bluuebunny/crossref_metadata_2025_split huggingface dataset:
THU364 A Rare Case Of Concurrent Diabetic Ketoacidosis And Grave’s Thyrotoxicosis
Authors: Quadros Teixeira Aline De , Ukponmwan Esosa , Kachhadia Palak , Aldasouqi Saleh , Abu Limon Ahmad 
Published: October 2023

Abstract
Disclosure: A.D. Teixeira: None. E. Ukponmwan: None. P. Kachhadia: None. S. Aldasouqi: None. A. Abu Limon: None.
Introduction: Type 1 Diabetes Mellitus (T1DM) is marked by deranged glycemic control due to the autoimmune destruction of insulin producing β cells in the pancreas. It affects 1.5 million adults in the United States. Approximately one-third of these patients may develop autoimmune polyglandular syndrome (APS). Autoimmune Thyroid Disease (AITD) is the most commonly associated autoimmune disease, with Hashimoto’s Thyroiditis more commonly observed than Graves Disease (GD). Patients with AITD and T1DM meet criteria for APS type 3A. Here, we present a case of a patient hospitalized for T1DM with diabetic ketoacidosis (DKA) who was also found to have concurrent GD. Case Presentation: Our patient was a 50 year old male who presented to the hospital with complaints of nausea and vomiting for a two day duration. He had symptoms of unintentional weight loss, polyuria and polydipsia for about two months prior to presentation. He was found to have blood sugar level of 438 mg/dL, with pH of 7.05 (7.35-7.45), anion gap of 30, bicarbonate level of 7.0 mmol/L (20-30 mmol/L), Beta-hydroxybutyrate level of 82mg/dL (n&lt;4.10 mg/dL). Hemoglobin A1C was 15.1% . EKG revealed atrial fibrillation with RVR, and therefore thyroid function tests (TFTs) were ordered and showed a thyroid stimulating hormone (TSH) level of 0.01uIU/mL (0.35-4 uIU/mL), free thyroxine (FT4) of 1.29 ng/dL (0.61-1.37 ng/dL) and free triiodothyronine (FT3) levels of 4.4 pg/mL (2.8-4.4 pg/mL). Endocrinology evaluation of the patient’s Thyroid US showed some mild vascularity. Cardiac evaluation of patient’s atrial fibrillation did not reveal any other causes of arrythmia. Further labs showed TSI of 2.6 (n&lt;1.3 TSI index) with normal TRAb and TPO levels. T1DM antibody testing revealed GAD-65 antibody (Ab) level of 51.3 nmol/L (n &lt;0.02 nmol/L), Zinc Transporter 8 Ab level of &gt;500 U/mL (n&lt;15 U/mL). He was started on methimazole with good tolerance and was discharged upon resolution of his DKA with multiple daily injections of insulin. Discussion: AITD is the most prevalent autoimmune disease associated with T1DM, with GD being a less common association compared to Hashimoto’s thyroiditis. Many patients diagnosed with T1DM may develop other autoimmune conditions. On rare occasions these diseases can present concurrently, as it did with our patient. Recognition and awareness of APS types helps physicians recognize and screen for other autoimmune conditions that have previously been seen together. Literature search shows very few cases with both diseases presenting at the same time on hospitalization. However, with the recent COVID-19 pandemic, 5 cases were reported of simultaneous disease following vaccination. Our patient had no known exposure to COVID-19 virus or vaccine when he developed symptoms.
Presentation: Thursday, June 15, 2023
THU367 Hyperosmolar Hyperglycemic State In A Middle-old Male With Primary Hyperparathyroidism
Authors: Mandocdoc Dimayuga Diana Colleen , Capuli Isidro Maria Jocelyn 
Published: October 2023

Abstract
Disclosure: D.M. Dimayuga: None. M.C. Isidro: None.
