Glucose Levels Research Articles

7975 TLR4 Signaling Modulates Reproductive and Metabolic Outcomes in a Mouse Model of Polycystic Ovary Syndrome

Abstract Disclosure: K.D. Wiggins: None. Z. Del Mundo: None. J.A. Ayala Angulo: None. M. Lopez: None. C. Garcia: None. C. Nguyen: None. J. De La Torre: None. A. Saba: None. D. Trinh: None. D. Nicholas: None. Polycystic Ovarian Syndrome (PCOS), characterized by disruptions in both reproductive and metabolic functions, is associated with abnormal immune system activity and chronic inflammation. Although the precise mechanistic drivers of chronic inflammation in PCOS are not fully elucidated, elevated serum levels of lipopolysaccharide (LPS) have been observed. We propose that Toll-like receptor 4 (TLR4) signaling, influenced by dysregulated LPS levels, is a central driver of chronic inflammation affecting both reproductive and metabolic pathways. To investigate this hypothesis, we subcutaneously implanted a nonsteroidal aromatase inhibitor, Letrozole (LET), in pubertal TLR4 knockout mice (TLR4KO) and C57BL/6J (wild type) mice. Our five-week LET treatment revealed that TLR4KO mice successfully entered all phases of the estrous cycle, with normalized Luteinizing Hormone (LH) and increased Follicle Stimulating Hormone (FSH) levels. These findings highlight TLR4's role in shaping cycling patterns and regulating fundamental hormonal pathways vital for reproductive health. Despite the genetic manipulation of the inflammatory pathway leading to a reduction in overall body weight gain, it had no discernible impact on the overall body composition of fat and lean mass. Additionally, our study found that dysregulation of blood glucose levels over time was independent of reduced body weight. TLR4KO mice demonstrated inefficient glucose clearance compared to wild-type mice, hinting at potential increases in insulin resistance, imbalances in adipose tissue inflammation, or possible alterations in the gut microbiota. Our study underscores the significance of disrupting the pro-inflammatory TLR4 pathway in shaping the reproductive and metabolic phenotypes in Letrozole-induced PCOS. The investigation into TLR4 becomes pivotal for comprehending the role of chronic inflammation in PCOS development or progression, offering valuable insights into potential therapeutic targets. Presentation: 6/2/2024

12288 Diabetes Wearable Technology In Children Less Than Six Years At A Large Urban Diabetes Center

Abstract Disclosure: K. Citron-Zafrin: None. L. Richter: None. K. Williams: None. R. Gandica: None. I. Vargas: None. N. Leibel: None. Introduction/Background: Type 1 diabetes (T1D) is one of the most common chronic diseases in pediatrics. T1D is particularly challenging to manage in children under 6 years old due to unpredictable eating patterns, rapid growth, and risk of extreme blood glucose levels. Diabetes wearable technology (insulin pumps and continuous glucose monitors (CGMs)) has become increasingly prominent, but its use has not been well described in this age group. Objectives: We sought to characterize our experience with technology use in children with T1D less than 6 years old. Design/Methods: Retrospective chart review of 82 youth diagnosed with T1D before 6 years old, seen at our center from 2019-2023. Data was collected on demographic information, insurance type, use of insulin pump and CGM, hemoglobin A1c (A1c), diabetic ketoacidosis (DKA) and hypoglycemic events. We used chi-square statistics to compare variables in our population with reported national data. Results: In this cohort, 80% used insulin pumps and 100% used CGMs, an increase from previously reported data (56% insulin pump use and 44% CGM use in those less than 6yo, p<0.001). 54% had private insurance. There were more individuals with family members with T1D compared to reported data (35% vs. 22%, p=0.0041). The median age at diagnosis was 34 months, median time from diagnosis to pump start was 3.5 months. After diagnosis, 1 pump user and 1 multiple daily injections (MDI) user had DKA. One MDI user had hypoglycemia requiring intervention. Average A1C 12 months after diagnosis was 7.9% in the pump group and 8.2% in the MDI group. Hybrid closed loop pump users had an average A1C 6 months after placement of 7.7%. Conclusions: At our urban academic diabetes center, there was higher use of diabetes wearable technology as compared with previously reported data in this age group. There were more individuals with relatives with T1D compared to reported averages. The low rates of DKA and hypoglycemic events seen in this population support that these technologies can be used safely and soon after diagnosis. Although improved from national data, tight glycemic control remains a challenge in this very young age group. Presentation: 6/1/2024

8481 A 32 Year Old Male With Recurrent Acute Pancreatits and Severe Hypertriglyceridemia: Importance of Considering Genetic Variants

Abstract Disclosure: M.F. Salazar Zelaya: None. J.D. Sibaja Jiménez: None. Background : Hypertriglyceridemia is a common medical scenario in daily practice, causing a variety of symptoms including recurrent episodes of acute pancreatits, which can be severe. Multiple genetic variants can lead to different spectrums of the disease. CLINICAL CASE: A 32 year old male police officer presented to our Endocrinology Outpatient Clinic with a history of long standing hypertriglyceridemia and six previous episodes of acute pancreatits, two in the last twelve months. Familiy history was negative for lipid disorders. The patient had adecuate adherence to diet and exercise as well to prescribed medications, which included Fenofibrate 250 mgs/day and Rosuvastatin 40 mgs/day. The patient denied consumption of alcoholic beverages. Recent abdominal ultrasound was reported without abnormalities. His lipid panel reported elevated triglycerides at 5831 mg/dl (n<150 mg/dl), Total Cholesterol normal at 147 (n<200 mg/dl), low HDL levels at 12 mg/dl (range 12-92 mg/dl) and direct LDL Cholesterol at 120 mg/dl. His TSH value was normal at 1.02 uUI/mL (range 0.55-4.78 uUI/mL). Creatinine level was normal at 0.81 mg/dl (range 0.7-1.3 mg/dl). Liver function tests were normal with AST level at 25 IU/L (range 13-39 IU/L) ALT levels at 22 IU/L (range 7-52 IU/L) and alcaline phosphatase at 62 IU/L (range 34-104 IU/L).His fasting glucose level were normal at 82 mg/dl (n<100 mg/dl). Due to a high Familial Chylomicronemia Syndrome clinical score (13 points) we proceeded with genetic analysis of this patient. Next Generation Sequencing for genes related with chylomicronemia (APOA5, APOC2, GPIHBP1,LMFI, LPL) was performed to determine gene sequence plus copy number variation.Two heterocigote variants were reported, both in the LPL gene. The first one: LPL (NM 000237.3) c.644>A;p.Gly215Glu heterozygous is a missense variant already reported in the literature, registered in ClinVar (ID 1522) and the Leiden Open Variation Database. This variant is classified as pathogenic according to criteria PS3, PM1, PP3, PP5 of the American College of Medical Genetics and Genomics. The second one: LPL (nm 000237.3): c.383C>A;p.Thr128Asn;heterozygous is also a missense variant which to the extent of our knowledge has previously been reported only once in the literature: ClinVar (ID 1520537). This variant is classified currently as of unknown clinical significance according to PM2 criteria. There is however and entry reported (PMID: 8778602) of another variant affecting the same codon (p.Thr128AIa) that is associated to chylomicronemia syndrome. Conclusion: In cases of severe hypertriglyceridemia, suspicion and determination of gene variants are of great importance nowadays as they could eventually guide treatment, given the availability in some countries (and currently pending FDA approval) of new pharmacological therapies such as apo C-III inhibitors. Presentation: 6/2/2024

