bluuebunny/crossref_metadata_2025 huggingface dataset:
ODP136 A Rare Case of Necrotizing Myopathy after Statin Use
Authors: Liu Zhao , Oktaei Hooman
Published: November 2022

Introduction

Statin associated necrotizing autoimmune myopathy is an extremely rare side effects of stain use. The incidence is approximately 2-3/100,000 Patients treated with statins. It usually associated with significant proximal muscle weakness, strikingly elevated creatine kinase (CK) levels and persistent symptoms despitestatin discontinuation. Here, we present a case with necrotizing myopathy after statin use as a reminder to clinicians for appropriately suspicious of this phenomenon while on treatment of statins. Clinical case: A 35 year old male with a past medical history of Autism, Type 2 Diabetes Mellitus, Hyperlipidemia, and Hypertension was brought to emergency room for right leg pain. Family states he had difficulty walking for a few weeks and had a fall from couch a week ago. Initial Vitals showed HR at 134 bpm, temp 35.9, BP 157/85 mmHg, RR 19 breaths/min. Labs showed Creatinine. 3.29 mg/dL, CO2 24 mmol/L, Na 141 mmol/L, K 4.2 mmol/L, Ca 9.5 mg/dL, glucose 265 mg/dL, AST/ALT 914/919 units/L, CK>14,000 units/L, WBC 9.2 thou/mcL, Hb 12.6 g/dL, TSH 9.42 mcIU/mL, Free T3 1.41 pg/mL, Free T4 0.95 mcg/dL. Urinalysis showed large blood with RBC of 1. Myoglobin>8750 mcg/L. Neuro motor exam showed strength 4/5 in bilateral lower extremities. His home medications including atorvastatin 20 mg nightly for 2 years, metformin and olmesartan, which all had been held. He was treated for rhabdomyolysis with aggressive hydration and Creatinine was improving. However, CK continued trending up to 42,915 units/L on day 5 with unreleased symptoms of lower extremity weakness. Neurology was consulted. Differential diagnosis of myopathy were suspected. His CK was continue to trend up to 45,585 units/L on day 10. Decision was made to have muscle biopsy with pathology showed: necrotizing myopathy without any clear evidence of inflammation. Although some autoimmune necrotizing myopathy may not show inflammation like those seen with HMG-CR antibodies or signal recognition antigen antibodies. Autoantibodies against 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase (HMGCR Ab) was above 550. Following the biopsy, he received IV Solu-medrol 1g daily×4 doses, and then PO Prednisone 80 mg daily and then tapered down to 40 mg daily. He was also promptly started on IVIG 400 mg/kg/day for 5 days and methotrexate 7.5 mg weekly. His CK started to improve, down to 5815 units/L three weeks later. No significant improvement of strength.

Conclusion

Our case demonstrates that the appropriate diagnosis of statin induced necrotizing autoimmune myopathy with muscle biopsy and HMGCR Ab. We also wanted to alert future clinicians to have an early suspicious of such rare side effect and initiate treatment as early as possible which may bring the maximum benefit for patients.

Presentation: No date and time listed
ODP137 Achilles Tendon Size and Characteristics for Diagnosis of Familial Hypercholesterolemia Among Thai Patients
Authors: Warachit Parksook Wasita , Gomutput Patrawon , Muanpetch Suwanna , Ganokgroj Poranee , Kerr Stephen , Numkarunarunrote Numphung , Khovidhunkit Weerapan
Published: November 2022

Background

The presence of tendon xanthomas, defined as thickening or nodularities of tendons, is subjective and remains largely undetected in patients with familial hypercholesterolemia (FH) in clinical practice. This study aimed to determine Achilles tendon thickness cutoff values associated with the highest diagnostic accuracy for identifying FH among Thai patients.

Methods

63 subjects with possible, probable or definite FH according to the Dutch Lipid Clinic Network criteria, 58 subjects with hypercholesterolemia not compatible with FH and 55 normolipidemia subjects were recruited. Achilles tendon thickness was measured on each side separately at the point of maximum thickness using Lange skinfold calipers, Slim Guide skinfold calipers, plain radiograph of lateral ankles and ultrasonography. Ultrasonographic characteristics of the tendons were also recorded. The diagnostic performance of the maximum Achilles tendon thickness (maximum value of either left or right Achilles tendon of each person) obtained by each method was determined by Receiver-Operating Characteristic curves and optimal cut-points determined by Youden's index. Spearman rank-order correlation coefficient assessed factors associated with Achilles tendon thickness.

