bluuebunny/crossref_metadata_2025_split huggingface dataset:
9238 Application of DREADD Tools Offers New Insights About the Paracrine Cellular Crosstalk in the Islet of Langerhans
Authors: Rodriguez Rayner , Tamayo Alejandro , Rodriguez Dayleen Hakim , Alcazar Oscar , Pereira Elizabeth , Makhmutova M A dina , Almaca Joana , Goncalves Luciana 
Published: October 2024

Abstract
Disclosure: R. Rodriguez: None. A. Tamayo: None. D. Hakim Rodriguez: None. O. Alcazar: None. E. Pereira: None. M. Makhmutova: None. J. Almaca: None. L. Goncalves: None.
The δ-cell is envisioned as a main suppressive component in the islet of Langerhans, which provides functional negative feedback to its neighboring α- and β-cells by secreting somatostatin. Considering that changes in the dynamics and amount of insulin and glucagon are associated to the natural history of Diabetes, more knowledge about the role that δ-cell and somatostatin play in the deregulation of islet glucoregulatory hormone secretion is of remarkable importance. Here we aimed to revisit the kinetics of the cellular crosstalk between β- and α-cell with the δ-cells and vice versa by taking advantage of a chemogenetic tool allowing the specific activation of any cell subset genetically modified to express DREADD (Designed Receptors Exclusively Activated by Designed Drugs). We bred mice that expressed the activator-DREADD (hM3Dq) in either α-, β-, or δ-cells. Immunohistochemical staining of pancreas sections confirmed the great cellular specificity and the effective translocation of the DREADD to the membrane of each targeted cell. Perifusion assays showed that α-, β-, and δ-cells bearing DREADD secreted glucagon, insulin and somatostatin respectively in a dose-response manner upon simulation with CNO; and as expected, the targeted stimulation of every specific cell type generated subsequent co-stimulatory or rebound responses in the other neighboring cell subsets. The data evidenced the complex network of paracrine cellular crosstalk within the islet, however the dynamics of hormone secretion in several instances did not fit into the current way we think α-, β- and δ-cells interact with each other’s. The data showed an overall increase of hormone secretion in instances we expected lessening of secretion resulting from inhibitory paracrine cellular crosstalk, such as 1) the burst of glucagon responses in non-permissive 16 mM glucose following the activation of either β- or δ-cells, and 2) net increment of insulin secretion following δ-cell activation. The results suggested more complex insights about the notion of inhibitory paracrine crosstalk within the Islet of Langerhans, where inhibition-mediated excitatory rebound responses might have more physiological relevance and be more significant for islet biology.
Presentation: 6/3/2024
9338 Approximation Of Serum Bicarbonate Concentration Using Serum Carbon Dioxide Combining Power In Patients With Diabetic Ketoacidosis
Authors: Aliño Meghan Marie Auza , Panilagao Gorgonia Padilla 
Published: October 2024

Abstract
Disclosure: M.A. Aliño: None. G.P. Panilagao: None.
Background: Determination of serum bicarbonate (HCO3-) using arterial blood gas analysis in patients with diabetic ketoacidosis allows for the evaluation of the severity of the condition, determines whether HCO3- therapy is required, and tracks the progression and resolution of the disease. Serum carbon dioxide combining power (CO2CP) has often been used as an indicator of metabolic acidosis. This study investigated the relationship between HCO3- and CO2CP and developed an approximation formula for serum bicarbonate concentration using predictor variables, as this may lessen the need to repeat arterial blood gas analysis or be used in settings in which blood gas analyzers are unavailable. Methodology: This single-center, retrospective, cross-sectional study investigated a total of 77 patients diagnosed with diabetic ketoacidosis. Assessment of the bivariate correlations between serum HCO3- and serum CO2CP as well as other potential predictor variables was done via Pearson’s correlation coefficient. Predictor variables that were significantly correlated with serum HCO3- were identified and an approximation formula was developed by regression analysis. Evaluation of the correlation between the approximated HCO3- value and the actual serum HCO3- concentration was performed using correlation coefficient and residual statistics to assess agreement. Results: Serum CO2CP had significant correlation with serum HCO3- (r = 0.768, p &lt; 0.05). By multiple regression analysis, the following approximation formula was therefore expressed: HCO3- = 12.682 + (0.612 x CO2CP) - (Ketones) + (0.085 x BUN) - (0.026 x SGPT) - (1.23 x Creatinine) - (0.067 x Chloride). Examination of residuals revealed a mean of zero (0), indicating no significant difference between the actual and approximated levels of serum HCO3-. Conclusion: The predictor variables included in the formula collectively contribute significantly to the approximation of serum HCO3-. The approximated serum HCO3- values also showed significant correlation with actual serum HCO3- concentration; thus, the formula may be utilized to derive an approximation of serum bicarbonate concentration in patients with diabetic ketoacidosis.
