bluuebunny/crossref_metadata_2025_split huggingface dataset:
8093 The Interplay Between Hypertriglyceridemia And Pancreatogenic Diabetes Mellitus
Authors: Tselovalnikova Tatiana , Bhattacharya Rajib Kumar , Drees Betty M , Tan Ngo Emmeline Monique 
Published: October 2024

Abstract
Disclosure: T. Tselovalnikova: None. R.K. Bhattacharya: None. B.M. Drees: None. E.T. Ngo: None.
Severe hypertriglyceridemia may induce acute pancreatitis with subsequent development of ketosis-prone pancreatogenic diabetes. This presentation is rare. We present a case of a 36-year-old female referred to our clinic for management of diabetes mellitus. At the age of 12 years, her menarche coincided with an episode of acute pancreatitis (AP) in the setting of severe hypertriglyceridemia, as well as diabetic ketoacidosis (DKA). No other causes of AP were identified - no cholecystitis, no alcohol use, no illicit substance abuse. Family history of dyslipidemia or diabetes is unclear. She was managed with insulin for hypertriglyceridemia-induced pancreatitis as well as DKA. She developed significant insulin resistance, along with elevated BMI (30.25 kg/m2), and was subsequently diagnosed with polycystic ovary syndrome, requiring metformin. Autoimmune antibodies for type 1 diabetes mellitus were all negative. Sequence analysis of the HNF1A, HNF4A, and GCK genes did not identify any sequence variants associated with maturity-onset diabetes in the young. Her diabetes has been poorly controlled with HgbA1c as high as 14.4%. Management has been complicated by non-adherence. She subsequently developed diabetic proliferative retinopathy with vitreal hemorrhages, diabetic nephropathy, and diabetic neuropathy complicated by osteomyelitis with right toe amputation. She continued to have severe hypertriglyceridemia up to 8,216 mg/dL (reference range: 0-150) associated with numerous episodes of AP with concomitant DKA, prompting frequent hospitalizations. She does not have any xanthomas or lipodystrophy on examination. No genetic testing to confirm familial causes of hypertriglyceridemia was performed as yet. There is no pre-existing cardiac conditions. She is being managed with insulin glargine, insulin aspart, metformin, pancrelipase, fenofibrate, atorvastatin, and omega-3 polyunsaturated fatty acid; however, her triglyceride level remains high at 5,353 mg/dL and diabetes remains uncontrolled with most recent HbA1c of 9%. Given the timeline of presentation in this patient, a physiological increase in estrogen level may aggravate pre-existing common or familial forms of severe hypertriglyceridemia, causing chylomicron buildup, eventually leading to recurrent pancreatitis. The manifestation of diabetes with DKA along with severe hypertriglyceridemia-induced pancreatitis is rare. Uncontrolled hypertriglyceridemia leads to frequent pancreatitis exacerbations, resulting in chronic pancreatitis and eventual overlap of pancreatogenic (Type 3c) diabetes and insulin resistance.
Presentation: 6/1/2024
8254 The Risk Of Thrombotic Complications In Patients With Post-COVID Syndrome Is High Even With Normal Coagulogram Values
Authors: ALIEVA Anna 
Published: October 2024

Abstract
Disclosure: A. Alieva: None.
The high risk of thrombotic complications in patients with diabetes, even more increased in the post-Covid period, requires practicing physicians to be especially vigilant and carefully monitor the state of the hemostatic system and the function of the vascular endothelium. Routine laboratory tests may be insufficient for dynamic monitoring and timely detection of abnormalities. In this article, the author proposes the determination of cell adhesion molecules as a predictor of thrombotic complications in patients with type 2 diabetes mellitus in the post-Covid period. In our current study, VCAM-1 levels were elevated in all patients with type 2 diabetes within 24 months of COVID-19 infection and were not associated with increased von Willebrand factor or D-dimer or other coagulation abnormalities. This means that routine determination of coagulogram, D-dimer and von Willebrand factor may miss the stage of prothrombotic changes in the microvasculature. It is possible that an increase in the level of cell adhesion molecules precedes the appearance of other abnormalities in the hemostasiogram. Therefore, for patients with type 2 diabetes after a coronavirus infection with normal coagulogram values, it seems promising to determine the level of VCAM-1 molecules to prevent the occurrence of thrombotic complications. In addition, monitoring this indicator may be useful in determining the effectiveness of preventive therapy.
