Pancreatic Autoantibodies Research Articles

Simultaneous Pancreas-Kidney Transplant Outcomes Stratified by Autoantibodies Status and Pretransplant Fasting C-peptide.

Pancreatic beta cell function and islet autoantibodies classically distinguish types of diabetes (type 1 diabetes mellitus [DM] or type 2 DM). Here, we sought to evaluate simultaneous pancreas-kidney (SPK) transplant outcomes stratified by the presence or absence of beta cell function and autoantibodies. SPK recipients were eligible if pretransplant autoantibodies were measured against insulin, islet cell, or glutamic acid decarboxylase 65-kD isoform. Recipients were categorized as A+ or A- based on the detection of ≥1 autoantibodies. Recipients were similarly categorized on the basis of detectable pretransplant fasting C-peptide of ≥2 ng/mL (β+) or <2 ng/mL (β-). Thus, recipients were categorized into 4 groups: A+β-, A-β-, A-β+, and A+β+. Outcomes of interest were overall pancreas graft failure (non-death-censored), death-censored pancreas, or kidney graft failure (death-censored pancreas graft failure [DCGF]; kidney DCGF), composite outcomes with any of the 3 outcomes as pancreas DCGF, use of an antidiabetic agent, or hemoglobin A1c >6.5. One hundred eighty-three SPK recipients were included: A+β- (n = 72), A-β- (n = 42), A-β+ (n = 49), and A+β+ (n = 20). We did not detect a statistical difference in non-death-censored pancreas graft failure for A+β- recipients compared with other groups: A-β- (adjusted hazard ratio [aHR]: 0.44; 95% confidence interval [CI], 0.14-1.42), A-β+ (aHR: 1.02; 95% CI, 0.37-2.85), and A+β+ (aHR: 0.67; 95% CI, 0.13-3.33) in adjusted analyses. Similar outcomes were observed for other outcomes. In SPK recipients, outcomes were similar among recipients with classic features of type 1 DM and various other types of DM.

6985 Intravenous Immunoglobulin induced Type 1 diabetes remission

Abstract Disclosure: N. Shahid: None. D. Newbern: None. Introduction: Intravenous immunoglobulin [IVIG] is an immunomodulatory agent used for treatment of autoimmune and inflammatory conditions. However, it is not indicated in patients with type 1 diabetes [T1D] as its efficacy has not been established. Clinical Case: A 9-year-old previously healthy boy presented to the Emergency Department with several days of unexplained bruising and mucosal bleeding with no prior history of trauma, bleeding disorders or other systemic symptoms. Physical examination showed generalized petechiae, ecchymosis and purpura. Vitals were normal including weight and BMI. Initial labs confirmed Immune thrombocytopenic purpura [ITP] as his platelets were less than 1K/µL with otherwise normal peripheral blood cell counts and smear. Concomitantly, labs showed significant hyperglycemia [260mg/dL] with glycosuria and trace ketonuria. Glycated hemoglobin [Hba1c] was elevated at 10.5% and ultimately Pancreatic autoantibodies [GAD65, Zinc transporter-8 and islet cell antibody] came back positive confirming T1D. Other autoimmune disorders such as adrenal insufficiency, thyroiditis, and celiac disease were ruled out. For the treatment of ITP, he the patient received 1 dose of IVIG 1g/kg and responded well with a rise in platelets to 6K/µL. The morning following the infusion, due to fasting hyperglycemia, the patient was started on basal-bolus insulin regimen. By 2nd day post IVIG, he had hypoglycemia, so insulin was discontinued with normalization of blood sugars. He is now 7 months post IVIG with no recurrent episodes of thrombocytopenia. He also remains off insulin with Hba1c in the 5.9-6.5% range. He eats a regular diet with avoidance of simple carbohydrates. He wears onwears a a continuous glucose monitor, which shows that blood sugars are in range 93% of the time He remains euglycemic overnight with transient self-resolving mild post-prandial hyperglycemia. Pancreatic autoantibodies have been reassessed and remain positive Conclusions: This case demonstrates that IVIG used for the treatment of ITP has induced a state of remission in our patient with newly diagnosed with T1D. IVIG is not a standard of treatment for T1D, however, when given for other autoantibody- or T-cell-mediated autoimmune conditions, it may reduce the insulin need in patients with known diabetes or induce remission in patients with newly diagnosed diabetes.