Presentation: 6/1/2024
8084 Euglycemic Diabetic Ketoacidosis in Vulnerable Populations: A Case Series
Authors: Shah Mahabir Singh , Humayon Salman , Chawla Raghav , Peñaherrera Carlos 
Published: October 2024

Abstract
Disclosure: M.S. Shah: None. S. Humayon: None. R. Chawla: None. C. Peñaherrera: None.
This case series explores seven cases admitted to a community hospital's inpatient and ICU services in 2023, with resident physicians closely managing their care. Our focus was to compare presentations and highlight risk factors contributing to Euglycemic Diabetic Ketoacidosis (euDKA). The following seven patients have a history of type 2 diabetes mellitus (DM 2) and were on SGLT-2 inhibitors for either diabetic management or goal-directed medical therapy (GDMT) for heart failure. These patients either presented with or developed euDKA during hospitalization. Diagnostic criteria used for euDKA being HCO3 (&lt; 18 mEq/L) or arterial pH (&lt; 7.3 pH units), with a normal or mildly elevated blood glucose (&gt; 250 mg/dL) and Beta-hydroxybutyrate (&gt;3 mmol/L). All patients were treated with an insulin drip. IV fluids were provided cautiously given multiple patients with reduced ejection fraction and lack of severe dehydration seen in euDKA. Mrs. E, a 57-year-old female with DM 2 (HbA1c of 9.7%), presented to the hospital for ST elevation M.I and subsequently started on GDMT for heart failure. Initiated on Dapagliflozin inpatient, leading to euDKA amid poor oral intake. Mr. L, a 54-year-old male with DM 2 presented to the ED with hyponatremia. On Empagliflozin per GDMT for heart failure. He presented with euDKA, attributed to prolonged fasting from chronic nausea. Hospital course complicated by cardiac arrest and AKI on CKD requiring CRRT. Mr. S, a 56-year-old male with DM 2 (HbA1c of 7.7%), on Dapagliflozin. The patient was in euDKA on presentation to the hospital. The precipitating event included nausea and abdominal pain aggravated by food, leading to poor PO intake for 3 days prior to arrival to ED. Mr. L, an 86-year-old male with DM 2 and heart failure, on Empagliflozin per GDMT guidelines. EuDKA ensued due to starvation in the setting of failure to thrive and generalized weakness. Mr. A, an 81-year-old male with DM 2 on Empagliflozin. EuDKA manifested post fall leading to a prolonged period of caloric deprivation. Mr. G, a 74-year-old male with DM 2 and dementia, started on Dapagliflozin. EuDKA occurred following a period of starvation. Mr. Q, a 66-year-old male with DM 2 on insulin pump, heart failure and metastatic pancreatic cancer undergoing chemotherapy. Patient was on Empagliflozin per GDMT for heart failure. Starvation occurred due to PEG tube malfunction inciting euDKA. These cases confirm that starvation can raise the risk for EuDKA. Further research is essential to refine risk stratification and preventive strategies in this subset of patients. It would be ideal to hold SGLT-2 inhibitors inpatient if providers anticipate prolonged fasting or caloric restrictions. Educating patients on avoiding erratic eating habits is crucial to mitigate euDKA. Recognizing risks is vital in patient selection and counseling.
Presentation: 6/2/2024
12552 Hypoglycemia As Initial Manifestation Of Hepatocellular Carcinoma In A Patient With Diabetes
Authors: Zareva Emiliya , Choudhry Sara 
Published: October 2024

Abstract
Disclosure: E. Zareva: None. S. Choudhry: None.