Presentation: 6/3/2024
9366 The Rnf20 Histone Modifier Is A Crucial Mediator Of Pancreatic Beta Cell Identity And Function
Authors: Pierre Tanya Hans , Liu Yanping , Bethea Maigen Michelle , Coutinho Kristen , Hunter Chad 
Published: October 2024

Abstract
Disclosure: T.H. Pierre: None. Y. Liu: None. M.M. Bethea: None. K. Coutinho: None. C. Hunter: None.
Diabetes is characterized by the loss of pancreatic β-cell mass. As diabetes incidence continues to elevate, it is critical that we develop a better understanding of the factors that define functional β-cells in order to improve current therapeutics. One approach is through the study of transcription factors (TFs), which are essential for β-cell development and function. Prior work from our lab and others has examined Islet-1 (Isl1) a LIM-homeodomain TF that is required for the maturation of the endocrine pancreas and adult β-cell function. We have also extensively characterized several Isl1-interacting co-regulators (e.g., Ldb1 and SSBP3) that facilitate its roles in maintaining glucose homeostasis. Most recently, we have identified that Isl1 interacts with the ubiquitin ligases Ring Finger 20 (Rnf20) and Rnf40, whose histone H2B monoubiquitation (H2Bub1) activity support the gene regulatory functions of Isl1. With in vitro experiments, we demonstrated that Rnf20 and Rnf40 are important for glucose stimulated insulin secretion (GSIS) and mediate the expression of β-cell identity genes. Based on these findings, we hypothesize that Isl1-Rnf complexes modify histones to regulate β-cell gene expression and function. To address this hypothesis in vivo, we developed an adult inducible β-cell knockout of Rnf20 (Rnf20Δβ-cell). Rnf20Δβ-cell mice display fasting hyperglycemia and severe glucose intolerance that is driven by impaired GSIS, reduced insulin content, and the dysregulation of critical β-cell genes including Ins1, Ucn3, and Slc2a2. Additionally, loss of Rnf20 perturbs insulin processing and overall β-cell maturation as observed by measurement of proinsulin:insulin ratios, C-peptide levels, and whole islet RNA-seq. Phenotypes exhibited by Rnf20Δβ-cell mice are similar to those observed in Isl1 β-cell knockout mice, and comparative transcriptomics revealed an overlap of 570 genes involved in metabolism, zinc homeostasis, and islet proliferation including Slc30a8 and Matn2, both of which we found are occupied by Isl1 and Rnf20. Collectively, our findings demonstrate the importance of the Rnf20 histone modifier in regulating β-cell function and expand our understanding of the Isl1 regulatory network.
Presentation: 6/2/2024
7880 The Role Of PTHrP In Glucose Metabolism And Insulin Secretion
Authors: Max-Harry I M , Kantake N , Nunemaker C S , Rosol T J 
Published: October 2024

Abstract
Disclosure: I.M. Max-Harry: None. N. Kantake: None. C.S. Nunemaker: None. T.J. Rosol: None.