12491 Follow Up Of Glycemic Control In Patients Users Of Sensor Augmented Insulin Pump (sap) After Multi Dairy Injection (mdi) Or Change Of Technology

Abstract Disclosure: A. Medina: None. S. Tabares: None. C. Coronado: None. L. Burgos: None. A. Ely: None. Introduction: Sensor augmented insulin pump (SAP) is considered an efective therapy in type 1 diabetes (T1D) that combines continuous subcutaneous insulin infusion (CSII) with continuous glucose monitoring (CGM). A new metric of glycemic control is the time in range (TIR). More time in the expected range means less severe highs and lows. Objective: To describe glycemic control of a cohort of patients treated with multi-daily injection (MDI) or sensor-augmented insulin pump (SAP) VEO /640G who switched to a new therapy with 640G, 670G and 780G at 3 and 6 months. Methodology: A cohort study was analyzed with patients with T1D receiving SAP therapy in an university hospital. Patients with insulin therapy with MDI or SAP (VEO /640G) prior to SAP (670G /780G) were included and were followed up with glycemic control trough A1c, time in range (TIR), time in hypoglycemia and hyperglycemia, glycemic variability (GV) using continuous glucose monitoring (CGM) for 14 days, at 3 and 6 months after starting a new technology. Results: 40 patients were analyzed from 2022 to 2023, who attended check-ups every 3 months. The median age was 32 y and 65% were male. At baseline data, 40%, 22.5%, 37.5% were on MDI, VEO and 640G respectively, before changing therapy to 670G or 780G. The TIR increased by 97.6% of the patients and 75% reached the TIR (>70% between 70 and 180 mg/dl of glucose).Hypoglycemia decreased in 75% of patients, and of 27 patients in hyperglycemia, only 3, did not decrease glucose levels due to: lack of follow-up, sensor failure and misuse of the pump. In this cohort were included 12 patients in special conditions. The average initial GV was 37,2%, the normal being <36%, with an improvement at 3 and 6 months of 32,8 and 32,9%, respectively.The mean basal A1c was 7,32% . A1c decreased to 6,8 and 6,9% at 3 and 6 months after new therapy. Discusion: Regardless of the basal therapy (MDI, SAP), an improvement in TIR and A1c as measures of glycemic control is observed, as well as a decrease in the time in hypo and hyperglycemia and GV. The few patients who did not experience improvement had poor pump management, inappropriate carbohydrate counting, or poor adherence at checkups. Conclusion: SAP is an effective therapy in patients with (T1D) to reach metabolic goals, without increasing the rate of hypoglycemia. The most recent technologies in insulin pumps demonstrate better glycemic control. Presentation: 6/1/2024

7085 Myoclonus Seizure with Pseudo-Adrenal Insufficiency as the Clinical Manifestations Leading to the Diagnosed Multi-focal Insulinomas that Mimic Multiple Endocrine Neoplasia Type 1 Syndrome

Abstract Disclosure: P. Kiatpanabhikul: None. Background: Insulinoma is a rare disease that presents with varying symptoms and can be sporadic or associated with hereditary syndromes (1). These rare points of views of insulinoma-patient on clinical manifestations, hormonal responses and surgical pathology result for final diagnosis and management. Clinical Case: A 59-year-old woman presented with myoclonic seizure of right arm with consciousness duration 5-10 minutes every midday twice a week for 6 months and generalized convulsion for 20 minutes ago. She had a low FPG level (59 mg/dL; n 70-100) and was admitted to doing 72-hour fasting test that revealed hypoglycemia at 12-hour of fasting with a nadir glucose level of 55 mg/dL, insulin 3.7 uIU/mL (cutoff > 5), C-peptide 0.4 ng/mL (cutoff > 0.6), cortisol 6.22 mcg/dL (n 5-25) and normal morning ACTH level (29.8 pg/mL; n 10-65). These were appropriated response of endogenous insulinemia with inappropriate response of serum cortisol level in hypoglycemic feature. MRI pituitary gland was considered to evaluate secondary hypocortisolism which showed a small less enhancing lesion left anterior lobe 0.3x0.45-cm without any pituitary hormonal abnormalities that were considered non-functioning pituitary microadenoma which could not explain inappropriate response of cortisol level to hypoglycemic period in this patient. Five months later, she presented at the emergency room with myoclonic seizure on her extremities, blurred consciousness and slurred speech after having lunch for 1-2 hour and revealed CPG 30 mg%, severe hypoglycemia (26 mg/dL), hypocortisolism (4.49 mcg/dL), with endogenous hyperinsulinemia (insulin 55.2 uIU/mL, C-peptide 2.5 ng/mL). 250-mcg ACTH stimulation test was done and showed normal response of her HPA-axis function (serum cortisol level at 0, 30, 60 min was 9.12, 17.87, 18.61 mcg/dL). CT pancreatic protocol showed several arterial enhancing nodules scattering at pancreatic tails isoattenuation to pancreatic parenchyma on portovenous phase up to 1.7*1.6 cm. She was operated on to distal pancreatectomy with intraoperative insulin/glucose ratio monitoring. Surgical pathology confirmed 4-well-differentiated pancreatic neuroendocrine tumors with insulin-producing, sizes 0.5-1.7 cm in diameter. Her final diagnosis was multi-focal insulinomas with non-functioning pituitary microadenoma that mimic MEN-1 syndrome without secondary adrenal insufficiency. She underwent successful surgical resection with complete resolution of symptoms during 4 years of followed-up with no recurrence and no having any hypercalcemia and hyperprolactinemia. Conclusion: Multi-focal insulinomas can be presented as sporadic, more severe hypoglycemia and endogenous hyperinsulinemia during period after meal with myoclonic seizure and pseudo-adrenal insufficiency in older-aged, non-diabetes person without recurrence after treatment for 4-year of followed-up. Presentation: 6/2/2024

