bluuebunny/crossref_metadata_2025_split huggingface dataset:
FRI027 Regulation Of A Novel Sortilin Splice Variant Expression In Human Diabetic Adipocytes By GLP-1 To Maintain Glucose Homeostasis
Authors: Patel Niketa A , Patel Rekha S , Liu Ashley 
Published: October 2023

Abstract
Disclosure: N.A. Patel: None. R.S. Patel: None. A. Liu: None.
Type 2 diabetes mellitus (T2DM) is a chronic and progressive metabolic disease with no cure. 37.3 million Americans have T2DM as of 2021 and 96 million (1 in 3) are prediabetic. Globally 462 million people are estimated to be living with T2DM. T2DM is a complex, polygenic metabolic disease characterized by hyperglycemia and insulin resistance. Adipocytes play a crucial role in glucose homeostasis. In response to insulin, translocation of major glucose transporter-4 (Glut4) from cytoplasm to the plasma membrane facilitates uptake of glucose into the adipocytes. Sortilin, an important constituent of Glut4 storage vesicles, binds to Glut4 with its luminal domain while its C-terminal tail guides intracellular trafficking. In insulin resistant adipocytes, glucose uptake is impaired. In this study, we used human adipose stem cells (hASC) from diabetic (DM) and nondiabetic (NDM) donors and differentiated them in vitro to mature adipocytes. We report that in addition to constitutively spliced full-length sortilin (Sort_FL), we identified an alternatively spliced sortilin variant in human adipocytes. Results show that alternative exon inclusion resulted in inclusion of STOP codon which produced a truncated C-terminal (Sort_T) protein whose expression was significantly increased in DM adipocytes. We elucidated the role and function of Sort_T and our results show that hyperglycemic conditions promoted an increase in Sort_T levels in NDM adipocytes. Overexpression of Sort_T in NDM adipocytes resulted in reduced insulin-stimulated Glut4 translocation and decreased glucose uptake. However, overexpression of Sort_FL does not rescue glucose uptake in DM adipocytes. Computational modeling and molecular dynamics results suggested that Glut4 bound tightly to both Sort_T and Sort_FL. This was validated using co-immunoprecipitation assays which demonstrated robust binding of Sort_T to Glut4. Immunocytochemistry was performed to determine localization of sortilin variants in DM and NDM adipocytes. Results demonstrated that Glut4 co-localized with both Sort_T and Sort_FL and Pearson’s coefficient demonstrated increased Sort_T co-localization with Glut4 in DM adipocytes. Incretin hormone glucagon-like peptide-1 (GLP1) and its analog liraglutide is used to manage T2DM. We evaluated the effect of GLP1 and liraglutide treatment in DM adipocytes on sortilin variant expression and our results demonstrate decreased Sort_T levels at physiological doses (8nM). Using a sortilin splicing minigene, our results demonstrate that GLP1 regulates splicing of Sort_T pre-mRNA and splice factor SRSF10 is involved in GLP1-mediated sortilin alternative splicing in adipocytes. Our study concludes that Sort_T expression in diabetic adipocytes hinders glucose metabolism and Sort_T is a target of GLP1 for maintaining glucose homeostasis.
Presentation: Friday, June 16, 2023
FRI036 Trends In The Racial And Ethnic Disparity Of Metabolic Associated Fatty Liver Disease (MAFLD): Data From NHANES 1988 To 2018
Authors: Shaheen Magda , Schrode Katrina , Pan Deyu , Najjar Sonia Michael , Friedman Theodore C 
Published: October 2023

Abstract
Disclosure: M. Shaheen: None. K. Schrode: None. D. Pan: None. S.M. Najjar: None. T.C. Friedman: None.
