Stiff person syndrome is most common in adults between the ages of 20 to 50 and in female sex. The most frequently reported antibody in patients with SPS is antibodies developed against glutamic acid decarboxylase enzyme. In this article, two SPS cases from different age groups who presented with gait disturbance and painful spasms and were found to have glutamic acid decarboxylase antibody positivity were reported with clinical and electrophysiological findings in the light of the literature. As in our cases, SPS should be considered in the differential diagnosis of patients of all age presenting with muscle stiffness and spasms, specifically those that increase with stimulus.

Association of RPS26 gene polymorphism with different types of diabetes in Chinese individuals.

Different types of diabetes show distinct genetic characteristics, but the specific genetic susceptibility factors remain unclear. Our study aimed to explore the associations between the ribosomal protein S26 (RPS26) gene rs1131017 polymorphisms and susceptibility to type 1 diabetes mellitus, latent autoimmune diabetes in adults (LADA) and type 2 diabetes mellitus in the Chinese Han population, and their correlations with clinical features. Genotyping of the rs1131017 variant was carried out for 1,006 type 1 diabetes mellitus patients, 210 LADA patients, 642 type 2 diabetes mellitus patients and 2,099 control individuals. We found that the rs1131017 C allele was a risk locus for both type 1 diabetes mellitus and LADA (odds ratio [OR] 1.50, 95% confidence interval [CI] 1.33-1.69, P < 0.001; OR 1.31, 95% CI 1.04-1.64, P = 0.021, respectively). Nevertheless, this association was not found for type 2 diabetes mellitus. Carrying the C allele genotype was associated with a lower postprandial C-peptide for type 1 diabetes mellitus (OR 1.41, 95% CI 1.11-1.80, P = 0.006) and lower fasting C-peptide for LADA (OR 1.55, 95% CI 1.01-2.38, P = 0.047). Interestingly, a lower GC frequency was noted for LADA than for type 1 diabetes mellitus, regardless of classification based on age at diagnosis, C-peptide or glutamic acid decarboxylase antibody positivity. The RPS26 polymorphism was associated with susceptibility and clinical characteristics of type 1 diabetes mellitus and LADA in the Chinese population, but was not related to type 2 diabetes mellitus. Thus, it might serve as a novel biomarker for particular types of diabetes.

Real-world adherence to toxicity management guidelines for immune checkpoint inhibitor-induced diabetes mellitus.

Immune checkpoint inhibitors(ICIs) have improved survival and are increasingly used for cancer. However, ICIs use may be limited by immune-related adverse events (irAEs), such as ICI-induced diabetes mellitus(ICI-DM). The objective of the present study was to characterize ICI-DM patients and real-world adherence to guidelines. The present study was a retrospective review of electronic records of ICI-DM patients at the First Affiliated Hospital of Nanjing Medical University between July 2018 and October 2022. 34.8% (8/23)patients monitored blood glucose in every treatment cycle. The proportion of patients with severe diabetic ketoacidosis(DKA) was lower in the tight glycemic monitoring group than the non-tight glycemic monitoring group (16.7% vs. 55.6%, p = 0.049). 78.3%(18/23) patients with hyperglycemia visited a non-endocrinologist first, but 95.7% of patients were then referred to an endocrinologist. Twenty patients were tested for distinguishing the etiology of hyperglycemia and 20% patients with positive glutamic acid decarboxylase antibody(GADA), 55% with C-peptide <3.33pmol/L. High screening rates for other ICI-induced endocrinopathies were observed and half of the patients with ICI-DM developed other endocrine gland irAEs, with the most common being thyroiditis. Moreover, five patients developed non-endocrine serious adverse events(SAEs). Twelve (52.2%) patients were withdrawn from ICI due to ICI-DM. The time to progression of tumor in ICI-DM patients in the continue and interruption group was longer than in the withdrawal group (333.5 ± 82.5 days vs. 183.1 ± 62.4 days, p = 0.161). Only 17.4% of ICI-DM patients were completely managed according to guidelines. Thus, the present study proposed a screening, diagnosis, and management algorithm for ICI-DM in real-world practice. The present study reported the largest number of ICI-DM cases described in a single institute, providing insight into real-world ICI-DM management guideline adherence and highlighting the clinical challenges in ICI-DM management.

