Anti-glutamic Acid Decarboxylase Antibodies Research Articles

Anti-glutamate Dehydrogenase Antibody Positive Cerebellar Ataxia and Stiff Person Syndrome Responding to Dual Treatment with Steroids and Intravenous Immunoglobulin: A Case Presentation and Literature Review

Anti-glutamic acid decarboxylase (anti-GAD) antibody syndrome (aGAS) has various presentations including cerebellar ataxia (CA) and stiff person syndrome (SPS). This is a treatable cause of CA and SPS. We present a case of a 49-year-old man who developed blurred vision, slurred speech, difficulty walking, unsteady gait, and clumsiness which had progressed over four months. The patient was found to have anti-GAD ab (+) CA and SPS and experienced significant symptomatic improvements after treatment with intravenous (IV) steroids followed by intravenous immunoglobulin (IVIG). The patient’s improvement persisted when he was reevaluated at follow up one month later. Since anti-GAD ab related diseases, including anti-GAD CA and SPS, are rarely diagnosed, there is limited data regarding the treatment of this condition. As there are only a few cases in the literature similar to this one, highlighting the successful treatment of anti-GAD ab cerebellar ataxia and SPS with dual therapy (steroids followed by IVIG) is important.

Hyperglycemia caused by mutation of GCK gene in 10 patients analysis of clinical and mutation characteristics

Objective: To explore the gene mutation characteristics and detailed clinical presentations of hyperglycemia caused by GCK mutations in 10 patients. Methods: The clinical and follow-up data of 10 patients with hyperglycemia caused by mutation of GCK gene were reviewed. The patients were ascertained between January 1, 2014 and August 31, 2018 at the Department of Pediatrics, the First Affiliated Hospital of Zhejiang University and Ningbo Women & Children's Hospital. Clinical data were collected, including age, gender, main complaint, family history, fasting blood glucose, fasting blood insulin, 2-hour blood glucose, 2-hour blood insulin after oral glucose tolerance test, glycosylated hemoglobin, anti-glutamic acid decarboxylase antibody and body mass index. Mutations of GCK gene were detected by Sanger sequencing or high-throughput sequencing of diabetes-related genes in the patients and their family members. Results: There were ten patients, 8 of them were male, 2 were female.The ages at diagnosis varied between 4.7 to 12.3 years. The patients usually did not have obvious clinical symptoms of diabetes mellitus. Most of them were unexpectedly found to have hyperglycemia and with impaired glucose metabolism in three consecutive generations. The fasting blood glucose of patients was 6.8-7.7 mmol/L, 2-hour postprandial blood glucose was 7.8-11.6 mmol/L. Fasting blood insulin was 0.5-8.5 mU/L, glucose tolerance test results showed that 2 h postprondial blood insulin was 1.3-55.4 mU/L. The level of glycosylated hemoglobin was 6.1%-6.8%. Anti-glutamic acid decarboxylase antibody was negative in all patients. The GCK mutations identified in patients and one of their parents were located at exon5 (4 cases), exon9 (2 cases), exon2 (1 case), exon4 (1 case), exon6 (1 case) and exon7 (1 case). Conclusions: Most of the hyperglycemia patients caused by GCK mutations did not have typical clinical symptoms of diabetes. The fasting blood glucose was slightly elevated. Abnormal glucose tolerance test results were found in all 10 patients. Three consecutive generations of family had impaired glucose metabolism. GCK mutations located at exon 5 were common in 10 cases. There was no correlation between type of mutations and plasma glucose levels in domestic and international researches. When fasting glucose was found abnormal in clinic, a complete family history should be taken and the GCK gene should be sequenced to confirm the diagnosis in time.