Results

Of all subjects, the mean age was 47 (±13) years, and 45% were male. The study groups were comparable in baseline characteristics except for a higher LDL cholesterol burden, a longer duration of lipid lowering therapy and a higher percentage of subjects receiving high intensity statins and ezetimibe in the FH group. Both types of skinfold calipers demonstrated 61% accuracy for diagnosing FH. An anteroposterior (AP) diameter on plain radiographs ≥7.7 mm had an 80% accuracy with 75% sensitivity and 82% specificity, whereas ultrasonographic thickness ≥6.4 mm. showed a 76% accuracy with 46% sensitivity and 93% specificity. Tendon border irregularities, diffuse hypoechogenicity and calcification were reported in a higher percentage of patients with FH, compared with the other 2 groups. Factors showing a significant correlation with Achilles tendon thickness in the FH group were years since FH diagnosis, a higher Dutch Lipid Clinic Network score and a higher body mass index (BMI). In the overall cohort, factors showing a significant correlation were higher LDL cholesterol burden and higher BMI.

Conclusion

Achilles tendon thickness measured by calipers showed low accuracy for FH diagnosis. An AP diameter on plain radiographs demonstrated highest sensitivity, whereas ultrasonographic thickness and area of Achilles tendon showed high specificity. Tendon irregularities, diffuse hypoechogenicity and calcification might serve as supportive findings.

Presentation: No date and time listed
ODP141 Complement Activation and Homeostasis Works Primarily Through the Alternative Pathway in Polycystic Ovary Syndrome
Authors: Atkin Stephen , Butler Prof Alexandra , Sathyapalan Thozhukat
Published: November 2022

Introduction

It has been shown that complement factors are increased in polycystic ovary syndrome (PCOS) and that these may be affected by obesity and insulin resistance. Hypothetically, this may increase cardiometabolic risk but, paradoxically, increased clotting is not a feature of PCOS. To investigate this, proteomic analysis of the complement system was undertaken, including inhibitory proteins.

Methods

Plasma was collected from 244 women (147 with PCOS and all 3 diagnostic features and 97 controls). Somalogic proteomic analysis was undertaken for the following complement system proteins: C1q, C1r, C2, C3, C3a, iC3b, C3b, C3d, C3adesArg, C4, C4a, C4b, C5, C5a, C5b-6 complex, C8, properdin, Factor B, Factor D, Factor H, Factor I, Mannose-binding protein C (MBL), Mannan-binding lectin serine protease 1 (MASP3), Complement decay-accelerating factor (DAF) and Complement factor H-related protein 5 (CFHR5).

Results

The alternative pathway of the complement system was primarily activated in PCOS, with increased C3 (p<0. 05), properdin and Factor B (p<0. 01). In addition, inhibition of this pathway was also seen in PCOS, with increase in CFHR5, Factor H and Factor I (p<0. 01). There were also increases in the downstream complement factors of iC3b and C3d, associated with an enhanced B cell response, and C5a, associated with inflammatory cytokine release (p<0. 01).

Conclusion

This is the most comprehensive evaluation of the complement system in PCOS to date and reveals upregulation of the alternative complement system that appears to be offset by the concurrent upregulation of its inhibitors. However, any additional dysregulation of the system, such as occurs with COVID19 infection, may give rise to an increased risk for clotting in women with PCOS.

