bluuebunny/crossref_metadata_2025_split huggingface dataset:
8193 Mauriac Syndrome Uncovered, The Insulin Access Impact in Type 1 Diabetes Mellitus
Authors: Sacoto Daniel Hernan , Belokovskaya Regina , Gebran Karim , Madani Kulsum , De Rosairo Anne , Patel Dhara , Franco-Akel Alberto A 
Published: October 2024

Abstract
Disclosure: D.H. Sacoto: None. R. Belokovskaya: None. K. Gebran: None. K. Madani: None. A. De Rosairo: None. D. Patel: None. A.A. Franco-Akel: None.
Introduction: Mauriac syndrome is a rare complication of poorly controlled type 1 diabetes mellitus (T1DM). It is reversible with appropriate glycemic control; however, factors affecting healthcare access to insulin are leading to its re-emergence. We present a case of Mauriac syndrome as a complication of uncontrolled T1DM due to insulin access. Case: A 22-year-old Hispanic female with a history of T1DM presented to the emergency department with a two-day history of abdominal pain. She was diagnosed with diabetic ketoacidosis (DKA) (blood glucose: 802 mg/dL; pH 7.14; bicarbonate: 7 mmol/L; anion gap: 34; positive serum ketones). Incidental transaminitis was noted. R factor showed a cholestatic pattern of 0.6 (AST: 136 U/L, ALT: 49 U/L, alkaline phosphatase:286 U/L). US liver revealed an enlarged liver (craniocaudal: 16.5 cm) without biliary obstruction. Her phenotype consisted of short stature (4.8 feet) with a moon face and a protuberant abdomen. Her records revealed a normal karyotype 46 XX, with a bone age of 4 years, pubertal delay, low insulin-like growth factor-1 levels (58 ng/mL), and long-standing hyperlipidemia. Over the years, she experienced multiple DKA episodes in the context of uncontrolled T1DM (hemoglobin A1c:11-13 %). The main problem identified included difficulty with insulin access, specifically related to insurance coverage as well as managing her disease. Glycemic control has significantly improved with continuous glucose monitoring and updated insurance status. Discussion: Mauriac syndrome is characterized by hepatomegaly, transaminitis, delayed pubertal maturation, growth failure, and cushingoid features. Hyperglycemia leads to intrahepatic glycogen deposition and the lack of insulin to lipolysis and ketosis, leading to high cortisol levels and growth delay. Factors leading to uncontrolled T1DM include lack of insulin access. The high cost is considered a major barrier, with an average price per millimeter of insulin tripled from 231 to 736 US dollars. Even patients with insurance tend to have high co-pays and deductibles, with a 61% chance of delay or denial due to pre-approval requirements. Lower socioeconomic status, lack of access to devices such as insulin pumps, migratory status, social support, and ethnic background are other factors related to glycemic control. Our patient belongs to a family of immigrants with low socioeconomic status, which might have contributed to the development of Mauriac syndrome. Since clinical and laboratory abnormalities are reversible with appropriate glycemic control, advocating for policies that facilitate better insulin access is paramount.
Presentation: 6/2/2024
8182 New Mouse Model Mirrors Human MODY8: Opening Doors to Understanding Exocrine-Endocrine Crosstalk in the Diabetic Pancreas
Authors: Jellas Khadija El , Salerno Valeria , Katz Liora S , Hu Jiang , Fogarty Garrett , Mandal Ankita , DiStefano-Forti Ava , Scott Donald , Lowe Mark , Molven Anders , Kulkarni Rohit N 
Published: October 2024

Abstract
Disclosure: K. El Jellas: None. V. Salerno: None. L.S. Katz: None. J. Hu: None. G. Fogarty: None. A. Mandal: None. A. DiStefano-Forti: None. D. Scott: None. M. Lowe: None. A. Molven: None. R.N. Kulkarni: None.