8099 Pembrolizumab Induced Autoimmune Diabetes: An Abrupt Virulent Onset

Abstract Disclosure: H.F. Belal: None. N. Shaykh: None. A. Rajesh: None. J.M. Chehade: None. Background: Pembrolizumab is a programmed cell death protein 1 inhibitors (PD-1i) approved for the treatment of many solid cancers. Although thyroid abnormalities are among the most common endocrine adverse effects associated with PD-1i, insulin-dependent diabetes mellitus can also occur in up to 1% of patients treated with PD1-i.[1] Clinical Case: A 70-year-old female with past medical history of non-toxic multi-nodular goiter and surgical hypothyroidism was diagnosed with gastric cancer. She had no pancreatic abnormality on PET scan. Her management included four cycles of neo-adjuvant chemotherapy: fluorouracil, cisplatin, trastuzumab and pembrolizumab. She had no personal history of gestational diabetes. Prior to initiating neo-adjuvant chemotherapy her A1c was 5.9%. She was not prescribed any anti-diabetic medications. Her grandmother had type 2 diabetes mellitus. On exam her BMI was 23.73 kg/m². She had no acanthosis nigrans, skin tags or abdominal striae. Eighteen days after completing her second cycle of neo-adjuvant chemotherapy, she presented to the emergency department with nausea, vomiting, polyuria and confusion and was found to be in DKA. Her A1c during admission was 7.1%. Imaging revealed no pancreatitis. Labs showed suppressed C-peptide &amp;lt;0.1 ng/mL (1.1-4.4) in the setting of blood glucose 283 mg/dL (71-99). Her GAD-65 antibody was elevated at 902 U/mL (0.0-5.0). She was diagnosed with PD-1i induced autoimmune diabetes mellitus (PD-1i DM) and subsequently treated with basal and prandial insulin. Conclusion: The mechanism of PD-1i DM is unclear. A proposed mechanism is aberrant T cell activation towards pancreatic islet cells. One study found that 59% of patients with PD-1i DM presented with DKA.[1] In this study, the median time of PD-1i DM onset was 20 weeks after the first treatment cycle. Additionally, 40% of these patient had at least one positive pancreatic autoantibody. A recent meta-analysis found the relative risk of PD-1i DM to be 1.56 (95% CI = 0.95-2.57, P = 0.08).2 This relative risk increased to 2.06 (95% CI = 0.48-8.86, P = 0.33) when PD-1i were combined with cytotoxic T lymphocyte antigen-4 inhibitors.

Clinical Utility of Serial Monitoring of C-Peptide in Diagnostic Dilemmas of Young-Onset Diabetes: A Case-Based Discussion

Abstract Diabetes in the young has been traditionally defined as onset of diabetes below 35 years of age. In this age bracket, a variety of distinct types of diabetes might occur which poses a unique challenge in the diagnosis and management. Phenotypic features such as age of onset, presence of obesity and family history have traditionally been used in differentiating the various types of diabetes. With the increasing prevalence of obesity and T2DM in youth, these features have become less reliable in classifying diabetes in this age group. Along with detailed patient history and physical examination, biochemical parameters such as C-peptide and presence or absence of pancreatic autoantibodies (along with imaging studies for pancreatic pathology and genetic testing for monogenic forms of diabetes) are assuming greater importance in appropriate diagnosis and understanding the types of diabetes. C-peptide test which is a proxy for pancreatic beta cell function plays an important role in classifying type / subtypes of diabetes. When used appropriately it also helps in personalized approach to treatment and practice of Precision Diabetes.

