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BACKGROUND: Checkpoint inhibitor (CPI)-associated diabetes mellitus (CPI-DM) is a rare immune-related adverse event (irAE) that presents with variable clinical manifestations. Data about its pathogenesis have not yet been adequately studied. METHODS: Applying the recently updated diagnostic criteria from the American Diabetes Association, we retrospectively reviewed the medical records of all CPI-treated patients referred to our endocrinological unit for managing their endocrine irAEs and analyzed the incidence of CPI-DM, its clinical characteristics, and its management. RESULTS: Among the 326 CPI-treated patients with endocrine irAEs, 4 patients met the updated criteria for the diagnosis of CPI-DM, representing 1.22% of all endocrine irAEs in our cohort. These four patients presented with distinct clinical scenarios regarding the irAE onset, the underlying malignancy, the administered CPI regimen, and the type of circulating autoantibodies. CONCLUSION: The variable presentation of CPI-DM and the non-standard sensitivity of the presence of the type 1 DM traditional autoantibodies highlight the need for distinct guidelines and increased awareness of its diagnosis and management.

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Anti-glutamic acid decarboxylase (GAD) autoantibodies are a hallmark of stiff-person syndrome (SPS) and insulin-dependent diabetes mellitus (IDDM). However, patients with concurrent IDDM and SPS often manifest insulin resistance, and SPS-associated IDDM probably has heterogeneous causes. Some patients manifest IDDM associated only with high titers of anti-GAD65 caused by SPS. By contrast, other patients develop IDDM only after being treated with high-dose corticosteroids or they progress to insulin dependency following their treatment with high-dose corticosteroids. The profile of autoantibodies differs markedly between type 1 diabetes mellitus (T1DM), late-onset diabetes mellitus, and SPS-associated IDDM. Therefore, as with new-onset diabetes after transplantation (NODAT), SPS-associated IDDM should be classified as a specific diabetes entity, the pathophysiology of which requires increased attention.

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Type 1 diabetes mellitus (T1DM) is mainly triggered by autoimmune ß-cell destruction, usually leading to absolute insulin deficiency. Regarding the speed of ß-cell destruction, there are large variations depending on age. In some adult cases, sufficient ß-cell function is sometimes retained for a relatively long period and eventually they become dependent on insulin for survival. It is known that even in subjects with T1DM showing high titers of such antibodies, insulin secretory capacity is preserved under several conditions such as "honeymoon" period and slowly progressive T1DM (SPIDDM). Herein, we reported the acute onset T1DM subject with long-term preservation of ß-cell function, although his anti-GAD antibody and anti-IA-2 antibody titers were very high for more than 4 years. This case is very important in that his ß-cell function was preserved with dipeptidyl peptidase-4 inhibitor alone. This means that there are large variations in the speed of ß-cell destruction in the onset of T1DM.

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@#Introduction: Diabetes-associated autoantibodies (DAA) is the hallmark of T1DM and LADA which are frequently tested in young diabetes patients. It was noted that up to 10-15% of patients with initial diagnosis of T2DM also exhibit DAA. Regardless of the classification, the presence of DAA suggests an underlying islet autoimmunity which lead to progressive pancreatic β-cell failure. There is limited data reported on DAA in young diabetes patients in Malaysia. This study aims to determine the frequency of DAA positivity and its association with demographic and clinical characteristics among this cohort. Methods: A retrospective study using secondary data obtained from Allergy and Immunology Research Centre, Institute for Medical Research, Malaysia. This study included 194 diabetes patients who were diagnosed before the age of 40 years old and tested for GADA, ICA, IA2A and IAA. Results: From 194 patients, 91 (46.9%) were positive for least one of the following DAA: ICA (79, 40.7%), GADA (61, 31.4%), IA2A (37, 19.1%) and IAA (9, 4.6%). Multiple positivity was higher (73.6%) compared to single positivity. Highest combination of double positivity was ICA+GADA (54, 59.3%) and triple positivity was ICA+GADA+IA2A (25, 27.5%). Simultaneous positivity of four autoantibodies was seen in only one (1.1%) patient. ICA, GADA and IA2A were associated with age group and ethnicity (all p < 0.001). Only IA2A was associated with gender (p = 0.012). Conclusions: GADA, ICA ad IA2A are more significant in young Malaysian diabetes patients. IAA has a very low frequency in this studied population.

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INTRODUCTION: Type I diabetes (T1D) is an autoimmune disease with a prediabetic, asymptomatic period characterized by the selective destruction of insulin-producing ß cells. During the pre-clinical phase, various auto-antibodies are generated against several beta cell antigens such as anti glutamate acid decarboxylase (Anti-GAD), anti tyrosine phosphatase (Anti-IA2). Today, the coupled detection of Anti-IA2 with that of Anti-GAD proves its great importance in the diagnosis and prediction of type 1 diabetes. The combined positivity for both antibodies has a specificity and a positive predictive value of 100%. OBJECTIVES: In this work, we evaluate the diagnostic value of anti-GAD and anti-IA2 antibodies in a series based on 78 Moroccan subjects initially under 16, suspected T1D. RESULTS AND DISCUSSION: Our series consists mainly of 74% of newly diagnosed patients for T1D and 26% of confirmed diagnostic patients, of whom 52% are females. The mean age of diagnosis is 7 ± 4 years, the mean of HbA1c at the time of diagnosis is 11.63 ± 2.16%, and the percentage of family history in our series is 69%. The proportion of positive results for anti-IA2 antibodies and anti-GAD antibodies are, respectively, 76.92% and 62.82%, and 52.56% of patients are positive for both auto-antibodies. This study confirms that anti-GAD and anti-IA2 auto-antibodies assays can detect patients early and the autoantibodies can persist several years after diagnosis of type 1 diabetes. CONCLUSION: This study confirmed the diagnosis and classification of T1D (type 1A) in 87.18% of patients, and we reported that the prevalence of anti-GAD and anti-IA2 is higher in girls than in boys.

