Post-bariatric surgery hypoglycaemia is typically mediated by hyperinsulinaemia, although the exact mechanisms are incompletely understood. Two cases of non-insulin mediated, ketotic hypoglycaemia following sleeve gastrectomy are presented. After fasting for 40 and 65 h, respectively, both patients developed symptomatic hypoglycaemia, with corresponding low insulin, low c-peptide and elevated beta-hydroxybutyrate levels. Morning cortisol and IGF1 levels were normal. Potential mechanisms for ketotic hypoglycaemia following bariatric surgery include reduction in hepatic, renal and intestinal gluconeogenesis, or alternatively an underlying inborn error of metabolism such as a glycogen storage disorder unmasked by bariatric surgery. Most glycogen storage disorders present in childhood, but there have been rare case reports of glycogen storage disorders types I, III and IX diagnosed in adulthood. Neither of the above cases had other features of a glycogen storage disorder such as elevated lactate, hyperuricaemia, hypertriglyceridaemia, hepatomegaly, myopathy or an indicative family history. Both patients trialled first-line dietary management, which was inadequate in managing hypoglycaemia. Treatment with the glucagon-like peptide-1 receptor agonist semaglutide resulted in the resolution of hypoglycaemic episodes in one patient, and a significant reduction in hypoglycaemic episodes in the other patient.

Reversal of Roux-en-Y gastric bypass (RYGB) may be indicated for possible side effects such as malnutrition, intolerance, dumping syndrome, or late dumping. Reversal can however induce significant gastro-esophageal reflux disease (GERD).

We report the case of a 55 years old Caucasian woman, who had undergone conversion of Nissen fundoplication performed for GERD (Grade B) into RYGB because of recurrent reflux, though Grade A esophagitis and increasing obesity (37.5 kg/m2 BMI). She developed invalidating symptoms of late dumping syndrome and severe diarrhea. Pre- and postoperative evaluation an eso-gastroscopy with esophagitis grade evaluation. Treatment consisted of physiologic reversal of the RYGB, by reimplantation of the alimentary limb into the remnant stomach.

Pre-reversal endoscopy showed Grade A esophagitis. Oral glucose test demonstrated severe hypoglycemia persisting till 120 min post-ingestion and clinical symptoms of hypoglycemia (Whipple triad) (40 to 53 mg/dl). Three months after reversal the diagnostic tests had significantly improved, both in terms of glucose metabolism and GERD symptoms. At 22 months after surgery, the patient still did not suffer from diarrhea anymore, her glycemic profile was stable under antidiabetic medications and her BMI raised to 29 kg/m2.

Reversal of Roux-en-Y gastric bypass by incorporation of the alimentary limb between the gastric pouch and the gastric remnant seems to successfully address the dual issue of post-RYGB late dumping and preventing GERD, the different mechanisms involved will be explained latter in this paper.

The prevalence of obesity continues to increase worldwide. Obesity is associated with an increased risk of cardiometabolic and other diseases, reduced quality of life and shortened life expectancy. Highly effective therapies are required to achieve meaningful and sustained weight reduction to prevent, slow or reverse disease associated with obesity. Bariatric surgery is a highly effective intervention to induce weight loss, with observational data demonstrating durability of weight loss over 10 or more years. In addition, bariatric surgery improves cardiometabolic risk factors, including hyperglycaemia and type 2 diabetes, hypertension and dyslipidaemia. Observational data have shown a reduction in all-cause mortality, cardiovascular events and mortality and a reduction in cancer risk and mortality in patients who have undergone bariatric surgery compared to matched patients who did not have surgery. The emergence of newer incretin agonists, particularly semaglutide and tirzepatide, have demonstrated remarkable efficacy in inducing and maintaining weight loss with ongoing use. As for bariatric surgery, incretin agonist therapies also improve type 2 diabetes outcomes, cardiovascular mortality and other obesity-related complications, with new evidence emerging and long-term outcome data awaited. This perspective compares bariatric surgery and incretin agonist therapy, assessing their relative efficacies in weight reduction, impact on obesity-related complications, their respective risk profiles and considerations of cost-effectiveness and equity of access. These comparisons seek to evaluate whether these increasingly popular medications could make bariatric surgery a thing of the past.

Postprandial hypoglycaemia (PPHG) is a frequent late complication of Roux-en-Y gastric bypass (RYGB) in people without diabetes. We aimed to examine the pathogenetic mechanisms of PPHG and its clinical consequences in people with a history of type 2 diabetes.

In this case-control study, 24 participants with type 2 diabetes treated with RYGB (14 women; median [IQR] age 53.5 [13.8] years, BMI 29.3 [6.3] kg/m2, HbA1c 36.0 [6.2] mmol/mol [5.4% (0.6%)]) underwent a dual-tracer, frequently sampled, 300 min, 75 g OGTT for the diagnosis of PPHG (glucose nadir <3.0 mmol/l, or <3.3 mmol/l with symptoms). Plasma glucose, glucose tracers, insulin, C-peptide, glucagon-like peptide-1, gastric inhibitory polypeptide, glucagon, adrenaline (epinephrine), noradrenaline (norepinephrine), cortisol and NEFAs were measured. Mathematical models were implemented to estimate glucose metabolic fluxes and beta cell function. ECG recordings, cognitive testing and hypoglycaemia awareness assessments were repeated during the OGTT. Glycaemic levels and dietary habits were assessed under free-living conditions.