Prevalence of Organ-Specific Autoimmunity in Patients With Type 1 Diabetes Mellitus.

Type 1 diabetes mellitus (T1DM) is associated with other autoimmune disorders that are characterized by presence of organ-specific autoantibodies. The present study was undertaken to assess theprevalence of organ-specific autoantibodies amongnewly diagnosed T1DM subjects of Indiaand to studyits relationshipwith glutamic acid decarboxylase antibody (GADA). We also compared the clinical and biochemical parameters in GADA-positive and -negative T1DM subjects. In a hospital-based cross-sectional study, we studied 61 patients with newly diagnosed T1DM ≤ 30 years of age. T1DM was diagnosed on the basis of acute onset of osmotic symptoms with or without ketoacidosis, severe hyperglycaemia [blood glucose > 13.9 mmol/l (>250 mg/dl)] and insulin requirement from the onset of diabetes. Subjects were screened for autoimmune thyroid disease (thyroid peroxidase antibody [TPOAb]), celiac disease (tissue transglutaminase antibody [tTGAb]), and gastric autoimmunity (parietal cell antibody [PCA]). Of the 61 subjects, more than one-third (38%) had at least one positive organ-specific autoantibody. In particular, 13 (21.3%) were found to be positive for TPOAb, nine (14.8%) were positive for tTGAb and 11 (18%) were positive for PCA. GADA was positive in 15 (25%) subjects.The frequency of TPOAb tended to be higher in patients who had GADA positivity compared with those with no circulating GADA (40% vs.15.2%;p=0.07). Subjects positive for GADA were also more likely to be PCA positive compared with those who were GADA negative (40 vs.10.9%, p=0.02). There were no differences in frequency of diabetic ketoacidosis, body mass index, hemoglobin A1C (HbA1c), insulin requirement or fasting C-peptidein GADA-positive and -negative patients. We support the recommendation for regular screening of organ-specific autoantibodies, in particular TPOAb, tTGAb and PCA in all patients with T1DM. Detection of these autoantibodies at onset may prevent complications associated with delayed diagnosis of these disorders. We also conclude that there is higher frequency of TPOAb and PCA in GADA-positiveT1DM patients as compared to negative ones. However, patients with positive GADA had similar clinical and biochemical parameters compared to GADA-negative subjects. Lastly, low GADA positivity in our study cohort as compared to Western populations suggests the heterogenous nature of T1DM in the Indian population.

Abstract #1402868: Neurologic and Clinical Manifestations of Cancer Patients with Checkpoint Inhibitor Diabetes and GAD65 Antibody Positivity

Abstract #1402868: Neurologic and Clinical Manifestations of Cancer Patients with Checkpoint Inhibitor Diabetes and GAD65 Antibody Positivity

A case of Type 1 Diabetes Mellitus with Klinefelter’s Syndrome

Type 1 diabetes mellitus (T1DM) is a model of chronic autoimmune disease beginning with genetic susceptibility in affected individuals and progressing to autoimmune destruction of β cells, precipitated by environmental insult. Some of the patients with T1DM have associated genetic disorders, such as Klinefelter’s syndrome (KS), Down’s syndrome and Turner’s syndrome. This paper reports a case of T1DM accompanied by KS. The patient was a 14-year-old male who had been confirmed by absolute insulin deficiency and positive glutamic acid decarboxylase antibody (GADA). After chromosome analysis was performed because of the delay in his puberty, he was diagnosed with Klinefelter’s syndrome, 47 XXY karyotype, at his follow-up.

