Anti-glutamic Acid Decarboxylase Research Articles

Frequency of C-peptide and antibody levels (anti GAD, Islet cell antibodies, insulin auto antibodies) in children of Pakistan with Type-1 diabetes

Background and Objective: The autoimmune mechanism in T1DM causes gradual loss of pancreatic β-cell, which progresses to hyperglycemia and ultimate reliance on consistent insulin therapy. T1DM has been the commonest type of diabetes in children and this study will help in refining indulgent towards the problem and its pathophysiology in our people. The objective was to find out the prevalence of C-peptide and antibody levels (anti GAD, ICA, IAA and IA2) in children and adolescents of Pakistan with T1DM. Methods: We conducted this cross-sectional study at Department of Pediatric Endocrinology, National Institute of Child Health, Karachi between August 2019 to February 2020 and included 98 children who had T1DM for more than one month. Subjects whose GFR was <30ml/min were omitted from the study. Among those registered subjects, C-peptide, human islet cell antibody (ICA), insulin auto antibodies (IAA) and anti-glutamic acid decarboxylase were assessed. Demographical and laboratorial facts were noted on a pre-constructed proforma. Results: There were 77(78.3%) cases who had level of C-peptide <0.8 and anti-GAD was found in 47(48%) subjects. 35(35.7%) cases found positive for IA2 .and 7(7.1%) patients had insulin auto antibodies positive while ICA was negative in total 98(100%) subjects. Conclusion: Children with T1 DM possessed increased levels of anti-GAD antibodies, insulin autoantibodies and anti (IA2) but islet cells antibodies were negligible in our population when checked at a point of time. C-peptide may be normal in some, but its level declines with long duration of diabetes in children. doi: https://doi.org/10.12669/pjms.40.6.7794 How to cite this: Riaz M, Akram M, Ibrahim MN, Khoso ZA. Frequency of C-peptide and antibody levels (anti GAD, Islet cell antibodies, insulin auto antibodies) in children of Pakistan with Type-1 diabetes. Pak J Med Sci. 2024;40(6):1083-1086. doi: https://doi.org/10.12669/pjms.40.6.7794 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

The significance of precise diabetes diagnosis: a case of euglycemic diabetic ketoacidosis induced by the introduction of empagliflozin with simultaneous reduction of insulin dosage

Euglycemic diabetic ketoacidosis (euDKA) is a rare but severe metabolic complication of diabetes mellitus characterised by elevated anion gap metabolic acidosis despite normal or mildly elevated blood glucose levels. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have emerged as effective antidiabetic medications, yet their use is associated with an increased risk of euDKA, especially when coupled with insulin dose reduction. We present the case of a 50-year-old male with a 20-year history of diabetes mellitus, initially managed with insulin and metformin, who developed euDKA following the introduction of empagliflozin and sitagliptin alongside a reduction in insulin therapy. Despite normoglycaemia the patient exhibited symptoms of ketoacidosis, including chronic fatigue, polydipsia, and polyuria. Diagnostic workup revealed metabolic acidosis, elevated inflammatory markers, acute kidney injury and ketonuria. Subsequent specialised laboratory tests confirmed type 1 diabetes mellitus (T1DM) with the presence of anti-glutamic acid decarboxylase (anti-GAD) antibodies and the absence of C-peptide secretion. Management involved fluid therapy, intravenous insulin and glucose administration. This case underscores the diagnostic challenges of euDKA and emphasises the importance of differentiating between T1DM and T2DM, as management strategies vary significantly. Patient education on insulin therapy and injection techniques is crucial to prevent complications such as improper insulin delivery and dose reduction, which can precipitate euDKA. In conclusion, clinicians should be vigilant for euDKA in patients on SGLT2 inhibitors, particularly when insulin dose reduction is involved. Comprehensive patient education and accurate differentiation between diabetes types are essential for timely diagnosis and optimal management, thereby reducing the risk of severe complications.

Immune Ataxias: The Continuum of Latent Ataxia, Primary Ataxia and Clinical Ataxia.