Metabolic associated fatty liver disease is a serious and important problem and it affects Hispanics at a higher prevalence compared to Blacks and Whites. This disparity is an important public health concern. The purpose of this study was to examine the trend in the racial/ethnic disparity of MAFLD among a representative sample of the U.S. adult population from 1988 to 2018. Data from the National Health and Nutrition Examination Survey (NHANES) 1988 to 2018 were analyzed. The total sample size was 32,726. Hepatic steatosis was diagnosed using the U.S. fatty liver index (US-FLI). MAFLD was diagnosed among those with both HS and overweight/obesity, diabetes mellitus, and/or metabolic syndrome. We analyzed the data using logistic regression to test for trends over time for the overall sample and for each racial/ethnic group considering the design and sample weights. Prevalence was age-adjusted using the direct method and the census data published by the census bureau. We also estimated the percent change in the prevalence using the formula [(2018 prevalence – 1988 prevalence)/1988 prevalence)*100]. Overall, the age-adjusted prevalence of MAFLD increased over time from 16% in 1988 to 37% in 2018 for 131% percent increase (p&lt;0.05) while the age-adjusted rate of obesity increased from 23% in 1988 to 40% in 2018 for 74% increase (p&lt;0.05). Among Mexican Americans, the age-adjusted prevalence was higher at all times compared to the overall population and there was a significant increase in the age-adjusted prevalence of MAFLD over time (36% in 1988 to 58% in 2018 for a 61% increase) (p&lt;0.05). Among Blacks, a significant increase in the age adjusted prevalence of MAFLD was found (11% in 1988 to 25% in 2018 for a 56% increase) (p&lt;0.05). We also found a significant increase in the age-adjusted prevalence of MAFLD among the White population (15% in 1988 to 35% in 2018 for a 133% increase) (p&lt;0.05). Our study indicated that there is an increase in the age-adjusted prevalence of MAFLD over time that was greater than the increase in obesity. The racial/ethnic disparity in MAFLD persisted over time with Mexican Americans consistently having the highest prevalence that was highest in 2018. Grants: R01MD012579, R24DA017298, U54MD007598, S21MD000103, UL1TR001881
Presentation: Friday, June 16, 2023
SAT165 A Novel Mutation In The HNF4α Gene (C.691C&gt;T, P.arg231trp) Likely To Be Pathogenic For Maturity Onset Diabetes Of The Young Type 1 Presenting With Hyperinsulinemic Hypoglycemia In An Infant
Authors: Rodriguez Adriana , Sastry Shruti , Chemaitilly Wassim , Gurtunca Nursen 
Published: October 2023

Abstract
Disclosure: A. Rodriguez: None. S. Sastry: None. W. Chemaitilly: None. N. Gurtunca: None.
Background: Maturity Onset Diabetes of the Young type 1 (MODY 1) is a monogenic form of diabetes mellitus caused by a defective HNF4α gene, resulting in reduced insulin secretion and diabetes in early adolescence and young adulthood. MODY 1 is also known to be associated with increased insulin secretion during fetal, neonatal and childhood periods with consequences that range from fetal macrosomia to persistent hyperinsulinism. Traditionally, HNF4α gene mutations represents 5% of all cases of diazoxide-responsive hyperinsulinism. Clinical Case: A 1 month old male born full term and large for gestational age (birth weight of 4920g) following an uncomplicated pregnancy and delivery developed hypoglycemia soon after birth and required hospital admission on day of life 2 with a serum glucose of 30 mg/dL and an insulin level of 5 uIU/mL. A fasting challenge showed hypoglycemia at 9 hours with a serum glucose of 47 mg/dL and an insulin level of 10.3 uIU/mL confirming hyperinsulinemic hypoglycemia. He was started on diazoxide to which he responded well and was placed on a continuous glucose monitor (CGM). He was originally started on diazoxide 8mg/kg/day that later was decreased to 6.6mg/kg/day due to blood glucoses in the 200’s. He passed the fasting study 5 days after starting diazoxide and went home with the CGM with subsequent dose titration made with guidance from remote data sharing. A neonatal hypoglycemia panel was sent and showed a novel mutation, c.691C&gt;T, p.ARG231Trp in the HNF4α gene classified as a variant of uncertain significance. Computer modeling software suggested that this gene might disrupts the gene structure and function. This variant is present in population databases at a 0.0009% frequency and this missense change has been observed in individuals with clinical features of maturity onset diabetes of the young. Patient’s father carries the same mutation and paternal grandmother carries a diagnosis of type 2 diabetes mellitus. Conclusion: This is a novel mutation that should be considered pathogenic based on this patient’s neonatal presentation and previous literature. This case also presents possible uses of CGM in infants with diazoxide responsive congenital hyperinsulinism in order to decrease burden from monitoring and streamline communication with the medical team
Presentation: Saturday, June 17, 2023
SAT655 Modifying Effects Of Dash Diet On Food Addiction Two Years After Sleeve Gastrostomy: A Randomized Controlled Clinical Trial
Authors: Ariyanfar Shadi , Tabesh Mastaneh , Noormohammadi Morvarid , Jahromi Soodeh Razeghi , Rashidbeigi Elahe 
Published: October 2023

Abstract
Disclosure: S. Ariyanfar: None. M. Tabesh: None. M. Noormohammadi: None. S. Razeghi Jahromi: None. E. Rashidbeigi: None.
