Clinical trials often face challenges in efficient data collection and participant monitoring. To address these issues, we developed the IMPACT platform, comprising a real-time mobile application for data collection and a web-based dashboard for remote monitoring and management.

This article presents the design, development, and usability assessment of the IMPACT platform customized for patients with post-bariatric surgery hypoglycemia (PBH). We focus on adapting key IMPACT components, including continuous glucose monitoring (CGM), symptom tracking, and meal logging, as crucial elements for user-friendly and efficient PBH monitoring.

The adapted IMPACT platform demonstrated effectiveness in data collection and remote participant monitoring. The mobile application allowed patients to easily track their data, while the clinician dashboard provided a comprehensive overview of enrolled patients, featuring filtering options and alert mechanisms for identifying data collection issues. The platform incorporated various visual representations, including time plots and category-based visualizations, which greatly facilitated data interpretation and analysis. The System Usability Scale questionnaire results indicated a high level of usability for the web dashboard, with an average score of 86.3 out of 100. The active involvement of clinicians throughout the development process ensured that the platform allowed for the collection and visualization of clinically meaningful data.

By leveraging IMPACT's existing features and infrastructure, the adapted version streamlined data collection, analysis, and trial customization for PBH research. The platform's high usability underscores its alignment with the requirements for conducting research using continuous real-world data in PBH patients and other populations of interest.

BACKGROUND Nesidioblastosis is an uncommon cause of hypoglycemia and is part of a group of diseases known as non-insulinoma pancreatogenic hypoglycemia syndrome (NIHPS). The objective of this report is to provide a comprehensive discussion on the diagnostic and therapeutic management of a case of nesidioblastosis, a rare and potentially fatal condition. CASE REPORT A 42-year-old non-diabetic man with a history of coronary artery disease and systemic arterial hypertension underwent extensive diagnostic investigation because he had been hospitalized several times over a period of approximately 2 years with a clinical history compatible with persistent refractory hypoglycemia. Despite laboratory and imaging tests, the underlying cause of the hypoglycemia remained unclear. Comprehensive investigation included computed tomography (CT), magnetic resonance imaging (MRI), upper endoscopy, PET/CT, and selective pancreatic arteriography. Persistent hypoglycemia associated with high insulin levels led to the suspicion of nesidioblastosis. After exhausting all clinical therapeutic options and after multidisciplinary discussion considering risks and benefits, we decided to perform total pancreatectomy and splenectomy. Anatomopathological and immunohistochemical examination confirmed the diagnosis of nesidioblastosis. CONCLUSIONS The diagnosis of nesidioblastosis is complex and requires a multidisciplinary approach. The decision to perform a total pancreatectomy was essential to control severe hypoglycemia and improve the patient's quality of life. This case report describes the diagnostic and therapeutic management of persistent endogenous hyperinsulinemic hypoglycemia and highlights the importance of diagnostic accuracy and early therapeutic intervention.

One anastomosis gastric bypass (OAGB) is now the third most common metabolic and bariatric surgery around the world, but the impact of different long-term complications such as dumping syndrome (DS) need still to be addressed. This study aims to the incidence of DS after OAGB through a systematic review of published papers on PubMed, and Scopus. Finally, 17 studies included 3420 patients were included. The mean postoperative follow-up was 11.91 ± 1.5 months. The incidence of DS was reported between 9 to 42.9% and 0.5% to 27.8% in studies using the Sigstad dumping score and patients' self-reported DS, respectively. Treatment of DS after OAGB included mainly dietary changes and medications. Up to date, DS seems to be a rare long-term complication after OAGB and revisional/conversional interventions might not be needed. Further time is necessary to reach out about the consequences of OAGB in the future.

While Roux-en-Y gastric bypass is an effective treatment for obesity and type 2 diabetes, up to one-third of patients develop post-bariatric hypoglycaemia (PBH). Individuals with PBH exhibit increased postprandial secretion of the intestinal hormone fibroblast growth factor 19 (FGF19, Fgf15 in mice). However, the underlying mechanisms contributing to PBH remain uncertain. Here we demonstrate that faecal and plasma bile acid (BA) profiles are significantly altered in postoperative individuals with PBH versus those without hypoglycaemia. Furthermore, altered BAs in PBH induce FGF19 secretion in intestinal cells in a manner dependent on the apical sodium-dependent BA transporter (ASBT). We demonstrate that ASBT inhibition reduces Fgf15 expression and increases postprandial glucose in hypoglycaemic mice. Our data suggest that dysregulation of luminal BA profiles and transport may contribute to PBH and provide proof of concept that ASBT inhibition could be developed as a new therapeutic strategy for PBH.

Cardiotonic steroids (CTSs) were known as steroidal plant compounds that exert cellular effects by the binding to Na,K-ATPase. Earlier, plant (exogenous) CTSs were used to treat chronic heart failure. By now, endogenous CTS have been identified in mammals, and their concentrations in the blood, normally in a subnanomolar range, are altered in numerous pathologies. This indicates their role as endogenous regulators of physiological processes. CTS transport occurs primarily in the blood, yet the CTS effects on blood cells remain poorly understood. This review summarizes the CTS effects on blood cells of animals and humans under normal and pathological conditions, and analyzes their action based on known mechanisms of action in mammalian cells. At high concentrations (greater than 10-9 M), CTS binding to Na,K-ATPase inhibits the enzyme, whereas lower concentrations of CTSs induce signaling cascades or activate the enzyme. All these mechanisms are shown to be present in blood cells. The particular CTS effect is determined by the CTS type, its concentration, the isoform composition of the catalytic α-subunit of Na,K-ATPase in the cell, and other cell features. It has been demonstrated that all blood cell types (erythrocytes, leukocytes, and platelets) expressed both ubiquitously distributed α1-isoform and tissue-specific α3-subunit, which exhibits a different ion and CTS affinity compared to α1. This results in a wide spectrum of blood cell responses to fluctuations in CTS levels in the blood. In particular, an increase in the level of endogenous CTSs by a more twofold is sufficient to induce a decline in the activity of erythrocyte Na,K-ATPase. The administration of exogenous CTSs is able to modulate the proinflammatory activity of leukocytes, which is attributed to the activation of signaling cascades, and to exert an influence on platelet activation. Hence, alterations of CTS levels in bloodstream significantly affect the functionality of blood cells, contributing to the organism's adaptive response. On top of this, a comparison of the effects of CTSs on human leukocytes and rodent leukocytes carrying the CTS-resistant α1-isoform often reveals opposite effects, thus indicating that rodents are an unsuitable model for studying CTS effects on these cells.