1734-P: A Considerable Mismatch of Measurements between Radioimmunoassay and Enzyme-Linked Immunosorbent Assay Tests for Anti-Glutamic Acid Decarboxylase Antibody

Most cases of type 1 diabetes mellitus are considered to be caused by pancreatic β-cell destruction through islet cell autoimmunity. Anti-glutamic acid decarboxylase antibody (GADA) is an important islet cell-associated autoantibody in the diagnosis of autoimmune type 1 diabetes mellitus. In Japan, the GADA assay kit was changed from radioimmunoassay (RIA) to enzyme-linked immunosorbent assay (ELISA) in 2015. Thereafter, a mismatch of measurements between the two tests became apparent in clinical situations. The aim of this study was to clarify the extent of the mismatch between the two tests on a larger scale. In this cross-sectional non-local/non-hospital-based study, we collected anonymized data on GADA levels of 598 randomly selected participants in whom GADA levels were simultaneously measured by GADA-RIA and GADA-ELISA tests. We found that 34% (= 162/477) of the GADA-RIA-positive participants showed negative results in the GADA-ELISA test; the mismatch was predominantly observed in participants with relatively low GADA-RIA levels. Concretely, when considering lower GADA-RIA levels alone (1.5-32 U/mL), GADA-ELISA-negative participants accounted for 44.8% (= 162/362) of the GADA-RIA-positive participants. These findings suggest that a single application of the GADA-ELISA test may affect the precise diagnosis of type 1 diabetes mellitus, and cause physicians’ confusion on the diagnosis. Therefore, the cause for the mismatch should be promptly identified. Disclosure Y. Oikawa: None. T. Kondo: None. A. Shimada: Advisory Panel; Self; Terumo Medical Corporation. Speaker's Bureau; Self; Abbott, Eli Lilly and Company, Novo Nordisk A/S, Sanofi-Aventis. Y. Seino: Research Support; Self; Arkray, Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited, Terumo Medical Corporation. M. Kitaoka: Research Support; Self; AstraZeneca, Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Co., Ltd.

Clinical characteristics and classification diagnosis of newly diagnosed diabetes onset with ketosis or ketoacidosis in adult patients

Objective: To describe the clinical characteristics and classification diagnosis of newly diagnosed diabetes onset with ketosis or ketoacidosis in adult patients. Methods: Medical records of newly diagnosed diabetes onset with ketosis or ketoacidosis in the Third Affiliated Hospital of Sun Yat-sen University between January 2011 and August 2016 were reviewed. Patients aged 18 years or older were included, while other diseases that may cause urinary ketoacidosis and special types of diabetes were excluded. Patients were classified as type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM) or diabetes mellitus untyped based on discharged diagnosis, and groups were compared for differences in clinical profiles. Then the patient's medication, final diagnosis and outcome within 2 years of discharge were tracked through the inpatient and the outpatient medical record systems. Receiver operating characteristics (ROC) curves were analyzed to check the ability of clinical indicators such as onset age, body mass index (BMI) and C-peptide to discriminate T1DM from T2DM, and to find the best diagnostic cut-off points. Results: A total of 123 patients (88 males) were enrolled [with a mean age of (41.1±13.6) years old], with 37 patients (30.1%) diagnosed as T1DM, 60 patients (48.8%) diagnosed as T2DM and 26 patients (21.1%) diagnosed as Untyped. There was a statistically significant difference in onset age, BMI, blood pressure, blood gas pH and bicarbonate, blood lipids, fasting, 0.5 h and 2 h C-peptide level, any diabetic antibody and anti-glutamic acid decarboxylase antibody (GADA) positive rate, combined fatty liver ratio and family history among the three groups (all P<0.05). ROC curve analysis was performed on patients diagnosed with T1DM (n=36) and T2DM (n=87) after 2 years follow-up, and the area under the curve (AUC) of onset age, BMI, fasting C-peptide, 0.5 h and 2 h C-peptide was 0.735, 0.813, 0.855, 0.898, and 0.882, respectively. Conclusion: The ROC curve analysis indicates that C-peptide, onset age and BMI can provide effective diagnostic value, and the diagnostic value of C peptide is better than BMI and onset age.

