Postbariatric hypoglycaemia (PBH) is a complex medical condition with a significant impact on patients' quality of life. The underlying mechanisms remain to be elucidated. We have shown that food ingestion increases IL-1β and subsequently stimulates insulin secretion. We therefore hypothesised that overactivation of the IL-1β pathway could lead to PBH by promoting excessive insulin secretion after a meal. In a proof-of-concept study, we have shown that acute treatment with the IL-1 receptor antagonist anakinra can attenuate PBH after a single liquid mixed meal. This study aims to validate this therapeutic approach over a longer period of time using the long-acting anti-IL-1β antibody canakinumab.

In this prospective, randomised, double-blind, placebo-controlled, multicentre trial, we plan to enrol 62 adult patients after bariatric surgery with frequent, postprandial hypoglycaemia (ie, <3.0 mmol/L and at least five hypoglycaemic episodes per week). Eligible subjects will be randomised to receive either single-dose 150 mg canakinumab (Ilaris, Novartis) subcutaneously (s.c.) or matched placebo (1.0 mL physiologic saline). For 28 days, patients are required to wear a blinded continuous glucose monitoring device (CGMS, Dexcom G6) and use a diary to track their hypoglycaemic episodes. Primary outcomes include health-related quality of life, measured by the SF-36, as well as postprandial hypoglycaemic events (glucose <3.0 mmol/L). A significant improvement in any one of these outcomes will be considered sufficient to demonstrate the clinical superiority of canakinumab over placebo. Secondary outcomes include patient-oriented measures such as postprandial hypoglycaemic symptoms, hypoglycaemia unawareness, fear of hypoglycaemia, as well as metabolic measures and safety assessments.

The trial was approved by the Cantonal Ethics Committee 'Ethikkommission Nordwest- und Zentralschweiz' in January 2022 (#2021-02325), as well as by Swissmedic in April 2022 (#701280). Current, approved protocol version 1.3 of 28.03.2023. The study is actively recruiting. Results will be published in a relevant scientific journal and communicated to participants and relevant institutions through dissemination activities. Individual data are accessible on request.

The study is registered with the www.

gov registry (NCT05401578) and the Swiss National Clinical Trials Portal (SNCTP) on www.kofam.ch (SNCTP000004838).

Defining recurrent weight gain after metabolic bariatric surgery poses a significant challenge. Our study aimed to standardize recurrent weight gain measurements in patients undergoing laparoscopic sleeve gastrectomy (LSG) and ascertain its association with comorbidity progression.

We conducted a retrospective data analysis on 122 patients who underwent LSG, tracking their progress over 2-7 years. Data on weight, blood pressure measurements, and laboratory tests were collected, focusing on the postoperative period to identify nadir weight, total weight loss, and recurrent weight gain.

Significant weight loss and comorbidity remission were noted, with diabetes, hypertension, and dyslipidemia showing substantial remission rates of 85.71%, 68.24%, and 85.37%, respectively. The median recurrent weight gain was 6.30 kg within 12 months of the nadir. Progression proportion of diabetes, hypertension, and dyslipidemia were 8.20%, 44.26%, and 40.98%, respectively. Hypertension progression was strongly associated with a recurrent weight gain ≥ 10 kg and ≥ 20% of maximum weight loss. Dyslipidemia progression was significantly correlated with recurrent weight gain ≥ 10 kg and ≥ 20% of maximum weight loss. Diabetes progression was significantly correlated with recurrent weight gain ≥ 10% of pre-surgery body weight and ≥ 25% of maximum weight loss. A ≥ 10% weight gain of maximum weight loss did not significantly impact the progression of these conditions.

Recurrent weight gain ≥ 20% of maximum weight loss can be treated as a specific threshold indicating comorbidity progression post-LSG. Standardizing the measurement of recurrent weight gain can help healthcare providers to implement targeted management strategies to optimize long-term health outcomes.

Obesity is a complex chronic disease and requires a long-term multidisciplinary management. Even patients undergoing bariatric surgery, one the most effective treatments for obesity, can have insufficient weight loss (IWL) than expected (primary non responder) or weight regain (WR) after a successful primary procedure (secondary non responder). A poor response represents a challenge of bariatric surgery that can induce persistence or recurrence of obesity-related comorbidities, prejudicing benefits of surgery. Increasing evidence suggests that weight loss medications represent a useful strategy in obesity care also after bariatric surgery procedures. This narrative review summarizes the evidence concerning anti-obesity therapy in the management of no-responders to primary bariatric surgery. Available data on liraglutide (one randomized double-blind placebo-controlled trial, three prospective and three retrospective studies), naltrexone/bupropion (three retrospective studies), orlistat (one case control prospective and one retrospective studies) and topiramate and phentermine (five retrospective studies) have been considered. Available data suggest that weight loss medications could offer a significant adjunctive benefit to lifestyle and behavioral modifications in the life-long management of obesity. Newer treatment modalities including the use of anti-obesity drugs provide patients and healthcare providers with more options in the management of poor response after bariatric surgery.

Patients undergoing metabolic surgery have factors ranging from anatomo-surgical, endocrine metabolic, eating patterns and physical activity, mental health and psychological factors. Some of the latter can explain the possible pathophysiological neuroendocrine, metabolic, and adaptive mechanisms that cause the high prevalence of weight regain in postbariatric patients. Even metabolic surgery has proven to be effective in reducing excess weight in patients with obesity; some of them regain weight after this intervention. In this vein, several studies have been conducted to search factors and mechanisms involved in weight regain, to stablish strategies to manage this complication by combining metabolic surgery with either lifestyle changes, behavioral therapies, pharmacotherapy, endoscopic interventions, or finally, surgical revision. The aim of this revision is to describe certain aspects and mechanisms behind weight regain after metabolic surgery, along with preventive and therapeutic strategies for this complication.

