Postprandial Hypoglycemia Research Articles

BS SO07 - NHS Tertiary Centre Experience with Bariatric Tourism; A Call for National Registry

Abstract Background Bariatric surgery has demonstrated notable efficacy and is becoming an increasingly popular practice. Nonetheless, patients often opt for bariatric tourism due to the unaffordability of bariatric procedures or the lengthy waiting lists. The postoperative care for such patients not only imposes financial burdens on a different health system, necessitating costly interventions for complex cases but also affects the allocation of resources for patients receiving care in the public health services. A national guidance platform and registry are required to measure the impact of bariatric tourism on the modern NHS and plan future resource allocation. Method This is a retrospective review of patients referred to one of the bariatric units in the United Kingdom for complications following bariatric procedures abroad. Patient demographics, bariatric intervention, presenting complications, length of hospital stay and management received were recorded. Results Between 2022 and 2024, our unit admitted nine patients. Eight had sleeve gastrectomy in Turkey, and one had a gastric balloon in Thailand. In the sleeve group, five patients had intractable vomiting, one had small bowel ischemia, one leaked, and one had reactive hypoglycemia. The patient with the gastric balloon had vomiting and abdominal pain, leading to balloon removal. Three sleeve patients had a conversion to Roux-en-Y bypass, one is under investigation, and one is awaiting bypass surgery, one required three surgeries for small bowel ischemia, and one with a leak was treated with a pigtail and gastric stent. Conclusion Medical tourism for bariatric procedures is an appealing option for obese patients due to its affordability and shorter wait times. Patients typically receive brief pre-operative preparation and education in addition to a limited post-operative care. However, managing complex bariatric cases is expensive, necessitates extended hospital stays and nutritional and emotional support, and can only be done in specialised centres. It's important to create a national bariatric surgery guidance platform providing recognised centre details internationally and a national registry of bariatric tourism patients to assess the impact on the healthcare system and to plan for future resource allocation.

Clinical features and search for genetic determinants of postprandial hypoglycemia.

To test whether postprandial hypoglycaemia is an extreme and repeatable phenotype of glucose metabolism. Secondly, we explored the genetic determinants of this phenotype. We conducted this study using data from Pinggu Metabolic Disease Study database (n = 3,345). We selected subjects after an oral glucose tolerance test (OGTT) (2 h, glucose <3 mmol/L_ and compared clinical features with those of normal glucose tolerance (NGT). We additionally selected 75 subjects as super-healthy control group. Whole-exome sequencing (WES) was performed on postprandial hypoglycaemic and super-healthy controls. We also evaluated several candidate genes believed to be important in pancreatic hypoglycaemia. We found 13 participants (0.39%) had an OGTT 2 h glucose <3 mmol/L. Ten patients were men (76.9%). All 13 participants had insulin > 3 uU/mL when postprandial blood glucose levels were <3 mmol/L. WES analysis identified one gene, paternally expressed 3 (PEG3), which had three rare mutations in four patients (30.8%). Minor allele frequencies (MAF) of rare PEG3 mutations were significantly higher in subjects with postprandial hypoglycaemia than in super-healthy controls. Among all four subjects with PEG3 gene mutations, 71.4% were men, and their body mass index (BMI) was significantly lower than that of the NGT. Postprandial hypoglycaemia is an extreme and reproducible phenotype in the general population. PEG3 mutations may represent a potential genetic aetiology for postprandial hypoglycaemia. Further research with larger and more diverse populations and a broader genetic focus is needed to understand the genetic basis of postprandial hypoglycaemia.

