Hypoglycemia Research Articles

Association of accelerometer-measured sedentary time, light intensity physical activity levels with cardiometabolic disease risk in Indian office workers: Insights from the SMART-STEP study

Background and aimsSedentary time (ST) is found to be an independent risk for cardiometabolic disease (CMD). While moderate to vigorous physical activity has demonstrated clear benefits in reducing the risk of CMD, only a fraction of the world's population meets the recommended levels. The benefits of easily attainable light-intensity physical activity (LIPA) on CMD risk factors are seldom explored. Our study aimed to explore the association of accelerometer-measured ST and LIPA with CMD risk among Indian office workers. MethodsST and LIPA were recorded using a hip-worn accelerometer (Actigraph) for seven consecutive days, while CMD risk factors were evaluated in 130 insufficiently active office workers. The association of accelerometer-measured ST and LIPA with CMD risk factors were examined using multivariate regression. ResultsHigher ST were positively associated with high body mass index (β = 0.330, p < 0.001) and body fat percentage (β = 0.422, p < 0.001), while LIPA exhibited an inverse relationship with the above variables. Additionally, higher LIPA was associated to low fasting blood sugar levels (FBS) (β = −0.308, p = 0.023). Similarly, high ST was associated with low heart rate variability (HRV) (β = −0.407, p = 0.024) while high LIPA was associated with high HRV (β = 0.379, p = 0.003). However, the associations remain insignificant for majority of other CMD risk factors. ConclusionElevated ST is consistently linked to higher body mass, FBS and lower HRV (an indicator of autonomic stability). LIPA is associated with lower risk of above variables. Still, the association of ST and LIPA with other CMD risk factors remain uncertain. Longitudinal studies with larger samples of Indian office workers is needed to validate the present study findings.

Clopidogrel-induced non-diabetic hypoglycemia reported from Tikur Anbessa Specialized Hospital, Addis Ababa, Ethiopia: a case report

BackgroundRecurrent episodes of hypoglycemia may be caused by several factors, including drugs, critical illnesses, hormonal deficiency, non-islet cell tumor endogenous hyperinsulinism, and accidental, surreptitious, or malicious hypoglycemia. Multiple drugs have been previously reported as causes of hypoglycemia, with moderate and low-quality evidence. However, Clopidogrel as a cause of non-diabetic hypoglycemia is rarely reported. Here we describe a single non-diabetic patient who experienced recurrent episodes of hypoglycemia after initiation of clopidogrel for clinical suspicion of acute coronary syndrome.Case presentationThe patient, a 33-year-old Ethiopian male with documented hypertension on antihypertensive medication, has started receiving treatment for acute coronary syndrome after experiencing angina symptoms. He experienced hypoglycemia following the start of Clopidogrel, but it subsided once it was stopped. Currently, he has a follow-up at the cardiac clinic with a normal measurement of his serum blood glucose level.ConclusionNon-diabetic hypoglycemia is a rare illness characterized by low blood glucose levels in people who do not have diabetes. Patients with severe hypoglycemia may become unconscious or have seizures as a result of low blood sugar. Severe hypoglycemia is fatal and must be treated as soon as possible. Therefore, if non-diabetic hypoglycemia occurs, a thorough evaluation of the causes is essential, particularly any potential drug as a cause of hypoglycemia should be evaluated.

Gene deletion of the PACAP/VIP receptor, VPAC2R, alters glycemic responses during metabolic and psychogenic stress in adult female mice.

Pituitary adenylate cyclase-activating polypeptide (PACAP) and the homologous peptide, vasoactive intestinal peptide (VIP), participate in glucose homeostasis using insulinotropic and counterregulatory processes. The role of VIP receptor 2 (VPAC2R) in these opposing actions needs further characterization. In this study, we examined the participation of VPAC2R on basal glycemia, fasted levels of glucoregulatory hormones and on glycemia responses during metabolic and psychogenic stress using gene-deleted (Vipr2-/- ) female mice. The mean basal glycemia was significantly greater in Vipr2-/- in the fed state and after an 8-h overnight fast as compared to wild-type (WT) mice. Insulin tolerance testing following a 5-h fast (morning fast, 0.38 U/kg insulin) indicated no effect of genotype. However, during a more intense metabolic challenge (8 h, ON fast, 0.25 U/kg insulin), Vipr2-/- females displayed significantly impaired insulin hypoglycemia. During immobilization stress, the hyperglycemic response and plasma epinephrine levels were significantly elevated above basal in Vipr2-/- , but not WT mice, in spite of similar stress levels of plasma corticosterone. Together, these results implicate participation of VPAC2R in upregulated counterregulatory processes influenced by enhanced sympathoexcitation. Moreover, the suppression of plasma GLP-1 levels in Vipr2-/- mice may have removed the inhibition on hepatic glucose production and the promotion of glucose disposal by GLP-1. qPCR analysis indicated deregulation of central gene markers of PACAP/VIP signaling in Vipr2-/- , upregulated medulla tyrosine hydroxylase (Th) and downregulated hypothalamic Vip transcripts. These results demonstrate a physiological role for VPAC2R in glucose metabolism, especially during insulin challenge and psychogenic stress, likely involving the participation of sympathoadrenal activity and/or metabolic hormones.