To determine the normalization of postprandial blood glucose (PG) and triglyceride (TG) excursions in 30 morbidly obese patients with or without diabetes mellitus (DM) 1-year after they underwent a laparoscopic sleeve gastrectomy (LSG) vs. their pre-surgery data, we administered the 75-g oral glucose tolerance test (OGTT) and a meal tolerance test (MTT) using a 75-g glucose-equivalent carbohydrate- and fat-containing meal. The results were as follows; (i) Postoperative body-weight reduction was associated with DM remission and reduced multiple cardiometabolic risks. (ii) OGTT data showing postprandial hyper-insulinemic hypoglycemia in many post-surgery patients were associated with overdiagnosis of improved glucose tolerance. However, postoperative MTT data without hypoglycemia showed no improvement in the glucose tolerance vs. pre-surgery data. (iii) The disposition index (DI) i.e., [Matsuda index] × (Glucose-induced insulin secretion) was progressively worsened from normal glucose tolerance to DM patients after LSG. These post-surgery DI values measured by the MTT were correlated with 2h-plasma glucose levels and were not normalized in DM patients. (iv) The baseline, 2h-TG, and an increase in 2h-TG values above baseline were correlated with the insulin resistance index, DI, or HbA1c; These TG values were normalized post-LSG. In conclusion, the glucose tolerance curve measured by the MTT was not normalized in T2DM patients, which was associated with impaired normalization of the DI values in those patients 1-year after the LSG. However, the baseline TG and a fat-induced 2h-TG values were normalized postoperatively. The MTT can be used to assess normalization in postprandial glucose and TG excursions after LSG.

Bariatric Surgery (BS) is a therapeutic option in patients with severe obesity whose non-surgical techniques have failed. No work has previously explored trajectories of weight loss and how long this was maintained. Aim of study is to describe effect of BS and nutritional intervention on body weight trend in patients with obesity.

792 patients who underwent BS from 1996 to 2021 were included. The Protocol provides Laparoscopic Sleeve Gastrectomy (LSG), Vertical Gastroplasty (VBG) and Roux-en-Y Gastric Bypass (GB). %Total Weight Loss (%TWL) and %Excess Weight Loss (%EWL) were evaluated in three cohort of patients. Cumulative incidence of clinical goal after surgery was calculated at two and five years after BS.

At two years of follow-up, average %TWL and %EWL were 31.2% (95% CI = 29.0-33.4%) and 71% (95% CI = 65.4-76.5%) for VBG, 34.7% (95% CI = 33.8-35.6%) and 78.0% (95% CI = 75.9-89.1%) for GB and 33.8% (95% CI = 32.5-35.1%) and 68.8% (95% CI = 66.1-71.6%) for LSG. At two years from surgery the cumulative incidence of clinical goal was 70.7% (95% CI = 59.1-79.1%) for VBG, 86.4% (95% CI = 82.4-89.6%) for GB and 83.4% (95% CI = 76.0-87.1%) for LSG. At five years from surgery, average % TWL and % EWL were 22.5% (95% CI = 10.2-34.8%) and 58.2% (95% CI = 28.4-88.1%) for VBG, 31.8% (95% CI = 30.2-33.3%) and 70.8% (95% CI = 67.5-74.1%) for GB and 29.5% (95% CI = 26.2-32.8%) and 62.0% (95% CI = 53.4-70.6%) for LSG respectively. At five years after having reached clinical goal the share of people who were able to maintain their weight was 49.5% (95% CI = 30.8-79.6%) for VBG, 69.5% (95% CI = 58.3-82.8%) for GB and 55.9% (95% CI = 42.1-74.3%) for LSG. The median time of clinical goal maintaining was 4.8 years for VBG (95% CI lower limit = 4.1), 6.6 years for GB (95% CI lower limit = 6.2) and 5.3 years for LSG (95% CI lower limit = 4.8).

Our work confirm effectiveness of BS in patients with obesity and show that who do not reach clinical goal within 2 years, hardly will reach it later and suggest necessity for a medium and long-term follow-up to prevent weight regain.

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.

Metabolic and bariatric surgery (MBS) is an effective treatment for patients with morbid obesity and its comorbidities. However, many patients experience weight regain (WR) after achieving their nadir weight. Establishing the definition of WR is challenging as postoperative WR has various definitions. Risk factors for WR after MBS include anatomical, racial, hormonal, metabolic, behavioral, and psychological factors, and evaluating such factors preoperatively is necessary. Long-term regular follow-up and timely treatment by a multidisciplinary team are important because WR after surgery is multi-factorial. Although lifestyle interventions that focus on appropriate dietary education, physical activity education or interventions, and behavioral psychological interventions are suggested, more well-designed studies are needed because studies evaluating intervention methods and the effectiveness of WR prevention are lacking. Anti-obesity drugs can be used to prevent and manage patients with WR after MBS; however, more research is needed to determine the timing, duration, and type of anti-obesity drugs used to prevent WR.

The goal of this study was to compare measures of weight regain (WR) and their association with the glucose metabolism deterioration within 3 years following bariatric surgery among Chinese patients with obesity and type 2 diabetes mellitus (T2DM).

Among a retrospective cohort of 249 patients with obesity and T2DM who underwent bariatric surgery and were followed up to 3 years, WR was assessed by weight changes, BMI changes, percentage of presurgery weight, percentage of nadir weight, and percentage of maximum weight lost (%MWL). Glucose metabolism deterioration was defined as a change from an absence of antidiabetic medication use to use, or absence of insulin use to use, or an increase in glycated hemoglobin by at least 0.5% to 5.7% or greater.

A comparison of C-index of glucose metabolism deterioration indicated %MWL had better discriminatory ability versus weight change, BMI change, percentage of presurgery weight, or percentage of nadir weight (all p < 0.01). The %MWL also had the highest prediction accuracy. The optimal %MWL cutoff point was 20%.

Among Chinese patients with obesity and T2DM who underwent bariatric surgery, WR quantified as %MWL predicted 3-year postoperative glucose metabolism deterioration better than the alternatives; 20% MWL was the optimal cutoff point.

Scarce evidence exists in the literature about the factors influencing the long-term quality of life (QoL) and weight regain (WR) after Roux-en-Y gastric bypass (RYGB). The aim of the present study was to investigate factors associated with WR and QoL, measured by obesity specific Moorehead-Ardelt Quality of Life Questionnaire II (M-A QoLQ II), 12 years after RYGB.

This prospective longitudinal cohort study included 74 patients with obesity who had RYGB at the Lithuanian University of Health Sciences hospital Surgery department in 2005. Gastrointestinal and dumping symptoms, hypoglycemia, depression and anxiety disorders, hunger, satiety after meals, portion size, and grazing were assessed in the patients who agreed to participate in the study. General linear models were constructed to estimate the effect of variables on the WR and QoL.

