bluuebunny/crossref_metadata_2025 huggingface dataset:
THU276 The Use of Continuous Glucose Monitors for Management of Postbariatric Hypoglycemia
Authors: Jani Shivani , Bao Shichun
Published: October 2023

Disclosure: S. Jani: None. S. Bao: None.

Postprandial hypoglycemia is a known complication of bariatric surgery. Mixed meal tolerance test performed in these patients often revealed hypoglycemia 1-3 hours after meals. Recent clinical studies using continuous glucose monitors (CGM) have shown the incidence of postbariatric hypoglycemia is much higher than previously identified. In addition to diet modification and medication treatment, CGM has become a more popular and useful tool in managing severe cases. We present a case of using CGM to manage postbariatric hypoglycemia.

A 47 year old female with prior history of class 3 obesity treated with sleeve gastrectomy presented with hypoglycemia 2.5 years after her bariatric surgery. She complained of headache, anxiety, dizziness, and fatigue during a routine clinic visit, two hours after consuming a carbohydrate rich meal with simple sugars. Blood glucose was obtained and revealed severe hypoglycemia (glucose 38 mg/dL). This prompted an urgent referral to endocrinology. Review of glucose trends revealed multiple instances of postprandial hypoglycemia. Further labs suggested a low likelihood for insulinoma with no fasting hypoglycemia and HA1C normal at 5.3%. Postprandial hyperinsulinemic hypoglycemia was suspected clinically. Dietary modification with multiple small meals consisting of high protein, fiber and complex carbohydrates was recommended. Additionally, she was started on Libre 2 CGM for monitoring and prevention of severe hypoglycemia. Review of her CGM data during follow up visit demonstrated very low incidence of hypoglycemia and absence of severe hypoglycemia. Over time with continued use of her CGM and low incidence of hypoglycemia, she did not require medical therapy.

Postprandial hypoglycemia after bariatric surgery can be severe and lead to disabling neuroglycopenic symptoms. With increased utilization of bariatric surgery, these postoperative complications will likely become more prevalent. In a Swedish nationwide study, the prevalence of postbariatric hypoglycemia was close to 0.2% in a cohort of 5040 patients. However, a more recent prospective study with a two-year observation of 333 patients after bariatric surgery using 2-hour glucose tolerance test revealed much higher prevalence of severe postprandial hypoglycemia (25.6%). Hypoglycemia was highest after gastric bypass surgery (32.6%), followed by sleeve gastrectomy (22.6%). Currently, there is no official guideline on utilization of CGM in management of hypoglycemia in nondiabetic patients. This case highlights the role of CGM in managing postbariatric hypoglycemia. CGM provides continuous glucose data, trends and alerts that can be a critical tool for patients to monitor, anticipate and prevent hypoglycemic events. Additionally, the real time data provided by CGM’s can help clinicians identify high risk patients who may benefit from the addition of medications to treat hypoglycemia.

Presentation: Thursday, June 15, 2023
THU293 Enhancement Of Best Practices In Diabetic Ketoacidosis Management Using Standardized Order-sets vs Individual Practitioner Orders
Authors: Yim Carly , Li Qinghao , Arnason Terra G
Published: October 2023

Disclosure: C. Yim: None. Q. Li: None. T.G. Arnason: None.

Diabetic ketoacidosis (DKA) is a hyperglycemic emergency occurring in diabetics due to insulin deficiency. This results in urinary losses of water and electrolytes (sodium, potassium, chloride) and ultimately extracellular fluid volume depletion. Hallmark features of DKA include ketoacidosis, arterial pH < 7.3, bicarbonate <15 mmol/L and an anion gap of >12 mmol/L.

The 2018 Diabetes Canada (DC) guidelines outline the key steps of DKA management including fluid resuscitation, resolution of ketoacidosis, correction of electrolytes and management of precipitating factors. Its detailed algorithm identifies three pillars to DKA treatment: IV fluids, serum potassium and acidosis.

A 2016 DKA outcome audit at the Royal University Hospital (RUH) in Saskatoon identified that practitioners diverged considerably from (2013) Canadian Diabetes Association guidelines. Subsequently, two standardized preprinted DKA order sets were developed incorporating the 2018 DC recommendations for i) INITIAL and ii) MAINTENANCE DKA management. Their rollout overlapped with annual academic half day sessions on DKA management for postgraduate year 1 residents in internal medicine. These order-sets were initially implemented at RUH in November 2018 and subsequently adopted by some practitioners at St. Paul’s Hospital (SPH).

To ensure the order-sets were promoting improved outcomes and adhering to best practices, a retrospective chart review was conducted of all adult DKA admissions at RUH and SPH from Nov. 13, 2018 to December 31, 2020. In total, 279 hospital admissions were reviewed: 99 used practitioners’ own orders, 115 used both initial and maintenance order-sets, 26 used only the initial order-set and 38 used only the maintenance order-set.

Use of the INITIAL order set significantly improved compliance (p < 0.0001) with DC 2018 guidelines for recommended insulin dose and timing, fluid resuscitation as well as potassium, sodium and dextrose replacement. Use of the MAINTENANCE order set consistently enhanced outcomes for intravenous fluid selection, subcutaneous insulin overlap, and ensuring a closed anion gap at transition (p < 0.0001).

Additionally, the chart review revealed that there were hospital differences for uptake of order sets and compliance to DC 2018 guidelines. There was a significant uptake of order sets at RUH versus SPH (p < 0.0001). RUH consistently met outcomes for appropriate insulin dosing, potassium and dextrose replacement (p < 0.0001). RUH also consistently overlapped IV and SC insulin and ensured a closed insulin gap. The anion gap remained consistently closed post-transition at RUH versus SPH (p = 0.035).

These results suggest that utilization of a DKA order set does significantly promote adherence to key best practices outlined in the DC 2018 guidelines.