SUN-583 Immune Thrombocytopenic Purpura Associated with Stiff Person Syndrome and Polyglandular Autoimmune Syndrome Type 2

Background Idiopathic thrombocytopenic purpura (ITP) is an acquired autoimmune disease caused by antibodies against platelet glycoproteins. Stiff person syndrome (SPS) is a progressive neurological disorder characterized by axial muscle rigidity and involuntary spasms associated with anti-glutamic acid decarboxylase (GAD) antibodies. Polyglandular autoimmune syndrome type 2 (APS-2) is defined by the occurrence of Addison disease with thyroid autoimmune disease and/or Type 1 diabetes mellitus (T1DM). SPS has been associated with APS-2 as well as to T1DM and autoimmune thyroid disease alone. ITP has been linked T1DM in rare cases as well as autoimmune thyroid disease, yet SPS and ITP have not previously been associated. We present the first reported case to our knowledge of a patient with ITP subsequent to Graves disease, SPS and T1DM. Clinical Case The patient is a 35-year-old female evaluated in endocrinology clinic for follow up of Graves disease treated with RAI ablation 5 years prior. She presented with fluctuating muscle rigidity and spasms involving the axial muscles leading to gait disturbance and frequent falls. She displayed the classic “wooden-man” appearance when ambulating first described by Moersch and Wotmann which lead to the name of SPS. She was treated with diazepam due to clinical suspicion for SPS. Neurology was consulted, both the referring physician and neurologist agreed with the diagnosis of SPS. Her symptoms gradually improved yet they have proven to be relapsing and remitting in nature requiring modification of dosing depending on response. 7 years later she was diagnosed with T1DM, presenting to the ED with generalized weakness and fatigue. Initial laboratory work was consistent with DKA. During her hospitalization routine laboratory work showed incidental thrombocytopenia with a platelet count of 15,000. Over the next few days her platelet count dropped to 5,000 prompting diagnostic bone marrow aspiration and biopsy which revealed a hypercellular marrow and adequate megakaryopoiesis. ITP was the working diagnosis and patient was discharged with prednisone. A favorable response to therapy was noted and prednisone was tapered accordingly. 2 years later she presented with a relapse of ITP with a platelet count of 6,000; treatment was initiated with intermittent prednisone and IVIG. At this time T1DM and thyroid disease were well controlled. Serum GAD-antibodies tested after presentation of ITP were >250 IU/ml (0-5.0 IU/ml). Conclusion To our knowledge ITP has not previously been documented in a patient with SPS. Our goal is to create physician awareness regarding the association between these disorders as well as the need for regular monitoring of patients with an endocrine autoimmune disease. SPS has been linked to APS-2; yet is it possible that SPS can independently be associated with ITP?

Anti Glutamic Acid Decarboxylase Antibody Syndromes Occur At An Earlier Age In African Americans. (P2.2-034)

Anti Glutamic Acid Decarboxylase Antibody Syndromes Occur At An Earlier Age In African Americans. (P2.2-034)

Anti-glutamic acid decarboxylase (GAD) positive cerebellar Ataxia with transitioning to progressive encephalomyelitis with rigidity and myoclonus (PERM), responsive to immunotherapy: A case report and review of literature

We present a case of a 65-year-old African American male, immunosuppressed on Tacrolimus, who initially presented with cerebellar ataxia and rapidly developed Progressive Encephalomyelitis with Rigidity and Myoclonus (PERM) with positive anti-glutamic acid decarboxylase (GAD65) antibodies, no underlying malignancy, and normal neuroimaging. PERM is a rare spectrum of Stiff Person Syndrome (SPS), which is strongly associated with anti-GAD antibodies and characterized by flare-ups and remissions of encephalopathy, myelopathy and rigidity with myoclonus. PERM is diagnosed clinically and has been successfully treated with both Intravenous Immunoglobulin (IVIg) and plasmapheresis. Our patient was successfully treated with IVIg. On day 14 after starting IVIg treatment, his neurological symptoms started to improve and ultimately returned to baseline.

