Hypoglycemia Research Articles

Hypoglycemia unawareness identified by continuous glucose monitoring system is frequent in outpatients with type 2 diabetes without receiving intensive therapeutic interventions

BackgroundPatients with diabetes are prone to asymptomatic hypoglycemia (AH) due to diminished ability to perceive the onset of hypoglycemia. However, the actual prevalence and influencing factors of AH in outpatients with type 2 diabetes (T2DM) have not been well investigated.MethodsA total of 351 outpatients with T2DM underwent glucose monitoring by continuous glucose monitoring system (CGMS) for consecutive 72 h without changing their lifestyle and treatment regimens. Hypoglycemia is defined as a blood glucose level less than 3.9 mmol/L, which was further divided into Level 1 hypoglycemia (blood glucose 3.0–3.9 mmol/L) and Level 2 hypoglycemia (blood glucose < 3.0 mmol/L). Univariate and multivariate logistic regression analyses were used to determine the possible risk factors of AH.ResultsIn all 351 subjects studied, 137 outpatients (39.0%) were captured AH events, in which Level 1 AH and Level 2 AH accounted for 61.3% and 38.7%, respectively. 85 (62.0%) of the AH patients experienced nocturnal asymptomatic hypoglycemia (NAH) and 25 (18.2%) exclusively NAH. Multivariate logistic regression analysis demonstrated that patients with younger age, lower hemoglobin A1c (HbA1c), and higher systolic blood pressure (SBP) levels were associated with increased risk of AH. While after further grading of AH, male sex and Dipeptidylpeptidase-4 inhibitors (DPP4i) regime were shown to be associated with lower risk of Level 2 AH.ConclusionsHypoglycemia unawareness could be frequently observed at either daytime or nighttime, although NAH was more common, in outpatients with T2DM. Relative relax HbA1c targets should be considered for patients who are prone to AH.

Assessment and comparison of IVth and Vth year dentistry students’ knowledge of the impact systemic diseases have on dental extraction procedures

Radvilė Raubaitė1, Rūta Rastenienė1 1Vilnius University, Faculty of Medicine, Institute of Odontology, Vilnius, Lithuania Abstract Background. Dentistry students lack confidence to treat patients with systemic diseases. Many referrals to oral surgery departments are considered as routine procedures, which may cause a delay of service to more critical patients. Reluctance to perform dental extraction procedures on patients with systemic diseases may be due to lack of knowledge in managing potential postoperative complications (e.g. postoperative bleeding, delayed wound healing, hypoglycaemic shock). Aim. To assess and compare the knowledge of 4th– and 5th-year Lithuanian dentistry students on the influence systemic diseases have on dental extraction procedures, determine factors leading to one’s better knowledge and assess the need for practical guidelines. Methods. An anonymous survey was presented electronically to 4th– and 5th– year Lithuanian dentistry students. Statistical data analysis was performed with program R. Results. On average, 40.3 percent of answers to theoretical questions were correct. 5th year students’ knowledge on hypertension and diabetes was significantly better than 4th year students (p < 0.05). The knowledge of students, who expressed further interest in minimal surgical interventions, was significantly more extensive (p = 0.02). Most respondents (96.2 percent) indicated the need for practical guidelines on the topic. Conclusions. Although being a final-year student was a significant factor in deeper understanding of the effect diabetes and hypertension have on dental extraction procedures, all students generally may lack expertise in this field. Further interest in surgical interventions, including attending conferences, courses or reading scientific literature contribute to ones’ better knowledge. The need for practical guidelines on this topic is significant. Keywords: systemic diseases, tooth extraction, complications after tooth extraction.

Findings for iGlarLixi versus BIAsp 30 confirmed in groups of people with type 2 diabetes with different biomedical characteristics.