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AIM OF THE STUDY: Evaluate the added value of screening anti-ZnT8 antibodies (ZnT8A) in addition to the classical anti-GAD (GADA) and anti-IA-2 (IA-2A) antibodies for the diagnosis of type-1 diabetes (T1D) within a large cohort of both children and adults. MATERIALS AND METHODS: Retrospective 2-year study including 516 patients (215 children, 301 adults) who had blood tests at diabetes onset and/or for diabetes classification. ZnT8A, GADA, and IA-2A were analyzed in all samples. RESULTS: Among those individuals included, 142 (28%) were ZnT8A-positive. A total of 228/516 suffered from T1D, of whom 110 (48%) were ZnT8A-positive and 166 (73%) GADA and/or IA-2A positive. When adding ZnT8A to GADA/IA-2A, 184 (81%) patients were positive for ≥1 Ab. Regarding the 122 patients at T1D onset, 75 (61%) were positive for ZnT8A and the proportion of patients with T1D with ≥1 Ab reached 89%. The highest prevalence of ZnT8A was observed in children aged 6-10years. Fourteen of the 124 patients positive for ZnT8A with a known clinical diagnosis suffered from a disease other than T1D. CONCLUSIONS: ZnT8A should be included in routine evaluation at diabetes onset and is a valuable biological marker to classify newly-diagnosed diabetics. The predictive value in our high-risk subjects has to be confirmed.

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BACKGROUND: It is being increasingly reported that some of the youth onset diabetes patients cannot be classified clearly as type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM) based on usual criteria and the term double diabetes (DD) coined for these cases. AIM: The objective of the study was to find out the prevalence of DD in youth onset diabetes patients from east Delhi and neighboring NCR region. METHODS: A total of 200 patients with youth onset diabetes below 25 years of age were recruited from a tertiary care hospital in East Delhi. Clinical history, family history of diabetes and anthropometry of patients were recorded. Fasting serum C-peptide, Anti-IA2-antibody and Anti-GAD-antibody were measured in all patients. Patients positive for Anti-GAD-antibody (>1.05U/ml) and C-peptide level >0.3nmol/l were characterized as DD patients. Patients negative for Anti-GAD-antibody and C-peptide >0.3nmol/l were kept under the category of T2DM. Patients with low C-peptide level along with one of the following, positive Anti-GAD-antibody, positive Anti-IA2-antibody and diabetic ketoacidosis (DKA) were considered as T1DM. Remaining patients were kept under the unknown category. RESULTS: Mean age of study subjects was 18.2±7.1years. Seven percent (7%) of the subjects were classified as DD, 51% as T1DM, 13% as T2DM and 29% were kept under the unknown category. Mean age of subjects with 22.2±9.7, 16.9±6.7, 20.6±7.7 and 19.4±7.4 years in DD, T1DM, T2DM and unknown category respectively. Mean BMI of subjects with DD, T1DM, T2DM and unknown category was 19.8±5.7, 16.6±3.7, 19.3±4.1 and 18.0±4.6 kg/m2 respectively. CONCLUSION: Double diabetes is an important occurrence among youth onset diabetes subjects. Only half of the subjects with youth onset of diabetes had T1DM.

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INTRODUCTION: Anti GAD (antibodies on glutamic acid decarboxylase) and anti-IA2 antibodies (against tyrosine phosphatase), today, have their place and importance in diagnosis and prognosis of Type 1 diabetes. Huge number of patients with diabetes mellitus type 1 have these antibodies. Insulin antibodies are of critical importance in diagnosis of diabetes mellitus type 1 for pediatric population. MATERIALS AND METHODS: During 2014, the samples of 80 patients from Clinical Center University Sarajevo (CCUS) Pediatrics clinic's, Endocrinology department were analyzed on anti-GAD and IA2 antibodies. The samples of serums of all patients were analyzed with ELISA tests using Anti GAD ELISA (IgG) kites from EUROIMMUN company. These are quantitative in vitro tests for human antibodies against decarboxylase of glutamine acid (GAD) and IA2, in serum or EDTA plasm. RESULTS: During the period of one year, in CCUS's Organizational unit, Institute for Clinical Immunology, 80 samples of patients with anti GAD and IA2 antibodies were analyzed. Out of total number of samples, 41 were male patients, or 51% and 39 female, or 49%. The youngest patient was born in 2012, and the oldest in 1993. Age average was represented by the patients born in 2001. Share of positive results for IA2 antibodies and GAD antibodies was 37% for IA2 antibodies, and 63% for GAD antibodies. DISCUSSION: During an autoimmune - mediated Diabetes mellitus type 1 leads to T-cell mediated destruction of beta cells of pancreatic islets, reduced production of insulin and glucose metabolism. Studies have shown that these bodies are the most intense single marker for identifying persons with increased risk for diabetes development.