Spontaneous recurrent non-insulin dependent hypoglycaemia associated with malignant phyllodes tumour of the breast: a rare case report

Spontaneous recurrent non-insulin dependent hypoglycaemia associated with malignant phyllodes tumour of the breast: a rare case report

Wearable room-temperature ethanol sensor based on Ti3C2Tx/Polypyrrole functionalized face mask for drunk driving monitoring

As one of the most encountered volatile organic compounds (VOCs), ethanol, especially with high blood concentrations, could cause adverse effects such as nausea, vomiting, skin allergies, low blood pressure, low blood sugar, and Parkinson's disease, seriously threatening human health and safety driving. In this study, we demonstrate a wearable ethanol sensor through drop-coating Ti3C2Tx suspension followed by chemical polymerization of pyrrole on a disposable face mask substrate. The as-fabricated PP/Ti3C2Tx/PPy composite sensor exhibited a rapid response/recovery speed (49s/18s), a good sensing response of 76.3 % toward 400 ppm ethanol, an admirable theoretical limit of detection of 2.21 ppm, reliable flexibility, high selectivity, and excellent reproducibility. The outstanding sensing characteristics of the composite sensor are ascribed to the abundant functional groups (e.g., amino groups in PPy, terminal groups in Ti3C2Tx) and the formation of the Schottky junction between Ti3C2Tx and PPy. Moreover, the composite sensor exhibits stable sensing performance around room temperatures (20–40 °C), and even at different bending states (0–150°). In addition, we developed a portable and wearable Bluetooth sensor module for human alcohol breath detection, suggesting the PP/Ti3C2Tx/PPy composite sensor can be used for human drunk driving monitoring and health assessment.

GLYCEMIC SECURITY OF AN ACTIVE VIDEO-GAME SESSION AND RUNNING IN TYPE 1 DIABETICS

Abstract: This research aimed to analyze blood glucose in running (treadmill) and active video game (AVG) in DM1. A case study was carried out with a male DM1 patient performing AVG and preparation (30 minutes). Capillary blood glucose was analyzed at the beginning of the study, immediately and 30 minutes later, and every 6 hours up to 48 hours. Cardiovascular and motivation responses were verified. Descriptive analysis performed. As a result, rates increased cardiovascular parameters and running reached 12 points of perceived exertion at 72% of heart rate. AVG, 11 points and 62%. Both immediately after the session take blood glucose compared to rest and maintain values below the estimated blood glucose. He highlighted that running promotes nocturnal hypoglycemia. In an AVG session we present motivation values (99 vs 79 points). Through this research, it is concluded that AVG was glycemically interesting for male DM1.

Magnetic resonance imaging features to evaluate the neonatal hypoglycemia brain injury and investigation of related risk factors under the fuzzy C‐means clustering intelligent algorithm

AbstractThis research was aimed to analyse the application value of magnetic resonance imaging based on Fuzzy C‐means (FCM) algorithm in neonatal hypoglycemia brain injury (HBI), and explore the risk factors related to the occurrence of brain injury in children, to provide guidance for clinical diagnosis and treatment. 114 children with hypoglycemia were divided into brain injury group (58 cases) and no brain injury group (56 cases) according to whether they had brain injury or not. The MRI image signal performance, general data, average minimum blood glucose value, duration of hypoglycemia, first feeding time, age of onset of hypoglycemia, and algorithm segmentation performance of the two groups of patients were observed and compared. Furthermore, the Logistic factor analysis was carried out to summarize the MRI characteristics and related risk factors of neonatal hypoglycemic brain injury. The results showed that the average minimum blood glucose (1.09 ± 0.53 mmoL/L) in the brain injury group was lower than that in the non‐brain injury group (1.75 ± 0.49 mmoL/L), and the duration of hypoglycemia (43.1 ± 21.07 h) was higher than that in the non‐brain injury group (13.79 ± 6.81 h), p &lt; 0.05. The first feeding time and age of hypoglycemia in the brain injury group were higher than those in the non‐brain injury group, showing a difference with p &lt; 0.05. In the brain injury group, all 58 cases showed high DWI (diffusion weighted imaging) signal at the damaged site at the early stage of MRI (magnetic resonance imaging), and 23 cases (39.66%) were involved in parieto‐occipital lobe. Image segmentation coefficient of Vpc increased significantly under FCM clustering algorithm (p &lt; 0.05). Late first feeding time, low blood sugar level, and long duration were high risk factors for hypoglycemic brain injury. In conclusion, MRI images based on FCM clustering algorithm had higher image quality. Late first feeding time, low blood sugar level, and long duration of hypoglycemia were high risk factors for hypoglycemic brain injury.

Investigation and Causes of Spontaneous (Non-Diabetic) Hypoglycaemia in Adults: Pitfalls to Avoid.

Although adult spontaneous (non-diabetic) hypoglycaemia is rare, its recognition is important for the preventative or curative treatment of the underlying cause. Establishing Whipple's triad-low blood glucose, neuroglycopaenia and resolution of neuroglycopaenia on increasing blood glucose levels to normal or above-is essential to verify hypoglycaemia. Awareness that hypoglycaemia may occur in severely ill patients is important for its prevention. Further investigation in such cases is unnecessary unless another cause of hypoglycaemia is suspected. Patients are often asymptomatic and normoglycaemic at review. Their history of medication, self-medication, access to hypoglycaemic drugs, alcohol use and comorbidity may provide aetiological clues. The investigation involves obtaining blood samples during symptoms for laboratory glucose measurement or provoking fasting or postprandial hypoglycaemia as directed by symptoms. If confirmed, insulin, c-peptide, proinsulin and beta-hydroxybutyrate are analysed in hypoglycaemic samples. These will classify hypoglycaemia due to non-ketotic hyperinsulinaemia, non-ketotic hypoinsulinaemia and ketotic hypoinsulinaemia, and direct investigations to identify the underlying cause. There are, however, many pitfalls that may mislabel healthy individuals as "hypoglycaemic" or misdiagnose treatable or preventable causes of spontaneous hypoglycaemia. Clinical acumen and appropriate investigations will mostly identify hypoglycaemia and its cause.

