bluuebunny/crossref_metadata_2025_split huggingface dataset:
FRI023 Increased Fibrosis In White Adipose Tissue Of Male And Female bGH Transgenic Mice Appears Independent Of TGF-β Action
Authors: Lach Grace , Bell Stephen , Young Jonathan A , List Edward O , Basu Reetobrata , Geitgey Delaney , Lee Kevin Y , Swegan Deborah , Caggiano Lydia J , Okada Shigeru , Kopchick John J , Berryman Darlene E 
Published: October 2023

Abstract
Disclosure: G. Lach: None. S. Bell: None. J.A. Young: None. E.O. List: None. R. Basu: None. D. Geitgey: None. K.Y. Lee: None. D. Swegan: None. L.J. Caggiano: None. S. Okada: None. J.J. Kopchick: None. D.E. Berryman: None.
Fibrosis is a pathological state caused by excess deposition of extracellular matrix proteins, which can disrupt tissue structure and function. Previous work has shown that male bovine growth hormone (bGH) transgenic mice have high levels of circulating growth hormone (GH) and insulin-like growth factor 1 (IGF-1), marked decrease in lifespan, and increased fibrosis in several tissues including white adipose tissue (WAT), which is more pronounced in the subcutaneous (Sc) depot. The current study expanded on these findings, evaluating: 1) WAT fibrosis in female bGH mice, 2) levels of circulating factors implicated in fibrosis, and 3) the role of TGF-β, a central mediator of fibrogenesis, in the development of bGH WAT fibrosis. Our findings confirmed that female bGH mice exhibit increased WAT fibrosis, most prominent in the Sc depot, like male bGH mice, but also significantly increased in the perigonadal depot, unlike male bGH mice. bGH mice of both sexes have elevated circulating levels of several markers of collagen turnover (plasma P1NP, P3NP and ICTP) and FGF21 relative to controls but no genotype-dependent alteration in fibroblast activation protein (FAP). TGF-β and TGF-β signaling in serum or WAT was either unchanged or reduced in male and female bGH mice at both young and mature ages. The treatment of bGH mice with a TGF-β antagonist, pirfenidone, did not attenuate bGH WAT fibrosis. Contrary to the effects of the chronic exposure to excess GH, acute GH treatments in vivo or in vitro did elicit a modest increase in TGF-β signaling. Finally, single nucleus RNA sequencing confirmed no perturbation in TGF-β or its receptor gene expression in any WAT cell population within subcutaneous bGH WAT; however, a striking increase in B lymphocyte infiltration in Sc bGH WAT was observed. Overall, these data suggest that bGH WAT fibrosis is independent of the action of TGF-β and reveals an intriguing shift in immune cells, particularly B cells, in bGH WAT that should be further explored considering the increasing importance of B cell-mediated WAT fibrosis and aging. Acknowledgements:This work was sponsored, in part, by ASPIRE grant funding from Pfizer. This work was also supported by the State of Ohio’s Eminent Scholar Program to J. J. K. that includes a gift from Milton and Lawrence Goll and by the startup funds from the Heritage College of Osteopathic Medicine at Ohio University, Athens, OH.
Presentation: Friday, June 16, 2023
FRI070 The Urinary Extracellular Vesicles Small RNA Profile Of Obesity Displays Distinct Patterns By RNA Subclass
Authors: Choi Dughyun , Kim Sewon , Kwon Soon Hyo 
Published: October 2023

Abstract
Disclosure: D. Choi: None. S. Kim: None. S. Kwon: None.
Introduction: Urinary extracellular vesicles (EVs) small RNAs are thought to function as potential biomarkers for various physiological states and various diseases. Since urine contains a relatively small amount of microRNA compared to other biofluids, analyzing the distinct pattern of each subclass of small RNAs may provide additional information about gene expression. We attempted to analyze urinary EVs small RNAs by subclass in obesity before and after weight loss. Methods: Urinary extracellular vesicles small RNA sequencing was performed on 6 obese patients before and after their weight loss, which was achieved through bariatric surgery, and the results were compared with those of 6 healthy volunteers. Each distinct subclass of urinary small EVs RNAs was analyzed using a multi-dimensional scaling (MDS) plot. Results: RNA sequencing revealed total number of 5205 urinary EVs small RNAs. In the MDS plot comparing distinct subclass of urinary EVs small RNAs, there were different patterns observed between obesity and healthy volunteers, however, no significant patterns were found between obesity before and after weight loss. More distinct difference patterns between obesity and healthy volunteers were observed in miRNA, tRNA, snoRNA, and snRNA subclasses of urinary EVs small RNAs, whereas piRNA and YRNA subclasses showed indistinct difference patterns (Figure).
