Anti-islet Cell Antibodies Research Articles

7316 A Unique Presentation of Diabetes Mellitus in an 8-Year-Old Male Positive For 3 Different Mutations Related to MODY

Abstract Disclosure: R. Senguttuvan: None. A. Pamfil: None. Background: Maturity-Onset Diabetes of the Young (MODY) is the most common form of inherited non-autoimmune diabetes mellitus, characterized by autosomal dominant inheritance, young age at onset and beta cell dysfunction. There are at least 14 MODY mutations and we present a pediatric case not meeting criteria for type 1[T1DM] or type 2 diabetes mellitus[T2DM], who tested positive for mutations in 3 different genes known to cause MODY. Case: An 8-year-old male, born full term, 2776 grams and 48.3 cm, without history of neonatal hypoglycemia or hyperglycemia, was referred for new onset diabetes mellitus management. While undergoing evaluation for abdominal pain and constipation, he was found to have a fasting glucose of 126 mg/dL (7 mmol/L) and hemoglobin A1C of 6.5%. He endorsed polyuria, but no polydipsia. He had no clinical signs of insulin resistance (e.g., acanthosis nigricans) and a BMI of 23.65 kg/m2, at the 97th percentile. Family history is positive for diabetes mellitus requiring insulin, in father (diagnosed at 11 years) and paternal grandmother and T2DM in paternal aunt. Laboratory evaluation was negative for all 5 antibodies (GAD, IA-2, Anti-islet cell antibody, Zinc Transporter 8 and Insulin antibodies) and revealed an insulin level of 15.9 uIU/mL (RR: <2.0-13.0) and C peptide: 2.3 ng/mL (RR: 1.1-4.4). Lacking diagnostic criteria for T1DM or T2DM, genetic testing was performed. Patient tested heterozygous for mutations in 3 genes known to cause MODY: GCK [(c.350 G>T p. (G117V)], ABCC8 [(c.2270 C>G p.(T757R)], and HNF1B [(c.68A>G p.(K23R)], all variant of uncertain significance. Over an 8-month period, patient's weight decreased from 98 lbs. (44.9 kg) to 90 lbs. (41.1 kg) after meeting with our dietician and implementing healthy dietary changes, and his beta cell function markers improved from diagnosis: Fasting insulin (4.5 uIU/mL), C peptide (1.3 ng/mL), and glucose 119 mg/dL; Hemoglobin A1C remained relatively stable at 6.1%. A kidney ultrasound was normal. No medical intervention were started yet, and patient is being monitored clinically and biochemically every 3-4 months. Discussion: Clinical monitoring over time, genetic testing in the parents, are critical in this patient’s long-term treatment plan and prognosis. To our knowledge, this may be the first case of diabetes mellitus in a pediatric patient, positive for mutations in 3 different genes known to cause MODY. South Texas has one of the highest incidences of T2DM in the USA. In addition to screening for genetic forms of diabetes, in patients with negative T1DM antibodies and atypical phenotype for T2DM, we should consider genetic screening in mildly obese pediatric and young adult patients without significant acanthosis nigricans, who were already diagnosed as T2DM. Presentation: 6/1/2024

Evaluation of the Presentation of Newly Diagnosed Type 1 Diabetes Mellitus in Children During and After the COVID-19 Pandemic

Background: The COVID-19 pandemic has been a global health problem with high morbidity and mortality. In this study, it was aimed to compare the clinical and laboratory findings of patients diagnosed with type 1 diabetes(T1D) during the pandemic and after the pandemic. Method: This is a 30-month, single-center, cross-sectional study. Between October 2020 and December 2021 was defined as the pandemic period, and between January 2022 and March 2023 as the post-pandemic period. The clinical and laboratory parameters of the newly diagnosed T1D patients who applied in these two time periods were compared. Results: While 87 patients were diagnosed during the pandemic period, 86 patients were diagnosed during the post-pandemic period. The rate of male patients diagnosed during the pandemic period was significantly higher (56%, 36%, respectively, p=0.007). Anti-islet Cell antibody (ICA) positivity was statistically significantly higher in those diagnosed during the pandemic period. (52.6%, 18.6%, respectively, p<0.001). There was no difference between the groups in terms of hemoglobin A1C, thyroid autoantibodies and tissue transglutaminase antibodies (p>0.05).C peptide levels were significantly lower in those diagnosed during the pandemic period (0.39±0.4, 0.63±0.6, respectively, p=0.021). Admissions with severe acidosis were more common during the pandemic than those admitted after the pandemic (29.9%, 16.3%, respectively, p=0.151). Conclusions: The numbers of children with T1D newly diagnosed in a secondary health center were similar during and after the pandemic. In the pandemic period, admissions with autoantibody positivity, low C-peptide and severe acidosis were more common.

