bluuebunny/crossref_metadata_2025 huggingface dataset:
6490 Microalbuminuria and Steatotic Liver Disease in Patients with Type 2 Diabetes: A Retrospective Cross-Sectional Study in Mexico City
Authors: Martinez-Sanchez Froylan , Diaz-Jarquin Alejandra , Feria-Agudelo Sandra Milena , Corredor-Nassar Maria Juliana , Martinez-Perez Carolina , Soto-Montes Zeltzin , Vargas-Abonce Valerie Paola , Paz-Zarza Victor Manuel , Gonzalez-Alvarez Gibran , Tenorio-Aguirre Erika Karina , Cordova-Gallardo Jacqueline , Mendez-Sanchez Nahum
Published: October 2024

Disclosure: F. Martinez-Sanchez: None. A. Diaz-Jarquin: None. S. Feria-Agudelo: None. M. Corredor-Nassar: None. C. Martinez-Perez: None. Z. Soto-Montes: None. V. Vargas-Abonce: None. V. Paz-Zarza: None. G. Gonzalez-Alvarez: None. E. Tenorio-Aguirre: None. J. Cordova-Gallardo: None. N. Mendez-Sanchez: None.

Introduction: Microalbuminuria (MAU) is an independent cardiovascular risk factor in patients with type 2 diabetes. Albuminuria has been associated with increased hepatic steatosis in various population studies, with conflicting results. Although the definition of Metabolic dysfunction associated steatotic liver disease (MASLD) has been modified in recent years, the relationship between MASLD and albuminuria in patients with type 2 diabetes has not been fully yielded. Objective: To evaluate the association between MAU and hepatic steatosis in patients with type 2 diabetes. Materials and Methods: Retrospective cross-sectional observational study of 1115 patients with type 2 diabetes. The data were collected from the internal medicine outpatient clinic from 2018 to 2023. Clinical and biochemical data were also collected. Patients with ICD-10 codes for alcoholism and alcoholic hepatitis were excluded. MAU was determined by 24-hour urine collection. Hepatic steatosis was defined by a Fatty Liver Index (FLI) > 60. Binary logistic regression analysis was used to determine the independent association between MAU and hepatic steatosis. Results: The mean age of the patients was 59.6 ± 14.1 years, 68.2% were women, the mean body mass index (BMI) was 28.6 ± 6.2 kg/m2, and had a mean waist circumference of 88 ± 16.6 cm. The median duration of diabetes before the first medical consultation at our institution was 7 (3-14) years. The median FLI was 61 (35 - 83), and median MAU was 9.44 (2.14 – 49.95) mg/24h; 71.7%, 20.1%, and 8.2% had MAU in <30, 30-300, and >300 mg/24h, respectively. Multivariate analysis showed that having 30-300 and >300 mg/24h of MAU had an Odds Ratio of 4.317 (2.485 – 7.500) and 5.480 (2.306 - 13.023) for hepatic steatosis. Conclusion: Microalbuminuria was associated with increased odds for hepatic steatosis in patients with type 2 diabetes, independently of age, sex, hemoglobin A1c, duration of diabetes, glucose-lowering drugs (metformin, insulin, SGLT-2i, GLP-1, DPP-4i, thiazolidinediones, and sulfonylureas), fibrates, statins, total cholesterol, and serum creatinine. The results cannot determine whether MAU is a risk factor for hepatic steatosis or vice versa. Prospective cohort studies are required to determine if there is a risk between both entities.

Presentation: 6/2/2024
7807 Significance of Assessing QTc Interval in Chronic Hypoparathyroidism and its Clinical and Biochemical Correlates
Authors: Namjoshi P V , Saha S , Sharma V , Narang R , Mani K , Goswami R
Published: October 2024

Disclosure: P.V. Namjoshi: None. S. Saha: None. V. Sharma: None. R. Narang: None. K. Mani: None. R. Goswami: None.

Background: Patients with chronic hypoparathyroidism (cHypoPT) and hypocalcemia are at risk of QTc prolongation and life-threatening arrhythmias. Information on clinical and biochemical correlates of QTc in cHypoPT is limited. Design: Observational study in cHypoPT cohort, tertiary-care-center.Materials and methods: Eighty-eight nonsurgical cHypoPT patients (age 44.1±15.4 years, 45 males) were assessed for QTc interval and its possible correlates including arrhythmic symptoms (palpitations/giddiness/syncope), and serum total calcium, phosphorus, 25(OH)D, and iPTH. Results: The mean QTc was 428±34 ms and showed a significant inverse correlation with serum total calcium measured on the same day (r=-0.43, p<0.001). 13.6% of cHypoPT had prolonged QTc. The mean serum total calcium (7.05±1.94 vs. 8.49±1.01 mg/dL, p=0.02) was significantly lower in patients with prolonged QTc. Patients with arrhythmic symptoms had significantly higher mean QTc (p=0.02) and tended to have lower average serum total calcium during follow-up (p=0.06). Multivariable regression showed female gender, higher current age, BMI, and low serum calcium as the significant independent determinants of QTc. For every mg/dL decrease in serum total calcium, QTc increased by 13 ms. Receiver operating characteristic (ROC) analysis revealed serum total calcium at cut-off 8.27 mg/dL discriminated prolonged QTc with area-under-curve being 0.72 [95% CI: 0.51, 0.93]. Conclusion: cHypoPT patients have an increased risk of QTc prolongation which was associated with arrhythmic symptoms, female sex, higher age, BMI, and low serum total calcium. ROC analysis indicated maintaining serum total calcium level of at least 8.27 mg/dL to minimize the risk of prolonged QTc. The study indicates the need for close monitoring of arrhythmic symptoms as well as ECG in cHypoPT patients.

Presentation: 6/1/2024
8185 The diagnosis of primary aldosteronism: testing 2 screening approachesin a large reference laboratory population
Authors: Marcelli Marco , Bi Caixia , Funder John W , McPhaul Michael J
Published: October 2024

Disclosure: M. Marcelli: Employee; Self; Quest Diagnostics. Stock Owner; Self; Quest Diagnostics. C. Bi: Employee; Self; Quest Diagnostics. J.W. Funder: None. M.J. McPhaul: Employee; Self; Quest Diagnostics.