The psychosocial burdens of living with diabetes.

To better understand the prevalence of self-reported psychosocial burdens and the unmet needs identified by people with diabetes in relation to routine diabetes visits. An English language, online survey was distributed via social media, key stakeholder networks, charity and advocacy groups to adults with type 1 diabetes or type 2 diabetes. Survey items were designed by members of the FDA RESCUE Collaborative Community Governing Committee prior to pilot testing with potential participants. Descriptive statistical analyses were conducted, as well as thematic analyses on free-text responses using NVivo v14. Four hundred and seventy-eight participants completed the survey: 373 (78%) had type 1 diabetes, 346 (73%) identified as a woman and 433 (91%) were white. Most participants had experienced self-reported (rather than diagnosed) anxiety and depression (n = 323 and n = 313, respectively), as well as fear of low blood sugars (n = 294), low mood (n = 290) and diabetes-related distress (n = 257). Sixty-eight percent reported that diabetes had negatively affected self-esteem, 62% reported the feelings of loneliness, but 93% reported that friends/family/work colleagues were supportive when needed. Two hundred and seventy-two percent (57%) reported that their diabetes team had never raised the topic of mental health. The overwhelming majority stated that the best thing their diabetes team could do to help was to simply ask about mental well-being, listen with empathy and without judgement, and practice skills to understand psychosocial issues in diabetes. Integrating psychosocial discussions and support within routine healthcare visits is crucial to improve outcomes for people with diabetes. Such a biopsychosocial model of healthcare has long been advocated by regulatory bodies.

Combining uncertainty-aware predictive modeling and a bedtime Smart Snack intervention to prevent nocturnal hypoglycemia in people with type 1 diabetes on multiple daily injections.

Nocturnal hypoglycemia is a known challenge for people with type 1 diabetes, especially for physically active individuals or those on multiple daily injections. We developed an evidential neural network (ENN) to predict at bedtime the probability and timing of nocturnal hypoglycemia (0-4 vs 4-8h after bedtime) based on several glucose metrics and physical activity patterns. We utilized these predictions in silico to prescribe bedtime carbohydrates with a Smart Snack intervention specific to the predicted minimum nocturnal glucose and timing of nocturnal hypoglycemia. We leveraged free-living datasets collected from 366 individuals from the T1DEXI Study and Glooko. Inputs to the ENN used to model nocturnal hypoglycemia were derived from demographic information, continuous glucose monitoring, and physical activity data. We assessed the accuracy of the ENN using area under the receiver operating curve, and the clinical impact of the Smart Snack intervention through simulations. The ENN achieved an area under the receiver operating curve of 0.80 and 0.71 to predict nocturnal hypoglycemic events during 0-4 and 4-8h after bedtime, respectively, outperforming all evaluated baseline methods. Use of the Smart Snack intervention reduced probability of nocturnal hypoglycemia from 23.9 ± 14.1% to 14.0 ± 13.3% and duration from 7.4 ± 7.0% to 2.4 ± 3.3% in silico. Our findings indicate that the ENN-based Smart Snack intervention has the potential to significantly reduce the frequency and duration of nocturnal hypoglycemic events. A decision support system that combines prediction of minimum nocturnal glucose and proactive recommendations for bedtime carbohydrate intake might effectively prevent nocturnal hypoglycemia and reduce the burden of glycemic self-management.