Clinical Characteristics of Four Cases of Focal Epilepsy with Elevated Anti-glutamic Acid Decarboxylase Antibodies

Clinical Characteristics of Four Cases of Focal Epilepsy with Elevated Anti-glutamic Acid Decarboxylase Antibodies

Clinical characteristics of anti-glutamic acid decarboxylase antibody-positive fulminant type 1 diabetes.

This research aimed to examine the relationship between anti-glutamic acid decarboxylase antibody (GADA) titers and clinical parameters at onset and to clarify the association between clinical severity and GADA titers in GADA-positive fulminant type 1 diabetes. This cross-sectional observational study included 20 cases with GADA-positive fulminant type 1 diabetes (4 cases from our hospital and 16 from cases reported in the literature). The association between GADA titers and clinical parameters [age, sex, body weight, body mass index, period from appearance of any prodromal symptoms to diagnosis, period from development of hyperglycemic symptoms to diagnosis, GADA titer, HbA1c level, blood pH and HCO3- level, serum levels of ketone bodies and pancreatic exocrine enzymes] were analyzed. Spearman's rank correlation coefficient (rs) was used for the correlation analysis. The results showed that there was a significant inverse correlation between GADA titers and the "period from appearance of any prodromal symptoms to diagnosis" (rs = -0.559, p < 0.05). Moreover, GADA titers were inversely correlated with blood pH and HCO3- level (rs = -0.576, p < 0.05, rs = -0.578, p < 0.05, respectively), and positively correlated with serum levels of total ketone bodies, acetoacetate, and 3-hydroxybutyrate (rs = 0.661, p < 0.05; rs = 0.700, p < 0.05; and rs = 0.782, p < 0.01, respectively). These findings suggest that higher GADA titers may be linked to more severe clinical severity of GADA-positive fulminant type 1 diabetes at onset. This association may be attributed to possible pre-existence of autoimmunity-related β-cell damage before the onset of fulminant type 1 diabetes.

A case of musicogenic epilepsy with high level of anti-glutamic acid decarboxylase antibodies

A case of musicogenic epilepsy with high level of anti-glutamic acid decarboxylase antibodies

Catatonia in Dual Diagnosis: a Case Report

Catatonia is a syndrome resulting in both severe motor and speech disturbances. Catatonia in a dual diagnosis of cannabis dependence and depressive disorder is presented. A 28-year-old male, who had background diagnoses of cannabis dependence and moderate depressive episode, was admitted involuntarily to a psychiatry unit due to aggressiveness. A diagnosis of catatonia was made (Bush-Francis Catatonia Rating Scale score = 19/69). Routine blood profile, CT scan brain, anti-NMDA, anti-potassium channel and anti-glutamic acid decarboxylase (GAD) antibodies were all normal. He was treated with lorazepam. His symptoms resolved completely after 5 days.

Actual condition survey regarding mismatch of measurements between radioimmunoassay and enzyme-linked immunosorbent assay tests for anti-glutamic acid decarboxylase antibody in real-world clinical practice.

Anti‐glutamic acid decarboxylase antibody (GADA) is an important islet cell‐associated autoantibody for the diagnosis of autoimmune type 1 diabetes mellitus. In Japan, the GADA assay kit was recently changed from radioimmunoassay (RIA) to enzyme‐linked immunosorbent assay (ELISA). Thereafter, a mismatched measurement between the two tests became apparent in clinical situations. The present study aimed to clarify the actual extent of mismatch between the two measurements on a larger‐scale real‐world clinical practice. In this cross‐sectional non‐local/non‐hospital‐based study, we collected anonymized data on GADA levels of 598 participants, who were simultaneously measured with GADA‐RIA and GADA enzyme‐linked immunosorbent assay tests. We found that 34% of the GADA‐RIA‐positive participants showed negative results in the GADA enzyme‐linked immunosorbent assay test; the mismatch was predominantly observed in participants with relatively low GADA‐RIA levels (<32 U/mL). This considerable mismatch might lead to physicians’ confusion in diagnosing type 1 diabetes mellitus.