Introduction: Non-islet cell tumor hypoglycemia (NICTH) is a known but rare paraneoplastic syndrome associated with tumors of epithelial and mesenchymal origin. It is reported in 4-27% of patients with hepatocellular carcinoma (HCC) and is associated with poor prognosis. Here we present a case of hypoglycemia as the initial manifestation of malignancy in a patient with diabetes. Case: A 69 year old male with a history of type 2 diabetes mellitus presented due to confusion and diaphoresis, with blood glucose in the 20s on EMS arrival and improvement in mental status after dextrose administration. He had multiple ED visits due to hypoglycemia over the prior 3 months and his antidiabetic agents had been discontinued. Hepatomegaly was noted on physical exam. CT abdomen and pelvis and abdominal MRI demonstrated multiple hepatic lesions concerning for malignancy and liver biopsy confirmed HCC. Fasting protocol was initiated and labs obtained during a hypoglycemic episode. Insulin was 0.14 uIU/mL (Reference range (RR) 2.6-24.9uIU/mL); C-peptide 0.4 ng/mL (RR 1.1-4.4 ng/mL) ; Proinsulin 1.2 pmol/L (RR 0.0-10/0pmol/L); Random and A.M. cortisol were normal and sulfonylurea screen and was negative - findings consistent with non-insulin dependent hypoglycemia. Further workup showed IGF-1 of 17 ng/mL (RR 59-230 ng/mL), IGF-2 of 515 ng/mL (RR 333-967 ng/mL), and IGFBP-2 of 1467 ng/mL (RR 151-740 ng/mL), with IGF-2: IGF-1 ratio of 30.3 confirming the diagnosis of NICTH. The patient was not a surgical candidate and treated with 10% dextrose infusion, dietary intervention, Prednisone and Octreotide. He was discharged after stabilization of serum glucose, and readmitted 2 weeks later due to pneumonia, AKI and refractory hypoglycemia. Embolization was performed by IR with devascularization of 80% of tumor parenchyma. His clinical status continued to decline, and he ultimately elected comfort-directed care and expired. Discussion: NICTH is a rare but serious paraneoplastic syndrome associated with significant morbidity and mortality. Proposed mechanisms include increased production of IGF-2 or pro-IGF-2 (known as “big IGF-2”) leading to stimulation of the insulin receptor, high tumor burden in the liver leading to impairment of gluconeogenesis or increased glucose consumption, and infiltration of the adrenals with resultant adrenal insufficiency. An IGF-2:IGF-1 ratio more than 10 confirms the diagnosis in IGF-2 producing neoplasms. Treatment focuses on surgical removal or debulking with chemo- and/or radiation therapy, and embolization. Glucocorticoids are a mainstay in medical management, with case reports describing the use of somatostatin analogs, glucagon, and growth hormone. Diagnostic delays can occur, particularly in patients with diabetes taking multiple glucose-lowering medications, which highlights the importance of a systematic approach to the hypoglycemic patient.
Presentation: 6/1/2024
7916 Melas Syndrome: A Case Report
Authors: Yacobi Michal , Serebro Merav , Greenman Yona 
Published: October 2024

Abstract
Disclosure: M. Yacobi Bach: None. M. Serebro: None. Y. Greenman: None.
A 43-year-old married woman with two children of Ashkenazi descent was referred for endocrine evaluation due to suspected excess cortisol secretion. Extensive laboratory investigations yielded no evidence of pathological findings over time, raising the possibility of pseudo-Cushing syndrome related to a depressive episode, in contrast to a much less probable cyclic Cushing syndrome. As part of the endocrine follow-up, a comprehensive medical history was obtained, revealing a diagnosis of diabetes around the age of 30. Initially managed as type 2 diabetes, subsequent evaluation at our clinic raised the possibility of a mitochondrial disorder due to the combination of diabetes, early-onset sensorineural hearing loss, and premature ovarian insufficiency. The fact that patient's mother, has also been diagnosed with diabetes, hearing impairment and stroke-like episodes, further strengthened this hypothesis. Given the family history and the patient's clinical presentation, genetic testing was recommended, revealing a mitochondrial DNA mutation M.3243 A&gt;G associated with MELAS syndrome (Mitochondrial Encephalopathy, Lactic Acidosis, and Stroke-like Episodes) with a heteroplasmy level of 1 9%.Based on the genetic findings, a metabolic workup was initiated, leading to the recommendation of supplementing with ubiquinol, citrulline, arginine, taurine, riboflavin, and alpha-lipoic acid. Medications capable of inducing lactic acidosis, such as metformin and statins, were discontinued. SGLT2 inhibitors were also stopped due to concerns about ketoacidosis. The patient received guidance on emergency arginine therapy in suspected stroke-like episodes, characterized by altered consciousness, focal deficits, or seizures. Furthermore, comprehensive education on metabolic crises triggered by infections, psychological stress, or prolonged fasting was provided, emphasizing the importance of seeking medical attention for any changes in her baseline or cognitive status. The significance of updating healthcare providers on her medical condition before any surgical intervention was stressed. Genetic counseling was recommended for first-degree relatives. This case underscores the intricate interplay between mitochondrial disorders and endocrine manifestations, emphasizing the importance of a multidisciplinary approach for accurate diagnosis and management.
