bluuebunny/crossref_metadata_2025 huggingface dataset:
8727 Treatment of Hypertriglyceridemia Induced Pancreatitis
Authors: KC Shreeyanta , Tan Marie , Salim Anzi , Goyal Aakash , Maan Ramanpreet K , Mahat Sanjeev , Kattel Trishna , Wendell Gary D
Published: October 2024

Disclosure: S. Kc: None. M. Tan: None. A. Salim, MD: None. A. Goyal, MD: None. R.K. Maan, MD: None. S. Mahat, MD: None. T. Kattel,MD: None. G.D. Wendell, MD: None.

Introduction : Hypertriglyceridemia less commonly causes acute pancreatitis compared to gallstones or alcohol consumption, estimated to be almost 10% of all cases of acute pancreatitis. Hypertriglyceridemia induced pancreatitis is most often caused by primary hyperlipidemia, pregnancy, uncontrolled diabetes, or alcohol consumption. Diagnosis of HTGP includes evaluation of risk factors, physical examination findings and lipid panels. Treatment and management includes diet restriction, plasmapheresis, insulin, and fibrates. Case Report : We present a 39 year old male with a past medical history of hyperlipidemia, alcohol use disorder, depression who presented to the emergency room with left sided abdominal pain and flank pain for the past 2 days. He had nausea but no vomiting and had been off of hypertriglyceridemia treatment for over a year. He smoked half a pack of cigarettes for 15 years and drinks 3-4 alcoholic beverages a day. Physical examination was notable for soft, left lower quadrant tenderness. His triglyceride levels on admission were over 10,000 (normal: <150 mg/dL). LFTs were slightly elevated (AST: 77, ALT: 64, ALP: 150, normal ranges: 5-30 IU/L, 4-46 IU/L, 30-120 IU/L, respectively). He was afebrile with no leukocytosis. Abdominal CT scan showed acute edematous interstitial pancreatitis. The patient was admitted to the ICU. He was made NPO, placed on saline infusions, started Insulin drip, Dextrose drip for recurrent hypoglycemia from the insulin drip, and fenofibrate. Hydromorphone and ketorolac used for pain. On hospital day 2, the patient’s triglyceride level was below 800, and insulin and dextrose drips were discontinued. The patient started on a clear diet. He was transferred over to the floors, where his triglycerides continued to downtrend and abdominal pain improved. Patient was discharged back home on hospital day 5 with fenofibrate, atorvastatin, thiamine, and folic acid. Conclusion : This case report serves as a valuable learning experience by showcasing the interplay of risk factors, the importance of diligent treatment, and the effectiveness of prompt and multi-faceted management of triglyceride-induced pancreatitis. This case also highlights the importance of adhering to treatment to prevent recurrence of HTGP. Finally, aggressive lipid lowering therapy like insulin and fenofibrate reduced the patient’s triglyceride levels in a short time frame.

Presentation: 6/3/2024
7368 Triglyceride Tales: Two Cases Unveiling Pegaspargase-Induced Hypertriglyceridemia
Authors: Noguchi S , Singh A , Rajpal A
Published: October 2024

Disclosure: S. Noguchi: None. A. Singh: None. A. Rajpal: None.