PPHG occurred in 12 (50%) participants, mostly without symptoms, due to excessive tracer-derived glucose clearance (mean group difference ± SE in AUC0-180 min +261±72 ml min-1 kg-1 × min) driven by higher whole-body insulin sensitivity and early glucose-stimulated hyperinsulinaemia, the latter depending on lower insulin clearance and enhanced beta cell function, regardless of incretin hormones. PPHG participants also had defective counterregulatory hormone responses to hypoglycaemia, preventing a physiological increase in endogenous glucose production and the appearance of symptoms and signs of sympathetic cardiovascular activation and neuroglycopenia. PPHG was associated with more frequent and prolonged hypoglycaemia on 14 day continuous glucose monitoring and alterations in free-living dietary habits.

Our results demonstrate that post-bypass PPHG occurs frequently in individuals with a history of type 2 diabetes, often without warning symptoms, and expose its complex pathogenetic mechanisms, revealing potential therapeutic targets.

Metabolic and bariatric surgery (MBS) is an effective intervention for patients with severe obesity and metabolic comorbidities, particularly when non-surgical weight loss methods prove insufficient. MBS has shown significant potential for improving quality of life and metabolic health outcomes in individuals with obesity, yet it carries inherent risks. Although these procedures offer a multifaceted approach to obesity treatment and its clinical advantages are well-documented, the limited understanding of its long-term outcomes and the role of multidisciplinary care pose challenges. With an emphasis on quality-of-life enhancements and the handling of postoperative difficulties, the present narrative review seeks to compile the most recent findings on MBS while emphasizing the value of an integrated approach to maximize patient outcomes. Effective MBS and patients' management require a collaborative team approach, involving surgeons, dietitians, psychologists, pharmacists, and other healthcare providers to address not only physiological but also psychosocial patient needs. Comparative studies demonstrate the efficacy of various MBS methods, including Roux-en-Y gastric bypass and laparoscopic sleeve gastrectomy that may considerably decrease morbidity and mortality in individuals with obesity. Future studies should target long-term patient treatment, and decision making should be aided by knowledge of obesity, comorbidity recurrence rates, and permanence of benefits.

Postprandial hypoglycemia (PPH) is a challenging and significant complication that can occur following bariatric and metabolic surgery. Symptoms of PPH are typical of hypoglycemia, such as sweating, weakness, disorientation, palpitation, etc. The complex nature of PPH is essential to achieve accurate diagnosis and effective management. This review aims to give extensive coverage of the intricate nature of PPH common with bariatric and metabolic surgery, outlining its pathogenesis, risk factors, clinical presentation, diagnostic strategies, and treatment options. The study explores various clinical forms and pathogenic mechanisms behind PPH while discussing diagnostic tools like continuous glucose monitoring or mixed meal tolerance tests. Furthermore, it considers possible interventions, including dietary changes, pharmaceutical therapies, and surgeries, to relieve symptoms and improve patient's quality of life. It aims to comprehensively understand how healthcare professionals can effectively manage this disorder for patients undergoing bariatric and metabolic surgery.

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.

Abdominal pain and postbariatric hypoglycemia (PBH) are common after bariatric surgery.

This study aimed to explore the potential relationship between abdominal pain, gastrointestinal symptoms, and PBH more than a decade after Roux-en-Y gastric bypass (RYGB) and whether continuous glucose monitoring (CGM) with dietary intervention has an educational role in reducing symptoms.

At two public hospitals in Norway (one University Hospital) 22 of 46 invited patients who reported abdominal pain more than weekly took part. Recruited from a prospective follow-up study of 546 patients 14.5 years after RYGB.

They used a CGM for two 14-day periods, with a dietary intervention between periods. The Gastrointestinal Symptom Rating Scale (GSRS) and the Dumping Severity Score (DSS) questionnaires were completed at the start and end of the study.

The 22 women had preoperative age 39.6 ± 7.7 years and body mass index (BMI) 42.0 ± 4.0 kg/m2, present age 54.6 ± 7.7 years and BMI 29.8 ± 4.8 kg/m2. The total GSRS score and DSS of early dumping decreased after the diet intervention. The number of events with Level 1 (<3.9 mmol/L) or Level 2 (<3.0 mmol/L) hypoglycemia did not change in the second period. Half of the patients had fewer, three had unchanged, and eight had more frequent events with Level 1 hypoglycemia after the intervention. Ten patients had Level 2 hypoglycemia.

Though inconclusive findings, a personalized dietary intervention reduces GSRS. This intervention was accompanied by lower mean absolute glucose in patients with recurrent abdominal pain after bariatric surgery. However, further studies are needed to explore the benefits of CGM in this setting.

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.

Postprandial hypoglycemia is a complication of Roux-en-Y gastric bypass (RYGB), but the effects of postprandial exercise and meal glycemic index (GI) on postprandial glucose and glucoregulatory hormone responses are unknown. Ten RYGB-operated and 10 age and weight-matched unoperated women completed four test days in random order ingesting mixed meals with high GI (HGI, GI = 93) or low GI (LGI, GI = 54), but matched on energy and macronutrient content. Ten minutes after meal completion, participants rested or cycled for 30 min at 70% of maximum oxygen uptake (V̇o2max). Blood was collected for 4 h. Postprandial exercise did not lower plasma nadir glucose in RYGB after HGI (HGI/rest 3.7 ± 0.5 vs. HGI/Ex 4.1 ± 0.4 mmol/L, P = 0.070). Replacing HGI with LGI meals raised glucose nadir in RYGB (LGI/rest 4.1 ± 0.5 mmol/L, P = 0.034) and reduced glucose excursions (Δpeak-nadir) but less so in RYGB (-14% [95% CI: -27; -1]) compared with controls (-33% [-51; -14]). Insulin responses mirrored glucose concentrations. Glucagon-like peptide 1 (GLP-1) responses were greater in RYGB versus controls, and higher with HGI versus LGI. Glucose-dependent insulinotropic polypeptide (GIP) responses were greater after HGI versus LGI in both groups. Postexercise glucagon responses were lower in RYGB than controls, and noradrenaline responses tended to be lower in RYGB, whereas adrenaline responses were similar between groups. In conclusion, moderate intensity cycling shortly after meal intake did not increase the risk of postprandial hypoglycemia after RYGB. The low GI meal increased nadir glucose and reduced glucose excursions compared with the high GI meal. RYGB participants had lower postexercise glucagon responses compared with controls.NEW & NOTEWORTHY We investigate the effect of moderate exercise after a high or a low glycemic index meal on nadir glucose and glucoregulatory hormones in gastric bypass-operated individuals and in matched unoperated controls. Cycling shortly after meal intake did not increase the risk of hypoglycemia in operated individuals. The low glycemic index meal increased glucose nadir and reduced excursions compared with the high glycemic index meal. Operated individuals had lower postexercise glucagon responses compared with controls.

