bluuebunny/crossref_metadata_2025_split huggingface dataset:
7799 Nesidioblastosis Concurrent with Anatomically Confirmed Metastatic Gastric Cancer
Authors: Cho Y , Jo K , Han J H , Moon S d , Kim E 
Published: October 2024

Abstract
Disclosure: Y. Cho: None. K. Jo: None. J. Han: None. S. Moon: None. E. Kim: None.
Background: Nesidioblastosis is a rare condition that should be considered in cases of pancreatogenic hyperinsulinemic hypoglycemia without evidence of insulinoma on imaging. We present the first case of nesidioblastosis concomitant with anatomically confirmed metastatic gastric cancer of the pancreas. Case Report A 57-year-old male presented with recurrent episodes of loss of consciousness and hypoglycemia, with a glucose level of 26 mg/dl upon arrival at the emergency room. Despite a history of advanced gastric cancer and previous chemotherapy, the patient had not been diagnosed with diabetes and was not taking medications associated with hypoglycemia. Four months prior, he underwent total gastrectomy. The fasting plasma glucose levels was 38 mg/dl, accompanied by C-peptide levels of 6.10 ng/mL, insulin levels exceeding 1000 uIU/ml, and proinsulin levels at 8.8 pmol/L. The insulin antibody level was more than 100%, and the highest cortisol level reached 15.60 ug/dL during the rapid ACTH stimulation test. The patient's postprandial 2-hour glucose level reached 233 mg/dl during the 75g glucose tolerance test. Imaging studies, including whole-body PET CT and abdominal CT, showed no evidence of suspected metastatic lesions, and the pancreas appeared normal on MRI. Endoscopic ultrasound could not be performed due to anatomical changes following the surgery. A selective arterial calcium stimulation test demonstrated a substantial over twofold increase in insulin concentrations in the gastroduodenal artery, splenic artery, and superior mesenteric artery. The patient received methylprednisolone 125 mg once daily but insulin levels remained elevated, exceeding 1000 uIU/ml, requiring continuous dextrose infusion. Octreotide therapy was initiated, resulting in an improvement in insulin levels to 589 uIU/ml, although discontinuation of dextrose fluid remained unfeasible. After consultation with the surgeon, a open subtotal pancreatectomy was performed, allowing discontinuation of dextrose on the second post-surgery day, with improved glucose and insulin levels. Histological examination showed three clusters of atypical cells with perineural infiltration. Immunostaining indicated negative synaptophysin and positive CK20, suggesting possible gastric cancer metastasis, consistent with prior gastrectomy findings. Moreover, an increased number of variable-sized Langerhans islets exhibited positive insulin and glucagon immunostaining within the islets, indicative of nesidioblastosis. Conclusion: Nesidioblastosis should be considered in cases of unexplained post-surgery hypoglycemia following metastatic gastric cancer treatment. Furthermore, given the potential link with metastatic gastric cancer, which may elude detection via imaging alone, aggressive surgical intervention should be contemplated as a nesidioblastosis treatment strategy.
Presentation: 6/3/2024
6984 New Onset Diabetes After Transplant: Need for Strict Glucose Monitoring
Authors: Chaudhary Taibah , Syed Omar , Nawaz Maria , Kaur Ravleen , Iqbal Aimen , Deck Charles 
Published: October 2024

Abstract
Disclosure: T. Chaudhary: None. O. Syed: None. M. Nawaz: None. R. Kaur: None.