Occurrence of Hypothyroidism, Diabetes Mellitus, and Celiac Disease in Emirati Children with Down's Syndrome.

Autoimmune diseases are known to occur in people with Down's syndrome (DS), especially celiac disease, type 1 diabetes mellitus (DM), and hypothyroidism. Since there are common genetic risk factors involved in the occurrence of these autoimmune disorders, the risks would differ in different populations. We sought to determine the prevalence of type 1 DM, celiac disease, and hypothyroidism in Emirati patients with DS in Abu Dhabi, UAE. Ninety-two patients with DS were investigated for the presence of anti-thyroid antibodies, antithyroglobulin, and anti-thyroid peroxidase antibodies for hypothyroidism, anti-glutamic acid decarboxylase antibodies for type 1 DM, and anti-tissue transglutaminase immunoglobulin A antibodies for celiac disease. Karyotyping was performed on 89 patients. Eighty-seven had non-disjunction of chromosome 21 (97.8%), one was a mosaic, and one had translocation. Of the patients studied, 19.6% had hypothyroidism, 4.3% had type 1 DM, and 1.1% had celiac disease. Out of the 92 patients studied, 66 (71.7%) did not have any autoimmune disease, 25 (27.2%) had one autoimmune disease, and one (1.1%) had two autoimmune diseases. Celiac disease was the least prevalent autoimmune disease in patients with DS patients, while type 1 DM and hypothyroidism were both significantly associated with DS.

Uso de plasmaféresis para el manejo del síndrome de la persona rígida

Introducción: el síndrome de la persona rígida (SPR) es una patología infrecuente caracterizada por la activación involuntaria de la unidad motora, causando rigidez fluctuante de la musculatura axial, espasmos musculares dolorosos y actividad motora continua en la electromiografía. En la mayoría de pacientes se encuentran niveles elevados de anticuerpos antiácido glutámico descarboxilasa. Presentación del caso: paciente de género femenino de 60 años de edad, con persistencia de sintomatología espasmódica muscular a pesar del manejo con medicamentos agonistas GABA e inmunomoduladores, por lo que se consideró el uso de plasmaféresis como tercera línea de tratamiento. Conclusiones: la experiencia con el uso de la técnica es favorable, hay disminución de los espasmos musculares en más del 50% al cabo de 7 sesiones. Aunque la plasmaféresis produjo alivio sintomático, son necesarios nuevos ensayos clínicos y reportes de caso para determinar su beneficio clínico y así protocolizar su aplicación.&#x0D;

Association of Autoimmune Thyroid Disease with Anti-GAD Antibody ELISA Test Positivity and Risk for Insulin Deficiency in Slowly Progressive Type 1 Diabetes.

The presence of antiglutamic acid decarboxylase antibody (GADA) is required for the diagnosis of slowly progressive type 1 diabetes (SPT1D). We examined the factors influencing GADA determination by radioimmunoassay (GADA-RIA) and by enzyme-linked immunosorbent assay (GADA-ELISA). Sixty patients with SPT1D and 154 patients with type 2 diabetes were examined by both GADA-RIA and GADA-ELISA and for the presence of autoimmune thyroid disease (AITD). We compared the clinical characteristics of these patients based on the positivity or negativity of GADA-RIA and GADA-ELISA, and the existence or nonexistence of AITD. Thirty of 60 (50.0%) GADA-RIA-positive patients were GADA-ELISA negative, whereas none of the 154 GADA-RIA-negative patients were GADA-ELISA positive. Concomitant AITD was significantly less in patients with GADA-RIA and without GADA-ELISA and was significantly more in patients with GADA-RIA and GADA-ELISA. In GADA-RIA-positive patients, there was no significant difference in the GADA-RIA titer among the GADA-ELISA-negative patients with and without AITD, and the GADA-ELISA-positive patients without AITD; whereas the frequency of insulin deficiency was significantly higher in the patients with AITD and/or GADA-ELISA than in those without AITD and GADA-ELISA. Examination of GADA-ELISA and AITD in GADA-RIA-positive patients might be useful in predicting insulin deficiency in these patients.