To report prespecified and post hoc analyses of the SoliMix dataset exploring the impact of baseline participant characteristics on the original SoliMix study outcomes, to enable informed treatment choices for people with different biomedical characteristics. SoliMix (EudraCT 2017-003370-13) compared once-daily iGlarLixi (a fixed-ratio combination of insulin glargine 100 U/mL and the glucagon-like peptide-1 receptor agonist lixisenatide) with twice-daily BIAsp 30 (30% insulin aspart and 70% insulin aspart protamine). In this analysis, the original primary outcomes of noninferiority of iGlarLixi versus BIAsp 30 in terms of glycated haemoglobin (HbA1c) change and superiority in terms of body weight change, together with change in basal insulin dose and hypoglycaemia outcomes, were investigated by baseline age, duration of diabetes, insulin dose, HbA1c level, body mass index (BMI), and renal function. No evidence of difference in comparative treatment effect was detected across baseline age, duration of diabetes, insulin dose, HbA1c level, BMI and renal function subgroups for any endpoint (all heterogeneity P> 0.05), except American Diabetes Association Level 2 hypoglycaemia event rate when stratified by insulin dose (P= 0.011), which may be a chance difference given multiple testing and the small numbers of Level 2 events. Treatment effects of iGlarLixi were consistent irrespective of baseline HbA1c, insulin dose, BMI, age, duration of diabetes and renal function, supporting the use of iGlarLixi as an efficacious and well-tolerated treatment option in people with type 2 diabetes with a wide range of biomedical characteristics.

Assessment of innate immune response modulating impurities in glucagon for injection.

Glucagon for Injection is a polypeptide hormone medication used to treat patients with severe hypoglycemia or low blood sugar. Only recently, was a generic version of glucagon for injection approved by the FDA. While the generic version was deemed equivalent to its brand-name counterpart, the two glucagon products were produced using different manufacturing processes. The brand-name glucagon is produced via recombinant DNA while the generic glucagon is produced by peptide synthesis. Different manufacturing processes can result in different levels of innate immune response modulating impurities (IIRMIs). This study utilized a cell-based assay method, which allows for detection of a broad spectrum of impurities, to investigate the IIRMI risks of the generic glucagon to make sure it has similar or less immunogenicity risks than the brand-name glucagon product. Three commercial cell lines (RAW-Blue™, HEK-Blue™-hNOD1 and HEK-Blue™-hNOD2) carrying a secreted embryonic alkaline phosphatase reporter construct were used to quantify the level of innate immune responses after being treated with the glucagon drugs. The study results showed that despite differences in manufacturing process, the innate immunogenicity risk in the synthetic (generic) glucagon was at negligible level and comparable to the recombinant (brand-name) glucagon product.

Is graphene the rock upon which new era continuous glucose monitors could be built?

Diabetes mellitus' (DM) prevalence worldwide is estimated to be around 10% and is expected to rise over the next decades. Monitoring blood glucose levels aims to determine whether glucose targets are met to minimize the risk for the development of symptoms related to high or low blood sugar and avoid long-term diabetes complications. Continuous glucose monitoring (CGMs) systems emerged almost two decades ago and have revolutionized the way diabetes is managed. Especially in Type 1 DM, the combination of a CGM with an insulin pump (known as a closed-loop system or artificial pancreas) allows an autonomous regulation of patients' insulin with minimal intervention from the user. However, there is still an unmet need for high accuracy, precision and repeatability of CGMs. Graphene was isolated in 2004 and found immediately fertile ground in various biomedical applications and devices due to its unique combination of properties including its high electrical conductivity. In the last decade, various graphene family nanomaterials have been exploited for the development of enzymatic and non-enzymatic biosensors to determine glucose in biological fluids, such as blood, sweat, and so on. Although great progress has been achieved in the field, several issues need to be addressed for graphene sensors to become a predominant material in the new era of CGMs.

Abstract 13573: Machine Learning to Identify Predictors of Lapses in a Beginners’ Exercise Program for Adults With Type 1 Diabetes

Introduction: People with type 1 diabetes (T1D) are advised to perform the amounts of exercise recommended for the general population but encounter additional barriers including blood glucose management and fear of hypoglycemia. We previously reported that 20 adults with T1D (55% female) that received personalized biosensor feedback, completed mood diaries, and accessed on-demand instructional videos for 10 weeks increased their exercise to levels that partially met recommendations (median 64 [IQR 20, 129] minutes/week). Herein we use machine learning methods to predict the occurrence of lapses (i.e., days when exercise was not performed). Methods: We modeled exercise lapses using 95 possible predictive features derived from the prior 7 days of: 1) continuous glucose monitor summary statistics (mean, variability, time &gt;180, 70-180, &lt;70 mg/dL) for each daytime, nighttime, and 24hr window; 2) negative glycemic experiences around exercise (hypo/hyperglycemia, excessive insulin-on-board, nocturnal hypoglycemia); 3) subjective fear of hypoglycemia entered each morning and evening; 4) subjective sleep quality; and 5) illness. We created three different models using Random Forest (RF), Support Vector Machine (SVM), and Deep Neural Network (DNN) with an 80:20 train-test split of the data (960 training &amp; 240 testing days). We used upsampling to balance the data between lapse and non-lapse days. Results: First, the SVM achieved 71.2% with the most important features being sickness, mean nighttime glucose levels, 24hr time &lt;70 mg/dL, and variability. Next, the RF achieved a higher accuracy (74.1%) with the most important feature being sleep (significance 0.16) followed by the negative glycemic experiences around exercise (0.09 - 0.14). The most accurate model was the DNN with 5-fold cross-validation (75.2% accuracy, 77.5% precision, 71.4% sensitivity). Conclusion: Machine learning models that leverage biosensor, mood, and sleep data may be used to predict exercise lapses for adults with T1D, which could inform just-in-time motivational prompts in future mobile exercise interventions. Model performance might be improved by including subject-level features (e.g., demographics) and adding a sleep biosensor to complement sleep ratings.