6660 Euglycemic DKA Induced by SGLT-2 Inhibitor Following Administration ofTirzepatide

Abstract Disclosure: K. Gurel: None. S. Mathew: None. M. Zeidan: None. S. Al Barznji: None. F. Alkhankan: None. Introduction Tirzepatide has side effects of diarrhea, nausea, vomiting, and loss of appetite(2). SGLT-2 inhibitors may cause Euglycemic Diabetic ketoacidosis(EDKA) by inducing carbohydrate starvation and volume depletion(1). Clinical Case A 72-year-old male with a past medical history of T2DM(Hg A1c 8.4[≤ 6%]) on empagliflozin, metformin, hyperlipidemia, obesity on tirzepatide who presents with complaining of nausea, vomiting, and abdominal pain. The patient noted that he started experiencing symptoms two days before admission following receiving tirzepatide dose. He takes Tirzepatide every 10 days and he was started on empagliflozin 1 month ago. The patient started to have a loss of appetite, nausea, and vomiting on the day he received his tirzepatide injection. Over the next two days, the patient’s nausea and vomiting worsened and the patient was not able to tolerate food. On admission, ABG demonstrated pure metabolic acidosis (pH of 7.24[7.30-7.40], bicarb of 11.8 [21 - 28 mmol/L] PCO2 of 27.4[ 41 - 51 mmHg]). BMP showed anion gap of 20(3-15 mmol/L) with glucose level of 145(74-106 mg/dl) . Beta-Hydroxybutyrate level was 6.3(0.0 -0.27 mmol/L). UA was only significant for glucose level of >1000(negative) and ketone level of 40(negative). Lipase level was 539(73-393 U/L). CT abdomen ruled out acute pancreatitis. No infection source was identified. Upon admission to the ICU unit, the patient was started on D5 with KCL 20 mEq and Insulin drip. The patient was followed up with a glucose check every hour and BMP every 4 hours. On day 2 of admission, the Anion gap was normalized and the insulin regimen was transitioned to subcutaneous insulin. The patient was placed on carbohydrate consistent diet. On discharge, the patient was advised to avoid taking SGLT-2 inhibitors including empagliflozin. Conclusion Tirzepatide's potential side effects, including diarrhea, vomiting, and appetite loss, may contribute to volume depletion and carbohydrate starvation(2). Individuals using both SGLT-2 inhibitors and Tirzepatide should be closely monitored for these symptoms. Reference 1-)Baggio LL, Drucker DJ. Glucagon-like peptide-1 receptor co-agonists for treating metabolic disease. Mol Metab. 2021 Apr;46:101090. doi: 10.1016/j.molmet.2020.101090. Epub 2020 Sep 25. PMID: 32987188; PMCID: PMC8085566. 2-)Plewa MC, Bryant M, King-Thiele R. Euglycemic Diabetic Ketoacidosis. [Updated 2023 Jan 29]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK554570/ Presentation: 6/2/2024

7788 Importance of Neuronal STAT3, but Not ERK2 or mTOR, for Pubertal Timing and Reproductive Activity in Mice

Abstract Disclosure: R.A. Lord: None. M.A. Inglis: None. G.M. Anderson: None. The adipose-derived hormone leptin is important for regulating reproduction. The canonical JAK2/STAT3 pathway is the best-characterised leptin receptor signalling pathway. Neural STAT3 deletion is known to cause obesity; however, its reproductive influence is less understood. This experiment investigated whether STAT3 knockout from brain neurons or AgRP neurons, a neuronal population necessary for normal pubertal timing and reproduction, would unveil the necessity of STAT3 in reproductive function. We also tested the role of ERK2 and mTOR, two alternative leptin signalling molecules.Transgenic mice with a neuronal knockout were created via the Cre-loxP system. CamKinaseIIα-Cre mice were crossed with STAT3, mTOR or ERK2 floxed mice. AgRP-Cre mice were crossed with STAT3 floxed mice for STAT3 knockout in AgRP neurons. All groups were compared to Cre-negative littermate controls (n=6-12/group). Puberty onset was assessed post-weaning by examining genitalia development. Reproductive cyclicity and organ weights were measured in adults. Metabolic effects were evaluated through body weight, abdominal fat and fasting glucose measurements. Brain tissue analysis evaluated cellular responses to leptin for STAT3, ERK2, and mTOR. Data presented as mean ± SEM.Mice with ERK2 KO or mTOR KO showed no reproductive or metabolic deficits compared to controls. In marked contrast, neuronal STAT3 KO mice showed significantly increased body weight by 5 weeks of age and a 6-fold increase in abdominal adiposity as adults (both p<0.001 using two-way ANOVA and Student’s t-test respectively) compared to controls. Males had a significant 5-day delay in age at preputial separation (KO: 32.1±2.09 d; Control: 26.8±0.45 d, p<0.01, Student’s t-test) while females had a significant 7-day delay in vaginal opening (KO: 33.0±1.85 d, Control: 26.6±0.37 d, p<0.05, Student’s t-test), a 9-day delay in first estrus (KO: 37.8±1.89 d; Control: 29.4±0.65 d, p<0.01, Student’s t-test) and pronounced acyclicity. Neuronal STAT3 KO mice also had a >2-fold elevation in fasting glucose levels (p<0.001, Student’s t-test) and regressed reproductive organs. Female mice with STAT3 knockout in AgRP neurons showed significantly increased body weight (by 3 weeks [p<0.001], two-way ANOVA) and a significant 3-day delay in first estrus (KO: 31.1±0.71 d, Control: 28.6±0.45 d, p<0.01, Student’s t-test). These data show that neuronal STAT3 is critical for correctly timed puberty and subsequent fertility in male and female mice, whereas mTOR and ERK2 are not essential. These results have prompted a re-evaluation of previous conclusions about the role of STAT3 from experiments using LepR-Cre mice. Additionally, AgRP neuronal requirements for STAT3 exactly recapitulate AgRP requirements for leptin receptors. A better grasp of leptin signalling pathways will improve our understanding of how infertility arises due to metabolic disease. Presentation: 6/3/2024