Presentation: Thursday, June 15, 2023
THU307 Landscapes Of MaternalAnd Neonatal Bacterial And Metabolic SignaturesAnd Their Interaction In Gestational Diabetes Mellitus
Authors: Ding Lu , Liu Jieying , Zhai Xiao , Xiao Xinhua
Published: October 2023

Disclosure: L. Ding: None. J. Liu: None. X. Zhai: None. X. Xiao: None.

Background: Gestational diabetes mellitus (GDM) is strongly correlated with considerable risks to both the mother and the developing fetus. Although evidence indicates an association between the altered gut microbiota and GDM, the microbial and metabolic mechanisms that link the metabolic state between mothers and offspring are unknown. This study aims to characterize the maternal and neonatal bacterial and metabolic signatures and their interaction in gestational diabetes mellitus. Methods: Sixty-six mothers (39 women with GDM and 27 normal pregnant women) and eighty-nine newborns (44 from GDM mothers and 45 from normal mothers) were included in this study. Using 16S rRNA gene sequencing and untargeted metabolomic methods, we determined the gut microbiota and serum metabolomics both for mothers and newborns. Results: We found that the microbial and metabolic signatures of GDM mothers and newborns were significantly different from those of the Control group (Ctr), respectively. Intriguingly, we identified 14 genera (Phyllobacterium, etc.) that exhibited identical alterations in mothers and newborns between groups. Among the overlapped differential metabolites in mothers and newborns, 23 (Glutamyl-methionine, etc.) showed consistent alterations between groups, while 19 (Cyclotetradecane, etc.) metabolites exhibited opposite alterations. Metabolic KEGG pathway analysis revealed that 6 pathways, including fatty acid metabolism, sphingolipid metabolism, TCA cycle, transsulfuration pathway, bile acid metabolism, and carnitine metabolism were both enriched in mothers and newborns. Significantly, correlation analysis revealed the notable association between pyroglutamic acid and maternal glucose level in Ctr group was disrupted in GDM group (Ctr: r = -0.46, p = 0.02; GDM: r = 0.04, p = 0.82). Simultaneously, pyroglutamic acid was significantly correlated with neonate serum high-density lipoprotein cholesterol level, which was disrupted in newborns of GDM mothers (Ctr: r = 0.33, p = 0.03; GDM: r = -0.05, p = 0.80). Conclusion: Altogether, we demonstrated that GDM could consistently alter the microbiota and serum metabolome in mothers and newborns, which is significantly associated with their metabolic state respectively. These findings indicate that serum metabolites serve as promising targets to intervene in metabolic transmission in GDM, which needs further validation.

Presentation: Thursday, June 15, 2023
THU327 Characterization Of New Onset Diabetes Mellitus Concurrent With COVID-19; A Single Institution Experience
Authors: Haque Tania , Gaddis Monica , Asad Reda , Simon Stephen , Drees Betty M
Published: October 2023

Disclosure: T. Haque: None. M. Gaddis: None. R. Asad: None. S. Simon: None. B.M. Drees: None.

Objective: The global pandemic of novel SARS-COV2 virus causing Covid-19 infection, is reported to lead to development of new onset diabetes mellitus (DM). This study describes the types of DM following Covid-19 infection, the patient characteristics and the disease course up to 12 months. Methods: A database of patients with DM treated at the institution was searched for a positive PCR Covid-19 test between March 1, 2020, and November 30, 2021. Charts were manually reviewed for diagnosis of co-morbidities, laboratory results, medications, disposition, and verification of type of DM. Outcomes data were collected at 0, 6, and 12 months. Results: Among 1643 Covid-19 positive patients with DM, 96 were diagnosed with new onset DM. There were 42% Black, 24% White, and 23% Hispanic; 94 had type 2 DM and two had type 1 DM. Average age was 50; half were women. Patients with more severe Covid (inpatient and ER visits) were more likely to require insulin, multiple DM medications, and had higher HbA1c levels. Insulin use and multiple DM medications decreased over time (25% and 25% at diagnosis; 10% and 18% at 12 months, respectively). HbA1c decreased over time (9.1% at diagnosis and 7.3% at 12 months). One-year follow-up was available on 73 patients, of whom 19 were on no medications for DM. Conclusion: New onset diabetes mellitus following Covid-19 infection is common and predominantly type 2 DM. However, glucose levels tend to improve over time requiring less medication, with 26% requiring no DM medications at one year.

Presentation: Thursday, June 15, 2023
THU339 Neutrophil Gelatinase-associated Lipocalin And B2-microglobulin May Reflect Early Diabetic Nephropathy In Asymptomatic Patients With Type 1 Diabetes
Authors: Papadopoulou Nektaria , Arkoumani Maira , Papassotiriou Ioannis , Mantzou Aimilia , Chrousos George P , Tentolouris Nikolaos , Kanaka-Gantenbein Christina
Published: October 2023

Disclosure: N. Papadopoulou: None. M. Arkoumani: None. I. Papassotiriou: None. A. Mantzou: None. G.P. Chrousos: None. N. Tentolouris: None. C. Kanaka-Gantenbein: None.