Presentation: Friday, June 16, 2023
FRI071 Changes In Branched-chain Amino Acids One-year After Sleeve Gastrectomy In Youth With Obesity And Its Association With Changes In Insulin Resistance
Authors: Becetti Imen , Lauze Meghan , Lee Hang , Bredella Miriam , Misra Madhusmita , Singhal Vibha 
Published: October 2023

Abstract
Disclosure: I. Becetti: None. M. Lauze: None. H. Lee: None. M. Bredella: None. M. Misra: None. V. Singhal: None.
Introduction: Branched-chain amino acids (BCAAs), isoleucine, leucine and valine, have been linked to obesity, insulin resistance (IR) and risk for type 2 diabetes. Adults with obesity have a reduction in BCAA levels following metabolic and bariatric surgery (MBS), which may contribute to the modulation of metabolic advantages of MBS. We examine for the first time this relationship in youth with moderate-to-severe obesity who underwent sleeve gastrectomy (SG). Objective: To examine changes in dietary intake and serum BCAAs in youth with obesity one-year after SG, and their associations with changes in markers of IR. Methods: 53 youth 13-25 years old with severe obesity (41 females) were followed for a year; 25 had SG and 28 were non-surgical controls (NS). Subjects had fasting glucose and insulin levels and a 24-hour food recall. We assessed baseline and 12-month change within (Wilcoxon signed-rank test) and between (Student’s t-test/Wilcoxon Rank Sum test) groups, and associations between BCAAs and markers of IR (Spearman’s correlation). Results: SG and NS groups were similar for age, sex and race. SG had higher median body mass index (BMI) vs. NS at baseline [45.3 (42.1, 53.7) vs. 41.9 (38.4, 47.1) kg/m2; p=0.02]. At baseline, SG and NS did not differ for intake or serum levels of isoleucine, leucine, valine or total BCAAs. SG and NS groups also did not differ at baseline for glycated hemoglobin (HbA1C) or Homeostatic Model Assessment for Insulin Resistance (HOMA-IR, marker of IR). Over a year, SG vs. NS had greater reductions in BMI, serum isoleucine, leucine, valine and BCAAs (p≤0.02), and SG had significant within group reductions in intake of isoleucine, leucine, valine and BCAAs (p≤0.048). Further, SG vs. NS groups had greater reductions in HbA1c and HOMA-IR (p≤0.007). Serum BCAA levels were not associated with their dietary intake. Baseline HOMA-IR was positively associated with baseline serum levels of leucine (ρ=0.56, p=0.01). Over one year, decreases in HOMA-IR and HbA1c were positively associated with decreases in serum valine (ρ=0.60 and ρ=0.63, p=0.01 and p=0.007, respectively). Associations between changes in HOMA-IR and serum valine held after controlling for BMI (baseline and change) and dietary intake of valine. Conclusion: We demonstrate decreases in BCAA intake and serum levels one-year post-SG in youth with obesity. Associations between BCAAs and IR markers, even after controlling for BMI, suggest a potential role of BCAA in regulating metabolic health. Reducing serum levels of BCAAs may reduce IR.
Presentation: Friday, June 16, 2023
FRI105 Getting Fam-iliar With Familial Chylomicronemia Syndrome: A Case Report
Authors: Jimenez Aaron-Ross , Azul Jamesson 
Published: October 2023

Abstract
Background: Familial chylomicronemia syndrome (FCS) is a rare autosomal recessive lipid disorder of chylomicron metabolism causing severe hypertriglyceridemia that affects ∼1/1,000,000 individuals. Case Presentation: A 36-year-old male with a history of severely elevated triglyceride levels, recurrent pancreatitis, and biopsy-proven focal segmental glomerulosclerosis presented with severely elevated triglycerides. His initial acute pancreatitis episode was at 30 years old and attributed to alcohol intake. Triglyceride levels were not obtained at the time. He abstained from alcohol; however, his follow up triglyceride level was elevated (5,005 mg/dL, n=35-160 mg/dL) which normalized on an insulin infusion. He started fenofibrate and fish oil. After several additional hospital admissions for either pancreatitis or asymptomatic hypertriglyceridemia with a peak triglyceride level of 14,385 mg/dL, he committed to a low fat and vegan diet. Generic fish oil was transitioned to icosapent ethyl, and he was additionally started on niacin and atorvastatin. Even after following a strict diet and medication adherence, he continued having multiple admissions for acute pancreatitis, most recently complicated by dialysis dependent acute kidney injury in the setting of necrotizing pancreatitis. He has no known history of hypertriglyceridemia in his family. Due to persistent and severe hypertriglyceridemia despite conventional treatment, we suspected an underlying genetic cause, such as FCS. FCS should be suspected in those with recurrent pancreatitis, lipemia retinalis, and/or milky colored blood specimens. Eruptive xanthomas may also be present. Our patient did not have evidence of eruptive xanthomas on physical examination, but ophthalmology evaluation did show lipemia retinalis. The most common genetic pathologic variant in FCS is in the lipoprotein lipase-1 gene (LPL) that codes for an enzyme which assists in the lipolysis of plasma triglycerides (TG) in chylomicrons. Other common genes associated with severe hypertriglyceridemia are APOC2, APOAV, LMF-1, and GPIHBP-1. The mainstay of treatment for FCS are medications to reduce triglyceride levels and a significantly low-fat diet below 25 grams daily. Medium chain triglycerides can be utilized as they do not require enzymes to break down. Otherwise, there are currently no FDA-available therapies specifically targeted for use in those with FCS. Conclusions: This case demonstrates the unfortunate outcome of familial chylomicronemia syndrome despite concerted efforts to reduce triglyceride levels and eliminate additional risk factors.
