bluuebunny/crossref_metadata_2025_split huggingface dataset:
ODP156 A Case Report of Clomiphene induced Severe Hypertriglyceridemia
Authors: Tan Zi , Ahmed Ammar , Zainal Abir , Bingham Robert 
Published: November 2022

Abstract

Background
The effects of estrogen on lipids have been well studied whereby estrogen has been shown to decrease total cholesterol and low-density lipoprotein (LDL) cholesterol concentrations and increase high-density lipoprotein (HDL) cholesterol and triglyceride (TG) levels. On the other hand, the effects of clomiphene, a selective estrogen receptor modulator have not been well established.

Clinical Case
A 34-year-old woman with a significant history of type II diabetes who recently started taking self-prescribed clomiphene presented with epigastric pain, nausea, and vomiting. Abdominal examination revealed generalized abdominal tenderness. Laboratory testing revealed normal lipase (30 U/L, normal range 6-51 U/L), increased serum glucose (268 mg/dL, normal range 60-140 mg/dL), and significant elevated TG level (6576 mg/dL, normal range 0-149 mg/dL). Her TG level was 345 mg/dl five months prior to presentation. Abdominal ultrasonography was revealed with no evidence of gallstones and a heterogenous pancreas. She was treated with an insulin infusion and aggressive fluid resuscitation, and her TG level improved to 255 mg/dL after treatment. Given her recent clomiphene use, the patient was deemed to have developed clomiphene-induced severe hypertriglyceridemia. The patient was advised to stop further clomiphene indefinitely and was discharged with fenofibrate 145mg daily and fish oil i. e. omega-3 fatty acid 4g daily for her hypertriglyceridemia. She was asked to follow up with endocrinology outpatient after discharge; however, she was unfortunately lost to follow-up.

Conclusion
This is a rare case report of hypertriglyceridemia caused by using clomiphene citrate. Serum lipid levels should be measured and followed up closely for patients having risk factors predisposing to hyperlipidemia while using clomiphene citrate. Reference: Castro, M. R., T. T. Nguyen, and T. O'Brien, Clomiphene-induced severe hypertriglyceridemia and pancreatitis. Mayo Clin Proc, 1999. 74(11): p. 1125-8.
Presentation: No date and time listed
OR02-3 SLAMF-1 mediates Hepatocyte Death in Non-Alcoholic Fatty Liver Disease and is Plasma values correlates with the Severity of the Disease in Human
Authors: Alexander Jonathan S , Burgos-Ramos Emma , Chapa-Rodriguez Adrian , Cohen Ari , Cruz-Topete Diana , Dhaibar Hemangini , Gomez-Torres Oscar , Kamberov Lilly , Khanna Pranshu , Nunez Kelly , Orr Wayne A , Ron Orem , Samant Hrishikesh , Thevenot Paul , Yurgadul Arif , Amatya Shripa 
Published: November 2022

Abstract
The signaling lymphocytic activation molecule 1 (SLAMF1) exerts a role in regulating the immune response to some viruses and parasite infections. In the present study, we identified SLAMF1 as a potential therapeutic target and biomarker for Non-Alcoholic Fatty Liver Disease (NASH) in humans. We found that SLAMF1 is highly expressed in liver samples from mice and humans with NASH. Our data also show SLAMF1 is detected in plasma, and its levels correlate with the severity of the disease. To uncover a molecular role for SLAMF1 in hepatocytes, we treated two hepatocyte cell lines (HepG2 and HuH-7) and primary mouse hepatocyte with palmitic acid (PA) to induce lipotoxicity, characteristic of NASH. We found that PA treatment leads to a significant increase in SLAMF1 protein levels in the cell lines and primary hepatocytes. We found an increase in HepG2 cell apoptosis in response to PA treatment, and downregulation of SLAMF1 in hepatocytes with siRNA improved cell viability and reduced cytotoxicity, apoptosis, and the expression of inflammatory mediators. Moreover, we found that PA-treated HepG2 cells secrete SLAMF1 in the culture medium, which may be mediating part of these effects through paracrine action. Our findings suggest a role for SLAMF1 in NASH's pathogenesis and highlight SLAMF1 as a reliable clinical biomarker of the disease.
Presentation: Saturday, June 11, 2022 12:00 p.m. - 12:15 p.m.
LBODP031 Evaluation Of Artifactual Hypoglycemia: A Case-based Review
Authors: Mohammed ALShehri Sara , Enani Jawaher , Alfadda Assim Abdulaziz , AlSofiani Mohammed 
Published: November 2022