Introduction: Immunosuppressant use comes at a cost of challenging side effects, which are being discovered more as its use increases. One such example is our case of new-onset diabetes after transplant (NODAT).Patient presentation: A 36-year-old male with a past medical history of end-stage renal disease status post renal transplant (6/2023), hypertension, and hyperlipidemia who presented to the hospital in 10/2023 with fever, chills, and diarrhea. His vitals at that time were as follows: temperature 36.1C, blood pressure 148/84 mmHg, pulse 87 bpm, and a respiratory rate of 22. Lab work was significant for blood glucose 1144, anion gap 22, bicarbonate 13, potassium 7.3, Sodium 135, lipase 427, pH 7.3, urine ketones 80, HbA1C 11.5 %. CT scan of the abdomen revealed loss of peripancreatic fat and inflammatory changes surrounding the pancreas. His medication review included Tacrolimus 12 mg daily, Mycophenolate 500 mg BID, Valtrex 500mg daily, and fluconazole 200mg every other day. He was treated with 2 liters of normal saline bolus and started on maintenance fluid, and insulin drip as per DKA protocol. Calcium gluconate and an albuterol nebulizer were given for hyperkalemia. Tacrolimus and prednisone were held. Endocrinology and Nephrology were consulted. The patient was thought to have diabetes due to steroid use which were discontinued and the patient was discharged on subcutaneous insulin regimen and lower dose of tacrolimus. Despite discontinuation of steroids, patients continued to have raised glucose readings confirming the causative agent as tacrolimus. Conclusion: The current guidelines for post-kidney transplant patients recommend checking fasting blood glucose weekly for the first four weeks, then biweekly for two months, and then monthly thereafter. HbA1C should be checked every 3 months and if it is &gt;6% then home glucose monitoring should be done as well. Although the frequency of these check-ups decreases, it is imperative for physicians to remember that patients can still develop NODAT months post-transplant. It is also essential to reinforce the importance of these glucose checks for the patient as missed diagnosis can lead to dangerous complications such as DKA.
Presentation: 6/2/2024
7431 Non-Insulin Treatment of Type 1 Diabetes Mellitus: The Power of GLP-1 and GLP-1/GIP RA
Authors: Ferri-Guerra J , Kasper-Guerra E , Abdulhussein O , Madrigal Loria G , Ambalavanan J , Zhou K 
Published: October 2024

Abstract
Disclosure: J. Ferri-Guerra: None. E. Kasper-Guerra: None. O. Abdulhussein: None. G. Madrigal Loria: None. J. Ambalavanan: None. K. Zhou: None.
Background: Insulin is the mainstay of treatment of patients with type 1 diabetes mellitus (T1D). However, patients with T1D can also potentially benefit from adjunctive therapies such as GLP-1 receptor agonists or GLP-1/GIP receptor agonists, especially when obesity and elevated cardiovascular risk are present. Case 1: A 64-year-old male with severe coronary artery disease requiring revascularization and obesity with T1D has been wearing a pump for insulin delivery since the age of 43, started on closed loop system Control IQ with Tandem in April 2022. In December 2022, patient had myocardial infarction. At that time, Hba1c was elevated at 7.6% and BMI was elevated at 32.5 kg/m2, and patient was considered a good candidate for tirzepatide, which was prescribed. The tirzepatide dose was slowly increased, up to 10 mg weekly. The new therapy resulted in loss of 17 kg (20.1% decrease of body weight) with only some mild nausea. There was an improvement in HbA1c to 7.1% and a dramatic reduction in daily average insulin use from 90 units to 52 units. Case 2: A 59-year-old female with obesity and T1D diagnosed at the age of 8 had been wearing insulin pump, Medtronic 670G in manual mode, for insulin delivery for the past few years with poor glycemic control. In August 2021, patient was prescribed semaglutide for post prandial hyperglycemia and obesity management (BMI at 31.6kg/m2). Since being on the medication, she lost 12kg (16.8% decrease in body weight), despite being on the lowest dose of 0.25 mg (maximum tolerated). Her HbA1c has improved from 8.2% when therapy was initiated, to 7% with just the introduction of semaglutide to her insulin regimen. Conclusion: Although insulin is a required therapy for patients with T1D, adjunctive therapies may improve glycemic control, reduce insulin requirements and promote weight loss. GLP-1 and dual GLP-1/GIP receptor agonists should be considered for these patients.
Presentation: 6/1/2024
7187 Non-islet Cell Tumor Hypoglycemia in a Patient With Metastatic Renal Cell Carcinoma
Authors: Bao Ginny W , Yin Anthony Y 
Published: October 2024

Abstract
Disclosure: G.W. Bao: None. A.Y. Yin: None.