Presentation: No date and time listed
ODP155 Successful Treatment of PEG-Asparaginase Related Hypertriglyceridemia with Omega-3 Acid Ethyl Esters
Authors: Radovanovic Natasa , Crawford Andrew
Published: November 2022

Introduction

Young adults diagnosed with acute lymphoblastic leukemia (ALL) have been increasingly treated with a pediatric-inspired regimen including asparaginase, to improve both quality and quantity of survival. Peg-asparaginase (PEG-ASP) is a long-acting formulation of L-asparaginase (L-ASP), an enzyme that selectively kills leukemic cells by depleting plasma asparagine. Treatment with PEG-ASP provides multiple benefits including increased complete remission rates and overall survival, however, numerous toxicities can occur including fatigue, nausea, vomiting, hypersensitivity, thrombosis, pancreatitis, hepatotoxicity, and, less commonly, hypertriglyceridemia (HTG). Several treatment approaches have been reported for patients with PEG-ASP induced HTG but strong evidence supporting any specific option is lacking. Clinical case: A 24-year-old woman presented with sacral joint septic arthritis that led to the discovery of underlying B-cell acute lymphoblastic leukemia (B-ALL). Soon after diagnosis the CALGB 10403 protocol, which contains PEG-ASP, was initiated. Sixteen days after the initial PEG-ASP dose of 3,750 units it was noted her plasma serum was lipemic with TG of 669 mg/dL, which peaked the next day to 1,314 mg/dL while the patient remained asymptomatic and without signs or symptoms of pancreatitis. She was started on a brief course of insulin drip (lasting 6 hours) and a low-fat diet. Four days later fish oil (omega-3 acid ethyl esters) 2 gm twice daily was added, and two days later micronized fenofibrate 67 mg as well. She was tolerating this regimen for three days when fenofibrate had to be discontinued due to elevated liver enzymes while fish oil was continued. Triglycerides continued to successfully trend down over the course of two weeks, and after reaching a level of 111 mg/dL she was re-challenged with another dose of PEG-ASP 3,750 units. After the second dose of PEG-ASP, her TGs became elevated again but peaked at 542 mg/dL. She received a third dose of PEG-ASP 3,750 units two months later when TG remained below 200 mg/dL. A month later she received a fourth/final dose of PEG-ASP 3,750 units which led to transient elevation of TGs peaking at 437 mg/dL but returning to levels below 200 mg/dl within two months. Throughout the course of her treatment with PEG-ASP, she continued to take fish oil.

Conclusion

Multiple studies showed that the benefit to toxicity ratio of asparaginase in young adults with ALL is favorable. Our conclusion is that in patients who develop HTG, fish oil can be utilized as a treatment and continued as long as they are receiving PEG-ASP, especially in patients unable to tolerate fenofibrate. We would like to bring attention to this case with the current positive outcome given the fact there is currently limited evidence on the safety of re-challenging patients with PEG-ASP after experiencing HTG.

Presentation: No date and time listed
ODP156 A Case Report of Clomiphene induced Severe Hypertriglyceridemia
Authors: Tan Zi , Ahmed Ammar , Zainal Abir , Bingham Robert
Published: November 2022

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

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

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

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

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

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

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 >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

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 >9. 0). Advanced fibrosis had a significant(p<. 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

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
ODP197 Familial Hypertriglyceridemia Initially Presenting with Hypertriglyceridemia-induced Pancreatitis: A Case Report
Authors: Arora Gunjan , Laskova Anna , Kim Keun Young
Published: November 2022

Case Presentation

A 28 year old male with a past medical history of diabetes mellitus type 2 (T2DM) and hypertension presented to the emergency room with acute onset, progressive epigastric pain associated with nausea. The pain suddenly started earlier that day after a large meal. He denied alcohol use. He was previously on insulin Glargine 55 units nightly but was not using it for several months. Vitals signs were within normal limits, BMI was 38.5 kg/m 2 . Physical examination revealed marked epigastric tenderness and multiple yellow papules on the abdomen and extensor surfaces of extremities. Lab findings revealed WBC 14.3 k/mm cu, lipase 437 IU/L, triglycerides greater than 3000 mg/dl with VLDL greater than 3000 mg/dl. Computerized tomography of the abdomen was consistent with acute pancreatitis. He was diagnosed with familial hypertriglyceridemia presenting with hypertriglyceridemia-induced pancreatitis and was admitted to the intensive care unit (ICU). Treatment with regular insulin infusion was started. On day 3, triglyceride levels decreased to 543 mg/dl and insulin infusion was stopped. He reported symptomatic improvement and was able to tolerate oral diet. He was counseled on significance of lifestyle modifications and medication compliance and was discharged on Niacin, Omega 3, Fenofibrate, Ezetimibe, and Pravastatin with plans to follow up with an Endocrinologist.