Risk for progression to type 1 diabetes in first-degree relatives under 50 years of age.

The detection of pancreatic autoantibodies in first-degree relatives of patients with type 1 diabetes (T1D) is considered a risk factor for disease. Novel available immunotherapies to delay T1D progression highlight the importance of identifying individuals at risk who might benefit from emerging treatments. The objective was to assess the autoimmunity in first-degree relatives of patients with T1D, estimate the time from autoimmunity detection to the onset of clinical diabetes, and identify the associated risk factors. Retrospective multicenter study of 3,015 first-degree relatives of patients with T1D recruited between 1992 and 2018. Pancreatic autoantibodies (IAA, GADA, IA2A, and ZnT8A) were determined by radioimmunoassay, starting the analyses at diagnosis of the proband. All those with positive autoimmunity and normal fasting blood glucose without clinical symptoms of diabetes were followed up in the study. The progression rate to T1D was assessed according to sex, relationship with the proband, age at autoimmunity detection, type/number of autoantibodies, and HLA-DRB1 genotype. Cox proportional-hazard models and Kaplan-Meier survival plots were used for statistical analyses. Among the relatives, 21 progenitors [43.7 years (IQR: 38.1-47.7)] and 27 siblings [7.6 years (IQR: 5.8-16.1)] had positive autoantibodies. Of these, 54.2% (95% CI: 39.2%-68.6%) developed T1D (age at autoimmunity detection 11 months to 39 years) in a median of 5 years (IQR: 3.6-8.7; ranged from 0.9 to 22.6 years). Risk factors associated with faster progression to T1D were multiple autoimmunity and <20 years at autoimmunity detection. Younger relatives (<20 years) with multiple autoantibodies had a 5-year cumulative risk of developing diabetes of 52.9% (95% CI: 22.1%-71.6%) and a 20-year risk of 91.2% (95% CI: 50.5%-98.4%). The 20-year risk decreased to 59.9% (95% CI: 21.9%-79.5%) if only one risk factor was met and to 35.7% (95% CI: 0.0%-66.2%) if the relative was older than 20 years with one autoantibody. In first-degree relatives with autoimmunity, the time to progression to T1D is faster in children and adolescents with multiple autoantibodies. Young adults are also at risk, which supports their consideration in screening strategies for people at risk of developing T1D.

Diabetic Ketoacidosis in Patients with Maturity-Onset Diabetes of the Young.

Maturity-onset diabetes of the young (MODY) is the most frequent monogenetic diabetes form. It is caused by mutations in genes important for the development and function of pancreatic beta-cells, resulting in impaired insulin secretion capacity. Up to now, 14 different types have been described. The inheritance pattern is autosomal dominant, leading to a strong family history with more than three affected generations. Young age at diagnosis and lack of pancreatic autoantibodies are further characteristics of MODY. The presence of diabetic ketoacidosis (DKA) was long regarded as an exclusion criterion for MODY. However, in recent years, several case reports on MODY patients presenting with DKA have been published. The present study aimed to give an overview of the current knowledge of DKA in MODY patients, with a collection of published case studies as a prerequisite for this review.

Stress-Induced Diabetic Ketoacidosis Due to Transient Beta Cell Stunning in a Youth with Type 2 Diabetes Mellitus: A Case Report