Insulin and glucagon are the two most important hormones for blood glucose homeostasis. Identifying the key players in their regulation will contribute greatly towards combatting types 1 and 2 diabetes. Parathyroid Hormone-related protein (PTHrP), a protein expressed by pancreatic beta cells, has been implicated in various developmental and physiological roles, but particularly, PTHrP increases beta-cell proliferation and insulin secretion in pancreatic islets. Incubating mouse pancreatic islets and Min6 cells with 10nM exogenous PTHrP showed a significant increase in both insulin secretion (for islets, PTHrP: 865.4ng/ml ± 77.66, con: 498.5ng/ml ± 40.63, p=0.024, n=4) and glucagon secretion (PTHrP: 20.87pmol/l ± 3.776, con: 8.798pmol/l ± 1.616, p= 0.068, n=3) after 24hours. In order to further investigate the effects observed, min6 cells were transiently transfected to overexpress PTHrP, and a glucose-stimulated insulin secretion (GSIS) assay was carried out with 2mM and 20mM glucose. The results showed a reduction in basal insulin secretion at 2mM glucose and an increase in insulin secretion at 20mM glucose for the PTHrP transfected cells. PTHrP improved the stimulation index of Min6 cells (PTHrP: 2.279 ± 0.2056, con: 1.659 ± 0.1386, p= 0.03, n=6) and enhanced their sensitivity to glucose. Preliminary proliferation assays showed that cells transfected with PTHrP have increased proliferation and a protection from cell death when incubated in serum-free media. This study, in addition to our previously published research showing that a lack of intact PTHrP leads to islet dysfunction, revealed that PTHrP may be crucial to appropriate glucose sensitivity of beta cells. Further studies are being carried out to understand the mechanism behind these effects and the genes/proteins involved in the regulation of insulin secretion by PTHrP.
Presentation: 6/1/2024
12246 The Stage-Dependent Transcriptome And Methylome Reveal Significance Of The Neonatal Period In Postnatal Metabolic Maturation Of The Mouse Liver
Authors: Yano Seiichi , Sato Naoichi , Araki Hiromitsu , Miura Fumihito , Ito Takashi , Ogawa Yoshihiro 
Published: October 2024

Abstract
Disclosure: S. Yano: None. N. Sato: None. H. Araki: None. F. Miura: None. T. Ito: None. Y. Ogawa: None.
The mammalian liver serves as an extramedullary hematopoietic organ during the fetus and matures into a metabolic organ after birth, adapting to changes in the nutritional environment. DNA demethylation upregulates fatty acid β-oxidation (FAO) genes in the postnatal mouse liver to produce energy from breast milk lipids. However, the detailed interactions between DNA methylation (DNAme) and gene expression through the perinatal stages remain poorly understood. Here, we perform an integrative analysis of the transcriptome and methylome of the mouse liver at the fetal, neonatal, and postweaning stages. We found a drastic loss of DNAme at the neonatal stage in specific regions associated with metabolic pathways such as FAO and gluconeogenesis in concordance with the activation of metabolic processes. Moreover, in silico analysis predicted transcription factors including HNF4α, PPARα, and NR1H2 as key epigenetic regulators within the neonatal period. We also observed an inactivation of erythrocyte development with a concordant gain of DNAme. This analysis extends the epigenetic landscape of postnatal hepatic maturation, suggesting the importance of the nutritional environment during the neonatal period for epigenetic regulation.
Presentation: 6/3/2024
5176 Time In Range Preferred Over A1c And Fructosamine To Monitor Glycemic Control In Sickle Cell Disease
Authors: Patel Anjani , Simon Barbara 
Published: October 2024

Abstract
Disclosure: A. Patel: None. B. Simon: None.