Abstract

Background
Artifactual Hypoglycemia (AH), is defined as a discrepancy between the measured and actual blood glucose level. The absence of classical symptoms of hypoglycemia in patients with low measured glucose levels should raise the suspicion of AH. Here we describe a case of AH in a patient with chronic myeloid leukemia (CML).

Clinical Case
A 47-year-old woman was hospitalized for the evaluation of a four-month history of headache, anorexia, and weight loss. After further workup, she was diagnosed with CML; and upon evaluation, she was found to have a very low serum glucose level of 22 mg/dL. She reported no symptoms of hypoglycemia at the time and no personal or family history of diabetes. She was not using any glucose-lowering medication. Physical examination findings, including vital signs, were unremarkable. Laboratory studies revealed a serum glucose of 22 mg/dL with a simultaneous point-of-care (POC) capillary glucose level of 81 mg/dL. This discrepancy in glucose levels raised the suspicion of artifactual hypoglycemia. To further explore this, we drew three simultaneous venous blood samples and processed them differently to examine the impact of sample processing on serum glucose level in this patient. Two samples were drawn in tubes with no antiglycolytic agent (one sample was centrifuged immediately after the blood draw, and the second one was processed 5 hours after the blood draw). Whereas, the third sample was drawn in a tube containing sodium fluoride, an inhibitor of aerobic glycolysis, and was processed after one hour of the blood draw. Glucose concentrations in the three samples were as follows: 79 mg/dl, 41.4 mg/dl, and 77.4 mg/dl, respectively. The diagnosis of artifactual hypoglycemia due to excessive glucose consumption by leukocytes was established based on the findings of normal capillary blood glucose and normal plasma glucose levels when a tube prefilled with a glycolysis inhibitor is used.

Conclusion
Artifactual hypoglycemia should be considered in patients with asymptomatic hypoglycemia, especially when there is a discrepancy between the capillary and venous glucose levels. Patients with marked leukocytosis can have artifactually low serum glucose, an erroneous finding that can be mitigated by a) rapid processing of the blood sample or b) utilization of tubes pre-filled with a glycolysis inhibitor.
Presentation: No date and time listed
LBSUN178 Teniposide Improves Adeno-associated Virus-mediated Insulin Gene Therapy In Diabetic Mice.
Authors: Akcan Tugce , Spyra Sam , Sollinger Hans W , Alam Tausif 
Published: November 2022

Abstract
Type 1 Diabetes Mellitus (T1DM) results from the autoimmune destruction of insulin-producing pancreatic β cells. Despite advances in our understanding of the pathogenesis and management of diabetes, as well as treatment options, which primarily include injectable insulin and whole pancreas transplant, these advancements remain unsatisfactory, with only a small percentage of patients achieving their glycemic goals. Insulin gene therapy refers to the development of β cell substitutes by introducing an insulin producing gene into endogenous cell populations that do not normally produce insulin. This strategy has the promise to overcome the limitations of current treatments. Adeno-associated viral (AAV) vector-based gene therapy holds great promise for the treatment of inherited and many complex acquired disorders. The success of AAV vectors is determined by two major factors: 1) cell transduction efficiency, and 2) persistence of the introduced gene with minimal or no host immune response following vector administration. Previous research has suggested that certain small molecules can improve AAV vector transduction efficiency and lower the vector dose below the immunological response threshold. We explore the use of teniposide, a chemotherapeutic agent, in improving the efficacy of gene therapy using AAV. We co-administered teniposide at a final dosage of 20 mg/kg with an AAV vector encoding an insulin gene controlled by a liver-specific promotor into streptozotocin (STZ) induced diabetic Hsd: ICR mice. Teniposide co-treatment produced up to a 3-fold decrease in AAV dose compared to vector alone while reducing diabetic hyperglycemia to comparable degrees as AAV delivery alone. There was no additional systemic toxicity. While the mechanism of action of teniposide-enhanced viral delivery of gene therapy is unknown, our data suggest that teniposide co-administration could significantly enhance AAV transduction in vivo and provide a novel, useful strategy to improve the clinical efficacy of gene therapy.
Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.
LBSUN293 Diabetic Hand Infection: A Case Report
Authors: Huancas Claudia Córdova , Noronha Andrés Gómez 
Published: November 2022