Postprandial hypoglycemia as a complication of bariatric and metabolic surgery: a comprehensive review of literature

Postprandial hypoglycemia as a complication of bariatric and metabolic surgery: a comprehensive review of literature

The development of functionalized alginate-based hydrogels for the management of postprandial hyperglycemia and weight reduction

Polysaccharide-derived functional food ingredients are increasingly prevalent in the food industry for their health benefits and functional versatility. Among them, sodium alginate (SA), a natural polysaccharide, is widely valued for its sustainability, renewability, non-toxic nature, and broad applicability. However, its poor water solubility has limited its use as biomedical materials and food additives. Here, we enhanced SA through carboxymethylation to produce carboxymethylated SA (CMSA), aiming to develop functional food ingredients with improved physicochemical properties for health management. The synthesized CMSA was characterized for its physical properties and ability to form a hydrogel through cross-linking with Ca2+. We assessed its encapsulation efficiency for food particles in simulated gastric and intestinal fluids and evaluated its physiological effects in a rat model. Our findings demonstrated that CMSA-based hydrogels effectively encapsulate ingredients in the stomach, reducing nutrient diffusion in the intestine, and helping to manage postprandial hypoglycemia. Additionally, the hydrogel expands in the stomach and small intestine, contributing to modest weight loss. These findings suggest that CMSA-based hydrogels offer significant potential as functional food ingredients for managing postprandial hypoglycemia and supporting weight management. The development of such gelling systems presents promising applications in both medical and nutritional sciences, offering innovative strategies for addressing diet-related health concerns.

Skeletal muscle from TBC1D4 p.Arg684Ter variant carriers is severely insulin resistant but exhibits normal metabolic responses during exercise.

In the Greenlandic Inuit population, 4% are homozygous carriers of a genetic nonsense TBC1D4 p.Arg684Ter variant leading to loss of the muscle-specific isoform of TBC1D4 and an approximately tenfold increased risk of type 2 diabetes1. Here we show the metabolic consequences of this variant in four female and four male homozygous carriers and matched controls. An extended glucose tolerance test reveals prolonged hyperglycaemia followed by reactive hypoglycaemia in the carriers. Whole-body glucose disposal is impaired during euglycaemic-hyperinsulinaemic clamp conditions and associates with severe insulin resistance in skeletal muscle only. Notably, a marked reduction in muscle glucose transporter GLUT4 and associated proteins is observed. While metabolic regulation during exercise remains normal, the insulin-sensitizing effect of a single exercise bout is compromised. Thus, loss of the muscle-specific isoform of TBC1D4 causes severe skeletal muscle insulin resistance without baseline hyperinsulinaemia. However, physical activity can ameliorate this condition. These observations offer avenues for personalized interventions and targeted preventive strategies.

Surgical or medical treatment of obesity-associated type 2 diabetes-an increasing clinical conundrum

In this editorial, we comment on the article by He et al , specifically in relation to the efficacy of bariatric surgery vs glucagon-like peptide-1 receptor agonist (GLP-1RA) therapy in the management of type 2 diabetes (T2D) associated with obesity. Bariatric surgery has now also been shown to be safe and effective in pre-teens and teenagers with obesity and T2D, but information on newer GLP-1RAs in these groups is predictably limited. In older individuals (age &gt; 65 years), both bariatric surgery and GLP-1RA therapy improve cardiovascular outcomes. Bariatric surgery is not infrequently associated with post-operative postprandial hypoglycemia, which is not the case with GLP-1RAs and, paradoxically, there is evidence that GLP-1RAs may reduce both the frequency and severity of postprandial hypoglycemia. Comparative trials of the long-term efficacy of bariatric surgery and GLP-1RAs are indicated.

Potential of GLP-1 Analogs in Managing Hyperphagia and Obesity in Prader-Willi Syndrome: A Review of Efficacy and Safety

Introduction: Prader-Willi Syndrome (PWS) is a genetic disorder marked by hyperphagia, obesity, developmental delays, and behavioral challenges. Traditional treatments like dietary control and growth hormone therapy often fail to effectively manage these symptoms. Recently, glucagon-like peptide-1 (GLP-1) analogs have shown potential in treating PWS. This review assesses the efficacy, safety and mechanisms of GLP-1 analogs in PWS treatment. They improve glycemic control, cardiovascular health, and appetite regulation, contributing to better weight management and overall health in PWS patients. These analogs enhance insulin secretion, inhibit glucagon release, and slow gastric emptying, helping to reduce postprandial glucose spikes and caloric intake. Results: Several small-scale studies and case reports have shown mixed results regarding the effectiveness of GLP-1 analogs in reducing BMI and hyperphagia in PWS patients. Although the studies demonstrated varied outcomes in terms of BMI reduction, all of them reported improvement in satiety or appetite levels.Conclusions: Overall, GLP-1 analogs hold promise for addressing hyperphagia, obesity, and glycemic control in PWS patients, improving their overall health and quality of life. Continued research and long-term studies are essential to establish these benefits and optimize treatment strategies.