Presentation: Friday, June 16, 2023
SAT148 A Rare Case Of Proinsulinoma In A Patient With Type 2 Diabetes Mellitus
Authors: Tirthani Ekta , Erenler Feyza 
Published: October 2023

Abstract
Disclosure: E. Tirthani: None. F. Erenler: None.
Background: A proinsulinoma is a very rare neuroendocrine tumor of the pancreas, which predominantly secretes proinsulin, the precursor hormone of insulin. Even though not as potent as insulin, proinsulin in higher amounts can bind to insulin receptors and result in hypoglycemia. Most patients present with initial hypoglycemia symptoms at the time of diagnosis of the tumor. The diagnosis becomes challenging in patients with underlying type 2 diabetes mellitus (T2DM) who may initially have a spontaneous remission of diabetes, followed by hypoglycemia episodes later in the disease course. Clinical Case: A 66-year-old man presented to our clinic in October 2020 with frequent episodes of dizziness and diaphoresis, which were relieved by eating food. The patient's symptoms began in 2018, occurred during the daytime, and were exacerbated by exercise. He had a past medical history of T2DM diagnosed in 2009 (HbA1c=10%) and treated with glipizide and metformin; however, over the years, his HbA1c improved, and glipizide was discontinued. By 2018 his HbA1c was down to 5.9%, and metformin was also stopped. The patient denied any change in his weight, diet, or exercise frequency during this time course. A fingerstick blood glucose (BG) checked during one of these episodes was 51 mg/dL. An abdominal CT scan in August 2020 revealed a 12x13 mm enhancing mass within the neck of the pancreas concerning for a neuroendocrine tumor. The patient was further evaluated with a 14-day continuous glucose monitor (CGM), which showed that the patient's BG was &lt;70 mg/dL 31% of the time and &lt;55 mg/dL 6% of the time. Additional fasting blood work showed a proinsulin level of 191.3 pmol/L (normal ≤18 pmol/L), insulin 15.5 uIU/mL (2-25 uIU/mL), BG 103mg/dL, C-peptide 2.44 ng/mL (0.80-3.85 ng/mL) and chromogranin A 124 ng/mL (25-140 ng/mL) which suggested the diagnosis of proinsulinoma. A Gallium-DOTATATE scan showed a localized tumor within the pancreas with no metastasis. The patient underwent enucleation of the tumor in November 2020. Pathology showed a well-differentiated neuroendocrine tumor staged T1 pN0 with immunohistochemistry staining diffusely positive for chromogranin, synaptophysin, and insulin with a Ki67 index &lt;3%. In January 2021, at a post-surgery follow-up visit, blood work showed HbA1c 7.1%, proinsulin 31 pmol/L, insulin 13.4 uIU/mL, C-peptide 1.6 ng/mL, BG 193 mg/dl, and chromogranin A 118 ng/mL. HbA1c continued to trend up to 8.0% in January 2022, confirming the resurgence of diabetes, and metformin and pioglitazone were started. Conclusion: Per our literature review, this is the first reported case of a proinsulinoma in a patient with T2DM. In a patient with uncontrolled T2DM, an unexpected amelioration of the disease should raise concern for insulin-secreting tumors, and further workup should be considered. A CGM can be a valuable tool to assess the severity of hypoglycemia in patients with these tumors.