SAT144 Hospital Hypoglycemia: An Analysis Of Risk Factors And Patients Outcomes

Abstract Disclosure: A.R. Pichardo-Lowden: None. S.G. Goud: None. T.M. Gallagher: None. E.B. Lehman: None. M.D. Bolton: None. P.A. Homburger: None. K.M. Kearcher: None. Inpatient hypoglycemia (HG) is prevalent and often preventable. Whether an indicator of disease severity or a consequence of management, it conveys worse outcomes and costs. HG prevention is a quality and safety endeavor denoting hospitals performance. We examined risk factors and HG contribution to mortality, hospital length of stay (LOS), charges and readmissions. We defined HG as glucose ≤40 mg/dl (severe), &amp;gt;40 - ≤70 mg/dl (moderate), and euglycemia &amp;gt;70 mg/dl. Electronic health record data was extracted using a business intelligence tool. A retrospective analysis of adults (≥18 y) with diabetes (DM) admitted to a quaternary center compared HG vs. euglycemia. HG was the primary outcome predictor in multivariable models adjusted for covariates, including severity of illness (SOI). The analysis included 54,358 admissions with type 1 (7.2%) or 2 (92.8%) DM admitted to medical (66.8%), surgical (30.3%), and other services (2.9%) in intensive (ICU) (7.3%) and non-ICU (92.7%) over 10 years. Subjects had at least one moderate (M) 9,713 (17.9%) or severe (S) 1,950 (3.6%) HG event. Factors significantly associated with either M or S HG in the hospital included TIDM (P=&amp;lt;0.001), preadmission insulin (P=&amp;lt;0.001) or DM treatment (P=&amp;lt;0.001), receiving insulin (P=&amp;lt;0.001), fasting status (S P=0.001), enteral or parenteral nutrition (P=&amp;lt;0.001), restraints orders (S P=0.002, M P=&amp;lt;0.001), first point-of-care glucose test &amp;gt;12 hours from admission (P=&amp;lt;0.001), ICU status (P=&amp;lt;0.001), high SOI (P=&amp;lt;0.001), altered mental status (P=&amp;lt;0.001), prior admission for HG (P=&amp;lt;0.001), sepsis, acute and chronic kidney injury, and HG unawareness, (P=&amp;lt;0.001) chronic congestive heart failure HF) (S P=0.005, M P=&amp;lt;0.001), acute HF (S P=0.002, M P=&amp;lt;0.001), fall risk (S P=0.006, M P=&amp;lt;0.001), chronic liver disease (M P=0.012). Outcomes analysis revealed that severe HG was associated with in-hospital mortality (P=0.001). Moderate HG was associated with 30-day readmission (P=0.014). Both severe and moderate HG were associated with 90-day mortality (S P=0.002, M P=&amp;lt;0.001,), discharge requiring home care (S P=&amp;lt;0.001, M P&amp;lt;0.001), to a rehabilitation facility (S P=&amp;lt;0.001, M P=&amp;lt;0.001), or skilled nursing facility (S P=&amp;lt;0.001, M P=&amp;lt;0.001), all independent of SOI. Moderate and severe HG increased median LOS (P=&amp;lt;0.001) and median hospital charges (P=&amp;lt;0.001) among severely and non-severely ill subjects. These increases were greater in the high-SOI group versus low-SOI for moderate HG (P=0.044, P=0.027), but not for severe HG (P=1.0, P=1.0). The deleterious consequences of HG independent of SOI, as reported here, depicts HG as the likely cause of poor outcomes, and not just a byproduct of illness. Many factors predisposing to HG are recognizable and can be anticipated in clinical practice. These findings reaffirm the need for preventive measures deployed to hospitals’ systems of practice as strategies to improve outcomes. Presentation: Saturday, June 17, 2023

SAT157 Management Of Spontaneous Hypoglycemia In Dialysis-dependent Chronic Kidney Disease Using Diazoxide

Abstract Disclosure: A. Schledwitz: None. S.S. Habbsa: None. F. Sotomayor Villanueva: None. Y. Kim: None. Background: Patients with end-stage renal disease (ESRD) are at increased risk of spontaneous hypoglycemia due to decreased renal insulin clearance. Due to its inhibitory effect on pancreatic beta cell insulin secretion, oral diazoxide has been used to treat hypoglycemia due to insulinoma or congenital hyperinsulinemic hypoglycemia, but few cases detail the use of diazoxide in the ESRD population. Here, we present 4 cases of spontaneous hyperinsulinemic hypoglycemia in ESRD successfully treated with diazoxide. Clinical Cases: A 66-year-old man with ESRD presented with altered mental status secondary to severe hypoglycemia despite continuous IV 20% dextrose. Labs revealed glucose 50 mg/dL, insulin 7 (0-3 mcIU/mL), C-peptide 7.8 (0-0.6 ng/mL), proinsulin 35.7 (0-5 pmol/L), beta-hydroxybutyrate [bOH] 0.4 (0-2.7 mg/dL), negative sulfonylurea panel, normal cosyntropin stimulation test and undetectable insulin antibodies, without radiographic evidence of insulinoma. He was started on diazoxide 50 mg TID and remained euglycemic for the remainder of his course. On similar readmission 3 months later, he was restarted on diazoxide with resolution of hypoglycemia within 1 day. A 66-year-old male with ESRD and T1DM treated with pancreas transplant presented with toe gangrene and persistent hypoglycemia. Fasting labs revealed insulin 4, C-peptide 4.5, proinsulin 4.5, and bOH 4.5, without radiographic evidence of insulinoma. He maintained euglycemia 4 days after diazoxide 70 mg BID was started. A 67-year-old male with T2DM and ESRD was admitted for osteomyelitis and 2 years of episodic symptomatic hypoglycemia despite dietary adjustments. Labs showed glucose 59, insulin 7, C-peptide 5.2, proinsulin 7.5, bOH 0.04, and unremarkable imaging. Within 1 day of starting diazoxide 100 mg daily, his blood glucose stabilized, and he was discharged. Finally, a 42-year-old male with ESRD presented with 4 years of persistent episodic hypoglycemia, now refractory to continuous IV dextrose. He was found to have glucose 64, insulin 15, C-peptide 11.5, proinsulin 29, and bOH 0.1, with imaging revealing bulky pancreas without a discrete mass. His hypoglycemic episodes resolved within 1 day of starting diazoxide 100 mg daily. He was readmitted 3 months later for catheter site infection and had no episodes of hypoglycemia with continuation of diazoxide. Conclusion: Diazoxide may be a viable option for the treatment of refractory spontaneous hypoglycemia in patients with dialysis dependent ESRD. Presentation: Saturday, June 17, 2023

SAT142 Utilization Of Continuous Glucose Monitoring In Diagnosis And Management Of Insulinoma