We report a rare case of non-islet cell tumor hypoglycemia (NICTH) in a patient with metastatic renal cell carcinoma. NICTH is a paraneoplastic syndrome due to increased production of an incompletely processed form of insulin-like growth factor 2 (“big IGF-2”). It requires a high-level of suspicion for diagnosis and is challenging to manage. Our patient is a 69 year old gentleman with a history of deceased donor renal transplant in 1994 and 2008. He was diagnosed with renal cell carcinoma (RCC) metastatic to bone, lymph nodes, and lungs, which was initially treated with cabozantinib, later switched to lenvatinib and everolimus due to disease progression. On admission, he presented with anasarca and weakness. He had recurrent fasting hypoglycemia associated with confusion and lethargy. The lowest serum glucose was 28 mg/dL. He was also diagnosed with primary hypothyroidism (TSH 25.1 uIU/mL and free T4 0.31 ng/dL), suspected to be due to tyrosine kinase inhibitor therapy. Levothyroxine was initiated. Cosyntropin stimulation resulted in a post-stimulation cortisol of 7 ug/dL, although this was felt not to be reliably diagnostic of adrenal insufficiency in the setting of profound hypoalbuminemia. IGF-1 and IGF-2 were 16 ng/mL and 388 ng/mL, respectively; IGF-2: IGF-1 ratio was 24.3. He was treated with intravenous dextrose and prednisone 30mg daily with stabilization of glucoses for a few days. On hospital day 19, he acutely decompensated and passed away shortly after being transitioned to comfort-focused care. Non-diabetic hypoglycemia is relatively uncommon, and may be seen in patients with liver disease, sepsis, adrenal insufficiency, and malignancy. We report a case of NICTH in a patient with metastatic RCC, which is a particularly rare cause of hypoglycemia. NICTH is due to tumor production of “big IGF-2”, a precursor of IGF-2, which mimics the effects of insulin and causes fasting hypoglycemia. NICTH is more commonly associated with mesenchymal and epithelial tumors such as fibromas, fibrosarcomas, and hepatocellular carcinomas. NICTH due to RCC appears to be a much more rare entity, with as few as four cases reported in the literature. Laboratory findings of NICTH include low insulin, pro-insulin, C-peptide, and β-hydroxybutyrate during hypoglycemia. An IGF-2: IGF-1 ratio &gt;10 is considered virtually diagnostic. Surgical excision is curative, although often delayed or not feasible, and patients frequently require intravenous dextrose. High-dose steroids (ie, prednisone 30-60mg daily) can be used, which promotes “big IGF-2” clearance. NICTH is likely under-recognized in patients with advanced malignancies. This diagnosis should be considered in those with refractory hypoglycemia, although management is challenging if tumor control cannot be achieved.
Presentation: 6/1/2024
8538 Pancreatic Islet Adaptations to Hyperglycemia Are Prevented by Glycolytic Inhibition and Amplified by Inhibiting Membrane Depolarization
Authors: Whitticar N B , List B P , Bruce N , Bertram R , Nunemaker C S 
Published: October 2024

Abstract
Disclosure: N.B. Whitticar: None. B.P. List: None. N. Bruce: None. R. Bertram: None. C.S. Nunemaker: None.
Long before type 2 diabetes ensues, pancreatic islets undergo functional changes to compensate for increasing insulin resistance. Primarily, the islets increase their ability to secrete insulin by augmenting the glucose-stimulated insulin secretion (GSIS) pathway. As metabolic syndrome worsens, islets become functionally exhausted, leading to cellular dysfunction and apoptosis. To avoid the negative consequences of this compensatory response, various steps of the GSIS pathway can be attenuated to restore normal functional levels before the islets fail. Determining which inhibitors can prevent the earliest adaptations to hyperglycemia may reveal the processes that play a causal role in islet failure. The chemicals mannoheptulose (MH), diazoxide (DZ), and nifedipine (NP) were chosen to inhibit the glucokinase enzyme, KATP-channel closure, and voltage-gated calcium channels, respectively. CD-1 mouse islets were placed in 20 mM glucose to simulate hyperglycemia along with a concentration of each inhibitory drug that reduced insulin secretion by 30-40%. After 48-hour treatment, glucose-stimulated calcium tests were performed to determine if the treatments could prevent the negative adaptation to hyperglycemia. Only islets treated with MH to reduce glycolytic activity maintained a normal calcium response. Islets in the MH group also retained a strong insulin response to glucose and were not depleted of insulin content. Unexpectedly, inhibition of calcium influx and insulin secretion with DZ or NF caused a substantial increase in basal insulin secretion compared to islets in standard culture (P&lt;0.01, n=6; P=0.06, n=6, respectively). These results indicate that the signaling pathway that causes the adaptation to hyperglycemia lies upstream of KATP channels and downstream of glucokinase. Mathematical modeling using the Integrated Oscillator Model was able to replicate our results and suggests that high rates of glycolytic and mitochondrial metabolism are associated with the signal that adapts islets to hyperglycemia, and that reducing intracellular calcium in the face of high glucose further increases basal insulin secretion. Ongoing studies will determine if metabolic acceleration or altered membrane conductance are responsible for the earliest islet adaptations to hyperglycemia. Our results suggest that reducing metabolic activity, but not calcium influx, prevents adaptations to hyperglycemia in mouse islets. These findings can be applied to potentially prevent the progression of obesity and hyperinsulinemia into type 2 diabetes.