Type 1 diabetes (T1D) is a frequent autoimmune disease in childhood, adolescence and young adulthood and may cause microvascular complications. Several studies have shown that increased serum or urine Neutrophil Gelatinase-Associated Lipocalin (NGAL) and beta 2 microglobulin (b2-microglobulin) are associated with microvascular complications like nephropathy. Hypothesis and Underlying Question the Research Addresses: We assessed the role of serum and urine NGAL and b2-microglobulin, biomarkers of renal dysfunction, in unravelling early renal dysfunction in T1D. Overview of Experimental Design and Methodology: Two patient groups who took part in two-centers’ prospective cohorts were studied. Sixty-one patients with T1D, aged 5-17 years from the Diabetes Center of Aghia Sophia Children’s Hospital, University of Athens, Greece, and 34 patients with T1D aged 18-44 years from the Diabetes Center, 1st Propaedeutic Department Laiko of the Laikon University Hospital of Athens, Greece were recruited. Sixty age- and sex-matched apparently healthy controls were also included in the study . Along with standard blood and urine chemistry, serum and urine NGAL concentrations and serum b2-microglobulin were determined by means of immunoenzymatic techniques. Estimated glomerular filtration rate (eGFR) was calculated with CKD EPI. Both physical and laboratory examinations were obtained in 2 time-points, at baseline and 12 months later. Main Results: In both young and adult groups with T1D, urine NGAL correlated positively with microalbuminuria (r=0.33, p=0.003) and decreased eGFR (r= -0.37, p=0.0008) irrespectively of gender or age. Decreased values of eGFR were correlated with increased values of b2-microglobulin (r= -0.30, p=0.002). Interpretation of Results and Conclusions: Urine NGAL as well as serum b2-microglobulin levels, proposed biomarkers of renal dysfunction, correlated with indices of early diabetic nephropathy, characterized by both microalbuminuria and decreased eGFR in patients with T1D, showing similar results in a broad patients’ age range. Thus, this marker may unmask early reversible renal dysfunction before overt nephropathy appears. However, prior to its clinical application, this biomarker must undergo thorough validation in several cohorts.

Presentation: Thursday, June 15, 2023
THU345 SGLT2 Inhibitors Reduce Mortality In Patients With Acute Myocardial Infarction And Percutaneous Coronary Intervention: A Systematic Review And Meta-analysis
Authors: Goncalves Ribeiro Sandro Augusto , Carvalho Pedro E P , do Amaral Neto Augusto Barreto , Felix Nicole , Teixeira Larissa , Gauza Mateus Miranda , Schramm Guisso Maria Eduarda , Campelo Jorge Carlos Alberto , da Camara Pedro Matos , Costa Neto Jose Amir , do Amaral Adilaine Rosa , de Sa Joao Roberto
Published: October 2023

Disclosure: S.G. Ribeiro: None. P.E. Carvalho: None. A.B. Neto: None. N. Felix: None. L. Teixeira: None. M.M. Gauza: None. M.S. Guisso: None. C.C. Jorge: None. P.M. Camara: None. J.C. Neto: None. A.R. Amaral: None. J.D. Sa: None.

Background: The effects of sodium-glucose cotransporter 2 inhibitors (SGLT2i) on the prognosis of patients with acute myocardial infarction (MI) undergoing percutaneous coronary intervention (PCI) is not well established. Objectives: We performed a systematic review and meta-analysis to compare cardiovascular endpoints in patients undergoing PCI after acute MI treated with versus without SGLT2i. Methods: Medline, Cochrane, and Embase were systematically searched for randomized and non-randomized controlled trials that reported cardiovascular outcomes after SGLT2i initiation following PCI in patients with acute MI. Odds ratio (OR) with 95% confidence intervals (CI) were pooled with a random-effects model. Risk of bias assessment was performed as outlined by Cochrane recommendations. Results: There were 6 included studies, with 2,147 patients with acute MI and PCI, of whom 597 (27.8%) received SGLT2i therapy; 1,085 (50.5%) had diabetes mellitus. Two studies were randomized, whereas 4 studies were non-randomized cohorts. Treatment with SGLT2i reduced all-cause mortality (OR 0.49; 95% CI 0.26-0.95; p=0.03; I2=0%) and severe arrhythmia (OR 0.31; 95% CI 0.12-0.79; p=0.01; I2=0%) compared with no SGLT2i therapy. In contrast, there was no difference between groups in the incidence of myocardial infarction (OR 0.47; 95% CI 20-1.10; p=0.09; I2=40%) and repeat revascularizations (OR 0.86; 95% CI 0.34-2.13; I2=61%). Conclusion: In this meta-analysis of 2,147 patients with acute MI undergoing PCI, SGLT2i significantly reduced all-cause mortality and severe arrhythmia compared to no SGLT2i therapy.

Presentation: Thursday, June 15, 2023
THU359 A Classical Case Of SGLT-2 Inhibitor Euglycemic Ketoacidosis In A Patient With Glucotoxicity
Authors: Amankwah Samuel , Bolaji Olajide Omolola
Published: October 2023

Disclosure: S. Amankwah: None. O.B. Olajide: None.

Background: SGLT-2 inhibitors have been demonstrated to be beneficial in protecting comorbid cardiovascular or kidney disease while providing modest improvement in glycemia. However, they are not ideal for initial therapy for patients with very poorly controlled type 2 diabetes. This is a case where SGLT-2 inhibitor monotherapy led to diabetic ketoacidosis. Clinical Case: A 68-year-old woman with type 2 diabetes for 30 years, hypertension, hyperlipidemia, and depression presented to the hospital with complaints of headache, nausea, vomiting, dizziness, fatigue for the past three days. She had no fever, cough, shortness of breath or dysuria. She had not been taking any oral hypoglycemic agents for many months as she was trying to control her diabetes with lifestyle modifications. However, after the passing of her husband three months prior, she became less motivated in managing her health. Ten days prior to her hospitalization, the patient was newly prescribed empagliflozin 10 mg daily by her primary care provider due to uncontrolled hyperglycemia. She refused to resume metformin due to her history of gastrointestinal intolerance. She was previously on glipizide, but this was not restarted as she previously had poor glycemic control on it. On arrival at the ER, her temperature was 97.9 F, heart rate 112 bpm, respiratory rate 22 bpm, blood pressure 105/63 mmHg, and pulse oximetry on room air was 97%. Physical exam was unremarkable. Her serum glucose was 228 mg/dL, anion gap 15, pH 7.1, serum bicarbonate 15 mEq/L, serum acetone 3+, urine ketones greater than 150 mg/dL, serum creatinine 1.26 mg/dL and hemoglobin A1c was 13.2%. Her chest X-ray was unremarkable and COVID 19 test was negative. Euglycemic diabetic ketoacidosis (EDKA) was suspected secondary to the use of empagliflozin. This was discontinued and the patient was treated with intravenous insulin and fluids. Her serial blood tests showed resolution of ketoacidosis within 12 hours, and she was then transitioned to subcutaneous insulin. She was discharged home after 2 days of hospitalization on insulin therapy. Discussion: This case demonstrates the potential for SGLT-2 inhibitors to cause EDKA. It is important to acknowledge this complication can happen in cases where SGLT-2 inhibitors are used as monotherapy in diabetic patients with glucotoxicity. The mechanism of action of SGLT2 inhibitors is to enhance excretion and block reabsorption of filtered glucose from the proximal convoluted tubule.  The resultant glycosuria creates a state of carbohydrate starvation and volume depletion, increasing the glucagon/insulin ratio, resulting in a state of severe dehydration and ketosis. Patients with glucotoxicity are at a higher risk to develop ketoacidosis as they have marked beta cell insufficiency. It is thus highly recommended to initially treat these patients with insulin rather than oral agents.