Maturity-onset diabetes of the young, type 8 (MODY8) is a dominantly inherited form of monogenic diabetes, caused by heterozygous mutations in the carboxyl ester lipase (CEL) gene expressed in pancreatic acinar cells. MODY8 is characterized by chronic pancreatitis and exocrine dysfunction. Despite the intimate anatomical relationship between the endocrine and exocrine pancreas, little is known about the biological components mediating exocrine-endocrine communication in regulating glucose homeostasis. Here, we report a refined mouse model that bears the mutation present in MODY8 patients on one allele, and the humanized normal variable number of tandem repeat (VNTR) of CEL with 16 repeats (16R) on the other, mimicking the genetic make-up seen in MODY8 patients. Examination of glucose homeostasis revealed that inducing stress (e.g. by high-fat diet) leads to glucose intolerance in MODY8/16R mice and a blunted glucose-stimulated insulin-secretion compared to their control littermates. Histopathological analyses demonstrated features of chronic pancreatitis in some pancreatic lobes, including inflammation, acinar atrophy, acinar-to-ductal metaplasia, fibrosis and fat infiltration, mirroring the morphology of the human disease. Moreover, we applied immunolabeling-enabled three-dimensional imaging of solvent-cleared organs (iDISCO) to intact pancreata and found that beta-cell mass was significantly decreased in the MODY8/16R mice, with a large number of islets located within fatty lobes. These results are coupled with comparative proteomics and lipidomic profiling with the aim of understanding the molecular signatures of exocrine and endocrine cells during pathogenesis. In conclusion, we have generated a mouse that recapitulates several features of the exocrine and endocrine phenotype characteristic of human MODY8. This novel model provides a unique opportunity, not possible in humans, to characterize pancreatic endocrine-exocrine communication in a longitudinal manner as a response to diverse environmental stressors.
Presentation: 6/2/2024
6370 New-Onset Autoimmune Diabetes Following COVID-19 Infection and its Implications for Identical Twin Siblings
Authors: Wintermyer Gelareh , Gillis-Funderburk Sheri 
Published: October 2024

Abstract
Disclosure: G. Wintermyer: None. S. Gillis-Funderburk: None.
COVID-19 patients face many post-recovery complications,including autoimmune disorders. Late autoimmune diabetes ofadults (LADA) is one such disorder. Studies suggest that SARS-CoV may trigger proinflammatory cytokines that damage beta cellsand impair insulin secretion. Here, we explore a case of new-onsetLADA in a patient after recovery from COVID-19. Further, asidentical twins of LADA patients have a higher risk of developingit, we discuss how we approached the patient’s identical twin.A 29-year-old female with history of obesity (BMI 32.3) presentedto our endocrinology clinic. She complained of difficulty losingweight and fatigue and reported having COVID-19 three monthsearlier. She also mentioned having polyuria. She underwent labtests, including CBC, CMP, TSH, A1C, and a lipid panel. The testresults were within normal limits, except for her A1C of 11.3%.She was started on metformin and weekly Semaglutide injections.Given her recent COVID-19 history, she was assessed for LADA.Anti-GAD-65 and ZNT8 antibodies were 120 U/mL and 150U/mL, respectively. Serum C-peptide and IA-antibodies werewithin normal ranges. The patient informed us of her twin sister’sconcurrent COVID-19 infection. Due to the risk of LADA in hertwin sister, we recommended an evaluation by our clinic. Duringthe sister’s first visit, her BMI was 37.5, and she asked for weightloss medication. Comprehensive testing, including LADAantibodies, was conducted, with results within normal ranges andA1C level of 4.9%. The sister was also started on Semaglutide forweight management.The patient had quarterly follow-up appointments at the clinic.After a year, her A1C and continuous glucose monitoring machine(CGM) readings showed improvement. Her BMI decreased to 24.She never required insulin therapy, as her diabetes was well-managed and her average monthly glucose level on GCM readings were 125, 123 and 119 mg/dL in three different periods. Antibodieswere retested. This time IA-2 antibody was also elevated.Similarly, her twin sister continued to follow-up at our clinic. Thesister achieved significant weight loss without complications. HerLADA antibodies remained negative, and her A1C remainednormal. Clinicians should be vigilant for post-COVID LADA. In this case,Semaglutide aided weight loss, which benefits diabetesmanagement. Ongoing studies explore the potential of GLP-1medications in early-stage LADA. Historically, LADA patientswere started on insulin. However, CGM has enabled close glucosemonitoring, offering management of LADA with non-insulinmedications. It is also important to remember that autoimmunedisease risk is elevated in identical twins. In this case, although thetwin sister did not develop antibodies, the risk remains. Regularevaluation of high-risk patients is crucial for early detection ofantibodies, facilitating timely treatment to prevent adverseoutcomes.