Comparison of Once-daily Versus Twice-daily Injection of Insulin Detemir in Children with Type 1 Diabetes Mellitus

Background: The purpose of this study was to compare the effectiveness of once-daily versus twice-daily insulin detemir injection in children with type 1 diabetes mellitus (T1DM). Methods: In this randomized 4-month clinical trial, 60 children aged 33 - 156 months with T1DM were randomly assigned into two groups, once-daily (group 1) and twice-daily (group 2) detemir insulin injection with pre-meal insulin Aspart. The first month of the study was devoted to educating the patients and insulin dose titration. Hemoglobin A1C (HbA1C) measured at the end of the first month and again after the fourth month. Hypoglycemia as one of the major complications was defined as blood glucose lower than 70 mg/dL with clinical symptoms or blood glucose lower than 50 mg/dL in the absence of clinical symptoms. Results: Mean HbA1C in the fourth month was 8.5% ± 1% in group 1 and 8.5% ± 1.1% in group 2 (P = 0.98). Mean changes in the fourth month compared to baseline were -0.09% (95% CI: -0.47 - 0.3) in group 1, and -0.42% (95% CI: -0.94 - 0.09) in group 2 (P = 0.273). The treatment modification rate was 39% and 15% in groups 1 and 2, respectively (P = 0.02). However, there were no statistically significant differences between the two groups in terms of insulin dose, hypoglycemia, and other complications. Conclusions: Twice-daily injections did not change HbA1c in comparison with once-daily injections. However, the lower treatment modification rate in the twice-daily group in the age group of our study was considerable.

A randomized controlled trial examining the effects of treatment with propylene glycol and injectable cyanocobalamin on naturally occurring disease, milk production, and reproductive outcomes of dairy cows diagnosed with concurrent hyperketonemia and hypoglycemia.

The objective of this study was to assess the effects of treatment with propylene glycol (PG) and cyanocobalamin (B12) on health, milk production, and reproductive outcomes of cows diagnosed with hyperketonemia (HK), hypoglycemia (HG), or concurrent HKHG. Glucose and β-hydroxybutyric acid (BHBA) concentrations were assessed in whole blood using a handheld device in lactating dairy cows (n = 2,418) between 3 and 9 d postpartum. Cows categorized as HK (n = 232, BHBA ≥1.2 mmol/L), HG (n = 161, glucose ≤2.2 mmol/L), and concurrent HKHG (n = 204, BHBA ≥1.2 mmol/L, and glucose ≤2.2 mmol/L) were randomized to receive treatment or to remain untreated (control). Treatment consisted of a single dose of B12 (10 mg, intramuscularly) and 300 mL of PG orally for 5 d, starting on the day of cow-side testing. Milk production, health, and reproductive outcomes were analyzed according to groups. Statistical analysis was carried out using SAS version 9.4 (SAS/STAT, SAS Institute Inc.). Treatment in HG cows decreased clinical ketosis, increased milk production in the fifth week of lactation for multiparous cows, and tended to increase 305-d mature-equivalent milk yield (305ME) for primiparous cows compared with untreated cows with the same metabolic profile. For cows with HKHG, treatment increased 305ME in multiparous cows and tended to increase 305ME in primiparous cows. No differences were found for treatment among any of the metabolic groups regarding reproductive outcomes, nor were any treatment effects found among HK cows. Glycemic status may help identify metabolically challenged early postpartum dairy cows, which may have differential response to PG and B12 treatment.