The clinical category of immune-mediated cerebellar ataxias (IMCAs) is now recognized after 3 decades of clinical and experimental research. The cerebellum gathers about 60% of neurons in the brain, is enriched in numerous plasticity mechanisms, and presents a large variety of antigens at the neuroglial level: ion channels and related proteins, synaptic adhesion/organizing proteins, transmitter receptors, and glial cells. Cerebellar circuitry is especially vulnerable to immune attacks. After the loss of immune tolerance, IMCAs present in an acute or subacute manner with various combinations of a vestibulocerebellar syndrome (VCS), a cerebellar motor syndrome (CMS), and a cerebellar cognitive affective syndrome/Schmahmann's syndrome (CCAS/SS). IMCAs include gluten ataxia (GA), post-infectious cerebellitis (PIC), Miller Fisher syndrome (MFS), paraneoplastic cerebellar degeneration (PCD), opsoclonus myoclonus syndrome (OMS), anti-glutamic acid decarboxylase (anti-GAD) ataxia, and glial fibrillary acidic protein (GFAP) astrocytopathy (GFAP-A). In addition, multiple sclerosis (MS), acute disseminated encephalomyelitis (ADEM), Behçet disease, and collagen-vascular disorders may also present with cerebellar symptoms when lesions involve cerebellar afferences/efferences. Patients whose clinical profiles do not fit with IMCAs are now gathered in the group of primary autoimmune cerebellar ataxias (PACAs). Latent auto-immune cerebellar ataxia (LACA) refers to a clinical stage with a slow progressive course and a lack of obvious auto-immune background. At a pre-symptomatic stage, patients remain asymptomatic, whereas at the prodromal stage aspecific symptoms occur, announcing the symptomatic neuronal loss. LACA corresponds to a time-window where an intervention could lead to preservation of plasticity mechanisms. Patients may evolve from LACA to PACA and typical IMCAs, highlighting a continuum. Immune ataxias represent a model to elucidate the sequence of events leading to destruction of cerebellar neuronal reserve and develop novel strategies aiming to restore plasticity mechanisms.

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.

Successfully treated anti-GAD limbic encephalitis in a 15-year-old diabetic boy with intravenous immunoglobulin: case report

Introduction and importance: Limbic encephalitides (LE) have symptoms and signs of new-onset seizures accompanied by cognitive impairment and signal changes in the MRI of the limbic system in the brain. Numerous antibodies against the neurons and synapses have been detected so far. Of those, antiglutamic acid decarboxylase antibody (Anti-GAD Ab) impairs the gamma amino butyric acid, one of the primary mediators that naturally prevents abnormal neuronal activity causing seizure. Case presentation: The authors have reported a case of anti-GAD Ab LE in a diabetic male adolescent who responded dramatically to intravenous immunoglobulin and reviewed all similar pediatric cases for 15 years now. Clinical discussion: The symptoms in children suffering from anti-GAD LE in three categories, systemic, psychiatric, and neurological, are heterogeneous. The most common manifestations were seizures followed by altered mental status and behavioral changes, respectively. The two main clinical scenarios described in GAD65-mediated autoimmune epilepsy are (1) an acute/subacute onset of seizures alone or seizures (including new-onset refractory status epilepticus, NORSE) accompanied by some degrees of cognitive and psychiatric manifestations, including amnesia and mesiotemporal inflammatory involvement consistent with LE and (2) epilepsy without clinical or MRI evidence of active central nervous system inflammation. Conclusion: Although rare, the neurologist should consider the potential role of anti-GAD ab-associated encephalitis in the presence of diabetes mellitus.