Obesity and Acanthosis Nigricans as the Clinical Markers of Insulin Resistance and Type-2 Diabetes Mellitus in Young Patients; A Case Report of Two Cases

Two young girls, aged 11 and 12 years, presented with obesity and Acanthosis Nigricans. They were found to have severe insulin resistance and type-2 diabetes mellitus. Anti-glutamic acid decarboxylase and anti-islet cell antibodies were negative. Tests for hypothyroidism and Cushing’s syndrome were negative. They were managed with lifestyle modification and metformin.

P-32 A Seckel syndrome patient exhibited with metabolic problems

Abstract Introduction Seckel syndrome is a disease with nine distinct phenotypes that is inherited autosomally recessively and is caused by DNA damage on chromosomes 3, 13, and 18. It is also known as 'bird-headed dwarfism' due to the disease's characteristic phenotypic features, microcephaly and dwarfism. In addition to mental retardation, other possible complications include bilateral optic atrophy, strabismus, hearing difficulties, micrognathia, microdontia, hypodontia, malocclusion of the mandible, scoliosis, bone anomalies, hematological, endocrinological, genitourinary, neurological anomalies (epilepsy, etc.), and cancers. Presented here is a patient with metabolic dysfunction who has been diagnosed with Seckel's syndrome. Clinical Case A male patient, age 22, was admitted to the endocrinology outpatient clinic for regulation of hyperglycemia. The patient's medical history included diabetes of type 2 since 2021, hypothyroidism, mental retardation, and hepatosteatosis. His parents were related as first cousins. One of the patient's two brothers has been diagnosed with Seckel syndrome. On his physical examination, his temperature was 36.1°C, his blood pressure was 92/61 mmHg, his heart rate was 76 beats per minute, his height was 125 cm, his weight was 19 kg, and his BMI was 12 kg/m2. Microcephaly, hypodontia, and micrognotia were observed. The patient was using insulin glargin 32 units, insulin aspart 2×18 units, metformin 500mg once day, and levothyroxine sodium 50mcg. In blood glucose follow-ups, the highest was 304 mg/dl and the lowest was 127 mg/dl, whereas Hba1c was 7.5% and c-peptide was 2.44 ng/ml. Anti-GAD, anti-islet cell, anti-TPO, and antithyroglobulin antibodies were negative. Insulin glargine was changed to 34 units, and insulin aspart was changed to 2×20 units. Due to mental retardation and hypodontia, it was discovered that the patient could not pay attention to his diet, could hardly eat solid foods, and was provided primarily liquids, particularly sugar-sweetened, flavored, and carbonated soft drinks. The patient was referred to the dental polyclinic and dietitian, while the family was monitored at the genetics polyclinic. Conclusion Follow-up care for patients with Seckel syndrome should include routine metabolic screening. Due to the patient's mental cooperation and dietary habits resulting from dental anomalies, metabolic control may be challenging. To ensure metabolic homeostasis in these patients, a multidisciplinary approach is necessary, involving the patient, his or her family, in multidisciplinary setting.

THU310 A Presentation Of Diabetic Ketoacidosis In Gestational Diabetes

Abstract Disclosure: C. Yim: None. S.L. Liu: None. T. Spaic: None. Diabetic ketoacidosis (DKA) is a diabetic emergency characterized by wide anion gap acidosis, presence of ketones (in serum and/or urine) and, frequently, uncontrolled hyperglycemia. In pregnancy, DKA more commonly occurs in women with pre-existing diabetes, usually type 1 diabetes, and is exceptionally rare in women with gestational diabetes mellitus (GDM). We report a case of a 37-year-old woman in her second pregnancy who presented to hospital with DKA at 29+3 weeks gestation shortly after diagnosis of GDM 4 days earlier. In her first pregnancy, she was diagnosed with GDM at 28 weeks, required treatment with metformin at 35 weeks, which she stopped postpartum. She conceived her second pregnancy 3 months postpartum so was not screened for diabetes postpartum. In her second pregnancy, there was no evidence of diabetes on early antenatal labwork at 7 weeks: Hemoglobin A1c (HbA1c) 5.6%, random glucose 3.6 mmol/L. Early GDM screening at 21+1 weeks with 75 gram oral glucose tolerance test (OGTT) was normal: fasting glucose 4.4 mmol/L 1-hour glucose 9.0 mmol/L, 2-hour glucose 6.5 mmol/L. She presented to hospital at 29+3 weeks gestation with a 2-day history of polyuria, polydipsia, dizziness, and decreased oral intake without nausea or vomiting. Four days prior to presentation, she was diagnosed with GDM on a 75g OGTT (fasting glucose 6.2 mmol/L, 1-hour glucose 15.1 mmol/L, 2-hour glucose 11.9mmol/L). Admission labwork showed serum glucose 34.8 mmol/L, anion gap 18, pH 7.29, bicarbonate 17 and beta-hydroxybutyrate 2.97. She was treated with IV fluids and insulin and initiated on multiple daily injections of insulin. Other than pregnancy, no clear precipitating factor was found. HbA1C was 6.4%, serum insulin and C-peptide levels were inappropriately low at 22 pmol/L and 296 pmol/L respectively. Her anti-glutamic acid decarboxylase and anti-islet cell antibodies were negative. Lipase was mildly elevated at 226U/L but improved to 144U/L with treatment. Abdominal ultrasound did not demonstrate any findings suggestive of acute pancreatitis. Her 24-hour urinary free cortisol was 366 nmol and 442 nmol, both within normal trimester-specific range. Her salivary cortisol was in the normal range (10.5nmol and 10.9nmol). Following discharge, she remained significantly insulin resistant with suboptimal glycemic control (total daily insulin requirements ∼3.5 units/kg/day, HbA1C 7.9% at 35+6 weeks). Due to increased insulin resistance in pregnancy, DKA can progress more rapidly compared to nonpregnancy. Given increased rates of perinatal morbidity and mortality associated with DKA, treatment and monitoring should be promptly initiated. A high index of suspicion is especially important given that DKA is a rare presentation in GDM. Other precipitating factors of newly decompensated diabetes should also be ruled out. Presentation: Thursday, June 15, 2023