12-year follow-up data were available for 50 patients (38 female, median body mass index (BMI) before surgery 42.4). The mean % excess BMI loss (%EBMIL) after 12 years was 63.1 (24.6) and the average %WR was 32.2 (19.4). The mean M-A QoLQ II score was 1.44 (1.3). Majority of the patients (76.6%) reported good or very good QoL. In multivariable analysis, only grazing (17.41% 95% CI 7.61-27.21; P = 0.001) was found to be a significant independent factor associated with WR. Factors independently associated with worse QoL were grazing (- 0.97 95% CI - 1.72, - 0.22; P = 0.013) and frequency of abdominal pain once or more per month (- 1.82 95% CI - 2.79, - 0.85; P = 0.001).

12 years after RYGB majority of the patients report good or very good QoL and despite some WR have achieved and maintained significant weight loss. Grazing was associated with both WR and worse QoL, while the frequency of abdominal pain once or more per month was associated with only decreased QoL.

Some patients experience weight regain (WR) or insufficient weight loss (IWL) after bariatric surgery (BS). We undertook a scoping review of WR and IWL after BS. We searched electronic databases for studies addressing the definitions, prevalence, mechanisms, clinical significance, preoperative predictors, and preventive and treatment approaches including behavioral, pharmacological, and surgical management strategies of WR and IWL. Many definitions exist for WR, less so for IWL, resulting in inconsistencies in the reported prevalence of these two conditions. Mechanisms and preoperative predictors contributing to WR are complex and multifactorial. A range of the current knowledge gaps are identified and questions that need to be addressed are outlined. Therefore, there is an urgent need to address these knowledge gaps for a better evidence base that would guide patient counseling, selection, and lead to improved outcomes.

After Roux-en-Y gastric bypass (RYGB), postprandial hyperinsulinemic hypoglycemia (PPHH) is particularly critical because of the risk of trauma. The aim of this study was to assess the incidence and identify risk factors for symptomatic PPHH.

Patients with RYGB were classified into moderate PPHH (MH) or severe hypoglycemia (SH), which is defined as patients with neuroglycopenic symptoms. Logistic multivariate linear regressions were performed to identify predictive factors for symptomatic PPHH and more specifically for SH with neuroglycopenic symptoms. Patients with diabetes and those with a follow-up shorter than 2 years were excluded.

Among the 1,138 patients, 44.2% had at least one episode of hypoglycemia with a mean delay of 25.5 (21.3) months, 32.6% had MH, and 11.6% had SH. The annual incidence rate of SH was 2.5% the first year, 3.7% the second year, and 1.5% the third year. Independent predictive factors for higher risk of SH were: younger age (odds ratio [OR] = 1.01; 95% CI: 1.05-16.69; P = 0.0007), lower BMI after RYGB (OR = 1.61; 95% CI: 1.17-2.22; P = 0.0035), and maximal weight loss (OR = 1.04; 95% CI = 1.39-1.23; P = 0.0106), whereas higher preoperative BMI was protective (OR = 0.78; 95% CI: 0.64-0.95; P = 0.0112).

This observational cohort study showed that the incidence of severe PPHH with neuroglycopenic symptoms after RYGB was higher than expected.

To systematically review the literature to assess the incidence and risk factors of weight regain (WR) after bariatric surgery. Bariatric surgery is the most effective intervention for sustained weight loss of morbidly obese patients, but WR remains a concern.

A PRISMA compliant systematic literature review was performed using the PubMed database, Embase and the Cochrane Library in July of 2019. Studies that reported ≥ 10% WR after Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) were included. The Newcastle-Ottawa scale (NOS) was used for assessing study quality.

Out of 2915 retrieved abstracts, 272 full papers were reviewed, and 32 studies included (25 of high and 7 of fair quality) reporting weight outcomes on 7391 RYGB and 5872 SG patients. 17.6% (95% CI 16.9-18.3) had a WR ≥ 10%. Risk factors related with WR fell into 5 categories, namely anatomical, genetic, dietary, psychiatric, and temporal. Specifically, gastrojejunal stoma diameter, gastric volume following sleeve, anxiety, time after surgery, sweet consumption, emotional eating, portion size, food urges, binge eating, loss of control/disinhibition when eating, and genetics have been positively associated with WR while postprandial GLP-1, eagerness to change physical activity habits, self-esteem, social support, fruit and zinc consumption, HDL, quality of life have been negatively associated.

At least 1 in 6 patients after bariatric surgery had ≥ 10% WR. This review identified several factors related to WR that can be used to counsel patients preoperatively and direct postoperative strategies that minimize WR risk.

To evaluate the glucose and insulin profiles during an oral glucose tolerance test (OGTT) after Roux-en-Y gastric bypass (RYGB) in symptomatic and asymptomatic patients.

This retrospective study consisted of two groups that had undergone RYGB. The symptomatic (S) group (n = 27) had an OGTT at presentation, whereas the asymptomatic (A) group (n = 99) had an OGTT 1 year after RYGB. Each group was subdivided into two groups, namely, those with glycaemia <54 mg/dL (S1/A1) and those with glycaemia >54 mg/dL (S2/A2) during OGTT. Most of the patients underwent OGTT preoperatively.

Preoperatively, the glucose and insulin levels, as well as the speed of increase and decrease, were similar in all groups. Postoperatively, the minimum glucose levels during the OGTT did not differ between the symptomatic and asymptomatic groups (55 ± 19 vs. 54 ± 17 mg/dL) or between the S1 and A1 subgroups (39 ± 7 vs. 43 ± 8 mg/dL). The peak glucose values were higher in the symptomatic versus the asymptomatic group (236 ± 52 vs. 189 ± 43 mg/dL; P <0.05) and in the S1 and S2 versus the A1 and A2 subgroups. The speed of glucose increase and decline was significantly higher in the symptomatic group versus the asymptomatic group, with the speed of glucose decline being the highest in the S1 subgroup.

Assessing hypoglycaemia after a gastric bypass remains challenging. Our study suggests that the main difference in glucose dynamics between symptomatic and asymptomatic patients might be the speed of glucose and insulin increase and decline during OGTT rather than the absolute values obtained.