Co-Occurring NMDA-Receptor and Anti-GAD65 Antibodies in the CSF of a Patient With Encephalitis: Case Report

Objective We describe a 58-year-old woman who presented with rapid cognitive changes and was found to have concurrent CSF NMDA and GAD65 receptor antibodies. Background Antibodies against NMDA and GAD65 receptors are associated with highly morbid autoimmune encephalitides. One case of co-occurring NMDA-R and anti-GAD65 antibodies in a patient with progressive cognitive changes and type I diabetes has previously been described. Herein, we describe a case of a previously high-functioning woman who experienced rapidly progressive cognitive changes secondary to autoimmune encephalitis (AE) with co-existent NMDAR and GAD65 antibodies. Design/Methods NA. Results A 58-year-old woman with adult-onset insulin-dependent diabetes mellitus, hypertension, and prior left-sided Bell's palsy presented to medical care for subacute cognitive decline characterized initially by inattention and difficulty with activities of daily living, progressing to profound global aphasia and seizures. Diagnostic testing revealed GAD65 antibody positivity in serum (33 nmol/L) and CSF (17.3 nmol/L) and negative serum but positive CSF NMDAR antibody. CSF showed pleocytosis (37 nucleated cells, 97% lymphocytes), elevated glucose (109 mg/dL), and normal protein (41 mg/dL). EEG showed right temporal epileptiform discharges. MRI was unrevealing. She was treated with IV steroids, IVIg, and rituximab, and has slowly improved on follow-up. Conclusions Co-existent CSF anti-NMDAR and anti-GAD65 AE is not well-described in the literature. While this patient's serum GAD65 titer was in a range that correlates with neurologic autoimmunity, it was not as high as is typically reported in AE, and could simply be a marker of her insulin-dependent diabetes. However, it was also definitively positive from the CSF, which usually correlates well with GAD65-associated AE. Clinically, the patient had AE features that can be seen associated with either NMDAR and/or GAD65 antibodies. It is interesting to consider whether the GAD65 positivity is most likely to correlate with the patient's adult-onset diabetes, her AE, or both.

ODP260 New Type of Autoimmune Diabetes

Abstract Immune checkpoint inhibitors (ICIs) are an emerging therapy that has revolutionized the management of certain cancers. Data on long-term side effects of these drugs are now showing a risk for development of new endocrinopathies. In this case report, a patient with new Type I diabetes (DMI) is discussed. The patient is a 67 year old male with past medical history of metastatic renal cell carcinoma with multiple recurrences of disease. A brief review of the patient's oncologic history revealed multiple surgeries, including complete nephrectomy, multiple drugs, including ICIs, and radiation therapy. Over the course of his treatment, he received Nivolumab (anti-PD1 agent) for 5 cycles with HbA1c increased from 5.4% to 6.9% from pre-treatment to post-treatment, but the HbA1c improved to 5.8% one year after drug cessation. Later he was started on Pembrolizumab (anti-PD1) and has had 10 cycles of therapy to date. Random blood glucose frequently exceeded 200 after start of pembrolizumab therapy. Ipilimumab (anti CTLA-4) was started in combination with pembrolizumab six months later, but it was held after the second cycle due to development of diabetes with HbA1c of 11.1%. He was also found to have persistent, severe hyperglycemia noted during routine bloodwork. Autoimmune DM was confirmed with a positive glutamic acid decarboxylase antibody (GAD65) of 8 nmol/L. Consequently, the patient had multiple hospital admissions for glucose exceeding 400. His condition was exacerbated by the fact that he had difficulty coming to terms with his diagnosis, and he was noncompliant with medication. At that time, the patient stated that he had not done anything wrong and did not understand why this had happened to him. He was resistant to starting therapy and had difficulty understanding insulin dosing, blood glucose monitoring, and the consequences of hyperglycemia/hypoglycemia. After extensive education during a 2 week hospitalization, the patient was eventually place on an appropriate dose of basal-bolus insulin therapy and is currently doing well. It is important to note some emerging challenges to treating this new population of patients with DM1 due to ICI therapy. Firstly, many patients in this scenario live alone and have poor support systems. They have difficulty learning new technology (glucometer, insulin pen, etc.) and self adjusting medication (sliding scale). Older patients can also be more resistance to change in diet and lifestyle. They may have pre-existing insulin resistance that makes initial insulin dosage difficult. Finally, noncompliance is dangerous due to risk of hypoglycemia, diabetic ketoacidosis, and exacerbation of other comorbidities. Clinicians should also consider the patient's psychosocial ability to understand and manage this condition. Presentation: No date and time listed