Suppression of the postprandial hyperglycemia in patients with type 2 diabetes by a raw medicinal herb powder is weakened when consumed in ordinary hard gelatin capsules: A randomized crossover clinical trial.

Contradictory claims about the efficacy of several medicinal plants to promote glycemic control in patients with type 2 diabetes mellitus (T2DM) have been explained by divergences in the administration form and by extrapolation of data obtained from healthy individuals. It is not known whether the antidiabetic effects of traditional herbal medicines are influenced by gelatin capsules. This randomized crossover trial aimed to evaluate the acute effect of a single dose of raw cinnamon consumed orally either dissolved in water as a beverage or as ordinary hard gelatin capsules on postprandial hyperglycemia (>140 mg/dL; >7.8 mmol/L) in T2DM patients elicited by a nutritionally-balanced meal providing 50 g of complex carbohydrates. Fasting T2DM patients (n = 19) randomly ingested a standardized meal in five experimental sessions, one alone (Control) and the other after prior intake of 3 or 6 g of crude cinnamon in the form of hard gelatin capsules or powder dissolved in water. Blood glucose was measured at fasting and at 0.25, 0.5, 0.75, 1, 1.5 and 2 hours postprandially. After each breakfast, its palatability scores for visual appeal, smell and pleasantness of taste were assessed, as well as the taste intensity sweetness, saltiness, bitterness, sourness and creaminess. The intake of raw cinnamon dissolved in water, independently of the dose, decreased the meal-induced large glucose spike (peak-rise of +87 mg/dL and Δ1-hour glycemia of +79 mg/dL) and the hyperglycemic blood glucose peak. When cinnamon was taken as capsules, these anti-hyperglycemic effects were lost or significantly diminished. Raw cinnamon intake did not change time-to-peak or the 2-h post-meal glycaemia, but flattened the glycemic curve (lower iAUC) without changing the shape that is typical of T2DM patients. This cinnamon's antihyperglycemic action confirms its acarbose-like property to inhibit the activities of the carbohydrate-digesting enzymes α-amylases/α-glucosidases, which is in accordance with its exceptionally high content of raw insoluble fiber. The efficacy of using raw cinnamon as a diabetes treatment strategy seems to require its intake at a specific time before/concomitantly the main hyperglycemic daily meals. Trial registration: Registro Brasileiro de Ensaios Clínicos (ReBEC), number RBR-98tx28b.

6567 Novel Indication of GLP-1 Receptor Agonists Beyond Weight Loss: Addressing Post-Gastric Bypass Late Dumping Syndrome