Abstract

Background
Diabetes Mellitus is related to musculoskeletal and soft tissues complications in a very diverse way, and with no doubt, hands are also affected. Almost 40% of people living with Diabetes have significant problems in the hands that require medical attention. (1) Clinical Case: A 59-year-old women with history of Diabetes Mellitus diagnosed 20 years ago without control, treated with NPH and Lispro insulin (basal bolus regimen). She was admitted to the emergency room due to a third-degree boiling water burn in her right index finger. Before she came to the hospital, she was previously evaluated by a physician who prescribed antibiotics (clindamycin) for 5 days without response. At physical examination, erythema, edema, purulent secretion was found in the finger. In addition, fever and high glucose levels were also noted. During hospitalization, intravenous antibiotics such as tigecycline and oxacillin were used with no improvement. Blood samples demonstrated leukocytosis and C-reactive protein (CPR) elevated levels. Secretion culture was positive to Methicillin-sensible Staphylococcus Aureus. Electromyography revealed severe lesions at sensory-motor peripheral nerves with chronic denervation in upper limbs. Due to the poor evolution of the injury, traumatologists indicated surgical cleaning. After 2 days, leukocytosis and CPR elevated levels persisted and despite all the efforts done to save the finger, traumatologists decided to perform an amputation. After 2 weeks of antibiotic treatment, the patient was discharged with normalized hemogram and CPR levels.

Conclusion
Diabetic hand infection is less recognized in the literature that the diabetic foot, main reason why it is easily ignored and underestimated; resulting in increased morbidity among diabetic patients. The combination of neuropathy, peripheral artery disease and impaired glucose levels made this patient had a poor outcome, resulting in the loss of a finger. It is very important to evaluate the hands during routine controls to avoid these sad events. References: 1. Alpesh G, Vivek T, Yashdeep G. Diabetic Hand: A Neglected Complication of Diabetes Mellitus. Cureus. 2018 Jun 9;10(6)
Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.
LBSUN331 Rescuing Alpha Cell Responses To Hypoglycemia In Type 1 Diabetes
Authors: Panzer Julia , Tamayo Alejandro , Borowsky Nicholas S , Caicedo Alejandro 
Published: November 2022

Abstract
Increased glucagon secretion from the pancreatic alpha cell is the first and most important defense against hypoglycemia. In type 1 diabetes this defensive mechanism is lost, increasing the mortality risk. In addition to the reduced glucagon response to hypoglycemia in T1D, basal glucagon secretion is elevated further stimulating hyperglycemia and desensitizing autocrine signaling pathways. Furthermore, alpha cells lose their ability to respond appropriately to rising glucose levels. In healthy individuals, rising glucose levels lead to increased insulin secretion, resulting in inhibition of glucagon secretion. In T1D however, the loss of beta cells results in the absence of these paracrine signals that mediate glucagon suppression under hyperglycemic conditions. We tested the hypothesis that reactivating paracrine and autocrine signaling pathways pharmacologically reverses alpha cell glucose blindness. We used living pancreas slices, which allow functional assessments of damaged and infiltrated islets within their native environment. We studied tissues from non-diabetic donors and donors with type 1 diabetes to determine alpha cell responses to (a) changes in glycemia, (b) agonists, antagonists, and positive allosteric modulators of autocrine and paracrine signaling pathways, and (c) reference stimuli such as adrenaline and KCl depolarization using functional recordings. We further performed in vivo studies using mouse models with defective glucose counterregulation to determine whether alpha cell responses to hypoglycemia could be restored. We found that human alpha cells in slices from type 1 diabetic donors had normal glucagon content and responded to KCl depolarization but failed to respond to decreases in glucose concentration. Furthermore, we found severely diminished Ca2+ responses to both lowering in glucose concentration and glutamate receptor stimulation. Our in vitro results not only reproduced important features seen in vivo but also revealed mechanistic defects related to autocrine and paracrine inputs. Importantly, reestablishing these inputs pharmacologically rescued glucagon secretion in response to a lowering in glucose concentration in human tissue slices/islets from donors with T1D as well as to hypoglycemia in the nonobese diabetic (NOD) mouse model. Several of these signaling molecules are used in other medical indications and could be repurposed to develop therapies aimed at preventing hypoglycemia in T1D.
Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.
ODP169 Challenges with use of HbA1C for Evaluation of Blood Glucose Control
Authors: Maletkovic Jelena 
Published: November 2022