Published estimates of weight regain (WR) after bariatric surgery vary greatly. Understanding the sources of variability in the literature and clarifying the magnitude of WR after Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) are critical for informing expectations and planning interventions. A literature search through January 2019 yielded 15 English-language studies that reported WR in at least 30 participants, not selected based on weight loss or WR, at least 3 years after primary RYGB (n = 11) or SG (n = 5). Median follow-up was 5.0 (range, 3.2-10.0) years. Median sample size was 62 (range, 33-464). Samples represented a median of 54.3% (range, 10.7%-100%) of eligible participants. Nadir weight was determined by serial research assessments (n = 1), medical records (n = 7), participant recall (n = 4), or an undisclosed method (n = 4). Three continuous and 8 binary WR measures (the latter, based on various thresholds for clinically meaningful WR) were reported. To enable comparison across studies, the percentage difference in WR in each study versus a reference sample (n = 1433 RYGB), matched on time since surgery and WR measure, was calculated. Median WR in the reference sample increased from 8.2 (25th-75th percentile: 0-19.5) to 23.8 (25th-75th percentile: 9.0-33.9) percent of maximum weight lost, 3 to 6 years post RYGB surgery. Studies of RYGB versus SG, with larger versus smaller samples, with higher versus lower participation rates, that determined nadir weight via participant recall versus medical records, and reported continuous versus binary WR measures tended to have WR values closer to the reference sample and each other. Variation in WR estimates was explained by heterogeneity in WR measures, timing of assessment, surgical procedure, and study design characteristics. The best estimate of WR after RYGB likely comes from the large reference sample. WR after SG versus RYGB appears higher. However, additional high-quality studies with uniform reporting of WR by surgical procedure are needed.

Postprandial hypoglycemia is a disabling complication of the treatment of obesity by gastric bypass surgery. So far, no therapy exists, and the underlying mechanisms remain unclear. Here, we hypothesized that glucose-induced IL-1β leads to an exaggerated insulin response in this condition. Therefore, we conducted a placebo-controlled, randomized, double-blind, crossover study with the SGLT2-inhibitor empagliflozin and the IL-1 receptor antagonist anakinra (clinicaltrials.govNCT03200782; n = 12). Both drugs reduced postprandial insulin release and prevented hypoglycemia (symptomatic events requiring rescue glucose: placebo = 7/12, empagliflozin = 2/12, and anakinra = 2/12, pvallikelihood ratio test (LRT) = 0.013; nadir blood glucose for placebo = 2.4 mmol/L, 95% CI 2.18-2.62, empagliflozin = 2.69 mmol/L, 95% CI 2.31-3.08, and anakinra = 2.99 mmol/L, 95% CI 2.43-3.55, pvalLRT = 0.048). Moreover, analysis of monocytes ex vivo revealed a hyper-reactive inflammatory state that has features of an exaggerated response to a meal. Our study proposes a role for glucose-induced IL-1β in postprandial hypoglycemia after gastric bypass surgery and suggests that SGLT2-inhibitors and IL-1 antagonism may improve this condition.

Diets that include some aspect of fasting have dramatically increased in popularity. In addition, fasting reduces inflammasome activity in the brain while improving learning. Here, we examine the impact of refeeding a low-fat diet (LFD) or high-fat diet (HFD) after fasting.

Male wildtype (WT), caspase-1 knockout (KO) and/or IL-1 receptor 1 (IL-1R1) KO mice were fasted for 24 h or allowed ad libitum access to food (chow). Immediately after fasting, mice were allowed to refeed for 2 h in the presence of LFD, HFD or chow. Mouse learning was examined using novel object recognition (NOR) and novel location recognition (NLR). Caspase-1 activity was quantified in the brain using histochemistry (HC) and image analysis.

Refeeding with a HFD but not a LFD or chow fully impaired both NOR and NLR. Likewise, HFD when compared to LFD refeeding increased caspase-1 activity in the whole amygdala and, particularly, in the posterior basolateral nuclei (BLp) by 2.5-fold and 4.6-fold, respectively. When caspase-1 KO or IL-1R1 KO mice were examined, learning impairment secondary to HFD refeeding did not occur. Equally, administration of n-acetylcysteine to fasted WT mice prevented HFD-dependent learning impairment and caspase-1 activation in the BLp. Finally, the free-fatty acid receptor 1 (FFAR1) antagonist, DC260126, mitigated learning impairment associated with HFD refeeding while blocking caspase-1 activation in the BLp.

Consumption of a HFD after fasting impairs learning by a mechanism that is dependent on caspase-1 and the IL-1R1 receptor. These consequences of a HFD refeeding on the BLP of the amygdala appear linked to oxidative stress and FFAR1.

Women with anorexia nervosa (AN) develop visceral adiposity associated with insulin resistance after partial weight restoration, but little is known about the glucose homeostasis after full weight restoration. In this investigation, we studied glucose homeostasis in twenty-four women with AN before (AN) and after weight restoration (WR) at a single institution, with both restricting and binge-purge subtypes (>70% binge-purge), compared to gender-, age- and BMI-matched healthy controls (HC). Participants underwent fasting plasma hormone analysis, oral glucose tolerance test (OGTT), and body composition analysis. Glucose homeostasis was assessed by the homeostasis model assessment (HOMA) and OGTT, and parameters were analyzed for association with body composition. We observed that a subset of the WR patients (21%) had metabolically unhealthy HOMA insulin resistance estimates (HOMA-IR), while this was not seen in the control group. Overall mean HOMA-IR between groups were not significantly different. Mean glucose reactivity was higher in the WR group than HC women (p = 0.008, Hedges' g = 0.811), and time-adjusted glucose reactivity in the WR group was inversely associated with visceral adiposity (r = -0.559, p = 0.006), but not with fat mass (r = -273, p = 0.208) or lean mass (r = -0.002, p = 0.994). Our findings suggest that glucose response during the OGTT in women with AN is altered in association with visceral adiposity acutely after full weight restoration, but that they do not develop overt insulin resistance. Glucometabolic profiling could offer novel insights to energy homeostasis acutely after weight restoration.

The frequency of postprandial hypoglycaemia after different operative procedures of bariatric surgery (BS) is unknown, although this complication is potentially dangerous. Predictors and severity of hypoglycaemia after Roux-en-Y gastric bypass (RYGB), sleeve gastrectomy, and gastric banding were investigated in a large prospective study.