Roux-en-Y gastric bypass (RYGB) increases the risk of postprandial hypoglycemia, whereas pregnancy decreases insulin sensitivity, which could be expected to counteract hypoglycemia. We examined if RYGB performed prior to pregnancy altered the postprandial glucose metabolism and enteropancreatic hormone responses to a mixed meal test (MMT).

Twenty-three women with RYGB and 23 women matched on prepregnancy body mass index and parity underwent a 4-hour MMT in the first and third trimester of pregnancy with measurement of circulating levels of glucose, insulin, C-peptide, glucose-dependent insulin peptide (GIP), glucagon-like peptide 1 (GLP-1), glucagon, free fatty acids, and lactate. Biochemical hypoglycemia was defined as plasma glucose <3.5 mmol/L.

Women with RYGB had earlier and higher peak glucose, lower nadir glucose levels, and a higher frequency of biochemical hypoglycemia compared with women without RYGB in both the first and third trimester. The lower glucose levels were preceded by markedly elevated total GLP-1 and insulin levels in women with RYGB, whereas total GIP levels were unaltered. The glucagon levels were lower in women with RYGB. In the first trimester MMT, peak and area under the curve of total plasma GLP-1 and serum insulin levels were negatively associated with nadir plasma glucose, while the early postmeal response of plasma glucagon was positively associated with nadir plasma glucose in the third trimester.

These results provide novel insights into the combined effects of RYGB and pregnancy on postmeal glucose metabolism and enteropancreatic hormone responses during pregnancy, and how these changes associate with an increased risk of postprandial hypoglycemia.

NCT03713060.

Post-bariatric hypoglycemia (PBH) is a metabolic complication of individuals with obesity who have undergone bariatric surgery, characterized by rapid glycemic excursions followed by hypoglycemic events usually occurring 1-3 h post-meal. Without an approved pharmacotherapy, dietary modifications are essential for managing PBH, with continuous glucose monitoring (CGM) devices emerging as crucial tools for capturing postprandial glucose responses that can guide intervention strategies to prevent PBH. The effectiveness of such interventions is based on the availability of rich datasets, containing both CGM and meal data. However, meal information is often incomplete, being its manual recording burdensome and prone to user-related errors. In response, we proposed a template match algorithm (TMA) for the retrospective identification of unreported meals using CGM data only. TMA relies on a similarity score calculated between a post-prandial glycemic curve template and the glycemic trace of interest. Our study demonstrates promising results: TMA correctly identifies 1237 out of 1340 meals, generating 208 false positives within a dataset of 20 PBH subjects monitored in free-living conditions for nearly 50 days, yielding a median F1-score of 0.90. The effectiveness of TMA enables its use to enhance data quality in long-term studies involving PBH patients, facilitating the development of new approaches to manage PBH.

Obesity and its related complications are growing in prevalence worldwide, with increasing impact to individuals and healthcare systems alike. Currently, the leading treatment approaches for effective and sustained weight loss are bariatric surgery and gut peptide therapeutics. At a high level, both treatment strategies work by hijacking gut-brain axis signaling to reduce food intake. However, we predict that each modality has distinct neuronal mechanisms that are responsible for their success and complications. This review compares the neurobiology of feeding behavior between these two weight loss strategies via a discussion of both clinical and pre-clinical data. The most compelling evidence points to signaling within the hindbrain, hypothalamus, and reward circuits contributing to weight loss. Considerations for treatment, including differing complications between the two treatment approaches, will also be discussed. Based on the data, we pose the hypothesis that these two interventions are acting via distinct mechanisms to induce weight loss. Both interventions have variable degrees of weight loss across the patient population, thus, understanding these distinct mechanisms could help drive individualized medicine to optimize weight loss. This article is part of the Special Issue on "Food intake and feeding states".

A woman in her 40s presented with severe post-bariatric hypoglycaemia that persisted despite nutritional therapy and pharmacological therapy with acarbose and subcutaneous octreotide with meals. The nutritional limitations were difficult to sustain, and she developed adverse effects to the pharmacological therapy, and hence, doses could not be increased. She was subsequently treated with subcutaneous octreotide via an insulin pump, with a continuous basal rate and additional bolus doses with meals. This led to significant improvements in hypoglycaemia and less side effects, as well as the ability to titrate doses. This report describes the course of her treatment, illustrating continuous octreotide treatment via an insulin pump as a potential additional treatment option in post-bariatric hypoglycaemia.

Post bariatric hypoglycaemic (PBH) is a late complication of weight loss surgery, characterised by critically low blood glucose levels following meal-induced glycaemic excursions. The disabling consequences of PBH underline the need for the development of a decision support system (DSS) that can warn individuals about upcoming PBH events, thus enabling preventive actions to avoid impending episodes. In view of this, we developed various algorithms based on linear and deep learning models to forecast PBH episodes in the short-term.

We leveraged a dataset obtained from 50 patients with PBH after Roux-en-Y gastric bypass, monitored for up to 50 days under unrestricted real-life conditions. Algorithms' performance was assessed by measuring Precision, Recall, F1-score, False-alarms-per-day and Time Gain (TG).

The run-to-run forecasting algorithm based on recursive autoregressive model (rAR) outperformed the other techniques, achieving Precision of 64.38%, Recall of 84.43%, F1-score of 73.06%, a median TG of 10 min and 1 false alarm every 6 days. More complex deep learning models demonstrated similar median TG but inferior forecasting capabilities with F1-score ranging from 54.88% to 64.10%.

Real-time forecasting of PBH events using CGM data as a single input imposes high demands on various types of prediction algorithms, with CGM data noise and rapid postprandial glucose dynamics representing the key challenges. In this study, the run-to-run rAR yielded most satisfactory results with accurate PBH event predictive capacity and few false alarms, thereby indicating potential for the development of DSS for people with PBH.

The American Diabetes Association (ADA) "Standards of Care in Diabetes" includes the ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, an interprofessional expert committee, are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations and a full list of Professional Practice Committee members, please refer to Introduction and Methodology. Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC.