Discussion

This case of a young male presenting with hypertriglyceridemia-induced pancreatitis due to underlying familial hypertriglyceridemia emphasizes the significance of comprehensive history taking and work up for patients initially presenting to the clinic with risk factors such as obesity and insulin resistance. Our patient classically had a history of T2DM, and as cardiovascular complications are the leading cause of mortality in diabetic patients, screening for and managing dyslipidemia is pivotal. Eruptive xanthomas are erythematous-yellow papules typically located on extensor surfaces which appear when triglyceride levels exceed 1500-2000 mg/dl. This characteristic skin finding led to a prompt suspicion for familial hypertriglyceridemia in our patient. Our patient was stabilized in the ICU and subsequently discharged on multiple oral agents. The current consensus is that single statin therapy is not recommended; however, further research is indicated to specify the optimal combination of triglyceride lowering agents based on the severity of hypertriglyceridemia.

Presentation: No date and time listed
ODP207 Histone methylase MLL attenuates insulin secretion by reducing glucose sensitivity in mouse pancreas
Authors: Yoshino Satoshi , Horiguchi Emi Ishida Kazuhiko , Matsumoto Shunichi , Yamada Eijiro , Yamada Masanobu
Published: November 2022

Background

Myeloid / Lymphoid or Mixed-lineage leukemia gene (MLL) is translocated to chromosome 11 long arm q23 region (11q23) and the MLL fusion gene expressed as a result of translocation reconstruction plays an important role in MLL-related leukemia development. It has also been reported that MLL and MLL protein play an important role in tumor development as a Menin-binding protein in Multiple Endocrine Neoplasia Type I (MEN1). More recently, normal MLL protein has been shown to have histone H3 lysine 4-methylation (H3K4-HMT) activity and to be an epigenetic transcriptional regulator. In addition, the function of MLL protein as a histone methylase has been reported in the gene region involved in metabolism regions. Here, we analyzed the involvement of MLL in glucose metabolism in the pancreas using MLL knockout mice.

Methods

Glucose metabolism in MLL knockout mice and the function of MLL in cultured cells were analyzed. Result: Since the homozygotes of MLL knockout mice are embryonic lethal, we analyzed them using Heterozygous mice. MLL heterozygous mice showed significantly weight loss compared to the wild type mice. MLL heterozygous mice showed no difference in food intake compared to wild type mice. IPGTT showed impaired glucose tolerance in MLL heterozygous mice. However, ITT showed no insulin resistance and decreased insulin secretion during glucose loading. In GSIS tests, Islets isolated from heterozygous mice pancreas have been observed to decrease insulin secretion in the response to glucose stimulation. In comprehensive gene analysis using Microarray analysis of mRNA extracted from mice islet, the gene expression changes related insulin secretion and apoptosis have been revealed in MLL heterozygous mice. Histological search showed no decrease in β-cell number, and immunohistological search showed no difference in insulin, glucagon, and TUNEL staining between heterozygous and wild type mice. And also, MLL knockdown was performed in a cultured cell line. Insulin secretion was decreased to glucose stimulation in MLL knockdown cell line same as in MLL knockout mice. In addition, RNA microarrays were performed to these cell lines, several same genes that have confirmed in MLL mouse islets were observed in MLL knockdown cell. In common to both MLL knockout mice and MLL knockdown cell line, the expression levels of GLUT1 and GLUT2 were decreased. In conclusion, MLL knockout mice showed decreased insulin secretion. It was suggested that MLL may be involved in insulin secretion through decreased expression of the GULT1 gene and GLUT2 genes in islets.

Presentation: No date and time listed
ODP216 Interventional Study To Reduce The Readmission Rate In Type 1 Diabetics Hospitalized For Diabetic Ketoacidosis
Authors: Hashmi Syed Salman Hamid , Bahtiyar Gul , Rodriguez Giovanna , Bagar Darin Daw , Sadiq Nazia , Milla Cristian , Gorbonos Allen
Published: November 2022

Introduction

Diabetic ketoacidosis (DKA) is an emergency associated with a high mortality rate. 25% of DKA readmissions in the U. S. A are preventable and they lead to an increase in the mortality rate and the length of the hospital stay with each new admission. In our study, we set out to decrease the DKA readmission rate at our hospital which is a community teaching hospital by assessing the predictors of readmission in adults with type 1 diabetics hospitalized for DKA.