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.

With a rise in obesity and more patients opting for bariatric surgery, it becomes crucial to understand associated complications like postprandial hypoglycemia (PPH). After bariatric surgery, significant changes are seen in insulin sensitivity, beta cell function, glucagon-like peptide 1 (GLP-1) levels, the gut microbiome, and bile acid metabolism. And in a small subset of patients, exaggerated imbalances in these functional and metabolic processes lead to insulin-glucose mismatch and hypoglycemia. The main treatment for PPH involves dietary modifications. For those that do not respond, medications or surgical interventions are considered to reverse some of the imbalances. We present a few case reports of patients that safely tolerated GLP-1 agonists. However, larger randomized control trials are needed to further characterize PPH and understand its treatment.

While bariatric surgery remains the most effective treatment for obesity that allows substantial weight loss with improvement and possibly remission of obesity-associated comorbidities, some postoperative complications may occur. Managing physicians need to be familiar with the common problems to ensure timely and effective management. Of these complications, postoperative hypoglycemia is an increasingly recognized complication of bariatric surgery that remains underreported and underdiagnosed.

This article highlights the importance of identifying hypoglycemia in patients with a history of bariatric surgery, reviews pathophysiology and addresses available nutritional, pharmacological and surgical management options. Systemic evaluation including careful history taking, confirmation of hypoglycemia and biochemical assessment is essential to establish accurate diagnosis. Understanding the weight-dependent and weight-independent mechanisms of improved postoperative glycemic control can provide better insight into the causes of the exaggerated responses that lead to postoperative hypoglycemia.

Management of post-operative hypoglycemia can be challenging and requires a multidisciplinary approach. While dietary modification is the mainstay of treatment for most patients, some patients may benefit from pharmacotherapy (e.g. GLP-1 receptor antagonist); Surgery (e.g. reversal of gastric bypass) is reserved for unresponsive severe cases. Additional research is needed to understand the underlying pathophysiology with a primary aim in optimizing diagnostics and treatment options.

Hypoglycaemia in non-diabetic pregnancy is rare, the majority of reported cases being due to insulinoma, acute fatty liver of pregnancy, malaria and inborn errors of metabolism. A case of hypoglycaemia in a woman with previous laparoscopic sleeve gastrectomy, and hypothalamic-pituitary-adrenal axis insufficiency in the setting of opioid dependence is presented. The timing of low interstitial glucose levels was atypical for late dumping syndrome following bariatric surgery, and a change in the woman's glucocorticoid replacement resulted in resolution of hypoglycaemic symptoms. The incidence of opioid dependence in pregnancy is increasing rapidly. Health professionals should be aware of the possibility of opioids causing hypothalamic-pituitary-adrenal axis insufficiency, and the additional mechanisms by which opioids may cause hypoglycaemia.

Patients with chronic gastrointestinal disease such as inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), celiac disease, gastroesophageal reflux disease (GERD), pancreatitis, and chronic liver disease (CLD) often suffer from obesity because of coincidence (IBD, IBS, celiac disease) or related pathophysiology (GERD, pancreatitis and CLD). It is unclear if such patients need a particular diagnostic and treatment that differs from the needs of lean gastrointestinal patients. The present guideline addresses this question according to current knowledge and evidence.

The present practical guideline is intended for clinicians and practitioners in general medicine, gastroenterology, surgery and other obesity management, including dietitians and focuses on obesity care in patients with chronic gastrointestinal diseases.

The present practical guideline is the shortened version of a previously published scientific guideline developed according to the standard operating procedure for ESPEN guidelines. The content has been re-structured and transformed into flow-charts that allow a quick navigation through the text.

In 100 recommendations (3× A, 33× B, 24 × 0, 40× GPP, all with a consensus grade of 90% or more) care of gastrointestinal patients with obesity - including sarcopenic obesity - is addressed in a multidisciplinary way. A particular emphasis is on CLD, especially metabolic associated liver disease, since such diseases are closely related to obesity, whereas liver cirrhosis is rather associated with sarcopenic obesity. A special chapter is dedicated to obesity care in patients undergoing bariatric surgery. The guideline focuses on adults, not on children, for whom data are scarce. Whether some of the recommendations apply to children must be left to the judgment of the experienced pediatrician.

The present practical guideline offers in a condensed way evidence-based advice how to care for patients with chronic gastrointestinal diseases and concomitant obesity, an increasingly frequent constellation in clinical practice.

Post-bariatric-surgery hypoglycemia (PBH) is a serious complication of bariatric surgery (BS). In our previous study about three quarters of the patients developed PBH. However long-term follow-up data is lacking to determine whether this condition improves with time. The aim of the current study was to re-assess post-BS patients who participated in our previous study and determine whether there are changes in the frequency and/or severity of hypoglycemic events.