Few real-life studies have analyzed the glycemic response to nutrients in individuals without diabetes. We investigated the glycemic response to evening meals in relation to individual characteristics, nutrient components, and preprandial and postprandial routines.

A cross-sectional study of 489 individuals without diabetes from a randomly selected general adult population (310 women, median age 46 years, range 18-84 years) was conducted using a continuous glucose monitoring device for 7 days. The study recorded the participants' glycemic profile at 6 h after dinner, the food consumed at dinner, the fasting duration before dinner, and the duration between the end of dinner and going to bed. Principal component analysis and multilevel functional data analysis were used to interpret the data.

On average, a postprandial glycemic peak was observed at 45 min, followed by a decline to baseline levels from 90 min onwards. Older age, higher body mass index, and large meals (especially those high in starch and dairy products) were all significantly associated with higher glucose levels throughout the 6 h after dinner. The fruit component was associated with a higher initial glycemic peak, followed by a lowering glycemic effect thereafter (p < 0.001). The alcohol component was associated with an initial hypoglycemic effect (p = 0.006). The participants who fasted longer before dinner had higher postprandial glycemic peaks (p = 0.001), and those who went to bed later had higher postprandial glucose levels than those who went to bed earlier (p = 0.003).

The participants' characteristics, nutrient components, and pre- and post-dinner routines have divergent effects on post-dinner glycemic response.

Postbariatric hypoglycemia (PBH) is a challenging condition affecting quality of life of patients after bariatric surgery. However, its incidence and predictive factors remain debated.

To determine the incidence of PBH, identify predictors of PBH and assess its association with weight trajectory after bariatric surgery.

University Hospital.

Prospective observational cohort study including 222 nondiabetic patients who underwent Roux-en-Y gastric bypass between 2014 and 2021, had an oral glucose tolerance test (OGTT) and/or A1C (glycated hemoglobin) measurement prior to surgery and were followed for at least 12 months. Diagnosis of PBH was made when symptoms of hypoglycemia were accompanied by a postprandial plasma glucose level < 3.9 mmol/l or a glycemia < 3.9 mmol/l during continuous glucose monitoring, with resolution of symptomatology after carbohydrate consumption. Univariable and multivariable logistic regression analyses were performed to identify factors associated with PBH.

Out of 222 patients, 71 (32%) were diagnosed with PBH. The highest incidence rate was observed at 2 years postbariatric surgery with a cumulative incidence of 26.5%. Predictive factors for higher risk of PBH were younger age at surgery (OR = .97; 95% CI: .94-.99; P = .049) and early dumping syndrome (OR = 3.05; 95% CI: 1.62-6.04; P = .0008). In multivariable logistic regression, higher glycemia at 2 hours during preoperative OGTT was associated with lower risk of PBH (OR = .8; 95% CI: .63-.98; P = .04). PBH was not associated with weight trajectory after surgery in our cohort.

Younger age at time of surgery and lower blood glucose at 120 minute during preoperative OGTT are risk factors for PBH. Early dumping syndrome is significantly associated with PBH and could be used as a red flag to help identify patients at risk of PBH.

Early dumping syndrome (DS) and postbariatric hypoglycemia (PBH) are challenging conditions with limited treatment options. A 46-year-old woman with prediabetes, obesity, and sleeve gastrectomy presented with digestive symptoms suggestive of DS and postprandial hypoglycemia consistent with PBH. She started tirzepatide 2.5 mg weekly, which decreased postprandial blood glucose peaks, increased postprandial blood glucose nadirs, and improved overall time in range on continuous glucose monitoring (CGM). Her postprandial bloating and diarrhea resolved. To our knowledge, there have been no reported cases of DS or PBH treated with dual-incretin agonists. While glucagon-like peptide-1 (GLP-1) agonists have not been widely attempted in DS and have shown mixed benefit for PBH, combination GLP-1 and gastric inhibitory peptide agonism may represent a novel treatment both for PBH and DS, providing greater improvement in glycemic variation as well as better DS control than GLP-1 agonism alone.

Total pancreatectomy and islet autotransplantation (TPIAT) is an effective treatment for chronic and recurrent acute pancreatitis, and it provides a significant potential additional benefit of insulin independence. Spontaneous hypoglycemia in the absence of insulin therapy following TPIAT is a recognized complication, which has been attributed to lack of protective glucagon responses to hypoglycemia, following intrahepatic islet autotransplantation. We describe the use of liraglutide to treat spontaneous hypoglycemia following TPIAT. Continuous glucose monitoring was used to identify timing of hypoglycemia in relation to meals and monitor treatment effect. Liraglutide has been used for management of hypoglycemia following bariatric surgery, but, to our knowledge, this is the first application of its effective use to treat spontaneous severe hypoglycemia following TPIAT.

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 > 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.

Post-bariatric surgery hypoglycemia, also recognized as late dumping syndrome or postprandial hyperinsulinemic hypoglycemia, is a complex condition often driven by multifactorial roots, including postoperative anatomical changes, altered gut hormone responses, metabolic shifts, and other hidden conditions, necessitating a multidisciplinary approach for appropriate evaluation and treatment. We present the case of a 36-year-old female nurse who experienced recurrent hypoglycemia following gastric sleeve surgery. Despite significant weight loss and dietary adjustments, she continued to struggle with unstable blood glucose levels. A comprehensive dysglycemia evaluation revealed the presence of an autoimmune disorder consistent with the criteria for latent autoimmune diabetes in adults (LADA), as defined by "The Immunology of Diabetes Society" (IDS). This new diagnosis added complexity to her clinical management, leading us to reassess her treatment strategy. As a result, her treatment plan was modified to include the initiation of insulin and the introduction of the newly FDA-approved teplizumab, which may help delay the progression of autoimmune diabetes. This case underscores the importance of systematic hypoglycemia evaluations in bariatric surgery patients to optimize clinical outcomes. Managing hypoglycemia in these patients requires a collaborative effort involving endocrinologists, surgeons, and nutritionists to ensure the best outcomes and improve the patient's quality of life.