Methods

The study was an interventional study conducted between February 2021 and May 2021. All the type 1 diabetics who were on insulin and had DKA admissions in the past three months were included in the study. After a literature review of the risk factors of DKA readmission, a questionnaire was designed to gather information from the patients. The ABCD (A: age; B: behavioral health; C: coverage; D: drug/alcohol abuse) score was used for DKA readmission risk assessment on admission. The insulin delivery technique of the patients was assessed and proper training on the technique was given before discharge. All the DKA admissions received mandatory endocrinology consult and the note template of the endocrinology consult note in the electronic medical record system was modified to let the primary team know about the discharge instructions, medications, and follow-up appointments in detail. Patients were followed up with a telehealth visit in a week and physical endocrinology clinic follow-up 3 weeks after discharge.

Results

Our study included 69 patients admitted with a diagnosis of DKA. The average HbA1C in the study was 11.8. Predictors of readmission were female sex (Hazard Ratio [HR]: 1.74, 95% CI: 1.64 - 1.80, p<0. 001), hypertension (HR: 1.98, 95% CI: 1.80 - 1.95, p<0. 001), discharge against medical advice (HR: 1.74, 95% CI: 1.53 - 1.96, p<0. 001). The readmission rate at the hospital was 20.8% initially and dropped to 13.7% after the interventions. 78% of the population were administering insulin the wrong way. The 'ABCD' score of the patients had a statistically significant correlation with the readmission rate. A difference in difference study model was used to assess the significance of the interventions on the readmission rate. Linear regression was run with significant R square, F- test values.

Conclusions

The study revealed that the major risk factors for readmission were lower socioeconomic status, co-morbidities, poor health literacy, and drug abuse. The study highlighted the importance of inpatient education, specialty care, better discharge instructions, coordination of care, and post-discharge support to reduce the DKA readmission rate.

Presentation: No date and time listed
ODP219 Laparoscopic Gastrostomy tube (LGT) Placement for Management of Post Bariatric Surgery Hypoglycemia Syndrome (PBSHS).
Authors: Uwaifo Gabriel , Juneau Andrea Kate , Gridley Asahel
Published: November 2022

Introduction

Bariatric surgery is currently the most effective long term management for morbid obesity. Laparoscopic bariatric surgery whether gastric banding (LGB), sleeve gastrectomy (LSG) or gastric bypass (LRYGB) are now more commonly done. One major complication that can follow these procedures are the hypoglycemic syndromes; post bariatric surgery hypoglycemia syndrome (PBSHS). PBSHS is a spectrum ranging from mild reactive hypoglycemia to hypoglycemia with dumping syndrome to the most severe being post bariatric surgery nesidioblastosis (PBSN). Clinical case; The patient is a 33 yr old Caucasian lady with past history of morbid obesity who had LSG in 2012 with poor weight loss response. This was converted to LRYGB in 2016 with much better weight loss response. Within 1.5 yrs of the LRYGB however she started having recurrent hypoglycemic episodes which were initially mild and mostly postprandial (PP) but rapidly escalated to both fasting and PP states. Work up revealed that she had both reactive and fasting hypoglycemia and despite dietary interventions the episodes escalated and with "defensive eating" she progressively gained weight. Her hypoglycemic spells were confirmed as insulin mediated and consistent with PBSN. Medical therapy escalated to maximum dose acarbose, octreotide and high dose diazoxide. The frequency and severity of the hypoglycemic spells worsened and in 2021 she had over 7 hospital admissions from severe hypoglycemia with additional ED visits despite medication use including emergent glucagon use and CGMS monitoring with a DEXCOM device. She had hypoglycemia unawareness with progressively declining quality of life. Rather than possible attempted reversal of the LRYGB a LGT was placed to see if this would ameliorate her symptoms. She now drinks only non-caloric fluids per oral and all caloric intake is via the LGT. The clinical response has been swift and dramatic. Since LGT placement over 3 mths now she has had no symptomatic hypoglycemic episode and no ED nor hospital admissions. Post LGT placement CGMS profile demonstrated marked improvements in glycemic profile and post LGT mixed meal tests (MMT). A dichotomy was demonstrated between her glycemic profile on MMT for oral vs LGT caloric intake providing confirmation of the therapeutic effect of the LGT placement.

