bluuebunny/crossref_metadata_2025_split huggingface dataset:
7574 Diabetes Stem Cells: A Common Target for Abnormal Insulin Secretion and Insulin Resistance
Authors: Kojima Hideto , Katagi Miwako , Okano Junko , Nakagawa Takahiko 
Published: October 2024

Abstract
Disclosure: H. Kojima: None. M. Katagi: None. J. Okano: None. T. Nakagawa: None.
Diabetes is based on chronic inflammation and cannot be cured using only drugs that lower blood glucose levels. A culprit was lurking there that was hindering healing. We discovered abnormal hematopoietic stem cells that caused persistent chronic inflammation in the bone marrow of diabetic model animals. The real culprit is born after several days of hyperglycemia, never dies, and each time glycemic control deteriorates, it moves its progeny in large numbers throughout the body, fusing with unique cells in various organs and producing TNF-α from the organ cells. We have named these worst stem cells, which resemble cancer stem cells, "diabetes stem cells," and attempted to induce complete remission in diabetic model animals by eliminating them with drugs. In this study, we used streptozotocin (STZ)-induced insulin-deficient diabetes model mice. "Diabetes stem cells" were included in the CD106-positive short-term hematopoietic stem cell fraction, in which progenitor cells that play an important role in the regeneration of the thymus and peripheral tissues, and were characterized by abnormal expression of proinsulin and TNF-α. Furthermore, like cancer cells, the expression of histone deacetylases (HDACs) increased, and once the cells were born, they would not disappear. Therefore, we aimed to eliminate diabetes by administering an HDAC inhibitor and subcutaneously injecting insulin pellets to temporarily correct blood glucose levels. We treated diabetic mice with HDAC inhibitor for 8 weeks, along with several weeks of insulin therapy. Insulin aims to prevent the formation of new abnormal cells in the bone marrow and to prevent the inhibition of pancreatic islet wasting due to the forced insulin secretion caused by hyperglycemia. The combination therapy allowed the beta cells to regenerate and produce enough insulin to normalize blood glucose levels and maintain them even after treatment was discontinued. It also solved the mystery of how the abnormal cell population evades attacks from the T cells. In STZ diabetes, the supply of normal CD106-positive progenitor cells from the bone marrow for thymic regeneration was completely blocked, resulting in marked thymic atrophy. As a result, the thymus, which had lost its progenitor cells, was unable to establish an immune surveillance system to eliminate mutated cells throughout the body. In other words, the combination therapy completely broke the vicious cycle caused by atrophies in both the islet and the thymus. Moreover, when the thymus was surgically removed along with the adventitia to prevent regeneration, diabetes remission was completely inhibited, supporting the importance of thymic normalization. Diabetes is a hematopoietic stem cell disease accompanied by thymic dysfunction, and the removal of "diabetes stem cells" paves the way for the cure of diabetes.
Presentation: 6/2/2024
7086 Disrupted Mitochondrial Function in Alström Syndrome- A Monogenic Model of Insulin Resistance and Obesity
Authors: Ali Sadaf , Heising Silke , Veeranna Vishy , Vincent Amy , Xavier Gabriela S , Geberhiwot Tarekegn 
Published: October 2024

Abstract
Disclosure: S. Ali: None. S. Heising: None. V. Veeranna: None. A. Vincent: None. G.S. Xavier: None. T. Geberhiwot: None.