Twenty-four post-BS, post Roux-en-Y gastric-bypass (RYGB = 10), post omega-loop gastric-bypass (OLGB = 9) and post sleeve-gastrectomy (SG = 5) individuals were reevaluated in a follow-up study 34.4 ± 4 months after their previous assessment and 67 ± 17 months since surgery. The evaluation included: a dietitian assessment, a questionnaire, meal-tolerance test (MTT) and a one-week masked continuous glucose monitoring (CGM). Hypoglycemia and severe hypoglycemia were defined by glucose levels ≤54 mg/dl and ≤40 mg/dl, respectively. Thirteen patients reported questionnaire meal-related complaints, mainly non-specific. During MTT, hypoglycemia occurred in 75% of the patients, and severe hypoglycemia in a third, but none was associated with specific complaints. During CGM, 66% of patients developed hypoglycemia and 37% had severe hypoglycemia. We did not observe significant improvements in hypoglycemic events compared to the previous assessment. Despite the high frequency of hypoglycemia, it did not necessitate hospitalizations or lead to death.

PBH did not resolve within long-term follow-up. Intriguingly, most patient were unaware of these events which can lead to underestimation by the medical staff. Further studies are needed to determine possible long term sequela of repeated hypoglycemia.

Post-bariatric hypoglycaemia is an increasingly recognised complication of bariatric surgery, manifesting particularly after Roux-en-Y gastric bypass. While hyperinsulinaemia is an established pathophysiological feature, the role of counter-regulation remains unclear. We aimed to assess counter-regulatory hormones and glucose fluxes during insulin-induced postprandial hypoglycaemia in patients with post-bariatric hypoglycaemia after Roux-en-Y gastric bypass vs surgical and non-surgical control individuals.

In this case-control study, 32 adults belonging to four groups with comparable age, sex and BMI (patients with post-bariatric hypoglycaemia, Roux-en-Y gastric bypass, sleeve gastrectomy and non-surgical control individuals) underwent a postprandial hypoglycaemic clamp in our clinical research unit to reach the glycaemic target of 2.5 mmol/l 150-170 min after ingesting 15 g of glucose. Glucose fluxes were assessed during the postprandial and hypoglycaemic period using a dual-tracer approach. The primary outcome was the incremental AUC of glucagon during hypoglycaemia. Catecholamines, cortisol, growth hormone, pancreatic polypeptide and endogenous glucose production were also analysed during hypoglycaemia.

The rate of glucose appearance after oral administration, as well as the rates of total glucose appearance and glucose disappearance, were higher in both Roux-en-Y gastric bypass groups vs the non-surgical control group in the early postprandial period (all p<0.05). During hypoglycaemia, glucagon exposure was significantly lower in all surgical groups vs the non-surgical control group (all p<0.01). Pancreatic polypeptide levels were significantly lower in patients with post-bariatric hypoglycaemia vs the non-surgical control group (median [IQR]: 24.7 [10.9, 38.7] pmol/l vs 238.7 [186.3, 288.9] pmol/l) (p=0.005). Other hormonal responses to hypoglycaemia and endogenous glucose production did not significantly differ between the groups.

The glucagon response to insulin-induced postprandial hypoglycaemia is lower in post-bariatric surgery individuals compared with non-surgical control individuals, irrespective of the surgical modality. No significant differences were found between patients with post-bariatric hypoglycaemia and surgical control individuals, suggesting that impaired counter-regulation is not a root cause of post-bariatric hypoglycaemia.

ClinicalTrials.gov NCT04334161.

Postprandial reactive hypoglycemia, or late dumping syndrome, is a common but underrecognized complication from bypass surgery. We report an unusual case of postprandial reactive hypoglycemia in a patient with a severe esophageal stricture from corrosive agent ingestion who underwent ileocolic interposition and an antecolic Billroth-II gastrojejunostomy. A 22-year-old male patient with a one-year history of corrosive ingestion was referred to the hospital for a surgical correction of severe esophageal stricture. After the patient underwent ileocolic interposition and an antecolic Billroth-II gastrojejunostomy, he experienced multiple episodes of gastroesophageal refluxsymptoms during nasogastric feeding and had onset of hypoglycemic symptoms. His plasma glucose level was 59 mg/dL. After we had intraoperatively re-inserted a jejunostomy tube bypassing the ileocolic interposition, and reintroduced enteral nutrition, his hypoglycemic symptoms resolved. We performed a mixed meal tolerance test by nasogastric tube, but the results did not show postprandial hypoglycemia. Although the specific mechanism is unclear, this case suggests gastroesophageal reflux to the ileal interposition may have caused a state of exaggerated hyperinsulinemic response and rebound hypoglycemia. To the best of our knowledge, we are the first to report case of postprandial hypoglycemia after ileocolic interposition, which may have been caused by exaggerated hyperinsulinemic response due to gastroesophageal reflux to the ileal interposition. This syndrome should be considered in the patient who has had ileocolic interposition surgery and has developed postprandial hypoglycemia.

To evaluate medical and surgical treatment of postbariatric hypoglycaemia (PBH) in daily practice.

Retrospective data were extracted from medical records from four hospitals. PBH was defined by neuroglycopenic symptoms together with a documented glucose <3.0 mmol/L in the postprandial setting after previous bariatric surgery. Data were scored semiquantitatively on efficacy and side effects by two reviewers independently. Duration of efficacy and of use were calculated.