8353 Impact of a plant-based protein diet on bone health and body composition in Sprague Dawley rats

Abstract Disclosure: M.M. Gomes: None. I.M. de Araújo: None. S.V. Rodriguez: None. F.R. Jorge: None. F.J. de Paula: None. Introduction:Vegetarian and vegan diets are associated with some health benefits; this has contributed to their growing popularity. Although studies remain limited, there is evidence that these patients may be at greater risk of reduced bone mineral density (BMD) and increased fracture risk. The general objective of this study was to analyze the impact of a high-protein, plant-based diet on bone tissue and body composition in male Sprague Dawley rats. Methodology: The study was approved by the Animal Ethics Committee. This study was done with 10 rats in the control group (CG), which received a standard AIN-93M diet; 11 in the normoprotein vegetarian group (NVG), with a normoprotein AIN-93 diet modified with pea protein and methionine; and 11 in the high-protein vegetarian group (HVG), with a modified AIN-93 diet with 40% pea protein and methionine. The dietary intervention lasted 8 weeks. The weight of the animals was measured weekly. Basal blood glucose levels were measured at baseline. At the end of the study, 6 rats from the CG, 6 rats from the NVG, and 5 rats from the HVG were subjected to a glucose tolerance test (GTT). The dual-energy X-ray absorptiometry (DXA) technique was applied in the baseline and final periods of the experiment to evaluate body composition, bone mineral content (BMC) and BMD. After sacrifice, bone strength was measured via a three-point flexion mechanical test on the tibia; brown adipose, epididymal, and retroperitoneal tissues, as well as the liver, were weighed on an analytical balance. Blood was used to measure circulatory levels of insulin, CTX, and P1NP (n=6/group). Results: Basal weight was similar between the groups, but the final weight was lower in the HVG as compared to the CG. In the DXA evaluation, the final lean mass was not different between the groups. On the other hand, total fat mass was lower in the HVG than in the CG and the NVG and the fat percentage was lower in the HVG than in the CG. The weight of epididymal adipose tissue was lower in the HVG than in the NVG, but retroperitoneal and brown adipose tissues were lower in HVG than CG. Liver weight was similar between groups. BMD was similar between groups; however, BMC was lower in the HVG than in the CG and the NVG. Bone strength was similar between groups. There was no difference in glycemia at baseline or during GTT at the eighth week. Serum levels of insulin, CTX, and P1NP were similar between groups. Discussion and Conclusion: A normoprotein vegetarian diet that includes all essential amino acids appears to have no negative impact on body composition or BMD in rats. On the other hand, a high-protein diet with plant protein appears to have a negative impact on bone mineral content, in addition to reducing the amount of body fat and weight. This finding expands on previous results by showing that high-protein diets have a negative impact on bone even when the protein is of plant origin. Presentation: 6/1/2024

6849 Insulin Edema in newly diagnosed T1DM Pediatric Patient

Abstract Disclosure: A. Ansar: None. K. McNerney: None. Background: Insulin edema is a rare complication of insulin therapy, especially in the pediatric populations. The pathogenesis is not fully understood but has been linked to Insulin’s role in renal sodium handling and vascular permeability. It has been seen with the initiation of insulin in newly diagnosed patients or the intensification of insulin therapy in those with poor glycemic control.Clinical Case: A previously healthy 12 year old girl presented to the ED with polyuria, polydipsia and fatigue. She was alert and oriented but had kussmaul breathing. She was tachycardic but all other vitals were appropriate. Lab work up showed that she was in DKA with pH 7.07 and bicarbonate 7 mmol/L. Her corrected sodium and electrolytes were normal. Her HbA1C was elevated at 11.7% (4.0-5.6%). Initial fluid resuscitation was performed with 20 mL/kg NS fluids. She was transferred to our Pediatric ICU and was started on the DKA protocol consisting of intravenous insulin infusion at 0.1 unit/kg per hour and 2-bags of dextrose and non-dextrose containing intravenous fluids. She was given a new diagnosis of Type 1 Diabetes. She was transitioned to subcutaneous insulin 22 hours later with multiple daily injections with insulin lispro and glargine, with total dose of insulin at 0.7 unit/kg per day. She was transferred to the general care floor and received diabetes education while in the hospital. On the fifth day after discharge, patient started complaining of leg tightness, puffiness around her eyes and generalized swelling of both feet. She returned to the ED, where she was found to be hemodynamically stable and normotensive with a blood pressure of 113/54 mmHg. Her weight had increased 8.8 kg from the weight at discharge. Her physical exam was notable facial and bilateral periorbital edema, abdominal distension, and 2+ bilateral non-pitting non-tender edema of both legs extending to her medial malleolus. Neurologic exam was performed which was unremarkable. Work up was performed to rule out other causes of edema, including a complete blood count, electrolytes, kidney and liver function tests, all of which were normal. She received 20 mg of furosemide and was instructed to perform fluid restriction to 1 L/m2/day and sodium restriction to <2 grams per day at home. She followed up in clinic 3 days after her ED visit where her weight had decreased by 4.2 kg and her edema had mostly resolved with only 1+ bilateral non-pitting edema. Her total dose of insulin remained at 0.7 unit/kg per day, with acceptable blood glucose levels at home. Her fluid restriction was discontinued and patient was instructed to follow up as usual, and she had no further edema in follow-up. Conclusion: This was a rare case of a newly diagnosed pediatric patient presenting with Insulin edema, which is essential for clinicians to recognize, so they can identify patients presenting with this uncommon side effect to rule out conditions that may present in a similar manner. Presentation: 6/2/2024

12242 Enhancing Continuous Glucose Monitor Utilization In Lower Economic Community Hospital Outpatient Clinics: A Quality Improvement Initiative