Stiff-person Syndrome with Waldenström Macroglobulinemia

We herein report the case of stiff-person syndrome in a 73-year-old woman. She experienced episodes of painful muscle spasms and was admitted to another hospital. She was diagnosed with Waldenström macroglobulinemia. She showed improvement in muscle spasms post-chemotherapy, which was discontinued due to pancytopenia. Six months later, she was admitted to our hospital for repeated whole-body muscle spasms, at which point she was diagnosed with stiff-person syndrome. An anti-glutamic acid decarboxylase antibody text was negative. Her muscle spasms disappeared after the administration of corticosteroids and rituximab. Stiff-person syndrome may develop with Waldenström macroglobulinemia. In the present case, corticosteroids and rituximab provided effective treatment.

Characteristics and clinical course of type 1 diabetes mellitus related to anti-programmed cell death-1 therapy.

We conducted a national survey to clarify the characteristics and clinical course of type 1 diabetes related to anti-programmed cell death-1 therapy. We analyzed the detailed data of 22 patients that were collected using a Japan Diabetes Society survey and a literature database search. Among the 22 patients, 11 (50.0%) met the criteria for fulminant type 1 diabetes and 11 (50.0%) met the criteria for acute-onset type 1 diabetes. The average patient age was 63years. The mean duration between the date of the first anti-PD-1 antibody injection and development of type 1 diabetes was 155days and ranged from 13 to 504days. Flu-like symptoms, abdominal symptoms, and drowsiness were observed in 27.8, 31.6, and 16.7% patients, respectively. Mean ±standard deviation or median (first quartile-third quartile)glucose levels, HbA1c levels, urinary C-peptide immunoreactivity levels, and fasting serum C-peptide immunoreactivity levels were 617 ± 248mg/dl, 8.1 ± 1.3%, 4.1 (1.4-9.4) μg/day, and 0.46 (0.20-0.70) ng/ml, respectively. Seventeen of 20 patients (85.0%) developed ketosis, and 7 of 18 patients (38.9%) developed diabetic ketoacidosis. Ten of 19 patients (52.6%) showed at least one elevated pancreatic enzyme level at the onset and two of seven patients showed this elevation before diabetes onset. Only one of 21 patients was anti-glutamic acid decarboxylase antibody positive. Anti-programmed cell death-1 antibody-related type 1 diabetes varies from typical fulminant type 1 diabetes to acute-onset type 1 diabetes. However, diabetic ketoacidosis was frequently observed at the onset of diabetes. An appropriate diagnosis and treatment should be provided to avoid life-threatening metabolic alterations.

Prospective Study on Incidence of Cardiovascular-Renal Diseases, Severe Hypoglycaemia, and Death in Chinese with Latent Autoimmune Diabetes in Adults