In many practices, the screening for primary aldosteronism (PA) relies on a single blood draw for plasma aldosterone concentration (PAC) and plasma renin activity (PRA) to establish an aldosterone-to-renin ratio (ARR). ARR cut-off levels vary between expert centers and between repeated assays in the same individual, emphasizing the potential variability of this screening approach. We conducted a study in 2 cohorts and used 2 screening approaches to identify probable PA (ARR ≥30 vs PRA suppressed to <1 ng/mL/h). Methods: Cohort A consisted of 94,829 consecutive paired PRA and PAC samples submitted by clinicians to evaluate the presence of PA. Cohort B is a subgroup of cohort A consisting of 27,893 patients in whom serum K was measured on the same day as PRA and PAC. Results: Based on ARR, 13.9% of cohort A (95%CI 13.6-14.1) and 13.9% of cohort B (95%CI 13.4-14.3) tested positive; based on PRA, 45.9% of cohort A (95%CI 45.5-46.2) and 45.2% of cohort B (95%CI 44.6-45.8) tested positive. A range of aldosterone levels was observed in cohort A vs B samples that screened positive using ARR vs PRA. PAC >15 ng/dL was present in a similar proportion of patients in both cohorts, regardless of the screening test used; however, PAC 5 to 15 and <5 ng/dL were present in higher proportions of patients positive for PRA than ARR in both cohorts A (25.2% vs 8.4% and 15.1% vs 0.7%) and B (26% vs 8.6% and 13.3% vs 0.5%), respectively. Hypokalemia was tested in cohort B and was more frequent than in an equal number of random controls not tested for the ARR test code (5.4% vs 1.8%) and when examining specific age groups (eg, age 50-70) in both women (4.9% vs 1.3%) and men (7.5% vs 1.5%). Conclusions•In both cohorts screened for PA, more individuals were identified by focusing on PRA < 1 than on ARR ≥ 30. This finding prompts a reassessment of the screening procedures for PA. •The proportion of positives for PA identified by the 2 screening tools was similar in cohort A vs B, suggesting that serum K should not be a routine test in the workup for PA.•Compared with the ARR test, Tthe PRA screening test identified more patients than the ARR test with PAC with 5 to 15 and <5 ng/dL in both cohorts A and B, while thethe tests identified a similar proportion of patients with PAC >15 ng/dL in both cohorts. This indicates that an ARR test of ≥30 is as effective as the PRA <1 for identifying florid cases of PA, but unlike PRA, is unable to identify less florid (and more common) cases of PA. •Hypokalemia was more frequent in cohort B than random controls, even after controlling for age (50-70) and sex, indicating that this cohort is enriched with a classic biochemical marker of PA.

Presentation: 6/1/2024
7312 Tumor Size and Mutation Prevalence in Black Americans with Primary Aldosteronism
Authors: van Rooyen Desmaré , Nanba Kazutaka , Sapiro Dina R , Blinder Amy , Wachtel Heather , Cohen Debbie , Luther James M , Vaidya Anand , Giordano Thomas J , Turcu Adina , Udager Aaron , Rainey William E , Rege Juilee
Published: October 2024

Disclosure: D. van Rooyen: None. K. Nanba: Other; Self; AstraZeneca. D.R. Sapiro: None. A. Blinder: None. H. Wachtel: None. D. Cohen: None. J.M. Luther: Advisory Board Member; Self; consulted with Mineralys. A. Vaidya: None. T.J. Giordano: None. A. Turcu: None. A. Udager: None. W.E. Rainey: None. J. Rege: None.

Background: Primary aldosteronism (PA) is the most common cause of endocrine hypertension. The prevalence of aldosterone-driver somatic mutations varies with sex and race. KCNJ5 mutations are commonly found in White Americans and female patients with PA. In contrast, CACNA1D mutations are dominant in Black American PA patients, but existing data are limited to small cohorts. Objective: To determine the impact of tumor size on aldosterone-driver mutation prevalence in Black Americans with PA. Methods: 113 formalin-fixed, paraffin-embedded adrenal tumors from Black American patients with PA were included. Histological classification was made based on aldosterone synthase (CYP11B2) immunohistochemistry and tumor diameter: aldosterone-producing adenomas (APA), ≥10 mm and aldosterone-producing nodules (APN), ≥3 - <10 mm. Somatic mutations in CYP11B2-positive regions were analyzed using Sanger- and next generation sequencing. Results: Most aldosterone-driver somatic mutations in Black American tumors were seen in CACNA1D (48/113, 42%) followed by KCNJ5 (34%), ATP1A1 (11%), ATP2B3 (4%), and CADM1 (1%). 9% of tumors did not exhibit known mutations (mutation-negative; Mneg). Importantly, there was a correlation between mutation prevalence and tumor size. Adrenals from this Black American PA cohort exhibited APN in 59% (67/113) of patients, most of which harbored somatic mutations in CACNA1D (44/67, 66%), followed by ATP1A1 (12%), Mneg (10%), and KCNJ5 (7%). In contrast, most APAs (n=46) displayed mutations in KCNJ5 (33/46, 72%), and a lower detection rate for mutations in CACNA1D, ATP1A1, ATP2B3, and for Mneg samples (28%, collectively). Irrespective of size, KCNJ5 mutations were observed more frequently in tumors from females (50%; n=62) vs males (14%; n=51). However, CACNA1D was the dominant altered gene in APN, regardless of sex. Conclusion: Aldosterone-producing tumor size exhibited a higher correlation with mutation prevalence than sex. Smaller APN are the dominant histologic feature in Black Americans with PA, and most of these lesions harbor somatic CACNA1D mutations. In contrast, somatic KCNJ5 mutations are more common in APA, and particularly in women. Future studies are needed to determine if the combination of adrenal imaging and genotype-specific steroid profiles could assist with PA subtyping.

Presentation: 6/3/2024
12563 Very Severe Hypertriglyceridemia-Induced Pancreatitis
Authors: Abrams Jennifer , Fan Lena
Published: October 2024

Disclosure: J. Abrams: None. L. Fan: None.