Presentation: Saturday, June 17, 2023
SAT157 Management Of Spontaneous Hypoglycemia In Dialysis-dependent Chronic Kidney Disease Using Diazoxide
Authors: Schledwitz Alyssa , Habbsa Samima Sultana , Villanueva Fiorella Sotomayor , Kim Yoon Kook 
Published: October 2023

Abstract
Disclosure: A. Schledwitz: None. S.S. Habbsa: None. F. Sotomayor Villanueva: None. Y. Kim: None.
Background: Patients with end-stage renal disease (ESRD) are at increased risk of spontaneous hypoglycemia due to decreased renal insulin clearance. Due to its inhibitory effect on pancreatic beta cell insulin secretion, oral diazoxide has been used to treat hypoglycemia due to insulinoma or congenital hyperinsulinemic hypoglycemia, but few cases detail the use of diazoxide in the ESRD population. Here, we present 4 cases of spontaneous hyperinsulinemic hypoglycemia in ESRD successfully treated with diazoxide. Clinical Cases: A 66-year-old man with ESRD presented with altered mental status secondary to severe hypoglycemia despite continuous IV 20% dextrose. Labs revealed glucose 50 mg/dL, insulin 7 (0-3 mcIU/mL), C-peptide 7.8 (0-0.6 ng/mL), proinsulin 35.7 (0-5 pmol/L), beta-hydroxybutyrate [bOH] 0.4 (0-2.7 mg/dL), negative sulfonylurea panel, normal cosyntropin stimulation test and undetectable insulin antibodies, without radiographic evidence of insulinoma. He was started on diazoxide 50 mg TID and remained euglycemic for the remainder of his course. On similar readmission 3 months later, he was restarted on diazoxide with resolution of hypoglycemia within 1 day. A 66-year-old male with ESRD and T1DM treated with pancreas transplant presented with toe gangrene and persistent hypoglycemia. Fasting labs revealed insulin 4, C-peptide 4.5, proinsulin 4.5, and bOH 4.5, without radiographic evidence of insulinoma. He maintained euglycemia 4 days after diazoxide 70 mg BID was started. A 67-year-old male with T2DM and ESRD was admitted for osteomyelitis and 2 years of episodic symptomatic hypoglycemia despite dietary adjustments. Labs showed glucose 59, insulin 7, C-peptide 5.2, proinsulin 7.5, bOH 0.04, and unremarkable imaging. Within 1 day of starting diazoxide 100 mg daily, his blood glucose stabilized, and he was discharged. Finally, a 42-year-old male with ESRD presented with 4 years of persistent episodic hypoglycemia, now refractory to continuous IV dextrose. He was found to have glucose 64, insulin 15, C-peptide 11.5, proinsulin 29, and bOH 0.1, with imaging revealing bulky pancreas without a discrete mass. His hypoglycemic episodes resolved within 1 day of starting diazoxide 100 mg daily. He was readmitted 3 months later for catheter site infection and had no episodes of hypoglycemia with continuation of diazoxide. Conclusion: Diazoxide may be a viable option for the treatment of refractory spontaneous hypoglycemia in patients with dialysis dependent ESRD.
Presentation: Saturday, June 17, 2023
SAT160 Alcoholic Ketoacidosis : An Endocrine Emergency
Authors: Tiu Leo Jr Estabillo , Crisostomo Thelma D 
Published: October 2023

Abstract
Disclosure: L.E. Tiu: None. T.D. Crisostomo: None.
