bluuebunny/crossref_metadata_2025_split huggingface dataset:
7023 Hypoinsulinemic Hypoglycemia in a Severely Malnourished Patient with an Acute Liver Injury: A Marker of Poor Outcome!
Authors: Shrestha Ganesh , Qureshi Faisal , Yadav Kritika , Shrestha Sumira , Sapkota Supriya , Saad Eltaib 
Published: October 2024

Abstract
Disclosure: G. Shrestha: None. F. Qureshi: None. K. Yadav: None. S. Shrestha: None. S. Sapkota: None. E. Saad: None.
Background: Hypoglycemia is commonly seen in clinical practice, mostly observed in patients using insulin or oral hypoglycemic agents which is usually associated with hyperinsulinemia. We describe a challenging case of hypoinsulinemic hypoglycemia in a severely malnourished patient with acute liver injury. This rare clinical entity is often considered a poor prognostic feature and a marker of high mortality in patients with advanced multiorgan failure. Case Presentation: A 46-year-old male with a history of Huntington's disease was brought to the ED with altered mentation and moderate hypothermia. The exam revealed a malnourished patient with a BMI of 14. The initial serum glucose was very low (&lt; 20 mg/dl, n: 70-100 mg/dl) which improved after dextrose 50% bolus. He also had severe sepsis from aspiration pneumonia and received fluid resuscitation and broad-spectrum antibiotics. The patient had an episode of fluid-responsive hypotension on day 2 of admission, following which his liver function worsened as evidenced by elevated transaminases (AST& ALT levels were 2,000 units (n: 13-39 IU/L ) and 1,500 units (n: 7-52 IU/L ) resp compared to normal levels on admission). Additionally, deranged prothrombin time and INR on day 2 were 29 sec (n: 10-13 sec) and 2.6 (n: &lt;1.3) resp. Diagnostic work-up for acute hepatitis depicted no specific etiology and it was attributed to a shocked liver. The patient experienced frequent episodes of symptomatic hypoglycemia (serum glucose&lt; 20 mg/dl), necessitating a continuous infusion of dextrose-containing IV fluids. Endocrinology service recommended serum cortisol level, insulin level, and C-peptide levels to be drawn during a documented hypoglycemia episode. Serum cortisol was high at 60 mcg/dl (n: 0.4-22.6 mcg/dl) suggesting an appropriate neurohormonal stress response to the critical illness, interestingly, both insulin 0.9 (n: 1.9-23 IU/ml) and c-peptide levels 0.02 (n: 0.73-4.37 ng/ml) were below lower limits. The persistent hypoglycemia resolved when enteral feeding was initiated, and the liver function gradually improved following hemodynamic optimization. The patient, however, continued to suffer from various clinical syndromes related to poor nutrition status, and given his terminal neurologic disease he was eventually enrolled in hospice care. Conclusion: Our case reveals a rare scenario of hypoglycemia with low insulin and C-peptide levels in severely malnourished and shocked liver contrary to more commonly encountered hyperinsulinemic hypoglycemia in patients using insulin or oral hypoglycemic agents. Hypoinsulinemic hypoglycemia should be considered seriously, particularly in critically ill patients with poor nutritional status and liver injury, as it is usually associated with poor outcomes.
Presentation: 6/3/2024
7361 Identification of Novel Therapies for Monogenic Diabetes Using Connectivity Map (CMap)
Authors: Kreienkamp R J , Dos Santos F R , Bryan C , Florez J C , Claussnitzer M , Udler M S 
Published: October 2024

Abstract
Disclosure: R.J. Kreienkamp: None. F.R. Dos Santos: None. C. Bryan: None. J.C. Florez: None. M. Claussnitzer: None. M.S. Udler: None.