Introduction: Acute lymphoblastic leukemia (ALL) is a hematologic malignancy that has seen dramatic improvements in survival, owing to the development of multi-agent chemotherapy regimens. Pegaspargase (PEG), an enzyme that depletes serum asparagine and leads to apoptosis of leukemic cells, has long been a cornerstone of ALL chemotherapy regimens. While many toxicities have been recognized including hypersensitivity, thrombosis and hepatotoxicity, hypertriglyceridemia (HTG) is a much less documented complication. We present two patients who developed severe hypertriglyceridemia (sHTG) secondary to PEG, with differing outcomes. Both patients were re-challenged with PEG and again developed sHTG. Case description: A 31-year-old male presented with leukocytosis and blastemia and was diagnosed with Philadelphia chromosome negative B-cell ALL. He underwent chemotherapy induction via pediatric-inspired protocol CALBG 10403 which included PEG. Three weeks later triglyceride (TG) levels rose to 3,728 mg/dl, but normalized with gemfibrozil over the next month. He received two more doses of PEG, separated by four weeks, as part of consolidation chemotherapy. Eleven days following the third dose he presented with abdominal pain, lipase of 702 units/L, TG of 3,999 mg/dl and imaging consistent with necrotizing pancreatitis. With intravenous insulin and meropenem he eventually made a full recovery, however he had a persistent pancreatic pseudocyst. Thereafter, he was transitioned to HyperCVAD followed by POMP maintenance chemotherapy.Another patient, a 35-year-old female presented with cytopenia and was also diagnosed with Philadelphia chromosome negative B-cell ALL. She was also induced with CALBG 10403 protocol including PEG. One month later her TG levels rose to 1,295 mg/dl and was started on fenofibrate. Following resolution of the lipemia, she underwent consolidation chemotherapy which included two doses of PEG administered four weeks apart. Despite a 50% dose reduction, ten days after the third dose TGs rose to a peak of 3,363 mg/dl, however she did not develop pancreatitis. She was treated with intravenous insulin, gemfibrozil and omega-3-acid ethyl esters for sHTG. Given complications with CALGB, she is planned to transition to blinatumomab consolidation. Discussion: Albeit a rare complication of PEG, the presented cases highlight the severity of HTG that can result from this commonly used chemotherapy agent. There are currently no guidelines for the baseline assessment of TG levels in ALL patients receiving PEG. Awareness of this potential complication should prompt regular monitoring of TG levels in patients undergoing regimens involving PEG. There is a need for future studies to identify patients at higher risk of developing sHTG and evaluate the appropriate dose and frequency of PEG administration in patients who develop sHTG after initial exposure.

Presentation: 6/3/2024
9326 A Case Of Diabetic Ketoacidosis Obscured By Metabolic Alkalosis In An Individual With End-stage Renal Disease
Authors: Messersmith Andrew L , Bayrakdar Keenan , Killeen David
Published: October 2024

Disclosure: A.L. Messersmith: None. K. Bayrakdar: None. D. Killeen: None.

Diabetic ketoalkalosis (DKALK) is a term coined in the literature by Bleicher in 1967, characterized by diabetic ketoacidosis (DKA) with concomitant metabolic alkalosis. Patients with DKALK may present with normal to elevated bicarbonate and an alkalotic pH secondary to recurrent vomiting, ingestion of alkali, contraction alkalosis from hyperglycemia-induced osmotic diuresis, or diuretics. Here we discuss a 33-year-old female who presented to the hospital with non-bloody, nonbilious vomiting for two days and unremitting abdominal pain that started the day of arrival to the emergency department (ED) along with two ulcers localized to the lateral aspect of her foot with purulent discharge. Her past medical history was significant for insulin dependent diabetes mellitus complicated by recurrent DKA, diabetic peripheral neuropathy and retinopathy, amputation of the left fifth toe at the mid metatarsal secondary to osteomyelitis, hypertension, and end-stage renal disease (ESRD) on hemodialysis (HD). Blood glucose was 302 mg/dL, bicarbonate 30 mmol/L, chloride 96 mmol/L without an anion gap, lactic acid 3.6 mmol/L, and urinalysis positive for glucose and ketones. Blood cultures grew Staphylococcus hominis and epidermidis, and Actinetobacter lwoffii. Magnetic resonance imaging was compatible with chronic osteomyelitis of the fifth metatarsal stump. On the third day of hospitalization, after worsening abdominal pain, nausea, and vomiting, repeat laboratory results showed a blood glucose 580 mg/dL, chloride 95 mmol/L, beta-hydroxybutyrate 4.23 mmol/L; and a pH of 7.609 and bicarbonate of 23 mmol/L on ABG with an anion gap of 23 mmol/L. The patient was treated with insulin, intravenous fluids, potassium, and antibiotics with resolution of symptoms. Diabetic ketoalkalosis is a condition rarely reported in the literature. Case reports have included association with type I diabetes in patients with underlying gastroparesis presenting for abdominal discomfort and vomiting. Loss of hydrochloric acid from vomiting increases bicarbonate in the body. Volume contraction activates the renin-angiotensin-aldosterone system (RAAS), which acts on the kidneys to reabsorb sodium and bicarbonate, generate new bicarbonate, and excrete hydrogen ions into the urine. The delta ratio can be used to identify DKALK, along with the presence of serum or urine ketones, and an elevated anion gap. In DKALK the delta ratio (increase in anion gap/decrease in bicarbonate) is greater than 1.2; Our patient had a delta ratio of 11. This case highlights the importance of identifying DKALK, a mixed metabolic acidosis and alkalosis disorder, to prevent morbidity and mortality associated with misdiagnosis.