Abstract

Background
Glycated hemoglobin (A1C) is widely used to diagnose diabetes mellitus and monitor glucose control. It represents a measurement of a proportion of glycated hemoglobin which reflects average glycemia over the lifespan of a red blood cell. Genetic factors that affect A1C values have been extensively studied and there is a growing knowledge of some variants that lead to abnormal fasting glucose-A1C ratio. Still, in some patients, delayed diagnosis or suboptimal treatment of diabetes mellitus remains an existing problem when glycated hemoglobin is underestimating blood glucose levels.

Case
69-year-old man was seen in endocrine clinic following a hospital admission for newly diagnosed type 2 DM with hyperglycemic hyperosmolar state and a complicated urinary infection. Prior to admission the patient presented to primary care physician with symptoms of urinary infection and was found to have glucose &gt;500mg/dL on point-of-care test and A1C of 9.5% without known history of diabetes mellitus. After a short hospital course the patient was discharged to home on low dose basal insulin and metformin. His morning glucose in the week after hospital stay was ranging between 140-182mg/dL. At the time of first visit in endocrinology he endorsed symptoms suggestive of peripheral neuropathy and had long standing polyuria, normal BMI and no other medical history or complaints. He was educated about the new diagnosis, diabetic diet, treatment and monitoring and no medication change was made at that time. On the next follow up he reported home glucose readings of 134-191mg/dL and repeated A1C was 5.1%. Urine test was remarkable for microalbuminuria and blood test showed low Hb of 8.7g/dL. Work up for anemia revealed alpha talassemia minor, hemoglobin SC disease and G6PD deficiency. During the following year regular clinic follow up visits were conducted, insulin was discontinued and the patient remained on metformin and empagliflozin over the next 4 years to date. When goal glucose control was achieved with fasting glucose of 90-130mg/dL A1C was 3.8% without any hypoglycemia. Hemoglobin at that time was 9.1g/dL. Over the next 4 years and to date his A1C was still checked 1-2 times a year and remained between 4-4.6%. On review of this patient's chart prior to hospital admission his HbA1C was 5.7% so diabetes mellitus was not suspected before the patient developed diabetic emergency that carries high mortality Discussion: There are known genetic and non-genetic factors that affect HbA1C value. It is very likely that this patient as well as many others have significant delay in diagnosis of diabetes mellitus if only HbA1C is used as screening test. A possibility of genetic variant that affects A1C values, especially in patients of African descent should always be considered when there is a discrepancy between fasting glucose and glycated hemoglobin value.
Presentation: No date and time listed
ODP174 Correlation of Advanced Fibrosis and Coronary Artery Disease Risk Scores in People With Type 2 Diabetes in a Tertiary Care Centre
Authors: Tewari Ajoy , Tewari Jay , Tewari Vineeta 
Published: November 2022