Abstract Disclosure: G. Arevalo: None. S. Gra Menendez: None. D. Soliman: None. R.J. Galindo: Consulting Fee; Self; Novo Nordisk, Eli Lilly &amp; Company, Sanofi, Bayer, Inc., Boehringer Ingelheim, Pfizer, Inc., Abbott Laboratories. Grant Recipient; Self; National Institute of Diabetes and Digestive and Kidney Diseases (2P30DK111024), National Institute of Diabetes and Digestive and Kidney Diseases (K23DK123384). Other; Self; Novo Nordisk, Eli Lilly &amp; Company, Dexcom. Background: Late dumping syndrome, characterized by postprandial hyperinsulinemic hypoglycemia (PHH), represents a complex clinical challenge in post-bariatric patients. GLP-1 receptor agonists are being explored as an effective therapeutic option. Clinical Case: A 47-year-old overweight (BMI of 29.86 kg/m²) woman, with a medical history of scleroderma and esophageal dysmotility, underwent a gastric sleeve gastrectomy later requiring conversion to Roux-en-Y gastric bypass to improve esophageal motility. Eleven months post-bypass, she began experiencing recurrent episodes of hypoglycemia (venous glucose 49-70 mg/dL, n &amp;gt;70 mg/dL) accompanied by sweating, palpitations, drowsiness, and weakness. Initial tests were consistent with postprandial hyperinsulinemic hypoglycemia: serum insulin (13.5 µIU/mL, n &amp;lt; 3 µIU/mL), and c-peptide (4.1 ng/mL, n &amp;lt; 0.6 ng/mL). The Sigstad score and the Arts dumping severity score were positive for late dumping syndrome with a score of 26 and 14, respectively. During glucagon administration, the patient's blood glucose level increased by up to 50 mg/dL within 10 minutes of administration. Both sulfonylurea screening and insulin antibody tests were negative. Real-time CGM measurements showed patterns of postprandial hyperglycemic peaks, up to 160-180 mg/dL (n &amp;lt;140 mg/dL), approximately 30 to 60 min after meals, followed by rapidly declining glucose (1-2 hours later), resulting in hypoglycemic events as low as 49 mg/dL. Initial management with dietary changes and pharmacological treatment was unsuccessful due to poor medication tolerability of acarbose and diazoxide, and low adherence to the prescribed diet due to her esophageal dysmotility. The CGM patterns and symptom presentation raised suspicion that late dumping syndrome was triggered by rapid hyperglycemic responses after oral ingestions of typical meals, resulting in the desynchronization of hormonal responses (insulin and GLP-1), and post-prandial hypoglycemia. Hence, the consideration for a GLP-1 receptor agonist emerged. A weekly subcutaneous injection of a long-acting GLP-1 receptor agonist, semaglutide 0.25 mg exhibited marked improvement in her glycemic profile: fewer episodes of postprandial hyperglycemia, and the subsequent descents in blood glucose were less pronounced. The patient demonstrated a favorable response with no severe hypoglycemic episodes reported during a follow-up period of three months. Conclusion: This is the first case to demonstrate semaglutide's efficacy as a standalone treatment for PHH in post-bariatric patients. In this case, semaglutide effectively controlled glycemia and improved the patient's quality of life, presenting a promising therapeutic option for such complex cases. Presentation: 6/1/2024

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

9337 Postprandial And “Fasting” Hypoglycemia In A Patient With A History Of Gastric Bypass Surgery And Carcinoid Syndrome