O-07 Lipodystrophy: A disease to be considered in diabetes clinics

Abstract Introduction Lipodystrophy syndromes are disorders with no adipose tissue. Lipodystrophy is classified based on the degree of adipose tissue deficiency, distinguishing between partial and generalized forms, and considering if it is inherited or acquired. The condition is characterized by ectopic steatosis, severe dyslipidemia, insulin resistance, and severe comorbidities including uncontrolled diabetes mellitus (DM), acute pancreatitis, hepatic cirrhosis, proteinuria, renal failure, and premature cardiovascular disease. Congenital Generalized Lipodystrophy (CGL, Berardinelli-Seip Syndrome) is inherited autosomal recessively. Four genetic mutations linked to CGL have been identified: AGPAT2, BSCL2, CAV1, and PTRF. This report describes a case of a patient with uncontrolled diabetes and other health conditions. The patient was diagnosed with CGL2 as an adult after admission to our facility. Clinical Case This case involves a 43-year-old female patient seeking help for glycemic control and menstrual cycle irregularities. She was diagnosed with DM at 24 and received care at multiple hospitals. Her mother, older brother, and three sisters were diagnosed with DM before the age of 40. Her BMI was 23.4 kg/m2. The physical examination revealed muscularly prominent lipoatrophy in the upper and lower limbs and acanthosis nigricans in the axilla. Additionally, the person had facial features resembling acromegaly, with enlarged extremities and swelling of soft tissues. Blood pressure was regulated with ramipril, hydrochlorothiazide, and amlodipine. She had used various insulin and OAD regimens in the past. Despite this, euglycemia was challenging to achieve, and she frequently needed to be hospitalized for diabetic ketoacidosis. Anti-glutamic acid decarboxylase, anti-insulin, and islet antibodies were negative. HbA1c level was 13.3% and C-peptide level was 2.5 ng/ml. Moreover, grade 3 hepatosteatosis and hypertriglyceridemia were present. Polyneuropathy and diabetic nephropathy were also identified. Acromegaly and cushing syndrome were excluded. After excluding acquired lipodystrophy syndromes, she was consulted to the genetics department for CGL. Next-gen sequencing found a homozygous missense mutation (c.666G>C; p.Met222Ile) in exon 5 of the BSCL2 gene. Following this result, the patient was diagnosed as CGL2. Caloric and fat restricted dietary was recommended. Fat intake was below 20-30% of total energy. The patient was treated with insulin aspart, glargine U300/mL, metformin, alpha lipoic acid, and fenofibrate. The patient's blood glucose was more regulated, did not apply to the emergency department. Family members were also given genetic counseling. Conclusion Lipodystrophy is rare however medical professionals must exercise caution and consider lipodystrophy as a possible diagnosis for non-obese individuals who have difficulty maintaining euglycemia, fatty liver disease, and elevated triglyceride levels. The physical examination is crucial for diagnosis.

Altered antibody titers in patients with neuromuscular diseases after high-dose intravenous immunoglobulin therapy

We investigated the changes in antibody titers after intravenous immunoglobulin (IVIg) administration in patients with neuromuscular diseases. Among patients who received IVIg from April 1, 2020, to August 31, 2022, we retrospectively evaluated 15 patients with antibody measurements before and after IVIg administration for any rise in the following antibody levels and examined the data for subsequent changes of false positive results to negative ones. The levels of anti SS-A, anti-thyroglobulin, anti-thyroid peroxidase, anti-glutamic acid decarboxylase, HBs, and HBc antibodies transiently increased after IVIg administration and showed false-positive results. However, levels of rheumatoid factor and anti-nuclear and antineutrophil cytoplasmic antibodies were not elevated. The false-positive results became negative after 3 months. Here, we report on the changes in antibody levels before and after IVIg administration and note that levels of hepatitis B virus-related antibodies and various autoantibodies transiently rise after IVIg administration.

Anti-glutamic acid decarboxylase antibodies-associated cerebellar ataxia: A treatable ataxia