Alström syndrome (ALMS) is a rare monogenic disease typified by severe insulin resistance (IR) and obesity. IR and obesity are cardinal features of metabolic syndrome. The metabolic effects of insulin at key target tissues leads to metabolic haemostasis by promoting glucose and lipid uptake and metabolism to generate energy in cells. Although insulin is a major regulator of fuel metabolism, its effects on mitochondrial ATP production in severe insulin resistance are unclear. RNASeq data from adipose tissue (AT) from patients with ALMS show downregulation of the expression of genes associated with mitochondrial respiratory chain function, pointing towards possible altered mitochondrial function in ALMS. We therefore undertook a detailed assessment of mitochondrial oxidative phosphorylation capacity (OXPHOS) in skeletal muscle (SM) in ALMS. We performed SM biopsy in 10 ALMS and 10 healthy control volunteers that were age, gender and Body Mass Index matched. The SM was subjected to high resolution respirometry, the gold standard method to quantify mitochondrial function ex vivo, using OROBOROS Oxygraph -2k (O2k) system. Overall OXPHOS was higher in control SM compared to ALMS, with maximal respiration of 62.96±19.2 and 44.24 ± 12.53 pmol/(s*mg), respectively (p&lt;0.05).Reduced oxygen influx was observed in ALMS SM in comparison to controls for fatty acid ß oxidation (6.7±5.96 vs 7.87±2.7 pmol/(s*mg);p&lt;0.05, at complex I (19.4 ± 8.98 vs 29.7 ±5.3 pmol/(s*mg);p&lt;0.05, and at complex II (34.98 ±11.75 vs 53.52± 13.2 pmol/(s*mg) ;p&lt;0.05. Mitochondrial membrane integrity was unaffected during these experiments. Therefore, our analysis unveils a consistent reduction in mitochondrial respiration across all the electron transport pathway. This noteworthy finding suggests impairment in respiratory function and the electron transport chain in mitochondria, a crucial aspect of cellular energy metabolism. Several studies have previously linked IR with mitochondrial dysfunction, where insulin-resistant rodents and humans have shown blunted mitochondrial response to ATP generation. Our results align with this body of evidence emphasizing the significance of investigating the underlying mechanism contributing to this phenomenon. These findings could pave the way to exploring potential mitochondrial-targeted therapies to restore mitochondrial function and therefore, improve insulin sensitivity to tackle IR in ALMS.
Presentation: 6/2/2024
5104 Ectopic Insulinoma- a Rare Presentation of a Rare Tumor
Authors: Lavrynenko Olga , DeMarsilis Antea , Jiang Cherry , Middelbeek Roeland , Rosen Harold , Patti Mary Elizabeth 
Published: October 2024

Abstract
Disclosure: O. Lavrynenko: None. A. DeMarsilis: None. C. Jiang: None. R. Middelbeek: None. H. Rosen: None. M.E. Patti: None.
Background. Insulinoma is a rare, functioning neuroendocrine tumor (NET) typically localized within the pancreas, that secretes insulin, resulting in hypoglycemia. Ectopic insulinoma is even more rare than pancreatic insulinoma and is more difficult to diagnose. Case report. This 31-year-old previously healthy woman, who had an uncomplicated pregnancy and a healthy baby in October 2021, presented with intermittent hypoglycemia for more than 8 months. She denied any prior use of insulin or antidiabetic medications and was not currently taking any medications at all. There is no history of bariatric or other GI surgery. While nursing her baby in early 2022, she was noted to have a capillary blood glucose (BG) between 20-30 mg/dl, and reported both adrenergic and neuroglycopenic symptoms of hypoglycemia; these usually occurred in the morning or before lunch, especially if lunch was delayed. She wore a Libre CGM which revealed episodic hypoglycemia, which correlated with her timeline of symptoms. She reported weight gain of 8 lbs during this period. Laboratory data obtained after a 10-12 hour fast revealed hypoglycemia (venous glucose 39 mg/dL) with inappropriately high plasma insulin (42.3 mIU/ml), C- peptide (3.78 ng/ml), and proinsulin (99 pmol/L). Beta-hydroxybutyrate was 0.05 mmol/L (reference &lt;0.28) and insulin autoantibody and sulfonylurea screen were negative. Various imaging modalities for localization revealed a solitary omental mass outside the pancreas consistent with extra-pancreatic insulinoma. No pancreatic lesion or other findings were observed with MRCP, CT C/A/P or endoscopic ultrasound. The patient underwent CT-guided biopsy of the omental mass, which confirmed a well-differentiated NET, consistent with insulinoma. Due to persistent hypoglycemia, she was started on corn starch and diazoxide. She subsequently underwent laparoscopic resection of the mass. Postoperative pathology revealed a well-differentiated NET staining positive for insulin, consistent with an extra-pancreatic insulinoma. Following surgical resection of the insulinoma, her hypoglycemia resolved even off corn starch and diazoxide. Conclusion. Ectopic insulinoma is a rare insulin-secreting NET. Only 28 ectopic insulinomas have been described in the literature to date1. We describe a patient with symptomatic hypoglycemia who was found to have an omental neuroendocrine tumor; hypoglycemia completely resolved after laparoscopic enucleation of the ectopic insulinoma. 1Fernando Guerrero-Pérez, Nuria Vialarrasa, Lidia V. Huanuco et. al. Ectopic Insulinoma: a systemic review: Reviews in Endocrine and Metabolic Disorders, 2023
Presentation: 6/1/2024
7944 Elevated Serum Alkaline Phosphatase without other Abnormalities of Liver Associated Enzymes as an early Indicator of Glucose Intolerance: A Case Series
Authors: Bowens Brendan K , Godar Cassandra , LaChance David , Hoang Thanh Duc , Shakir Mohamed K M 
Published: October 2024

Abstract
Disclosure: B.K. Bowens: None. C. Godar: None. D. LaChance: None. T.D. Hoang: None. M.K. Shakir: None.