This case involves a 45-year-old woman with severe obesity who underwent Roux-en-Y gastric bypass (RYGB) surgery. After one year, she developed daily episodes of severe hypoglycemia, presenting with symptoms of palpitations, diaphoresis, and syncope. The patient was diagnosed with endogenous hyperinsulinemic hypoglycemia, a condition characterized by abnormally high insulin levels leading to low blood glucose, commonly associated with insulinoma. In rare instances, this can be due to nesidioblastosis, an overgrowth of pancreatic beta cells, which is more prevalent in individuals who have undergone bariatric surgery. Diagnostic evaluations included blood tests, abdominal computed tomography and magnetic resonance imaging, continuous glucose monitoring, and hepatic venous sampling to exclude insulinoma. This report details the diagnosis and unsuccessful treatment of endogenous hyperinsulinemic hypoglycemia following RYGB surgery. Interventions included dietary modifications (small, frequent, low-carbohydrate meals), medical management with acarbose 100 mg three times daily, diazoxide 150 mg three times daily, verapamil 40 mg twice daily, and surgical reversal of the RYGB. Ultimately, a percutaneous gastrostomy tube was placed for 24-hour continuous parenteral feeding. Despite these extensive treatment efforts, the patient continues to experience frequent hypoglycemic episodes four years after the bariatric procedure.

post-bariatric hypoglycemia (PBH) is considered a chronic complication after gastric bypass (RYGB) impacting roughly 30 % of patients. Current treatments often focus on nutritional interventions to reduce the frequency of episodes. This prospective study evaluated the effectiveness of Lisosan G (LG), a fermented wheat-based supplement added to the diet, in mitigating PBH episodes and elucidating its mechanism of action on the gut-pancreas axis.

twenty subjects with PBH, who had undergone RYGB between 2015 and 2018, were enrolled. Subjects underwent clinical examination, blood test, and a 3-hour oral glucose load test (OGTT). Then, they were monitored for 2-weeks on a free diet with continuous glucose monitoring (CGM), which was extended for another 2-weeks after introduction of LG supplementation (5 g, twice daily) on the same diet. Finally, subjects repeated OGTT and blood test. PBH was defined as interstitial glucose ≤ 54 mg/dl.

after treatment, a marked reduction in PBH time was observed (75[23-113] vs 16 [0-33], minutes, p < 0.001). During OGTT, there was an increase in glucose nadir (44 ± 11 vs 56 ± 10, mg/dl, p = 0.038), and a significantly decrease in total GLP-1 AUC (7.6 ± 4.1 vs 6.5 ± 3.8, nmol/L*min, p = 0.043), in potentiation factor ratio (p = 0.037) and in total insulin AUC (57 ± 12 vs 49 ± 9, nmol/L*min, p = 0.043).

LG effectively reduces PBH frequency and duration, probably by attenuating GLP-1 concentrations and leading to a decrease in the second phase of insulin secretion in response to glucose. These findings underscore the promise of LG as a novel adjunct therapy for PBH, particularly when added to the diet, and emphasize the need for further exploration into its microbiota-modulating and anti-inflammatory effects.

Diabetes mellitus (DM) and obesity have become public issues of global concern. Bariatric surgery for the treatment of obesity combined with type 2 DM has been shown to be a safe and effective approach; however, there are limited studies that have systematically addressed the challenges of surgical treatment of obesity combined with DM. In this review, we summarize and answer the most pressing questions in the field of surgical treatment of obesity-associated DM. I believe that our insights will be of great help to clinicians in their daily practice.

Bariatric surgery is an important weight loss tool in individuals with severe obesity. It is currently the most effective long-term weight loss treatment that lowers obesity-related comorbidities. It also has significant physiological and nutritional consequences that can result in gastrointestinal complications and micronutrient deficiencies. After gastric bypass, clinical events that negatively affect nutritional status include malabsorption, dumping syndrome, kidney stones, altered intestinal bile acid availability, bowel obstruction, ulcers, gastroesophageal reflux, and bacterial overgrowth. Risk factors for poor nutritional status and excessive loss of lean body mass and bone include reduced dietary quality and inadequate intake, altered nutrient absorption, and poor patient compliance with nutrient supplementation. There are unique concerns in adolescents, older individuals, and individuals who become pregnant postoperatively. With careful management, health-care professionals can assist with long-term weight loss success and minimize the risk of acute and long-term nutrition complications after bariatric surgery.

Post-bariatric hypoglycemia (PBH) is an increasingly recognized complication after metabolic bariatric surgery (MBS). The aim of this study is to investigate potential factors associated with PBH. A cohort of 24 patients with type 2 diabetes mellitus (T2DM) and body mass index (BMI) ≥40 kg/m2 who underwent laparoscopic Roux-en-Y gastric bypass (LRYGBP) was retrospectively investigated for PBH at 12 months. PBH was defined as postprandial glucose at 120 min below 60 mg/dL. Questionnaires based on the Edinburgh hypoglycemia scale were filled out by the participants. Glycemic parameters and gastrointestinal (GI) hormones were also investigated. Based on the questionnaires, five patients presented more than four symptoms that were highly indicative of PBH at 12 months. According to glucose values at 120 min, one patient experienced PBH at 6 months and four patients experienced it at 12 months. Postprandial insulin values at 30 min and 6 months seem to be a strong predictor for PBH (p < 0.001). GLP-1 and glucagon values were not significantly associated with PBH. PBH can affect patients with T2DM after MBS, reaching the edge of hypoglycemia. Postprandial insulin levels at 30 min and 6 months might predict the occurrence of PBH at 12 months, but this requires further validation with a larger sample size.

Metabolic surgery is the foremost treatment for obesity and its associated medical conditions. Nonetheless, post-bariatric hypoglycemia (PBH) emerges as a prevalent complication. PBH pathophysiology implicates heightened insulin and glucagon-like peptide 1 (GLP-1) levels, with bile acids (BA) contributing to GLP-1 release. A plausible association exists between cholecystectomy and PBH, which is attributed to alterations in BA metabolism and ensuing hormonal responses. The objective of this retrospective cohort study was to evaluate the impact of cholecystectomy on PBH pharmacological treatment, diagnostic timelines and metabolic parameters.

Patients diagnosed with PBH after bariatric surgery were evaluated based on their history of cholecystectomy. Demographic, anthropometric and clinical data were collected. Mixed meal tolerance tests (MMTT) results were compiled to assess metabolic responses.