THU374 Fulminant Type 1 Diabetes Mellitus And DKA Secondary To Pembrolizumab

Abstract Disclosure: I. Iqbal: None. M. Khan: None. M. Ahmad: None. R. Mehreen: None. Introduction: Pembrolizumab is a programmed cell death receptor (PD-1) binder on T cells, which promotes their activation against cancer cells. It can also cause unwanted T cell activation against the body’s own cells, leading to type 1 diabetes mellitus (DM1), among other autoimmune phenomena. We are reporting a case of a new onset pembrolizumab-induced fulminant DM1 who presented with diabetic ketoacidosis (DKA). Despite the emerging data on immune checkpoint inhibitors (ICPI), fulminant DM1 with DKA in a previously nondiabetic patient is still uncommon. Case Presentation: A 66-year-old female with a history of recurrent metastatic non-small cell lung cancer (NSCLC) presented to the emergency room (ER) with an extensive itchy rash. She was enrolled in a clinical trial for NSCLC, where she received immunotherapy with pembrolizumab for five months. Rash was treated outpatient for scabies, with no improvement. She was then started on prednisone 40mg daily and betamethasone 0.05% cream. She applied the cream daily but took prednisone orally for only one day, after which she could not tolerate it due to anxiety and restlessness. She ran out of betamethasone three days before coming to ER. On admission, vitals were: Heart rate 90 beats per minute, blood pressure 119/95 mmHg, respirations 20/minute. The exam showed flushed cheeks, red and dry macules on the skin with excoriations, and dry mucus membranes. Random blood glucose levels (BSL) were 660mg/dl. Labs were; HCO3 16mmol/L, Beta-hydroxy butyrate 20mmol/L, anion gap 17mmol/L, Hemoglobin A1c: 5.6%. For DKA, we started an insulin drip. Workup revealed very low C-peptide levels of 0.2ng/ml, with a concomitant BSL of 500mg/dL. Anti-islet cell and anti-glutamic acid decarboxylase antibodies (anti-GAD) were positive with levels of 0.04 nmol/L and 0.07 nmol/L, respectively. Once she stabilized and the anion gap closed, she was transitioned to subcutaneous insulin and discharged on 42 units of Lantus, along with 12 units of premeal Lispro and sliding-scale insulin. She was removed from the clinical trial due to complications. Unfortunately, she got readmitted with influenza A, Staphylococcus aureus bacteremia, and another episode of DKA, complicated with respiratory failure, and she decided on hospice. The patient passed away after two days. Conclusion: Immune-related adverse event of new-onset fulminant DM1, leading to DKA, is a serious and potentially fatal complication of pembrolizumab. For patients receiving pembrolizumab, who have uncontrolled BSL, we suggest checking the anti-islet cell and anti-GAD antibody levels and DKA risk stratification to allow the timely initiation of insulin and prevent further complications. Presentation: Thursday, June 15, 2023

La ricerca degli anticorpi anti-insula pancreatica in immunofluorescenza è ancora necessaria nell'inquadramento diagnostico del diabete autoimmune?