Glucose intolerance (GI) is defined as dysglycemia and includes impaired fasting glucose, impaired glucose tolerance, and prediabetes. Early detection of GI could lead to appropriate treatment and delay the progression to diabetes mellitus. The cases below detail two patients with elevated serum alkaline phosphatase (ALP) without other liver-associated enzyme abnormalities as an early indicator of GI. Case 1: A 54-year-old woman with a history of multinodular goiter status post thyroidectomy (2020), adrenal incidentaloma (2016), and asthma was incidentally found to have an elevated HbA1C (A1C) of 6.3% on screening labs in 2015. At that time, her ALP was 73 IU/L (ref 44−121). Her ALP levels slowly rose from 88 to 152 IU/L by September 2020. Work up did not reveal any etiological factors for the elevated ALP. One month later, HbA1C was found to be 7.6%. Metformin was initiated with improvement in A1C to 6.3% with an ALP of 130 IU/L. However, metformin was discontinued due to intolerance. In April 2023, her A1C was 9.3% with an ALP of 134 IU/L. A1C rose to 12.8% in Jun 2023 at which time she was started on insulin glargine, insulin aspart, sitagliptin, and was restarted on metformin. Her A1C decreased to 8.6% in August 2023 with normalization of ALP to 88 IU/L. Case 2: A 53-year-old woman with a history of hypertension, hyperlipidemia, obstructive sleep apnea, and non-ischemic cardiomyopathy in 2004 was found to have an elevated A1C of 5.8% on her screening labs in Jun 2019. Her ALP was notably in the high-normal range until Oct 2021 when it was found to be 138 IU/L. Her most recent A1C was 5.9% with an ALP of 142 IU/L. The patient was started on semaglutide (WegovyTM) briefly but was unable to tolerate the side effects. She was then started on metformin 500mg BID and dulaglutide with normalized ALP level. Discussion: Emerging evidence has shown that serum ALP activity is modestly increased in cardiometabolic diseases such as type 2 diabetes, dyslipidemia, hypertension, and peripheral arterial disease. These are increasingly being considered as inflammatory disorders and it has been shown that serum ALP level was positively and independently associated with metabolic syndrome both in men and women. It is possible that ALP could be an indicator of non-alcoholic fatty liver disease (NAFLD) which is associated with GI. Typically, NAFLD presents with higher ALT and GGT, however, occasionally isolated enzyme elevations or no elevated enzymes at all may occur. Conclusion: These cases suggest that an isolated elevation in ALP could be indicative of GI. Patients incidentally found to have an elevated ALP should be worked up further for possible evidence of GI. Early detection of GI could delay progression to diabetes and decrease morbidity.
Presentation: 6/1/2024
6869 Endocrinologist Perceptions of the Value of Digital Health Tools to Assist in the Management of Insulin Dosing
Authors: Davidson M B , Liao B , Heckman C 
Published: October 2024

Abstract
Disclosure: M.B. Davidson: Employee; Self; Eli Lilly & Company. B. Liao: Employee; Self; Eli Lilly & Company. C. Heckman: Employee; Self; Eli Lilly & Company.
Background and aims: Insulin management is complex for both people with diabetes (PwD) and the healthcare providers (HCP) who treat them. Digital tools, such as connected insulin pen (CIP) platforms may reduce burden and improve suboptimal insulin dosing, especially through automatic capture of insulin dose events and integration with glucose values. However, the acceptance and utilization of CIP platforms in clinical practice remains lower than expected, given this clinical care gap. This study attempted to ascertain beliefs of HCP leading to this finding. Methods: For this cross-sectional study, 190 members of The Endocrine Society who self-identified as “clinical endocrinologists who treat diabetes” completed a 10-question survey on their perception of digital health tools and their value in clinical practice. Results: In their patients using multiple daily injections (MDI), defined as three or more injections of insulin per day, documentation of insulin dosing data was identified as “important” or “very important’ to 81% of respondents. However, only 48% of respondents are “confident” or “very confident” in the reliability of manually captured insulin and glucose data. While 92% of respondents indicated that a digital platform that displays insulin and glucose data would be “beneficial” or “very beneficial” for making dosing recommendations, 60% have found that a CIP platforms had been “beneficial” or “very beneficial” in helping PwD improving their glycemic control. Conclusion: A group of almost 200 clinician members of the Endocrine Society, who actively treat PwD, indicated that in their PwD using MDI regimens, access to combined insulin and glucose data is important, and digital capture of this data would be beneficial. However, this data is often unavailable or unreliable. The survey revealed a gap between their belief that availability of glucose data and insulin dosing data can help them make dosing recommendations and their belief that these will translate into impacting glycemic control of patients. Further research would be helpful to determine how diabetes technology may better support these HCP and the PwD they treat in practice.