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

8262 Non-insulinoma pancreatogenous hypoglycemia syndrome (NIPHS) after gastric sleeve surgery

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

6666 Asymptomatic Fasting Hypoglycemia After Sleeve Gastrectomy

Abstract Disclosure: K. Mitrollari: None. H.K. Deveaux: None. A. Gundeti: None. A.P. Calimag: None. T. Yasmeen: None. Introduction: Post-bariatric surgery hypoglycemia (PBSH), though previously considered rare, is increasingly recognized, occurring not only after Roux-en-Y gastric bypass (RYGB,) but also following various bariatric procedures. PBSH can manifest as postprandial or fasting hypoglycemia, requiring thorough investigation and prevention due to potential asymptomatic presentations that may lead to severe consequences, including coma and death. Case Report A 45-year-old female with a history of type 2 DM, ESRD on HD, gastric sleeve surgery, bilateral trans-metatarsal amputations, coronary artery disease, and congestive heart failure presented with bilateral lower extremity wounds. On admission her venous blood glucose was 71 mg/dL. Glycohemoglobin was 3.9% and fructosamine was 225 (205-285 umol/L). Her glycohemoglobin levels consistently remained below 6.4% status post sleeve gastrectomy off diabetes medications. Throughout admission, she experienced almost daily episodes of fasting asymptomatic hypoglycemia correlated with venous sample with lowest blood glucose reading 38 mg/dL. Initially, these episodes were attributed to NPO status for procedures or decreased PO intake. Her diet consisted of fast food brought by her family, which she reported was similar to her diet at home. Workup during a hypoglycemic episode (glucose 51 mg/dL,) revealed insulin 4 mUnits/L, proinsulin 7.1 pmol/L (&amp;lt;=7.2 pmol/L), C-peptide 25.7 ng/mL (0.8-3.9 ng/mL), and beta-hydroxybutyrate 0.5 mmol/L (0.0-0.3 mmol/L). Negative insulin antibodies and sulfonylurea panel, normal cortisol, and ACTH levels were noted. The patient was placed on a 10% dextrose infusion to avoid further episodes of hypoglycemia. However, she continued to experience hypoglycemia and was started on oral diazoxide. A CT pancreas with and without contrast was unremarkable, and endoscopic ultrasonography only revealed a 10 mm accessory spleen. The patient was discharged with counseling on glucose monitoring, dietary changes, and follow-up with endocrinology. Conclusion: PBSH should be considered as a differential diagnosis in patients with unexplained hypoglycemia and a history of bariatric surgery. PBSH mimics insulinoma or non-insulinoma pancreatogenous hypoglycemia syndrome (NIPHS) with elevated insulin, proinsulin, C-peptide, and low beta-hydroxybutyrate during hypoglycemia, however NIPHS is exclusive to non-bariatric patients. Imaging is crucial to rule out insulinoma, and invasive tests such as endoscopic ultrasound aid diagnosis. PBSH is a diagnosis of exclusion; therefore, workup involves ruling out other causes of hypoglycemia. First-line treatment involves diet modification, with medications like diazoxide or acarbose considered if dietary changes prove insufficient. This case underscores the complexity of hypoglycemia, implicating bariatric surgery as a contributing factor. Presentation: 6/3/2024

6981 Atypical hypoglycemia in a teenage boy with prediabetes

Abstract Disclosure: N. Shahid: None. C. salgado: None. N. Gurtunca: None. Background: Hypoglycemia in teenagers is seen less commonly than in younger children. Overweight children with prediabetes presenting with hypoglycemia symptoms are often considered to have reactive post-prandial hypoglycemia due to the degree of hyperinsulinemia with insulin resistance seen in these children. We present a 13-year-old boy with prediabetes, who presented with episodes of altered mental status and was found to have hypoglycemia due to a solitary insulin secreting tumor. Case presentation: A 13-yr old boy with pre-diabetes presented to the ER with altered consciousness and non-ketotic, non-acidotic hypoglycemia [25 mg/dl] &amp; trace ketonuria in the setting of Influenza A infection. Weight and BMI above the 99th%ile and acanthosis nigricans in the skin creases. No access to oral hypoglycemic agents. Urine toxicology was negative. EEG was normal. Euglycemia and level of consciousness restored after IV dextrose &amp; this was considered a possible hypoglycemic seizure episode secondary to poor oral intake. 4 months later he had another episode of altered mental status, jittery movements and was found to be hypoglycemic [41 mg/dl]. He was admitted for further workup of recurrent hypoglycemia. Adrenal insufficiency was ruled out and a diagnostic fast was started. After 15 hours, he developed non-ketotic hypoglycemia [&amp;lt;50 mg/dl]. Critical sample [Table 1] and Glucagon challenge [Table 2] at the termination of the fast confirmed hyperinsulinemic hypoglycemia. Given the unusual age and presentation, an MRI abdomen was done which showed a 1.6 cm lesion in the pancreatic body [Fig 1]. Dotatate whole body PET scan confirmed the insulinoma with no evidence of nodal or distant metastasis [Fig 2]. He underwent surgical enucleation of the insulinoma. Intraoperative secretin showed no evidence of pancreatic duct dilatation or leakage. Hereditary endocrine tumor panel including multiple endocrine neoplasia [MEN] gene analysis was negative. The postoperative course was complicated by a persistent pancreatic leak and pancreatitis eventually requiring an ERCP and stent placement 2 months post operatively. Conclusion: Insulinomas are very rare neuroendocrine tumors in pediatric population, with a prevalence of one in 250,000 and median age at presentation of 45-50 years. About 90% insulinomas are benign and less than 10% are associated with MEN-1 syndrome. Chronic hypoglycemia irrespective of the underlying insulin resistance of prediabetes can be seen with insulinoma and can cause hypoglycemia unawareness as seen in our patient. This has also been reported in literature to be misdiagnosed as refractory epilepsy or psychiatric disorders. Hypoglycemic symptoms at any age should be promptly worked up. Ruling out associated neuroendocrine hereditary tumor syndromes is crucial and prognosis of benign solitary insulinomas after surgical removal is mostly favorable. Presentation: 6/3/2024