Abstract Background: Anti-glutamate decarboxylase 65 antibody-associated cerebellar ataxia (anti-GAD65Ab-associated CA) is the most widely studied immune-mediated CA. There are few case series evaluating the clinical, radiological, treatment profile, and outcome of anti-GAD65Ab-associated CA. Objective: To study the clinical, radiological profile, associated neoplasm, treatment outcome, and prognosis in patients diagnosed with anti-GAD65Ab-associated CA. Methods: A retrospective descriptive analysis of a cohort of patients diagnosed with anti-GAD65Ab-associated CA was performed and analyzed. Results: Thirteen patients were selected for the analysis with female predominance (70%). The mean age at presentation was 47.5 ± 11.1 years (range, 29–65 years), and the median duration of the symptoms was 4 months. All 13 patients (100%) had gait ataxia. Ten patients had limb ataxia along with gait ataxia (75%). Seven patients had cerebellar dysarthria (54%). Four patients (31%) had gaze-evoked jerky nystagmus. Five patients (39%) were diagnosed with type 2 diabetes mellitus, and one patient had hypothyroidism in addition to type 2 diabetes mellitus. Brain magnetic resonance imaging was normal in seven (54%) patients, and pure cerebellar atrophy was observed in six patients. One patient was detected with a colon neoplasm. All 13 patients received intravenous methylprednisolone, followed by oral steroids over 3 months. Six patients (50%) received plasma exchange along with intravenous methylprednisolone. Favorable outcomes (modified Rankin scale score ≤2) were observed in five patients and poor outcomes in two; six patients were lost to follow-up after the first admission. Conclusion: Anti-GAD65Ab-associated CA presents as subacute to chronic progressive CA with a favorable outcome with immunotherapy. Anti-GAD antibodies should be assessed in serum or cerebrospinal fluid in patients presenting subacute to chronic sporadic CA. The occurrence of a systemic neoplasm is rare in anti-GAD65Ab-associated CA.

Autoimmune Retinopathy in a Patient with Stiff-Person Syndrome: A Case Report.

To describe a patient who developed retinal degeneration associated with autoimmune retinopathy (AIR) and who was also found to have anti-glutamic acid decarboxylase (GAD65) autoantibodies and the diagnosis of stiff-person syndrome (SPS). Ophthalmologic workup consisted of clinical examination, multi-modality retinal imaging, and electrophysiologic testing. Further neurologic assessment including relevant serum and cerebrospinal fluid studies was also conducted. We highlight the case of a 45-year-old patient who developed subacute, sequential vision loss, along with bilateral lower extremity weakness. On initial presentation, optical coherence tomography (OCT) of the left eye was notable for diffuse attenuation of the outer retinal bands. Fundus autofluorescence demonstrated a ring of hyper-autofluorescence encircling the fovea of the left eye. At fifteen-month follow-up, the right eye also became similarly affected. He was found to have elevated serum and cerebrospinal anti-GAD65 autoantibodies and was diagnosed with both SPS and AIR. There is a potential association of anti-GAD65 autoantibodies with the development of AIR.

Paraneoplastic Neurologic Syndromes.

Progress is ongoing in understanding paraneoplastic neurologic disorders, with new syndromes and antibodies being described and more detailed evidence available to guide workup for diagnosis and treatment to improve outcomes. Many excellent reviews have summarized the molecular features of different antibodies, but this article emphasizes the clinical features of each syndrome that may help guide initial diagnosis and treatment, which often should occur before an antibody or cancer is found to confirm the diagnosis. Recent findings include updated diagnostic criteria with validated sensitivity and specificity, discovery of novel antibodies, and clinical findings that increase the likelihood of an underlying paraneoplastic disorder. Suggestive syndromes that have been recently identified include faciobrachial dystonic seizures and pilomotor auras in anti-leucine-rich glioma inactivated protein 1 encephalitis, extreme delta brush on EEG in N-methyl-d-aspartate (NMDA)-receptor encephalitis, déjà vu aura in anti-glutamic acid decarboxylase 65 (GAD65) encephalitis, and sleep disturbances in several disorders. In addition, there is confirmed utility of brain positron emission tomography (PET) and CSF markers, including carcinoembryonic antigen and oligoclonal bands, as well as improved tests for the presence of leptomeningeal cancer cells in CSF. Associations of cancer immunotherapies with paraneoplastic syndromes and herpes simplex virus encephalitis (and COVID-19) with NMDA-receptor encephalitis have been described. All neurologists should be aware of advances regarding paraneoplastic neurologic syndromes, as patients can present with a wide variety of neurologic symptoms and earlier diagnosis and treatment can improve outcomes.