Of the 131 patients with PBH included in the study, 29 had prior cholecystectomy. The time to PBH diagnosis was similar across groups. Patients with prior cholecystectomy required higher doses of acarbose (p = 0.046), compared to those without prior cholecystectomy. Additionally, MMTT revealed higher insulin (t = 60 min: p = 0.010 and t = 90 min: p = 0.034) and c-peptide levels (t = 60 min: p = 0.008) and greater glycemic variability in patients with prior cholecystectomy (p = 0.049), highlighting the impact of cholecystectomy on glucose metabolism.

Our study offers novel insights into PBH pharmacotherapy, indicating that PBH patients with a history of cholecystectomy require elevated doses of acarbose for symptom control than PBH patients without such surgical history. Furthermore, our findings underscore the pivotal role of hyperinsulinism in PBH aetiology, emphasizing the significance of the BA-GLP-1-insulin axis.

BACKGROUND Hypoglycemia is a common complication following total gastrectomy, primarily caused by dumping syndrome and severe malnutrition, with late dumping syndrome being particularly significant. However, for recurrent fasting hypoglycemia, the possibility of insulinoma should be considered. Hypoglycemia caused by insulinoma can lead to severe consequences, including seizures and even death. Thus, it is crucial to differentially diagnose hypoglycemia occurring after total gastrectomy. CASE REPORT In this report, we present the case of a 36-year-old Chinese woman who underwent total gastrectomy for gastric cancer and subsequently received chemotherapy. Four months after surgery, she began experiencing recurrent seizures, and multiple tests confirmed hypoglycemia. A series of laboratory and imaging examinations ultimately led to a diagnosis of insulinoma. After surgical resection of the tumor, the patient's hypoglycemic symptoms resolved, and pathology results confirmed an insulinoma. CONCLUSIONS This case report highlights the rapid weight loss and severe hypoglycemia observed in a patient only 4 months after total gastrectomy for gastric cancer. Although dumping syndrome was initially suspected based on the clinical course, the final diagnosis turned out to be insulinoma. The case underscores the importance of comprehensive evaluation and appropriate diagnostic investigations for patients experiencing hypoglycemia after total gastrectomy. Furthermore, the case suggests that the increased levels of enteroglucagon following changes in the gastrointestinal tract resulting from total gastrectomy may promote the development of insulinomas. This case report also contributes to the existing literature regarding atypical presentations of insulinomas and their association with gastric resection.

Post-bariatric hypoglycaemia (PBH) is a rare yet disabling clinical condition, mostly reported after Roux-en-Y gastric bypass (RYGB) surgery. RYGB is one of the most widely used and effective bariatric procedures. The pathophysiology of PBH remains unclear, and treatment options are limited in effectiveness and/or carry significant side effects. Acarbose slows carbohydrates digestion and absorption and is generally considered first-line pharmacological treatment for PBH but its gastrointestinal side effects limit patient compliance. Canagliflozin inhibits intestinal and renal sodium-dependent glucose absorption and reduces postprandial excursions of glucose, insulin and incretins after RYGB - effects that could be beneficial in ameliorating PBH.

The trial aims to investigate how blood glucose levels are affected during daily living in subjects with PBH during treatment with canagliflozin or acarbose compared with placebo, and to study the meal-induced entero-endocrine mechanisms implied in the treatment responses.

In a double-blinded, randomized, crossover clinical trial, HypoBar I will investigate the effectiveness in reducing the risk of PBH, safety, ambulatory glucose profile and entero-endocrine responses when PBH is treated with canagliflozin 300 mg twice daily during a 4-week intervention period, compared with acarbose 50 mg thrice daily or placebo.

HypoBar I is approved by the Local regulatory entities. Results will be published in peer-reviewed journals.

If effective, well-tolerated and safe, canagliflozin could be a novel treatment for people with PBH. HypoBar I might also unravel new mechanisms underlying PBH, potentially identifying new treatment targets.

EudraCT number 2022-000157-87.

Post bariatric hypoglycaemia (PBH) is typically a post-prandial hypoglycaemia occurring about 2-4 hours after eating in people who have undergone bariatric surgery. PBH develops relatively late after surgery and often after discharge from post-surgical follow-up by bariatric teams, leading to variability in diagnosis and management in non-specialist centres.

to improve and standardise clinical practice in the diagnosis and management of PBH.

(1) to undertake an up-to-date review of the current literature; (2) to formulate practical and evidence-based guidance with regards on the diagnosis and treatment of PBH; (3) to recommend future avenues for research in this condition.

A scoping review was undertaken after an extensive literature search. A consensus on the guidance and confidence in the recommendations was reached by the steering group authors prior to review by key stakeholders.

We make pragmatic recommendations for the practical diagnosis and management of PBH including criteria for diagnosis and recognition, as well as recommendations for research areas that should be explored.

Metabolic and bariatric surgery (MBS) is the most effective therapeutic intervention for patients with obesity, with sleeve gastrectomy (SG) being the most commonly performed primary MBS procedure. Long-term studies have demonstrated that 15-20% of patients require revisional bariatric surgery (RBS) due to weight-related issues or surgical complications. Despite the gold standard being laparoscopic revision, there are other available approaches such as open or robotic-assisted. An extensive literature review was performed for articles from their inception to February 2024. A descriptive review of MBS procedures (SG, Roux-en-Y gastric bypass (RYGB), single anastomosis duodeno-ileostomy (SADI) and biliopancreatic diversion-duodenal switch (BPD-DS)) was carried out to report and compare outcomes between primary and revisional bariatric surgery. A similar review was conducted to compare outcomes of revisional approaches (open, laparoscopic, robotic). RYGB remains the dominant RBS with a similar safety profile compared to revisional SADI and BPD-DS. In terms of the RBS surgical approach, all three options showed comparable short and long-term outcomes, with robotic RBS being associated with longer operative time and variable length of stay. Additional long-term studies are required to further validate our conclusions.