Monogenic diabetes is an underdiagnosed form of diabetes that is caused by DNA variation of strong effect in a single gene. While it is an exciting area for targeted drug development, as some forms of monogenic diabetes can be treated with gene-specific therapies, there are currently few targeted therapies available. Additionally, existing treatments are not able to cure or modify the underlying disease. Therefore, to identify novel disease-modifying therapies, we leveraged CMap, a data resource developed at the Broad Institute of MIT and Harvard that contains over one million gene expression signatures from treatment of cell types with perturbagens including drugs, bioactive small molecules, gene overexpression, and gene knockdown reagents. We analyzed the connectivity, i.e. the similarity, between two gene expression signatures, to search for perturbagen gene expression signatures opposing gene expression changes associated with monogenic diabetes. We were able to identify 15 classes of medications with significantly enriched connectivity with HNF1A-knockdown. Included in these classes were sulfonylureas, which are known to have preferential therapeutic benefit for this specific condition, supporting this method for drug discovery. Other medications included HDAC inhibitors, tyrosine kinase inhibitors, and riboflavin. We also surveyed other genes causing monogenic syndromes that include diabetes, such as PPARG, where CMap indicated high connectivity with thiazolidinediones, a type 2 diabetes drug class with known mechanism targeting PPARγ, opposing PPARγ-knockdown and beneficial for treating patients with PPARγ-driven familial partial lipodystrophy. We then validated CMap results in a high-fidelity cellular model system - primary human adipocytes constitutively expressing Cas9 - using a high-dimensional metabolic disease oriented read-out LipocyteProfiler for systematic image-based profiling of cellular phenotypes in metabolic cell types. To establish causality between the causal monogenic target PPARG and its agonizing compound effect, we performed a targeted CRISPR-Cas9 based knockout of PPARG in human adipocytes, and linked changes at the cellular level to changes related to thiazolidinediones. The data revealed a striking association between the PPARγ perturbation and the TZD effect, along with an increasing CMap absolute value and LipocyteProfiler connectivity (p=9.8 E-6). Our findings support the use of expression signature mapping as a novel approach for identifying therapies for monogenic diabetes. Further exploration of databases like CMap and validation of identified medication classes could lead to new pharmacological treatments for diabetes.
Presentation: 6/2/2024
7396 IGF-2 Induced Hypoglycemia Associated with Metastatic Hepatocellular Carcinoma
Authors: Benyaminov Fuad , Cascio Vincent , Sinha Avani G 
Published: October 2024

Abstract
Disclosure: F. Benyaminov: None. V. Cascio: None. A.G. Sinha: None.
Background: Non-islet-cell tumor hypoglycemia (NICTH) is a rare entity caused by tumoral secretion of IGF-2 and is associated with a wide variety of tumors. The diagnosis is made based on serum levels of IGF-1, IGF-2, and/or pro-IGF-2. Unfortunately, due to the limited access to testing in many laboratories, this pathology is often missed. We present a case of IGF-2 mediated hypoglycemia in a patient with metastatic HCC. Clinical case: A 31-year-old man with a remote history of hepatitis B infection and recently diagnosed liver and lung lesions, likely metastatic in etiology, presented to the ED with weakness, tremors, and diaphoresis. He reportedly recorded a POC glucose level of 38 mg/dL at home. Serum glucose levels in the ED confirmed severe hypoglycemia with a serum glucose level of 50 mg/dL. Laboratory workup for insulin-mediated hypoglycemia was negative, including serum insulin (&lt;0.4 uU/mL, n 2.6-24.9 uU/mL), proinsulin (0.7 pmol/L, n 0-10 pmol/L), C-peptide (0.1 ng/mL, n 1.1-4.4 ng/mL), BHB (0.0mmol/L), and insulin antibodies (&lt;5.0 uU/mL) in the setting a serum glucose of 48 mg/dL. Thyroid function was normal, adrenal insufficiency was ruled out, and a sulfonylurea panel was negative. Given the likely presence of metastatic cancer, NICTH was suspected. Laboratory evaluation including IGF-2 (644 ng/mL, n 333-987 ng/mL) and IGF-1 (42 ng/mL, n 82-244 ng/mL) was consistent with IGF-2 mediated hypoglycemia, due to IGF-2:IGF-1 ratio of 14, where a ratio &gt;10 is nearly diagnostic (1). Further laboratory workup was consistent with chronic hepatitis B, and a CT scan of the chest, abdomen, and pelvis confirmed numerous liver and lung lesions. A liver biopsy was performed with pathology demonstrating HCC. Initial treatment for hypoglycemia consisted of IV dextrose-containing fluids, with improvement of hypoglycemia. In preparation for discharge, non-pharmacological treatments were initially trialed. There have been case reports where patients were successfully treated for NICTH with cornstarch. Thus, the patient was then started on 30g of cornstarch daily, however they were unable to tolerate treatment due to nausea and the hypoglycemia persisted. The patient was instructed to eat frequent, high-carbohydrate meals including a bedtime snack which also failed to improve hypoglycemia. Subsequently, the patient was started on oral prednisone. They were eventually discharged on a dose of 20mg prednisone twice per day after achieving normoglycemia. Conclusion: NICTH due to tumoral secretion of IGF-2 is a rare cause of hypoglycemia that should be considered when labs reveal a non-insulin mediated etiology in the setting of malignancy. 1. Rana P, Kim B. A Unique Case of IGF-2 Induced Hypoglycemia Associated with Hepatocellular Carcinoma. Case Rep Endocrinol. 2019 Oct 13;2019:4601484.