Presentation: 6/3/2024
8813 Nivolumab-Induced Diabetes: A Hidden Danger
Authors: Case James , Chemitiganti Ramachandra Rahul V , Suravajjala Devi 
Published: October 2024

Abstract
Disclosure: J. Case: None. R.V. Chemitiganti: None. D. Suravajjala: None.
Immunomodulating therapy as utilized in chemotherapy for malignancy may lead to potential adverse events including immune-related adverse events(IRAEs). One such pathway by which this may occur is through alteration of the programmed cell death as affected by drugs such as nivolumab which inhibits appropriate matching of PD-1 and PD-L1 and may lead to a robust immune response with collateral damage to nontumor tissue. Multiple downstream effects may be seen leading to other pathologies including development of autoimmune diabetes as noted in the patient described herein. A 61 year old female presented to establish care for suspected type one diabetes mellitus. She had a history of renal cell cancer diagnosed about one year prior for which she was treated with nivolumab. She was found to have hyperglycemia on routine labwork with further labwork revealing inappropriately low c-peptide as measured at less than 0.10 ng/mL (0.8-3.85ng/mL) with a coincident glucose of 566mg/dL (74-106mg/dL). Further workup revealed no measurable presence of GAD65, antipancreatic islet cell or ZNT8 antibodies. Diagnosis was made of insulinopenic diabetes or otherwise autoimmune diabetes induced as an IRAE subsequent nivolumab use. She was subsequently started on a basal bolus regimen with insulin achieving blood glucose control. IRAEs are an unfortunate, albeit rare consequence of immune checkpoint inhibitors including nivolumab. Depending on the toxicity grade and prognosis the offending agent may be discontinued and steroids initiated to mitigate adverse effects. However sometimes the occurrence of an IRAE may go undetected until too late as noted in the above patient. Her presentation was atypical considering many present with DKA and as well IRAEs are less likely in monotherapy. Education of IRAEs as well as appropriate screening would aid in recognition of potential IRAEs at which time appropriate measures may be taken to alleviate collateral damage. Further elucidation of the mechanism by which this autoimmune response is activated against nontumor tissue may also lead to better understanding of autoimmune diabetes caused by other etiologies.
Presentation: 6/2/2024
8262 Non-insulinoma pancreatogenous hypoglycemia syndrome (NIPHS) after gastric sleeve surgery
Authors: Thomas Renu Eugene , Charales Ashley , Bangash Bushra , Haider Syed Basit , Ouais Samir , Ali Zuhair 
Published: October 2024

Abstract
Disclosure: R.E. Thomas: None. A. Charales: None. B. Bangash: None. S. Haider: None. S. Ouais: None.
Introduction: Non-insulinoma pancreatogenous hypoglycemia syndrome (NIPHS) is a rare condition characterized by endogenous hyperinsulinemic hypoglycemia after meals. This article explores NIPHS, emphasizing its occurrence post-gastric sleeve surgery. We delve into clinical features, diagnosis, treatment, and challenges, using a case presentation to illustrate complexities.Clinical Features and Classification:NIPHS entails endogenous hyperinsulinemic hypoglycemia without islet cell neoplasms, featuring islet cell hypertrophy. Formerly "Nesidioblastosis," post-RYGB cases constitute a distinct diagnosis. Common features include postprandial hyperinsulinemic hypoglycemia, negative radiologic localization, and a positive calcium stimulation test.Patients present postprandial hypoglycemia 2-4 hours after meals, with symptoms like tachycardia, tremors, confusion, and occasional seizures. Lab findings include elevated insulin, C peptide, and pro-insulin, low beta-hydroxybutyrate, and negative sulfonylurea/meglitinide screen.Diagnostic Workup:Evaluate glucose, insulin, pro-insulin, C peptide, beta-hydroxybutyrate, and sulfonylurea/meglitinide. Ultrasound differentiates insulinoma from diffuse processes. If negative, conduct SACST for localization.Case Presentation:A 37-year-old female post-gastric sleeve surgery presented with severe hypoglycemia. Symptoms included confusion, nausea, and palpitations, occurring postprandially, relieved by food or juice. Glucagon was administered, and consultations sought. Diazoxide stabilized blood glucose.Treatment Modalities:Dietary modifications reduce free carbohydrate intake, spaced meals minimize hyperinsulinemic episodes. Medical management (octreotide, verapamil, diazoxide, acarbose) proves effective, especially post-gastric bypass. Sub-total pancreatectomy is considered in severe refractory cases.Multidisciplinary Approach:Management involves endocrinologists, surgeons, radiologists, and dietitians. Regular monitoring assesses efficacy, adjusts medications, and addresses complications. Challenges and Future Perspectives: NIPHS complexities include variable presentation and diagnostic challenges. Research should refine criteria, explore interventions, and understand pathophysiology. Conclusion: Non-insulinoma pancreatogenous hypoglycemia syndrome, especially post-gastric sleeve surgery, presents complexities. This exploration highlights clinical aspects, diagnostics, and management challenges, emphasizing the need for a multidisciplinary approach. Continued research aims to enhance diagnostic precision and improve outcomes for those affected by this intriguing syndrome.