Discussion

With the increasing utilization of bariatric surgery for management of obesity and diabetes, the prevalence of PBSHS is expected to increase. This complication can be difficult and expensive to manage while negatively impacting weight loss and quality of life. Our case provides proof of principle evidence to suggest LGT placement as a management consideration in severe cases of PBSN.

Conclusions

LGT placement should be considered as an option in patients with severe PBSN that is poorly controlled with maximal medical and lifestyle interventions.

Presentation: No date and time listed
OR03-5 Identification of Four New Glucotypes during the First Year after Type 1 Diabetes Onset Using Continuous Glucose Monitoring Metrics
Authors: Delfosse Antoine , den Brinker Marieke , Gatto Laurent , Gies Inge , Lebrethon Marie-Christine , Louis Jacques , Lysy Philippe , Martin Manon , Mouraux Thierry , Seret Nicole , Polle Olivier
Published: November 2022

Current markers of β-cell function poorly reflect glucose homeostasis after diabetes onset, mainly because of the lack of integration of parameters of insulin sensitivity and β-cell responsiveness to glucose. Recently, the widespread use of continuous glucose monitoring (CGM) helped stratify glucose control in patients with long-term diabetes in new clinically relevant glucotypes. In our DIATAG study, we investigated how CGM metrics may help to segregate patients with new-onset type 1 diabetes (T1D) entering or not in partial remission (PR). We collected data from 66 pediatric patients with T1D (10.4±4.7 yo) during the first year after diabetes onset (Δ). Clinical parameters (i.e. A1C, insulin daily dose, insulin-dose adjusted A1c [IDAA1C]) and CGM data were collected at Δ+3, +6, +9, +12 months (n=168, 57% remitters [IDAA1C <9]). A panel of 46 CGM metrics was calculated on an hourly and daily basis using iglu package (1). Using unsupervised hierarchical clustering based on daily CGM metrics and clinical parameters, we identified four clusters of glucose metrics that differed from each other (p<0.05). Cluster 1 was characterized by an increased glucose stability (coefficient of variation [CV] 32±5%) within time in target (TIT [63-140 mg/dL], 83±6%) with 9% of sensor values in 63-70 mg/dL range in the early morning period. Cluster 2 exhibited a progressive decrease of TIT (60±14%) and an increase of target above range (TAR [>180 mg/dL], 20±9%) especially during the day while target in range (TIR [70-180 mg/dL]) was nearly equivalent to Cluster 1 (80±8%). Notably, CV remained low (32±5%) with little time spent below range (TBR [<70 mg/dL], 5±2%). Cluster 3 demonstrated a net increase of CV during all the nycthemere (46±7%) concomitantly to an increase of TBR (14±7%). Interestingly, TIT and TAR remained close to values from Cluster 2 (55±11%; 23±10%). Finally, Cluster 4 demonstrated major hyperglycemias (TAR, 55±13%) with increased CV (47±9%) and decreased TBR (8±6%). Interestingly, clustering allowed clinically relevant segregation of intermediate values of IDAA1C (i.e. 7.5-10) between Cluster 2 and Cluster 3, independently of the remission status. Moreover, participants at Δ+3 months distributed across all clusters (with respectively 38% in Cluster 1, 26% in Cluster 2, 29% in Cluster 3 and 7% in Cluster 4) highlighting the usefulness of CGM in characterizing disease heterogeneity from diabetes onset. In our study, a combination of CGM metrics and clinical parameters unraveled key clinical milestones of glucose homeostasis and remission status during the first year of T1D. 1. Broll et al, 2021;16(4): e0248560.

Presentation: Saturday, June 11, 2022 12:30 p.m. - 12:45 p.m.