Introduction: In sickle cell disease, hemoglobin A1c is unreliable due to anemia, hemolysis, transfusions, and increased red blood cell turnover. In this population, plasma glucose should be used to make a diagnosis of diabetes, but there are no reliable long-term measures of glycemic control. Measures of serum protein glycation such as fructosamine are often used as markers of short-term control[1]. Continuous glucose monitoring (CGM) time in range (TIR) may offer another more reliable metric of control in this population2. Case: A 58-year-old male presented to the office for uncontrolled type 2 diabetes mellitus. His medical history included sickle cell anemia (Hb SS disease), hypertension, monoclonal gammopathy, and priapism. He was diagnosed with type 2 diabetes mellitus approximately one year prior based on a fructosamine level of 470 umol/L (0-285 umol/L) and elevated fasting glucose level of 128 mg/dL. He started metformin 500 mg daily. Three months later, repeat fructosamine was 401 umol/L, and metformin was increased. Months later, fructosamine levels remained elevated at 419 umol/L; metformin was increased to 2 grams daily and he was referred to endocrinology. The patient was given a CGM (Freestyle Libre 2 system, Abbott Diabetes Care) as an additional method to assess control. CGM showed an excellent 2-week TIR (70-180mg/ dL) of 98%. Repeat fructosamine after 2 weeks of CGM wear was elevated at 500 umol/L. It was hypothesized that the history of IgG kappa monoclonal gammopathy was falsely elevating his fructosamine level. A glycated albumin level was 13.5% (10.7-13.5%). The patient was advised to discontinue his metformin. Four months later, his glycated albumin remained in range, and a 2-week TIR was 100%. Discussion: This case demonstrates how sickle cell disease and monoclonal gammopathy affect laboratory values typically used to diagnose and monitor type 2 diabetes. Fructosamine, a measure of non-enzymatic glycation of serum proteins, is non-specific2. Increased protein from monoclonal gammopathy (giving more protein glycation sites) was the probable cause of the persistently elevated fructosamine, leading to overtreatment of what may not have been a true diagnosis of diabetes. This case also demonstrates the value of CGM, with glucose values and TIR indicating near normoglycemia. Diagnostic CGM may be a useful measure of glucose control in patients with hemoglobinopathies. References: 1. Danese E. et al. Advantages and pitfalls of fructosamine and glycated albumin in the diagnosis and treatment of diabetes. Journal of Diabetes Science and Technology. 2015;9(2):169–176. 2. Beck, RW. et al. The Fallacy of Average: How Using HbA1c Alone to Assess Glycemic Control Can Be Misleading. Diabetes Care 2017; 40: 994–999.
Presentation: 6/1/2024
6978 Traumatic Presentation Of A Pancreatic Neuroendocrine Tumor
Authors: Kahn C J , Mai J , Cabrera A E , Anderson A D , Huynh D H 
Published: October 2024

Abstract
Disclosure: C.J. Kahn: None. J. Mai: None. A.E. Cabrera: None. A.D. Anderson: None. D.H. Huynh: None.
Background: Insulinomas are a subset of functional pancreatic neuroendocrine tumors associated with neuroglycopenic symptoms, fasting hypoglycemia, and rapid resolution of symptoms with glucose administration. Despite this classic presentation, patients often spend years undiagnosed before formal diagnosis and definitive management. Clinical Case: We report the case of a 37-year-old post-partum female with a history of gestational diabetes who presented to our trauma center after losing consciousness while driving and colliding with a utility pole. Emergency Medical Services reported seizure-like activity on the scene with altered sensorium. Her initial blood glucose level of 32 mg/dL improved to 100 mg/dL after 100 ml of 10% dextrose. Initial biochemical analysis obtained from the trauma bay demonstrated a negative serum ethanol level, negative urine toxicology and sulfonylurea level, and elevated C-peptide of 6.71 ng/mL. After stabilization, she underwent a 72-hour fasting test. At the 12-hour mark, she developed hypoglycemia (blood glucose 36 mg/dL) correlated with elevated insulin (28.8 mU/L), proinsulin (173.1 pmol/L), and C-peptide (7.86 ng/mL). Although an initial CT scan of the abdomen and pelvis did not demonstrate any pancreatic abnormalities, an abdominal MRI demonstrated a 13 mm lesion in the tail of the pancreas consistent with a pancreatic neuroendocrine tumor. She