12417 Atypical Patterns Of Hypoglycemia Post-bariatric Surgery Due To Pancreatic Insulinoma

Abstract Disclosure: K.A. Chopra: None. Accurately diagnosing an insulinoma in patients who have had bariatric surgery can be challenging because the autonomic symptoms of palpitations, tremors, anxiety and neuroglycopenic hypoglycemia symptoms of confusion and loss of consciousness may overlap with dumping syndrome or be attributed to non-insulinoma pancreatogenous hypoglycemia. When evaluating hypoglycemia, it is crucial to obtain a detailed history of the pattern and timing of hypoglycemia episodes and collect a critical sample of insulin, proinsulin, c-peptide levels during an episode of low glucose to prevent misdiagnosis. 58-year-old woman with hypertension, obesity, and history of laparoscopic sleeve gastrectomy presented for evaluation of hypoglycemia. The patient lost 100 pounds after her sleeve gastrectomy. Within the past year, the patient had two hospitalizations for severe symptomatic hypoglycemia with associated loss of consciousness. Imaging showed atrophic pancreas and she was discharged with a prescription for daily prednisone without critical sample testing for insulin or c-peptide levels. She sought a second opinion for her hypoglycemia at UCM. Since she was taking prednisone for 10 months prior to initial evaluation at UCM, evaluation for adrenal insufficiency could not be completed initially. She started continuous glucose monitoring which showed multiple daily episodes of hypoglycemia, fasting and at other various timepoints. Fasting labs showed low glucose of 20 mg/dL (RR 60-99 mg/dL), elevated proinsulin 120 pmol/L (RR 3.6- 22 pmol/L), inappropriately normal insulin 16.4 uIU/mL (RR &amp;lt;28.5 uIU/mL), and inappropriately normal c-peptide 0.82 pmol/mL (RR 0.30-2.35 pmol/mL), consistent with insulinoma. CT abdomen showed 1.4 cm arterially enhancing round lesion in the pancreatic body. Endoscopic ultrasound showed 13 mm mass in the pancreatic body with fine needle aspiration with pathology showing a well-differentiated neuroendocrine tumor. She received stress dose hydrocortisone preceding surgery and underwent successful enucleation of 1.6 cm pancreatic neuroendocrine tumor. A few weeks after her surgery, her HPA axis was re-evaluated, and steroids were discontinued. She has had no episodes of hypoglycemia since. Although hypoglycemia can be associated post-bariatric surgery, most patients develop postprandial hypoglycemia due to surgical alterations in alimentary flow leading to increased incretin and insulin secretion (Mulla et al 2016). Therefore, it is important to consider insulinoma in the differential diagnosis of post-bariatric surgery patients presenting without typical postprandial patterns of hypoglycemia. Reference: Mulla CM, Storino A, Yee EU, Lautz D, Sawnhey MS, Moser AJ, Patti ME, Insulinoma After Bariatric Surgery: Diagnostic Dilemma and Therapeutic Approaches. Obes Surg. 2016 Apr;26(4):874-81. Presentation: 6/1/2024

Platform for precise, personalised glucose forecasting through continuous glucose and physical activity monitoring and deep learning