Cerebral glucose hypometabolism and hypoperfusion of cingulate gyrus: an imaging biomarker of autoimmune encephalitis with psychiatric symptoms

BackgroundAbout 60% of autoimmune encephalitis (AE) patients present psychiatric symptoms, but the underlying mechanism remains unknown. This study examined the role of the cingulate cortex in such patients to identify predictive poor psychiatric factors.MethodsIn this study, 49 AE patients and 39 healthy controls were enrolled. AE patients were further divided into two groups based on the presence/absence of psychiatric symptoms. The ratio of the standardized uptake value (SUVR) and relative cerebral blood flow (rCBF) in different regions of the cingulate cortex were calculated through positron emission tomography–computed tomography (PET/CT) and arterial spin labeling (ASL) MRI, and the results were compared among the three groups. In addition, we followed-up on the psychiatric outcomes and identified the risk factors for poor psychiatric prognosis, focusing on the cingulate cortex.ResultsMore than half of the AE patients (27/49) exhibited psychiatric symptoms. Agitation and thought blocking were typical psychiatric phenotypes, except for anti-glutamic acid decarboxylase 65 (GAD65) encephalitis, which mainly presented with catatonia and a depressed mood. AE patients with psychiatric symptoms experienced reduced metabolism and perfusion of the anterior cingulate cortex (ACC), midcingulate cortex (MCC), and posterior cingulate cortex (PCC). The SUVR of ACC can be used as an independent risk factor of poor psychiatric outcomes, which had an area under the ROC curve (AUC) of 0.865.ConclusionImpaired cingulate cortex function in AE may be the potential mechanism of psychiatric symptoms. Hypometabolism of ACC is an independent prognostic factor predicting an unfavorable psychiatric prognosis in AE.

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

FRI645 A Case Of Diabetic Ketoacidosis After Initiation Of Decitabine And Venetoclax Chemotherapy

Abstract Disclosure: R. Maini: None. J. Milosavljevic: None. S. Aleksic: None. Background: Decitabine, a pyrimidine nucleotide analogue, and venetoclax, a Bcl-2 inhibitor (ABT-199), are chemotherapy agents used for the treatment of myelodysplastic syndromes. Clinical trials have shown hyperglycemia as an adverse reaction for both of these medications, but DKA has not been reported. Clinical Case: A 71-year-old woman with a history of T2D and myelodysplastic syndrome (MDS) presented with nausea, vomiting, and diarrhea for five days. Initial tests revealed blood glucose 839 mg/dL, an anion gap of 19 mEq/L (n 7-16), serum bicarbonate 14 mmol/L (n 20-30), venous pH of 7.24, and hydroxybutyrate >4 mmol/L (n< 0.3), consistent with diabetic ketoacidosis. Her anti-glutamic acid decarboxylase autoantibodies were negative. Chest CT showed bibasilar pulmonary opacities, concerning for multifocal pneumonia. She was placed on an insulin drip and fluids according to the institution's protocol and her anion gap closed within a day. She was transitioned to subcutaneous insulin. The patient had well-controlled T2D, with an HbA1c of 5.6% two weeks before her presentation and an admission fructosamine level of 377 umol/L (n 200-285). Her BMI was 25. Her only T2D medication was semaglutide 0.25 mg weekly but had not taken a dose in three weeks due to the national shortage. Five weeks prior to this presentation, she began weekly chemotherapy infusions of decitabine and oral venetoclax as part of a clinical trial (2021-13466) for MDS treatment, with her last infusion one week before her presentation. Conclusion: This is the first case to demonstrate DKA precipitated by decitabine and venetoclax treatment. While both agents have been linked to severe hyperglycemia in safety clinical trials, DKA has not been previously reported. Data from animal studies have shown that prolonged exposure of mouse islets to Bcl-2 antagonists increase levels of reactive oxygen species and induce pancreatic β cell apoptosis (1). Further research is needed to assess the benefits and risks of this chemotherapy regimen in patients with diabetes.