Presentation: 6/3/2024
7260 Nuclear Corepressor 1 (NCoR1) plays important role in the regulation of insulin gene transcription in mouse Min6 pancreatic beta cells
Authors: Shimizu Hiroaki , Horibata Yasuhiro , Amano Izuki , Ritter Megan J , Ohyama Masahide , Domae Mariko , Sugimoto Hiroyuki , Hollenberg Anthony Neil 
Published: October 2024

Abstract
Disclosure: H. Shimizu: None. Y. Horibata: None. I. Amano: None. M.J. Ritter: None. M. Ohyama: None. M. Domae: None. H. Sugimoto: None. A.N. Hollenberg: None.
Background: Nuclear Corepressor 1 (NCoR1) is a transcriptional corepressor which has been recognized as an important player in the regulation of hepatic lipogenesis and hematopoiesis in mouse embryo. NCoR1 is also widely expressed in mouse insulin sensitive organs, for instance adipocyte, skeletal muscle, and hepatocytes. Mouse genetic deletion strategies of either NCoR1 or SMRT(NCoR2; an ortholog corepressor of NCoR1) demonstrated that each corepressor effects the insulin sensitivity in the tissues. However, the role of each corepressor in pancreatic beta cell is not still elucidated. Methods: To clarify this, we took the gene-targeting strategy for NCoR1 using CRISPR Cas-9 and made the pancreatic beta Min6 clone which lacks NCoR1 protein (Min6-NCoR1KO; NKO cells). For this study, wild type Min6 cells (WT) and NKO cells were cultured in the Dulbecco's DMEM medium with 10% fetal bovine serum for 4-5 days, and the expression analyses compared between two cell types were performed. Results: Both comprehensive proteomics and following expression analyses compared between WT and NKO cells demonstrated that NKO cells have significantly lower expression level of insulin (INS-1 and INS-2), accompanied with high expression of histone deacetylase 6 (HDAC6). For further analyses, we also made the Min6 clone which lacks SMRT(Min6-SMRTKO; SKO cells). Interestingly, SKO cell had higher insulin and lower HDAC6 levels, accompanied with significant up-regulation of NCoR1. Conclusion: Taken together, these data indicate that NCoR1 has dominant effects in the regulation of both histone deacetylation and insulin gene transcription in Min6 cells. Further investigations for the function of NCoR1 in the insulin gene transcription observed in Min6 cells will be needed.
Presentation: 6/2/2024
9185 Pembrolizumab-Induced New-Onset Type 1 Diabetes Mellitus: A Case Report
Authors: Teng David , Connelly Tessa L , Ahmad Mobeen , Saeed Rehan 
Published: October 2024

Abstract
Disclosure: D. Teng: None. T.L. Connelly: None. M. Ahmad: None. R. Saeed: None.