Abstract
Nonalcoholic fatty liver disease (NAFLD) and Type 2 diabetes mellitus (T2DM) are common conditions that often coexist and can act synergistically to cause adverse effects. The presence of both NAFLD and T2DM increases the likelihood of developing diabetes complications (including both macro and microvascular complications), and enhances the risk of cirrhosis, hepatocellular carcinoma and death. NAFLD screening is often neglected in routine clinical practice. Fibro scan is a more sensitive modality for diagnosis of liver fibrosis and scarring. Liver stiffness measurements predict advanced fibrosis in people with diabetes The current study aims to correlate liver stiffness measurements and coronary artery disease risk scores in people with type 2 diabetes in a tertiary care centre Material and Methods: - A total of 181 people with diabetes coming for the first time at our centre underwent liver stiffness measurements using fibro scan after taking consent, people on prior lipid-lowering therapy and thiazolidinedione therapy were excluded from the study. We used the risk score model for the assessment of coronary artery disease in asymptomatic patients with type 2 diabetes [ https://paperpile.com/c/XKqsdv/PpmxP 1 ] because it was easy to use, specific for Asian population and validated with coronary computed tomographic angiography (CCTA) in asymptomatic people with type 2 diabetes. Out of the total of 181 subjects 51% were males and 49% were females, mean age was 50.2 years, duration of diabetes was 7.6years, Hba1c values ranged from 6. 0%-15%(mean 8.5%), median stiffness ranged from 2.3kpa to 34.8kpa (median of 8. 0kpa).50 out of 181(27.62%) had advanced fibrosis(liver stiffness measurements(LSM values of &gt;9. 0). Advanced fibrosis had a significant(p&lt;. 001) correlation with coronary artery risk scores with a correlation coefficient of 0.570. Advanced fibrosis is associated with increased risk of coronary artery disease in people with type 2 diabetes
BIBLIOGRAPHY
1. http://paperpile.com/b/XKqsdv/PpmxP. Park G-M, An H, Lee S-W, Cho Y-R, Gil EH, Her SH, et al. Risk Score Model for the Assessment of Coronary Artery Disease in Asymptomatic Patients With Type 2 Diabetes. Medicine [Internet]. 2015 Jan [cited 2020 Oct 14];94(4): e508. Available from: https://journals.lww.com/md-journal/Fulltext/2015/01040/Risk_Score_Model_for_the_Assessment_of_Coronary.44.aspx
Presentation: No date and time listed
ODP178 Development and Validation of a Noncompetitive Immunoassay Optimized for the Assessment of Pharmacokinetics of Biologically Active Efruxifermin in Humans
Authors: Hurst Jacob , Johnson Derrick , Tillman Erik , Rolph Timothy , Thystrup Jennifer , Bowsher Ronald 
Published: November 2022

Abstract
Efruxifermin (EFX) is a novel fusion biotherapeutic consisting of two modified human fibroblast growth factor (FGF21) variants tethered via short linkers to a hIgG1 Fc domain. EFX is under clinical development by Akero Therapeutics, Inc. for treatment of non-alcoholic steatohepatitis (NASH). Fusion to the IgG Fc moiety extends the circulating half-life of EFX, enabling once-weekly subcutaneous administration. In addition, point mutations in the FGF21 moiety of EFX, relative to native human FGF21, protect against degradation of the C-terminus by the endogenous endopeptidase fibroblast activation protein (FAP), and increase affinity for the FGF21 co-receptor b-Klotho, which together enhance in vivo PD activity of EFX. Accordingly, to support clinical PK a sensitive and specific assay is needed for determination of biologically active (i. e., C-terminal intact) EFX serum concentrations that is minimally cross-reactive with endogenous FGF21 or potential inactive metabolites of EFX. Moreover, the assay needs to have reliability with serum samples from NASH patients, in whom hyperlipidemia and insulin resistance are prevalent. To achieve the analytical aims, we undertook development of a noncompetitive immunosorbent assay design, wherein a biotinylated version of a rat mAb directed against EFX's intact C-terminus serves as the capture reagent, while an affinity purified chicken anti-EFX pAb labeled with Sulfo-TAG functions as the detection reagent. This novel ECLIA design permits measurement of an electrochemiluminescence signal for maximizing assay sensitivity. In brief, serum samples are diluted 1: 10 in buffer and added to the MSD plate coated with rat mAb. After incubation and washing, bound EFX is detected using an affinity purified chicken anti-EFX PAB labeled with SULFO-TAG. After washing and addition of read buffer, the signal responses are measured in a SQ120 reader and concentration in test samples is estimated by dose-interpolation using a weighted 5-PL curve fit with an EFX standard curve ranging from 10–2,000 ng/mL. The new assay allows measurement of serum EFX at concentrations as low at 20 ng/mL. Upon pre-study validation, the assay has met analytical performance criteria outlined in BMV regulatory guidances. We conclude the optimized ECLIA will be useful for reliable assessment of EFX PK in patients with NASH.
Presentation: No date and time listed