Presentation: 6/1/2024
12467 Ethical Challenges During Medication Scarcity
Authors: Seetharaman Kavita , Alvi Raza , Roth Virginia , Maheswaran Janane 
Published: October 2024

Abstract
Disclosure: K. Seetharaman: None. R. Alvi: None. V. Roth: None. J. Maheswaran: None.
Ethical considerations while rationing GLP-1 RA during medication scarcity crisis: The prevalence of type 2 diabetes and obesity have risen over the past decade. Type 2 diabetes affects nearly 29 million Americans, and one in 3 Americans are obese. Prompt treatment of type 2 diabetes can result in prevention and progression of several diabetes related complications. In the past 3 decades, advancements in scientific research has led to invention of newer therapeutic agents such as the glucagon like peptide-1 receptor agonist (GLP-1 RA) for management of type 2 diabetes and these medications have shown to provide cardiovascular benefit and renal protective effects. More recently, with increasing benefits of GLP-1 RA in treating obesity even in the absence of diabetes, the prescription rates of GLP-1 RA has increased sharply leading to acute medication scarcity and the resultant crisis has created a chaos in health care having multi-faceted repercussions.We present a short movie enacting 2 clinical scenarios with doctor and patients to initiate discussions on how to ration GLP-1 receptor agonists during times of medication scarcity crisis and the bioethical aspects to consider while making such decisions. We further include discussions by enacting pharmacy care coordinator, bioethicist, critique and defense discussion. Bioethics involved in medication scarcity crisis:https://hu-my.sharepoint.com/:v:/g/personal/kseetharaman_hsph_harvard_edu/EZIHpFRCgb5AsoKLk898TgUBsdp8JNjdAGQ6vOIpZIP1Qg?e=TkxRhz We hope our enacting of various scenarios has given you all valuable ethical perspectives to consider while rationing during times of medicine scarcity. References: National Diabetes statistics Report, https://www.cdc.gov/diabetes/data/statistics-CNN, Oprah on why she turned to weight-loss drugs. from https://www.cnn.com/videos/health/2024/03/21/oprah-weight-loss-drugs-kc-vpx.cnn Persad G, Wertheimer A, Emanuel EJ. Principles for allocation of scarce medical interventions. Lancet. 2009 Jan 31;373(9661):423-31. doi: 10.1016/S0140-6736(09)60137-9. Whitley HP, Trujillo JM, Neumiller JJ. Special Report: Potential Strategies for Addressing GLP-1 and Dual GLP-1/GIP Receptor Agonist Shortages. Clin Diabetes. 2023 Summer;41(3):467-473. doi: 10.2337/cd23-0023. Epub 2023 Diabetes medications as weight loss drugs https://www.youtube.com/watch?v=VPEaLNpCzTY
Presentation: 6/3/2024
8139 Examining the Association of GLP1-RA or DPP4i with Bullous Skin Diseases in Veterans
Authors: Saad-Omer Suhail , Kinaan Mustafa , Sami Naveed , Mansi Ishak 
Published: October 2024

Abstract
Disclosure: S. Saad-Omer: None. M. Kinaan: None. N. Sami: None. I. Mansi: None.