A 79-year-old male was brought to our hospital for drowsiness. He had low-grade fever with associated cough and anorexia 1 week prior. He had a previous history of hypertension and primary hyperparathyroidism (PHPT) maintained on cinacalcet. He did not have a history of diabetes and a family history of diabetes, and his HbA1c was 5.4% three months before. On admission, the results of his physical examination and vital signs were as follows: height, 152cm; weight, 56.0 kg; BMI, 24.2 kg/m2; temperature, 36.5C; heart rate, 85 beats/min; SpO2, 98% (on room air); respiratory rate, 22 breaths/min; and blood pressure, 115/60 mm Hg. His blood glucose level was 966 mg/dL, HbA1c 13.4%, and serum osmolality 324 mOsm/kg. Serum ketones were 15 mg/dL and blood gas analysis was normal. He was diagnosed with hyperglycemic hyperosmolar state (HHS) and infusion of insulin and saline was subsequently initiated. With clinical suspicion of chronic pancreatitis given the patient’s history of PHPT, serum lipase was checked, 105 U/L (NV: 12-53 U/L). Ionized calcium was 1.36 mmol/L. On CT scan of abdomen, there was no evidence of duct dilatation and calcification, and instead, “features of diffuse fatty atrophy of the pancreas” were seen. His endogenous insulin secretory capacity was sufficient (serum C-peptide: 2.76 ng/mL, NV: 0.78-5.19 ng/mL). Eventually, the patient’s level of consciousness improved and glycemic control was achieved. Soon after, insulin was shifted to basal-bolus regimen. On the 7th day of hospitalization, patient was discharged with minimal insulin requirements. Two weeks later, on follow up, his blood glucose levels were found to be stable. It was not clear whether our patient had new-onset autoimmune or type 2 diabetes. Although autoimmune diabetes generally occurs when about 90% of the pancreatic beta cells have been destroyed, the patient could have been in the honeymoon period wherein beta cell activity was transiently regained after commencement of insulin therapy. Our plan is to monitor his C-peptide titers and test his insulin antibodies. Evidence suggests that PHPT may cause insulin resistance and glucose intolerance. The rise in free intracellular calcium may reduce glucose transport in insulin-stimulated glucose transporters, increasing the need for insulin. This could be the case in our patient hence we diagnosed him with type 2 diabetes. To the best of our knowledge, this is the first case demonstrating the co-occurrence of HHS and PHPT.
Presentation: Thursday, June 15, 2023
THU371 Empagliflozin Associated Pancreatitis: A Case Report
Authors: Poloju Alekya , Majety Priyanka , Groysman Anna Y 
Published: October 2023

Abstract
Disclosure: A. Poloju: None. P. Majety: None. A.Y. Groysman: None.
Background/Objective: Sodium glucose cotransporter 2 (SGLT2) inhibitors are increasingly being used in the treatment of type 2diabetes mellitus (T2DM). With the recent FDA approval of these medications for treatment of heart failure, their use is expected to increase further. Common adverse events associated with SGLT2 inhibitors are genitourinary infections, hypotension, acute kidney injury and euglycemic diabetic ketoacidosis. Recently, SGLT2 inhibitors are increasingly associated with drug induced acute pancreatitis (DIAP). We present a case of empagliflozin associated DIAP, with the intent to add to the limited data on this possible adverse effect. Clinical Case: A 57-year-old woman with a history of T2DM presented to the hospital with severe abdominal pain. She had no recent alcohol use or prior episodes of pancreatitis. There was no history of trauma. Home medications include metformin, glipizide, empagliflozin, and lisinopril. Exam showed epigastric tenderness to palpation without guarding or rebound tenderness. Labs were notable for elevated white blood cell count, normal lipase, calcium, triglycerides, and liver function tests. CT abdomen showed induration of the peri-pancreatic fat, suggestive of pancreatitis. After ruling out common causes of pancreatitis, DIAP and idiopathic pancreatitis were considered possible etiologies. Obtaining further history revealed that patient was started on empagliflozin two weeks prior to this presentation. The only other medication that is known to cause pancreatitis is lisinopril but our patient was on this medication for several years. The Naranjo probability scale for empagliflozin showed a possible association between the drug and side effect. Empagliflozin was discontinued and the patient was discharged on metformin and glipizide. Conclusions: Pancreatitis is a common diagnosis requiring hospital admission and is associated with significant costs to the healthcare system. Although pancreatitis is a known side-effect with other medications used in treatment of T2DM, such as GLP1RAs and DPP-4inhibitors, it has not been well described with SGLT2 inhibitors. The prevalence of DIAP is difficult to assess since most of the existing data comes from individual case reports. Our patient had no known risk factors for pancreatitis. It is yet to be studied if genetic predisposition has a role in the development of pancreatitis with SGLT-2 inhibitors. With the increasing use of these medications in the treatment of type 2diabetes mellitus and heart failure, more cases of DIAP are being reported. It is important for physicians to consider SGLT2 inhibitors as a cause of pancreatitis after excluding other common etiologies. This may reduce episodes of recurrent pancreatitis and the burden of extensive workup for idiopathic pancreatitis.