Obesity remains a common metabolic disorder and a threat to health as it is associated with numerous complications. Lifestyle modifications and caloric restriction can achieve limited weight loss. Bariatric surgery is an effective way of achieving substantial weight loss as well as glycemic control secondary to weight-related type 2 diabetes mellitus. It has been suggested that an anorexigenic gut hormone response following bariatric surgery contributes to weight loss. Understanding the changes in gut hormones and their contribution to weight loss physiology can lead to new therapeutic treatments for weight loss. Two distinct types of neurons in the arcuate hypothalamic nuclei control food intake: proopiomelanocortin neurons activated by the anorexigenic (satiety) hormones and neurons activated by the orexigenic peptides that release neuropeptide Y and agouti-related peptide (hunger centre). The arcuate nucleus of the hypothalamus integrates hormonal inputs from the gut and adipose tissue (the anorexigenic hormones cholecystokinin, polypeptide YY, glucagon-like peptide-1, oxyntomodulin, leptin, and others) and orexigeneic peptides (ghrelin). Replicating the endocrine response to bariatric surgery through pharmacological mimicry holds promise for medical treatment. Obesity has genetic and environmental factors. New advances in genetic testing have identified both monogenic and polygenic obesity-related genes. Understanding the function of genes contributing to obesity will increase insights into the biology of obesity. This review includes the physiology of appetite control, the influence of genetics on obesity, and the changes that occur following bariatric surgery. This has the potential to lead to the development of more subtle, individualised, treatments for obesity.

Managing reactive hypoglycaemia (RH) poses challenges due to limited and often ineffective treatment options. We report a case series and draw on this to propose a stepwise treatment approach consisting of lifestyle modifications, metformin, GLP-1 analogues, and the use of flash glucose monitoring technology.

A retrospective review was conducted to analyse the management of 11 cases presenting with recurrent RH symptoms.

Two patients experienced successful resolution of symptoms through lifestyle modifications. Metformin alone was effective in treating seven out of nine patients who received pharmacological treatment. Two patients with previous upper gastrointestinal surgery showed a partial response to metformin and benefited further from additional long-acting GLP-1 analogue. Pharmacological intervention led to significant reductions in insulin and C-peptide levels in repeat mixed meal tolerance tests (P-values 0.043 for insulin and 0.006 for C-peptide). Finally, flash glucose monitoring technology was useful in early detection and preventing episodes of hypoglycaemia in one of these patients with persistent symptoms.

These findings highlight the potential efficacy of escalated treatment strategies for RH, including the use of metformin, GLP-1 analogues, and flash glucose monitoring technology.

Protein ingestion stimulates β-cell secretion and alters glucose flux. Enhanced action of glucagon-like peptide 1 (GLP-1) and increased plasma glucose excursion contribute to prandial hyperinsulinemia after gastric bypass surgery (GB) and sleeve gastrectomy (SG). We examined the contribution of endogenous GLP-1 to glucose kinetics and β-cell response to protein ingestion under basal glucose concentrations in humans, and whether these responses are affected by rerouted gut after GB or SG.

Glucose fluxes, insulin secretion rate (ISR), and incretin responses to a 50-gram oral protein load were compared between 10 non-diabetic individuals with GB, 9 matched subjects with SG and 7 non-operated controls (CN) with and without intravenous infusion of exendin-(9- 39) [Ex-9), a specific GLP-1 receptor (GLP-1R) antagonist.

Blocking GLP-1R increased the plasma glucose concentration before and after protein ingestion in all 3 groups (p<0.05) and decreased β-cell sensitivity to glucose in the first 30 minutes of protein ingestion (p<0.05). Reduction in the prandial ISR3h by Ex-9 infusion, however, only was observed in GB and SG (p<0.05 for interaction) and not in controls. Also, GLP-1R blockade increased post-protein insulin action in GB and SG, but not CN (p=0.09 for interaction). Endogenous glucose production (EGP) during the first 60 minutes after protein ingestion was increased in all 3 groups but EGP3h only was accentuated in GB by Ex-9 infusion (p<0.05 for interaction).

These findings are consistent with both a pancreatic and extrapancreatic role for GLP-1 during protein ingestion in humans, and GLP-1 actions are exaggerated by bariatric surgery.

Laparoscopic sleeve gastrectomy (SG) and laparoscopic Roux-en-Y gastric bypass (RYGB) are widely used bariatric procedures for which comparative efficacy and safety remain unclear.

To compare perioperative outcomes in SG and RYGB.

In this registry-based, multicenter randomized clinical trial (Bypass Equipoise Sleeve Trial), baseline and perioperative data for patients undergoing bariatric surgery from October 6, 2015, to March 31, 2022, were analyzed. Patients were from university, regional, county, and private hospitals in Sweden (n = 20) and Norway (n = 3). Adults (aged ≥18 years) eligible for bariatric surgery with body mass indexes (BMIs; calculated as weight in kilograms divided by height in meters squared) of 35 to 50 were studied.

Laparoscopic SG or RYGB.

Perioperative complications were analyzed as all adverse events and serious adverse events (Clavien-Dindo grade >IIIb). Ninety-day mortality was also assessed.

A total of 1735 of 14 182 eligible patients (12%; 1282 [73.9%] female; mean (SD) age, 42.9 [11.1] years; mean [SD] BMI, 40.8 [3.7]) were included in the study. Patients were randomized and underwent SG (n = 878) or RYGB (n = 857). The mean (SD) operating time was shorter in those undergoing SG vs RYGB (47 [18] vs 68 [25] minutes; P < .001). The median (IQR) postoperative hospital stay was 1 (1-1) day in both groups. The 30-day readmission rate was 3.1% after SG and 4.0% after RYGB (P = .33). There was no 90-day mortality. The 30-day incidence of any adverse event was 40 (4.6%) and 54 (6.3%) in the SG and RYGB groups, respectively (odds ratio, 0.71; 95% CI, 0.47-1.08; P = .11). Corresponding figures for serious adverse events were 15 (1.7%) for the SG group and 23 (2.7%) for the RYGB group (odds ratio, 0.63; 95% CI, 0.33-1.22; P = .19).

This randomized clinical trial of 1735 patients undergoing primary bariatric surgery found that both SG and RYGB were performed with a low perioperative risk without clinically significant differences between groups.

ClinicalTrials.gov Identifier: NCT02767505.

The American Diabetes Association (ADA) "Standards of Care in Diabetes" includes the ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, an interprofessional expert committee, are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations and a full list of Professional Practice Committee members, please refer to Introduction and Methodology. Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC.