PSUN257 Acute Onset Diabetes and GAD Antibody Positivity After COVID-19

Abstract Background Viral infections can trigger the development of auto-antibodies including against the pancreas (1). The Sars-CoV2 virus can infect the pancreas (2). Limited data exist linking COVID-19 infection and the development of islet related auto-antibodies and diabetes in adults. Case A 46-year-old healthy man (BMI 24.7kg/m2) developed upper respiratory symptoms in mid-July 2021. He did not have a family or personal history of autoimmune diseases. His mother has mild type 2 diabetes mellitus. He underwent Sars-CoV-2 testing in July which was positive. In August, upper respiratory symptoms resolved, however, he developed acute onset polyuria, polydipsia, fatigue, and weight loss. He lost 12.7kg within one month. On his own, he noticed that he felt worse after eating carbohydrates and modified his eating (limiting to 20g of carbohydrates per meal), which reduced his polyuria, polydipsia, and weight loss. In September, he presented to his primary care physician who diagnosed him with hyperglycemia and diabetes. Fasting blood glucose was 331mg/dL (18.4mmol/L) and hemoglobin A1C was 11.3%. He presented to endocrinology clinic in October for evaluation and was started on insulin therapy for diabetes. Laboratory studies included: glucose 194mg/dL (10.8mmol/L), repeat hemoglobin A1C 10.1%. Autoantibody testing was positive for GAD65 (glutamic acid decarboxylase 65 antibody 34.4nmol/L, reference &amp;lt;0.02nmol/L). Other type 1 diabetes related autoantibodies were negative. Blood glucose normalized on insulin therapy (average 115mg/dL (6.4mmol/L) on continuous glucose monitor). Op de Beeck, Anne and Decio L. Eizirik, Nature Reviews, May 2016.Muller, J, et al. Nature Metabolism, Feb 2021. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

Clinical characteristics and outcomes of immune checkpoint inhibitor-induced diabetes mellitus

ObjectiveTo better understand immune checkpoint inhibitor (ICI)-induced diabetes mellitus (DM) in cancer patients. Design and methodWe present a case of ICI-induced diabetic ketoacidosis (DKA) and conduct a systematic review of the PubMed and Web of Science databases up to September 2021 to identify all published cases of ICI-induced diabetes. ResultsIn addition to our case, a total of 171 published cases were identified during the literature search. Summary and statistical analyzes were conducted for all 172 cases. The median onset time from ICI initiation to DM diagnosis was 12 weeks (range: 0–122). DKA was present in 67.4% (116/172) of the cases, and low C-peptide levels were detected in 91.8% (123/134), indicating an acute onset of diabetes. Patients with positive glutamic acid decarboxylase antibodies (GADA) had an earlier onset of ICI-induced diabetes (median time 7 weeks vs. 16 weeks for GADA-negative patients, p < 0.001) and a higher frequency of DKA development (82.8 vs. 62.1%, p = 0.006). All but two patients developed insulin-dependent diabetes permanently. Immunotherapy rechallenge was reported in 53 cases after glycemia was well controlled. ConclusionICI-induced DM is a serious adverse event that often presents with life-threatening ketoacidosis. GADA positivity is related to an earlier onset of ICI-induced diabetes and a higher frequency of DKA development. Close monitoring of glucose levels is needed in patients receiving ICI treatment. ICI-induced DM is usually insulin-dependent since damage to β cells is irreversible. On the premise of well-controlled glycemia, immunotherapy rechallenge is feasible.

Gender Difference in Liver Enzymes in Newly Defined Subgroups of Diabetes Revealed by a Data-Driven Cluster Analysis.