A hypoglycemia early alarm method for patients with type 1 diabetes based on multi-dimensional sequential pattern mining

Hypoglycemia is a limiting factor for blood glucose management. Serious symptoms such as seizures, and coma may occur during severe hypoglycemia, and nocturnal hypoglycemia is particularly dangerous for patients with type 1 diabetes (T1D). An effective early alarm method is essential for hypoglycemia prevention but challenging, as blood glucose is affected by many factors and the hypoglycemia sequence patterns vary from person to person. In this paper, we proposed a hypoglycemia early alarm method for mining the hidden information in blood glucose based on multi-dimensional sequential pattern mining. The blood glucose, meal, and insulin time series information were used to construct a multi-dimensional database, then the UniSeq algorithm was used to extract multi-dimensional hypoglycemia sequence patterns. Hypoglycemia early alarm was realized through pattern matching with real-time blood glucose. The public OhioT1DM dataset was used for performance evaluation. The experiment results were: 75.76% Sensitivity, 75% Precision, 75.38% F1 score, and 25.17 minutes early alarm time. The result verified that multi-dimensional sequential pattern mining can extract more hidden information and demonstrate more potential significance in providing comprehensive diagnosis support for personalized treatment. Furthermore, early alarms for potential hypoglycemia can also reserve sufficient time for blood glucose management.

PSUN227 A retrospective comparison of Basal Bolus using Glargine U-300 and Glulisine with Premix Insulin

Abstract Objectives The objective of this retrospective analysis was to compare the occurrence of Level 1 hypoglycaemia, Level 2 hypoglycaemia, nocturnal hypoglycaemia and mean HBA1C reduction in patients treated with premixed insulin 30/70 (Insulin Isophane/NPH 70% + Human Insulin/Soluble Insulin 30%) and after initiating a basal bolus regime using Glargine U-300 and Glulisine. Level 1 hypoglycaemia is blood glucose less than 70 mg/dL but above 54 mg/dL. Level 2 hypoglycaemia is blood glucose less than 54 mg/dL. Methodology and Data Analysis Data was collected retrospectively over 6 months on adult outpatients who were on pre mix insulin 30/70 for at least 2 years and who frequently experienced hypoglycaemic episodes and after transitioning these patients to a basal bolus regime Glargine U-300 and Glulisine. Those were having an underlying etiology which would predispose them to hypoglycaemia were excluded. The exclusion criteria included malignancy, drug induced causes except premix insulin, Chronic Kidney disease stage 4 or 5 and acute or chronic hepatic failure. Blood glucose monitoring was done by a 7 point Self Monitoring of Blood Glucose. A total of 30 cases were randomly chosen and data were sought from patients’ home glucose logs, case notes and Electronic health care records. Data were analysed by Microsoft Excel and was compared with paired-T test. Results The average number of Level 1 hypoglycaemic episodes per week on premix insulin dropped from 6.517 to 0.9655 (t = -10.807456, p&amp;lt;0.00001) after initiating the basal bolus regime. The average number of level 2 hypoglycaemic episodes per week dropped from 2.034 to 0.379 (t = -8.733497, p&amp;lt;0.00001) after changing to basal bolus regime. There was also a reduction in the occurrence of average nocturnal hypoglycaemic episodes from 2.655 on pre mix insulin to 0.2068 on the basal bolus regimen (t = -8.635475, p&amp;lt;0.00001).The mean HbA1C reduction was 3.16% in three months after commencing the basal bolus regime (t = -27.554737, p&amp;lt;0.00001). Conclusions Outpatient treatment with the basal bolus regime consisting of Glargine U -300 and Glulisine as compared to the premix insulin use showed a marked reduction in Level 1 and Level 2 hypoglycaemic episodes and nocturnal hypoglycaemic episodes per week. The decreased hypoglycaemic event rates in hypoglycaemia resulted in better compliance and adherence which was reflected as a significant reduction in HbA1C. In the future more retrospective and prospective studies will be helpful with Glargine U-300 and Glulisine. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

Sleep and Circadian Rhythm Disturbances in Diabetes: A Narrative Review.

Sleep and circadian rhythm disturbances are less-known risk factors for the development and suboptimal outcomes of diabetes. The goal of this narrative review is to highlight the importance of sleep and circadian rhythm disturbances in the development and outcomes of type 1 diabetes (T1D) and type 2 diabetes (T2D), assess current treatment options and the possible mediating mechanisms. We performed a literature search using PubMed and selected relevant English and Dutch papers. Disturbances of sleep and circadian rhythm are common in people with diabetes. They are associated with an increased risk of developing T2D as well as with suboptimal diabetes outcomes (including higher HbA1c levels and reduced quality of life) for T1D and T2D. Preliminary data suggest that treatment of sleep and circadian rhythm disturbances could improve diabetes outcomes in people with T1D and T2D. Finally, the association with medical parameters appears to be mediated by disturbance in hormones, and by suboptimal self-care including forgetting or postponing glucose monitoring or medication use as well as higher consumption of high fat/high sugary foods. Diabetes may also disturb sleep, for example through nocturnal hypoglycemia and nocturia. We concluded that sleep and circadian rhythm disturbances are closely linked with diabetes. More attention to sleep in regular diabetes care is warranted, while further research is needed on treatment of sleep and circadian rhythm disturbances in the prevention of diabetes and its suboptimal outcomes.