Background: Very severe hypertriglyceridemia (HTG) (triglyceride (TG) > 2000 mg/dl) occurs in 1.8 per 10,000 adults and portends a >50% risk of pancreatitis. We present a rare case of HTG (TG > 10,000) induced pancreatitis. Clinical Case: A 33-year-old man presented with acute onset abdominal pain, nausea, and vomiting for 12 hours. Clinical presentation was similar to a prior admission for acute pancreatitis 4 months ago, where TG level was 705 mg/dL. At that time, he was made NPO, treated with lactated ringers at 150 cc/hour, and discharged on gemfibrozil 600 mg twice daily. The patient was lost to follow up after discharge. On this admission, patient reported non-adherence to gemfibrozil, only resuming medication after abdominal pain began 12 hours prior to admission. Initial tests showed Lipase 198 U/L (reference range: 8-78 U/L), WBC 8.2K/uL (reference range: 4.5-11 K/uL), Cr 0.69 mg/dL (reference range: 0.7-1.3 mg/dL), Total cholesterol 477 mg/dL (reference range <200 mg/dL), HDL 19 mg/dL (reference range: >40 mg/dL), LDL “unable to calculate”(reference range <130 mg/dL), A1c 6.3% (reference range: 4.0-5.6%), TG 11,772 mg/dL (reference range: <150 mg/dL desirable, 150-199 mg/dL borderline, 200-499 mg/dL high risk, >500 mg/dL very high risk), repeat TG 8,151 mg/dL. CT abdomen scan confirmed peripancreatic edema and fat stranding, consistent with acute pancreatitis. Pertinent exam revealed temperature 98.2⁰F, pulse 61 beats/min, respirations 16 breaths/min, blood pressure 166/110 mmHg, oxygen saturation 97%, BMI 29.69 kg/m2; skin negative for xanthomas; abdomen tender to palpation in epigastrium, no guarding or rebound, bowel sounds present. He was made NPO, treated with normal saline, and admitted to intensive care, and started on an insulin drip with a rate of 0.1 unit/kg/hour with D5 1/2NS initially at 100 cc/hr titrated to maintain glucose 150-200. The subsequent TG level drawn 37 hours after admission was 531 mg/dL, 427 mg/dL at 43 hours, 428 mg/dL at 51 hours, 532 mg/dL at 72 hours, and 419 mg/dL at 96 hours. The insulin drip was stopped after 16 hours and low fat (<20%) diet was started. Compliance with low fat diet and fibrate therapy (atorvastatin 40mg daily, fenofibrate 245mg daily) was emphasized to the patient at discharge. Conclusion: This patient is one of the few reported cases of severe (TG>10,000) hypertriglyceridemia induced pancreatitis.

Presentation: 6/3/2024
8784 Cold Fingers, False Numbers: A Case Report on Fingerstick Artefactual Hypoglycemia
Authors: Acharya Madhav P , Sharma Sapna , Bajgain Anjana , Leu James Ping-Hsun
Published: October 2024

Disclosure: M.P. Acharya: None. S. Sharma: None. A. Bajgain: None.

Artifactual hypoglycemia, characterized by discrepancies between capillary and plasma glucose levels, can lead to unnecessary testing and interventions. Fingerstick testing, a common method for blood glucose monitoring, may yield misleading results. We report a case highlighting the clinical implications of fingerstick artefactual hypoglycemia. A 93-year-old female, with multiple comorbidities, including severe malnutrition and cool digital extremities, was admitted after a motor vehicle accident. Subsequent diagnosis revealed sepsis due to acute cystitis. Throughout her hospitalization, the patient consistently displayed low blood sugar readings exclusively in fingerstick tests. Despite a lack of prior history of diabetes or hypoglycemia, clinical examination uncovered cold and cyanosed fingertips. At bedside, point-of-care testing (POCT) for glucose from the patient's index finger yielded a concerning reading of 47 mg/dL. Surprisingly, multiple episodes of apparent hypoglycemia were measured via glucometer, with no accompanying symptoms. Simultaneous testing from the antecubital fossa yielded a contrasting reading of 84 mg/dL, aligning with plasma blood sugar. Remarkably, when POCT was performed on the heel and antecubital fossa sites, normoglycemia consistently prevailed. A 48-hour fasting test, with POCT on the patient's heel instead of fingers, revealed no hypoglycemia. Recognition of pseudo hypoglycemia in this patient was crucial, considering the septic state and cold extremities. The case underscores the importance of accurate glucose measurement sites, especially in conditions affecting micro perfusion. Healthcare providers should interpret low glucose levels measured by fingerstick with caution, considering potential limitations in patients with impaired micro perfusion. Simultaneous alternative-site testing and confirmation with venous measurements are essential for accurate diagnosis and appropriate clinical management.

Presentation: 6/3/2024
8362 3 cases with Hyperosmolar Hyperglycemic Syndrome and Atypical Diabetic Ketoacidosis
Authors: Nakamura C , Ishimaru M , Tanimoto E , Fukui S , Ujita N , Miyagi H , Igarashi M , Kashima T , Doi H , Yoshii K , Naiki Y , Horikawa R
Published: October 2024

Disclosure: C. Nakamura: None. M. Ishimaru: None. E. Tanimoto: None. S. Fukui: None. N. Ujita: None. H. Miyagi: None. M. Igarashi: None. T. Kashima: None. H. Doi: None. K. Yoshii: None. Y. Naiki: None. R. Horikawa: None.