Emerging research has demonstrated the advantage of continuous glucose monitoring for use in artificial pancreas and diabetes management in general. Recent studies demonstrate that glucose level forecasting using deep learning can help avoid postprandial hyperglycemia (≥ 180 mg/dL) or hypoglycemia (≤70 mg/dL) from delayed or increased insulin dosing in artificial pancreas. In this paper, a novel hybrid deep learning framework with integration of content-based attention learning is presented, to effectively predict the glucose measurements with prediction horizons (PH) = 15, 30 and, 60 minutes for T1D and T2D patients based on past data. We also present a complete cloud-based system and mobile app used for collecting CGM sensor, physical activity data, CHO values and insulin measurements to perform glucose forecasts using the proposed model running on Cloud. This model was validated using clinical data of individual with Type 1 diabetes (OhioT1DM) and individual with Type 2 diabetes. The mean absolute relative difference (MARD) was 12.33±3.15, 7.14±1.76% for PH=60 and, 30 min respectively on OhioT1DM clinical Dataset. The root mean squared error (RMSE) was 29.41±5.92 mg/dL and 17.19±3.22 mg/dL and the mean absolute error (MAE) was 21.96±4.67 mg/dL and 12.58±2.34 mg/dL for PH=60 and, 30 min respectively on the same clinical dataset. It was observed that inclusion of physical activity leads to improved glucose forecasting accuracy. Furthermore, all these results were obtained by training the model on only 8 days of clinical data of a single patient, followed by testing on clinical data on the following days. The results indicate that training on a single patient data may lead to better personalisation and better glucose forecasting results compared to existing works.

Comparison of feature learning methods for non-invasive interstitial glucose prediction using wearable sensors in healthy cohorts: a pilot study

BackgroundAlterations in glucose metabolism, especially the postprandial glucose response (PPGR), are crucial contributors to metabolic dysfunction, which underlies the pathogenesis of metabolic syndrome (MetSyn). Personalized low-glycemic diets (PLGD) have shown promise in reducing postprandial glucose spikes. However, current methods such as invasive continuous glucose monitoring (CGM) or multi-omics data integration to assess PPGR come with limitations, including cost and invasiveness, hindering widespread adoption in primary disease prevention. Our aim is to assess machine-learning algorithms for predicting individual PPGR using non-invasive wearable data, thereby circumventing the limitations associated with existing approaches. By identifying the most accurate model, we seek to provide a more accessible and efficient method for managing glucose metabolism. MethodsThis data-driven analysis utilized the experimental dataset from the SENSE (”Systemische Ernährungsmedizin”) study. Healthy participants used an Empatica E4 wristband and Abbott Freestyle Libre 3 CGM for ten days. Blood volume pulse (BVP), electrodermal activity (EDA), heart rate (HR), skin temperature (TEMP), and the corresponding CGM values were measured. Subsequently, four data-driven deep learning (DL) model-convolutional neural network (CNN), lightweight transformer (LTF), long short-term memory with attention (LSTM-A), and Bi-directional LSTM (BiLSTM)-were implemented and compared to determine the potential of DL in predicting interstitial glucose levels without involving food and activity logs. ResultsThe proposed BiLSTM achieved the best interstitial glucose prediction performance, with an average root mean squared error (RMSE) of 13.42 mg/dL, an average mean absolute percentage error (MAPE) of 0.12, and only 3.01% values falling within area D in Clarke error grid analysis (CEGA), incorporating the leave-one-out cross-validation (LOOCV) strategy for a five-minute prediction horizon. ConclusionThe findings of this study may demonstrate the feasibility of transferring knowledge gained from invasive glucose monitoring devices to non-invasive approaches. Furthermore, it emphasizes the promising prospects of combining deep learning with wearable technologies to predict glucose levels in healthy individuals.

Quercetin slow-release system delays starch digestion via inhibiting transporters and enzymes

This study investigates the potential of a quercetin-based emulsion system to moderate starch digestion and manage blood glucose levels, addressing the lack of in vivo research. By enhancing quercetin bioaccessibility and targeting release in the small intestine, the emulsion system demonstrates significant inhibition of starch digestion and glucose spikes through both in vitro and in vivo experiments. The system inhibits α-amylase and α-glucosidase via competitive and mixed inhibition mechanisms, primarily involving hydrogen bonds and van der Waals forces, leading to static fluorescence quenching. Additionally, this system downregulates the protein expression and gene transcription of SGLT1 and GLUT2. These findings offer a novel approach to sustaining glucose equilibrium, providing a valuable foundation for further application of quercetin emulsion in food science.