Presentation: 6/2/2024
8337 A Case Report of Polypharmacy With Combined Adverse Effects of SGLT-2 Related Euglycemic DKA and Lithium Induced Nephrogenic DI
Authors: Gupta Uma Datta , Subedi Saphal Nath , Kunwar Kalendra , Ghimire Brijesh , Dhakal Govind , Bagain Jay B , Ishrat Syeda R
Published: October 2024

Disclosure: U.D. Gupta: None. S.N. Subedi: None. K. Kunwar: None. B. Ghimire: None. G. Dhakal: None. J.B. Bagain: None. S.R. Ishrat: None.

Polypharmacy, typically defined as the use of 5 to 10 medications, is linked to an elevated risk of adverse drug events (ADEs) and hospital admissions, independent of age. In the USA, 67 percent of hospitalizations are linked to four medications or classes: warfarin, insulins, oral antiplatelet agents, and oral hypoglycemic agents. A higher number of medications increases the likelihood of "prescribing cascades," where an ADE is mistaken for a new medical condition, leading to additional drug therapy. In our case report we are presenting a 41 years old female with a medical history of Hypertension, Diabetes Mellitus Type 2, Schizoaffective disorder, presented to the emergency department with left gluteal pain with subsequent CT scan shows Fournier's gangrene or perforated perirectal abscess and she received IV antibiotics, pain management, and fluids. Patient has been taking Lantus, Glipizide (sulfonylurea), and Empagliflozin, Bupropion and Aripiprazole at home. During her treatment of sepsis she was diagnosed with euglycemic DKA (A1c - 10.3, Blood glucose 240-180s, anion gap metabolic acidosis, glucosuria >1000, Ketone bodies of 40, beta hydroxybutyrate 3.18, serum osmolality 303, urine osmolality 140, urine output 13 liters/24 hrs). Furthermore Lithium Level reported 0.1(mild toxicity 1.5 mEq/L or 1.5 mmol/L). In literature, Sodium-glucose cotransporter 2 (SGLT2) inhibitors can reduce lithium levels. Polyuria and polydipsia are common in lithium-treated patients (70% cases), with potential risk factors including longer treatment duration, episodes of toxicity, and concurrent use of other psychotropic medications. In some cases, the lack of significant hyperglycemia (plasma glucose <250 mg/dL ) can lead to a delayed identification of issues by both patients and clinicians (risk is 2 times higher than other therapies), it is recommended to check for serum ketones. The patient received treatment for other comorbidities; however, Lithium and Empagliflozin were withheld during her hospital stay, leading to gradual improvement. This case report will enforce the importance of ensuring appropriate drug prescribing involves factors such as avoiding inappropriate medications, monitoring for side effects and drug levels, preventing drug interactions, and incorporating patient values through active involvement. This case is an unique opportunity to learn ADEs, contributing to diagnostic challenges which can increase mortality across various age groups without proper vigilance.