subsequently underwent a laparoscopic distal pancreatectomy during the same hospital admission and recovered expeditiously. Final pathology demonstrated a 10 by 15 mm, grade two, well-differentiated neuroendocrine tumor with negative margins. The specimen stained strongly positive for synaptophysin and chromogranin, consistent with the clinical diagnosis of insulinoma. During the patient's postoperative recovery, she had no further episodes of hypoglycemia and did not require insulin for post-pancreatectomy hyperglycemia. She was discharged home with a glucometer and a follow-up scheduled with endocrinology and general surgery. Conclusion: The presentation of patients with insulinomas can vary from vague, nonspecific symptoms to altered levels of consciousness placing patients in potentially lethal situations. Moreover, the insulin resistance experienced by pregnant patients may mask clinical manifestations of hypoglycemia during the peripartum period, making diagnosis more elusive for this population. A high index of suspicion along with prompt diagnosis, in this case, led to definitive surgical management, effectively preventing future traumatic incidents secondary to hypoglycemia. Reference: 1. Dobrindt EM, Mogl M, Goretzki PE, Pratschke J, Dukaczewska AK. Insulinoma in pregnancy (a case presentation and systematic review of the literature). Rare Tumors. 2021;13. doi:10.1177/2036361320986647
Presentation: 6/3/2024
7936 Type 1 Diabetes Therapeutic Compound MSB-61: Using RNA Sequencing To Identify The Mechanism
Authors: Khan Palwasha , Corbin Kathryn , Ajmal Nida , Bergmeir Stephen , Gu Guoqiang , Tong Xin , Nunemaker Craig Stuart 
Published: October 2024

Abstract
Disclosure: P. Khan: None. K. Corbin: None. N. Ajmal: None. S. Bergmeir: None. G. Gu: None. X. Tong: None. C.S. Nunemaker: None.
Abstract Type 1 diabetes (T1D) is a chronic autoimmune disease in which loss of insulin-producing beta-cells leads to hyperglycemia due to which patients eventually require lifelong insulin therapy to maintain normal glycemic control. Insulin remains the gold standard and the only effective treatment for T1D since its discovery 100 years ago. Protecting the pancreatic beta cells from cytokine-induced cell death and restoring insulin secretion are important to treat T1D, two properties that are currently lacking in present therapies. Our lab identified a chemical compound MSB-61 that increases insulin release and protects pancreatic islets against T1D-associated cytokines and endoplasmic reticulum (ER) stress. This study aims to identify the mechanism of action of MSB-61 in protecting pancreatic islets from ER stress-induced cell death. To achieve this aim pancreatic islets obtained from CD-1 strain mice were exposed for one hour to 50uM MSB-61 or vehicle control. After treatment, RNA was collected for RNA sequencing. In addition to RNA extraction for sequencing, MSB-61's ability to secrete insulin was verified by performing ELISA on control,10 and 50uM MSB-61-treated islets, and the activity of protection from cell death was assessed by performing cell death assay on islets treated with ER stressors in the presence and absence of 10 and 50uM MSB-61. Using Genialis, a bioinformatics service, we evaluated 57,010 genes (including non-coding transcripts) in our RNA sequencing data set. The DESeq2 technique of data analysis allowed us to identify 350 differentially expressed genes (DEGs), of which 251 were upregulated and 74 were downregulated. After removing non-coding/undefined transcripts and genes with &lt;5 counts per million, a total of 117 genes remained; 108 up and 9 down. According to the String database (string-db.org), many of the top DEGs formed a common network of genes associated with cell death protection and insulin secretion. A key component of that gene network is a stress-responsive orphan nuclear receptor with known protective effects in beta cells. Testing this orphan nuclear receptor as a possible direct or indirect target of MSB-61 for cell death prevention can aid in identifying the genes and pathways targeted by MSB-61, allowing us to improve our approaches to T1D treatment and develop better medications.
Presentation: 6/3/2024
9179 Type 2 Diabetes Alters Metabolic Fuel Selection During Intermittent Fasting
Authors: Conn Meghan O , Marko Daniel M , Schertzer Jonathan D 
Published: October 2024

Abstract
Disclosure: M.O. Conn: None. D.M. Marko: None. J.D. Schertzer: None.