Comparative efficacy and complications of long-acting and intermediate-acting insulin regimens for adults with type 1 diabetes: an individual patient data network meta-analysis

ObjectiveTo examine the comparative efficacy and complications of long-acting and intermediate-acting insulin for different patient characteristics for type 1 diabetes mellitus (T1DM).DesignSystematic review and individual patient data (IPD) network meta-analysis...

ODP157 A Case of Pancreatic Insulinoma With Hypoglycemia Unawareneness

Abstract Clinical Case An 84-year-old woman with hypertension, type 2 diabetes, and a history of frequent falls, presented to the hospital after one week of recurrent falls with progressive worsening right-sided weakness, speech difficulties, and urinary incontinence. She was found to have a 2.8cm subacute subdural hematoma with midline shift and underwent successful subdural evacuation placement, nevertheless, her course was complicated by asymptomatic hypoglycemia. During her prolonged hospitalization, she experienced a 15-pound weight loss, initially attributed to poor oral intake. She was previously on glimepiride for her diabetes but this was discontinued about two months prior for low sugars. The patient did not meet Whipple's triad, as she denied symptoms of hypoglycemia and felt no different once her glucoses normalized. However, nursing staff noticed a slight difference in her cognition and behavior during these hypoglycemic episodes, which improved after correction. Laboratory testing: A fasting protocol was initiated. After seven hours, her finger stick blood glucose dropped to 42 mg/dL. Her Insulin 23.8 uU/mL (1.9-23), Proinsulin 46.9 pmol/L (&amp;lt;10), and C-peptide 5.3 ng/mL (0.9-7.1) were relatively high at this time, despite a confirmed low plasma glucose of 47 mg/dL. Beta-hydroxybutyrate was 0.24 mmol/L (&amp;lt;0.3) with Hemoglobin 16.5 G/dL (11.7-15),and HbA1c 5.6%. Her blood glucoseimproved to 126 mg/dL after administration of 1mg glucagon. Anti-Insulin antibody &amp;lt;5 uU/mL and a sulfonylurea screen were negative. The fasting protocol was discontinued and she was started on Dextrose 10% infusion, then transitioned to diazoxide. A dedicated MRI of the abdomen did not demonstrate any pancreatic lesions. An esophagogastroduodenoscopy was then performed, revealing a 12-mm mass in the head/uncinate of the pancreatic body. FNA confirmeda low-grade, well-differentiated neuroendocrine tumor. Immunohistochemical stains were positive for Insulin and Synaptophysin, and negative for Chromogranin, supporting the diagnosis of insulinoma. Endoscopic ultrasound with successful ethanol ablation was completed. Subsequently, her hypoglycemia rapidly improved off treatment. Conclusion Per the 2009 Endocrine Society guidelines, evaluation of recurrent low blood sugar is only recommended if Whipple's triad is present. However, this case highlights that hypoglycemia unawareness can mask Whipple's triad. It is not unusual for patients with longstanding hypoglycemia to lose neurogenic and neuroglycopenic symptoms. This can complicate and delay the diagnosis of insulinoma, as it did in this patient with multiple falls. Her documented weight loss, decreased oral intake, and relatively high HbA1c are not classic of insulinoma and were further obstacles for diagnosis. Endocrine guidelines should incorporate the importance of hypoglycemia unawareness into its algorithm. In this setting, we should consider a lower threshold to initiate fasting protocol and biochemical testing during a hypoglycemic event (&amp;lt;55mg/dL). Presentation: No date and time listed

Longitudinal modeling of fasting blood sugar with diabetes: A case study of Adama Hospital Medical College, Ethiopia.