Abstract Disclosure: V. Phan: None. P. kretschmer: None. A.G. Pittas: None. Background: Insulinoma is a rare condition that can cause life-threatening hypoglycemia. Its diagnosis and management are challenging due to the requirement of a prolonged fasting test and frequent blood glucose testing. Continuous glucose monitoring (CGM) is widely available in diabetes management; however, its usage in people without diabetes is limited due to lack of evidence. Here, we report an acutely ill patient where we used professional CGM to streamline and expedite the diagnosis of insulinoma, and personal CGM to titrate medical management with diazoxide. Clinical Case: An 81-year-old woman with complex past medical history was admitted for chest pain and shortness of breath, found to have non-ST-elevation myocardial infarction. During inpatient work up, she experienced several hypoglycemia episodes that resolved with oral glucose intake. She had a history of recurrent hypoglycemia and prior MRI showing pancreatic tumor; however, outside records did not reveal biochemical work-up for insulinoma. Her symptoms were unpredictable, so a professional CGM (Freestyle Libre) was placed. CGM data revealed persistent nocturnal hypoglycemia, and occasional postprandial hypoglycemia. Patient-recorded symptoms were present in less than half of the hypoglycemic periods detected by CGM, indicating hypoglycemia unawareness. Given her acute cardiac condition and knowing her nocturnal hypoglycemia pattern from CGM, we performed a modified 72-hour fasting test that started at midnight and was able to capture a hypoglycemia episode within only 2.5 hours of initiation. Her plasma glucose was 57 mg/dL, insulin was 13 uIU/mL, C-peptide was 1.33 uIU/mL, and proinsulin was 9.5 pmol/L. She had a negative screen for sulfonylurea and there was no evidence of antibodies to insulin, suggesting a diagnosis of insulinoma. While awaiting localization studies, the patient was started on diazoxide. We used the personal CGM connected to our clinic portal to monitor glycemia at home and titrate diazoxide dose and frequency. CGM data showed nocturnal hypoglycemia and minimal daytime hypoglycemia, therefore, we recommended diazoxide only at bedtime to minimize daytime side effects and hyperglycemia. On one occasion, the patient was on as short course of prednisone which typically causes hyperglycemia during the day and hypoglycemia in early morning. CGM allowed us to monitor patterns of steroid-induced hyperglycemia, and we moved the prednisone dose to bedtime which resulted in euglycemia overnight. Conclusion: CGM can be a valuable tool in diagnosing and managing people with insulinomas. The CGM provides information about hypoglycemia frequency and pattern. It also helps detect hypoglycemia unawareness. With CGM, we can choose the right timing for 72-hour fasting test to minimize the length of the procedure. As outpatient, CGM also makes monitoring response to diazoxide a seamless process. Presentation: Saturday, June 17, 2023

THU391 A Case Of Unrecognized Hypoglycemia Due To Methadone Use In A Non-Diabetes Patient

Abstract Disclosure: D. Owais: None. J.R. Fredrick: None. Y. Jamal: None. S. Sajnani: None. Introduction: Methadone is a rare cause of insulin-mediated hypoglycemia. Hypoglycemia can be manifested as autonomic instability (palpitations and diaphoresis) and neuroglycopenia (agitation and altered mentation). We present the case of hypoglycemia in a non-diabetic patient with no renal insufficiency and who was on a high dose of Methadone. Case: A 76-year-old male with a medical history of HTN, CAD, CVA, dementia, chronic opioid use (on methadone 80 mg) initially presented two times to an outside hospital for intractable seizures. The diagnosis of seizure disorder was made and was discharged on valproate. Per his wife, he had a few low blood sugars during those hospitalizations. Within a month of discharge, he was admitted to another hospital for severe bradycardia and had undergone pacemaker implantation. He was then discharged to nursing home (NH). In the NH, the routine laboratory work showed a serum blood glucose of 42; however, it was interpreted as a lab error. The next day, he developed severe metabolic encephalopathy, intractable seizures and transferred to our hospital. On arrival, serum blood sugar was 59, corrected by 50% of dextrose. His physical examination was significant for a thin-built elderly male, lethargic but in no acute distress. The dose of antiseizure medication was adjusted. The Methadone 80 mg daily was resumed. He continued to have intermittent hypoglycemia to as low as 33 despite being on intravenous (IV) dextrose solutions. His symptoms used to improve temporarily after the correction of hypoglycemia. (Positive Whipple’s triad). Blood cultures and urine cultures were negative. Serum cortisol level, IGF -1, TSH levels, blood pressure, and electrolytes were within normal limits. The hypoglycemia workup performed in a fasting state (off IV dextrose) showed endogenous hyperinsulinism with insulin level &amp;gt;3, C-peptide level &amp;gt;0.2, beta-hydroxybutyrate level of &amp;lt;2.7, and negative sulfonylurea screen. CT scan and ultrasound of the abdomen were performed to rule out insulinoma; however, it demonstrated complete atrophy of the pancreas. Therefore, a high dose of methadone was assumed to cause hypoglycemia, as the patient had no hypoglycemic episodes when he could not receive two doses of methadone due to encephalopathy. The trough levels of methadone in the blood were high at 650 ng/dl. Methadone dose was tapered to 60 mg daily. He was also started on octreotide to manage his hypoglycemia. However, the patient developed severe pneumonia, and family opted for hospice. Conclusion: Our case is unique as the patient was developing severe signs of hypoglycemia, including bradycardia and seizures, and treated with a pacemaker and antiseizure medications. His Methadone-induced hypoglycemia was identified late as the cause of his symptoms. Therefore, it is crucial to recognize this side effect of Methadone in differentials in a patient with hypoglycemia. Presentation: Thursday, June 15, 2023

FRI654 Concentrated Regular U-500 Insulin In An Automated Insulin Delivery System: A Case Report