This study was performed at an excellence centre for BS at a tertiary care institution. Data of 333 patients (mean BMI: 44.9 ± 9.6 kg/m2; mean age: 40 ± 10 years; 80.7% women) were analysed in a prospective study with a 2-year observation period after BS. All patients underwent a 2-hour oral glucose tolerance test (OGTT) with measurements of blood glucose (BG) and insulin. For the purpose of this study, hypoglycaemia was defined as a post-challenge BG <2.8 mmol/L during the OGTT.

72 (25.6%) of 281 patients showed post-challenge hypoglycaemia after surgery. Hypoglycaemia was different after various procedures: 32.6% of patients after RYGB, 22.6% after sleeve gastrectomy, but only 2.3% after gastric banding had hypoglycaemia. In the whole group, patients with hypoglycaemia had lost more weight (p = 0.013), had a slightly greater decrease in BMI (p = 0.037), a greater change in 2-hour post-challenge BG (p = 0.001), and a smaller change in 1-hour post-challenge insulin (p = 0.004) compared to patients without hypoglycaemia.

This prospective study shows a higher prevalence of severe hypoglycaemia (25.6%) after BS than anticipated from retrospective registers. A systematic evaluation of glucose and insulin levels by OGTT 2 years post-surgery may help to identify patients at increased risk for symptomatic and asymptomatic hypoglycaemia.

Estimates of weight regain following bariatric surgery vary widely.

To describe weight regain after reaching nadir weight following Roux-en-Y gastric bypass (RYGB) surgery and compare weight regain measures for association with outcomes.

Prospective cohort study of 2458 adults who underwent bariatric surgery at 10 hospitals in 6 US cities between March 2006 and April 2009. Assessments were conducted within 30 days' presurgery, at 6 months' postsurgery, and then annually until January 2015. Of the 1703 participants who underwent RYGB surgery, 1406 (83%) were followed up for 5 years or longer and had 5 or more weight measurements (excluding those who died or underwent surgical reversal).

Weight regain assessed by 5 continuous measures (weight in kilograms, body mass index [BMI], percentage of presurgery weight, percentage of nadir weight, and percentage of maximum weight lost) and 8 dichotomous measures (per established thresholds) were compared in relation to clinical outcomes based on statistical significance, magnitude of association, and model fit.

Progression of diabetes, hyperlipidemia, and hypertension and declines in physical and mental health-related quality of life and satisfaction with surgery.

Among the 1406 participants who underwent RYGB surgery, the median age was 47 years (25th-75th percentile, 38-55 years) and the median BMI was 46.3 (25th-75th percentile, 42.3-51.8) prior to surgery. Most participants were female (80.3%) and white (85.6%). The median follow-up was 6.6 years (25th-75th percentile, 5.9-7.0 years). The median percentage of maximum weight loss was 37.4% (25th-75th percentile, 31.6%-43.3%) of presurgery weight and occurred a median of 2.0 years after RYGB surgery (25th-75th percentile, 1.0-3.2 years). The rate of weight regain was highest during the first year after reaching nadir weight, but weight regain continued to increase throughout follow-up (range, a median of 9.5% of maximum weight lost [25th-75th percentile, 4.7%-17.2%] to 26.8% of maximum weight lost [25th-75th percentile, 16.7%-41.5%] 1 to 5 years after reaching nadir weight). The percentage of participants who regained weight depended on threshold (eg, 5 years after nadir weight, 43.6% regained ≥5 BMI points; 50.2% regained ≥15% of nadir weight; and 67.3% regained ≥20% of maximum weight lost). Compared with other continuous weight regain measures, the percentage of maximum weight lost had the strongest association and best model fit for all outcomes except hyperlipidemia, which had a slightly stronger association with BMI. Of the dichotomous measures, 20% or greater of maximum weight lost performed better or similarly with most of the outcomes, and was the second best measure for hyperlipidemia (after ≥10 kg of weight) and hypertension (after ≥10% of maximum weight lost).

Among a large cohort of adults who underwent RYGB surgery, weight regain quantified as percentage of maximum weight lost performed better for association with most clinical outcomes than the alternatives examined. These findings may inform standardizing the measurement of weight regain in studies of bariatric surgery.

Postprandial hypoglycemia is an infrequent but disabling complication of Roux-en-Y gastric bypass (RYGB) surgery. Controversy still exists as to whether the postprandial hyperinsulinemia observed is due to inherent changes in pancreatic β-cell mass or function or to reversible alterations caused by RYGB anatomy. We aimed to determine if gastric feeding or reversal of RYGB would normalize postprandial glucose and hormone excursions in patients with symptomatic hypoglycemia.

We completed a prospective study of six patients with severe symptomatic RYGB hypoglycemia who underwent RYGB reversal. An additional subject without hypoglycemia who underwent RYGB reversal was also studied prospectively. Mixed meal tolerance testing (MTT) was done orally (RYGB anatomy), via gastrostomy tube in the excluded stomach in the setting of RYGB, and several months after RYGB reversal.

All subjects reported symptomatic improvement of hypoglycemia after reversal of RYGB. Weight gain after reversal was moderate and variable. Postprandial glucose, insulin, and GLP-1 excursions were significantly diminished with gastric feeding and after reversal. Insulin secretion changed proportional to glucose levels and insulin clearance increased after reversal. Glucagon/insulin ratios were similar throughout study. We further compared the impact of modified sleeve gastrectomy reversal surgery to those with restoration of complete stomach and found no significant differences in weight regain or in postprandial glucose or hormone levels.

Reversal of RYGB is an effective treatment option for severe postprandial hypoglycemia. The pathophysiology of this disorder is primarily due to RYGB anatomy resulting in altered glucose, gut, and pancreatic hormone levels and decreased insulin clearance, rather than inherent β-cell hyperplasia or hyperfunction.

While hypoglycemia during an oral glucose tolerance test (OGTT) has been shown to occur in a considerable portion of nonpregnant post-bariatric surgery (BS) patients, its incidence among pregnant post-BS patients evaluated for gestational diabetes has only been sparsely studied.

We investigated OGTT results and pregnancy outcomes in pregnant women who underwent 3 types of bariatric procedures before pregnancy.

A university hospital.

From medical records, data were collected on glucose measurements during a 100-g, 3-hour OGTT, as well as maternal and fetal outcomes.