Recently, a newly proposed data-driven approach for classifying diabetes has challenged the status quo of the classification of adult-onset patients with diabetes. This study investigated the association between liver injury and diabetes, classified by data-driven cluster analysis, as liver injury is a significant risk factor for diabetes. We enrolled 822 adult patients with newly diagnosed diabetes. Two-step cluster analysis was performed using six parameters, including age at diagnosis, body mass index, hemoglobin A1C, homoeostatic assessment model 2 estimates about insulin resistance (HOAM2-IR) and beta-cell function (HOMA2-B), and glutamic acid decarboxylase antibodies (GADA) positivity. Patients were allocated into five clusters. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity were compared as indicators of liver injury among clusters. Serum ALT and AST activities were significantly different among clusters (P=0.002), even among those without GADA positivity (P=0.004). Patients with severe insulin-resistant diabetes (SIRD) and mild obesity-related diabetes (MOD) had a more severe liver injury. Gender dimorphism was also found for serum ALT and AST activities among subgroups. Female patients had better liver function than males with SIRD and MOD. We verified the feasibility of a newly proposed diabetes classification system and found robust and significant relationship and gender differences between serum ALT and AST activities and diabetes in some specific subgroups. Our findings indicate that more attention should be paid to diabetes subgroups when studying risk factors, indicators, or treatment in diabetic research.

The polymorphism of the CARD8 inflammasome-related gene is associated with glutamic-acid-decarboxylase-antibody positivity in patients with type 1 diabetes mellitus.

BackgroundThis study sought to examine the correlation between 2 single-nucleotide polymorphisms (SNPs; rs10403848 and rs2043211) in the caspase recruitment domain-containing protein 8 (CARD8) gene and the risks and clinical features of patients with type 1 diabetes mellitus (T1DM) in the Han Chinese population.MethodsA case-control study involving the Han Chinese population was designed, and individuals diagnosed with classical T1DM and healthy controls were enrolled in this study. MassARRAY genotyped the SNPs of rs10403848 and rs2043211. Logistic regression and chi-square analyses were conducted to compare the allele distributions and genotypes of the T1DM and healthy control participants. A Kruskal-Wallis 1-way analysis of variance was used to perform the genotype-phenotype analysis for the T1DM patients.ResultsIn total, 510 participants with classical T1DM and 531 sex-matched healthy control participants participated in this study. The CARD8 SNP of rs2043211 was significantly associated with the rate of glutamic-acid-decarboxylase-antibody (GADA) positivity among T1DM patients (P=0.021). However, no significant differences in the distributions of alleles or the genotypes of rs10403848 and rs2043211 were observed between the case and control groups, and these 2 SNPs were not associated with T1DM under various inheritance models.ConclusionsThe rs10403848 and rs2043211 polymorphisms of CARD8 were not associated with susceptibility to T1DM. However, rs2043211 was found to be correlated with GADA positivity in participants with T1DM.

2型糖尿病の経過中，GAD抗体陽性が判明した高齢糖尿病―疾患感受性と抵抗性の両HLAを持つ1例

2型糖尿病の経過中，GAD抗体陽性が判明した高齢糖尿病―疾患感受性と抵抗性の両HLAを持つ1例

Associated autoimmunity in Type 1 Diabetes and latent autoimmune diabetes of adults: The role of glutamic-acid decarboxylase autoantibodies

AimsTo determine the prevalence of Associated Autoimmune Diseases (AADs) in Latent Autoimmune Diabetes of Adults (LADA) versus autoimmune Type 1 Diabetes (T1D) and the role of glutamic-acid decarboxylase antibodies (GADA) and other factors. MethodsAdults with autoimmune diabetes mellitus (DM) were recruited from the Diabetes Center of Nikaia-Piraeus Hospital. Demographic and clinical parameters were recorded and anti-pancreatic and organ-specific antibodies were measured. ResultsOf 160 patients, 33.75% had one AAD and 24.37% had two or more. Patients with LADA had higher overall prevalence of AADs, mainly autoimmune thyroiditis and gastritis. Celiac disease was present only in T1D. GADA positive patients had higher prevalence of AADs and multiple autoimmunity, especially thyroiditis and gastritis. Patients with LADA had higher rates of positive GADA or islet-cell antibodies (ICA). After controlling for LADA, GADA remained a significant predictor of AADs. Female gender and chronological age were also significant predictors of AADs. ConclusionsAADs were present in 58.13% of patients. Patients with LADA were more prone to a generalized autoimmune disorder than those with T1D. AADs development was significantly associated with female sex, older age and positive GADA, which proved an independent marker of associated autoimmunity.