Multiple laboratory tests are used to diagnose and manage patients with diabetes mellitus and autoantibody assays are increasingly available to clinicians. However, the quality of the scientific evidence supporting the use of these tests varies substantially. The aim of this review is to evaluate the state of the art of antibody diagnostics in type 1 diabetes mellitus (T1D), examine all available autoantibodies, their frequency of use and the most established combinations, including advantages and disadvantages of the related dosages and alternative methods of detection. The use of autoantibody tests in diabetes must be optimized based on age, type of patient and diagnostic suspicion suggested by the clinical picture. To date, the combination of islet cell antibodies now available with sensitive, specific, and automated methods, allows the identification of 95-98% of T1D cases and the positive predictive value of the combination of autoantibody markers (GADA, IA-2A, ZnT8A) immunometrically measured is much higher than that provided by the anti-islet cell antibodies (ICA) test in immunofluorescence (IIF). According to the current literature, it is increasingly clear that measurement of ICA in IIF is no longer recommended, as it could reasonably be replaced by the direct measurement of individual autoantibodies.

Prevalência de outras doenças autoimunes em crianças e adolescentes com diabetes mellitus tipo 1

OBJECTIVE: To evaluate the prevalence of autoimmune markers associated with beta-pancreatic cells, autoimmune thyroid diseases and celiac disease through research of anti-glutamic acid decarboxylase antibodies (GADA), antiislet cell antibodies (ICA), anti-insulin antibodies (IAA), anti-tyrosine phosphatase (IA-2A), anti-transglutaminase antibodies (anti-tTG), anti-endomysium anti-transglutaminase antibodies (EMA ), immunoglobulin A (IgA), thyroperoxidase antibodies (anti-TPO) and thyroglobulin antibodies (anti-TG), in addition to related hormonal measurements in children and adolescents with type 1 diabetes mellitus. METHODS: Observational, longitudinal study, with retrospective data collection by reviewing the medical records of 92 children and adolescents, diagnosed with DM1 between January 2014 and December 2016, seen at a Pediatric Endocrinology service of a tertiary hospital in Curitiba- PR. RESULTS: At the diagnosis of DM1, the prevalence of anti-GAD antibody positivity was 69.6% (n = 79), ICA 42.9% (n = 70), IAA 32.8% (n = 64), IA2 of 60.6% (n = 33). Positivity for markers of other associated autoimmune diseases was 27.4%, EMA 6.0% (n = 50), anti t-TG IgA 12.5% (n = 8), anti-TPO 13, 1% (n = 84) and 22.9% anti-TG (n = 83). Autoimmune thyroid diseases were the most frequently found comorbidity at diagnosis (22.1%). Among patients with positivity for antithyroid antibodies, 19% developed clinical hypothyroidism. CONCLUSIONS: Patients with DM1 have a high prevalence of autoimmunity. The importance of screening for such diseases to diagnosis and clinical follow-up is reinforced, in order to assist in predicting the development of associated diseases and their complications, as well as providing adequate treatment.

Was It a Case of “Flatbush Diabetes” with Severe Hypertriglyceridemia?

AbstractWe present a case of a morbidly obese 27 years male patient who was admitted with sudden onset abdominal pain and crashed into diabetic ketoacidosis as new-onset diabetes and discuss the possible etiology of this combined picture of acute pancreatitis and severe hypertriglyceridemia. Flatbush diabetes was, meanwhile, thought of due to his morbid obesity that in turn raised our suspicion of acute insulin-requiring type 2 diabetes mellitus versus T1 diabetes mellitus. Ketosis-prone diabetes or Flatbush diabetes is a syndrome in which diabetes commences with ketoacidosis in patients who are glutamic acid decarboxylase and antiislet cell antibody negative and have no known precipitating causes. They are usually middle-aged, overweight, or mildly obese, and in many reports, they are likely to be male with a family history of type 2 diabetes mellitus; they present with new-onset severe hyperglycemia and ketosis or frank diabetic ketoacidosis. After intensive initial insulin therapy, many patients become insulin-independent and can be well controlled on diet plus oral medications or, more rarely, diet alone.

Abstract #1185190: New Onset Autoimmune Diabetes Associated with Acute SARS-COV-2 Infection