Presentation: 6/3/2024
8002 A Dose Beyond Limits: Semaglutide and Insulin Overdose - A Novel Approach to Management
Authors: Foo Francine Fane , Amin Tasnuva , Farhat Farah , Gonzalez Paula , Hu Katherine , Chalasani Krishna , Cheng Jennifer , Ong Raquel Kristin , Akula Monika Soujanya , Philip Rosily , Holland Soemiwati Weidris
Published: October 2024

Disclosure: F.F. Foo: None. T. Amin: None. F. Farhat: None. P. Gonzalez: None. K. Hu: None. K. Chalasani: None. J. Cheng: None. R. Ong: None. M.S. Akula: None. R. Philip: None. S.W. Holland: None.

Background: In the past decade, treatment of diabetes has expanded to include multiple classes of medication including GLP-1 agonists. Although newer medications offer better safety profiles, overdosing on these agents can have potentially fatal complications. Several cases of insulin overdose have been reported to date however, only a few cases of GLP-1 receptor agonist overdoses have been recorded and to our knowledge none have been reported on semaglutide specifically. We present a unique case of a patient who intentionally overdosed with massive amounts of both the injectable GLP-1 receptor agonist and multiple types of insulin and our approach to management. Case Presentation: This is a case of a 61 year old female with past medical history including depression, hypertension, stage 3 chronic kidney disease, and insulin dependent type 2 diabetes. She was brought by EMS to the emergency room after injecting herself with Toujeo Max 1800 units, Lantus 300 units, Humalog 300 units, and a pen of Ozempic (3mL). On initial EMS contact, the patient's blood glucose was 27 and she was given 50cc of D10W which improved her blood glucose to 110. Her admission was complicated by persistent hypoglycemia despite ongoing intravenous dextrose infusions, injections of octreotide and glucagon, and IV steroids. Given the long half life and massive dose of Toujeo, a decision was made to initiate hemodialysis to expedite insulin metabolism and removal. Insulin levels were monitored before and after dialysis to determine the efficacy of dialysis. After 1 session of dialysis insulin levels improved from 286.37 to 124.66 miU/mL and due to patient’s preference dialysis was discontinued. Following dialysis, the patient was able to be tapered off steroids and no longer required glucagon and octreotide injections. Her insulin levels continued to trend down daily and eventually she was resumed on her home basal - bolus insulin regimen. On day 10 of admission, she was deemed both medically and psychiatrically clear for discharge. She was sent home with a basal - bolus regimen, she was seen at our office for follow up and continues to do well. Conclusion: Newer diabetes medications and insulin formulations have become increasingly popular and physicians must remain vigilant in identifying potential complications that can arise from intentional overdose. Although hypoglycemia treatment has been well established, it is crucial to consider other methods and protocols.

Presentation: 6/3/2024
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

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

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 < 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

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 (< 18 mEq/L) or arterial pH (< 7.3 pH units), with a normal or mildly elevated blood glucose (> 250 mg/dL) and Beta-hydroxybutyrate (>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

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

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>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

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 < 3), C-peptide 22.1 ng/mL (expected < 0.6), and proinsulin 7.4 pM (expected < 5). Beta-hydroxybutyrate level was 0.1 mM (expected > 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 > 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

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

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
12461 The Impact Of Switching From A Glp-1 Analog To Tirzepatide On Blood Glucose Levels, Body Weight, And Liver Function In Patients With Type 2 Diabetes
Authors: Mizoguchi R , Sawamura T , Ohmori A , Yagishita N , Kometani M , Yoneda T , Karashima S
Published: October 2024

Disclosure: R. Mizoguchi: None. T. Sawamura: None. A. Ohmori: None. N. Yagishita: None. M. Kometani: None. T. Yoneda: None. S. Karashima: None.