The aim of this study was to evaluate the change in fasting blood sugar (FBS) over time and its determinants in diabetic patients. A longitudinal data analysis retrospective-based study was considered with a sample of 312 patients, and the linear mixed effect model was applied. Based on the linear mixed model, the 3-month change in time decreases the average FBSlevel by 0.0111. An increase of one unit of body mass index (BMI) increases the FBS level by 0.0434. Similarly, an increase in blood pressure (DBP) per unit increased the average log FBS level by 0.0005. Secondary and higher education levels lower log FBS levels by 99.41%and 99.45%, respectively, compared with noneducated individuals. The study showed that hypertension history, type of diet, age, status of education, type of drug, body mass index, diastolic blood pressure, and time were statistically significant factors. According to the study, eating a healthy diet, maintaining a healthy body weight, and a low blood sugar level are essential to controlling blood sugar and preventing long-term complications. The government should build an educational institution proportional to the population and open programs to increase awareness about the prevention mechanism of diabetes in communities.

PSUN374 Casting a Wide NET: A Case Report of Recurrent Hypoglycemia and 'Malignant' Insulinoma

Abstract Introduction Insulinomas are rare neuroendocrine tumors, with an incidence of 4 cases per one million patient-years. Malignant insulinomas are even rarer, with a paucity of data for specific treatment modalities. Surgery, the mainstay of treatment, needs to be determined by the disease extent prior to resection. Here, we describe a patient who presented to a Federally Qualified Health Center with a diagnosis of hypoglycemia and the barriers related to the evaluation and treatment of his insulinoma. Case Presentation A 40-year-old Hispanic man with no past medical history presented to the clinic with an 8-year history of syncopal episodes. Continuous glucose monitoring revealed nocturnal hypoglycemia with BG &amp;lt;50 mg/dL, but he discontinued its use due to frequent low blood glucose alerts. Physical exam was notable for central obesity and acanthosis nigricans. Labs showed a fasting glucose of 63 mg/dL, proinsulin 419.9 (&amp;lt;18.8 pmol/L), insulin 11.3 (&amp;lt;19.6 uIU/ml), C-peptide 2.24 (0.80-3.85 ng/mL), A1C 4.3%, and negative urine sulfonylurea screen. A diagnosis of insulinoma was suspected and he was started on acarbose. CT abdomen showed a centrally calcified, peripherally enhancing 24 mm lesion in the pancreatic head. 68Ga-DOTATATE PET/CT scan was recommended for further evaluation but was denied by his insurance. Biopsy of the mass using endoscopic ultrasound (EUS) was positive for neuroendocrine tumor with metastasis to a peripancreatic lymph node. Given the concern for metastatic insulinoma, he underwent a pancreaticoduodenectomy. Surgical pathology confirmed the diagnosis of insulinoma but without evidence of tumor in the lymph nodes. The most likely explanation for the tumor cells previously noted in the lymph node was the passage of the needle through the tumor during biopsy. The postoperative course was complicated by hyperglycemia requiring insulin infusion and a pancreatic fistula. The patient was followed in clinic where his repeat proinsulin level was normal. He had resolution of his hypoglycemic episodes, his fistula healed, and he is back at work. Discussion Our case reinforces the need for an accurate diagnosis and localization of neuroendocrine tumors prior to surgical intervention. A preoperative 68Ga-DOTATATE PET/CT would have demonstrated an absence of tumor outside the pancreatic mass and prompted a less invasive surgical approach. Because of insurance denial, the EUS biopsy findings suggesting metastatic insulinoma could not be confirmed and he underwent a pancreaticoduodenectomy. Patients with metastatic insulinoma are at risk for recurrence of hypoglycemia in the postoperative period. Persistence of postoperative hyperglycemia suggests either new-onset diabetes due to insulin deficiency or resistance and suppression of residual endogenous insulin secretion as a result of insulinoma-induced chronic hyperinsulinemia. Decreases in insulin requirements post-operatively can be explained by recovery of remnant pancreatic insulin production after alleviation of chronic suppression, and reduction in insulin resistance induced by surgery. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