Interaction Between GAD65 Antibodies and Dietary Fish Intake or Plasma Phospholipid n-3 Polyunsaturated Fatty Acids on Incident Adult-Onset Diabetes: The EPIC-InterAct Study.

OBJECTIVEIslet autoimmunity is associated with diabetes incidence. We investigated whether there was an interaction between dietary fish intake or plasma phospholipid n-3 polyunsaturated fatty acid (PUFA) concentration with the 65-kDa isoform of GAD (GAD65) antibody positivity on the risk of developing adult-onset diabetes.RESEARCH DESIGN AND METHODSWe used prospective data on 11,247 incident cases of adult-onset diabetes and 14,288 noncases from the EPIC-InterAct case-cohort study conducted in eight European countries. Baseline plasma samples were analyzed for GAD65 antibodies and phospholipid n-3 PUFAs. Adjusted hazard ratios (HRs) for incident diabetes in relation to GAD65 antibody status and tertiles of plasma phospholipid n-3 PUFA or fish intake were estimated using Prentice-weighted Cox regression. Additive (proportion attributable to interaction [AP]) and multiplicative interactions between GAD65 antibody positivity (≥65 units/mL) and low fish/n-3 PUFA were assessed.RESULTSThe hazard of diabetes in antibody-positive individuals with low intake of total and fatty fish, respectively, was significantly elevated (HR 2.52 [95% CI 1.76–3.63] and 2.48 [1.79–3.45]) compared with people who were GAD65 antibody negative and had high fish intake, with evidence of additive (AP 0.44 [95% CI 0.16–0.72] and 0.48 [0.24–0.72]) and multiplicative (P = 0.0465 and 0.0103) interactions. Individuals with high GAD65 antibody levels (≥167.5 units/mL) and low total plasma phospholipid n-3 PUFAs had a more than fourfold higher hazard of diabetes (HR 4.26 [2.70–6.72]) and an AP of 0.46 (0.12–0.80) compared with antibody-negative individuals with high n-3 PUFAs.CONCLUSIONSHigh fish intake or relative plasma phospholipid n-3 PUFA concentrations may partially counteract the increased diabetes risk conferred by GAD65 antibody positivity.

Glutamic acid decarboxylase antibodies in neurocritical patients: a culprit or a bystander?

BackgroundGlutamic acid decarboxylase (GAD) is an intracellular enzyme, which is widely expressed in central nervous system (CNS), pancreas, and other organs. GAD antibodies (GAD-Abs) are linked to various neurological disorders. However, the significance of GAD-Abs in neurocritical patients is undetermined.Materials and methodsPatients with serologically positive GAD-Abs and requiring neurocritical care were included. The clinical, laboratory, and outcome data were retrospectively collected.ResultsWe included 9 patients with serologically positive GAD-Abs. Clinical manifestations involved both CNS and peripheral nervous system (PNS). Six (66.7%) patients had other specific autoimmune antibodies. Non-specific autoimmune responses were observed in 8 (88.9%) patients. All patients clinically responded well to immunotherapy. The titers of GAD-Abs decreased in 7 (77.8%) patients but remained unchanged in the other 2 patients. One (11.1%) patient awoke before the negative conversion of GAD-Abs, and 3 (33.3%) patients remained unconscious and/or under mechanical ventilation for several weeks after the vanishing of GAD-Abs.ConclusionsMost neurocritical patients with serologically positive GAD-Abs had other specific autoimmune antibodies. All patients responded well to immunotherapy, but not parallel to the titers of GAD-Abs. These results indicated that GAD-Abs might be more a bystander than a culprit in neurocritical patients, suggesting that an underlying autoimmune disease should be explored.