Context: Tirzepatide belongs to a new class of anti-diabetic agents that stimulate both glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptors, which have strong blood glucose-lowering and large body weight reduction effect. Because of these characteristics of tirzepatide, it is expected to have beneficial effects for obese patients who need further blood glucose control. In the pharmacological approaches to glycemic treatment described by the American Diabetes Association, GLP-1 analogs are positioned as strong blood glucose-lowering agents that additionally reduce body weight (BW). Furthermore, GLP-1 analogs also improves liver injury in patients with fatty liver and diabetes. Tirzepatide reportedly has a greater blood glucose-lowering effect and body weight reduction than dulaglutide and semaglutide, which are common GLP-1 analogs in Japan. However, no data about the switching from these GLP-1 analogs to tirzepatide are available. In addition, The effect of tirzepatide on steatohepatitis is still unknown. Therefore, this study evaluated the effects of switching from dulaglutide to tirzepatide on blood glucose level, BW, and liver function. Material and Methods: Data from 40 patients with type 2 diabetes who received a prescription change from dulaglutide to tirzepatide were retrospectively analyzed at the 3 and 6 months after the switch. The analyzed data included glycosylated hemoglobin (HbA1c), BW, body mass index (BMI), aspartate aminotransferase (AST), alanine aminotransferase (ALT), γ-glutamyl transpeptidase levels (γ-GTP) levels, and fibrosis-4 index. In addition, factors influencing the changes in HbA1c, BW, ALT, and fibrosis-4 index at 6 months were evaluated. Results: The mean HbA1c levels decreased from 7.9 ± 1.1% at baseline to 7.0 ± 0.8% at 3 months (p < 0.001) and 6.7 ± 0.7% at 6 months (p < 0.001). The mean BW decreased from 74.9 ± 18.3 kg at baseline to 71.9 ± 17.9 kg at 3 months (p < 0.001) and 71.3 ± 18.0 kg at 6 months (p < 0.001). The change in HbA1c level was negatively correlated with baseline HbA1c level. However, the BW reduction was observed regardless of baseline characteristics. AST, ALT, and γ-GTP levels were also significantly lower 6 months after the switch. The decrease in ALT level was greater in patients with higher baseline AST, ALT, and γ-GTP levels. The fibrosis-4 index did not improve during the study period, but there was a decreasing trend in patients with higher baseline fibrosis-4 index. Conclusion: Switching from dulaglutide to tirzepatide may have beneficial effects on blood glucose levels, BW, and liver function in patients with type 2 diabetes.

Presentation: 6/2/2024
6399 Unmasking A Silent Threat
Authors: St. Jean Karen M , Upadhyay Jagriti , Aron Polina , Tchong Leo , Toraldo Gianluca
Published: October 2024

Disclosure: K.M. St. Jean: None. J. Upadhyay: None. P. Aron: None. L. Tchong: None. G. Toraldo: None.