PSUN254 Hirata's Disease - An Unexpected Surprise

Abstract The diagnosis of hypoglycemia in adults without diabetes mellitus is a medical challenge. Insulin autoimmune syndrome (IAS), also known as Hirata's Disease, is a rare condition characterized by episodes of spontaneous hypoglycemia secondary to hyperinsulinemia in the setting of positive insulin autoantibodies. 380 cases of IAS have been reported worldwide between 1970 and 2009 with majority of cases seen in patients of Asian descent. Here we present a case of a patient who presented with episodes of recurrent hypoglycemia secondary to IAS.85 year old Asian female presented to the endocrinology office for recurrent episodes of presyncope which were associated with presumed hypoglycemia. Patient denied a history of gastric bypass surgery, diabetes, use of oral hypoglycemic agents, change in eating habits, fevers, weight loss, or night sweats. A continuous glucose monitor was placed during the visit due to patient having difficulties using a glucometer and on follow-up, multiple episodes of hypoglycemia were noted, dropping down to 50mg/dL throughout the day. Due to recurrent symptomatic hypoglycemic episodes, she was admitted to the hospital for a workup. Point of care (POC) glucose on presentation to the ED was 166 mg/dL. 4 hours later in the ED, POC glucose was 42 mg/dL with serum confirmation of 44 mg/dL. Last meal was about 6 hours prior to this event and no dextrose containing solutions were used in the ER. Prior to correction of hypoglycemia, blood specimen sent for the following: c-peptide 3.4 ng/mL, beta-hydroxybutyrate 0.12 mmol/L, insulin level 285 µIU/mL, and proinsulin 93.7 pmol/L. Sulfonylurea screen was negative. CT pancreas with IV contrast showed no evidence of pancreatic mass suggestive of insulinoma. Due to recurrent episodes of hypoglycemia in the hospital, the patient was started on Diazoxide 50 mg every eight hours. An insulin antibody level sent from the initial specimen, eventually resulted and was elevated to above 50 U/mL. A comprehensive review of the patient's medications was performed; none were new or were associated with autoantibody formation. Patient denied recent symptoms of viral illness or family history of hypoglycemia. Literature review revealed the possible benefits of acarbose over diazoxide in management of IAS; diazoxide was switched to acarbose 50 mg three times a day before meals. Outpatient follow-up showed drastic reduced frequency of hypoglycemia while on Acarbose.IAS is a rare but important etiology of hypoglycemia in adults without diabetes mellitus. IAS involves the formation of insulin autoantibody complexes, which binds to the insulin receptors and prevents insulin from binding to its receptors in the postprandial phase. Insulin is then released from the complexes irrespective of blood glucose concentrations, therefore inducing postprandial hypoglycemia. Prompt recognition and diagnosis of IAS can allow for appropriate treatment and avoidance of performing unnecessary imaging and invasive procedures. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

Efficacy and Tolerability of Insulin Degludec Versus Other Long-acting Basal Insulin Analogues in the Treatment of Type 1 and Type 2 Diabetes Mellitus: A Systematic Review and Meta-analysis

PurposeThe goal of this study was to compare the efficacy and tolerability of insulin degludec with those of other long-acting insulin analogues (insulin glargine and insulin detemir) in patients with type 1 or 2 diabetes mellitus (T1D or T2D). MethodsThose randomized controlled trials comparing insulin degludec with other long-acting insulin analogues in the treatment of patients with T1D or T2D published on or before August 21, 2022, were retrieved from PubMed, Web of Science, the Cochrane Library, and EMBASE. The efficacy end points were the changes from baseline in hemoglobin A1c and fasting plasma glucose (FPG). The tolerability end point was the prevalence of hypoglycemia confirmed throughout the treatment period. FindingsData from a total of 20 trials (19,048 patients) were included. The differences in the reductions in glycosylated hemoglobin between insulin degludec and other long-acting basal insulin analogues (insulin glargine and insulin detemir) used for the treatment of patients with T1D or T2D were not significant. However, the reduction in FPG was greater with insulin degludec (–0.370 mmol/L; 95% CI, –0.473 to –0.267 mmol/L; P ≤ 0.001). Throughout the treatment periods of all of the available trials, the estimated rate ratios of overall and nocturnal hypoglycemia were significantly decreased with insulin degludec compared with insulin glargine or insulin detemir in patients with T1D or T2D; the differences in the risks for severe hypoglycemia were not significant. ImplicationsCompared with other long-acting insulin analogues (insulin glargine and insulin detemir), insulin degludec was associated with a significantly decreased FPG, with lower prevalences of overall and nocturnal hypoglycemia.