Presentation: Thursday, June 15, 2023
THU377 Arterio-enteric Fistula, A Rare Complication After Pancreatic Transplant
Authors: Herrera Chancay Azucena M , Calderon Andres , Manavalan Anjali 
Published: October 2023

Abstract
Disclosure: A.M. Herrera Chancay: None. A. Calderon: None. A. Manavalan: None.
Introduction: Areterio-enteric (AE) fistula is a rare but life-threatening complication of a failed pancreas transplant and most often presents with a gastrointestinal (GI) herald bleed. This case illustrates the importance of the prompt recognition and appropriate evaluation of GI bleeding in patients with a failed pancreas transplant and highlights the challenges associated with the management of an AE fistula. Case Description: A 53-year-old man with history of T1D complicated by retinopathy, neuropathy, nephropathy, end-stage renal disease (ESRD) and failed combined pancreas-renal transplant, presented to our hospital with diabetic ketoacidosis secondary to insulin pump malfunction. His course was complicated by a GI bleed. He was initiated on proton pump inhibitors but endoscopy was deferred due to resolution of bleeding. The patient was discharged from the hospital with plans for outpatient endoscopy however, he returned to the emergency room with hematemesis, malena and hemorrhagic shock complicated by cardiac arrest. Emergent endoscopy was performed but the source of bleeding could not be visualized due to large clots and fresh blood. A CT angiogram revealed brisk bleeding from the right common iliac pancreatic transplant graft. Coil embolization was attempted but unsuccessful and the patient was ultimately treated with two stents to the right iliac artery with subsequent resolution of bleeding. The patient was ultimately discharged home in stable condition. Conclusion: During pancreas transplant, the donor pancreas and duodenum are connected by a Roux en Y anastomosis to the small bowel of the recipient. The donor pancreas is placed in the right iliac fossa followed by anastomosis of the recipient right common iliac artery with the donor Y graft (Consisting of the iliac artery, its bifurcation, and the splenic and superior mesenteric arteries). AE fistula is an extremely rare complication of pancreatic transplant with only about 30 reported cases. This occurs in the setting of transplant failure, possibly due to the increased local inflammation. Endoscopy is often unsuccessful in locating the bleeding source. Angiography and stenting of the bleeding vessel seem to offer the most success and should be considered in patients with failed pancreas transplant presenting with GI bleeding.
Presentation: Thursday, June 15, 2023
FRI637 Missed MODY With Complex Mutation
Authors: Bulchandani Sheetal , Chandra Majety Sarat , Kundra Priya 
Published: October 2023

Abstract
Disclosure: S. Bulchandani: None. S. Majety: None. P. Kundra: None.
Introduction: The prevalence range of Maturity-Onset Diabetes of the Young (MODY) is 1-5% among all patients diagnosed with diabetes. Strong family history of diabetes is suggestive of autosomal dominant inheritance. The symptoms of MODY range from mild asymptomatic hyperglycemia to overt insulinopenia requiring insulin therapy. Clinical Case: 33-year-old male presented to the endocrinology clinic for evaluation. He was diagnosed with type 2 diabetes mellitus at the age of 13 years and was initially treated with insulin which was subsequently transitioned to repaglinide and metformin. Reported history of hypoglycemia at birth in self and recently born daughter. Family History was significant for diabetes mellitus diagnosed in biological father at the age of 16 years. Genetic testing for monogenic diabetes revealed pathogenic variant in hepatocyte nuclear factor 4 alpha (HNF4a) and variant of unknown significance in Paired Box Gene 4 (PAX4). Therapy was switched to glipizide 2.5 mg orally which resulted in adequate glycemic control. Genetic testing was recommended for his daughter. Conclusion: MODY is a rare condition and because of its wide clinical presentation, it is common for it to be missed. There are about 14 subtypes of MODY with different genetic mutations, each affecting the beta cell function in a different way. Our case is unique given that our patient had two genetic mutations. Amongst all forms of MODY, HNF4a with a prevalence of 5% to 10% is the third most common mutation of MODY. PAX4 is a transcription factor that is critical for the formation of beta cells, and is important as a regulator in commitment of progenitor cells to mature islet cells. Mutations in PAX gene associated with monogenic diabetes were first identified in two patients of Thai origin, who did not present with mutations in the other known MODY genes. There should be high vigilance and low threshold for genetic testing for MODY in patients who have high likelihood of possessing a form of MODY, particularly as the treatment can be tailored to the clinical presentation of the patient. References: 1. Abreu GM, Soares CAPD, Tarantino RM, da Fonseca ACP, de Souza RB, Pereira MFC, Cabello PH, Rodacki M, Zajdenverg L, Zembrzuski VM, Campos Junior M. Identification of the First PAX4-MODY Family Reported in Brazil. Diabetes Metab Syndr Obes. 2020 Jul 24; 13:2623-2631. doi: 10.2147/DMSO.S256858. PMID: 32801813; PMCID: PMC7399458. 2. Antal Z. Maturity-Onset Diabetes of the Young (MODY): Genetic Causes, Clinical Characteristics, Considerations for Testing, and Treatment Options. Endocrines. 2021; 2(4):485-501. https://doi.org/10.3390/endocrines2040043
Presentation: Friday, June 16, 2023
SAT053 Development Of A Novel Peptide-based Insulin Sensitizer Through Disruption Of Inositol Polyphosphate 5-Phosphatase K (SKIP) - p21-activated Kinase 1 (Pak1) Interactions
Authors: Kimbrough Alyssa M , Dev Gaddameedi Jitender , Lipchik Andrew M 
Published: October 2023

Abstract
Disclosure: A.M. Kimbrough: None. J. Dev Gaddameedi: None. A.M. Lipchik: None.