We have previously shown that prandial endogenous glucose production (EGP) during insulin-induced hypoglycemia is smaller in non-diabetic subjects with gastric bypass (GB), where prandial glucagon-like peptide 1 (GLP-1) concentrations are 5-10 times higher than those in non-operated controls. Here, we sought to determine the effect of endogenous GLP-1 on prandial counterregulatory response to hypoglycemia after GB. Glucose fluxes, and islet-cell and gut hormone responses before and after mixed-meal ingestion were compared during a hyperinsulinemic hypoglycemic (~3.2 mmol/l) clamp with and without a GLP-1 receptor (GLP-1R) antagonist exendin-(9-39) (Ex-9) in non-diabetic subjects with prior GB compared to matched subjects with SG and non-surgical controls. In this setting, GLP-1R blockade had no effect on insulin secretion or insulin action, whereas prandial glucagon was enhanced in all 3 groups. Ex-9 infusion raised prandial EGP response to hypoglycemia in every GB subject but had no consistent effects on EGP among subjects with SG or non-operated controls (P < 0.05 for interaction). These results indicate that impaired post-meal glucose counterregulatory response to hypoglycemia after GB is partly mediated by endogenous GLP-1, highlighting a novel mechanism of action of GLP-1R antagonists for the treatment of prandial hypoglycemia in this population.

Postbariatric hypoglycemia affects >50% of individuals who have undergone Roux-en-Y gastric bypass surgery. Despite the often debilitating nature of this complication, existing treatment options are limited and often inefficient. Dasiglucagon is a stable glucagon analog available in a ready-to-use formulation and was recently shown to mitigate postbariatric hypoglycemia in experimental settings. Here, we aimed to evaluate the hypoglycemic hindering potential of dasiglucagon in an outpatient trial.

We conducted a randomized, double-blind, placebo-controlled, crossover, proof-of-concept study at the Center for Clinical Metabolic Research at Gentofte Hospital in Denmark. The study included 24 individuals who had undergone Roux-en-Y gastric bypass surgery (n = 23 women) with continuous glucose monitor-verified postbariatric hypoglycemia (≥15 min at <3.9 mmol/L three or more times per week) randomly assigned to two treatment periods of 4 weeks of self-administered subcutaneous dasiglucagon at 120 μg or placebo. The primary and key secondary outcomes were continuous glucose monitor-captured percentage of time in level 1 and 2 hypoglycemia (<3.9 and <3.0 mmol/L), respectively.

Compared with placebo, treatment with dasiglucagon significantly reduced time in level 1 hypoglycemia by 33% (-1.2 percentage points; 95% CI -2.0 to -0.5; P = 0.002) and time in level 2 hypoglycemia by 54% (-0.4 percentage points; 95% CI -0.6 to -0.2; P < 0.0001). Furthermore, dasiglucagon corrected hypoglycemia within 15 min in 401 of 412 self-administrations, compared with 104 of 357 placebo self-administrations (97.3% vs. 29.1% correction of hypoglycemia rate; P < 0.001). Dasiglucagon was generally well tolerated, with mostly mild to moderate adverse events of nausea.

Compared with placebo, 4 weeks of self-administered dasiglucagon effectively reduced clinically relevant hypoglycemia in individuals who had undergone Roux-en-Y gastric bypass surgery.

The history and evolution of bariatric/metabolic surgical procedures allows for only a brief introduction to complications and surgical approaches for improved weight loss. Our specialty lacks standardization of our operations such as gastric pouch size, intestinal bypass lengths, and consensus on which procedure is best for each individual patient. Anatomic construct as well as adherence to lifestyle modifications can affect short- and long-term outcomes.

Bariatric surgery is the most effective treatment in individuals with obesity to achieve remission of type 2 diabetes. Post-bariatric surgery hypoglycaemia occurs frequently, and management remains suboptimal, because of a poor understanding of the underlying pathophysiology. The glucoregulatory hormone responses to nutrients in individuals with and without post-bariatric surgery hypoglycaemia have not been systematically examined.

The study protocol was prospectively registered with PROSPERO. PubMed, EMBASE, Web of Science and the Cochrane databases were searched for publications between January 1990 and November 2021 using MeSH terms related to post-bariatric surgery hypoglycaemia. Studies were included if they evaluated individuals with post-bariatric surgery hypoglycaemia and included measurements of plasma glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), insulin, C-peptide and/or glucagon concentrations following an ingested nutrient load. Glycated haemoglobin (HbA1c) was also evaluated. A random-effects meta-analysis was performed, and Hedges' g (standardised mean difference) and 95% confidence intervals were reported for all outcomes where sufficient studies were available. The τ2 estimate and I2 statistic were used as tests for heterogeneity and a funnel plot with the Egger regression-based test was used to evaluate for publication bias.

From 377 identified publications, 12 were included in the analysis. In all 12 studies, the type of bariatric surgery was Roux-en-Y gastric bypass (RYGB). Comparing individuals with and without post-bariatric surgery hypoglycaemia following an ingested nutrient load, the standardised mean difference in peak GLP-1 was 0.57 (95% CI, 0.32, 0.82), peak GIP 0.05 (-0.26, 0.36), peak insulin 0.84 (0.44, 1.23), peak C-peptide 0.69 (0.28, 1.1) and peak glucagon 0.05 (-0.26, 0.36). HbA1c was less in individuals with hypoglycaemia - 0.40 (-0.67, -0.12). There was no evidence of substantial heterogeneity in any outcome except for peak insulin: τ2 = 0.2, I2 = 54.3. No publication bias was evident.

Following RYGB, postprandial peak plasma GLP-1, insulin and C-peptide concentrations are greater in individuals with post-bariatric surgery hypoglycaemia, while HbA1c is less. These observations support the concept that antagonism of GLP-1 would prove beneficial in the management of individuals with hypoglycaemia following RYGB.PROSPERO Registration Number: CRD42021287515.

This Obesity Medicine Association (OMA) Clinical Practice Statement (CPS) provides an overview of the mechanisms and treatment of obesity and hypertension.

The scientific support for this CPS is based upon published citations, clinical perspectives of OMA authors, and peer review by the Obesity Medicine Association leadership.