Introduction: Diabetic ketoacidosis (DKA) and hyperosmotic hyperglycemia syndrome (HHS) are severe hyperglycemic emergencies as the spectrum of insulin deficiency and dehydration. HHS is known as a complication with type 2 diabetes mellitus(T2DM), likely to develop in elderly patients with hypertension and cardiac disease triggered by infections in Japan. In children and adolescents, as the incidence of T2DM rises, HHS is increasing. HHS and/or DKA cases in type 1 diabetes mellitus (T1DM) also have been reported, but it is not yet clear in which cases are more likely to develop. Clinical Cases Case 1> An 18-year-old girl with central diabetes insipidus and T2DM after operation for suprasellar germ cell tumor. She tended to neglect medication of desmopressin. She presented to the emergency department with fatigue, and had 6.6% weight loss in 1 week. Lab: Blood glucose 669 mg/dl, pH 7.306, b-hydroxybutyrate 1.3 mmol/L, Na 153 mEq/L, plasma osmolality 359 mOsm/kgH2O. She was diagnosed as HHS and needed enough hydration. > She was receiving artificial respiration and gastric tube feeding. She was brought to the emergency room with fever and hypoxemia, and she had lost 9.6% of weight in 2 weeks. Lab: Blood glucose 1322 mg/dl, pH 7.13, b-hydroxybutyrate 6.2 mmol/L, Na 160 mEq/L, plasma osmolality 446 mOsm/kgH2O. She was diagnosed as DKA and HHS combined with T1DM. She required enough hydration than usual treatment of DKA. Case 3> A 17-year-old boy with Prader-Willi syndrome. He presented to the emergency department with persistent low-grade fever and had 9.4% weight loss in 1 week. Lab: Blood glucose 519 mg/dl, pH 7.24, b-hydroxybutyrate 6.0 mmol/L, Na 136 mEq/L, plasma osmolality 334 mOsm/kgH2O. In addition to initial DKA treatment, he required aggressive dehydration correction with consideration of HHS. Clinical Lesson Three cases had underlying diseases that made it difficult for them to hydrate appropriately. They were easily dehydrated, and were high risk of developing/complicating HHS. In emergency hyperglycemia cases in children and young adults with those underlying diseases, we have to consider the possibility of the pathophysiology of both DKA and HHS at an early stage of treatment. Some symptoms which are not typical for DKA, like hypernatremia or abnormally high serum osmolality, the possibility of HHS should be considered.

Presentation: 6/1/2024
6957 5-Year Follow-Up of Acute, micro, and Macrovascular Complications of Patients With Type 2 Diabetes Managed by a Multi-Disciplinary Team In A Hospital in Northeastern Mexico
Authors: Romero Ibarguengoitia Maria Elena , Morales Rodríguez Devany Paola , Garza-Silva Arnulfo , Rivera-Cavazos Andrea , Francisco Fernández-Chau Iván , Cepeda-Medina Andrea Belinda , González-Cantú Arnulfo
Published: October 2024

Disclosure: M. Romero Ibarguengoitia: None. D.P. Morales Rodríguez: None. A. Garza-Silva: None. A. Rivera-Cavazos: None. I. Fernández-Chau: None. A. Cepeda-Medina: None. A. González-Cantú: None.

Type 2 Diabetes Mellitus (T2DM) is a condition associated with various acute and chronic complications, which constitute the leading cause of disability, morbidity and mortality globally. During the SARS-CoV-2 pandemic, vulnerable individuals such as those with T2DM faced a restriction in access to primary healthcare services. Therefore, we decided to compare the presence of micro and macrovascular complications before and during the SARS-CoV-2 pandemic, as well as the incidence of acute complications. A retrospective observational cohort study from 2018 to 2022 was conducted in a hospital in northeastern Mexico on patients with T2DM who were treated by a multidisciplinary team composed of an internist or geriatrician based on the patient's age, endocrinologist, nutritionist, and other diabetes-related specialties. Levels of HbA1C, fasting serum glucose (FSG), low-density lipoprotein cholesterol (LDLc), blood pressure (BP), and microalbuminuria were analyzed. Consequently, presence of micro and macrovascular complications and incidence of acute complications was described. A total of 999 subjects were analyzed, 516 (51.7%) males, with an average age (SD) of 60.1 (12.7) years. There was an increase in the proportion of patients with adequate glycemic control based on HbA1C of 15.2% between 2018 and 2022 (p<0.001) and a 42.3% increase in FSG control during the same period (p<0.001). LDLc showed a decrease in the control proportion of 5.1% between 2018 and 2022 (p<0.001). Systolic BP control in 2018 was 82.7% and 80.1% in 2022 (p<0.001). Diastolic BP control in 2018 was 89.6%, with an increase to 91.4% in 2022 (p=0.01). Microalbuminuria control increased from 80.5% in 2018 to 89% in 2022 (p=0.002). There were 78 (7.8%) cases of microvascular complications, with diabetic neuropathy being the most prevalent (n=35, 3.6%), and a higher incidence in 2021 with 15 (1.6%) cases. A total of 15 (1.5%) patients presented a macrovascular complication, with ischemic heart disease being the most frequent with 11 (1.1%) subjects, and a higher incidence of cases in 2021 (n=4, 0.4%). Hypoglycemia was found to be the most frequent acute complication with 14 (1.4%) cases, with a higher incidence in 2020 (n=5, 0.5%). The low incidence of complications in our population, emphasizes the importance of coordinating patient’s care between a multidisciplinary team to maintain an overall disease control, optimize T2DM treatment and enhance patient’s quality of life.

Presentation: 6/1/2024
8197 A Captivating Case Report of Teprotumumab Induced Hyperglycemic Hyperosmolar State
Authors: Tuna K M , Perdomo Rodriguez J P
Published: October 2024

Disclosure: K.M. Tuna: None. J.P. Perdomo Rodriguez: None.