IGF-2 mediated hypoglycemia and the paradox of an apparently benign lesion: a case report & review of the literature

BackgroundNon-islet cell tumour hypoglycemia (NICTH) is rarely encountered in clinical practice. Insulin-like growth factor 2 (IGF2) is the most common cause of NICTH observed in the setting of mesenchymal and epithelial neoplasia. This is a paraneoplastic syndrome caused by IGF2 activation of the insulin receptor.Case presentationAn 80 year old female presented with a short history of recurrent episodes of confusion with laboratory confirmed hypoglycemia with a plasma glucose of 2.7 mmol/L on fasting which fulfilled Whipple’s triad. Diagnostic clues to the aetiology at presentation include the fasting pattern of hypoglycemia, hypokalaemia and the absence of weight gain. A 72 hour fast with results showed early hypoglycemia and suppression of serum insulin, c-peptide, and proinsulin. Serum insulin antibody was not detected. Subsequent measurement of the serum IGF2:IGF1 ratio was elevated at 22.3 and consistent with IGF-2 mediated hypoglycemia and imaging studies demonstrated a pelvic mass. Dietary intervention and oral prednisolone abated hypoglycemia prior to surgery. Ultimately, hypoglycemia resolved following operative intervention and steroid therapy was successfully withdrawn. Histopathology was remarkable for dual neoplastic processes with uterine solitary fibrous tumour (SFT) confirmed as the source of IGF2 hypersecretion on IGF-2 immunohistochemistry and a coincidental invasive high grade serous carcinoma involving the fimbria of the right fallopian tube.ConclusionThe paradox in this case is that the benign solitary fibrous tumour accounted for patient morbidity through secretion of IGF2 and without treatment, posed a mortality risk. This is despite the synchronous presence of a highly malignant fallopian tube neoplasm. This case reinforces the need for thorough clinical evaluation of hypoglycemia to allow prompt and definitive management.

Barriers to Physical Activity in Children and Adults Living With Type 1 Diabetes: A Complex Link With Real-life Glycemic Excursions

ObjectivesEver since the first research on barriers to physical activity (PA) highlighting fear of hypoglycemia as a major barrier, many studies have attempted to understand their demographic and behavioural determinants. However, no research has been conducted on whether these perceived barriers toward PA are based on real-life–experienced adverse glycemic effects of exercise. MethodsSixty-two adults and 53 children/adolescents living with type 1 diabetes, along with their parents, completed the Barriers to Physical Activity in Type 1 Diabetes-1 (BAPAD-1) questionnaire on barriers to PA. Continuous glucose-monitoring data were collected during 1 week of everyday life for 26 adults and 33 children/adolescents. Multiple linear regressions were used to explore links between BAPAD-1 scores and glycemic excursions experienced during and after everyday-life self-reported PA sessions, controlling for behavioural (accelerometry) and demographic confounders. ResultsIn children/adolescents, the more time spent in hypoglycemia on nights after PA sessions, the more they reported hypoglycemic risk as a barrier (ß=+0.365, p=0.034). Conversely, in adults, the higher the proportion of PA sessions accompanied by a drop in blood glucose, the less hypoglycemia was a barrier (ß=−0.046, p=0.004). In parents, BAPAD-1 scores were unrelated to children/adolescents’ everyday-life exercise-induced hypo/hyperglycemia. ConclusionsIn children/adolescents, fear of hypoglycemia was predominant in those exposed to nocturnal hypoglycemia associated with PA sessions. In adults, fewer barriers may mean they accept a bigger drop in their glycemia during PA. This shows the importance of finding and promoting age-specific solutions to prevent exercise-induced hypoglycemia.

COVID 19 quarantine and its impact on lifestyle of diabetic patients and on their follow up in Madinah, KSA

Objectives: This article aims to discover the impact of the coronavirus pandemic lockdown on diabetes patients living in Almadina, Saudi Arabia, in terms of their lifestyle and on their follow-up. Methods: This is a cross-sectional, qualitative prospective study, a questionnaire was done to diabetic patients who underwent the quarantine period in Madinah, Saudi Arabia through an online questionnaire after getting informed consent to participation. The survey included personal, medical data, patient’s compliance to treatment and overall lifestyle manner before and during lockdown period and psychological assessment using 10 questions of the (K10) Kessler psychological distress scale. Data analysis was performed using SPSS program version 26. Results: A total of patients 350 participated in the study. 56.6% of them were females(n;198), and 43.4% were males(n:152), their ages ranged from 18 years to more than 60 years. The vast majority 96.3% of participated were of Saudi nationality, while 3.7% are non-Saudi. Participants-with types 2 Diabetes represent 31.4% while 26% suffer from type 1 diabetes and the rest they don’t which type they have. Results showed no significant differences in: (symptoms of low or high blood sugar, the extent to which a healthy diet is followed, the frequency of home blood sugar measurement) before and during the quarantine period. The rest of the variables shows a significant difference (P&lt;0.05) Conclusions: The study showed a difference in the extent of adherence to medication during the quarantine period compared to before. A reduction constructive in lifestyle habits is detected.