Type 2 Diabetes Alters Metabolic Fuel Selection During Intermittent Fasting Diabetes is characterized by elevated blood glucose resulting from defective insulin secretion and/or insulin resistance. Intermittent fasting, a popular weight loss strategy involving periodic reduction of caloric intake, can improve glycemia. Fasting shifts metabolism from carbohydrates to free fatty acids and ketones. However, high blood insulin can inhibit lipolysis and alter metabolic substrate selection in prediabetes, resulting in muscle catabolism to maintain energy homeostasis. Clinical studies have observed a significant decrease in muscle mass in subjects with obesity and diabetes. Our research aims to characterize lean mass versus fat loss after intermittent fasting in a mouse model of obesity and type 2 diabetes (T2D) and investigate the role of muscle alanine catabolism. We hypothesized that intermittent fasting would promote less lipolysis and more muscle alanine catabolism, causing more muscle loss in diabetic mice than controls. We compared male db/db mice manifesting obesity, hyperglycemia, and hyperinsulinemia to age-matched db/+ (control) mice. Our lab established a 5:2 repeated fasting protocol of ad-libitum access to food for 5 days a week and 2 days of fasting on non-consecutive days. Blood glucose was monitored weekly in fed and fasted states to assess glycemic control. While intermittent fasting lowered fasted blood glucose in both groups, no significant body weight or metabolic tissue mass changes were observed. Metabolic cage data demonstrated increased reliance on fat-based substrates for energy in control mice that underwent intermittent fasting during feeding and fasting periods. Diabetic mice did not show significant changes in the fasted state, but intermittent fasting led to increased reliance on carbohydrate oxidation during re-feeding periods, indicating impaired metabolic flexibility. After 10 weeks, the mice were sacrificed, and metabolic tissue histology (adipose, liver, skeletal muscle) will be performed. We will also analyze serum markers (alanine, fatty acids, glycerol, glucose, insulin) and the activity of the metabolic enzyme alanine transaminase (ALT) in the muscle and liver. This experiment will improve our understanding of how lipolysis and protein breakdown in muscle regulate lean mass versus fat mass loss in obesity and T2D, leading to more effective tailoring of fasting to specific populations.
Presentation: 6/3/2024
12619 Unraveling The Complexity Of Autoimmune Polyglandular Syndrome
Authors: Syed Usheem , Fretes Oviedo Natalia Elizabeth , Kraus-Horbal Cecilia E 
Published: October 2024

Abstract
Disclosure: U. Syed: None. N.E. Fretes Oviedo: None.
Background: Autoimmune polyglandular syndromes (APS) are polyendocrinopathies characterized by autoimmune dysfunction of multiple endocrine organs. APS remains a challenging yet frequently undiagnosed entity in clinical practice, characterized by the coexistence of multiple autoimmune endocrine disorders. Clinical Case: Presented here is the case of a 37-year-old female initially diagnosed with T1DM at age thirteen, subsequently developing primary adrenal insufficiency in her 20s, along with Graves' disease managed with radioiodine ablation and later Hashimoto thyroiditis requiring levothyroxine therapy. The patient's clinical presentation underscores the challenge of managing hypoglycemic episodes in the setting of APS, where multiple autoimmune endocrine disorders converge. Additionally, gastrointestinal symptoms prompted screening for celiac disease, yielding negative results. Family screening revealed her daughter's diagnosis of diabetes mellitus, emphasizing the familial predisposition to autoimmune endocrine abnormalities. Conclusion: This case underscores the importance of comprehensive screening for APS in patients with T1DM, autoimmune thyroid disease, or adrenal insufficiency, as they may harbor multiple autoimmune conditions. Early recognition and management are imperative to mitigate the risk of complications. Furthermore, familial screening should be considered to identify at-risk relatives, facilitating early intervention, and reducing morbidity associated with APS.
Presentation: 6/3/2024