In morbid obese individuals, bariatric surgery is considered an effective intervention due to failure of non-surgical weight management strategies. Sleeve gastrostomy (LSG) accounts for over half of bariatric surgeries. The prevalence of weight regains is 76% over 2-6 years after LSG due to binge eating disorder and food addiction. In our previous study, one-fifth of patients with LSG fulfilled the criteria for food addiction (FA). Various dietary patterns have been studied for their potential benefits in controlling FA in non-surgical weight loss programs. Among them, DASH diet attracted our attention, because, besides its effect on FA, the nature of this diet fully addresses other prevalent complications of patients with morbid obesity who undergoes LSG more than two years ago, i.e., vascular problems and gut microbiota changes. To study the effect of the DASH diet on food addiction after LSG we recruited 100 individuals with LSG two years prior to the study who had mild to moderate FA according to DSM-IV criteria and Yale Food Addiction Scale (YFAS) and weight regain of more than 25% of excess weight loss. Participants were randomly assigned to a calorie-restricted DASH diet (1000-1200 calories, containing 2-3 servings of whole grain, 3-4 servings of vegetables, 3 servings of fruit, 2 servings of skim or low-fat dairy products, 1-2 servings of meat, poultry, and fish, 3 servings of nuts, seeds, and legumes, 2 servings of oil) or a calorie-restricted diet (1000-1200 calories, 3-4 servings of whole grain, 3-4 servings of vegetables, 2 servings of fruit, 2 servings of skim or low-fat dairy products, 2-3 servings of meat, poultry, and fish, 1 serving of nuts, seeds, and legumes, 2 servings of oil, and 1 serving of sugar.) for 16 weeks. Food addiction, serum levels of FBS and insulin were assessed. No significant differences in calorie and macronutrient intake, BMI, amount of excess weight before surgery, physical activity level, depression, anxiety level, and YFAS mean were observed between to studied groups After 16 weeks, individuals in DASH diet group reported a significant reduction in YFAS (from3.64±0.63 to 2.66±0.63, P.Value &lt; 0.001), also Insulin levels and FBS decreased from 12.22±3.13 to 10.12±2.3 mcU/ml (P.Value&lt; 0.001) and from 91.92±8.9 to 86.98±6.8 mg/dl (P.Value&lt; 0.001), respectively. A significant reduction of insulin (13.21±2.97 to11.15±2.18 mcU/ml, P.Vaue&lt; 0.001) and FBS level (92.31±7.5 to 87.63±5.9 mg/dl) was observed among controls. A significantly higher reduction of insulin levels in DASH group was noticed at the endpoint (P.Value: 0.026). It could be concluded that adherence to DASH diet, 2 years after SLG, can combat food addiction by modifying serum insulin levels.
Presentation: Saturday, June 17, 2023
SAT170 Paraneoplastic Hypoglycemia Secondary To Hepatocellular Carcinoma
Authors: Dejhansathit Siroj , Sheung Nicole , Akofu Anota , Uddin Ashraf , Marium Fnu , Akabogu Nwamaka Gloria , Salam Waqar 
Published: October 2023

Abstract
Disclosure: S. Dejhansathit: None. N. Sheung: None. A. Akofu: None. A. Uddin: None. F. marium: None. N.G. Akabogu: None. W. Salam, MD: None.