Presentation: 6/2/2024
7918 Methadone Induced Hypoglycemia in a Patient with End-Stage Renal Disease
Authors: Anjum F , Imtiaz S , Jakoby M G 
Published: October 2024

Abstract
Disclosure: F. Anjum: None. S. Imtiaz: None. M.G. Jakoby: None.
Introduction: Methadone is a synthetic opiate and mu-receptor agonist used for the treatment of opioid dependence. We report a case of methadone induced hypoglycemia in a patient with end-stage renal disease (ESRD) that resolved after reducing the dose of methadone. Case Presentation: A 49-year-old male with hemodialysis dependent ESRD presented to the emergency department with complaints of weakness and tremulousness and found to have a capillary blood glucose of 34 mg/dL. Medical history was notable for opioid dependence and two months of treatment with methadone 110 mg daily. The patient denied previous episodes of hypoglycemia, and no one in his household was prescribed insulin or insulin secretagogues. Since the patient had been treated with dextrose fluids before consultation, a diagnostic fast was performed. After 2 hours of fasting, the patient experienced neuroglycopenic symptoms, and plasma glucose fell to 55 mg/dL. Insulin level was 3 mIU/L (expected &lt; 3), C-peptide 22.1 ng/mL (expected &lt; 0.6), and proinsulin 7.4 pM (expected &lt; 5). Beta-hydroxybutyrate level was 0.1 mM (expected &gt; 2.7), and no drugs were detected on an insulin secretagogues panel. Methadone was reduced to 40 mg daily, and the patient had no additional hypoglycemic events on the lower methadone maintenance dose. Discussion: Methadone and tramadol are the two opiates reported to cause hypoglycemia in the FDA Adverse Events Reporting System. There is a clear relationship between methadone dose and hypoglycemia risk, with odds of hypoglycemia increased approximately three-fold at methadone doses of &gt; 80 mg/d. Animal studies have linked the glucose lowering effects of methadone to mu-receptor activity, and the mu-receptor selective antagonist β-funaltrexamine blocks glucose lowering effects of the drug. It is not understood why other opioids (e.g. morphine) do not predispose to hypoglycemia. Mechanisms proposed for how methadone lowers blood glucose including increased insulin secretion, reduced gluconeogenesis, and suppression of counter-regulatory hormones. This patient was clearly hyperinsulinemic at time of hypoglycemia, and it unclear if impaired insulin clearance due to ESRD predisposed the patient to methadone induced hypoglycemia. Methadone is considered safe in ESRD due to limited accumulation as a result of fecal clearance of the drug. If hypoglycemia occurs during treatment with methadone, the dose should be reduced or methadone should be replaced with an alternative opioid.
Presentation: 6/3/2024
6674 Non-Progressive Diabetes Leading to Neurologic Diagnosis
Authors: Thelmo Franklin L , Murugesh Megana , Simon Barbara 
Published: October 2024

Abstract
Disclosure: F.L. Thelmo: None. M. Murugesh: None. B. Simon: None.