Introduction: Checkpoint inhibitor-associated autoimmune diabetes mellitus (CIADM) is a rare illness, with an incidence of 0.2-1.4%. However, its clinical implications are significant due to the high incidence of DKA at presentation, the lifelong persistent insulin deficiency, and the associated risk factors of diabetes complications and decreased life expectancy. This substantially impacts the patient's quality of life, healthcare costs, and treatment adherence. Case Description: A 63-year-old man with a history of type 2 DM well controlled with GLP-1A once a week presented to the hospital for persistent hyperglycemia in the 400s associated with nausea and vomiting. Upon admission, the patient had DKA with a pH of 7.3, bicarbonate 9 mmol/L, AG 29 mmol/L, elevated beta-hydroxybutyrate 10.42 mmol/L, and glucose of 655 mg/dL. The patient had a significant past medical history of stage IIA lung adenocarcinoma in 2019, s/p surgery and adjuvant chemoradiotherapy and was on surveillance till he got metastatic recurrence in 2023. Four weeks before his admission, patient was started on immunotherapy with pembrolizumab for recurrent disease.A complete workup in the hospital showed a positive GAD-65 and a low C-peptide 0.10 ng/dL consistent with diagnosis of insulin deficiency likely causing DKA. The patient was started on insulin, and blood sugars are now well controlled on insulin regimen. Discussion: Our case had a unique presentation, given the acute onset within four weeks of starting immunotherapy and the severity of his presentations by developing DKA. The median onset described in the literature for insulin deficiency from immunotherapy is typically between 12-25 weeks in different reports. DKA is a life-threatening illness with a 2-5% mortality rate in the United States. Hence, early identification of at-risk patients is vital to prevent hospitalizations and mortality.Limited data is available about CIADM, and the presence of autoantibodies appears to be associated with a more rapid and severe onset of CIADM. This highlights the need for identifying biomarkers or predictive factors to help identify patients at higher risk and potentially intervene earlier in their treatment.Finally, CIADM is characterized by sudden permanent b-cell failure occurring after immuno-therapy. Therefore, it is essential to be familiarized with CIADM and its unique characteristics to provide timely and appropriate care to affected individuals. Moreover, as immunotherapy becomes increasingly common in cancer treatment, awareness of CIADM becomes even more critical for managing potential complications and optimizing patient outcomes.

Presentation: 6/2/2024
8615 Unveiling The Muscle-Specific Role Of Fat-Specific Protein 27 In Regulating Muscle Performance And Whole-Body Glucose Homeostasis
Authors: Basri R , Balakrishnan B , Slayton M , Becker C , Hussein H , Puri I , Gupta A , Sharma V , Baumann C , Consitt L , Puri V
Published: October 2024

Disclosure: R. Basri: None. B. Balakrishnan: None. M. Slayton: None. C. Becker: None. H. Hussein: None. I. Puri: None. A. Gupta: None. V. Sharma: None. C. Baumann: None. L. Consitt: None. V. Puri: None.

Skeletal muscle (SkM) function, strength, and intrinsic muscle quality are closely linked to the pathogenesis and pathophysiology of metabolic disease. However, the regulatory molecular mechanisms in SkM performance remain elusive. Our study identifies Fat-Specific Protein (FSP27) as a novel player in muscle function. FSP27, previously found to be expressed in adipose and liver, is highly expressed in skeletal muscles (SkM). We recently found that the global FSP27 knockout (Fsp27-/-) mice have severely reduced muscle performance. Also, our human data identified a positive correlation of SkM FSP27 expression with indices of muscle performance such as aerobic capacity, muscle strength, and responsivity to exercise training. However, these studies could not explain the role of muscle-specific FSP27 Therefore, to study the physiological and mechanistic role of SkM-specific FSP27, we generated a loss-of-function Fsp27 knockout mouse model through muscle-specific ablation of FSP27 (M-Fsp27-/-). Treadmill running and hanging-grid tests were performed to study exercise endurance and muscle strength, respectively. M-Fsp27-/- showed significantly reduced running endurance and reduced muscle strength. In addition, glucose and insulin tolerance were significantly reduced in M-Fsp27-/- mice, suggesting the effect of muscle-specific FSP27 in whole-body glucose homeostasis. No sexual dimorphism was observed in muscle-specific functions of FSP27 and its effect on whole-body glucose homeostasis, with females showing similar results to males. Moreover, M-Fsp27-/- mice showed reduced energy expenditure compared to their littermate floxed controls. Interestingly, we found that FSP27 interacts with lactate dehydrogenase A (LDHA), and the rate of lactate production was found to be negatively associated with FSP27 expression in the SkM, indicating the molecular role of FSP27 in substrate utilization. Overall, our results identify a novel role of FSP27 in regulating muscle performance and metabolism via its effect on substrate utilization to produce energy.

Presentation: 6/1/2024