Abstract Disclosure: V. Mehta: None. S. Deshpande: None. M. Nieman: None. K. Pereira: None. B. Agrawal: None. S.R. Russell: None. Continuous glucose monitors (CGM) measure the blood glucose level (BGL) and have been used for better glucose control, especially in patients requiring insulin. Primary care physicians (PCP) manage diabetic patients on a large scale in the US, especially in rural settings, and data shows that CGMs are prescribed less in PCP settings than in endocrine clinics. Our study aimed to understand internal medicine (IM) residents' knowledge about CGMs and their application in a community hospital outpatient clinic serving lower-economic populations and demonstrates how a clinical pharmacist (PharmD) led educational intervention successfully increased the adoption of CGMs. A survey was done using a form with multiple-choice questions. 50 residents participated and responded anonymously. Data was analyzed by calculating percentages based on answers, providing understanding of their perspectives on CGMs. 78% knew about and correctly identified CGM. When asked to name indications of CGM, answers varied and included uncontrolled diabetes (34%), insulin-dependent diabetes (34%), elderly and non-compliant patients (14%), any diabetic (12%), and others. Only 14% reported to have had formal training in use and interpretation of CGMs, 70% had prescribed, 34% knew how to apply the device, and 42% knew how to interpret the BGL. More than 95% self-reported having either poor/beginner or fair knowledge about the usage, application, and interpretation, whereas more than 80% professed to need more training to be more confident about prescribing the device. After the survey, our PharmD conducted session demonstrating the indications, types, usage, application, and interpretation of CGM. Following this, an impactful increase in patients who were appropriately prescribed and received CGM was observed. Technologies used in medicine have increased, CGM, being one of them. More than 100 million Americans have prediabetes or diabetes, with more than 10 million using insulin. Hence, access to CGM is crucial for patients for better management. Despite the benefits, many factors play a role in limiting their use, including prescription, cost, insurance coverage, social factors, willingness of the patients, discomfort, and decreased knowledge. Non-compliance, difficulty in application and picking the device from pharmacy was also observed in our clinic. A study by Sherrill et al. on use of CGMs (2014-2020) showed that use of CGM increased almost ten times in 2020 (v/s2014); most patients were younger, employed, and had better insurance coverage.With advances in technology, easier and more efficient devices are available to assess patients' glycemic control. Pharmacists play key role in ensuring continued education among practitioners and trainees. Continued efforts to increase awareness is required to ensure that latest advances are adequately incorporated into graduate medical education. Presentation: 6/3/2024

7305 Pheochromocytoma Presenting With Resistant Hyperglycemia

Abstract Disclosure: M. Economou: None. A. Devine: None. Background: Pheochromocytoma is a rare catecholamine producing tumor arising from the adrenal gland. Impaired glucose tolerance is a well-recognized hormonal and metabolic manifestation of pheochromocytoma caused by catecholamine excess [1]. Insulin resistance requiring very high doses of insulin in association with pheochromocytoma is, however, rare. Here we report a case of pheochromocytoma in a woman with diabetes mellitus that proved difficult to control despite high-dose insulin therapy. Case presentation: A 72-year-old woman with a longstanding history of type 2 diabetes mellitus, uncontrolled hypertension, hyperlipidemia and CVA presented to the hospital after she was found to have a hemoglobin of 7.0 ng/mL on routine labs. Notably, over the past 4 years, her insulin requirement gradually increased from 20 units/day to 50 units/day despite an A1c level of 6.1%. On presentation, our patient was hypertensive to 170/90 with limited response to multiple antihypertensive medications. Additionally, her glucose was severely uncontrolled, fluctuating between 200-500 mg/dL. Within days, the patient’s total daily insulin requirement increased tremendously to as much as 300 units/day. As part of her anemia workup, she underwent a contrast-enhanced CT abdomen & pelvis which identified a left adrenal mass measuring 2.2 x 2.8 x 2.9 cm. Further evaluation with MRI confirmed an adrenal mass suspicious for pheochromocytoma. Evaluation of plasma hormone levels revealed an elevated normetanephrine level of 7.10 nmol/L (normal: less than 0.89 nmol/L). Furthermore, the 24-h urinary normetanephrine level and chromogranin A levels were elevated to 145 mcg/day and 1203 ng/mL, respectively. Initial treatment with alpha and beta blockade improved blood pressure but glucose levels remained persistently elevated. The patient underwent left laparoscopic adrenalectomy and pathology revealed pheochromocytoma, measuring, 3.2 cm in diameter, with stains positive for CD56, synaptophysin and chromogranin. Surgical resection margins were negative for tumor. Postoperatively, insulin requirements returned to roughly that of her baseline, 40 units/day. Conclusion: Impaired glucose tolerance is a known phenomenon associated with pheochromocytoma. Despite this, it is unusual to see an insulin requirement rise as abruptly and drastically as seen in this case. Our patient, with relatively controlled diabetes had an enormous increase in her insulin requirement during her hospital course as evidenced by her insulin regimen which increased sixfold. This case highlights the importance of maintaining a high degree of suspicion for pheochromocytoma in patients with a sudden rise in insulin requirement and uncontrolled hypertension. Reference: (1) Ronen JA, Gavin M, Ruppert MD, Peiris AN. Glycemic Disturbances in Pheochromocytoma and Paraganglioma. Cureus. 2019 Apr 27;11(4): e4551. Presentation: 6/3/2024

8227 Complex Case of Myxedema Coma Complicated by Cardiac Arrest in a Geriatric Patient with Multiple Comorbidities

Abstract Disclosure: M. Parvez: None. L. Makahleh: None. S. Nagpal: None. A. Kavarthapu: None. V. Vedantam: None. Introduction: This case report details a rare instance of cardiac arrest in a patient with myxedema coma, a severe form of hypothyroidism. It highlights the diagnostic and therapeutic challenges in managing such complex endocrine emergencies. Case Presentation: A 70-year-old female with a history of hypothyroidism, type 2 diabetes, atrial fibrillation, pacemaker implantation, and COPD presented with a 3 day history of progressive lethargy and weakness. EMS found her with critically low blood glucose level of 20. History and Examination revealed non-compliance with thyroid medication and myxedematous features including moon-like facies, periorbital edema, generalized edema, elevated JVP, and cold extremities with sluggish capillary refill. In the ER, she was hypotensive, labs showed a significantly elevated TSH level of 30.55 (0.45-4.5), free T3 level of 1.2 (2.3-4.2), free T4 level of 1.12 (0.93-1.70), high lactate, metabolic acidosis, renal impairment, and liver enzyme elevation. These findings, coupled with the clinical presentation, led to the diagnosis of myxedema coma. The patient's critical state was further complicated by distributive shock, shock liver and oliguric AKI. Management included sodium bicarbonate infusion for severe acidosis, IV hydrocortisone, IV levothyroxine, and broad-spectrum antibiotics. Amiodarone was discontinued due to its potential contribution to acute liver injury and hypothyroidism. Despite interventions, she developed acute respiratory failure, requiring intubation and norepinephrine for low mean arterial pressure. Her renal function improved with pressor support, and her lactic acidosis resolved. She recovered quickly and was subsequently extubated. After stabilization, she was switched to oral levothyroxine and discharged. Shortly after discharge, she returned again with generalized weakness, confusion, and dysuria. ER evaluation revealed lethargy, hypotension, hypoglycemia, severe metabolic acidosis, and a UTI. She tested positive for Influenza. While in the ER, she had cardiac arrest, presenting with agonal breathing and PEA. CPR was initiated, achieving ROSC after two rounds and one dose of epinephrine. She was treated again with IV levothyroxine, and IV antibiotics. She recovered well and was discharged to rehab facility with re-education on compliance. Conclusion: This case exemplifies the complexity and challenges in managing a geriatric patient with multiple comorbidities, particularly in the context of myxedema coma. The intricate interplay of endocrine, cardiovascular, respiratory, and infectious complications necessitated a multifaceted and dynamic therapeutic approach. This case underscores the importance of compliance, vigilant monitoring, prompt recognition of complicating factors, and the need for a coordinated multidisciplinary approach in managing similar cases. Presentation: 6/2/2024