Presentation: Thursday, June 15, 2023
THU373 Refractory Hypoglycemia In A Patient With Metastatic Cholangiocarcinoma: Abstract
Authors: Gabriela Fernandez Maria , Selen Daryl J
Published: October 2023

Disclosure: M.G. Fernandez: None. D.J. Selen: None.

Background: Nonislet cell tumor hypoglycemia is an uncommon but severe complication of cancer. It results from tumoral overproduction of insulin-like growth factor 2 (IGF-2), which inhibits hepatic glycogenolysis and the release of glucagon and growth hormone (GH). These three mechanisms can result in severe and refractory hypoglycemia. Clinical Case: We present a case of a 57-year-old female newly diagnosed with metastatic cholangiocarcinoma who was admitted to the hospital after an episode of syncope at home in the setting of hypoglycemia with a serum blood glucose of 17 mg/dL (N >60 mg/dL). During the hospital admission, evaluation of hypoglycemia included a normal TSH of 1.170 (reference range [RR] 0.3-5.5 mIU/ml), fasting morning cortisol of 23.3 (RR >14-15 μg/dL), and a negative sulfonylurea screen. In addition, the patient had an undetectable level of Insulin <3.0 (RR 3-25 mU/L), Beta-hydroxybutyrate <0.10 (RR 0.02-0.27 mMol/L), C-peptide <0.1 (RR 0.5-3.3 ng/ml), and Pro-insulin <1.6 (RR 3-20 pmol/L). CT of the abdomen revealed disease progression with innumerable bilateral enhanced hypoattenuating masses in the liver. Management for refractory hypoglycemia required nutrition optimization, nausea control, close glucose monitoring, IV dextrose infusion, and intermittent intravenous glucagon for episodes of severe hypoglycemia (<40 mg/dL). During the hospitalization, the patient received the first cycle of chemotherapy with gemcitabine, cisplatin, and dexamethasone. On day 10 of admission, the IGF-2 resulted at 120 ng/ml (RR 180-580ng/ml) and IGF-1<10 (RR 50-317 ng/ml) with an IGF-2/IGF-1 ratio greater than 100 (cut off>10), diagnostic of a large nonislet cell tumor as the most likely cause of her severe hypoglycemia. Artificial nutrition did not align with this patient’s goals of care, so she was discharged from the hospital with a FreeStyle Libre 2 for continuous glucose monitoring. However, two weeks later, she returned to the emergency department with hypoglycemia (<40 mg/dL), ultimately choosing to pursue hospice. Conclusion: Patients with large liver tumor burden can experience hypoglycemia due to low glycogen content in the liver. In addition, these patients can have decreased oral intake and weight loss, which confounds the clinical scenario and can delay diagnostic workup. Patients with refractory hypoglycemia and nonislet cell tumors require further evaluation for IGF-2 production, and alternative temporary nutritional options should be discussed with the patient immediately. Therapeutic options depend on the ability to treat underlying cancer. Palliative chemotherapy, surgery, or radiation can be considered to control the tumor and improve hypoglycemia for quality of life when the cancer is otherwise untreatable.

Presentation: Thursday, June 15, 2023
THU374 Fulminant Type 1 Diabetes Mellitus And DKA Secondary To Pembrolizumab
Authors: Iqbal Iqra , Alam Khan Muhammad Atique , Ahmad Mobeen , Mehreen Rameesha
Published: October 2023

Disclosure: I. Iqbal: None. M. Khan: None. M. Ahmad: None. R. Mehreen: None.