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

Proliferative diabetic retinopathy as the initial presenting feature of type 1 diabetes.

Type 1 diabetes mellitus (T1DM) is an autoimmune disorder caused by the destruction of the pancreatic beta cells, which produce insulin. Individuals with T1DM usually require at least 3-5 years to develop microvascular complications in comparison to people with type 2 diabetes (T2DM), who may develop complications even before the diagnosis of diabetes. We discuss a patient who presented with proliferative diabetic retinopathy subsequently diagnosed with T1DM and diabetic neuropathy following investigations. Diabetic retinopathy or other microvascular complications as the presenting feature of T1DM is rarely known or reported in the literature. A 33-year-old healthcare worker had been seen by the opticians due to 1-week history of blurred vision. The ophthalmology assessment had confirmed proliferative retinopathy in the right eye and severe non-proliferative retinopathy in the left eye with bilateral clinically significant macular oedema. His BMI was 24.9 kg/m2. The nervous system examination revealed bilateral stocking type peripheral neuropathy. The random venous glucose was 24.9 mmol/L. Plasma ketones were 0.7 mmol/L and HbA1c was 137 mmol/mol. On further evaluation, the anti-glutamic acid decarboxylase (GAD) antibody was positive, confirming the diagnosis of T1DM. He was started on aflibercept injections in both eyes, followed by panretinal photocoagulation. Subsequent nerve conduction studies confirmed the presence of symmetrical polyneuropathy. The pathogenesis of the development of microvascular complications in T1DM is multifactorial. Usually, the development of complications is seen at least a few years following the diagnosis. The occurrence of microvascular complications at presentation is rare. This makes the management challenging and extremely important in preventing the progression of the disease. The pathogenesis of the development of microvascular complications in type 1 diabetes mellitus is multifactorial. The development of complications is seen at least a few years following the diagnosis. Occurrence of microvascular complications at presentation is rare. This makes the management challenging and extremely important to prevent the progression of the disease.

OA17 Rheumatoid meningitis - a rare complication of rheumatoid arthritis

Abstract Introduction A wide spectrum of neurological complications can occur in rheumatoid arthritis (RA) including peripheral neuropathy, mononeuritis multiplex and rheumatoid vasculitis. Cerebrovascular disease is also common. We describe a rare neurological complication of RA. Case description The patient was first diagnosed with seropositive RA in 2015 at the age of 68. His rheumatoid factor at presentation was 144 kIU/L and CCP antibodies >340 U/mL. His background include alcohol excess and obstructive sleep apnoea with peripheral neuropathy attributed to alcohol. Nerve conduction studies demonstrated axonal neuropathy. By 2016, he had achieved good disease control with combination methotrexate and sulfasalazine. In 2018, he was admitted to stroke services with right arm weakness and focal neurological deficit on examination. An urgent CT head showed possible right parietal extra dural haemmorhage. His CRP was <5, ESR 24 with a normal ANA. Borrelia, syphilis and HIV screening were normal. Anti-glutamic acid decarboxylase (GAD), anti-amphiphysin, anti-Hu, anti-Yo and anti-Ri antibodies were all negative. Lumbar puncture revealed a normal glucose and red blood cells count but the CSF protein was raised at 851 mg/L with a lymphocyte count of 9/ul. Gram stain, culture, viral PCR for HSV, VZV, enterovirus, parechovirus and adenovirus were normal and CSF cytology demonstrated a lymphocyte pleocytosis. Subsequent contrast MRI head scan showed leptomeningeal enhancement with gadolinium contrast. MRI of the cervical spine and brachial plexus was normal and an EMG/NCS of the upper limb demonstrated an incidental ulnar nerve compression at the elbow. Following neurology input, the leptomeningeal enhancement was thought to represent rheumatoid meningitis (RM). He was treated with 1 mg/kg prednisolone and rituximab with prompt and complete recovery. He remains well from both the perspective of his RA and RM. Discussion RM is a rare form of aseptic meningitis. Aseptic meningitis is commonly defined as clinical and CSF evidence of meningeal inflammation in the absence of an infectious aetiology. The vast differential includes malignancies, drug-induced and autoimmune diseases, for example lupus and sarcoidosis. The diagnosis of RM requires a high index of suspicion as well as exclusion of other causes. Historically RM was diagnosed at post-mortem but MRI scanning means pre-mortem diagnosis is possible. It is considered rare but serious manifestation of RA. Case reports suggest RM usually occurs in those with long standing seropositive RA but RM has been described in the early stages of RA and even as a presenting feature. Peripheral disease activity does not correlate with occurrence of RM. The clinical presentations vary depending on the brain structure involved and can include motor or sensory deficits, cognitive disturbance and seizures. It may mimic many other conditions. Radiological findings will not distinguish RM from other causes of aseptic meningitis. CSF finding of lymphocytosis and rheumatoid factor (if available) may help distinguish RM from other causes. Meningeal biopsy can confirm the diagnosis. Due to the rarity of RM, there are no current guidelines on treatment. Historically, corticosteroids are the main induction agent. There are case reports highlighting possible success from the addition of cyclophosphamide and rituximab. Case series also highlight a significant mortality rate in excess of 60% even despite treatment. This may represent publication and historical bias. Key learning points Rheumatoid meningitis (RM) is a rare but serious complication of rheumatoid arthritis. RM may not correlate with disease activity nor disease duration. Diagnosis is a challenge due to its wide clinical phenotype as well as the non-specificity of imaging, lumbar puncture and serological findings. Treatment options are based on case reports and series and include corticosteroids, rituximab and cyclophosphamide.