Infection with SARS-CoV-2 has been shown to cause complications affecting nearly all organ systems of the human body. Here, we outline a case of SARS-COV-2 associated with new onset of autoimmune diabetes. A 62-year-old female with past medical history of class III obesity, primary hypothyroidism, obstructive sleep apnea, and endometrial cancer established care with a multidisciplinary bariatric team in March 2021. This team included a dietician and psychologist to promote healthful lifestyle intervention with the intent to undergo bariatric surgery in December 2021. At a follow up visit in September 2021 her HbA1c was 6.7% (normal < 5.7 %) and she was diagnosed with type 2 diabetes treated with healthful lifestyle. After lifestyle modification the patient successfully lost 40 pounds. In December 2021, she presented to the ED (Emergency Department) complaining of fatigue and neuropathy. She was found to be hyperglycemic with glucose 369 mg/dL (normal 70-100 mg/dL). β-hydroxybutyrate was 32.1 mg/dL (normal 0.20-2.81 mg/dL) and anion gap was 10 mmol/L (normal 3-13 mmol/L). She was resuscitated with fluid and referred urgently to Endocrinology. One week later, she was seen in the office by her endocrinologist for initial consultation. She was acutely complaining of anosmia and ageusia and found to be positive for acute SARS-COV-2 infection. Bloodwork revealed an increase in HbA1c to 13.9 %, fasting glucose 303 mg/dL (normal 70-100 mg/dL), normal C-peptide 1.6 ng/dL (normal 0.5-3.3 ng/dL), elevated GAD antibody 154.3 IU/mL (normal 0-5 IU/mL), elevated anti-Islet Cell antibody IgG ratio 1:64 (normal < 1: 4), elevated anti-Islet Antigen 2 antibody >120 U/mL (normal 0–7.4U/mL), and elevated anti-Zinc Transporter 8 antibody 500 U/mL (normal 0–15 U/mL). Patient was diagnosed with autoimmune diabetes associated with acute SARS-COV-2 infection and was started on basal-bolus insulin with improvement in her hyperglycemia. She did not require hospital admission or steroid treatment for SARS-COV-2 infection. Although viral infections are associated with type I diabetes related autoimmunity in children, this case study is unique regarding its mechanism in association with SARS-CoV-2 infection. Potential mechanisms underlying onset of diabetes in patients with SARS-COV-2 infection are still under investigation. One potential mechanism involves pancreatic beta cell dysfunction with diminished insulin secretion due to a systemic inflammatory cascade. This case is unique in as the patient’s C-peptide was still detectable indicating intact beta cell function. Furthermore, the patient’s diabetes paradoxically worsened after a more healthful lifestyle and 40-pound weight loss. This patient’s case of autoimmune diabetes illustrates the need for further research into the mechanisms underlying the onset of diabetes after SARS-COV-2 infection.

Crohn's disease and peptic ulcer disease: A personal comparative analysis

Until the Hruska Postulate and its intellectual fulfillment [1-7], Crohn's disease was a disease entity without either cure or validation. The explanation put forward for its pathogenesis is that the body's immune system selectively turned against something within the gastrointestinal tract. That disruption of the immune system's pro-inflammatory Th1 response could produce evidence of mucosal healing and temporary abatement of disease was aggressively pushed as documentation of the concepts validity. Crohn's disease became the linchpin for 193 journals, 86 conferences and 15,631 articles about or related to autoimmunity. When sought for antibodies to a specific target organ could be demonstrated in a number of diseases. In congenital rubella, the presence of anti-islet cell antibodies introduced the hypothesis that autoimmunity was responsible for the higher incidence of abnormal glucose tolerance tests observed [9]. An equally plausible explanation was that the documented viral replication within islet cells of the pancreas sufficiently altered cellular structure so as to create cross-reacting antibodies. Most claims of autoimmunity have been based upon the demonstration of an antibody that cross-reacts with a cell or subunit within the target organ.

1184-P: Return to Normal Glucose Control by Weight Loss in Nonobese People with Type 2 Diabetes: The ReTUNE Study

Type 2 diabetes (T2D) in the non-obese has been regarded as etiologically distinct from that in obese people. However, clinical observation suggests that loss of fat mass above a personal fat threshold brings about remission in the same way. ReTUNE aimed to determine what proportion of T2D people with BMI &amp;lt;27kg/m2 could achieve remission, and to assess the fat threshold for this. 25 participants have been studied to date (T2D: 4M/10F, 58.3±2.1years, BMI 24.5±0.6kg/m2; matched nondiabetic controls: n=11). Other types of diabetes were excluded by anti-islet cell antibodies and MODY gene tests (2/14). From baseline, weight loss of 5% was achieved in 2-4 weeks using low calorie diet (800 kcal/day), then 6 weeks of weight maintenance. The cycle of weight loss plus maintenance was repeated 2-3 times until the clinical end point of remission was reached (HbA1c &amp;lt; 6.5%). Only 2 cycles (~10% weight loss) were required in 8/12 participants. The planned decrease in weight (baseline to clinical endpoint: 69.0±3.5 to 60.8±2.9kg, p&amp;lt;0.001) decreased total body fat from 33.1±1.9 to 27.4±2.0% (p&amp;lt;0.001). Fasting plasma glucose decreased from 7.3±0.3 to 6.3±0.3 mmol/l, p&amp;lt;0.05). HbA1c decreased from 7.1±0.2 to 6.5±0.1%, p&amp;lt;0.05 with 8/12 in remission (&amp;lt;6.5%). Fasting plasma insulin decreased (52.2±9.5 to 23.7±3.6 pmol/L, p=0.007) as did plasma triglyceride (1.6±0.2 to 1.0±0.1mmol/L, p=0.002). Liver fat fell from 4.4±0.8 to 1.4±0.1% (p=0.004) becoming similar to 11 matched healthy controls (1.9%). Pancreas fat content in T2D fell (5.1± 0.6 to 4.5±0.6%, p=0.026) towards control levels (3.3±0.3%, p=0.029 vs. T2D at baseline). Post meal insulin sensitivity (Si) and insulin secretion (disposition index and β-cell responsivity Φtot) improved after weight loss. In conclusion, 2/14 people with BMI &amp;lt;27kg/m2 were found to have other diagnoses, and weight loss brought about remission in 8/12 people accompanied by pathophysiological changes similar to those seen during remission in obesity-associated T2D. Disclosure A. Al-mrabeh: None. A. C. Barnes: None. K. M. Irvine: None. T. L. Kelly: Employee; Self; Diabetes Digital Media. K. G. Hollingsworth: None. D. Romeres: None. C. Cobelli: None. R. Taylor: Speaker's Bureau; Self; Novartis AG. Funding Diabetes UK (17/0005645)