Type 2 diabetes (T2D) is a prominent, chronic metabolic disease that affects approximately 462 million people worldwide. The driving force behind T2D is insulin resistance (IR), defined as an impaired biological response to insulin, and leads to a multitude of more severe conditions including heart disease, stroke, and neuropathy. Most therapies fail to improve insulin sensitivity, and instead drive physiological compensation. It is imperative to develop new therapies to correct the underlying pathology by targeting mechanisms of IR. Inositol polyphosphate 5-phosphatase K (INPP5K/SKIP) is a potential target to treat IR. SKIP resides in the endoplasmic reticulum (ER) in resting cells, and translocates to the plasma membrane (PM) following growth factor stimulation. SKIP is recruited to the PM through binding to p21 activated kinase 1 (Pak1) and inhibits growth factor signaling through dephosphorylation of phosphoinositol-(3,4,5)-triphosphate. In obesity and IR, SKIP is overexpressed leading to PM localization and suppression of insulin signaling. Here, we developed a novel insulin sensitizer utilizing a peptide derived from Pak1 to inhibit SKIP-Pak1 interactions and prevent PM localization. We found that the Pak1 derived peptide displayed alpha helical properties and thermostabilized SKIP. In controlled in vitro assays, the Pak1 peptide was successfully taken up in target tissues. Additionally, treatment with the Pak1 peptides was sufficient to restore insulin sensitivity in skeletal muscle, adipose, and liver models of IR. Together these results demonstrate the use of a peptide-based insulin sensitizer as a novel therapeutic for T2D that requires further investigation.
Presentation: Saturday, June 17, 2023
SAT066 Leukotriene B4 Receptor 2 Mediates Macrophage Migration To Injured β Cells
Authors: Ermis Ebru , Nargis Titli , Kulkarni Abhishek , May Sarah , Tersey Sarah A , Mirmira Raghavendra G , Anderson Ryan M 
Published: October 2023

Abstract
Disclosure: E. Ermis: None. T. Nargis: None. A. Kulkarni: None. S. May: None. S.A. Tersey: None. R.G. Mirmira: None. R.M. Anderson: None.