Abstract A 15-year-old boy was admitted to the intensive care unit of our hospital with complaints of increased urination, extreme tiredness, and nausea for the past 15 days. He had also lost 6.5 kg of weight (almost 10% of total body weight) in 1 month. On admission, his plasma glucose was 780 mg/dL, glycated haemoglobin (HbA1c) 11.6%, serum ketones &gt;10.0 mmol/L, osmolality 346 mosm/kg, arterial pH 7.28, and bicarbonate 9 mEq/L. The C-peptide report initially indicated poor pancreatic beta cell reserve (fasting: 0.41 pmol/mL and stimulated: 0.46 pmol/mL). He was diagnosed with diabetic ketoacidosis and responded well to treatment, after which time he was switched to subcutaneous insulin. Ten days later, in the outpatient clinic, his fasting blood glucose was 132 mg/dL, postprandial blood glucose was 183 mg/dL, and C-peptide had improved to fasting: 0.89 pmol/mL and stimulated: 1.42 pmol/mL. Considering the presence of acanthosis nigricans on the neck, a body mass index in the overweight range, a positive family history of diabetes, and negative tests for pancreatic autoantibodies, an early onset diagnosis of type 2 diabetes mellitus was considered. Insulin was gradually withdrawn, and he was switched to metformin. Sustained recovery of C-peptide in this case indicates that lack of insulin at admission was due to beta cell stunning, rather than a total and irreversible loss of beta cells as expected in type 1 diabetes mellitus. Beta cell stunning is often reversible, as shown in this case.

Maturity-onset diabetes of the young type 3 complicated with type 5: A case report and literature review.

This report describes a case of maturity-onset diabetes of the young (MODY) type 3 (MODY3) complicated with type 5 (MODY5), including the patient's clinical features, diagnosis, and treatment, and reviews relevant literature. Using next-generation sequencing of MODY (types 1-14) gene exons and Sanger sequencing for verification, the patient and her mother were assessed. Based on the clinical phenotype and genetic test results, the patient was diagnosed as MODY3 combined with MODY5. Treatment included insulin and linagliptin, with monitoring of blood glucose changes. Clinicians should enhance their understanding of MODY clinical phenotypes. In adolescents with diabetes who have congenital pancreatic and renal developmental defects, elevated high-density lipoprotein cholesterol, no spontaneous ketosis, insulin secretion defects, negative pancreatic autoantibodies, no significant insulin resistance, and who are not obese, gene testing should be conducted to screen for MODY. Accurate diagnosis and personalized treatment can aid in achieving glycemic control, improving quality of life, and optimizing reproductive planning.

Primary disease of adipose tissue: When to think about and how to evaluate it in clinical practice?

Primary diseases of adipose tissue are rare disorders resulting from impairments in the physiological functions of adipose tissue (lipid stockage and endocrine function). It mainly refers to lipodystrophy syndromes with subcutaneous adipose tissue atrophy and/or altered body distribution of adipose tissue leading to insulin resistance, diabetes, hepatic steatosis, dyslipidemia, cardiovascular complications and polycystic ovary syndrome in women. Those syndromes are congenital or acquired, and lipoatrophy is partial or generalized. The diagnosis of lipodystrophy syndromes is often unrecognized, delayed and/or inaccurate, while it is of major importance to adapt investigations to search for specific comorbidities, in particular cardiovascular involvement, and set up multidisciplinary care, and in some cases specific treatment. Physicians have to recognize the clinical and biological elements allowing to establish the diagnosis. Lipodystrophic syndromes should be considered, notably, in patients with diabetes at a young age, with a normal or low BMI, negative pancreatic autoantibodies, presenting clinical signs of lipodystrophy and insulin resistance (acanthosis nigricans, hyperandrogenism, hepatic steatosis, high insulin doses). The association of diabetes and a family history of severe and/or early cardiovascular disease (coronary atherosclerosis, cardiomyopathy with rhythm and/or conduction disorders) may reveal Dunnigan syndrome, the most frequent form of familial lipodystrophy, due to LMNA pathogenic variants. Clinical assessment is primarily done through clinical examination: acanthosis nigricans, abnormal adipose tissue distribution, lipoatrophy, muscular hypertrophy, acromegaloid or Cushingoid features, lipomas, highly visible subcutaneous veins, may be revealing signs. The amount of circulating adipokines may reflect of adipose dysfunction with low leptinemia and adiponectinemia. Other biological metabolic parameters (hypertriglyceridemia, hyperinsulinemia, increased glycemia and hepatic enzymes) may also represent markers of insulin resistance. Quantification of total body fat by impedancemetry or dual-photon X-ray absorptiometry (DEXA) reveals decreased total body mass, in correlation with adipose tissue atrophy; metabolic magnetic resonance imaging can also quantify intraperitoneal and abdominal fat and the degree of hepatic steatosis. Histological analysis of adipose tissue showing structural abnormalities should be reserved for clinical research. Acquired lipodystrophic syndromes most often lead to similar clinical phenotype as congenital syndromes with generalized or partial lipoatrophy. The most frequent causes are old anti-HIV therapy or glucocorticoid treatments. Family history, history of treatments and clinical examination, including a careful physical examination, are keys for diagnosis.