Of 119 post-BS pregnant patients included in the study, 55 underwent laparoscopic sleeve gastrectomy, 34 laparoscopic adjustable gastric banding, and 30 laparoscopic Roux-en-Y gastric bypass surgery. Hypoglycemia (<55 mg/dL) was encountered in 59 (49.6%) patients during the OGTT. Among them, the nadir plasma glucose levels occurred 2 hours after glucose ingestion in 25 (42.4%) and after 3 hours in 34 (57.6%), with a median value of 47 (44-52) mg/dL. The risk of hypoglycemia was higher among women with prior laparoscopic Roux-en-Y gastric bypass surgery (83.3%) than among those with prior laparoscopic sleeve gastrectomy (54.5%; P = .009) or laparoscopic adjustable gastric banding (11.8%; P<.0001). Time from surgery to conception was significantly shorter among women with evidence of hypoglycemia during OGTT (median 711 versus 1246 days, P = .002). Compared with patients without evidence of hypoglycemia, patients who experienced hypoglycemia had lower rates of gestational diabetes (P = .03) but higher proportions of low birth weight (P = .01) and small for gestational age infants (P = .03).

Because hypoglycemia is common during OGTT among post-BS parturients, other diagnostic methods should be considered in this setting. The association found between hypoglycemia and poor fetal growth warrants investigation as to whether interventions to prevent hypoglycemia will improve fetal outcome.

Roux-en-Y gastric bypass (RYGB) surgery is currently the most effective treatment for diabetes and obesity. An increasingly recognized and highly disabling complication of RYGB is postprandial hypoglycaemia (PPH). The pathophysiology of PPH remains unclear with multiple mechanisms suggested including nesidioblastosis, altered insulin clearance and increased glucagon-like peptide-1 (GLP-1) secretion. Whilst many PPH patients respond to dietary modification, some have severely disabling symptoms. Multiple treatments are proposed, including dietary modification, GLP-1 antagonism, GLP-1 analogues and even surgical reversal, with none showing a more decided advantage over the others. A greater understanding of the pathophysiology of PPH could guide the development of new therapeutic strategies.

We studied a cohort of PPH patients at the Imperial Weight Center. We performed continuous glucose monitoring to characterize their altered glycaemic variability. We also performed a mixed meal test (MMT) and measured gut hormone concentrations.

We found increased glycaemic variability in our cohort of PPH patients, specifically a higher mean amplitude glucose excursion (MAGE) score of 4.9. We observed significantly greater and earlier increases in insulin, GLP-1 and glucagon in patients who had hypoglycaemia in response to an MMT (MMT Hypo) relative to those that did not (MMT Non-Hypo). No significant differences in oxyntomodulin, GIP or peptide YY secretion were seen between these two groups.

An early peak in GLP-1 and glucagon may together trigger an exaggerated insulinotropic response to eating and consequent hypoglycaemia in patients with PPH.

Postprandial hyperinsulinemic hypoglycemia (pHH) is an increasingly reported complication after Roux-en-Y gastric bypass (RYGB). As pHH can cause life-threatening emergencies if occurring without warning symptoms, challenge testing may detect patients at risk. The study objective was to determine the frequency of occurrence of pHH with or without symptoms of hypoglycemia after RYGB.

We undertook an observational cohort study of consecutive, unselected patients approximately one year after uncomplicated RYGB. To simulate normal habits, all patients received a standardized carbohydrate-rich solid mixed meal. Plasma glucose and insulin were measured at 30, 60, 90, 120, and 150 min thereafter. Symptoms were classified as autonomous or neuroglycopenic. Patients with hypoglycemia (plasma glucose <3.0 mmol/L [55 mg/dL]), were tested a second time with a protein-rich solid mixed meal.

113 patients were included. Total weight loss at the first follow-up check (14 ± 0.4 months) was 33.97 ± 9.3%. After the carbohydrate-rich meal, glucose dropped to <3.0 mmol/L in 13.2% (n = 15) of patients vs no drop to <3.0 mmol/L after a protein-rich meal. The pHH occurred in 11.5% (n = 13) of patients. Asymptomatic patients (5.3%, n = 6) carried an increased risk (p = 0.008) for pHH. One patient needed emergency treatment after sudden loss of consciousness after the carbohydrate-rich meal.

The occurrence of pHH was quite high in our study population with 11.5% thereof 5.3% asymptomatic. We therefore suggest that detection of these patients warrants a screening of patients after RYGB. At-risk patients should than be adequately advised to avoid carbohydrate-rich meals in order to optimize risk management.

Obesity is a global public health problem and attempts to treat this condition using life style with and without pharmacological interventions have not been successful in majority of obese individuals. To date, the most effective treatment for obesity is weight loss surgery. One of the most widely used procedures to treat obesity worldwide, Roux-en-Y gastric bypass surgery (RYGB), has shown to induce diabetes remission in addition to significant and sustainable weight loss. As the number of this procedure performed over the last two decades increased, it has become clear that a subgroup of individuals develop postprandial hypoglycemia several years after surgery. This debilitating late complication of RYGB is often associated with loss of consciousness or seizures, and in severe cases, it is only partially responsive to diet modification or other available therapeutic options. The diagnosis is often a challenge resulting in delays in receiving care in the affected individuals. Although the underlying mechanisms are under current investigations, growing evidence suggest that a combination of exaggerated meal-derived nutrient appearance to systemic circulation and altered islet and gut hormone response after eating have a role in pathogenesis of this condition. The goal of this review is to highlight new perspectives regarding this life-threatening complication of RYGB. The etiology, diagnosis, recommendation on how to distinguish from classic dumping and current available treatment based on literature review will be discussed. In addition, physiologic changes after gastric bypass predisposing to hypoglycemia syndrome will be highlighted.International Journal of Obesity advance online publication, 31 October 2017; doi:10.1038/ijo.2017.257.

Severe postprandial hypoglycemia with neuroglycopenia is an increasingly recognized, debilitating complication of Roux-en-Y gastric bypass (RYGB) surgery. Increased secretion of insulin and incretin hormones is implicated in its pathogenesis. Histopathologic examination of pancreas has demonstrated increased islet size and/or nuclear diameter in post-RYGB patients who underwent pancreatectomy for severe refractory hypoglycemia with neuroglycopenia (RYGB + NG). We aimed to determine whether β-cell proliferation or apoptosis is altered in RYGB + NG.

We performed an observational study to analyze markers of proliferation, apoptosis, cell cycle, and transcription factor expression in pancreatic tissue from affected RYGB + NG patients (n = 12), normoglycemic patients undergoing pancreatic surgery for benign lesions (controls, n = 6), and individuals with hypoglycemia due to insulinoma (n = 52).