Presentation: 6/1/2024
12469 Impact Of Covid-19 Infection On Diabetic Ketoacidosis Severity And Outcomes In Adult Population- A Retrospective Observational Study
Authors: Niedzialkowska Ewelina Marta , Childers Karen , Qu Lihua , Misra Lynda , Brennan Michael Roger 
Published: October 2024

Abstract
Disclosure: E.M. Niedzialkowska: None. K. Childers: None. L. Qu: None. L. Misra: None. M.R. Brennan: Consulting Fee; Self; Insulet Corporation, Bayer, Inc., Novo Nordisk.
Background: Diabetic ketoacidosis (DKA) is a life-threatening complication of diabetes mellitus (DM) that can be precipitated by SARS-CoV2 infection. We analyzed clinical and demographic characteristics of patients admitted with DKA to investigate if SARS-CoV2 infection affects DKA severity on admission and outcomes. Methods: We conducted a retrospective cohort study that included adult patients admitted with a diagnosis of DKA between March 1, 2020, and March 1, 2023. Patients' demographic data including age, sex, race, ethnicity, laboratory test results on admission, ICU admissions and length of hospital stay (LOS) were compared. Patient characteristics and outcomes of interest were stratified by COVID-19 test results and compared using the Kruskal-Wallis test for continuous variables and Fisher’s exact test for categorical variables. DKA severity was classified based on HCO3 values: mild 15-18 mEq/L, moderate 10-14 mEq/L, severe &lt;10 mEq/L. Results: The study included 902 patients, of which 734 tested negative (COVID-) and 168 tested positive (COVID+) for SARS-CoV2. The mean age was significantly higher (54.09) in COVID-19+ group compared to COVID-19- group (48.25) (p&lt;0.001). The cohort included 49.1% females, 51.7% Whites, 43.3% Blacks, 89.8% Non-Hispanic/Latino, 2.7% Hispanic/Latino. We did not find statistically significant differences in sex (p= 0.608), race (p =0.277), ethnicity (p=0.072) anion gap (p=0.783), glucose (p=0.140), hemoglobin a1c (ha1c) values on admission (p=0.876) and ICU admissions (p=0.266) between both groups. The majority (55.3%) of the patients presented with severe DKA, followed by moderate DKA in 26.6% and mild disease in 18.1% of patients without statistically significant differences between groups (p= 0.128). The mean LOS in COVID + group (11.94 days) was longer than COVID- (6.85) group (p&lt;0.001). Mean venous pH was significantly lower in COVID-19- (7.14) compared to COVID+ (7.17) group (p= 0.016). Betahydroxybutyrate (BHB) levels on admission were higher in COVID- group (7.98 mmol/L, N 0.02-0.27 mmol/L) compared to COVID + (7.10mmol/L) cohort. Conclusion: Patients diagnosed with COVID-19 and DKA on admission did not present with more severe disease compared to patients that tested negative. COVID+ patients were older (54.09 vs 48.2) and had significantly longer LOS (11.94 vs 6.85 days). We did not identify statistically significant differences between race, ethnicity, sex, glucose, anion gap, Ha1c on admission and ICU admission rate. BHB levels on admission were higher in patients that tested negative. Interestingly, mean pH was higher in COVID-19 positive group possibly due to respiratory disorders.
Presentation: 6/1/2024
8359 Increased hepatic SGK1 activity promotes metabolic dysfunction-associated fatty liver disease in a sex-dependent manner
Authors: Vastola-Mascolo Arianna , Hernández Guadalberto , Alvarez de la Rosa Diego 
Published: October 2024

Abstract
Disclosure: A. Vastola-Mascolo: None. G. Hernández: None. D. Alvarez de la Rosa: None.