A Rare Cause of Diabetes: COVID-19

A Rare Cause of Diabetes: COVID-19 Introduction: Environmental factors like viruses have been described in the mechanism of pancreatic beta cell destruction. Various viruses can trigger autoimmunity in individuals genetically predisposed to diabetes. Severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) has been shown to bind to angiotensin-converting enzyme 2 (ACE 2) which is expressed throughout the body, including pancreatic cells, leading to direct injury of the endocrine pancreas. We report a case of coronavirus infection disease 2019 (COVID-19) causing a new onset of diabetes mellitus presentation with hyperglycemia, polyuria, polydipsia and weight loss. Case Presentation: A 53 year-old, previously healthy, male presented with five days of fever, fatigue, dry cough, dyspnea and diarrhea. On admission he was hypoxic, with a body mass index of 25 kg/m2 and no evidence of insulin resistance on physical exam. He was diagnosed with SARS CoV-2 and admitted for high requirements of oxygen without the need of the intensive care unit. He was treated with tocilizumab, atazanavir, hydroxychloroquine, full dose anticoagulation and azithromycin. Dexamethasone 4 mg every 8 hours was given for three days. During this admission, his fasting glucose was 75–108 mg/dL. Once started on steroids his fasting and prandial glucose was 85–96 mg/dL and 140 mg/dL on one occasion. He was eventually discharged with 2 liters of nasal cannula which he required for one week. One and a half months after, he presented to the emergency department due to a 6 kg weight loss, polyuria, polydipsia, malaise and fatigue. On arrival his glucose was 549 mg/dL, without anion gap or ketones. He had no evidence of new infection and SARS CoV-2 test was negative. He was started on insulin glargine at night and insulin Humalog before each meal with corrections. Hemoglobin A1c was 13.4% with a C-peptide 0.36 ng/mL and glucose of 195 mg/dL at the time of C-peptide test. His antibodies, anti-islet cell antibody, zinc transporter 8 and glutamic acid decarboxylase-65, were negative. He was discharged with basal/bolus regimen and followed up outpatient with Endocrinology. During follow-up, his c-peptide normalized and he was tapered off insulin. Discussion: In 2003, atypical pneumonia caused by SARS CoV-2 was reported to be associated with hyperglycemia in patients without prior history of diabetes. At 3 year follow-up, the patients no longer had diabetes. Moreover, patients with mild SARS CoV-2 during the first day of hospitalization had a higher fasting plasma glucose than patients admitted for other causes of pneumonia. It is known that SARS CoV-2 binds to ACE 2 which downregulates the receptor, leading to impairment of insulin secretion and hyperglycemia. SARS CoV-2 also produces a direct injury in beta pancreatic cells. It is imperative to monitor patients post COVID-19 to evaluate for new onset diabetes and likely resolution.

A case of newly diagnosed autoimmune diabetes in pregnancy presenting after acute onset of diabetic ketoacidosis

Abstract Objectives We present a case of immune-mediated diabetes mellitus, diagnosed in pregnancy upon presentation with diabetic ketoacidosis, found to have normal glucose control postpartum. Case presentation A 28-year-old medically uncomplicated G1P0 presented in diabetic ketoacidosis at 28.2 weeks gestation. Workup for pancreatic autoantibodies revealed indeterminate anti-islet cell antibodies and positive anti-glutamic acid antibodies. She was stabilized with intravenous fluids and insulin, and transitioned to long and short acting subcutaneous insulin. Her insulin requirements decreased over the course of her pregnancy. Spontaneous vaginal delivery occurred at 37 weeks. Her postpartum glucose control was normal without re-initiation of insulin. Conclusions The diagnosis of diabetic ketoacidosis during pregnancy should prompt further investigation into an underlying diagnosis of immune mediated diabetes. These patients should be followed closely in the postpartum period.