Introduction: Pembrolizumab is a programmed cell death receptor (PD-1) binder on T cells, which promotes their activation against cancer cells. It can also cause unwanted T cell activation against the body’s own cells, leading to type 1 diabetes mellitus (DM1), among other autoimmune phenomena. We are reporting a case of a new onset pembrolizumab-induced fulminant DM1 who presented with diabetic ketoacidosis (DKA). Despite the emerging data on immune checkpoint inhibitors (ICPI), fulminant DM1 with DKA in a previously nondiabetic patient is still uncommon. Case Presentation: A 66-year-old female with a history of recurrent metastatic non-small cell lung cancer (NSCLC) presented to the emergency room (ER) with an extensive itchy rash. She was enrolled in a clinical trial for NSCLC, where she received immunotherapy with pembrolizumab for five months. Rash was treated outpatient for scabies, with no improvement. She was then started on prednisone 40mg daily and betamethasone 0.05% cream. She applied the cream daily but took prednisone orally for only one day, after which she could not tolerate it due to anxiety and restlessness. She ran out of betamethasone three days before coming to ER. On admission, vitals were: Heart rate 90 beats per minute, blood pressure 119/95 mmHg, respirations 20/minute. The exam showed flushed cheeks, red and dry macules on the skin with excoriations, and dry mucus membranes. Random blood glucose levels (BSL) were 660mg/dl. Labs were; HCO3 16mmol/L, Beta-hydroxy butyrate 20mmol/L, anion gap 17mmol/L, Hemoglobin A1c: 5.6%. For DKA, we started an insulin drip. Workup revealed very low C-peptide levels of 0.2ng/ml, with a concomitant BSL of 500mg/dL. Anti-islet cell and anti-glutamic acid decarboxylase antibodies (anti-GAD) were positive with levels of 0.04 nmol/L and 0.07 nmol/L, respectively. Once she stabilized and the anion gap closed, she was transitioned to subcutaneous insulin and discharged on 42 units of Lantus, along with 12 units of premeal Lispro and sliding-scale insulin. She was removed from the clinical trial due to complications. Unfortunately, she got readmitted with influenza A, Staphylococcus aureus bacteremia, and another episode of DKA, complicated with respiratory failure, and she decided on hospice. The patient passed away after two days. Conclusion: Immune-related adverse event of new-onset fulminant DM1, leading to DKA, is a serious and potentially fatal complication of pembrolizumab. For patients receiving pembrolizumab, who have uncontrolled BSL, we suggest checking the anti-islet cell and anti-GAD antibody levels and DKA risk stratification to allow the timely initiation of insulin and prevent further complications.

Presentation: Thursday, June 15, 2023
THU384 Too Sweet To Digest; A Case Of Persistent Lactic Acidosis Secondary To Glycogenic Hepatopathy
Authors: Ayub Tooba , Alejandra Robles Lydia , Sami Faria , Saleem Sania , Guntupalli Saroja
Published: October 2023

Disclosure: T. Ayub: None. L.A. Robles: None. F. Sami: None. S. Saleem: None. S. Guntupalli: None.

Glycogenic hepatopathy (GH) is an under-recognized cause of persistent lactic acidosis and hepatomegaly in patients with uncontrolled DM and diabetic ketoacidosis (DKA). A 19-year-old female with history of type 1 DM with recurrent DKA presented with complaints of nausea, vomiting and abdominal pain for 1 week. Physical exam showed normal vitals and lower abdominal tenderness. Her initial labs showed glucose 250 mg/dl, high anion gap metabolic acidosis with beta hydroxy butyrate of 11.3 mmol/l, lactic acid 3.2mm/l, and mild transaminitis. She was diagnosed with DKA and started on insulin drip. Anion gap responded to IV insulin and fluid therapy and was transitioned to SQ insulin. However, she had increase in her lactic acid (8.2mm/l), without hemodynamic compromise, despite fluid resuscitation. Secondary work up including blood, urine, sputum cultures were non diagnostic for an infectious etiology. Abdominal imaging showed a liver span of 26 cm. There were no signs of end organ hypoperfusion, medication or toxin mediated insult as evident by normal transthoracic echo, iron studies, urine drug screen, alcohol level and negative hepatitis panel. Review of prior hospitalizations showed recurrent episodes of DKA with similar uptrend in lactic acid levels with negative secondary work up. Prior imaging revealed hepatomegaly during DKA episodes with resolution after strict glycemic control. Given uncontrolled DM type 1 with reversible and recurrent hepatomegaly, transaminitis, hyperlipidemia and elevated lactic acid, a clinical diagnosis of glycogenic hepatopathy was made. Patient declined liver biopsy due to concerns for complications. She was discharged on home insulin regimen with outpatient follow up. GH or hepatic glycogenosis is a reversible cause of lactic acidosis and hepatomegaly seen in uncontrolled DM type 1. Pathogenesis involves presence of fluctuating levels of hyperglycemia and insulin, concomitantly, that leads to glycogen storage. Insulin inhibits gluconeogenesis resulting in decreased conversion of pyruvate to glucose and high lactic acid levels, in the absence of any infectious, metabolic and hypoxic etiology. Lactic acidosis can be worsened when treated with high dose Insulin. Definite diagnosis of GH requires liver biopsy or gradient dual-echo MRI but can be made clinically in the setting of uncontrolled DM1, hepatomegaly, transaminitis and elevated lactic acid levels. Prompt recognition of GH can prevent unnecessary diagnostic testing and can decrease the duration of hospital stay. Treatment is strict glycemic control with resolution of condition and no long-term complications.

Presentation: Thursday, June 15, 2023
FRI626 Association Between Fasting Serum C-peptide Values And The Presence Of Chronic Kidney Disease In Patients With Type 2 Diabetes Mellitus
Authors: Leyva Figueroa Laura , Gomez-Perez Francisco J , Gonzalez-Valdivia Fernando , Cuevas-Ramos Daniel
Published: October 2023

Disclosure: L. Leyva Figueroa: None. F.J. Gomez-Perez: None. F. Gonzalez-Valdivia: None. D. Cuevas-Ramos: None.