Investigation of Monogenic Diabetes Genes in Thai Children with Autoantibody Negative Diabetes Requiring Insulin.

The objective of this study was to clarify the phenotypic characteristics of monogenic diabetes abnormalities in Thai children with autoantibody-negative insulin. Two hundred and thirty-one Thai type 1 diabetes (T1D) patients out of 300 participants with recent-onset diabetes were analyzed for GAD65 and IA2 pancreatic autoantibodies. A total of 30 individuals with T1D patients with negative autoantibody were screened for 32 monogenic diabetes genes by whole-exome sequencing (WES). All participants were ten men and twenty women. The median age to onset of diabetes was 8 years and 3 months. A total of 20 people with monogenic diabetes carried genes related to monogenic diabetes. The PAX4 (rs2233580) in ten patients with monogenic diabetes was found. Seven variants of WFS1 (Val412Ala, Glu737Lys, Gly576Ser, Cys673Tyr, Arg456His, Lys424Glu, and Gly736fs) were investigated in patients in this study. Furthermore, the pathogenic variant, rs115099192 (Pro407Gln) in the GATA4 gene was found. Most patients who carried PAX4 (c.575G>A, rs2233580) did not have a history of DKA. The pathogenic variant GATA4 variant (c.1220C>A, rs115099192) was found in a patient with a history of DKA. This study demonstrated significant genetic overlap between autoantibody-negative diabetes and monogenic diabetes using WES. All candidate variants were considered disease risk with clinically significant variants. WES screening was the first implemented to diagnose monogenic diabetes in Thai children, and fourteen novel variants were identified in this study and need to be investigated in the future.

Distinct changes to pancreatic volume rather than pancreatic autoantibody positivity: insights into immune checkpoint inhibitors induced diabetes mellitus

BackgroundImmune checkpoint inhibitors (ICI) are promising treatment options for various cancers. However, their use is associated with immune-related adverse events (irAEs), including ICI-induced diabetes mellitus (ICI-DM). This study aimed to investigate the clinical features of ICI-DM, with a particular focus on alterations to pancreatic volume.MethodsWe conducted a retrospective review of 2829 patients who received ICI treatment at the Chang Gung Memorial Hospital, Linkou, between January 2014 and December 2021. New-onset diabetes or diabetic ketoacidosis (DKA) was identified in ten patients receiving ICI therapy. Pancreatic volumes were assessed by manual segmentation of computed tomography (CT) images before and after ICI-DM diagnosis.ResultsAmong these ten patients, nivolumab was the most commonly used ICI (50.0%), followed by pembrolizumab (30.0%) and atezolizumab (20.0%). One patient received combination therapy with nivolumab and ipilimumab. The median age was 63.01 years (range: 40.1 − 87.8). ICI-DM developed after a median of 13.5 cycles (range: 2 − 42) of ICI treatment or 9.85 months (range:1.5 − 21.3) since ICI initiation. The initial presentation was DKA in 60.0% of patients. All patients had low or undetectable C-peptide levels (range: <0.033 − 0.133 nmol/L) and were negative for most type 1 diabetes mellitus (T1DM)-related autoantibodies; only one patient tested positive for glutamic acid decarboxylase antibodies. CT imaging revealed significant pancreatic atrophy, with a median pancreatic volume decrease of 19.92% (P = 0.038) from baseline and sustained significant decline at last follow-up (median − 37.14%, P = 0.012).ConclusionsICI-DM is often accompanied by pancreatic atrophy and approximately two-thirds of patients initially present with DKA. Although the majority of ICI-DM patients lack T1DM-related autoantibodies, identifying diminished pancreatic volumes through CT imaging provides valuable clues into the subclinical aspects of ICI-DM development, aiding in the prevention of diabetic emergencies.Trial registrationNot applicable.