In total, 120 patients were included with a median follow-up of 27 months with a mean baseline age of 41 years, total weight loss of 33% and glucose nadir 2.3 mmol/L. Pharmacotherapy consisted of acarbose, diazoxide, short- and long-acting octreotide and glucagon-like peptide-1 receptor agonist analogues (liraglutide and semaglutide) with an overall efficacy in 45%-75% of patients. Combination therapy with two drugs was used by 30 (25%) patients. The addition of a second drug was successful in over half of the patients. Long-acting octreotide and the glucagon-like peptide-1 receptor agonist analogues scored best in terms of efficacy and side effects with a median duration of use of 35 months for octreotide. Finally, 23 (19%) patients were referred for surgical intervention. Efficacy of the surgical procedures, pouch banding, G-tube placement in remnant stomach and Roux-en-Y gastric bypass reversal, pooled together, was 79% with a median duration of initial effect of 13 months.

In daily practice, pharmacotherapy for PBH was successful in half to three quarters of patients. Combination therapy was often of value. One in five patients finally needed a surgical procedure, with overall good results.

Although promising therapeutics are in the pipeline, bariatric surgery (also known as metabolic surgery) remains our most effective strategy for the treatment of obesity and type 2 diabetes mellitus (T2DM). Of the many available options, Roux-en-Y gastric bypass (RYGB) and vertical sleeve gastrectomy (VSG) are currently the most widely used procedures. RYGB and VSG have very different anatomical restructuring but both surgeries are effective, to varying degrees, at inducing weight loss and T2DM remission. Both weight loss-dependent and weight loss-independent alterations in multiple tissues (such as the intestine, liver, pancreas, adipose tissue and skeletal muscle) yield net improvements in insulin resistance, insulin secretion and insulin-independent glucose metabolism. In a subset of patients, post-bariatric hypoglycaemia can develop months to years after surgery, potentially reflecting the extreme effects of potent glucose reduction after surgery. This Review addresses the effects of bariatric surgery on glucose regulation and the potential mechanisms responsible for both the resolution of T2DM and the induction of hypoglycaemia.

This manuscript provides a review of post-bariatric hypoglycemia (PBH) with a special focus on the role of the registered dietitian-nutritionist (RDN) and medical nutrition therapy (MNT) recommendations as foundational for management.

As the number of bariatric surgeries rises yearly, with 256,000 performed in 2019, PBH is an increasingly encountered late complication. Following Roux-en-Y (RYGB) or vertical sleeve gastrectomy (VSG), about 1/3 of patients report symptoms suggestive of at least mild postprandial hypoglycemia, with severe and/or medically confirmed hypoglycemia in 1-10%. Anatomical alterations, changes in GLP1 and other intestinally derived hormones, excessive insulin response, reduced insulin clearance, impaired counterregulatory hormone response to hypoglycemia, and other factors contribute to PBH. MNT is the cornerstone of multidisciplinary treatment, with utilization of personal continuous glucose monitoring to improve safety when possible. While many individuals require pharmacotherapy, there are no currently approved medications for PBH. Increasing awareness and identification of individuals at risk for or with PBH is critical given the potential impact on safety, nutrition, and quality of life. A team-based approach involving the individual, the RDN, and other clinicians is essential in providing ongoing assessment and individualization of MNT in the long-term management of PBH.

Postprandial hyperinsulinaemic hypoglycaemia is a common complication of bariatric surgery. Although in general its evolution is mild and self-limited, it can lead to neuroglycopaenia and compromise the patient's safety and quality of life. The aim of this document is to offer some recommendations to facilitate the clinical care of these complex patients, reviewing the aetiopathogenesis, its diagnosis and treatment that, sequentially, will include dietary and pharmacological measures and surgery in refractory cases. In the absence of high-quality studies, the diagnostic and therapeutic approach proposed is based on the consensus of experts of the Grupo de Obesidad de la Sociedad Española de Endocrinología y Nutrición [Obesity Group of the Spanish Society of Endocrinology and Nutrition], GOSEEN. Those undergoing bariatric surgery should be informed of the possibility of developing this complication.

Patients with chronic gastrointestinal (GI) disease such as inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), celiac disease, gastroesophageal reflux disease (GERD), pancreatitis, and chronic liver disease (CLD) often suffer from obesity because of coincidence (IBD, IBS, celiac disease) or related pathophysiology (GERD, pancreatitis and CLD). It is unclear if such patients need a particular diagnostic and treatment that differs from the needs of lean GI patients. The present guideline addresses this question according to current knowledge and evidence.

The objective of the guideline is to give advice to all professionals working in the field of gastroenterology care including physicians, surgeons, dietitians and others how to handle patients with GI disease and obesity.

The present guideline was developed according to the standard operating procedure for ESPEN guidelines, following the Scottish Intercollegiate Guidelines Network (SIGN) grading system (A, B, 0, and good practice point (GPP)). The procedure included an online voting (Delphi) and a final consensus conference.

In 100 recommendations (3x A, 33x B, 24x 0, 40x GPP, all with a consensus grade of 90% or more) care of GI patients with obesity - including sarcopenic obesity - is addressed in a multidisciplinary way. A particular emphasis is on CLD, especially fatty liver disease, since such diseases are closely related to obesity, whereas liver cirrhosis is rather associated with sarcopenic obesity. A special chapter is dedicated to obesity care in patients undergoing bariatric surgery. The guideline focuses on adults, not on children, for whom data are scarce. Whether some of the recommendations apply to children must be left to the judgment of the experienced pediatrician.

The present guideline offers for the first time evidence-based advice how to care for patients with chronic GI diseases and concomitant obesity, an increasingly frequent constellation in clinical practice.