Newly diagnosed type 1 diabetes mellitus in a human immunodeficiency virus-infected patient with antiretroviral therapy-induced immune reconstitution inflammatory syndrome: a case report

BackgroundDiabetes that develops in human immunodeficiency virus (HIV)-infected patients who receive antiretroviral therapy (ART) is usually type 2 diabetes mellitus (T2DM); however, autoimmune diabetes, such as type 1 diabetes mellitus (T1DM) can also develop in this population. After treatment with ART, patients might experience clinical deterioration following an increase in the CD4 cell count, which is termed immune reconstitution inflammatory syndrome (IRIS). Here, we describe an HIV-infected patient on ART who developed T1DMat due to IRIS, highlighting the clinical complexity in diagnosis and treatment.Case presentationA 36-year-old man infected with HIV had a nadir CD4 cell count of 15.53/μL before medication, which increased to 429.09/μL after 9 months of regular ART. The fasting serum glucose at 9 months was between 96 mg/dL and 117 mg/dL. After 11 months of ART, the patient was admitted to hospital for diabetic ketoacidosis (DKA) and Graves’ disease (GD). Noninsulin antidiabetics (NIADs) were prescribed following the resolution of DKA. However, poor glycemic control was noted despite well-titrated NIADs. Further investigation demonstrated poor pancreatic beta cell function and elevated anti-glutamic acid decarboxylase (anti-GAD) and anti-tyrosine phosphatase-like insulinoma antigen 2 (anti-IA2) titers. According to the results, he was diagnosed with T1DM and received multiple daily injections(MDI) of insulin. The regimen of MDI was insulin degludec as basal insulin and insulin aspart as prandial insulin. After MDI therapy, his glycemic control was improved.ConclusionIn this case, T1DM was ascribed to IRIS. Although this phenomenon has been demonstrated in previous case reports, further study is necessary to realize the mechanism of this association. Therefore, we emphasize that when HIV-infected patients on ART experience an unstable blood glucose level and abnormal thyroid function, physicians should consider T1DM and GD associated with ART-induced IRIS to reduce the subsequent complications and more serious endocrine dysfunction.