Abstract Disclosure: J. Aurora: None. A. Saraswat: None. Background: Concentrated regular U-500 (U-500R) insulin is commonly used in patients with T2DM who are highly insulin-resistant, requiring more than 200 units of insulin per day. Utilizing U-500R reduces the number of daily injections, decreases injection volume, and improves cost effectiveness. There have been clinical trials using U-500R for continuous subcutaneous insulin infusion (CSII), particularly in Omnipod which has been shown to improve glycemic control and patient satisfaction without an increase in hypoglycemia (1). In addition, U-500R administration via multiple daily injections (MDI) and an investigational U-500R CSII, have been compared and demonstrated improved glycemic control with both modalities, but an increase in nocturnal hypoglycemia with CSII (2). Automated insulin delivery (AID) systems, or hybrid closed loop systems, have not formally been studied in patients with T2DM using U-500R. We present a case of a patient with T2DM with high insulin resistance using U-500R with Omnipod 5 AID system. Clinical Case: A 54-year-old female with T2DM with high insulin resistance was initially on Omnipod Dash with U-100 insulin lispro with baseline A1c 12.1%. She was transitioned to Omnipod 5 in 2022, and over 4 months A1c improved to 8.8%, GMI 8.8%, TIR 38%, TAR 62%, TBR 0%, CV 35.9%, and automated mode 97%. However, her total daily dose was 134 units leading to pod changes every 1.5 days. She expressed interest in switching to U-500R to reduce pod changes while utilizing her current CSII technology. We switched to U-500R, continued automated mode, increased her 24-hour BG target from 120 mg/dL to 130 mg/dL to reduce hypoglycemia risk, and increased her active insulin time from 3 to 6 hours to reflect U-500R kinetics. After 4 weeks, her GMI improved to 8.0%, TIR 47%, TAR 52%, TBR 1%, CV 45.9%, and automated mode 94%. Although nocturnal BG readings were normal, ranging from 70-130 mg/dL, she was having nightly symptoms of relative hypoglycemia. We then adjusted her BG target overnight to 150 mg/dL, which kept BG between 80-130 mg/dL with resolution of her symptoms. Conclusion: U-500R proved to be safe and effective with Omnipod 5 AID. Despite setting a higher BG target, the algorithm continuously kept BG well below this, particularly overnight. However, the safety mechanisms incorporated with the CSII suspended insulin delivery for predicted hypoglycemia. Further research will be required to adapt the automated dosing algorithm to U-500R to reduce the risk of nocturnal hypoglycemia.

SAT140 A Rare Case Of Asymptomatic Severe Refractory Hypoglycemia Due To Hyper-Warburgism In A Young Patient With T-cell Acute Lymphoblastic Leukemia (ALL)

Abstract Disclosure: S. Choe: None. Background: Hyper-Warburgism, exaggerated Warburg effect, is a rare but serious paraneoplastic syndrome caused by excess glucose consumption by cancer cells through glycolytic pathway leading to lactic acidosis and treatment refractory hypoglycemia. Neuroglycopenic symptoms are absent in these patients hence patients do not meet Whipple triad. Clinical Case: A 33yo African American male with past medical history of recently diagnosed cardiomyopathy and atrial fibrillation was initially admitted to outside institution for cardiac ablation then subsequently transferred to our institution for escalation of care in the setting of post-procedural persistent hypoglycemia. He reported symptoms of fatigue and poor appetite. He noted an unintentional weight loss of 30lb over the past 2 weeks. However, he denied fever, night sweats, classic signs and symptoms of hypoglycemia. Vital signs and physical examination were unremarkable. Clinical manifestation of neuroglycopenia was absent despite serum glucose as low as 46 while serum lactate of 23.8 mmol/L (0.5-2 mmol/L). Initial laboratory test notable for lactic acid of 24.2 mmol/L, glucose of 57 mg/dL, bicarbonate of 12 mEq/L, anionic gap of 39 mEq/L, beta hydroxybutyrate of 5.3 mmol/L, IGF-1 of 192 ng/mL (75–212 ng/ml), IGF-II of 570 ng/mL (288–736 ng/ml), AM cortisol of 14.3 μg/dl, ACTH of 41.6 pg/ml, hemoglobin A1c of 4.8 %, fasting insulin of 1 IU/liter, C-peptide of 0.4 ng/ml, and pro-insulin of 2.9 pg/ml. Given suppression of insulin and proinsulin levels and IGF-II level &amp;gt;275 ng/ml, noninsulin-mediated hypoglycemia was suspected. A CT of chest/abdomen/pelvis revealed a subpleural soft tissue mass involving the posterior mediastinum measuring 4.4 x 3.6 x 3.7 cm, diffuse bilateral renal involvement suspicious for renal lymphoma, adenopathy in the bilateral inguinal, axillary, and external iliac chains. Bone marrow biopsy was performed and result was consistent with T-cell ALL. 20% dextrose infusion was titrated up to keep his BG above 70 mg/dl and high dose steroids was initiated to bridge to chemotherapy. Chemotherapy was initiated soon after confirmation of diagnosis by bone marrow biopsy. The lactic acidosis and hypoglycemia dramatically improved shortly after. PET/CT done 4 weeks after first cycle of chemotherapy failed to identify active disease proving the patient’s good response to chemotherapy. Conclusion: The patient presented with noninsulin-mediated hypoglycemia due to rapid glucose use by cancer cell leading to hyper-Warburgism, evident by severe lactic acidosis, spontaneous hypoglycemia, and large tumor burden on CT scan. Absence of neuroglycopenia presumable due to brain using lactate as fuel and, for this reason, Whipple triad cannot be applied to diagnose hypoglycemia in this case. Chemotherapy must be initiated timely manner as it would resolve metabolic abnormalities dramatically as it was seen in our patient. Presentation: Saturday, June 17, 2023