Introduction: Teprotumumab, a monoclonal antibody targeting the IGF-1 receptor, is increasingly utilized for moderate to severe thyroid eye disease. Initial trials noted mild hyperglycemia in patients with diabetes, while recent trials revealed a significant elevation in Hemoglobin A1c (HbA1c) among those with diabetes or pre-diabetes post-infusion. Here, we discuss a case of a patient with diet-controlled diabetes who developed hyperglycemic hyperosmolar state (HHS) two months after Teprotumumab infusion. Case Presentation: A 43-year-old male, with class III obesity, obstructive sleep apnea, dyslipidemia, coronary artery disease, and diet-controlled diabetes (HbA1c 6.5%) presented with worsening proptosis, decreased color vision, severe visual field depression. Laboratory evaluation revealed elevated TSH (6.3 mIU/ml), normal free T4 (0.67 ng/dl, ref: 0.60-1.2 ng/dl), and undetectable Thyroid Stimulating Immunoglobulin (<0.1 IU/L). Blood cell count, renal and liver function tests were normal. Due to high clinical suspicion of thyroid eye disease, he was treated with timolol, dorzolamide, brimonidine, and methylprednisolone 1g daily for 3 days. Glycemic control was achieved with 30 units of daily insulin while on pulse steroids. On outpatient ophthalmology follow-up, Teprotumumab was initiated and he received 2 doses. Eight weeks later, the patient was hospitalized with altered mental status caused by HHS (glucose 617 mg/dl, serum osmolality 316 osm). HbA1c was found to be significantly increased to 12% and the patient required 150 units total daily insulin and metformin upon discharge. Of note, the patient did not have significant weight changes during this time. GAD, IA2, and Zinc Transporter-8 antibodies were obtained prior to discharge and results are pending. Discussion: The IGF-1 receptor, a partial homologue of the insulin receptor, plays a pivotal role in glucose homeostasis. Inhibiting this receptor can lead to hyperglycemia. Initial randomized controlled trials (RCTs) reported a 10% incidence of mild hyperglycemia. A recent RCT from a cohort of 42 patients demonstrated a 50% incidence of hyperglycemia, in which two-thirds of the patients remained in a dysglycemic state with one patient with pre-existing prediabetes developing diabetic ketoacidosis (DKA). Our patient mirrored this scenario with no identifiable confounding factors. Conclusion: Teprotumumab-induced hyperglycemia, though rare, can lead to life-threatening complications. Baseline glycemic assessment, identification of high-risk patients, and comprehensive discussions on risks and benefits are crucial before initiating therapy. Close monitoring, especially in those with prediabetes, is recommended. Patient education plays a pivotal role in early symptom recognition, averting delayed diagnoses, and subsequent hospitalization.

Presentation: 6/3/2024
8494 A Case of Diabetic Ketoacidosis in Setting of COVID-19 Infection and SGLT-2 Inhibitor Use
Authors: Abrahimi Nora , Bajpay Shreya , Abrahimi Aryan
Published: October 2024

Disclosure: N. Abrahimi: None. S. Bajpay: None. A. Abrahimi: None.

Background: COVID-19 infection can cause endocrine system disruptions leading to the development of diabetic ketoacidosis (DKA) in patients with type 1, 2 or new onset diabetes mellitus. (1) DKA is a side effect of SGLT-2 inhibitor use and its development on the medication can lead to discontinuation of SGLT-2 inhibitor. (2) SGLT-2 inhibitors are part of guideline directed medical therapy for management of heart failure with reduced ejection fraction (HFrEF). (3) Case: 67-year-old female history of non-insulin dependent diabetes mellitus type 2 on Empagliflozin presented with shortness of breath and hypoxia. Initial BMP: Glucose 141 mg/dL, bicarb 24 mmol/L, anion gap of 10 mmol/L. Patient test positive for COVID-19 and was admitted for acute hypoxic respiratory failure in setting of COVID-19 infection. Six hours after patient received first dose of dexamethasone, labs showed BMP: Glucose 582 mg/dL, bicarb 14 mmol/L, anion gap of 20 mmol/L. ABG: pH 7.09, bicarb 13.2 mmol/L, glucose 509 mg/dL, lactate 9.6, beta-hydroxybutyrate 1.15 mmol/L. Patient was diagnosed and treated for DKA. Patient had an echocardiogram which showed new HFrEF. There was initial hesitation to restart patient on home Empagliflozin due to recent development of DKA. Literature review showed cases of DKA associated with COVID-19 infection. Etiology of DKA remained unclear. Ultimately, it was decided to restart patient on home Empagliflozin for management of diabetes and HFrEF. Conclusion: An abundance of evidence support the benefits of SGLT-2 inhibitors for patients with and without type 2 diabetes mellitus. (4) It is important to consider other causes of DKA for patients who develop DKA on SGLT-2 Inhibitors. Furthermore, additional research into endocrinopathies related to COVID-19 infections should be considered. References: (1) Alamuri TT, Mahesh S, Dell'Aquila K, Leong TJ, Jennings R, Duong TQ. RCOVID-19 associated ketosis and diabetic ketoacidosis: A rapid review. Diabetes Obes Metab. 2023 Jul;25(7):1785-1793. doi: 10.1111/dom.15036. Epub 2023 Mar 17. PMID: 36855317. (2) Goldenberg RM, Berard LD, Cheng AYY, Gilbert JD, Verma S, Woo VC, Yale JF. SGLT2 Inhibitor-associated Diabetic Ketoacidosis: Clinical Review and Recommendations for Prevention and Diagnosis. Clin Ther. 2016 Dec;38(12):2654-2664.e1. doi: 10.1016/j.clinthera.2016.11.002. PMID: 28003053. (3) Patel J, Rassekh N, Fonarow GC, Deedwania P, Sheikh FH, Ahmed A, Lam PH. Guideline-Directed Medical Therapy for the Treatment of Heart Failure with Reduced Ejection Fraction. Drugs. 2023 Jun;83(9):747-759. doi: 10.1007/s40265-023-01887-4. Epub 2023 May 31. PMID: 37254024. (4) Brown E, Heerspink HJL, Cuthbertson DJ, Wilding JPH. SGLT2 inhibitors and GLP-1 receptor agonists: established and emerging indications. Lancet. 2021 Jul 17;398(10296):262-276. doi: 10.1016/S0140-6736(21)00536-5. Epub 2021 Jun 30.PMID: 34216571.

Presentation: 6/3/2024
6617 A Case of Doege-Potter Syndrome With Normal IGF-II
Authors: Yip A T , Donangelo I
Published: October 2024

Disclosure: A.T. Yip: None. I. Donangelo: None.