Prevalence of markers of beta cell autoimmunity and thyroid disease in children with coeliac disease

BackgroundOver the last decades, the prevalence of coeliac disease (CD), an autoimmune disorder, rose to 1–2%. Whether patients with CD have higher risk of developing other autoimmune disorders such as type 1 diabetes, Hashimoto thyroiditis, or Graves` disease remains unclear.AimThe aim of this study was to determine the prevalence of biomarkers of beta cell and thyroid autoimmunity in children with CD.MethodsRetrospective cross-sectional cohort study comparing pediatric patients suffering from CD with age and sex-matched healthy controls (HC). Participant`s serum was tested by immunoassay for following autoantibodies (aAb): TSH-receptor antibodies (TRAb), anti-thyroglobulin (anti-Tg), anti-thyroid peroxidase (anti-TPO), anti-glutamic acid decarboxylase (anti-GAD), anti-zinc transporter 8 (anti-ZnT8), anti-islet antigen 2 (anti-IA2) and anti-insulin.ResultsA total of 95 patients with CD (mean age 8.9 years; 63% female) and 199 matched healthy controls (mean age 9.2 years; 59.8% female) were included in the study. For patients with CD, a seroprevalence of 2.1% (vs. 1.5% in HC) was calculated for anti-GAD, 1.1% for anti-IA2 (vs. 1.5% in HC), 3.2% for anti-ZnT8 (vs. 4.2% in HC), and 1.1% (vs. 1% in HC) for anti-insulin. For thyroid disease, a seroprevalence of 2.2% for TRAb (vs. 1% in HC), 0% for anti-TPO (vs. 2.5% in HC) and 4.3% for anti-Tg (vs. 3.5% in HC) was found for patients with CD.ConclusionThis study suggests a higher prevalence of autoimmune antibodies againstthyroid in children with CD compared to HC, whilst it is similar for pancreatic antibodies. Prospective cohort studies are needed to first evaluate the occurrence of autoimmune antibodies against beta cells and thyroid over a longer follow-up time and second to explore their clinical relevance.

Stiff Person Syndrome Mimicking as Atypical Parkinson’s Disease - A Diagnostic Dilemma

Stiff person syndrome (SPS) is a rare neurological disorder characterized by stiffness and spasm of the truncal muscles and subsequent postural deformities. In this report, we present a case of a woman in her early 60s who presented to us with muscle stiffness, back pain, and frequent falls. On examination, she was found to have increased muscle tone and mild tremors. Given her age and presentation, a provisional diagnosis of Atypical Parkinson’s was made. Patient was treated with Diazepam. Because of presence of autoimmune co-morbid conditions, anti-glutamic acid decarboxylase (GAD) antibodies were tested, which were positive, and thus, diagnosis of SPS was made. Treatment with Diazepam was continued, and her symptoms significantly improved. Even though SPS is a rare disorder, our case report highlights the need to keep it in differential diagnoses when an elderly patient presents with stiffness and postural instability, as treatment for SPS and atypical Parkinson’s vary considerably.

Intrapancreatic autologous stem cell therapy for type 1 diabetes - an experimental study.

Type 1 diabetes, also known as juvenile diabetes or insulin-dependent diabetes, is a chronic autoimmune condition in which the pancreas makes little or no insulin leading to resultant hyperglycemia. The incidence of type 1 diabetes in India is 0.26 per 1000 children. The author treated 25 patients with type 1 diabetes with autologous intrapancreatic stem cell therapy in the last 5 years. A group of 26 patients of type 1 diabetes with conventional treatment of insulin injections was put as a control group in the same period. The results of the therapy group were substantially superior to the control group, which came statistically highly significant. The variable compared were weight gain, the daily requirement of insulin and its drop after therapy, the rise of C-peptide levels and drop in anti-glutamic acid decarboxylase antibody, drop in HbA1c levels, and drop in fasting and postprandial blood sugar. When stem cells are given intravenously, the majority are engulfed by the lungs and only a small fraction is delivered to the pancreas. When injected into the pancreas, through its arterial blood supply, due to the larger size and irregular shape of stem cells, they are retained in tissue spaces and do not escape from the venous side, thus achieving far higher concentration in the pancreas compared to the intravenous route. Intrapancreatic stem cell therapy for type 1 diabetes is safe, affordable, and effective. It has the potential to become a viable treatment option for type 1 diabetes patients.