SAT149 In Vitro Characterization Of A Novel Long-acting Glucagon Analog (HM15136) And Its Potential Effect In Animal Models Of Chronic Hypoglycemic Diseases

Abstract Disclosure: J. Kim: Employee; Self; Hanmi Pharm. Co., Ltd. Y. Kim: Employee; Self; Hanmi Pharm. Co., Ltd. B. Ye: Employee; Self; Hanmi Pharm. Co., Ltd. W. Kim: Employee; Self; Hanmi Pharm. Co., Ltd. J. Kim: Employee; Self; Hanmi Pharm. Co., Ltd. S. Bae: Employee; Self; Hanmi Pharm. Co., Ltd. D. Kim: Employee; Self; Hanmi Pharm. Co., Ltd. S. Lee: Employee; Self; Hanmi Pharm. Co., Ltd. I. Choi: Employee; Self; Hanmi Pharm. Co., Ltd. Glucagon plays an essential role in glucose homeostasis, and has been used to treat acute hypoglycemia in diabetic patients. However, due to poor solubility and stability at physiological pH as well as short duration of action, its utility was hampered when managing chronic hypoglycemic diseases. One such example is congenital hyperinsulinism (CHI). CHI is a rare genetic disorder characterized by unregulated insulin secretion which leads to severe hypoglycemia especially during fasting condition. Another example is post-bariatric hypoglycemia (PBH) which can also lead to postprandial neuroglycopenia. Despite this life-threatening condition, no drugs are approved for CHI and/or PBH, and available glucagon therapies are very inefficient and inconvenient due to abovementioned limitations. Thus, to provide more optimal therapy for these chronic hypoglycemic diseases, a novel long-acting glucagon analog (HM15136) was developed. Here, we evaluated HM15136’s 1) solubility and stability at physiologic pH, 2) in vitro properties, and 3) potential therapeutic effect in animal models of CHI or PBH. First, we demonstrated improved solubility of HM15136 (≥150 vs. 0.03 mg/mL) at pH 7.0 and stability at day 20, compared to those of native glucagon. Next, in vitro cAMP assay was performed in CHO cells expressing human glucagon receptor (hGCGR), and HM15136 selectively activated hGCGR as a full agonist (EC50 = 0.024 vs. 0.003 nM; relative activity = ca.12.7%). In line with this, HM15136 promoted glycogenolysis and gluconeogenesis in rat primary hepatocytes in a dose dependent manner (relative potency = ca.20%), confirming glucose producing nature of HM15136. To investigate in vivo therapeutic effect on CHI and PBH, chronic hypoglycemia rats induced by SC infusion of insulin (CHI rats) and postprandial hypoglycemia rats induced by vertical sleeve gastrectomy (VSG rats) were established, respectively. Notably, HM15136 treatment significantly restored FBG by 37.3 ∼ 69.7% (p&amp;lt;0.05 ∼ 0.001) in CHI rats. Consistently, HM15136 treatment significantly prevented a massive BG reduction during MMTT in VSG rats (ΔBG between 0 and 45 min = +21 vs. -30 mg/dL, p&amp;lt;0.001). Furthermore, weekly dosing potential and BG elevation effect of HM15136 were also demonstrated in healthy human subjects (1). Based on these results, HM15136 could be a potential therapeutic option for chronic hypoglycemic diseases including CHI and PBH. Phase 2 clinical study in CHI subjects is on-going to assess the clinical relevance of these findings. Reference: (1) Diabetes Obes Metab. 2022 Mar; 23(3):411-20 Presentation: Saturday, June 17, 2023

FRI665 Hirata's Syndrome: Autoimmune Hypoglycemia Diagnostic Pathway, A Mexican Case Report

Abstract Disclosure: G. Gonzalez De La Cruz: None. D. Porras Farret: None. Introduction: Autoimmune hypoglycemia or Hirata syndrome is a very rare cause of hypoglycemia in western populations, as an example, in Mexico until 2015, there was only a single case reported with these characteristics. Diagnosis is based on episodes of spontaneous, fasting or postprandial hypoglycemia, with endogenous hyperinsulinism, without pancreatic lesions on imaging and positive tests. Objective: To describe the approach to a patient with hypoglycemia, specifically to those with characteristics of autoimmune hypoglycemia syndrome, as well as the general approach to hypoglycemia of endogenous origin and the differential approach in those with a history of type 2 diabetes or drug use with secondary effects. Case description: An 86-year-old woman with a history of high blood pressure, prediabetes, and osteoporosis, presented episodes of dizziness, palpitations, diaphoresis, and syncope, documenting plasma glucose of 40 mg/dl. She was attended by paramedics responding adequately to oral glucose. She was evaluated by Cardiology, Holter was performed with predominant sinus rhythm, frequent atrial extrasystoles (2%) and infrequent ventricular extrasystoles. Next, she was referred to Endocrinology for evaluation and treatment, she was taken empagliflozin as prediabetes medication, and it was suspender. Laboratory studies are requested to address hypoglycemia, with serum insulin levels greater than 600 mU/l, c-peptide 3.9 ng/ml, TSH 6.1, T4T 7.5, T3T 67.8, T4L 1.1, ALT 26 U/L, AST 18 U/L, DHL 247 U/L, GGT 26 U/L, Cortisol 13.8 mcg/dl. An MRI of the upper abdomen was performed where there is no evidence of pancreatic injury. A profile of serum hypoglycemic agents (sulfonylureas in blood) was requested, which were not detected. Subsequently, anti-insulin studies were requested, which were reported in amounts greater than 100 U/ml. The diagnosis of autoimmune hypoglycemia syndrome was made, starting management with prednisone 70 mg every 24 hours, in addition to dietary changes. Conclusion: The approach to hypoglycemia in patients without clear evidence of exogenous administration of hypoglycemic agents must be ordered, taking into account differential diagnoses such as autoimmune causes. In the case of autoimmune hypoglycemia, remission is expected at 6 months, with constant monitoring and adjustment of drugs for underlying pathologies. Presentation: Friday, June 16, 2023