Assessing the influence of insulin type (ultra-rapid vs rapid insulin) and exercise timing on postprandial exercise-induced hypoglycaemia risk in individuals with type 1 diabetes: a randomised controlled trial.

The relationship between pre-meal insulin type, exercise timing and the risk of postprandial exercise-induced hypoglycaemia in people living with type 1 diabetes is unknown. We aimed to evaluate the effects of exercise timing (60 vs 120 min post meal) and different insulin types (aspart vs ultra-rapid aspart) on hypoglycaemic risk. This was a four-way crossover randomised trial including 40 individuals with type 1 diabetes using multiple daily injections (mean HbA1c 56 mmol/mol [7.4%]). Participants, who were recruited from the Montreal Clinical Research Institute, undertook 60 min cycling sessions (60% of ) after breakfast (60 min [EX60min] or 120 min [EX120min] post meal) with 50% of their usual insulin dose (aspart or ultra-rapid aspart). Eligibility criteria included age ≥18 years old, clinical diagnosis of type 1 diabetes for at least 1 year and HbA1c ≤80 mmol/mol (9.5%). Participants were allocated using sequentially numbered, opaque sealed envelopes. Participants were masked to their group assignment, and each participant was allocated a unique identification number to ensure anonymisation. The primary outcome was change in blood glucose levels between exercise onset and nadir. Prior to exercise onset, time spent in hyperglycaemia was lower for EX60min vs EX120min (time >10.0 mmol/l: 56.6% [1.2-100%] vs 78.0% [52.7-97.9%]; p<0.001). The glucose reduction between exercise onset and nadir was less pronounced with EX60min vs EX120min (-3.8±2.7 vs -4.7±2.5 mmol/l; p<0.001). A similar number of hypoglycaemic events occurred during both exercise timings. Blood glucose between exercise onset and nadir decreased less with ultra-rapid aspart compared with aspart (-4.1±2.3 vs -4.4±2.8 mmol/l; p=0.037). While a similar number of hypoglycaemic events during exercise were observed, less post-exercise hypoglycaemia occurred with ultra-rapid aspart (n=0, 0%, vs n=15, 38%; p=0.003). No interactions between insulin types and exercise timings were found. EX60min blunted the pre-exercise glucose increase following breakfast and was associated with a smaller glucose reduction during exercise. Ultra-rapid aspart led to a smaller blood glucose reduction during exercise and might be associated with diminished post-exercise hypoglycaemia. ClinicalTrials.gov NCT03659799 FUNDING: This study was funded by Novo Nordisk Canada.

Current and Future Strategies in Insulin Development and Treatment.

Recent advances in insulin research open new avenues for treatment, both, for type 1 and type 2 diabetes. In developed countries, standardized "ultra-rapid-acting insulins" are now also used in addition to rapid-acting insulins. First- and second-generation basal analogs are available. Third-generation basal analogs, which only need to be applied once a week, are in the pipeline. Second-generation "ultra-rapid-acting insulins" insulins with faster onset and offset of action may be particularly useful for multiple daily injections and automated insulin delivery systems. An improved time-action profile of bolus insulin would be able to cover the rapid increase in glucose after meals with a rapid fall thereafter to avoid postprandial hypoglycemia. The third-generation basal insulins allowing once-weekly dosing made major steps toward becoming a clinical reality. However, issues with insulin affordability and availability remain problematic even in more affluent countries. Biosimilar insulins products can provide people with additional safe, high-quality, and potentially cost-effective options for treating diabetes. Particularly in low-middle income countries insulin therapy is facing issues not only of access but also storage, lack of diabetes education, and stigma. With the new bolus insulins, the physiological insulin secretion pattern can be mimicked better and better and hypoglycemia can be avoided. With the ever longer pharmacokinetic action profiles of the basal analogs, the injection frequency is reduced, which leads to better adherence and quality of life, but these insulins are not available for everyone who needs it worldwide.