Introduction: The autoantibody GAD (anti-glutamic acid decarboxylase) is highly associated with Type 1 diabetes (T1DM) and Latent Autoimmune Diabetes in Adulthood (LADA). If GAD is detected before the onset of overt diabetes, typically 80% of patients with abnormal glucose tolerance progress to insulin deficiency and the need for insulin treatment after 5 years.[1] Stiff Person Syndrome (SPS) is also associated with GAD antibodies, but in SPS, the GAD antibodies are believed to be different epitopes that target GABA production in neuromuscular pathways. We present a case of presumed LADA that did not progress for 30 years, with progressive neurologic symptoms leading to a diagnosis of SPS in later adulthood.Case: A 52-year-old female presented for evaluation of T1DM and worsening neuropathies. She had a long history of prediabetes, with mildly elevated glucose values noted on labs since her early twenties. There was no family history of T1DM or autoimmune conditions. Six years ago, she sought endocrine evaluation. HgbA1c values were 6.1 to 6.6%. Intermittent use of continuous glucose monitoring (CGM) revealed post-prandial hyperglycemia up to 180mg/dL, occasionally (but rarely) exceeding 200mg/dL. She recalls being told that she had positive antibodies (unclear which ones tested) and given a diagnosis of T1DM. She declined insulin and maintained glycemic control with carbohydrate restriction and exercise; there were no episodes of diabetic ketoacidosis. She then developed neurologic symptoms: fullness, tightness and bloating in the abdomen (diagnosed with gastroparesis on scanning) and after a COVID 19 booster in 2021, muscle spasms in the legs and back with worsening abdominal tightness. At the time of her current presentation, A1C was 6.4%, glycated albumin was 14.4% (prediabetes range 13.6 - 15.5%) and CGM time in range was 99%. A non-fasting C-peptide was 3.6 ng/mL (1.1- 4.4ng/mL) with glucose of 119 mg/dL. Repeat antibody testing revealed undetectable IA-2 and ZnT8 antibodies, but GAD was grossly elevated at 1,015.3 U/mL. Given the unusually high GAD titer, SPS was suspected, and this diagnosis was confirmed on referral to neurology. The patient was advised to liberalize diet and will be monitored with HgbA1c and serial C-peptide levels to assess progression in the future. Discussion: While high GAD antibody levels are associated with progression to insulin dependence in adults with LADA, in SPS the GAD titers tend to be even higher2. The presence of only one auto-antibody for T1DM (and not multiple), long-standing non-progressive hyperglycemia, and normal C-peptide pointed away from autoimmune diabetes being the etiology for mild glucose intolerance in this patient. If neurologic symptoms are present, high GAD should prompt the evaluation for other syndromes associated with GAD antibody epitopes such as SPS.
Presentation: 6/2/2024
8007 The Effect of Glucagon-Like Peptide-1 Receptor Agonists in Reducing Major Adverse Cardiovascular Events in Patients With Type 2 Diabetes Mellitus: A Bayesian Network Meta-Analysis
Authors: Romeiro P H , Silva C R , Mello T T , Godoi A , Hespanhol L C , Silva C H , Balieiro C A , Ferreira H B 
Published: October 2024

Abstract
Disclosure: P.H. Romeiro: None. C.R. Silva: None. T.T. Mello: None. A. Godoi: None. L.C. Hespanhol: None. C.H. Silva: None. C.A. Balieiro: None. H.B. Ferreira: None.
Background: The use of glucagon-like peptide-1 receptor agonists (GLP-1RA) is associated with a significant reduction in the incidence of major cardiovascular events (MACE) in patients with type 2 diabetes mellitus (T2DM), suggesting a cardioprotective role for some drugs. However, which GLP-1RA is most effective at reducing MACE is unknown. Methods: PubMed, Embase and Cochrane Central databases were searched to identify randomized controlled trials (RCTs) that compared the safety of GLP-1RA with that of placebo in patients with T2DM. Studies were included if they had a primary outcome of cardiovascular mortality, non-fatal myocardial infarction, or non-fatal stroke (outcomes required by regulatory agencies for cardiovascular safety studies in diabetes). A Bayesian network meta-analysis was conducted to estimate the relative effects between treatments using risk ratios (RR) and to rank each one according to the Surface Under the Cumulative Ranking Curve (SUCRA). Results: Nine RCTs comprising 60.080 patients with T2DM were included. The assessment of SUCRA values indicated that Semaglutide (0.74) and efpeglenatide (0.71) emerged as the most effective treatments for reducing MACE. Moreover, semaglutide demonstrated superior efficacy compared to albiglutide (0.67), oral semaglutide (0.60), liraglutide (0.51), dulaglutide (0.44), exenatide (0.33), lixisenatide (0.21), and placebo (0.20). The risk of MACE was significantly higher for lixisenatide (RR 1.0; credible interval [CrI] 0.66, 1.6), exenatide (RR 0.93; CrI 0.62, 1.4), dulaglutide (RR 0.88; CrI 0.6, 1.3), liraglutide (RR 0.86; CrI 0.58, 1.3), oral semaglutide (RR 0.79; CrI 0.48, 1.3), albiglutide (0.77; CrI 0.52, 1.2), efpeglenatide (RR 0.74; CrI 0.46, 1.2), semaglutide (RR 0.72; CrI 0.45, 1.2). Conclusion: In this network meta-analysis comparing the use of different GLP-1RA in patients with T2DM, semaglutide is the GLP-1RA with the highest likelihood of lower MACE and may be a preferable option in these patients. Lixisenatide showed the lowest likelihood for preventing MACE. Further analyses are needed to establish the effect of different GLP-1 analogues on patients with a previous history of CVD
Presentation: 6/3/2024