Exaggerated postprandial incretin and insulin responses are well documented in postbariatric surgery hypoglycemia (PBH) after Roux-en-Y gastric bypass (RYGB). However, less is known about PBH after sleeve gastrectomy (SG).

We sought to compare meal-stimulated hormonal response in those with PBH after SG vs RYGB.

We enrolled 23 post-SG (12 with and 11 without PBH) and 20 post-RYGB (7 with and 13 without PBH) individuals who underwent bariatric surgery at our institution. PBH was defined as plasma glucose less than 60 mg/dL on 4-hour mixed-meal tolerance test (MTT). Islet and incretin hormones were compared across the 4 groups.

Participants (N = 43) were on average 5 years post surgery, with a mean age of 48 years, mean preoperative body mass index of 48.4, 81% female, 61% White, and 53% post SG. Regardless of PBH, the SG group showed lower glucose, glucagon, and glucagon-like peptide 1 (GLP-1) responses to MTT and similar insulin and glucose-dependent insulinotropic polypeptide (GIP) responses compared to the RYGB group. Among those with PBH, the SG group following the MTT showed a lower peak glucose (P = .02), a similar peak insulin (90.3 mU/L vs 171mU/L; P = .18), lower glucagon (P < .01), early GLP-1 response (AUC0-60 min; P = .01), and slower time to peak GIP (P = .02) compared to PBH after RYGB.

Among individuals with PBH, those who underwent SG were significantly different compared to RYGB in meal-stimulated hormonal responses, including lower glucagon and GLP-1 responses, but similar insulin and GIP responses. Future studies are needed to better understand the differential contribution of insulin and non-insulin-mediated mechanisms behind PBH after SG vs RYGB.

To investigate the efficacy and safety of dasiglucagon, a novel stable glucagon analog in a liquid formulation, in Roux-en-Y gastric bypass (RYGB)-operated individuals suffering from postbariatric hypoglycemia (PBH).

In a randomized, double-blind, placebo-controlled, crossover trial, 10 RYGB-operated participants with continuous glucose monitoring-verified PBH were randomly assigned to 3 trial days, each consisting of a 240-min standardized liquid mixed-meal test with the subcutaneous injection of placebo or 80 μg or 200 μg dasiglucagon.

Compared with placebo, treatment with both 80 and 200 μg dasiglucagon raised nadir plasma glucose (PG) (placebo: 3.0 ± 0.2 mmol/L [mean ± SEM]; 80 μg dasiglucagon: 3.9 ± 0.3 mmol/L, P = 0.002; 200 μg dasiglucagon: 4.5 ± 0.2 mmol/L, P = 0.0002) and reduced time in hypoglycemia (PG <3.9 mmol/L) by 70.0 min (P = 0.030 and P = 0.008).

Single-dose administration of dasiglucagon effectively mitigated postprandial hypoglycemia.

Following bariatric surgery, patients can develop non-specific symptoms self-described as hypoglycemia. However, confirming hypoglycemia can be technically challenging, and therefore, these individuals are frequently treated empirically. This study aimed to describe what diagnostic evaluation and therapeutic interventions patients referred for post-bariatric surgery hypoglycemia undergo.

Retrospective observational cohort study of patients with a history of bariatric surgery was evaluated for post-bariatric surgery hypoglycemia in a tertiary referral center from 2008 to 2017. We collected demographic and bariatric surgery information, clinical presentation of symptoms referred to as hypoglycemia, laboratory and imaging studies performed to evaluate these symptoms, and symptom management and outcomes.

A total of 60/2450 (2.4%) patients who underwent bariatric surgery were evaluated in the Department of Endocrinology for hypoglycemia-related symptoms. The majority were middle-aged women without type 2 diabetes who had undergone Roux-en-Y gastric bypass. Thirty-nine patients (65%) completed a biochemical assessment for hypoglycemia episodes. Six (10%) had confirmed hypoglycemia by Whipple's triad, and four (6.7%) met the criteria for post-bariatric surgery hypoglycemia based on clinical and biochemical criteria. All patients were recommended dietary modification as the initial line of treatment, and this intervention resulted in most patients reporting at least some improvement in their symptoms. Eight patients (13%) were prescribed pharmacotherapy, and two patients required additional interventions for symptom control.

In our experience, evaluation for hypoglycemia-related symptoms after bariatric surgery was rare. Hypoglycemia was confirmed in the minority of patients. Even without establishing a diagnosis of hypoglycemia, dietary changes were a helpful strategy for symptom management for most patients.

Secretion of insulin from pancreatic β-cells is complex, but physiological glucose-dependent secretion is dominated by electrical activity, in turn controlled by ATP-sensitive potassium (KATP) channel activity. Accordingly, loss-of-function mutations of the KATP channel Kir6.2 (KCNJ11) or SUR1 (ABCC8) subunit increase electrical excitability and secretion, resulting in congenital hyperinsulinism (CHI), whereas gain-of-function mutations cause underexcitability and undersecretion, resulting in neonatal diabetes mellitus (NDM). Thus, diazoxide, which activates KATP channels, and sulfonylureas, which inhibit KATP channels, have dramatically improved therapies for CHI and NDM, respectively. However, key findings do not fit within this simple paradigm: mice with complete absence of β-cell KATP activity are not hyperinsulinemic; instead, they are paradoxically glucose intolerant and prone to diabetes, as are older human CHI patients. Critically, despite these advances, there has been little insight into any role of KATP channel activity changes in the development of type 2 diabetes (T2D). Intriguingly, the CHI progression from hypersecretion to undersecretion actually mirrors the classical response to insulin resistance in the progression of T2D. In seeking to explain the progression of CHI, multiple lines of evidence lead us to propose that underlying mechanisms are also similar and that development of T2D may involve loss of KATP activity.