Whole Exome Sequencing in Children With Type 1 Diabetes Before Age 6 Years Reveals Insights Into Disease Heterogeneity.

Aims: This study is aimed at comparing whole exome sequencing (WES) data with the clinical presentation in children with type 1 diabetes onset ≤ 5 years of age (EOT1D). Methods: WES was performed in 99 unrelated children with EOT1D with subsequent analysis to identify potentially deleterious rare variants in MODY genes. High-resolution HLA class II haplotyping, SNP genotyping, and T1D-genetic risk score (T1D-GRS) were also evaluated. Results: Eight of the ninety-nine EOT1D participants carried a potentially deleterious rare variant in a MODY gene. Rare variants affected five genes: GCK (n = 1), HNF1B (n = 2), HNF4A (n = 1), PDX1 (n = 2), and RFX6 (n = 2). At diagnosis, these children had a mean age of 3.0 years, a mean HbA1c of 10.5%, a detectable C-peptide in 5/8, and a positive islet autoantibody in 6/7. Children with MODY variants tend to exhibit a lower number of pancreatic autoantibodies and a lower fasting C-peptide compared to EOT1D without MODY rare variants. They also carried at least one high-risk DR3-DQ2 or DR4-DQ8 haplotype and exhibited a T1D-GRS similar to the other individuals in the EOT1D cohort, but higher than healthy controls. Conclusions: WES found potentially deleterious rare variants in MODY genes in 8.1% of EOT1D, occurring in the context of a T1D genetic background. Such genetic variants may contribute to disease precipitation by a β-cell dysfunction mechanism. This supports the concept of different endotypes of T1D, and WES at T1D onset may be a prerequisite for the implementation of precision therapies in children with autoimmune diabetes.

Autoantibodies in Type 1 Diabetes: A Retrospective Study of Children Diagnosed Under Ten Years of Age

INTRODUCTION: Type 1 diabetes is a chronic disease characterized by a selective loss of pancreatic ?-cells with a disproportionate recent increase at ages under 5-years old. Its etiology is multifactorial, to which immune factors contribute through pancreatic autoantibodies. Our main aim is to assess whether the type of pancreatic autoantibody influence the clinical symptoms, glycated hemoglobin and glycemia at diagnosis of type 1 diabetes in children diagnosed under ten-years of age.METHODS: Observational, retrospective and analytical study carried out with a total of 95 patients included. We compared two groups (aged ?60 months and &gt;60 months) and each type of autoantibody (positive/negative) regarding demographic, immune, clinical and laboratory characteristics. The autoantibodies studied were islet cell autoantibodies (against cytoplasmic proteins in the ?-cell), antibodies to glutamic acid decarboxylase, anti-insulin and anti-zinc transporter 8. The impact of autoimmunity, glycated hemoglobin, gender and age on clinical and laboratory parameters of these children was analyzed.RESULTS: Children diagnosed over 60 months had a higher glycated hemoglobin value (p=0.005) and this laboratory parameter was the only one that showed an impact on the initial presentation as diabetic ketoacidosis (CI95%: OR=1.66;p=0.001). The value of glycemia at admission showed to be influenced negatively by age (?=--0.25;p=0.022) and positively by glycated hemoglobin (?=0.35;p=0.001). None of the autoantibodies evaluated seemed to interfere in the clinical and laboratory manifestations of type 1 diabetes.CONCLUSION: Demographic, clinical and laboratory characteristics showed no statistically significant differences between two groups of positive/negative pancreatic autoantibodies analyzed. It is crucial to develop further studies in the scope of autoimmunity that allow to structure potential immune phenotypes and assist in the discovery of new therapeutic targets.