Mechanisms contributing to obesity-related hypertension include unhealthful nutrition, physical inactivity, insulin resistance, increased sympathetic nervous system activity, renal dysfunction, vascular dysfunction, heart dysfunction, increased pancreatic insulin secretion, sleep apnea, and psychosocial stress. Adiposopathic factors that may contribute to hypertension include increased release of free fatty acids, increased leptin, decreased adiponectin, increased renin-angiotensin-aldosterone system activation, increased 11 beta-hydroxysteroid dehydrogenase type 1, reduced nitric oxide activity, and increased inflammation.

Increase in body fat is the most common cause of hypertension. Among patients with obesity and hypertension, weight reduction via healthful nutrition, physical activity, behavior modification, bariatric surgery, and anti-obesity medications mostly decrease blood pressure, with the greatest degree of weight reduction generally correlated with the greatest degree of blood pressure reduction.

Prandial hyperinsulinemia after Roux-en-Y gastric bypass surgery (GB), and to lesser degree after sleeve gastrectomy (SG), has been attributed to rapid glucose flux from the gut and increased insulinotropic gut hormones. However, β-cell sensitivity to exogenous incretin is reduced after GB. This study examines the effect of GB versus SG on prandial glycemia and β-cell response to increasing concentrations of endogenous incretins.

Glucose kinetics, insulin secretion rate (ISR), and incretin responses to 50-g oral glucose ingestion were compared between ten nondiabetic participants with GB versus nine matched individuals with SG and seven nonoperated normal glucose tolerant control individuals (CN) with and without administration of 200 mg of sitagliptin.

Fasting glucose and hormonal levels were similar among three groups. Increasing plasma concentrations of endogenous incretins by two- to three-fold diminished prandial glycemia and increased β-cell secretion in all three groups (p < 0.05), but insulin secretion per insulin sensitivity (i.e., disposition index) was increased only in GB (p < 0.05 for interaction). However, plot of the slope of ISR (from premeal to peak values) versus plasma glucagon-like peptide-1 concentration was smaller after GB compared with SG and CN.

After GB, increasing incretin activity augments prandial β-cell response whereas the β-cell sensitivity to increasing plasma concentrations of endogenous incretin is diminished.

Symptomatic postbariatric hypoglycemia (PBH) is a known complication that can occur a few years after Roux-en-Y gastric bypass (RYGB). There is currently no established rating scale for PBH-associated symptoms developed for use in Swedish populations. The aim of the study was to translate an already existing questionnaire into Swedish and to test its reliability.

The study included forward and backward translations of the original Dumping Severity Scale (DSS) questionnaire with 8 items regarding symptoms of early dumping and 6 items regarding hypoglycemia, with each item graded on a 4-point Likert scale. The reliability of the Swedish translated questionnaire (DSS-Swe) was estimated using internal consistency and test-retest methods.

A total of 200 patients were included in the study. Good internal consistency was demonstrated regarding the items related to early dumping symptoms, with a Cronbach's alpha coefficient of 0.82, and very good agreement in terms of test-retest reliability, with an overall intraclass correlation coefficient (ICC) of 0.91 (95% CI 0.88-0.93). The items related to hypoglycemia yielded a good Cronbach's alpha coefficient of 0.76 and an ICC of 0.89 (95% CI 0.85-0.91).

The DSS-Swe questionnaire shows good reliability regarding both internal consistency and test-retest performance for use in Swedish populations.

Postprandial hyperinsulinemic hypoglycemia, although rare, is a well-documented complication that can manifest after upper gastrointestinal surgery. Despite its potential for severe morbidity, the underlying pathogenesis and optimal treatment strategies for this condition remain insufficiently understood. This report presents a compelling case of postprandial hypoglycemia following Billroth-II gastrojejunostomy, characterized by a marked increase in postprandial insulin levels, accompanied by the exaggerated response of incretin hormones. The incretin effect in this patient was found to be exceptionally high, measuring at approximately 90%. While nutritional interventions proved ineffective in alleviating the patient's symptoms, the administration of octreotide significantly attenuated the exaggerated postprandial insulin and incretin response, substantially ameliorating both the symptoms and postprandial hypoglycemia. Monthly subcutaneous injections of long-acting repeatable octreotide were initiated, resulting in the complete resolution of symptomatic postprandial hypoglycemia. Although the patient developed acalculous cholecystitis and gallstone cholangitis 2 years after commencing octreotide therapy, she has remained free from symptomatic postprandial hypoglycemia for more than 4 years. Our case underscores the efficacy of somatostatin analogs in the management of postprandial hyperinsulinemia after gastrointestinal surgery, shedding light on the potential involvement of incretin hormones in the pathophysiology of this condition.

Post-bariatric surgery hypoglycemia (PBH) is a metabolic complication of Roux-en-Y gastric bypass (RYGB). Since symptoms are a key component of the Whipple's triad to diagnose nondiabetic hypoglycemia, we evaluated the relationship between self-reported symptoms and postprandial sensor glucose profiles.

Thirty patients with PBH after RYGB (age: 50.1 [41.6-60.6] years, 86.7% female, BMI: 26.5 [23.5-31.2] kg/m2; median [interquartile range]) wore a blinded Dexcom G6 sensor while recording autonomic, neuroglycopenic, and gastrointestinal symptoms over 50 days. Symptoms (overall and each type) were categorized into those occurring in postprandial periods (PPPs) without hypoglycemia, or in the preceding dynamic or hypoglycemic phase of PPPs with hypoglycemia (nadir sensor glucose <3.9 mmol/L). We further explored the relationship between symptoms and the maximum negative rate of sensor glucose change and nadir sensor glucose levels.

In 5,851 PPPs, 775 symptoms were reported, of which 30.6 (0.0-59.9)% were perceived in PPPs without hypoglycemia, 16.7 (0.0-30.1)% in the preceding dynamic phase and 45.0 (13.7-84.7)% in the hypoglycemic phase of PPPs with hypoglycemia. Per symptom type, 53.6 (23.8-100.0)% of the autonomic, 30.0 (5.6-80.0)% of the neuroglycopenic, and 10.4 (0.0-50.0)% of the gastrointestinal symptoms occurred in the hypoglycemic phase of PPPs with hypoglycemia. Both faster glucose dynamics and lower nadir sensor glucose levels were related with symptom perception.

The relationship between symptom perception and PBH is complex, challenging clinical judgement and decision-making in this population.