Background: Doege-Potter syndrome is a rare presentation of non-islet cell tumor hypoglycemia that results from ectopic secretion of IGF-II prohormone from a solitary fibrous tumor (SFT). Case: A 57-year-old woman came to medical attention after a syncopal episode requiring hospitalization for severe hypoglycemia. She had an unremarkable brain MRI but chest CT showed a 18cm pleural based mass in the right thorax with biopsy consistent with SFT. The patient left the hospital against medical advice but had recurring events of severe hypoglycemia occurring overnight. She had resorted to taking glucose tabs nightly and had her spouse routinely wake her up at 2AM to take more glucose tabs. She required direct hospital re-admission for refractory hypoglycemia and expedited investigation and surgical intervention. Blood work revealed serum glucose 31 mg/dL (65-99 mg/dL), C-peptide <0.5 ng/mL (1.1-4.3 ng/mL), insulin<1 uU/mL (3-25 uU/mL), beta-hydroxybutarate <1.0 mg/dL (≤3.0 mg/dL), negative serum and urine sulfonylurea screen, negative insulin antibody, IGF-II 130 ng/mL (180-580 ng/mL), and IGF-I 31 ng/mL(50-317 ng/mL) which confirmed suspicion for a non-insulin mediated process although her IGF-II levels were not elevated with a IGF-II to IGF-I ratio of 4. She was placed on a continuous dextrose infusion with the rate titrated to target euglycemia. She underwent right pleural mass resection and post-operatively was liberated from the dextrose infusion without subsequent episodes of hypoglycemia. Pathology sections demonstrated a well-circumscribed tumor composed of bland spindle cells arranged in a pattern-less architecture. The tumor cells stained positively for CD34 (cytoplasmic) and STAT6 (nuclear) which were consistent with SFT. During her 3-month post-op follow up she denied any further episodes of hypoglycemia. Her follow up labs showed serum glucose 81 mg/dL (65-99 mg/dL), C-peptide 1.3 ng/mL (1.1-4.3 ng/mL), insulin 3 uU/mL (3-25 uU/mL), IGF-II 467 ng/mL (180-580 ng/mL), and IGF-I 128 ng/mL (50-317 ng/mL). Oncology recommended routine surveillance with PET CT scans. Clinical Lessons: Although rare, Doege-Potter syndrome should be on the differential diagnosis for non-insulin mediated hypoglycemia. Despite being an IGF-II mediated process, SFTs most commonly produce a high molecular weight “big” IGF-II molecule that is usually not detected by commercial laboratory assays thus leading to non-elevated levels of IGF-II, normal IGF-II:IGF-I ratios, and potential a delay in diagnosis of cases where a tumor has yet to be identified. Additionally, when IGF-II tumor immunostaining is unavailable, STAT6 serves as a highly sensitive and specific marker for SFT. This tumor generally does not have malignant potential and the associated hypoglycemia typically resolves after surgical resection of the SFT.

Presentation: 6/1/2024
8299 A Case of Hypoglycemia in a Patient with Cirrhosis and Previous Bariatric Surgery
Authors: Risbud A , Bao G , Kirkeby K M
Published: October 2024

Disclosure: A. Risbud: None. G. Bao: None. K.M. Kirkeby: None.

Background: Hypoglycemia is a known complication of both chronic liver and kidney disease as well as gastric bypass surgery. It can be challenging to treat in the setting of multiple medical conditions without definitive treatment, such as organ transplantation. Clinical case: A 47-year-old woman presented with symptomatic hypoglycemia. Her past medical history included obesity, for which she had undergone Roux-en-Y gastric bypass surgery 9 years prior; alcohol and metabolic dysfunction-associated cirrhosis complicated by hepatic encephalopathy and ascites, for which she was actively listed for liver transplantation; and stage 3 chronic kidney disease. Continuous glucose monitoring elucidated that hypoglycemic episodes (as low as 30 mg/dl) often followed periods of significant postprandial hyperglycemia (up to 300 mg/dl) without the use of exogenous insulin or insulin secretagogues. Hypoglycemia persisted despite smaller, more frequent meals with more complex and fewer simple carbohydrates, but was better managed with subcutaneous octreotide injections before meals for the next 11 months. Hypoglycemia eventually resolved after she underwent liver transplantation approximately 16 months after her initial presentation. Conclusion: Postprandial hyperinsulinemic hypoglycemia has been reported following gastric bypass surgery, sometimes occurring years after surgery. While nutrition intervention and somatostatin analogs such as octreotide may be helpful, hypoglycemia may be worsened by concurrent liver and/or kidney disease, wherein gluconeogenesis is impaired. Liver transplantation may be an effective strategy. References: Mala, T. (2014). Postprandial hyperinsulinemic hypoglycemia after gastric bypass surgical treatment. Surgery for Obesity and Related Diseases, 10(6), 1220-1225.Pfortmueller, C.A., Wiemann, C., Funk, G.C., Leichtle, A.B., Fiedler, G.M., Exadaktylos, A.K., & Lindner, G. (2014). Hypoglycemia is associated with increased mortality in patients with acute decompensated liver cirrhosis. Journal of critical care, 29(2), 316-e7.Singh, E., & Vella, A. (2012). Hypoglycemia after gastric bypass surgery. Diabetes Spectrum, 25(4), 217-221.

Presentation: 6/3/2024
6852 A Delayed Diagnosis of Diabetic Myonecrosis: Case Report
Authors: Taleb M , Stephan J , Vo T , Estrada K
Published: October 2024

Disclosure: M. Taleb: None. J. Stephan: None. T. Vo: None. K. Estrada: None.