Pancreatic autoantibodies in individuals with a clinical diagnosis of type 2 diabetes mellitus

Objectives: It can be challenging to accurately diagnose type 2 diabetes (T2D) in children based on clinical features alone. We aimed to describe pediatric patients with a clinical diagnosis of T2D who are positive for pancreatic autoantibodies and compare their clinical features to patients with T2D without autoantibodies. Material and Methods: This cross-sectional study and medical record review included patients aged 10–30 years with T2D seen at our pediatric diabetes clinic between January 01, 2013, and December 31, 2020. We compared the characteristics of autoantibody-positive patients with autoantibody-negative patients using Chi-square tests for binary variables and t-tests for continuous variables. Results: Eleven out of 87 (12.6%) patients with a clinical diagnosis of T2D had positive autoantibody results. The groups with and without antibodies were not significantly different in terms of age, sex, and body mass index (BMI) Z-score. However, the hemoglobin A1c (HbA1c) closest to the time of the first autoantibody test was significantly lower in the autoantibody-positive group. Two of the 11 antibody-positive patients had two positive autoantibodies and one had four positive autoantibodies. The other eight patients were positive for one autoantibody only. One of the 11 antibody-positive patients had an episode of diabetic ketoacidosis (DKA). Conclusion: While age, sex, and BMI were similar in both groups, patients with autoantibodies had significantly lower HbA1c at the time of antibody testing and one patient went into DKA. Autoantibodies should be measured in all patients diagnosed with diabetes to avoid the consequences of potential misclassification.

Pancreatic autoantibody and other organ-specific autoantibodies and their relevance in diabetes mellitus

Pancreatic autoantibody and other organ-specific autoantibodies and their relevance in diabetes mellitus

Antibodies to Glutamic Acid Decarboxylase-65 is Associated with Total Daily Dose of Insulin Requirement in Children with Type 1 Diabetes

BACKGROUND: Type 1 diabetes (T1D) mostly occurs due to the destruction of pancreatic beta cells due to autoimmune processes. Diagnosis of T1D can be established by examining the c-peptide levels and the markers of pancreatic autoantibodies, including glutamic acid decarboxylase 65 autoantibodies (GAD-65). However, the association between c-peptide and anti-GAD-65 toward patients’ clinical manifestations needs to be further explored. Hence, the aim of current study was to identify the association of anti-GAD65 with c-peptide and clinical characteristics in children with T1D.METHODS: Case-control study involving 47 T1D children (T1D group) and 41 healthy children (control group) younger than 18 years old was conducted. Secondary data regarding subjects’ demographic characteristics and medical history were collected from subjects, and serum blood was drawn from each subject for the anti-GAD65 and c-peptide measurement. Anti-GAD65 and c-peptide levels were measured using an Enzyme-Linked Immunosorbent Assay (ELISA) methods.RESULTS: Anti-GAD65 antibody was detected in 78.7% T1D group, while only 2.43% were detected in control group subject (p=0.0000). The c-peptide level of T1D group was 0.07±0.19 nmol/L and control group was 1.5±0.77 nmol/L (p=0.0000). The total daily dose of insulin in subjects with positive anti-GAD65 was greater than in the negative anti-GAD65 (p=0.012). The sensitivity and specificity of the anti-GAD65 were 85.4% was 66.7%, respectively.CONCLUSION: The results of this study show that anti-GAD65 was associated with total daily dose of insulin requirement in children with T1D.KEYWORDS: diabetes mellitus, type 1 diabetes, anti-GAD65, c-peptide