Background: Alcoholic Ketoacidosis is a complex metabolic condition frequently confused with Diabetic Ketoacidosis. Currently, there remains an undefined consensus guideline in the diagnosis and management of this disorder that leads to unreported cases. Clinical Case: A 47-year-old male presented with 2-day history of poor dietary intake due to abdominal pain and vomiting after an alcoholic binge drinking. He is a chronic alcoholic beverage drinker (2 liters of beer per day for 10 years). He has family history of Type 2 Diabetes Mellitus but has no known co-morbidities. Upon admission, vital signs were normal, but he was drowsy and incoherent with signs of dehydration and epigastric tenderness. Initial capillary blood glucose was 52 mg/dL. D50W 50ml intravenously was given with repeat CBG of 222 mg/dL. Arterial blood gas (ABG) showed high anion gap metabolic acidosis (pH 7.0 and anion gap of 42) with undetectable bicarbonate and elevated lactate at 17mmol/L. Serum ketones were elevated at 6mmol/L but Hba1c was normal at 4.6 %. Thus, Alcoholic Ketoacidosis was highly considered. Intravenous hydration with saline solution was instituted then shifted to D10W 125mL/hour to allow insulin infusion therapy at initial rate of 2units/hour. Sodium bicarbonate 100 mEqs was given intravenously with recovery of sensorium thereafter. Oral Vitamin B supplement was started, and two doses of Thiamine 100 mg/IV were given. Other tests showed hyperkalemia (5.28meq/L), hypochloridemia (89.7meq/L), hyperuricemia (12.74mg/dL), and hyperphosphatemia (5.8mg/dL). Serial monitoring and correction of electrolytes were done. Moreover, management integrated simultaneous referrals to other subspecialties to rule out other causes of encephalopathy, to evaluate and manage Hypertriglyceridemic Pancreatitis and Alcoholic Liver Disease, and to facilitate nutritional, psychosocial support and rehabilitation. On 2nd hour, repeat ABG showed improvement of pH to 7.3 and HCO3 to 9.80mmol/L. Lactate decreased to 12.70mmol/L. On the 17th hour, ABG showed metabolic alkalosis with resolution of ketosis hence insulin was discontinued. CBG levels for the next 24-48 hours were within normal limits. Oral feeding was supplemented with parenteral nutrition due to decreased appetite. On 48th hour, he displayed combative behavior with visual hallucinations, but there was no consent for psychiatric referral. On 72nd hour, there was spontaneous marked improvement in his behavior. He was discharged clinically stable. Conclusion: Early recognition of Alcoholic Ketoacidosis is imperative. This is an unrecognized endocrine emergency that portends good outcome with timely diagnosis and management. Treatment includes 1. adequate fluid resuscitation 2. thiamine 3. judicious use of insulin and bicarbonate 4. correction of electrolytes 5. multidisciplinary team management.
Presentation: Saturday, June 17, 2023
SAT162 Management Of Hypoglycemia In Von Gierke's Disease
Authors: Makda Aamir , Sood Aayushi , Syed Omar , Nihan Khuld 
Published: October 2023

Abstract
Disclosure: A. Makda: None. A. Sood: None. O. Syed: None. K. Nihan: None.
Introduction: Glycogen Storage Disease Type-1 (GSD-1)is due to deficiency in Glucose-6-Phosphatase (G6P) results in excessive accumulation of glycogen and fat in the liver, kidney. GSD-1 have a wide spectrum of symptoms including hepatomegaly, hypoglycemia, lactic acidemia, hyperlipidemia, hyperuricemia, and growth retardation. Manifestations of the disease vary in age of onset, rate of disease progression, and severity. Case:18-year-old male with GSD-1a, Von Gierke's disease, hyperuricemia and hypertension presented to the hospital with nausea and vomiting. Patient followed an hourly cornstarch regimen during the day and overnight through infusion via PEG tube. The complaints started at work where he was unable to tolerate oral cornstarch. ABG showed metabolic acidosis, labs showed Leukocytosis, hyperkalemia, acute kidney injury, elevated liver enzymes, hypertriglyceridemia, lactic acidosis. CT abdomen showed hepatomegaly and fatty infiltration with PEG tube intact.
He was admitted to the ICU and started on D5NS for hypoglycemia and lactic acidosis. Per request by the patient's pediatrician, he was transitioned to IV D10- 0.45NS at 110mL/Hr to maintain blood glucose above 75 mg/L. Frequent accuchecks were done till he could tolerate his dietary regimen with cornstarch. Lactic Acid downtrended to 2.9 and accuchecks ranged between 100-110. Cr improved to 1.3, and his home medications (Allopurinol and Lisinopril) were resumed. He was discharged in stable condition with plans for further genetic therapy work up. Discussion: Mainstay therapy for Von Gierke's Disease is prevention of metabolic derangements for which dietary and lifestyle changes are recommended. A low fructose and sucrose diet is recommended with limiting the intake of galactose and lactose to one serving per day. Hypoglycemia treatment in such patients is two fold; utilizing both quick and stable release sources. Cornstarch has been once such therapy since the 1980, its slow digestion provides a steady release of glucose over a longer period of time as compared with other sources of carbohydrates. Dosing guidelines vary from age to age and person to person but it is highly recommended to check BG levels frequently to maintain a BG &gt; 70 mg/dL. Associated high levels of triglycerides and cholesterol can be treated with statins, fibrates, etc. Conclusion: The management of hypoglycemia in GSD 1 disease presents various obstacles which could prove to be fatal. Due to the deficiency of G6P, treatment with a specialized hypoglycemic regimen is warranted. A D10 ½ NS infusion can be used to maintain blood sugar levels as well as correct metabolic or lactate imbalances. Infusion should be gradually weaned off after the patient can tolerate oral feeds as this can help prevent the risk of hypoglycemia and other derangements. Further research is needed in regards to these patients for more sustainable regimens.
Presentation: Saturday, June 17, 2023