Background: Diabetic myonecrosis, also termed diabetic muscle infarction, is a rare microvascular complication of diabetes mellitus (DM). Although it can manifest in patients with all types of DM, it is more common in type 1 DM. It presents with pain and swelling localized in a muscle group and is associated with significant morbidity. The most commonly affected area is the anterior thigh, followed by the posterior thigh or calf. Clinical Case: A 34-year-old woman presented with two months of left thigh pain and swelling. She had a history of long-standing type 1 DM complicated by end-stage kidney disease for which she had been initiated on peritoneal dialysis (PD) six months prior to presentation. Her localized symptoms started after a fall and persisted since then. Our patient’s initial workup showed an elevated CPK level of 1340 IU/L (normal <178 IU/L), and limb radiographs were negative for fracture or dislocation. Her symptoms were attributed to musculoskeletal pain. She subsequently presented to the emergency departments multiple times with the same symptoms. On one presentation, she was diagnosed with nontraumatic rhabdomyolysis in the setting of hematuria and persistent left thigh pain. On another presentation, CT of the left femur was done and showed skin thickening, subcutaneous fat stranding, and edema without osseous abnormalities; she was diagnosed with complex regional pain syndrome (CRPS) and discharged home on gabapentin, which did not improve her symptoms. Ultimately, she was admitted to the hospital with the inability to ambulate due to her persistent and severe symptoms. MRI of the left hip and femur showed signs of diffuse myositis and areas of myonecrosis consistent with diabetic myonecrosis. Prior to initiation of PD, our patient’s HbA1c had been well controlled at the target of <7%. Due to the high dextrose content in dialysate, she had an increase in her HbA1c to 9.0% within a span of three months despite no changes in her medications or diet. Once the diagnosis was established, aspirin was initiated and insulin regimen was adjusted for tighter glucose control. Two weeks after treatment our patient had resolution of her symptoms. Conclusion: We highlight a case of diabetic myonecrosis, a complication of DM, that can be missed due to its rarity and nonspecific presentation. Index of suspicion should be high in patients with persistent unexplained musculoskeletal symptoms. Despite MRI being the diagnostic modality of choice, obtaining it was delayed due to multiple factors including initial radiologic findings negative for acute fractures and previous misdiagnosis of rhabdomyolysis and CRPS. Management of diabetic myonecrosis is centered around tight glycemic control. This highlights the importance of close monitoring of glycemic control when initiating a patient with diabetes mellitus on PD, given the constituents of the dialysate used, to prevent complications of diabetes.

Presentation: 6/1/2024
7449 A Genome-wide CRISPR Screen Identifies Drivers of Impaired Glucose Uptake in Human Insulin Resistance
Authors: Haider N , Lee Y C , Yi P , Kahn C R
Published: October 2024

Disclosure: N. Haider: None. Y. Lee: None. P. Yi: None. C.R. Kahn: None.

Insulin resistance is a major risk factor in the development of type 2 diabetes (T2D), and metabolic syndrome. Although 25% of people within the general non-diabetic population are insulin resistant, the primary underlying cause of insulin resistance remains elusive. In this study, we have used induced pluripotent stem cells (iPSC) derived from non-diabetic humans at both ends of the insulin sensitivity spectrum, i.e., the top 20% of insulin resistance vs. the top 20% of insulin sensitive, as well as individuals with T2D to model human insulin resistance. We find that iPSCs differentiated into myoblasts (iMyos) from T2D and non-diabetic individuals in the highest quintile of insulin resistance (I-Res) show impaired insulin signaling and defective insulin-stimulated glucose uptake, as compared to iMyos from the insulin sensitive individuals (I-Sen), indicating that these cells in vitro mirror the alterations seen in vivo in a cell autonomous manner. To uncover the primary upstream drivers that contribute to the impaired glucose uptake associated with insulin resistance, we conducted a genome-wide loss-of-function screen using a CRISPR-based approach to identify genes that positively or negatively regulated glucose uptake in I-Res and T2D iMyos. Knockdown of ∼525 genes show effect to rescue the impaired glucose uptake in both I-Res and T2D iMyos, i.e., were negative regulators of glucose uptake. We hypothesized that important negative regulators of glucose uptake might be over-expressed at the protein level in I-Res and T2D iMyos and crossing the iMyos proteomics data with the CRISPR screen revealed 8 top candidates that are increased at the protein level and whose knockdown rescued glucose uptake in I-Res and T2D iMyos. These included candidates associated with cytoskeleton changes, protein kinases, transmembrane transport, mitochondrial and nuclear proteins. In summary, iPSC derived myoblasts from patients with insulin resistance and T2D mirror defects in glucose uptake observed in vivo. Combining CRISPR screening and global proteomics, we have identified important upstream regulators of insulin resistance in humans.

Presentation: 6/2/2024
8090 A Gut Commensal, Parabacteroides distasonis, and Molecular Mimicry in Type 1 Diabetes
Authors: Randall Audrey , Girdhar Khyati , Altindis Emrah
Published: October 2024

Disclosure: A. Randall: None.

Type 1 diabetes (T1D) is a chronic autoimmune disease characterized by the destruction of pancreatic, insulin-producing beta cells by autoreactive T-cells. The trigger(s) of T1D are unclear and genetics alone cannot explain the recent increase in T1D incidence. The gut microbiome composition in T1D patients is altered and thought to play a key role in T1D pathogenesis. Most longitudinal studies have been descriptive. However, a direct cause-and-effect relationship hasn't been established yet. Insulin is a key autoantigen in T1D autoimmunity, and insulin B-chain amino acids 9-23 (insB:9-23) is an important, commonly recognized T-cell epitope. Molecular mimicry is an autoimmunity mechanism where host-like microbial proteins trigger autoimmune responses. We previously identified a peptide mimic of insB:9-23, amino acids 4-18 of hypoxanthine phosphoribosyl transferase (HPRT:4-18) of Parabacteroides distasonis (Girdhar et al., 2022). HPRT:4-18 stimulated insB:9-23-specific human and non-obese diabetic (NOD) mice T-cells. We hypothesize that P. distasonis HPRT:4-18 is required to accelerate diabetes via molecular mimicry of insB:9-23. By orally gavaging NOD mice (n=40 mice/group), we showed that P. distasonis accelerated diabetes onset. Next, we colonized NOD mice with another common gut commensal, Bacteroides fragilis, as a control, and did not observe any effect on islet infiltration. In addition, P. distasonis colonization increased infiltration of immune cells into the islets of germ-free NOD mice (n=6-8 mice/group), while the diabetes incidence experiment in mice is ongoing. P. distasonis-colonized mice had significantly more splenic CD8 and naïve T-cells, dendritic cells and macrophages but fewer FOXP3 cells (n=3-6 mice/group). To determine whether P. distasonis’s effect is specific to the pancreas, we checked intestinal barrier function and intestinal immune cell composition. Disruption of intestinal barrier function has been associated with diabetes. P. distasonis colonization did not alter gut permeability. Furthermore, P. distasonis did not increase intestinal inflammation. Among the intestinal intraepithelial lymphocytes (IELs), there were fewer naïve, central and effector T-cells and B-cells. The findings indicate that P. distasonis does not stimulate an unspecific immune response and its inflammatory effect is specific to the pancreas, supporting our initial hypothesis. Taken together, our results indicate that exposure to P. distasonis in the first years of life has the potential to stimulate molecular mimicry mechanism and cause T1D onset. Reference: Girdhar, K., Huang, Q., Chow, I. T., Vatanen, T., Brady, C., Raisingani, A., . . . Altindis, E. (2022). A gut microbial peptide and molecular mimicry in the pathogenesis of type 1 diabetes. Proc Natl Acad Sci U S A, 119(31), e2120028119. doi:10.1073/pnas.2120028119