Introduction: Pemphigus vulgaris (PV) and bullous pemphigoid (BP) are Autoimmune Blistering Disorders (AIBDs). GLP-1 Receptor Agonists (GLP1-RA) and Dipeptidyl peptidase 4 inhibitors (DPP4i) have been noted in various case reports and case control studies to be linked with certain AIBDs; however, their overall role in these diseases is not completely understood, despite the exponential increase in use of these medications. This study aims to be the first study to investigate the association of DPP-4 inhibitors and GLP-1 agonists with incidence of AIBD, PV, and BP in a large cohort of American veterans. Methods: This retrospective cohort study of veterans enrolled in the Veterans Health Administration (VHA) used Corporate Data Warehouse (CDW). We extracted data of patients from fiscal years (FY) 2006 to end of FY 2021 who filled either GLP1-RA or DPP4i prescriptions. CDW is a comprehensive data source that encompasses vital status, demographic data, inpatient and outpatient diagnoses and procedure codes, vital signs, laboratory data, and pharmacy fill data. The study groups included: 1) GLP1-RA group: patients who initiated GLP1-RA; and 2) DPP4i group: patients who initiated DPP4i. Our primary outcome was the incidence of AIBDs. We compared baseline characteristics of patients who experienced the outcome and those who did not among GLP1-RA or DDP4i users. We, thereafter, examined factors associated with incidence of AIBD, PV, and BP among GLP1-RA users and DPP4i users. Results: The initial cohort of GLP1-RA or DPP4i users comprised a total of 415,895 patients, from which we excluded 397 (0.095%) patients with prior bullous skin diseases before starting GLP1-RA or DPP4i medications. Overall, a total of 154 patients developed PV/BP disease after initiation of either DPP4i or GLP1-RA. Of these 154 patients, 123 of these patients were on DPP4i and 31 of these patients were on GLP1-RA. The mean age (SD) of PV/BP patients was 72 (11) years compared to an average age of 66 (10) years in patients who did not develop PV/BP. Patients were also found to be predominately white (77.9%). Factors associated with increased risk of BP were use of DPP4i (Odds Ratio [OR] 1.90, 95% confidence interval [95% CI: 1.14-3.47, p=&lt;0.01), and older age (OR: 1.07, 95%CI: 1.04-1.09, p&lt;0.01). Use of GLP1-RA or DPP4i was not associated with PV incidence. (OR: 1.31, 95% CI: 0.65-2.62, p=&lt;0.45). Conclusion: In conclusion, our study supports existing literature that DPP4i use is associated with an increased risk of developing BP. Our data does not find association with GLP-1 agonists nor DPP4 inhibitors in increasing the risk of PV.
Presentation: 6/3/2024
7148 Fake Fingerstick: Artifactual Hypoglycemia in a Hospitalized patient with Systemic Sclerosis
Authors: Shteyman S , Mirza F 
Published: October 2024

Abstract
Disclosure: S. Shteyman: None. F. Mirza: None.
Introduction: Artifactual hypoglycemia is a problem in hospitalized patients. It often leads to unnecessary use of resources and creates anxiety for the patient and medical team. We describe a case of a 60-year-old female with history of systemic sclerosis (Raynaud, telangiectasias, esophageal dysmotility, interstitial lung disease, pulmonary hypertension), rheumatoid arthritis, autoimmune hepatitis and hypothyroidism who initially presented to the hospital emergency department with bilateral lower extremity radiculopathy, and new onset urine incontinence. She underwent spine surgery initially, followed by emergent left upper extremity thrombectomy two days later. Postoperatively, she was noted to have fingerstick glucose of 34 mg/dL. Dextrose and juice were given, and endocrinology service was consulted. The patient was monitored with 2 hourly fingerstick glucose and was noted to have frequent hypoglycemia on fingerstick monitoring. Serum glucose in AM labs was consistently within normal limits. Patient denied both adrenergic and neuroglycopenic symptoms during periods of “hypoglycemia”. She was asked to fast till fingerstick glucose was noted to be at 43 mg/dl, when blood was drawn for serum glucose, insulin, proinsulin, C-peptide, B-hydroxybutyric acid, IGF-2, insulin AB, and sulfonylurea panel, prior to giving her any dextrose. She was asymptomatic at the time. All labs were within normal limits, with serum glucose at 119 mg/dL. At that point, artifactual hypoglycemia was suspected. Serum glucose was checked twice again when fingerstick glucose was noted to be &lt;45mg/dL, and corresponding serum glucose was noted to be normal at both times (&gt;100 mg/dL). Decision of artifactual hypoglycemia was made and fingerstick glucose monitoring was discontinued in this non-diabetic patient, with recommendation to check serum glucose only if symptoms of hypoglycemia occur, as fingerstick glucose values were not reliable. Fasting serum glucose continued to be normal for the remainder of the hospitalization. Discussion: There have been a handful cases of artifactual hypoglycemia reported in patients with CREST, systemic sclerosis, and Raynaud’s disease. It is thought to be due to abnormal small vasculature causing delayed transit of blood through capillaries, and increased uptake of glucose into the interstitial tissue. Some recommend using earlobe sticks as a replacement for fingerstick glucose monitoring in these patients. Future research can explore if continuous glucose monitoring can be used reliably in these patients.
Presentation: 6/1/2024