Introduction: Immune checkpoint inhibitors are becoming essential in the treatment of various cancers. Pembrolizumab is a monoclonal antibody that binds PD-1 receptors, thereby enabling an anti-tumor response by preventing T-cell suppression. Common side effects associated with pembrolizumab include thyroid disorders, hepatitis, pneumonitis, and acute kidney injury, among others. We describe an interesting case of a woman presenting with diabetic ketoacidosis (DKA) in the setting of pembrolizumab-associated new-onset type 1 diabetes mellitus, which was reported at 0.1% during initial clinical trials but is now being increasingly recognized as a complication of immune checkpoint therapy. Case Description: The patient is a 70-year-old female with past medical history notable for stage IIIA vulvar squamous cell carcinoma initially diagnosed and treated in 2017, with recurrence in 2022 and in 2023, at which point pembrolizumab therapy was initiated. Approximately one month after her first dose, the patient presented to the emergency department with palpitations, nausea, non-bloody vomiting, polydipsia, and non-bloody diarrhea. On arrival, the patient’s vital signs were as follows: 97.2 °F, BP 128/74 mmHg, heart rate 80 bpm, respiratory rate 18 per minute, and SpO2 100% on room air. No acute findings were noted on physical exam. Initial blood work was notable for: pH 7.146, lactate 2.4 mmol/L, bicarbonate 8 mmol/L, anion gap 37 mmol/L, creatinine 1.59 mg/dL, glucose 563 mg/dL, C-peptide 0.16 ng/mL, HbA1c 6.9%, and WBC 18.8 B/L with neutrophilic predominance. Urinalysis was notable for 4+ glucose and 4+ ketones. The patient was admitted to the progressive care unit and DKA protocol was initiated including the administration of IV fluids, insulin infusion, and electrolyte replacement. Additional blood work was unrevealing, including insulin autoantibodies &lt;0.4 U/mL, negative islet cell IgG cytoplasmic autoantibodies, and negative anti-GAD65 antibodies. The patient was eventually discharged with outpatient Endocrinology follow-up. Discussion: Immunotherapy is quickly redefining the standard of care in the treatment of several types of malignancies through the leveraging of the body’s immune defense apparatus. Pembrolizumab prevents the deactivation of T-cells via the PD-1/PD-L1 pathway. Unfortunately, this also predisposes non-cancerous cells to autoimmune destruction by these T-cells. It is proposed that such is the mechanism by which pancreatic beta islet cells are destroyed in the setting of pembrolizumab use, thereby resulting in a rapid reduction in insulin production capability. New-onset type 1 diabetes complicated by DKA is potentially life-threatening, and so we believe this case highlights the need for both pre-treatment counseling as well as follow-up screening following initiation of pembrolizumab therapy.
Presentation: 6/2/2024
8241 Post-Covid complications in patients with diabetes mellitus are high during 24 month after acute infection
Authors: Alieva Anna 
Published: October 2024

Abstract
Disclosure: A. Alieva: None.
The consequences of coronavirus infection in patients with diabetes have not been fully studied. The purpose of the work was to study post-Covid complications in patients with diabetes. Materials and methods. We examined 188 patients with diabetes mellitus who had a coronavirus infection in 2020 and applied to the RSSPMCE clinic for inpatient treatment within 1-24 months after the acute period of viral infection. The criteria for inclusion in the study were: the presence of type 2 diabetes mellitus (DM), diagnosed before 2020, a history of COVID-19 infection confirmed by PCR. Exclusion criteria were pregnancy and diabetes diagnosed in 2020 and later. Results and discussion. An increase in D-dimer levels was observed at 0-3, 7-9 and 19-24 months, which was accompanied by an increase in von Willebrand factor at 4-9 months and thrombosis at 4-6 months after COVID-19. The period of 4-6 months after coronavirus infection was also characterized by an increase in inflammatory markers and the development of purulent complications. The progression of polyneuropathy was noted during the first 6 months after COVID-19; for periods of 6-12 months, the development of vasculitis was typical. In the periods of 1-3 months and 10-24 months after COVID-19, cases of the development of newly registered hypertension were observed. Conclusion. Patients with type 2 diabetes mellitus for 2 years after coronavirus infection remain at risk of developing thrombotic complications, new-onset arterial hypertension and accelerated progression of chronic complications of diabetes mellitus, which requires careful targeted monitoring of such patients.
Presentation: 6/3/2024