Introduction: Hypoglycemia is a known but rare Paraneoplastic manifestation of hepatocellular carcinoma and can lead to significant morbidity and mortality. Even though HCC-related hypoglycemia is a known entity, knowledge about prevention and treatment is limited. Case Description: We report a 36-year-old male with no significant past medical history presenting initially to emergency room for abdominal pain and distension for 2 months. He reported associated 10 pounds unintentional weight loss, fatigue, night sweat and loss of appetite in the past 3 months. The patient noted to have hypoglycemia with blood glucose of 20 mg/dl on admission. He was given 2 ampoules of 50% dextrose and started on 5% dextrose solution intravenously. A CT abdomen and pelvis showed enlarged heterogenous liver with numerous hepatic lesions, concerning for multifocal hepatocellular carcinoma. A liver biopsy was done and confirmed hepatocellular carcinoma. Labs showed alpha fetoprotein level over 60500 ng/mL (0-8.3 ng/mL). Hepatitis B surface antigen was reactive with positive hepatitis B DNA, confirming the diagnosis of chronic hepatitis B infection. Gastroenterology, Oncology and Surgical Oncology were consulted. Patient was felt not to be a good surgical or transarterial chemo-embolization. Endocrinology was consulted when patient develops scrotal and legs swelling after receiving high rate of dextrose fluid since admission to maintain blood glucose. Prednisone 20 mg twice a day was initiated and later increased to 30 mg twice day after 2 days without significant improvement. Prednisone was then switched to dexamethasone 4 mg four times a day for longer half-life. 10% dextrose was slowly decreased from 200cc/hr to100cc/hr but resulted in rebound hypoglycemia. Somatropin 4 mg daily was also added with a goal to further decrease fluid rate in order to help with his discomfort from swelling. 10% dextrose was eventually decreased to 75 cc/hr. Patient subsequently opted for hospice care and passed away within 24 hours. Discussion: The paraneoplastic hypoglycemia associated with HCC can be classified into two categories. Type A hypoglycemia is usually found in the late-stage HCC when tumor burden is high. Type B hypoglycemia is caused by an increase in pro-IGF-2 level that is incompletely processed by the tumor cells, stimulating insulin receptors. It is likely our patient had type A hypoglycemia due to the extensive tumor burden. Overall, paraneoplastic hypoglycemia associated with HCC has very poor prognosis and high mortality rate. There is no single effective management and combination of steroids and Somatropin may provide palliative improvement as seen in our patient.
Presentation: Saturday, June 17, 2023
SAT175 Noninsulinoma Pancreatogenous Hypoglycemia Syndrome As A Complication Of Nissen Fundoplication
Authors: Rinn Ryan , Lacount Stephen , Muuse Janelle 
Published: October 2023

Abstract
Disclosure: R. Rinn: None. S. Lacount: None. J. Muuse: None.
Hypoglycemia is a common condition that is typically diagnosed with Whipple’s Triad (hypoglycemic symptoms, low blood glucose, resolution of symptoms with treatment). It is important to recognize and treat early as it has the potential for lethal outcomes. Dumping syndrome is a rare presentation after Nissen’s fundoplication and predominantly reported in children. Here we present a case of an adult with persistent postprandial hypoglycemia after Nissen Fundoplication. A 79-year-old male with a recent Nissen’s fundoplication presented with repeated episodes of extreme fatigue and diaphoresis after eating. Other complaints included weakness and significant weight loss. Finger stick glucose on multiple checks were found to be in 40s. He was hospitalized and underwent extensive workup with Endocrinology and Gastroenterology. Important labs revealed elevated insulin 10.2, C-peptide level at 7.3 and pro-insulin at 27.7, negative insulin antibodies, a normal Insulin like growth factor (IGF-1) at 74, Beta-hydroxybutyrate level 0.1, and a negative screen for sulfonylureas. He was discharged home on a low carbohydrate diet but continued having repeated Whipple’s triad positive hypoglycemic episodes. In terms of imaging, CT of the abdomen did not reveal a mass, other localization studies were deferred since the episodes were mostly post-prandial concerning for NIPHS than insulinoma. For management, he had minimal response to octreotide and verapamil. His symptoms are currently being managed on acarbose and diazoxide with dietary modifications consisting of high protein and limited complex carbohydrates. Postprandial hypoglycemia as a complication of Nissen’s fundoplication is thought to be secondary to dumping syndrome (DS). DS is divided into two stages- early/osmotic stage and late/ hypoglycemic stage. Both types are caused by a large amount of gastric contents emptying into the duodenum, resulting in vasomotor symptoms from changes in blood pressure, pulse and glucose levels, as well as gastrointestinal symptoms. Glucagon like peptide-1 is responsible for the second phase and the levels are directly related to gastric emptying and inversely related to plasma glucose concentration. Accelerated gastric emptying causes increased GLP-1 levels leading to exaggerated insulin response resulting in rebound severe hypoglycemia. It is important to realize that diet plays an important role in symptom management. After Nissen’s fundoplication, a decrease occurs in the storage capacity of the fundus and gastric distensibility, which causes increased gastric motility with rapid emptying. Dietary modifications include reduction of carbohydrate intake and supplementation of dietary fibers with meals greatly help relieve symptoms associated with dumping syndrome in addition to drug therapy.
Presentation: Saturday, June 17, 2023
SAT443 Prevalence Of Immune Checkpoint Inhibitor-related Endocrinopathies In Patients With Cancers
Authors: Pittampalli Shanti , Lubin Sarah R , Acharya Runa 
Published: October 2023

Abstract
Disclosure: S. Pittampalli: None. S.R. Lubin: None. R. Acharya: None.