7354 A Case of Continuous Glucose Monitoring in Children with Glutamate Dehydrogenase Hyperinsulinism

Abstract Disclosure: K. Kim: None. E. Mun: None. C. Jung Eun: None. R. Lee: None. K. Hae Soon: None. A Case of Continuous Glucose Monitoring in Children with Glutamate Dehydrogenase(GLUD1) Hyperinsulinism Background: Continuous glucose monitoring (CGM) is increasingly being used in pediatric patients with diabetes. CGM can help prevent hypoglycemia and support the management of hypoglycemic problems. Congenital hyperinsulinism is a rare condition in which hypoglycemia occurs due to hyperinsulinemia caused by the dysregulation of insulin secretion, and it can lead to complications such as developmental delay and seizures. Case presentation: A 14 months years old, male infant was referred to the pediatric emergency room representing symptoms of GTC type seizure during 2-3 minutes and hypoglycemia. He had no perinatal problems with no significant family history. During seizure, He was found to have a blood glucose of 39mg/dL, ammonia of 183μmol/L, insulin of 28.3 mcg/mL and ketone 203.4μmol/L. C-peptide was 1.4 ng/mL (≥ 0.5ng/mL) and free fatty acid was 0.492mmol/L (<1.7mmol/L) for evaluation. He was thought to have GDH hyperinsulinism. Blood glucose level was followed up with feeding frequency and protein restricted diet. Congenital hyperinsulinism genetic test was requested. Brain CT showed normal. EEG revealed no focal abnormalities, no persistent asymmetries. CGM was used in patient. Diazoxide was started with 5mg/kg/day in 2 divided doses and then blood glucose level was observed below 60mg/dL 3-4 times for day. Complete blood counts and uric acid levels were measured at baseline and 5 days after starting diazoxide therapy, and thereafter increase to 6.25mg/kg/day Conclusions: In children with GDH hyperinsulinism, the utilization of CGM can serve as a tool to assess the impact of treatment before and after medication therapy, as well as also aiding in hypoglycemia prevention. Presentation: 6/2/2024

6588 Insulin Autoimmune Syndrome Presenting with Severe Insulin Resistance and Recurrent Diabetic Ketoacidosis

Abstract Disclosure: E. Looi: None. R. Rosenberg: None. S. Sugar: None. H. Stone: None. A.W. Michels: None. D. Saxon: None. Background: Insulin autoimmune syndrome (IAS) is a rare cause of severe insulin resistance and is typically associated with intermittent hypoglycemia due to insulin antibodies (IA) with high binding capacity and low insulin affinity. However, consideration should be given for atypical presentation of IAS or co-presentation of IAS with type B insulin resistance syndrome (TBIRS) in the absence of hypoglycemia, as described in this case. Case: A 78-year-old African American female (BMI 21 kg/m2) with poorly controlled type 2 diabetes (A1c 11%) experienced recurrent episodes of diabetic ketoacidosis (DKA) despite adherence to escalating insulin doses (310 units daily, 5 u/kg/day). She was referred to endocrinology and continuous glucose monitoring revealed consistently elevated glucose levels (300-400 mg/dL) without hypoglycemia. She had normal renal function, hepatic function, and lipid panel. During a subsequent hospitalization, she required insulin drip rates of 50-70 u/hr. Insulin resistance workup revealed significantly elevated IA level (8.346, normal ≤ 0.010) measured using a fluid-phase radiobinding assay with high insulin binding capacity (1040 U insulin-binding/L blood) and low insulin binding affinity (1.9x107 M), which supported the diagnosis of IAS. Rheumatologic workup for other autoimmune diseases was negative. Due to recurrent DKA episodes, severe insulin resistance without obvious alternative cause, and lack of hypoglycemic events despite low IA binding affinity, co-morbid TBIRS was considered. As there are no commercially available insulin receptor antibody (IRAb) assays, diagnosis could not be confirmed before her condition worsened, and she was admitted for another episode of DKA within a week of being discharged. Due to clinical deterioration and high suspicion for IAS ± TBIRS, treatment with a combination of immunosuppressive agents was initiated in accordance with an NIH protocol (Klubo-Gwiezdzinska J, et al. 2018). Intravenous immune globulin (0.5g/kg/day) was administered over 2 days which resulted in a brief reprieve and followed by significant relapse. Two doses of rituximab (750 mg/m2) and 2 steroid pulses (dexamethasone 40 mg PO daily for 4 days) were then administered 2 weeks apart. Cyclophosphamide 100 mg daily was also started. Her hyperglycemia and insulin requirements subsequently improved, and she was eventually discharged with good glycemic control on a total daily dose of 40 units of insulin (0.5 u/kg/day), an 87.1% reduction in daily insulin requirement. Conclusion: This case demonstrates that IAS - although classically associated with hypoglycemic episodes - may also present with severe insulin resistance and recurrent DKA without hypoglycemia. Whether characterized by high IA binding capacity and affinity or coexisting with IRAb, a combination of immunosuppressants proved effective in treating both TBIRS and IAS in this instance. Presentation: 6/3/2024