Background: High C-peptide levels have been associated with microvascular complications, although there is controversial evidence in patients with T2DM. Objective: To correlate fasting serum C-peptide values in patients with T2DM with diabetic nephropathy. Hypothesis: In patients with type 2 diabetes mellitus there is a positive correlation of minimum r=0.3 between fasting C-peptide, albumin/creatinine ratio (ACR) and glomerular filtration rate (eGFR). Research Question: Is there a significant and independent correlation between fasting C-peptide values, ACR, and eGFR in patients with type 2 diabetes mellitus? Methods: Retrospective, cross-sectional, observational, real-world study, in 551 type 2 diabetic patients. Data was collected from the electronic clinical records. Microalbuminuria was defined as an ACR equal or greater than 30, and eGFR was calculated by CKD-EPI 2021. Fasting C-peptide was measured by immunochemiluminescence. Continuous variables were expressed as means +/− standard deviation, while categorical variables will be expressed as percentages. We used one-way ANOVA to compare continuous variables between groups, and Chi-square test to compare categorical variables. Multivariate logistic regression analysis was used to analyze the independent relationship between C-peptide quartiles, eGFR, and ACR, adjusted for weight, insulin, and disease duration. Results: 551 patients were evaluated (63% were women), with mean age of 62 ±11 years old, and a HbA1c of 8.4%. Median (interquartile range) of disease duration was 20 years (12-25), with a C-peptide median level of 1.6 (0.9-2.4 ng/ml), with no significant difference by gender. A statistically significant direct relationship was found between a higher C-peptide quartile and higher ACR (F=9.8, p= 0.03). A significant correlation was also found between C-peptide and ACR (r=0.16, p<0.001), and also with eGFR (r=−0.11, p=0.01). Using a multivariate regression analysis we identified an independent association between C-peptide and ACR (beta=44.7, CI95%, 16-73, p=0.002), and also with eGFR (beta −2.7, CI95% −4.7 to −0.6, p=0.01). Conclusions: A significant and independent association was found between C-peptide levels and kidney function and albuminuria. Future studies may confirm that C-peptide can stand as an early marker for diabetic nephropathy.

Presentation: Friday, June 16, 2023
FRI640 Adherence To Diabetic Retinopathy Screening Guidelines In An Adolescent Patient Population
Authors: Sami Asra , Gurnurkar Shilpa , Vyas Neha
Published: October 2023

Disclosure: A. Sami: None. S. Gurnurkar: None. N. Vyas: None.

Diabetic retinopathy (DR) is a microvascular complication of diabetes mellitus (DM) and a major cause of vision loss. Risk factors for development of DR include duration of diabetes and poor glycemic control. Adolescents with diabetes face unique challenges in attaining glycemic control due to hormonal changes and transition from pediatric to adult care. The aim of this study was to determine the adherence to ADA DR screening guidelines in an ambulatory Endocrine clinic’s adolescent patient population, and to determine factors associated with non-adherence. Methods: A retrospective chart review was conducted on patients (ages 12-18) with type 1 diabetes (T1D) and type 2 diabetes (T2D) at Nemours Children’s Hospital between 2015 and 2022, with 142 charts included. Based on the ADA DR screening guidelines, patients with T1D were included if they had diabetes for at least 5 years and all patients with T2D between the ages of 12-18 were included. Patients were considered adherent if they met one of the following criteria: Recorded eye exam within the past 1 year (for T2D) or the past 2 years (for T1D) documented in chart OR attendance to an appointment with Nemours ophthalmology within a year of referral. Age, sex, ethnicity, race, insurance type, and HbA1c were recorded. Univariate binomial logistic regression analysis was completed to determine the association of the factors to DR guideline adherence. Results: Data analysis showed 69% adherence and 31% non-adherence to DR screening guidelines. The non-adherence rate was comparable to other studies in adult and youth populations. Patients with T2D were 58.3% less adherent to DR screening guidelines compared to patients with T1D (OR= 0.417, 95% CI 0.178-0.978). We did not find statistical significance with other factors. The results highlight adolescent patients with T2D as a target population for future studies aimed at improving adherence to DR screening guidelines.

Presentation: Friday, June 16, 2023
FRI643 Tirzepatide Associated Partial Small Bowel Obstruction: A Case Report
Authors: Mathew Anoopa , Hannoodee Hanan
Published: October 2023

Disclosure: A. Mathew: None. H. Hannoodee: None.

Glucagon-like peptide-1 receptor agonists (GLP1 RA) are quickly becoming an adjunctive treatment modality for people with type-2 diabetes and is approved for chronic weight management. Tirzepatide has a dual GIP/GLP-1 RA action and has a synergistic effect when administered together. GLP-1 RA are associated with improved cardiovascular and all-cause mortality outcomes in patients with type-2 diabetes. Tirzepatide is associated with gastrointestinal (GI) side effects like nausea, diarrhea, abdominal pain, decreased appetite, and constipation. This case report discusses a case of small bowel obstruction (SBO) that was noted after patient was changed from dulaglutide to tirzepatide. Mr. X is a 61 y/o male with PMHx of type-2 DM, HTN, and HLD who presented to ER for severe epigastric pressure- like 7/10 abdominal pain. No association with food intake. He had 1 episode of semi-loose stools. Denied any abdomen cramping, sick contacts, nausea/vomiting, fever/chills, or constipation. His previous endoscopy was only relevant for benign colonic polyps, which were removed. He had been on GLP1 RA for more than a year, and previously on dulaglutide 3mg, which was switched to tirzepatide 2.5mg 5 weeks ago. He was able to tolerate the medication without significant side effects and was recently up-titrated to 5 mg. Labs showed WBC 7.2, Hb 13.6, Cr 1.45, BUN 12, lipase 25, and normal LFTs. Abdominal X-ray and CT abdomen were noted to be significant for a partial vs evolving SBO without any identifiable small bowel intrinsic pathology. Mr. X was managed conservatively with fluids, NPO diet, and pain medications. Serial abdominal images were obtained, and he was eventually advanced to soft diet. Tirzepatide was discontinued on discharge. As a response to enteral nutrition, distal small bowel and colon release GLP-1 hormone. Exogenous and endogenous GLP-1 are associated with reduced gastric motility. GLP 1 RA and dual GIP/GLP-1 RA are advised to be used with caution in patients with established gastroparesis, as they can worsen the symptoms. GLP-1 effect on small intestinal motility is not extensively studied, however, small bowel motility inhibition was noted in animal models. Some of these actions were dose-dependent. There are some case reports of SBO due to GLP-1 RA. An observational cohort study noted an increased incidence of SBO with GLP1 RA when compared to SGLT2i. They noted most incidents of SBO happened early within the initiation of therapy (within 3 months). At the time of writing this abstract, there are no published SBO case reports associated with tirzepatide. Further large-scale clinical trials need to be conducted to explore the association of SBO in patients with GIP/GLP-1 and GLP-1 RA. These studies will help guide if these drugs should be contraindicated or used with caution in people with a previous history of SBO or colonic obstruction.