ISLET: individual-specific reference panel recovery improves cell-type-specific inference

We propose a statistical framework ISLET to infer individual-specific and cell-type-specific transcriptome reference panels. ISLET models the repeatedly measured bulk gene expression data, to optimize the usage of shared information within each subject. ISLET is the first available method to achieve individual-specific reference estimation in repeated samples. Using simulation studies, we show outstanding performance of ISLET in the reference estimation and downstream cell-type-specific differentially expressed genes testing. We apply ISLET to longitudinal transcriptomes profiled from blood samples in a large observational study of young children and confirm the cell-type-specific gene signatures for pancreatic islet autoantibody. ISLET is available at https://bioconductor.org/packages/ISLET.

Early Intervention by Family Physicians to Delay Type 1 Diabetes.

Type 1 diabetes (T1D) is an autoimmune disease mediated by T cells that target and destroy insulin-producing beta cells. Individuals with genetic risk of T1D will progress at variable rates through 3 stages of immune activation and development of islet autoimmunity. Measuring pancreatic islet cell autoantibodies predicts risk for progression that can take weeks to years before the onset of T1D. Screening options available to family physicians can identify persons at risk or in the early stages of T1D, such as first- and second-degree relatives or those with a family history of autoimmune disorders, to ultimately offer proven interventions that may delay or prevent the condition. Screening can reduce emergency room visits, hospitalizations, and intensive care unit admissions for diabetic ketoacidosis, which can be fatal, and can educate and prepare individuals and families for a smoother transition to insulin therapy when necessary. Recent advances in technology and understanding of the immune pathogenesis of T1D has resulted in emerging disease-modifying therapies that are changing how family physicians approach delaying and potentially preventing or reversing the disease.

Prevalence and characteristics of misdiagnosed adult-onset type 1 diabetes mellitus in Thai people by random plasma C-peptide testing

BackgroundIt is critical to determine the exact type of diabetes because misclassification led to inappropriate treatments. The classification of DM can be aided by the measurement of pancreatic autoantibodies and plasma C-peptide levels. Previous studies suggested that random plasma C-peptide testing in those with clinically diagnosed adult T1DM of at least 3 years duration has led to reclassification in some cases. AimThis study aimed to assess the prevalence and characteristics of misdiagnosed adult-onset type 1 diabetes mellitus in Thai people by random plasma C-peptide testing. MethodsA cross-sectional study of adult Thai patients diagnosed with clinically diagnosed T1DM and DM duration of at least 3 years at Theptarin Hospital, a diabetes center in Bangkok, Thailand was studied. Clinically misdiagnosis of T1DM was defined by preserved endogenous insulin secretion. Characteristics of the misdiagnosed patients were compared with definite T1DM patients. ResultsA total of 73 patients (females 52.1%, mean age 42.2 ± 12.5 years, duration of DM 20.3 ± 11.3 years) were studied. The prevalence of available anti-GAD and anti-IA2 were 53.3% and 20.8%, respectively. Preserved endogenous insulin secretion evaluated by random C-peptide or stimulated C-peptide was found in 8 patients (11.0%). The misdiagnosed patients had higher prevalence of hypertension and diabetic complications. Three patients were suspected to have monogenic diabetes and five patients were reclassified as possible T2DM. ConclusionsApproximately one-tenth of adult T1DM patients were misdiagnosed. Random plasma C-peptide testing at least 3 years after a diagnosis of T1DM was superior to the measurement of pancreatic autoantibodies. Our present study highlights the need to increase accuracy in the diagnosis of T1DM patients by re-assessing endogenous insulin production with measurement of random plasma C-peptide levels.

Update information on type 1 diabetes in children/adolescents and adults.

Update information on type 1 diabetes in children/adolescents and adults.