8202 Retrospective Analysis of Mixed-Meal Testing in People with Suspected Spontaneous Post-Prandial Hypoglycemia

Abstract Disclosure: N. Sankaran: None. R. Jalleh: None. C. Bischoff: None. C. Marathe: None. Introduction: While there is no consensus on the optimal confirmatory test for postprandial hypoglycemia, guidelines suggest evaluation with a mixed meal test that is most likely to provoke symptoms of hypoglycemia as nominated by the patient. However, studies evaluating post-bariatric surgery hypoglycemia indicate that meals with a lower carbohydrate content are less likely to be associated with postprandial hypoglycemia. It is hypothesized that a greater carbohydrate load may result in an excessive second-phase insulin response resulting in hypoglycemia. We evaluated the outcomes of consecutive mixed meal tests in individuals with suspected spontaneous postprandial hypoglycemia and the relationship with the percentage carbohydrate content of the test meal. Methods: We retrospectively analysed the data of 103 unselected patients who were referred to undergo a 5-hour mixed meal test following an overnight fast, between the years 2010 - 2023 at the Royal Adelaide Hospital. Correlations were determined using a linear regression model and Student’s t-test was used to compare the mean carbohydrate meal content in those with and without postprandial hypoglycemia. Outcomes: Outcomes that were measured included post-meal blood glucose, plasma insulin, plasma C-peptide levels and the macronutrient composition of the meal. Subjective reporting of symptoms during the test were also noted and correlated with the symptoms included in the Edinburgh Hypoglycemia Score. Results: 33/103 participants were excluded as they had previously undergone islet cell transplant or bariatric surgery. Out of the remaining 70 participants referred for confirmatory MMT testing, 51 were female and 19 were male. The ages of the participants ranged from 16 to 74, with the median age of 40 years. 9 participants (6 females and 3 males) had abnormal results with glucose below 3.0mmol/L. 34 participants experienced hypoglycemia with glucose levels recorded below 4.0mmol/L during the test. There was no difference in carbohydrate content consumed (61.1g, P=0.30) or percentage carbohydrate (64.5%, P=0.17) in the group without postprandial hypoglycemia compared with those with postprandial hypoglycemia (carbohydrate content 67.9 g, 69.6% carbohydrate). No correlation could be identified between the percentage of carbohydrate content of the meal with the glucose nadir (P=0.75), peak insulin concentration (P=0.99) or peak C-peptide concentration (P=0.40). The percentage of carbohydrate content of the meal was neither associated with hypoglycemia (P=0.17) or symptoms (P=0.41). Conclusion: On mixed meal testing, postprandial symptoms and hypoglycemia does not correlate with either carbohydrate load or the percentage carbohydrate content of the nominated meal. Presentation: 6/1/2024

7647 Myxedema Coma- A Rare and Fatal Manifestation of Severe Hypothyroidism

Abstract Disclosure: B.K. Ray: None. R. Kaur: None. L. Kaur: None. M. Thakur: None. Introduction: Myxedema coma is a severe and life-threatening form of hypothyroidism. It is a rare occurrence with an incidence of 0.22 per million per year, associated with a high mortality rate ranging from 30 to 60% even with early diagnosis and treatment. This condition arises when the body's response to hypothyroidism is overwhelmed by factors like infection, surgery, and medication noncompliance. The definitive management is with thyroid hormones but supportive measures and identification and treatment of the precipitating factors is also vital. The case discussed concerns an elderly woman with myxedema coma due to noncompliance to Levothyroxine. This case stresses the importance of consistent medical follow-ups. Case Presentation: A 73 year old female presented to the hospital with altered mental status for about 32 hours. Vital signs at presentation showed hypotension (80/50 mmHg), bradycardia (54 beats per minute), tachypnea (32 breaths per minute) and hypothermia (33.2 °C). A computed tomography scan of the brain and Computed tomography angiography of the head/neck showed no stenosis or large vessel occlusion of the vasculature. Initial pertinent laboratory test results revealed a white blood cell count of 6.1 (3.7–11.0×103/uL), hemoglobin level of 14.3 (11.5–16.0 g/dL), sodium level of 131 (136–145 mmol/L), glucose level of 142 (65–125 mg/dL). Troponin, lactate and procalcitonin were normal. She was intubated and transferred to the Intensive care unit. Thyroid function tests revealed a markedly elevated TSH of 37.9 (0.4 to 4.0 mIU/L) and a decreased T4 of 0.3 (0.9-1.7 ng/dL). She was immediately started on hydrocortisone 100 mg Three times daily and initiated on intravenous levothyroxine monotherapy with a loading dose of 200 mcg followed by 100 mcg daily. Her T4 level was trended daily and she demonstrated gradual improvement. She was successfully extubated. On discussion she reported noncompliance with her medications. Hydrocortisone was tapered and she was started on her home dose of oral Levothyroxine (200 mcg) after four days of Intravenous levothyroxine. She was counselled on medication compliance and discharged to home. Conclusion: Myxedema, an extreme form of hypothyroidism, is life-threatening and requires immediate admission to intensive care. Symptoms are usually vague, and require a high degree of suspicion. Treatments include thyroid hormone supplementation, steroid replacement and supportive care. Early detection and quick intervention are crucial for survival. Patient education on medication compliance, regular testing, and reporting new medication to prevent interference with thyroid metabolism is crucial. Presentation: 6/1/2024

12397 Predictors Of Hospital Readmission Within Three Months Among Patients Admitted For Diabetic Ketoacidosis (dka)

Abstract Disclosure: O. Onwudiwe: None. L. Yerashevich: None. C. Onwudiwe: None. B. Baral: None. A. Acharya: None. H. Nguyen: None. Purpose: Diabetic ketoacidosis (DKA) represents a critical, life-threatening complication of diabetes, with higher rates of re-admission noted among individuals from lower socioeconomic backgrounds, those lacking insurance coverage, and those with suboptimal follow-up care. This study seeks to identify predictors of hospital readmission within three months among patients admitted for DKA in a community hospital setting. Methods: Patient data were extracted from electronic medical records from 2019 to 2021 for individuals admitted due to DKA using ICD codes. DKA diagnosis was based on the presence of hyperglycemia, high anion gap metabolic acidosis, and ketonemia. Demographic information, results of routine biochemical tests, insurance status, follow-up with primary care providers (PCP) or endocrinologists, and clinical progression were retrospectively collected from patients' records. Multivariable logistic regression analyses were conducted to identify predictors of readmission. Results: A total of 222 unique DKA admission visits were analyzed. The mean age (standard deviation) of the patients was 48 (16) years, and 58% of them were male. Among these visits, 39% had type 1 diabetes, 43% had type 2 diabetes, and 18% were newly diagnosed diabetes cases. The majority of patients were overweight, with a mean body mass index (BMI) of 27, and the mean glycated hemoglobin level was 10.8. Common triggers for DKA included insulin non-adherence (52%), infection (37.8%), and alcohol use (8.6%). Logistic regression analysis revealed that lack of follow-up significantly increased the odds of readmission within three months (B = 2.025, p = .003, Exp(B) = 7.576, 95% CI [1.952, 29.401]), as did having type 1 diabetes (B = 1.473, p = .019, Exp(B) = 4.364, 95% CI [1.272, 14.978]). However, the association between insulin adherence and readmission was not statistically significant at the conventional alpha level of 0.05 (B = 1.329, p = .112, Exp(B) = 3.777, 95% CI [0.733, 19.458]). Other demographic (age, gender, employment status, insurance status, medication compliance,) and clinical [insulin adherence, presence of infection, blood glucose level at diagnosis of DKA, and level of glycated hemoglobin (Hba1c)] variables did not significantly predict readmission within 3 months. Conclusion: DKA, being preventable with adequate insulin adherence, is also influenced by factors such as infection and lifestyle choices. The findings highlight the critical role of post-discharge follow-up care in reducing readmission rates among DKA patients. Healthcare providers should prioritize ensuring timely and comprehensive follow-up, particularly for patients with type 1 diabetes, to optimize post-hospitalization management and prevent avoidable readmissions. Presentation: 6/3/2024