Presentation: Friday, June 16, 2023
FRI645 A Case Of Diabetic Ketoacidosis After Initiation Of Decitabine And Venetoclax Chemotherapy
Authors: Maini Rohan , Milosavljevic Jovan , Aleksic Sandra
Published: October 2023

Disclosure: R. Maini: None. J. Milosavljevic: None. S. Aleksic: None.

Background: Decitabine, a pyrimidine nucleotide analogue, and venetoclax, a Bcl-2 inhibitor (ABT-199), are chemotherapy agents used for the treatment of myelodysplastic syndromes. Clinical trials have shown hyperglycemia as an adverse reaction for both of these medications, but DKA has not been reported. Clinical Case: A 71-year-old woman with a history of T2D and myelodysplastic syndrome (MDS) presented with nausea, vomiting, and diarrhea for five days. Initial tests revealed blood glucose 839 mg/dL, an anion gap of 19 mEq/L (n 7-16), serum bicarbonate 14 mmol/L (n 20-30), venous pH of 7.24, and hydroxybutyrate >4 mmol/L (n< 0.3), consistent with diabetic ketoacidosis. Her anti-glutamic acid decarboxylase autoantibodies were negative. Chest CT showed bibasilar pulmonary opacities, concerning for multifocal pneumonia. She was placed on an insulin drip and fluids according to the institution's protocol and her anion gap closed within a day. She was transitioned to subcutaneous insulin. The patient had well-controlled T2D, with an HbA1c of 5.6% two weeks before her presentation and an admission fructosamine level of 377 umol/L (n 200-285). Her BMI was 25. Her only T2D medication was semaglutide 0.25 mg weekly but had not taken a dose in three weeks due to the national shortage. Five weeks prior to this presentation, she began weekly chemotherapy infusions of decitabine and oral venetoclax as part of a clinical trial (2021-13466) for MDS treatment, with her last infusion one week before her presentation. Conclusion: This is the first case to demonstrate DKA precipitated by decitabine and venetoclax treatment. While both agents have been linked to severe hyperglycemia in safety clinical trials, DKA has not been previously reported. Data from animal studies have shown that prolonged exposure of mouse islets to Bcl-2 antagonists increase levels of reactive oxygen species and induce pancreatic β cell apoptosis (1). Further research is needed to assess the benefits and risks of this chemotherapy regimen in patients with diabetes. References: 1.) Aharoni-Simon M, et al. Bcl-2 Regulates Reactive Oxygen Species Signaling and a Redox-Sensitive Mitochondrial Proton Leak in Mouse Pancreatic β-Cells. Endocrinology. 2016 Jun.

Presentation: Friday, June 16, 2023
FRI646 Dulaglutide-induced Acute Liver Injury - A Case Report
Authors: Shahid Maham , Hamza Ameer , Vather-Wu Daniel , Sultan Senan , Nabizadeh Payam
Published: October 2023

Disclosure: M. Shahid: None. A. Hamza: None. D. Vather-Wu: None. S. Sultan: None. P. Nabizadeh: None.

Introduction: Drug-induced liver injury (DILI) accounts for almost 10% of all cases of acute hepatitis and can occur within days to months of initiation of a medication. Outcomes can vary from spontaneous resolution on discontinuation of the offending agent to fulminant hepatic failure requiring transplant or even death. Dulaglutide is a GLP-1 receptor agonist that augments glucose-dependent insulin secretion and slows gastric emptying. It is a weekly injectable medication for management of type 2 diabetes mellitus (T2DM). Commonly reported side effects include nausea, vomiting, appetite suppression, and diarrhea or constipation. To date, there have been less than five published case reports of Dulaglutide-induced acute liver injury (ALI). Hereby, we present a case of Dulaglutide-induced ALI with coagulopathy that resolved with the use of N-acetylcysteine (NAC), steroids, and cessation of the medication. Clinical Case: A 38-year-old female with past medical history of T2DM, hypertension, dyslipidemia, and hypothyroidism presented with complaints of nausea, vomiting and epigastric discomfort for 5 days. She reported having malaise and lethargy for a month since she was started on Dulaglutide for management of her T2DM. Her physical examination was unremarkable. The laboratory workup showed AST >6000 U/L, ALT >3300 U/L, ALP 231 U/L, total bilirubin 3.3 mg/dL, direct bilirubin 2.3 mg/dL, indirect bilirubin 1.0 mg/dL, PT 40.3 seconds, INR 3.36 and negative toxicology screening. She was started empirically on intravenous NAC and methylprednisolone, and was followed by serial biochemical measurements. Further workup revealed no evidence of acute viral hepatitis, autoimmune hepatitis, metabolic (alpha-1-antitrypsin deficiency, Wilson disease, hemochromatosis) or alcohol-related ALI. There were no clinical or imaging findings suggestive of ischemic hepatopathy, venous outflow obstruction or biliary obstruction. After ruling out other causes, the ALI was attributed to Dulaglutide use. AST and ALT improved significantly within 7 days and subsequently normalized within 3-4 weeks. Hepatic synthetic function also normalized within 2 weeks without any sequelae. Conclusion: This report highlights the need for awareness regarding potential but not insignificant risk of dulaglutide as cause of DILI. Extensive testing for other causes of ALI was negative and Dulaglutide-induced ALI was the most likely etiology in our case. Given limited data on hepatotoxicity induced by GLP-1 receptor agonists, further research is needed to ascertain this potentially fatal adverse reaction. We hope to contribute to the current medical literature.