THU390 Case Report On Hirata Syndrome: A Rare Cause Of Hypoglycemia

Abstract Disclosure: M. Pranala: None. V. Kuttiyil Oommen: None. V. Sanker: None. S. Vallabhaneni: None. K. Ajith: None. A. Thomas: None. Introduction: Hirata's disease, also known as insulin autoimmune syndrome (IAS), is a rare cause of hypoglycemia that is characterized by episodes of spontaneous hypoglycemia and insulin autoantibodies in patients who have not received exogenous insulin. IAS has been associated with rheumatoid arthritis and Graves' disease in 96% of Japanese IAS patients, and it has also been associated with other autoimmune disorders like Graves' disease. Case History: We report a case of 73-year-old male presented with the complaints of episodes of profuse sweating, palpitation and numbness over his head. Patient was initially treated symptomatically and since the symptoms were not resolving further evaluation was done. Two hourly GRBS, c- peptide, insulin levels and serum cortisol of our patient was monitored. Patient had extremely high serum insulin levels. Serum insulin antibodies level was also high (&amp;gt;300 U/ml). CT abdomen ruled out pancreatic pathology. It has been speculated that hypoglycemia occurring in IAS is due to dissociation of insulin from its antibodies in the post absorptive state. Our patient was diagnosed with IAS based on the criteria of Hirata. The age at onset, sex, and duration of hypoglycemic attacks, outcome or treatment, medication taken prior to the onset of IAS and background disease were all taken into consideration. In our patient, hypoglycemia occurred spontaneously in the post-absorptive state 4–6 hours after meal rather than after a 72-hour fast test. Extremely high levels of insulin (&amp;gt;200 µIU/mL) and Serum insulin antibodies found to be &amp;gt;30 U/ml were constructive in the diagnosis of IAS. The patient improved on dietary management alone consisting of frequent small meals. Conclusion: In order to facilitate early recognition and prevent unnecessary investigations, this could be the most significant syndrome in the differential diagnosis of endogenous hyper-insulinemic hypoglycemia (EHH). In such patients with a high index of suspicion, insulin autoantibodies should be examined. IAA prevents insulin to bind its receptor in the postprandial phase, possibly resulting in mild hyperglycemia; thereafter, insulin is released from the complexes irrespective of blood glucose concentrations, thus inducing hypoglycemia Presentation: Thursday, June 15, 2023

SAT172 Unmasking A Pediatric Disease In Adult, A Belated Diagnosis

Abstract Disclosure: H. Syed: None. P. Au: None. M.J. Gardner: None. Background: Glycogen storage diseases (GSD) are a rare group of diseases that change the way the body uses and stores glycogen. They are usually diagnosed in the pediatric population. Hypoglycemia can be a sign. Clinical Case: A 32 year old female presented with worsening and more frequent episodes of hypoglycemia. She had no history of diabetes and was not on any hypoglycemic agents. She had been having episodes of spontaneous hypoglycemia since childhood and would get symptomatic as well. No comprehensive workup had been done prior. The episodes were becoming more frequent. A blinded continuous glucose monitor was placed on the patient to monitor her glucose levels. Results indeed showed few episodes of hypoglycemia with glucose levels in the 40s. Interestingly, she also had postprandial hyperglycemia with glucose level above 180 following an episode of hypoglycemia. She underwent a 72 hour fast in the hospital and became hypoglycemic within 24 hours with a low blood glucose of 55, consistent with hypoglycemia, and she was also symptomatic as well. At the same time, her beta hydroxybutyrate increased to 3.91 mmol/L, consistent with ketosis. Her insulin level and C-peptide level at the time of hypoglycemia were 4.35 mcunit/mL and 0.239 nmol/L, respectively, and thus insulinoma was ruled out. She next underwent a mixed meal study during which her postprandial blood glucose increased to at least 198 indicating postprandial hyperglycemia. At the same time, patient's postprandial lactate also elevated to 4 mmol/L, consistent with lactic acidosis. Her symptoms of hypoglycemia resolved once her blood sugar (BG) improved. She met criteria for Whipple’s triad. She also had had an 8 am cortisol of 13.06 mcg/dL and had an appropriate response to the ACTH stimulation test with a 60 minute post cortisol above 20 mcg/dL, thus ruling out adrenal insufficiency as a cause of hypoglycemia. These findings of the 72 hour fast that resulted in hypoglycemia, followed by postprandial hyperglycemia with lactic acidosis are consistent with Glycogen Storage Disorder Type 0. Treatment involves intake of uncooked cornstarch with protein. Patient incorporated both uncooked cornstarch along with increasing amount of protein in her diet and started using a continuous glucose monitor with alarm to monitor her BGs. As a result her episodes of frequent hypoglycemia improved. Conclusion: This case illustrates a rare case of hypoglycemia in an adult that was not thoroughly investigated when she was in her childhood and adolescence. This case teaches the importance of being familiar with pediatric conditions since it is possible that pediatric conditions, especially if they are missed by providers and not appropriately diagnosed. Presentation: Saturday, June 17, 2023