Presentation: 6/2/2024
12374 A Prospective Study Of Plasma Levels Of Asprosin And Incident Type 2 Diabetes Among Postmenopausal Women In The Women’s Health Initiative
Authors: Yang B , Li J , Silva E S , Phillips L S , Manson J E , Reiner A P , Chopra A R , Liu S
Published: October 2024

Disclosure: B. Yang: None. J. Li: None. E.S. Silva: None. L.S. Phillips: None. J.E. Manson: None. A.P. Reiner: None. A.R. Chopra: None. S. Liu: None.

Background: Asprosin, a 30-kDa hormone identified from white adipose tissue, has been shown to play key roles in regulating hepatic glucose release and appetite stimulation. Despite an increasing body of experimental studies demonstrating asprosin as a promising therapeutic target, little is known about its distribution in the general population particularly concerning its association with incident type 2 diabetes (T2D). Objectives: To evaluate whether higher plasma levels of asprosin are associated with incident T2D among postmenopausal women independently of known risk factors for T2D. Methods: We conducted a case-control study nested in the Women’s Health Initiative (WHI), including 5,198 participants free of diabetes, cardiovascular diseases, and cancer at baseline (2,602 incident T2D cases and 2,596 controls). Plasma levels of asprosin were measured using a sandwich enzyme-linked immunosorbent (ELISA) assay. We used conditional logistic regression models to estimate the association between asprosin and T2D risk with adjustment for matching variables (age, race, sampling batch), education, body mass index (BMI), physical activity, tobacco smoking, alcohol drinking, family history of diabetes, age at menopause, total energy intake, the Alternate Healthy Eating Index (AHEI), and multivitamin use. Results: Approximately 43% of participants were white and the mean age at baseline was 63 years. The median plasma levels of asprosin were 38 (IQR: 30, 50) pmoL/L in the controls and 39 (IQR: 31, 50) pmoL/L among those who developed T2D during follow-up. Compared with the participants in the lowest quintile of plasma levels of asprosin at baseline, those in the highest quintile had a 26% increased risk of T2D (adjusted odds ratio: OR: 1.26 [95% CIs, 1.01, 1.57], p for trend=0.03) in the fully adjusted model. The OR estimates exhibited a large variation across race and BMI, although there was a linear dose-response relation between levels of asprosin and T2D risk (p for nonlinear=0.44). Genetic analysis revealed that women with the heterozygous allele (CG) at single nucleotide polymorphisms (SNP) rs56407701 had higher levels of asprosin compared to women with the homozygous reference allele (CC). Further, Mendelian Randomization analysis revealed that genetically predicted asprosin levels were associated with higher T2D risk. Conclusion: Among postmenopausal women, higher plasma levels of asprosin were prospectively associated with elevated T2D risk independent of known T2D risk factors. Further work is needed to confirm the potential causal role of this peptide hormone in the clinical risk stratification and potential prevention of T2D.

Presentation: 6/2/2024
6663 Amputation Rate in Hospitalized Patients With Diabetic Foot Ulcer at Montefiore Medical Center, Bronx, NY
Authors: Lopez Fanas Raul , Herrera Chancay Azucena , Tabassum Humera , Milosavljevic Jovan , Xu Shiming , Daily Johanna , Myers Alyson K
Published: October 2024

Disclosure: R. Lopez Fanas: None. A. Herrera Chancay: None. H. Tabassum: None. J. Milosavljevic: None. S. Xu: None. J. Daily: None. A.K. Myers: None.

Introduction: Diabetic foot ulcers (DFU) are associated with poor outcomes including lower extremity amputations and death in individuals with diabetes. Our study aims to define health outcomes and explore the association of sociodemographic and clinical factors on amputation rates in patients hospitalized with DFU addressing an existing knowledge gap in our population. Methods: This was a retrospective review of the electronic health record of adult patients hospitalized with DFU at one of the three major Montefiore Medical Center hospitals in the Bronx, New York between 06/01/2016 and 05/30/2021. Patient data extracted from the index admission included demographics, comorbidities, and laboratory values. Survival and amputation rates were calculated for each patient over the five-year study period. Results: In our analysis of 650 patients, 88% self-identified as non-white, and only 23% had commercial insurance. The amputation rate during the initial DFU admission was 44%, with 76% experiencing at least one amputation over five years. Male sex, low BMI, and smoking were associated with amputation during the study period, with an OR of 0.62 (p=0.01), 0.98 (p=0.05), and 1.45 (p=0.05) respectively. Patients with history of osteomyelitis had a higher risk of any amputation during the index admission (OR 2.05, p<0.0001), and the 5-year study period (OR 3.03, p<0.0001). PAD or prior history of amputation increased the risk of any amputation during the study period, OR 2.11 (p=0.0002) and OR 7.92 (p<0.001) ESRD was associated with a higher risk of AKA and BKA during the index admission (OR 2.31, p=0.05). Elevated ESR, CRP, WBC, and low albumin were associated with amputation during admission, with ORs of 1.01 (p=0.0006), 1.05 (p<0.0001), 1.11 (p<0.0001), and 0.41 (p<0.0001), respectively. Discussion: This study revealed a 44% amputation rate during the initial DFU admission, with 76% experiencing at least one amputation within five years. Bivariate analyses identified male sex, lower BMI, and smoking as correlated with a heightened amputation risk, consistent with previous studies. Prior amputation, PAD, ESRD, and osteomyelitis were also associated with an increased risk. Multiple regression analysis found significant associations between elevated ESR, CRP, WBC, and low albumin with amputations. As a result, interventions need to be devised for patients with these characteristics to prevent this high rate of amputation.

Presentation: 6/2/2024