Older age of childhood type 1 diabetes onset is associated with islet autoantibody positivity >30 years later: the Pittsburgh Epidemiology of Diabetes Complications Study.

To examine the association between islet autoantibody positivity and clinical characteristics, residual β-cell function (C-peptide) and prevalence of complications in a childhood-onset (age <17 years), long-duration (≥32 years) type 1 diabetes cohort. Islet autoantibodies (glutamic acid decarboxylase, insulinoma-associated protein 2 and zinc transporter-8 antibodies) were measured in the serum of participants who attended the 2011-2013 Pittsburgh Epidemiology of Diabetes Complications study follow-up examination (n=177, mean age 51 years, diabetes duration 43 years). Prevalences of islet autoantibodies were: glutamic acid decarboxylase, 32%; insulinoma-associated protein 2, 22%; and zinc transporter-8, 4%. Positivity for each islet autoantibody was associated with older age at diabetes onset (glutamic acid decarboxylase antibodies, P=0.03; insulinoma-associated protein 2 antibodies, P=0.001; zinc transporter-8 antibodies, P<0.0001). Older age at onset was also associated with an increasing number of autoantibodies (P = 0.001). Glutamic acid decarboxylase antibody positivity was also associated with lower HbA1c (P = 0.02), insulinoma-associated protein 2 antibody positivity was associated with lower prevalence of severe hypoglycaemic episodes (P=0.02) and both distal and autonomic neuropathy (P=0.04 for both), and zinc transporter-8 antibody positivity was associated with higher total and LDL cholesterol (P=0.01). No association between autoantibody positivity and C-peptide was observed. The strong association between islet autoantibody positivity and older age at type 1 diabetes onset supports the hypothesis of a less aggressive, and thus more persistent, immune process in those with older age at onset. This observation suggests that there may be long-term persistence of heterogeneity in the underlying autoimmune process.

Profile of Auto-antibodies (Disease Related and Other) in Children with Type 1 Diabetes.

Background:Type 1 diabetes is associated with several disease-related and other organ-specific autoimmune disorders. Data related to various auto-antibodies in Type 1 diabetes in India is limited.Materials and Methods:In this cross sectional study, 92 subjects with T1DM (33 males, 59 females) were evaluated for T1DM related antibodies (autoantibodies to glutamic acid decarboxylase (anti-GAD), autoantibodies to protein tyrosine phosphatise (anti-IA2), anti-islet cell antibody (ICA), insulin autoantibody (IAA), anti-Zinc Transporter(ZnT8) and other organ specific auto antibodies like anti–thyroid peroxidase (anti-TPO), anti-thyroglobulin (TgAb), IgA anti-tissue transglutaminase (IgA anti-tTG), anti-21-hydroxylase, and anti-ovarian antibody (in females).Results:Anti-GAD, IA-2, islet cell antibody, insulin autoantibodies (IAA), ZnT8 antibody were present in 79.3%, 32.6%, 61.9%, 63%, and 20.65% subjects, respectively. Only 2.2% patients with Type 1 diabetes were antibody negative. At least one antibody was found in 97.8% and at least two antibodies in 67.3%. The presence of anti-TPO, anti-thyroglobulin, IgA anti-tissue transglutaminase, anti 21-hydroxylase were found in 51%, 25%, 22.8%, and 2.1%, respectively. Anti-ovarian antibody was absent in all females of our study population. The duration of diabetes positively correlated with the number of T1DM specific antibody and also with GAD antibody positivity. Anti TPO positivity correlated with the age of onset of T1DM, but not with the duration of disease or presence of other T1DM specific autoantibody.Conclusions:T1DM is associated with a high prevalence of autoantibodies and antibody negative T1DM is rare. The association with other organ specific antibody (especially thyroid and adrenal glands) and celiac disease is also substantial, which reinforces the importance of regular thyroid and celiac disease screening in T1DM subjects. The duration of diabetes positively correlated with number of T1DM specific antibodies.