Presentation: 6/2/2024
8330 Pancreatic neurons in neuron-islet complexes and activation of these neurons promotes insulin secretion under high glucose level
Authors: Liu Y , Yang Z , Feng Q , Hu M , Sha L 
Published: October 2024

Abstract
Disclosure: Y. Liu: None. Z. Yang: None. Q. Feng: None. M. Hu: None. L. Sha: None.
Islets are rich in pancreatic nerve innervation. Pancreatic ganglionic neurons, as an integrating center, receive central and peripheral nerve innervation regulating endocrine and exocrine of pancreas. Neurons in pancreatic ganglia have been studied intensely in our lab and a few other labs. Neurons located in islets forming neuron-islet complexes have been demonstrated. However, the properties and function of these neurons has not been studied. In this study, pancreatic neurons in the neuron-islet complex and the effects of activation of these neurons on insulin release were investigated. Methods: Eight week old rats were used. Pancreas was digested and a method was developed to identify neuron-islet complexes from islets. Results: CHAT and TUBB3 were co-localized in nearly all neurons in the neuron-islet complex indicating that these neurons were mainly cholinergic neurons. A small portion (&lt;10%) of TUBB3 positive cells were also positive for nNOS. Nicotinic tartrate was used to activate neurons in the complexes. After one hour of administration of nicotinic tartrate, with 5.6 mM glucose, ACh level was increased significantly from 15.26±5.46 μM to 23.24±4.18 μM and insulin level were slightly increased from 37.21±2.04 μM to 39.27±1.23μM (P &gt; 0.05). With 16.7 mM glucose, ACh level were increased significantly from 23.83±2.28 μM to 30.92±1.03 μM and insulin increased significantly from 41.93±1.30 μM to 49.04±1.68 μM. Conclusion: The neurons in neuron-islet complexes are mainly cholinergic neurons and activation of these neuron under high glucose level stimulate insulin secretion.
Presentation: 6/2/2024
9337 Postprandial And “Fasting” Hypoglycemia In A Patient With A History Of Gastric Bypass Surgery And Carcinoid Syndrome
Authors: Ntelis Spyridon , Pennant Marjorie 
Published: October 2024

Abstract
Disclosure: S. Ntelis: None. M. Pennant: None.
Background: Hypoglycemia is an increasingly recognized complication of bariatric surgery that can occur years after the procedure. Episodes most commonly occur 1-3 hours after meals. Fasting hypoglycemia is not typical and raises concerns for other etiologies, including adrenal insufficiency and other causes of endogenous hyperinsulinism. Clinical Case: A 51-year-old woman with a history of carcinoid tumor of unknown origin with liver metastases, treated with monthly octreotide injections, and history of Roux-en-Y gastric bypass presented with multiple episodes of symptomatic hypoglycemia up to 24 mg/dl. Symptoms included tremor and diaphoresis and improved with juice. Morning cortisol was 22.7 mcg/dL (n &gt; 19.4 mc/dL), ruling out adrenal insufficiency. A continuous glucose monitor (CGM) was placed, and she was advised to have frequent low-carbohydrate meals mixed with healthy fats and protein. She was also advised to add cornstarch to meals, until mixed-meal testing could be performed. She was hospitalized for a seizure provoked by hypoglycemia after a heavy high-carbohydrate meal, and treatment with acarbose 25 mg three times daily was started. Mixed-meal testing was consistent with post-prandial hyper-insulinemic hypoglycemia, with elevated insulin (58 mcIU/ml, n: 2.6-24.9 mcIU/ml) and c-peptide (11.2 ng/ml, n: 1.1-4.4 ng/ml) levels during an episode of symptomatic hypoglycemia (glucose 22 mg/dL) 2.5 hours after the patient’s meal. CGM showed hypoglycemia mostly occurring after meals and some episodes of hypoglycemia early in the morning, that occurred after late-night snacks. Clinical picture and laboratory testing were suggestive of post-bariatric surgery