Proliferative cell nuclear antigen (PCNA) expression was increased in insulin-positive cells in RYGB + NG patients (4.5-fold increase, p < 0.001 vs. controls) and correlated with β-cell mass. Ki-67 immunoreactivity was low in both RYGB + NG and controls, but did not differ between groups. Phospho-histone H3 levels did not differ between RYGB + NG and controls. PCNA and Ki-67 were both significantly lower in both controls and RYGB + NG than insulinomas. Markers of apoptosis and cell cycle (M30, p27, and p21) did not differ between groups. PDX1 and menin exhibited similar expression patterns, while FOXO1 appeared to be more cytosolic in RYGB + NG.

Markers of proliferation are heterogeneous in patients with severe post-RYGB hypoglycemia. Increased β-cell proliferation in some individuals may contribute to increased β-cell mass observed in severely affected patients.

Postprandial hyperinsulinemic hypoglycemia (PHH) is often reported after Roux-en-Y gastric bypass (RYGB). In the absence of a prospective study, the clinical and biological determinants of PHH remain unclear.

To determine the incidence and predictive factors of PHH after RYGB.

Participants were 957 RYGB patients enrolled in an ongoing longitudinal cohort study. We analyzed the results of an oral glucose tolerance test (OGTT) routinely performed before surgery and 1 and/or 5 years after. PHH was defined as blood glucose < 50 mg/dL AND plasma insulin > 3 mU/L at 120 minutes post glucose challenge. Validated indices of insulin sensitivity (Matsuda index), beta-cell function (Insulinogenic index), and beta-cell mass (fasting C-peptide: glucose ratio) were calculated, from glucose, insulin, and c-peptide values measured during OGTT.

OGTT results were available in all patients at baseline, in 85.6% at 12 months and 52.8% at 60 months. The incidence of PHH was 0.5% at baseline, 9.1% * and 7.9%* at 12 months and 60 months following RYGB (*: P < 0.001). In multivariate logistic regression analysis, PHH after RYGB was independently associated with lower age (P = 0.005), greater weight loss (P = 0.031), as well as higher beta-cell function (P = 0.002) and insulin sensitivity (P < 0.001), but not with beta-cell mass (P = 0.381). A preoperative elevated beta-cell function was an independent predictor of PHH after RYGB (receiver operating characteristics curve area under the curve 0.68, P = 0.04).

The incidence of PHH significantly increased after RYGB but remained stable between 1 and 5 years. The estimation of beta-cell function with an OGTT before surgery can identify patients at risk for developing PHH after RYGB.

Recent studies discussed the benefit of bariatric surgery on obese patients diagnosed with type 2 diabetes mellitus (T2DM). Several factors play an essential role in predicting the impact of bariatric surgery on T2DM, such as ABCD score (age, BMI, C-peptide, and duration of the disease), HbA1c, and fasting blood glucose, incretins [glucagon-like peptide-1 (GLP-1) and gastric inhibitory peptide (GIP)]. DiaRem score known to include factors such as age, HbA1c, medication, and insulin usage used to predict the remission of T2DM, but it has some limitations. An extensive literature search was conducted on PubMed and Google Scholar using keywords such as gastric bypass, T2DM, bariatric surgery, GLP-1, GIP, and post bariatric hypoglycemia. Restrictive-malabsorptive procedures are most effective in treating T2DM patients based on changes induced in appetite through regulation of gastrointestinal hormones, with decreased hunger and increased satiation. We provide a review of bariatric surgery influence on T2DM and management of post-intervention hypoglycemic events. Post-bariatric surgery hypoglycemia is a serious complication especially when patients develop life-threatening neuroglycopenia with loss of consciousness and seizure. The avoidance of this adverse event may be achieved by strict dietary modification including a restriction on carbohydrates as well as foods with high glycemic index. Further research will provide more information on post-bariatric surgery hyperinsulinemic hypoglycemia pathophysiology and management.

Roux-en-Y gastric bypass (RYGB) is one of the most common operations performed for the patients with morbid obesity. Weight regain (WR) is a complication that may decrease efficiency of the surgical treatment and demand further interventions. Different factors including lifestyle, mental health, hormonal/metabolic and surgical plays role in WR after RYGB. Various treatment options have been proposed for WR. Conservative treatment is less effective than surgery. Endoscopic refashioning of gastric pouch/stoma fails to achieve sustainable weight loss. Surgical reduction of pouch has acceptable short-term results, but WR after 3 years is substantial. Banded gastric bypass achieves good short-term results, but long-term follow-up data are needed. Distalization of RYGB has a high risk of protein calorie malnutrition (PCM) and conversion to BP diversion (BPD)/duodenal switch (DS) is a technically demanding procedure. Both procedures achieve sustainable long-term weight loss. More studies are needed to explore long-term results of various surgical interventions for WR after RYGB.

Hypoglycaemia after gastric bypass can be severe, but is uncommon, and is sometimes only revealed through monitoring glucose concentrations. The published literature is limited by the heterogeneity of the criteria used for diagnosis, arguing in favour of the Whipple triad with a glycaemia threshold of 55 mg/dl as the diagnostic reference. Women who lost most of their excess weight after gastric bypass, long after the surgery was performed, and who did not have diabetes before surgery are at the greatest risk. In this context, hypoglycaemia results from hyperinsulinism, which is either generated by pancreas anomalies (nesidioblastosis) and/or caused by an overstimulation of β cells by incretins, mainly glucagon-like peptide-1 (GLP-1). Glucose absorption is both accelerated and increased because of the direct communication between the gastric pouch and the jejunum. This is a post-surgical exaggeration of a natural adaptation that is seen in patients who have not undergone surgery in whom glucose is infused directly into the jejunum. There is not always a correspondence between symptoms and biological traits; however, hyperinsulinism is constant if hypoglycaemia is severe and there are neuroglucopenic symptoms. The treatment relies firstly on changes in eating habits, splitting food intake into five to six daily meals, slowing gastric emptying, reducing the glycaemic load and glycaemic index of foods, using fructose and avoiding stress at meals. Pharmacological treatment with acarbose is efficient, but other drugs still need to be validated in a greater number of subjects (insulin, glucagon, calcium channel blockers, somatostatin analogues and GLP-1 analogues). Lastly, if the surgical option has to be used, the benefits (efficient symptom relief) and the risks (weight regain, diabetes) should be weighed carefully.