Objectives: Few studies have examined the progression to chronic complications in patients with latent autoimmune diabetes in adults (LADA). We compared incidence of cardiovascular-renal diseases, severe hypoglycaemia and death in patients with LADA and type 2 diabetes. Methods: Between 1995-2012, 1569 Chinese with young-onset (age of diagnosis &amp;lt;40 years) non-type 1 diabetes underwent comprehensive disease assessment at Prince of Wales Hospital, Hong Kong. LADA (n=124 [7.9%]) was identified by positive anti-glutamic acid decarboxylase antibodies measured from stored serum. Patients were followed for new events of cardiovascular disease (CVD), end-stage renal disease (ESRD), severe hypoglycaemia and all-cause death until June 2017. Results: At baseline, patients with LADA (mean age: 43.4 years, median diabetes duration: 6.0 years) had lower serum C-peptide, BMI and triglyceride but higher HbA1c than patients with type 2 diabetes (mean age: 41.7 years, median diabetes duration: 8.0 years). Use of insulin was more frequent in those with LADA whilst use of non-insulin glucose lowering drugs was comparable. Over follow-up period of 10 years, incidence (in 1000 person-year) of CVD, ESRD, severe hypoglycaemia and death were 4.1, 8.0, 20.2 and 5.5 in LADA, and 10.4, 9.5, 10.8 and 8.8 in type 2 diabetes, respectively. Using Cox regression, patients with LADA had lower hazard to have CVD (hazard ratio [HR] 0.41 [95% CI 0.19-0.89], p=0.024), higher hazard to have severe hypoglycaemia (HR 1.74 [95% CI 1.15-2.62], p=0.008) and similar risks for ESRD and mortality compared with type 2 diabetes, adjusted for age, gender, disease duration, smoking, glycaemic and metabolic indices, and baseline insulin use. Conclusions: Patients with LADA had lower risks of CVD but higher risks of severe hypoglycaemia than type 2 diabetes. Disclosure A. Luk: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc.. Research Support; Self; Sanofi. E.S. Lau: None. C.K.P. Lim: None. E. Chow: Research Support; Self; Sanofi. R.C. Ma: Research Support; Self; AstraZeneca, Bayer AG, Merck Sharp &amp; Dohme Corp., Pfizer Inc.. Advisory Panel; Self; Boehringer Ingelheim GmbH, Nippon Boehringer Ingelheim Co. Ltd. A.P. Kong: Research Support; Self; AstraZeneca. J.C. Chan: Consultant; Self; Bayer AG. Other Relationship; Self; Bayer AG. Consultant; Self; Sanofi. Other Relationship; Self; Sanofi, Eli Lilly and Company, Amgen Inc.. Consultant; Self; AstraZeneca, Merck &amp; Co., Inc., Pfizer Inc.. Other Relationship; Self; Pfizer Inc.. Board Member; Self; Asia Diabetes Foundation. Stock/Shareholder; Self; GemVCare. Other Relationship; Self; Merck Sharp &amp; Dohme Corp.. Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Novartis AG, Eli Lilly and Company.

A Cut-Off Value for Anti-GAD Ab ELISA Test for Predicting Future Insulin Dependency in SPIDDM May Not Exist

We previously demonstrated that patients initially diagnosed with slowly progressive insulin-dependent (type 1) diabetes mellitus (SPIDDM) using a radioimmunoassay (RIA) test for anti-glutamic acid decarboxylase antibody (GADA) (GADA-RIA), who were also positive on a GADA enzyme-linked immunosorbent assay (ELISA) test (GADA-ELISA), showed a reduced insulin secretory capacity early in the SPIDDM disease process [Endocr J. 2017;64:163]. When we used GADA-RIA test, in SPIDDM with non-insulin dependent state, a GADA-RIA value ≥10 U/mL(GADA-RIA-High) was believed to indicate a higher risk for future insulin dependency than a value &amp;lt;10 U/mL(GADA-RIA-Low). In our previous study also, the insulin secretory capacity may be lower in “GADA-RIA-High and GADA-ELISA-positive SPIDDM patients” (A group) than those with “GADA-RIA-Low and GADA-ELISA-positive SPIDDM patients” (B group) early in the disease process, but this point was not yet confirmed. Therefore, we have now performed additional analysis to compare serum C-peptide levels in these two patient groups (group A vs. B). When restricted to a shorter disease duration, &amp;lt;11 years based on our previous study, serum C-peptide levels were 0.73 ± 0.61 ng/mL in group B (n = 9) and 0.68 ± 0.65 ng/mL in group A(n = 15). There was no significant difference between the two measures, but each of these two measurements was significantly lower than those for patients with type 2 diabetes (2.20 ± 0.85 ng/mL; n = 15) and those for “GADA-RIA-Low and GADA-ELISA-NEGATIVE SPIDDM patients” (2.60 ± 1.66 ng/mL; n = 6). These findings suggest that, regardless of their GADA-RIA titer, GADA-ELISA-positive patients with SPIDDM may show a reduced insulin secretory capacity early in the disease process. In conclusion, unlike GADA-RIA test, a cut-off value for GADA-ELISA test for predicting future insulin dependency in SPIDDM may not exist. Disclosure Y. Oikawa: None. T. Katsuki: None. T. Kawai: None. A. Shimada: Speaker's Bureau; Self; Eli Lilly and Company, Sanofi-Aventis, Novo Nordisk A/S.