hypoglycemia. Poor hepatic glycogen reserve, secondary to the liver metastases, was considered a contributing factor. Interestingly, although hypoglycemia was mediated by hyperinsulinemia, treatment with a somatostatin analogue provided no benefit. The frequency of hypoglycemia decreased with adherence to a low-carbohydrate diet, and episodes mostly occurred when acarbose use was delayed. Octreotide was transitioned to lantreotide. Due to persistence of early-morning low glucose values on follow-up, further work-up was pursued to rule out etiologies of fasting hypoglycemia. Glucose values remained &gt;70 mg/dl during 72 hours of fasting. IGF-I (115 ng/ml, n: 53-287 ng/ml) and IGF-II (608 ng/ml, n: 267-616 ng/ml) levels were normal, and insulin antibodies were undetectable. Post-bariatric surgery hypoglycemia was confirmed and acarbose dose was increased to 50 mg three times daily. Conclusion: Postprandial hypoglycemia is a late complication of bariatric surgery. Early-morning hypoglycemia can also be seen after bariatric surgery in patients who have late-night meals and snacks.
Presentation: 6/1/2024
9253 Prediabetes As A Risk Factor For All-Cause And Cause-Specific Mortality In 117,227 Diabetes-Free Adults In Mexico City
Authors: Fermin-Martinez Carlos Alberto , Bello-Chavolla Omar Yaxmehen , Antonio-Villa Neftali Eduardo , Garcia Daniel Ramirez , Seiglie Jacqueline A 
Published: October 2024

Abstract
Disclosure: C.A. Fermin-Martinez: None. O.Y. Bello-Chavolla: None. N.E. Antonio-Villa: None. D. Ramirez Garcia: None. J.A. Seiglie: None.
Background: Prediabetes has been consistently linked to high risk of diabetes progression, cardiovascular disease, and all-cause mortality. However, no large-scale studies have been conducted in Mexico or Latin America examining these associations despite the growing prevalence of this condition in low- and middle-income countries. Methods: We analyzed data from 117,227 adults without diabetes aged ≥35 years who participated in the Mexico City Prospective Study (1998-2004). Individuals with self-reported chronic comorbidities at baseline were excluded to mitigate reverse causation. Participants were followed-up until January 1st, 2021 for cause-specific mortality. We defined prediabetes according to the American Diabetes Association (ADA, HbA1c ≥5.7%) and the International Expert Committee (IEC, HbA1c ≥6.0%) definitions. Cox regressions were used to estimate prediabetes-related risk for all-cause and cause-specific mortality, stratified by sex and age-at-risk and adjusted for municipality of residence, education level, physical activity, smoking, alcohol consumption, and adiposity markers. Results: Compared to individuals with normoglycemia, participants with IEC-defined prediabetes had a higher risk of all-cause (HR 1.16, 95%CI 1.05-1.27), cardiac (HR 1.29, 95%CI 1.05-1.59), renal (HR 1.59, 95%CI 1.14-2.23), and acute diabetes-related (HR 2.60, 95%CI 1.52-4.43) mortality at ages 40-74 years compared to normoglycemic participants. HRs were attenuated at older ages. Results were broadly similar irrespective of the definition of prediabetes except for cardiac deaths, in which the risk was non-significant using the ADA cutoff (HR 1.14, 95%CI 0.99-1.31). Long-term effects of prediabetes (IEC-defined) accounted for ∼37% of renal deaths and ∼61% of acute diabetes-related deaths in Mexican adults without diabetes at baseline. Conclusion: Prediabetes is an important risk factor that accounts for a significant fraction of all-cause, cardiac, renal, and acute diabetes-related deaths among Mexican adults, particularly when using the higher threshold of IEC-defined prediabetes. Endpoint-driven definitions of prediabetes should be considered for widespread implementation of screening and preventive strategies that minimize overdiagnosis and improve cardiometabolic outcomes in this population.
Presentation: 6/1/2024