Presentation: Friday, June 16, 2023
SAT051 The Effect Of High Fat Diet On Insulin Signaling In White Adipose Tissue Of Liver Androgen Receptor Knockout In Male Mice
Authors: O'neil Hill-Dick Johvan , Young Demarrius , Curry Dwight , Bolarinwa Elizabeth , Qutab Rabia , Carr Kiana , Falzarano Claire , Andrisse Stanley
Published: October 2023

Disclosure: J.O. Hill-Dick: None. D. Young: None. D. Curry: None. E. Bolarinwa: None. R. Qutab: None. K. Carr: None. C. Falzarano: None. S. Andrisse: None.

Insulin resistance affects up to 33% of the US adult population and polycystic ovary syndrome affects up to 10% of reproductive-age adult women. The liver and white adipose tissue play an essential role in the metabolism of insulin and androgen signaling. Hyperandrogenism in females can increase their predisposition to insulin resistance. It has been previously shown that deleting the liver androgen receptor (LivARKO) prevented female mice from developing hyperandrogenemia (HA)-induced insulin resistance. The goal of this research was to determine if LivARKO prevents high fructose diet (HFrD) induced insulin resistance. It was hypothesized that HFrD LivARKO male mice would display impaired insulin action in white adipose tissue in comparison to the control diet-fed LivARKO female mice, suggesting that AR does not play a significant role in regulating HFrD-induced insulin resistance. Male LivARKO mice were placed on either a control (Research Diets Inc, RDI D12450J) or High Fructose (HFrD, RDI D02022704) diet and sacrificed after 1 month. Half of the mice were given 0.5 U/kg of insulin before being sacrificed to investigate the effects of the diets on insulin signaling. Western blots were used to determine protein expression in tissue from the white adipose tissue (WAT) standardized using BCA assays. LivARKO male mice fed a chow or control diet for 1 month displayed no or low expression of p-AKT in the basal and insulin-stimulated state, suggesting that LivARKO had an indirect effect on insulin-stimulated signaling in WAT. Oddly, LivARKO male mice fed a HFrD displayed increased insulin-stimulated p-AKT compared to basal, suggesting functional insulin-stimulated p-AKT. This increased p-AKT may be a compensatory mechanism as HFrD is known to disrupt glucokinase and glycogen synthase. In normal physiology, on a chow diet, insulin should increase p-AKT. The data shows that in male LivARKO mice, insulin did not increase p-AKT in chow, control, or HFrD, suggesting that the male LivARKO mice are experiencing insulin resistance at the level of p-AKT in WAT. Additionally, HFrD is known to cause insulin resistance, however, it is not known to alter p-AKT levels. Thus, the change in p-AKT levels is presumably associated with the LivARKO. Further research is required into what components of the Control Diet are prompting this difference in insulin action and if it only takes place in the LivARKO mouse model.

Presentation: Saturday, June 17, 2023
SAT060 Hyperosmolar Hyperglycemic State Presenting As Seizures
Authors: Faber Alexis , Levy Shiri
Published: October 2023

Disclosure: A. Faber: None. S. Levy: None.

Introduction: Hyperosmolar hyperglycemic state (HHS), also known as hyperosmotic hyperglycemic nonketotic state (HHNK), is one of the most severe complications of diabetes mellitus. HHS is a medical emergency defined by high serum osmolality and hyperglycemia as well as the absence of ketoacidosis in most cases. We present an unusual case of a young man presenting with seizures who on further investigation was found to have HHS. Case Description: A 44-year-old man presented to the hospital for a possible seizure at home. His medical history is significant for EBV+ B-cell lymphoma receiving chemotherapy, HIV on HAART therapy, and prior history of cryptococcus meningitis in 2019. He did not have history of seizures or diabetes mellitus. He reported that five days prior to admission, he began experiencing polydipsia and polyuria, which later progressed to lethargy. The day of admission his mother found him on the floor with generalized body shaking with significant shaking of the right arm, urinary incontinence, and blood in his mouth from tongue biting. He was taken to the hospital due to concern for seizure. Workup revealed elevated blood glucose of 972 and elevated serum osmolality of 322. He did not present with overwhelming ketosis; his beta-hydroxybutyrate was 0.57, he did not have an anion gap, and ketones were not present in his urine. His A1c was elevated at 9.9%. The differential diagnosis for this patient’s seizure included chemotherapy side effect, intracranial pathology, infectious etiology in the setting of known HIV, or HHS. Hematology evaluated the chemotherapy regimen and stated it was not likely the cause of his seizures. Neurology assessed the patient with a CT head, MRI brain, EEG, and lumbar puncture, all of which were negative. The CSF from the lumbar puncture underwent intensive testing, which was negative for HSV, VDRL, CMV, EBV, VZV, Lyme disease, and JC virus. Neurology initially started the patient on anti-seizure medication, however later stated his seizure was likely provoked from hyperglycemia and discontinued the medication. Infectious workup included chest X-ray, blood cultures, and urinalysis, all of which were negative. Endocrinology was consulted and recommended initiating basal and bolus insulin as well as testing for GAD antibodies. Unfortunately, the patient left the hospital against medical advice and GAD antibody testing was not completed. Discussion: The most common symptoms of HSS include hyperglycemia, polyuria, and polydipsia. Though neurological symptoms can occur, they are not common. The neurologic symptoms are typically not seen until the serum osmolality reaches 320 - 330 mOs/kg, and this patient’s serum osmolality was elevated at 322 mOs/kg. Though seizure is not well understood in hyperglycemia, treatment for HHS-induced seizures focuses on aggressive management of the underlying hyperglycemic state.

Presentation: Saturday, June 17, 2023