Background: Immune checkpoint inhibitors (ICIs), emerged as the primary treatment modality for a wide range of cancers improving overall survival. Nevertheless, improved overall survival is complicated by endocrine dysfunctions including thyroid dysfunction, adrenalitis, diabetes mellitus, and hypophysitis. Such adverse events offset the benefits of ICI therapy and are associated with significant morbidity and mortality. Limited data exists concerning the burden of the ICI-related endocrinopathies in cancer treatment.Objective: To identify the prevalence and timing of onset of various endocrinopathies in patients with cancers receiving ICIs. Methods: A retrospective study was conducted at SUNY Upstate Medical University, NY comprising of adult patients. The study population consisted of all patients age 18 and above seen at Upstate Medical University between 1 January 2019 and 31 December 2021. Anonymized aggregate-level data was collected using an EPIC Slicer Dicer to identify all adult patients with cancer who underwent ICI therapy and a total of 199 patients were included. Demographic, clinical, histopathological, laboratory data were examined. The study was reviewed by IRB and deemed exempt.
The following ICI-related endocrinopathies were considered: Hypothyroidism, hyperthyroidism, diabetes mellitus, adrenal insuffiency, and hypophysitis. ICI treatments included: anti-PD-1 (nivolumab, pembrolizumab, cemiplimab), anti-PD-L1 (atezolizumab, avelumab, durvalumab), and combination therapy (ipilimumab and nivolumab, or any other ICI combinations). Statistical analysis including descriptive statistics, ANOVA was conducted using IBM SPSS software.Results: A total of fifty patients (25%) developed ICI-related endocrinopathy (n=28 M, 22 F) with a mean age of onset 63.69 years. Majority of the patients were being treated for lung cancers (51%) and had hypothyroidism (88%) followed by adrenal insufficiency (9%) and diabetes (2%). There were no cases of hyperthyroidism or hypophysitis observed. The average time of onset of endocrinopathies after initiation of ICI therapy was 22 weeks (anti-PD-1=122 days, anti-PD-L1=180 days and combination therapy= 252 days) with a significantly later onset with combined therapy when compared to anti-PD-1 inhibitors (252 vs 122 days, p= 0.004). Conclusion: With the increasing use of immune checkpoint inhibitors in cancer therapy, there is increased prevalence of endocrinopathies. Periodic hormonal assessment along with close monitoring of new symptoms results in early detection of endocrinopathies as the time of onset varies significantly with the type of ICI agent and the use of single vs combination therapy.
Presentation: Saturday, June 17, 2023
THU019 Osilodrostat As An Emergency Alternative For Hypercortisolism In A Patient With An Impaired Liver Function
Authors: Minasyan Mari , Bogusławska Anna , Gamrat Aleksandra , Hubalewska-Dydejczyk Alicja , Gilis-Januszewska Aleksandra 
Published: October 2023

Abstract
Disclosure: M. Minasyan: None. A. Bogusławska: None. A. Gamrat: None. A. Hubalewska-Dydejczyk: None. A. Gilis-Januszewska: None.
Osilodrostat as an emergency alternative for hypercortisolism in a patient with an impaired liver function. A case presents a 34 year old woman with an active Cushing Disease, who underwent non-radical surgery of invasive pituitary adenoma in 2014 and CyberKnife radiotherapy in 2018. Patient demonstrates many complications of long lasting hypercortisolemia- poorly controlled diabetes mellitus, heart failure, hypertension, hypercholesterolemia, mental disturbances and severe hepatic impairment. Challenges in this case are aggravated by very difficult compliance. Due to elevated liver function tests, the patient couldn’t have started ketoconazole and relacorilant treatment. Because of non-controlled DM, pasireotide treatment was contraindicated in her case. She didn’t agree either for metyrapone treatment or for adrenalectomy. Finally osilodrostat has been implemented as the last-chance alternative given at the time of severe hepatic impairment. At the dose of 2x2mg we observe clinical improvement, normalisation of UFC, decrease of Hba1c and spectacular improvement of liver function. However the current data on use of osilodrostat in patients with hepatic impairment are limited, our case shows that osilodrostat can be an emergency alternative for severe hypercortisolism with impaired liver function. The mechanism of improvement of liver function may be indirect through decreasing the level of hypercortisolemia, however potential direct beneficial influence of osilodrostat on liver function seems to be an interesting subject worth further investigation. More studies on the link between hypercortisolemia, liver function and steroidogenesis inhibitors are needed.
Presentation: Thursday, June 15, 2023