With the increasing performance of bariatric surgery, rare complications are becoming prevalent. We review the diagnosis and treatment of dysautonomia after bariatric surgery and the limited treatment options available. We summarize the suggested mechanisms and explain why a complete understanding of the etiology has yet to be determined.

In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a systematic review was performed.

Of 448 studies identified in the literature search, 4 studies were reviewed, describing 87 patients diagnosed with dysautonomia. We present a patient who developed severe dysautonomia following conversion of sleeve gastrectomy to gastric bypass.

Treatment needs to focus on optimizing nutrition, avoiding hypoglycemia, and optimizing volume status.

Metabolic surgery results in diverse glycemic status in patients with type 2 diabetes (T2D), including hyperglycemia without remission, significant amelioration of hyperglycemia with partial remission, complete restoration of euglycemia, or with prolonged remission, hyperglycemia recurrence in relapses after remission, or post-bariatric hypoglycemia. Unfortunately, it is not known how metabolic surgery leads to this diverse consequence. Here, we discuss the diversity of glycemic status associated with metabolic surgery and the potential mechanisms of T2D remission. We also highlight the relationship between the change in low-grade inflammation and T2D remission after metabolic surgery. We hypothesize that the level of inflammatory and anti-inflammatory cytokines controls the efficacy of metabolic surgery in patients with T2D. This hypothesis may provide further insight into the mechanism of the beneficial effects of metabolic surgery patients with T2D.

Hypoglycemia is a serious complication of bariatric surgery. The aim of the present meta-analysis was to evaluate the rate and the timing of post-bariatric hypoglycemia (PBH) with different bariatric procedures using reliable data from continuous glucose monitoring (CGM).

Studies were systematically searched in the Web of Science, Scopus and PubMed databases according to Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. The prevalence of PBH was expressed as weighted mean prevalence (WMP) with pertinent 95% confidence intervals (95%CI). A total of 8 studies (16 datasets) enrolling 280 bariatric subjects were identified. The total WMP of PBH was 54.3% (95%CI: 44.5%-63.8%) while the WMP of nocturnal PBH was 16.4% (95%CI: 7.0%-34%). We found a comparable rate of PBH after Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) (OR 1.62, 95%CI: 0.71-3.7; P = 0.248); likewise, the percent time spent in hypoglycemia was similar with the two procedures (mean difference 5.3%, 95%CI: -1.4%-12.0%; P = 0.122); however, RYGB was characterized by a higher glycemic variability than SG. Regression models showed that the time elapsed from surgical intervention was positively associated with a higher rate of both total PBH (Z-value: 3.32, P < 0.001) and nocturnal PBH (Z-value: 2.15, P = 0.013).

PBH, both post-prandial and nocturnal, is more prevalent than currently believed. The rate of PBH increases at increasing time from surgery and is comparable after RYGB and SG with a higher glucose variability after RYGB.

In case of repeated episodes of abdominal discomfort and vagal symptoms, especially occurring after ingestion of a rich meal, the diagnosis of intermittent volvulus could be considered. The sudden arrival of large amounts of partially digested food in the intestine after spontaneous resolution might be associated with a dumping syndrome.

Postbariatric hypoglycemia (PBH) can be a devastating complication for which current therapies are often incompletely effective. More information is needed regarding frequency, incidence, and risk factors for PBH.

To examine hypoglycemia symptoms following Roux-en-Y gastric bypass (RYGB) and laparoscopic adjustable gastric banding (LAGB) and baseline and in-study risk factors.

Multicenter, at 10 US hospitals in 6 geographically diverse clinical centers.

A prospective, longitudinal cohort study of adults undergoing RYGB or LAGB as part of clinical care between 2006 and 2009 were recruited and followed until January 31, 2015, with baseline and annual postoperative research assessments. We analyzed baseline prevalence and post-operative incidence and frequency of self-reported hypoglycemia symptoms as well as potential preoperative risk factors.

In all groups, postoperative prevalence of hypoglycemia symptoms was 38.5%. Symptom prevalence increased postoperatively from 2.8%-36.4% after RYGB in patients without preoperative diabetes (T2D), with similar patterns in prediabetes (4.9%-29.1%). Individuals with T2D had higher baseline hypoglycemia symptoms (28.9%), increasing after RYGB (57.9%). Hypoglycemia symptoms were lower after LAGB, with 39.1% reported hypoglycemia symptoms at only 1 postoperative visit with few (4.0%) having persistent symptoms at 6 or more annual visits. Timing of symptoms was not restricted to the postprandial state. Symptoms of severe hypoglycemia were reported in 2.6-3.6% after RYGB. The dominant risk factor for postoperative symptoms was preoperative symptoms; additionally, baseline selective serotonin (SSRI) and serotonin-norepinephrine (SNRI) reuptake inhibitor use was also associated with increased risk in multivariable analysis. Weight loss and regain were not related to hypoglycemia symptom reporting.

Hypoglycemia symptoms increase over time after RYGB, particularly in patients without diabetes. In a small percentage, symptoms can be persistent or severe and require hospitalization. Preoperative hypoglycemia symptoms and SSRI/SNRI use in RYGB patients without diabetes is associated with increased risk of symptoms.