Clinical and biochemical characteristics of familial type 1 diabetes mellitus (FT1DM) compared to non-familial type 1 DM (NFT1DM).

Familial type 1 diabetes mellitus (FT1DM) comprises parent-offspring and sib-pair subgroups. The clinical and genetic characteristics of FT1DM cases with and without affected family members have been previously studied with varying results. Some investigators found similarity of presenting features whereas others reported significant differences between the two groups. To describe the clinical and biochemical characteristics of children with FT1DM in comparison with those with non-familial type 1 diabetes mellitus (NFT1DM). We performed a cross-sectional retrospective study in a cohort of children and adolescents with T1DM (n=424) aged between 6 months - 16 years attending to Hamad General Hospital Pediatric Diabetes Center, Doha (Qatar) from 2012-2016. They were divided into 2 groups. Group 1 consisted of 62 children and adolescent with FT1DM (parent-offspring or sib-pair). The other group (Group 2) consisted of 431 children and adolescents with NFT1DM. The clinical presentation and prevalence of β-cell autoimmunity (anti-glutamic acid decarboxylase (GAD) antibodies , anti-islet cell and anti-insulin antibodies), thyroid function (Free thyroxine: FT4 and thyroid-stimulating hormone: TSH), anti-thyroid peroxidase antibody (TPO) and anti-tissue transglutaminase (ATT) at their first presentation were recorded, described and analyzed. FT1 DM was more prevalent in boys versus girls (1.4:1, respectively) whereas the prevalence of NFT1DM did not differ between genders (1:1.1, respectively). F1DM occurred relatively early in childhood (40.7% before the age of 4 years and 72% before 9 years of age) versus NFT1DM which occurred relatively later in life (80% after the age of 4 years and 40% after the age of 9 years). 35.2% of FT1DM presented with diabetic ketoacidosis (DKA) versus 32.5% of T1DM patients. Anti-islet antibodies (Ab) were detected more frequently in FT1DM versus NFT1DM. The prevalence of positive anti-insulin and anti- GAD antibodies did not differ between the two groups. Anti TPO were detected in 27.2% of NFT1DM and 35.5% of FT1DM. A primary hypothyroidism, with positive ATPO, was more prevalent in FT1DM versus NFT1DM. ATT IgA was high in 5% of NFT1DM and 19.8% of FT1DM whereas ATT IgG was high in 4.4 % of NFT1DM and 15.4% of FT1DM. FT1DM is more prevalent in boys versus girls and occurs earlier in childhood compared to NFT1DM. Primary hypothyroidism was more prevalent in NFT1DM versus FT1DM. Anti-islet Ab and ATT antibodies were more prevalent in the FT1DM versus NFT1DM. The genetic background may explain some differences between FT1DM and NFT1DM including the age of onset, gender affection, as well as associated autoimmune disorders.