Anti-Islet Cell Antibody and Anti-ovarian Antibody Levels in Iraqi Women with Polycystic Ovary Syndrome

Anti-Islet Cell Antibody and Anti-ovarian Antibody Levels in Iraqi Women with Polycystic Ovary Syndrome

Serum immune profiling of patients with polycystic ovary syndrome

Background: Polycystic ovary syndrome (PCOS), the most prevalent hormonal disorder in females, is characterized by low levels of progesterone, which causes increased estrogen levels leading to production of various anti and auto-antibodies. This study aimed to estimate and compare levels of anti-nuclear antibodies (ANA), anti-thyroid peroxidase (anti-TPO), anti-thyroglobulin (anti-TG), and anti-islet cell antibodies (anti-ICAb) in patients with PCOS and healthy controls. Methods: The present comparative study included 82 subjects divided into two groups with 41 individuals in each group. Group I included healthy subjects, while Group II included patients diagnosed with PCOS. Blood samples were collected to determine serum levels of ANA, anti-TPO, anti-TG, and anti-ICAb using commercially available ELISA kits. Data were analyzed by using SPSS 20.0. Results: Two (4.8%) subjects in Group II had ANA, but none of the other healthy individuals had these auto-antibodies. Levels of anti-TPO were higher in Group II (6.01 IU/ml) than in Group I (5.98 IU/ml). Levels of anti-TG and anti-ICAb were higher in Group I (19.86 and 32.49 IU/ml, respectively) than in Group II (19.78 and 26.07 IU/ml, respectively). Conclusion: Levels of ANA and anti-TPO were higher in patients with PCOS than in controls. By contrast, levels of anti-TG and anti-ICAb were higher in controls than in patients with PCOS.

SAT-LB116 Extreme Insulin Resistance: The Diagnostic Challenges When Cost Is a Limitation

Introduction: Insulin resistance occurs most commonly in association with obesity but may result from multiple causes, e.g. medications, lipodystrophy, or antibodies to insulin or insulin receptors. We review a case of an unusual presentation of insulin resistance. We highlight challenges of diagnostic testing and treatment when there are cost limitations. Clinical Case:A 41 year old Hispanic male with T2DM and a history of well-controlled BPD on quetiapine only presents for management of diabetes. His current treatment is metformin and a TDD of 170 U human insulin; A1C is 12.2%. He was diagnosed at age 32 via routine lab tests. At diagnosis BW was 96.4 kg, BMI 29, BP 100/70, CHOL 152, TG 247, HDL 35, LDL 68. Physical exam was unremarkable without acanthosis or lipodystrophy. Anti-GAD, anti-islet cell antibodies, insulin and C-peptide levels were ordered, but not obtained due to cost. He was managed with lifestyle modification for 2 years with maintenance of A1C <7%. At age 35 he developed symptomatic hyperglycemia with A1C 9.4% and was started on metformin and glyburide. At age 36 A1C was >11%, with no change in BW. Glargine 5 U was added, and glyburide was changed to glipizide. Glargine was increased to 40 U without changes in glycemia. At age 37 glipizide was stopped, and he could not afford glargine. He was switched to 70/30 human insulin. Insulin dosages were progressively increased to 220 U a day with no change in glycemia. Liraglutide was tried but not continued due to cost, and quetiapine was switched to trazodone without improvement in A1C. LFTs, CBC, HIV, Hepatitis C and B have been negative. The patient has had multiple visits for education with documented adequate disease understanding and performance of injections. Nonadherence was suspected; for its evaluation, the patient was observed in clinic self-injecting 30 U of regular insulin (brought from home); fasting was confirmed for 3hrs post-injection. BG was 327mg/dL pre-injection and 326mg/dL 3hrs post-injection. Insulin antibodies were requested but not obtained due to cost. Insulin receptor antibodies are not commercially available in the US. Potential empiric strategies, e.g. the NIH protocol for insulin type B resistance (rituximab + dexamethasone + cyclophosphamide) was considered but cost is a limitation. We discussed steroids or methotrexate for possible antibody mediated insulin resistance versus a trial of thiazolidinedione, which has been reported to decrease severe insulin resistance in patients with lipodystrophy. The patient opted to initially try a thiazolidinedione. Conclusion:Although poor adherence has not been excluded, the patient appears to have no response to high doses of injected human insulin, suggesting extreme insulin resistance. Cost limitations preclude optimal diagnostic evaluation. Empiric treatment with low cost options potentially may provide diagnostic information as well as efficacious treatment.