Postbariatric hypoglycaemia (PBH) is an increasingly recognized complication of bariatric surgery, but its effect on daily functioning remains unclear. In this randomized, single-blind, crossover trial we assessed driving performance in patients with PBH. Ten active drivers with PBH (eight females, age 38.2 ± 14.7 years, body mass index 27.2 ± 4.6 kg/m² ) received 75 g glucose to induce PBH in the late postprandial period and aspartame to leave glycaemia unchanged, on two different occasions. A simulator was driven during 10 minutes before (D0) and 20 (D1), 80 (D2), 125 (D3) and 140 minutes (D4) after the glucose/aspartame ingestion, reflecting the expected blood glucose (BG) increase (D1), decrease (D2) and hypoglycaemia (D3, D4). Seven driving features indicating impaired driving were integrated in a Bayesian hierarchical regression model to assess the difference in driving performance after glucose/aspartame ingestion. Mean ± standard deviation peak and nadir BG after glucose were 182 ± 24 and 47 ± 14 mg/dL, while BG was stable after aspartame (85 ± 4 mg/dL). Despite the lack of a difference in symptom perception, driving performance was significantly impaired after glucose versus aspartame during D4 (posterior probability 98.2%). Our findings suggest that PBH negatively affects driving performance.

To examine the incidence of hypoglycaemia-related events over a period of up to 31 years in patients treated with bariatric surgery in the prospective, controlled Swedish Obese Subjects (SOS) study.

The SOS study (n = 4047) is a prospective controlled intervention study. The present analysis included 1989 patients treated with bariatric surgery and 2027 control patients with obesity who received usual care. Diagnosed hypoglycaemia and events commonly attributed to hypoglycaemia (confusion, syncope, epilepsy and seizures), requiring hospital or specialist outpatient treatment, were identified by searching the National Patient Register. Analyses were stratified by baseline glycaemic status. Hazard ratios were adjusted for inclusion year, age, sex, smoking, glycated haemoglobin (HbA1c) level and body mass index at baseline. At the time of analysis (December 31, 2018), the median follow-up was 22 years.

Compared with usual care, bariatric surgery was associated with increased incidence of hypoglycaemia-related events in patients without baseline diabetes (168 and 219 events, respectively; log-rank P = .011), with a more pronounced risk during the first years of follow-up (test of time-treatment interaction P = .010). Multivariate analyses in patients without baseline diabetes indicated that male sex (P < .001), older age (P = .001) and higher HbA1c levels (P = .006) were associated with hypoglycaemia-related events. No association was found between risk of hypoglycaemia-related events and bariatric surgery in patients with baseline diabetes.

Bariatric surgery is associated with an increased incidence of hypoglycaemia-related events in patients without baseline diabetes, especially during the first years after treatment.

Bariatric surgery has been widely indicated for the management of obesity and related comorbidities. However, there are uncertainties pertaining to the risks of post-bariatric severe hypoglycaemia (SH), cardiovascular diseases (CVDs), end-stage kidney diseases (ESKDs) and all-cause mortality in obese patients with Type 2 diabetes mellitus (T2DM), especially among Asian populations.

A retrospective population-based cohort of 1702 obese T2DM patients who were free of CVD and ESKD were assembled based on the 2006-17 Hospital Authority database. One-to-five propensity-score matching was used to balance baseline covariates between patients in bariatric surgery and control groups. Incidence rates (IRs) of SH, CVD, Stage 4/5 chronic kidney diseases (CKD), ESKD and all-cause mortality events for two groups were calculated. Hazard ratios (HR) for SH, CVD and Stage 4/5 CKD events were assessed using Cox-proportional hazard models. Changes in estimated glomerular filtration rate (eGFR) and urine albumin-creatinine ratio (UACR) were measured up to 60 months.

Over a mean follow-up period of 32 months with 5725 person-years, cumulative incidences of mortality, CVD, Stage 4/5 CKD, ESKD and SH were 0, 0.036, 0.050, 0.017 and 0.020, respectively. The surgery group had a significant reduction in risk of CVD events (HR = 0.464, P = 0.015) and no occurrence of mortality events. However, there were no significant differences in risks of SH [HR = 0.469, 95% confidence interval (CI): 0.204-1.081], Stage 4/5 CKD (HR =0.896, 95% CI: 0.519-1.545) and ESKD (HR = 0.666, 95% CI: 0.264-1.683) between two groups, although IRs were lower in the surgery group. Surgical patients had significantly higher eGFR within 12 months and had significantly lower UACR until 48 months.

Among obese T2DM patients, bariatric surgery lowered the risk of CVD and mortality, and was beneficial towards the kidney outcomes.

Postprandial hypoglycemia (PPHG) is a well-known complication after bariatric surgery (BS). However, it is not known whether PPHG affects weight loss after BS.

To assess the impact of PPHG on weight loss after BS in subjects without and with type 2 diabetes mellitus (T2D).

Data from 338 subjects who had undergone gastric bypass (RYGB) or sleeve gastrectomy (LSG) and were followed up for at least 2 years were analyzed. At each follow-up visit, the patient's anthropometric and biochemical characteristics were recorded and the Edinburgh Questionnaire was performed to evaluate the presence of PPHG symptoms.

Before surgery: younger age and lower BMI predicted PPHG after BS (p = 0.02 and p = 0.0008, respectively). Also, the baseline OGTT indicated that subjects who developed PPHG had an earlier glucose peak and more often had low glucose levels at 2 h compared with the no-PPHG group (p = 0.03 and p = 0.004, respectively). After surgery: Mild-to-moderate PPHG occurred equally after RYGB and LSG (38% vs 25%, p = ns when accounting for confounders), and in T2D who achieved remission and those who did not (29.5% vs 28.6%, ns). At the 2-year follow-up, occurrence of PPHG was independently associated with smaller weight loss (p = 0.0006).

Mild-to-moderate PPHG is a frequent complication after bariatric surgery and results in smaller weight loss after 2 years. Age, baseline BMI, and an earlier glucose peak during OGTT predict PPHG after bariatric surgery.