Autoimmunity plays a role in the onset of diabetes after 40 years of age

Aims/hypothesisType 1 and type 2 diabetes differ with respect to pathophysiological factors such as beta cell function, insulin resistance and phenotypic appearance, but there may be overlap between the two forms of diabetes. However, there are relatively few prospective studies that have characterised the relationship between autoimmunity and incident diabetes. We investigated associations of antibodies against the 65 kDa isoform of GAD (GAD65) with type 1 diabetes and type 2 diabetes genetic risk scores and incident diabetes in adults in European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct, a case-cohort study nested in the EPIC cohort.MethodsGAD65 antibodies were analysed in EPIC participants (over 40 years of age and free of known diabetes at baseline) by radioligand binding assay in a random subcohort (n = 15,802) and in incident diabetes cases (n = 11,981). Type 1 diabetes and type 2 diabetes genetic risk scores were calculated. Associations between GAD65 antibodies and incident diabetes were estimated using Prentice-weighted Cox regression.ResultsGAD65 antibody positivity at baseline was associated with development of diabetes during a median follow-up time of 10.9 years (HR for GAD65 antibody positive vs negative 1.78; 95% CI 1.43, 2.20) after adjustment for sex, centre, physical activity, smoking status and education. The genetic risk score for type 1 diabetes but not type 2 diabetes was associated with GAD65 antibody positivity in both the subcohort (OR per SD genetic risk 1.24; 95% CI 1.03, 1.50) and incident cases (OR 1.97; 95% CI 1.72, 2.26) after adjusting for age and sex. The risk of incident diabetes in those in the top tertile of the type 1 diabetes genetic risk score who were also GAD65 antibody positive was 3.23 (95% CI 2.10, 4.97) compared with all other individuals, suggesting that 1.8% of incident diabetes in adults was attributable to this combination of risk factors.Conclusions/interpretationOur study indicates that incident diabetes in adults has an element of autoimmune aetiology. Thus, there might be a reason to re-evaluate the present subclassification of diabetes in adulthood.

Prevalence of positive islet autoantibody in type 2 diabetes patients: a cross-sectional study in a Chinese community.

BackgroundIslet autoantibodies occur in type 2 diabetes. Our study aimed to investigate the prevalence of positive islet autoimmunity in community patients with type 2 diabetes.MethodsA total of 495 community patients with type 2 diabetes were recruited using the method of cluster sampling in this cross-sectional study. Three islet autoantibodies including glutamic acid decarboxylase antibody (GADA), insulin autoantibody (IAA) and islet cell antibody (ICA) were measured, and clinical characteristics involved in those individuals were evaluated.ResultsThe positive rate of islet autoantibodies was 28.5% in total, while combinations of different autoantibodies were rarely seen. Compared with GADA-negative group, positive counterparts significantly tended to have lower levels of body mass index (BMI), waist-hip ratio (WHR), and urinary microalbumin (mALB) (P < 0.05). Adjusted for confounding factors, WHR, triglycerides (TG), and mALB seemed to be negative independent predictors of GADA (OR < 1, P < 0.05). Patients with positive IAA tended to receive insulin treatment (P < 0.0001). Besides, fasting blood glucose (FBG), serum levels of high-density lipoprotein cholesterol (HDL-CH), aspartate transaminase (AST), and γ-glutamyltransferase (GGT) were more likely to be higher in IAA positive subgroup in comparison with the negative counterparts. While after AST was adjusted by unconditional logistic regression analysis, history of insulin treatment, FBG, HDL-CH, and GGT were confirmed as positive predictors of IAA. Furthermore, in patients who were IAA positive, those treated with exogenous insulin tended to have longer duration of diabetes than non-insulin treatment counterparts (P < 0.0001). With regard to ICA, however, there were no significant differences between the two subgroups, except that serum level of AST/ALT seemed to be slightly different (P = 0.064).ConclusionThese data suggested that type 2 diabetic community patients with positive GADA tended to be lean and were able to maintain normal lipid metabolism, while patients with positivity of IAA were frequently accompanied with insulin treatment and more closely associated with diabetic liver damage.