7437 Harnessing Diabetes Technology for Management of Immune Checkpoint Inhibitor Associated Diabetes

Abstract Disclosure: A. Knape: None. A. Kotwal: None. D. Rohlfsen: None. A. Patel: None. W. Goldner: None. Background: Immune checkpoint inhibitors (ICIs) are a key treatment modality for many cancers. One percent of patients who receive ICIs can develop insulin deficient ICI associated diabetes (ICI-DM). These patients often have complex oncologic therapy plans making treatment of newly diagnosed insulin deficient diabetes challenging which often results in additional healthcare-related burden for the patient. Methods: This is a retrospective case series of five adults who developed ICI-DM after receiving either PD-1, CTLA-4 or PDL-1 inhibitors or a combination. Data on demographics, medical history and labs were collected in addition to mode of glucose monitoring and treatment after diagnosis of ICI-DM. Results: Patients were age 44-72 at diagnosis of ICI-DM, three were female. Two were admitted to the hospital in DKA, one was diagnosed in the ER with severe hyperglycemia without DKA, two had outpatient hyperglycemia without DKA. Glucose at diagnosis ranged from 215-510 mg/dL. C-peptide was low for all patients. Fingerstick blood sugar (FSBS) monitoring and basal/bolus insulin was immediately initiated for all patients. All were transitioned from FSBS to continuous glucose monitor (CGM) and 2/5 ultimately transitioned to sensor-augmented insulin pump therapy (AID). Time in range on CGM improved in four patients with percent time in range improving between 10-48%. In two patients, hypoglycemia frequency declined by 6% and 3%. Hyperglycemia frequency declined by 13% and 48% in patients on AID therapy and by 14% and 25% in two of those on basal/bolus insulin therapy. All patients preferred CGM over FSBS and remained on CGM therapy. Those who chose AID preferred it over basal/bolus insulin therapy stating it was less complicated than basal/bolus insulin with CGM. Conclusions: We report successful treatment of five cases of ICI-DM with CGM + basal/bolus insulin or AID. 80% demonstrated improved time in range and decreased overall frequency of hyperglycemia. 40% had decreased frequency of hypoglycemia. CGM allows for dynamic adjustment of insulin therapy in a population with complex medical regimens resulting in fluctuating glucose levels. The integrated pump and sensor technology in AID was less burdensome than basal/bolus in those who chose it. Managing ICI-DM is complicated. The burden of this entity can be lessened by harnessing the power of diabetes technology. Presentation: 6/2/2024

8330 Pancreatic neurons in neuron-islet complexes and activation of these neurons promotes insulin secretion under high glucose level

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 (<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 > 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

7765 Exploring the Synergistic Effect of GHRH Receptor Agonist MR-409 and Incretin-based Therapies in Type 1 Diabetes Using a Low-dose Streptozotocin Model

Abstract Disclosure: M. Gonzalez Medina: None. R. Louzada: None. V. Pita-Grisanti: None. M. Blandino: None. T. Cui: None. W. Sha: Owner/Co-Owner; Self; WS. is co-inventor on GHRH agonists MR-409 patent, assigned to the University of Miami and the Veterans Affairs. R. Cai: Owner/Co-Owner; Self; R.C. is co-inventor on GHRH agonists MR-409 patent, assigned to the University of Miami and the Veterans Affairs. A.V. Schally: Owner/Co-Owner; Self; A.V.S. is co-inventor on GHRH agonists MR-409 patent, assigned to the University of Miami and the Veterans Affairs.. E. Bernal-Mizrachi: None. Patients with type 1 diabetes (T1D) have decreased functional β-cell mass due to inflammatory cell infiltration and cytokine-induced β-cell death. Clinical trials using a combination of immunomodulatory agents and β-cell protecting medications such as GLP1-R agonists (GLP1-Ra) are being considered. A potential limitation for the clinical efficacy of GLP1-R agonists is the loss of GLP-1-R at the cell surface in states of hyperglycemia. Hence, novel agents that enhance β-cell survival and proliferation through parallel pathways could improve responses to GLP1-R agonists and/or synergistically potentiate β-cell responses. Previous studies have demonstrated beneficial effects of growth hormone-releasing hormone receptor agonists (GHRH-Ra), such as MR-409 on islet preconditioning in transplantation models. Our previous studies showed that GHRH-Ra protects β-cells from autoimmune injury in vitro and improves glucose levels in a model of high-dose streptozotocin-induced diabetes via stimulation of the cAMP/PKA/CREB/IRS2 axis. However, the effects of combination of incretin-based therapy with GHRHRa on β-cell survival in T1D models have not yet been explored. Using the low-dose STZ model in C57/B6 mice, we investigated how MR-409 alone or in combination with GLP1-R agonists (Exendin-4 or Ex-4) promotes β-cell survival and prevents T1D. Low-dose STZ treated mice received daily MR-409 and Ex-4 injections, either alone or in combination for six weeks. We found that, STZ-treated mice that received either MR-409, Ex-4 or combination exhibited better glucose homeostasis while the combination failed to induce any additional effect. Interestingly, glucose tolerance and insulin levels were improved only in the MR-409-treated mice. β-cell mass was similarly increased in mice that received MR-409, Ex-4 and combination groups compared to the vehicle-treated. Further, treatment of human islets with MR-409 and/or Ex-4 induced insulin receptor substrate 2 (IRS2) expression, a master regulator of survival and growth in β-cells, while the combination of both therapies did not have any additional effect. Experiments in human islets exposed to proinflammatory cytokines treatment demonstrated that MR-409 and/or Ex-4 was associated with a decrease in β-cell death and improved insulin secretory function by activation of the cAMP/PKA/CREB/IRS2 axis. These studies demonstrate that although there was no evidence for a synergistic effect between MR-409 and Ex-4, MR-409 appears to have more potent effects on improving glucose tolerance and insulin levels when compared to the long-term effect of Ex-4 in a low-dose STZ model, suggesting that MR-409 could be an alternative therapeutic agent in the treatment of β-cell death in T1D. Presentation: 6/2/2024