Type 1 diabetes (T1D) is an autoimmune disease, characterized in part by islet inflammation and macrophage infiltration leading to β-cell injury and loss. The inflammatory mediator 12/15-lipoxygenase (12/15-LOX) and its lipid product 12-hydroxyeicosatetraenoic acid (12-HETE) have both been implicated in T1D. 12-HETE activates the low affinity receptor leukotriene B4 receptor 2 (LTB4R2, or simply BLT2), which was reported as a low-affinity receptor for 12-HETE, suggesting that BLT2 may play a proinflammatory role. Here, we used both mouse and zebrafish models to probe the roles of BLT2 in macrophage activation and/or recruitment to pancreatic islets during T1D progression. First, we analyzed Blt2 gene expression in a variety of C57BL/6J mouse tissues. We found Blt2 gene expression in bone marrow derived macrophages and peritoneal macrophages, however we found little to no expression in pancreatic islets. Although Blt2-/- mice showed a significantly reduced expression of Blt2, they exhibited overall normal growth and glucose tolerance. To uncover roles for BLT2 in macrophage function, we first interrogated its involvement in the in vitro polarization of proinflammatory macrophages to the M1-like state using LPS and IFN-γ and the M2-like state using IL-4. Under these conditions, we found no differences between Blt2-/- and wildtype macrophages, as assessed by flow cytometry analysis, suggesting that BLT2 does not play a substantial role in macrophage polarization. Next, to query roles for BLT2 in macrophage migration, we employed the transgenic zebrafish line Tg(mpeg:EGFP) in which macrophages are labeled with green fluorescent protein (GFP). Following zebrafish tailfin injury, we quantified macrophage accumulation at the injury at 6 hours post amputation. Inhibitory treatments of zebrafish larvae with either a chemical BLT2 inhibitor (LY255283) or by knockdown of the blt2a gene using an antisense morpholino, both decreased the number of GFP+ macrophages found at the injury site. Moreover, in the latter approach ectopic expression of blt2a mRNA effectively restored the wild-type phenotype. To determine if BLT2 mediates macrophage migration to injured islets, we employed a transgenic zebrafish model of β-cell injury, Tg(ins:NTR), in which metronidazole treatment rapidly induces β-cell injury. We treated the Tg(mpeg: GFP); Tg(ins: NTR) zebrafish with metronidazole and monitored macrophage migration into injured islets. We observed a significant decrease in macrophage migration towards injured β-cells in blt2a-knockdown zebrafish. Collectively, these results show that BLT2 plays a role in macrophage migration associated with tissue injury, including the islet β cell as seen in T1D.
Presentation: Saturday, June 17, 2023
SAT075 Beta Cells Adapt To Insulin Resistance Via Posttranslational Modification Of The Translation Factor eIF5A
Authors: Anderson Cara , Kulkarni Abhishek , Maier Bernhard , Tersey Sarah A , Anderson Ryan , Mirmira Raghavendra G 
Published: October 2023

Abstract
Disclosure: C. Anderson: None. A. Kulkarni: None. B. Maier: None. S.A. Tersey: None. R. Anderson: None. R.G. Mirmira: None.
Prior to type 2 diabetes onset, β cells adapt to insulin resistance through compensation—a process that maintains insulin secretion and glucose homeostasis. Our lab has previously shown that β cell compensation requires the activity of deoxyhypusine synthase (DHPS), which post-translationally catalyzes the formation of the amino acid hypusine at Lys50 of eukaryotic initiation factor eIF5A. Although hypusinated eIF5A is required for β cell compensation, it is unclear if unhypusinated eIF5A limits this compensatory response. To identify the role of unhypusinated eIF5A, we used the following animal and cell-based models: RNAi knockdown and transgenic zebrafish; inducible, β cell-specific knockout mice fed a high fat diet; and cultured HEK-293 cells. Zebrafish embryos injected with morpholinos to reduce global DHPS (and accumulate unhypusinated eIF5A) showed stunted exocrine pancreas growth at 3 days post-fertilization. Although, those injected with anti-eIF5A morpholinos (to deplete all eIF5A) showed normal pancreas growth. Transgenic overexpression of a mutant eIF5A incapable of hypusination resulted in reduced pancreas size in zebrafish. Although a unique function of unhypusinated eIF5A has not yet been documented, these findings suggest that the presence of unhypusinated eIF5A may be the major driver of altered pancreas phenotypes. Similarly, following 4 weeks of high fat diet feeding and obesity, mice lacking total eIF5A in β cells had improved glucose tolerance compared to mice lacking DHPS in β cells, despite similar weight gain and insulin sensitivity. To clarify the molecular mechanisms behind the damaging role of unhypusinated eIF5A, we performed polyribosome profiling to measure translation in lysates from HEK-293 cells in which either DHPS or total eIF5A were depleted by RNAi. Whereas loss of total eIF5A slightly reduced mRNA translation elongation, loss of DHPS (and accumulation of unhypusinated eIF5A) reduced mRNA translation initiation. Further experiments in HEK-293 cells suggest that unhypusinated eIF5A increases levels of phosphorylated eIF2α (an inhibitor of global mRNA translation) by specifically interacting with the kinase GCN2. Taken together, our data provide evidence that DHPS deficiency and obesity conditions impair β cell function, in part, from the accumulation of the unhypusinated form of eIF5A. Our studies reveal a mechanism in which β cells respond to obesity by regulating mRNA translation through the balance between hypusinated and unhypusinated forms of eIF5A.
Presentation: Saturday, June 17, 2023