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.

Determination of anti-pancreatic islet cell antibodies for the prevention of type 1 diabetes mellitus as an immune-related adverse event secondary to treatment with immune checkpoint inhibitors

Abstract Background Type 1 diabetes mellitus (T1D) as an immune-mediated effect of immunotherapy-based oncology treatments is observed in 0.5-5% of the patients. Prevention of these symptoms is based on the determination of the basal sugar levels on an empty stomach after the administration of each dose of the drug. The objective of this clinical review is assessing the incorporation of anti-pancreatic islet cell antibodies in the prevention of these events. Methods A clinical review was carried out with the published cases of T1D secondary to immunotherapy between the years 2012 and 2019 in the current medical literature. We analyzed the determination of anti-pancreatic islet cell antibodies in patients who presented diabetes as an immune-mediated effect, as well as their phenotypic characteristics, the analysis levels and the drugs that had been used. Results Between 2012 and 2019 a total of 81 cases have been reported. The two most commonly described molecules were Nivolumab and Pembrolizumab (72/81, 90%), with an average age of 67 years and a predominance of men. Anti-b cell antibodies were observed in 36/81 patients (44%), with a similar frequency between the monotherapy group (31/70, 44%) and the group with combined therapy of anti-CTLA4 and anti-PD1 or PDL1 (5/11, 45%). The most commonly found antibody related to these events was antiglutamic acid decarboxylase (GAD) (34/81, 42%). No antibodies were found prior to the administration of the drug. Table . 65P Diabetes-related autoantibodies • Anti-GAD 34/81 (42%) • Anti-islet cell antibody (ICA) 1/81 (1.2%) • Anti-insulin antibody (IAA) 2/81 (2.5%) • Anti-islet antigen 2 antibody (IA2A) 4/81 (5%) • Anti-zinc transporter 8 antibody (ZnT8A) 1/81 (1.2%) Conclusion Determining the level of antibodies related to diabetes prior to the treatment with immunotherapy and during the treatment may prevent immunemediated diabetes. An assessment of the positivity of antibodies at the beginning of the treatment or of seroconversion during administration (as described in the literature) may have an influence on the detection of the development of T1D. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.

MON-153 Spurious High HbA1c: Do We Need to Review the Guidelines?

Background: Diabetes UK welcomes the 2011 decision by the WHO to accept the use of HbA1c testing in diagnosing diabetes. HbA1c of 48mmol/mol (6.5%) is recommended as the cut off point for diagnosing diabetes. A value of less than 48mmol/mol (6.5%) does not exclude diabetes diagnosed using other glucose tests. NICE guidelines recommend use of two consecutive high HbA1c in absence of symptoms to diagnose type 2 diabetes. Case report: A 51-year-old female was referred for diabetologist review of her newly diagnosed type 2 diabetes. The diagnosis was made in accordance with the NICE and WHO guidelines, based on two consecutive HbA1c results of 8.1% (65 mmol/mol). Her repeated fasting and postprandial plasma glucose were normal and she has no osmotic symptoms. Her fructosamine was normal. Her oral glucose tolerance test was normal as well. Her anti GAD and anti-islet cell antibodies are negative. The patient’s haematological indices were normal and she was unaware of any family history of hemoglobinopathy. She has family history of type 1 diabetes. After all these normal blood sugar reading, the diagnosis of diabetes was refuted and her treating GP was contacted to erase the diagnosis of type 2 diabetes from her medical record.. She was rejected in more than one occasion as a blood donor due to autoantibodies. We are not aware of any correlation between falsely high HbA1c and the presence of autoantibodies, currently we are investigating that. We are sure during the conference of endo 2019; we will have a clear answer. We are aware of case report from Canada of similar scenario of false positive HbA1c published in 2015(1). Conclusion: 1. We are investigating now the cause of this lady spurious high HbA1c. Whatever cause would be found, this case questions the usefulness of HbA1c as solo in diagnosing type 2 diabetes. Although all the limitations of HbA1c must be addressed but we do not think it is cost effective to rule out all causes of false positive HbA1c before depend on HbA1c in the diagnosis of diabetes type especially in the presence of cheap and well validated other tests like oral glucose tolerance test, plasma fasting and postprandial blood glucose. 2. We recommend that high HbA1c must be confirmed by another well validated way of diabetes diagnosis such as osmotic symptoms or/and abnormal blood sugars readings to confirm the diagnosis of type 2. Reference: 1-Erroneous Diabetes Diagnosis: A Case of HbA1c Interference. Diabetes Care 2015;38:e154-e155.