The serum and glucocorticoid-induced kinase 1 (SGK1) is a Ser/Thr kinase with key roles in fluid and electrolyte homeostasis, blood pressure regulation and energy metabolism. Its expression is controlled by steroid hormones such as glucocorticoids, mineralocorticoids and estrogen, in addition to other stimuli such as glucose. SGK1 activation mainly depends on the PI3 kinase pathway, implicating it in insulin signaling. Previous work from our laboratory demonstrated that a systemic increase in SGK1 activity exacerbates diet-induced development of metabolic syndrome in mouse, characterized by obesity, glucose intolerance, insulin resistance, dyslipidemia and hypertension. In addition, a high-fat diet rapidly led to the development of hepatic steatosis. We now test the hypothesis that at least part of the effects of increased systemic SGK1 activity promoting the development of metabolic syndrome are due to alterations in liver glucose or lipid handling. To that end we developed a mouse strain with hepatocyte-specific transgenic SKG1 expression and challenged it with high-fat or high-fat/high-sucrose diets. Our results show sex differences in the development of obesity, with a marked increase in body weight in female, but not male transgenic animals. Glucose homeostasis was normal in both sexes. Increased obesity in females correlated with increased lipid accumulation in the liver. However, liver fibrosis, inflammation and dyslipidemia were more marked in male animals, further suggesting an interaction between SGK1 and sex steroid hormone signaling. Our results demonstrate a key role of SGK1 in liver lipid metabolism and suggest a crosstalk between this signaling pathway and sex hormones, which determine a more negative outcome in male animals.
Presentation: 6/1/2024
8443 Incretin-Mimetic Therapy In Hypertriglyceridemia-Induced Pancreatitis - A Case Report
Authors: Iqbal Anira , Alwahab Ula Abed 
Published: October 2024

Abstract
Disclosure: A. Iqbal: None. U. Alwahab: None.
Introduction The use of incretin-mimetic therapy (IMT), which includes human glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) agonists, in patients with a history of pancreatitis is controversial. While clinical trials have demonstrated a slightly increased incidence of acute pancreatitis (AP) in patients on IMT, it is unclear if patients with hypertriglyceridemia (HTG)-induced pancreatitis areat similar risk. In patients with type 2 diabetes (T2D) and HTG, control of diabetes and improvement of metabolic profile using IMT could decrease the risk of HTG-induced pancreatitis. Case Description We report a case of a patient with diabetes and a history of HTG-induced pancreatitis where IMT was successfully used without precipitation of AP. Patient A is a 44-year-old male with obesity (BMI 38.25 kg/m2 ), T2D, and severe HTG associated with recurrent episodes of AP. His triglyceride (TG) level has ranged from 983 to &gt;4,000 mg/dL. He is on fenofibrate, icosapent ethyl, and rosuvastatin. His last hospitalization for acute pancreatitis was 3months prior. His most recent hemoglobin A1c is 7.4%, TG is 302mg/dL, and he is being treated with glipizide, metformin, empagliflozin, and multiple daily injections of insulin. For management of his obesity and T2D, he is then started on tirzepatide, in conjunction with diet and lifestyle modification, which is slowly up-titrated to 7.5 mg weekly. After 12 months of tirzepatide treatment, he has lost 10 lbs, his A1C is now 5.9%, triglycerides have improved to 172 mg/dL, and he has had no precipitation of AP. Discussion While a history of pancreatitis is a relative contraindication to the use of IMT, attention should be paid to the cause of pancreatitis. Obesity and uncontrolled diabetes are frequent triggers of AP. IMT helps improve metabolic profile in patients with obesity, uncontrolled diabetes, and hypertriglyceridemia, thus decreasing triglyceride levels and preventing further episodes of AP as seen in our patient. The use of IMT in patients with a history of AP should be done on an individualized basis. Controlling the trigger for the AP (such as hypertriglyceridemia) should be prioritized and shared medical decision-making with the patient should be done regarding the benefits and risks of IMT.
Presentation: 6/3/2024
7923 Latent Autoimmune Diabetes of Adulthood (LADA) Complicating Common Variable Immunodeficiency (CVID)
Authors: Pathak Leilani , Jakoby Michael G 
Published: October 2024

Abstract
Disclosure: L. Pathak: None. M.G. Jakoby: None.
Introduction: CVID is caused by defective B-lymphocyte maturation that results in immunoglobulin deficiency. Patients with CVID are predisposed to both infections and autoimmune disorders, with approximately 20% experiencing at least one autoimmune complication. We present a patient with LADA complicating CVID. Case A 31-year-old woman was referred for newly diagnosed diabetes mellitus (DM). Medical history was notable for primary hypothyroidism and apparent chronic lymphocytic thyroiditis. A presumptive diagnosis of type 2 DM was made due to obesity, and the patient was treated with metformin. However, she could not tolerate the medication due to diarrhea. Semaglutide was substituted and tolerated without adverse effects. During the first six months of treatment with semaglutide 0.5 mg weekly, HbA1c improved from 6.4 to 5.6%. However, in the next six months, HbA1c increased to 6.6% despite full compliance with medication and stable weight. Anti-glutamic acid decarboxylase (GADA) titer was unequivocally elevated at 69.8 IU/mL (0.0-5.0), though anti-insulin and islet antigen-2 (IA-2) antibodies were undetectable. Insulin glargine was added to the patient’s diabetes regimen, and HbA1c improved to 5.5% three months later. Discussion This patient meets Immunology of Diabetes Society diagnostic criteria for LADA, namely diabetes diagnosed in adulthood (≥ 30 y), elevated diabetes-associated autoantibody titer, and insulin independence for at least six months after diagnosis. Patients with high-titer GADA tend to be younger and have more rapid and significant loss of β-cell function than patients with low GADA titers, and this patient’s rapidly waning glycemic response to semaglutide conforms with this observation. Until recently, autoimmune diabetes in the setting of CVID was thought to be an unusual complication, though the prevalence of type 1 diabetes among CVID patients in the European Society for Immunodeficiency registry is 1.6%, approximately four-fold higher than the general European population. LADA shares genetic features linked to childhood-onset type 1 DM, making it possible or evenly likely that LADA has occurred in cases of CVID, though a careful search of PubMed failed to identify reported cases. This patient illustrates the importance of considering LADA in CVID, particularly with abrupt loss of glycemic response to noninsulin therapeutic agents.
Presentation: 6/1/2024
7113 Liver Androgen Receptor Knockout Improved High-Fat Diet Induced Glucose Dysregulation in Female Mice But Not Male Mice
Authors: Andrisse S 
Published: October 2024

Abstract
Disclosure: S. Andrisse: None.
Previous research has indicated that liver androgen receptors may play a role in modulating disease. This study aims to investigate the pathophysiology of high fat diet (HFD) induced dysglycemia in male and female liver androgen receptor knockout (LivARKO) mice. We performed metabolic tests on LivARKO female and male mice fed a high fat diet (HFD) or a control diet (CD) (from Research Diets Inc) during months 1 or 2 after starting the diet. Additionally, we performed western blot and qRT-PCR analysis on the livers of the mice to examine intermediates in the insulin signaling pathway. LivARKO-HFD female mice displayed no difference in glucose tolerance compared to female LivARKO-Control mice. Whereas in WT female mice, HFD impaired glucose tolerance (IGT). Our data suggests that starting at one-month LivARKO may be protecting female mice from HFD-induced metabolic dysfunction. LivARKO-HFD female mice displayed significantly worse insulin sensitivity at 15 minutes compared to LivARKO-Control (Con) female mice; but, strangely, LivARKO-HFD female mice had significantly better insulin sensitivity at 60 and 90 minutes compared to LivARKO-Con female mice. Despite protecting against IGT, LivARKO did not protect against HFD-induced hyperinsulinemia (HI) in female mice. In contrast to females, male LivARKO-HFD mice displayed impaired glucose tolerance (IGT) compared to male LivARKO-Con mice. Thus, LivARKO is not protective against HFD-induced glucose metabolic dysfunction in male mice. Lastly, LivARKO-HFD female mice maintained hepatic insulin sensitivity whereas LivARKO-HFD male mice displayed hepatic insulin resistance. These findings suggest that LivARKO delayed the onset of HFD-Induced dysglycemia in female mice.
Presentation: 6/1/2024