The oral glucose tolerance test (OGTT) is used in the screening of gestational diabetes, in diagnosis of type 2 diabetes in conjunction with fasting blood glucose and glycated hemoglobin. The aim of this study was to examine the incidence and risk factors of adverse effects of OGTT in patients who underwent bariatric surgery, in addition to proposing standardization for ordering the OGTT in these patients.

This study assessed the incidence of adverse effects in 128 post-bariatric surgery patients who underwent the OGTT. Descriptive and logistic regression analysis were performed, the dependent variables were defined as the presence of signs (tremor, profuse sweating, tachycardia), symptoms (nausea, diarrhea, dizziness, weakness), and hypoglycemia (blood glucose ≤ 50 mg/dL).

One hundred and seventeen participants (91.4%) were female; 38 (29.7%) participants were pregnant. High incidence (64.8%) of adverse effects was observed: nausea (38.4%), dizziness (30.5%), weakness (25.8%), diarrhea (23.4%), hypoglycemia (14.8%), tachycardia (14.1%), tremor (13.3%), profuse sweating (12.5%) and one case of severe hypoglycemia (24 mg/dL). The presence of signs was associated with hypoglycemia (OR = 8.1, CI 95% 2.6-25.1). The arterial hypertension persisted as a risk factor for the incidence of signs (OR = 3.6, CI 95% 1.2-11.3). Fasting glucose below 75 mg/dL increased the risk of hypoglycemia during the test (OR = 9.5, CI 95% 2.6-35.1).

In this study, high incidence of adverse effects during the OGTT was observed in post-bariatric surgery patients. If these results are confirmed by further studies, the indication and regulation of the OGTT procedure must be reviewed for these patients.

After laparoscopic Roux-en-Y gastric bypass (LRYGB), many patients suffer from dumping syndrome. Oral glucose tolerance tests are usually carried out with 50-75 g of glucose. The aim of this study was to examine whether minimal glucose loads of 10 g and 25 g induce a reliable secretion of satiation peptides without dumping symptoms after LRYGB. In addition, lean and obese controls were examined.

The objective of this study was to determine the effects of low oral glucose loads on incretin release and gastric emptying.

All surgical procedures were performed by the same surgeon (RP) at the St. Claraspital Basel in Switzerland. Oral glucose challenges were carried out at the University Hospital of Basel (Phase 1 Research Unit).

Eight patients 10±.4 weeks after LRYGB (PostOP; body mass index [BMI]: 38.6 kg/m²±1.7) as well as 12 lean controls (LC; BMI: 21.8 kg/m²±.6) and 12 obese controls (OC; BMI 38.7 kg/m²±1.3) received 10 g and 25 g of oral glucose. We examined clinical signs of dumping syndrome; plasma glucose, insulin, glucagon-like peptide 1, glucose-dependent insulinotropic peptide, and peptide tyrosine tyrosine concentrations; and gastric emptying with a ¹³ C-sodium acetate breath test.

No signs of dumping were seen in PostOP. Compared with OC, LC showed lower fasting glucose, insulin, and C-peptide, and lower homeostasis model assessment (HOMA) and AUC-180 for insulin and C-peptide. In PostOP, fasting insulin, HOMA and AUC-180 for insulin was lower and no difference was found in fasting C-peptide or AUC-180 for C-peptide compared to OC. There was no significant difference in fasting glucose, insulin, C-peptide, HOMA and AUC-180 for insulin in PostOP compared to LC, but AUC-180 for C-peptide was higher in PostOP. AUC-60 for gut hormones was similar in OC and LC and higher in PostOP compared to OC or LC. gastric emptying was slower in LC and OC compared with PostOP.

After LRYGB, 25 g oral glucose is well tolerated and leads to reliable secretion of gut hormones. Fasting glucose, insulin and C-peptide are normalized, while glucagon-like peptide 1, glucose-dependent insulinotropic peptide and peptide tyrosine tyrosine are overcorrected. Pouch emptying is accelerated after LRYGB.

Abnormal glucose profiles have been described after Roux-en-Y gastric bypass (RYGB) with intense postprandial hyperglycemic peaks in some but not all the patients. The underlying mechanisms of these anomalies are not totally understood.

The aim of this study is to determine whether or not the composition of the meal impacts the existence and maximum interstitial glucose (IG) concentration, measured under real-life conditions.

Retrospective cohort.

Referral bariatric surgery left.

Continuous glucose monitoring (CGM) and meal composition were recorded for at least 3 days on an outpatient basis in 56 patients after RYGB. The presence of postprandial peaks defined by IG above 140 mg/dl, the maximum postprandial IG, the carbohydrate content, and the glycemic load of the meals were analyzed.

Thirty-two patients had a hyperglycemic peak (PEAK), and 24 did not (NO PEAK). The average max IG was 159.6 ± 33.0 mg/dl in PEAK individuals and 111.8 ± 13.0 mg/dl in NO PEAK. Age was significantly higher in PEAK, but no other parameter was different between the two groups, including meal composition. In the PEAK patients, in multivariate analyses, carbohydrate content in model one and glucose load in model two explained respectively 50 and 26 % of maximum IG variance. For each gram of ingested carbohydrates, interstitial glucose increased by 1.68 mg/dl.

Following a gastric bypass, under real-life conditions, irrespective of the carbohydrate content of the meal, some patients develop postprandial hyperglycemic peaks, whereas others do not. In patients with postprandial hyperglycemic peaks, the maximum IG depends on the carbohydrate content of the meal.

In spite of its evident success, several late complications can occur after gastric bypass surgery. One of these is post-gastric bypass hypoglycaemia. No evidence-based guidelines exist in the literature on how to confirm the presence of this syndrome. This study aims to describe and compare the tests aimed at making a diagnosis of post-gastric bypass hypoglycaemia and to provide a diagnostic approach based upon the available evidence. A search was conducted in PubMed, Cochrane and Embase. A few questionnaires have been developed to measure the severity of symptoms in post-gastric bypass hypoglycaemia but none has been validated. The gold standard for provocation of a hypoglycaemic event is the oral glucose tolerance test or the liquid mixed meal tolerance test. Both show a high prevalence of hypoglycaemia in post-gastric bypass patients with and without hypoglycaemic complaints as well as in healthy volunteers. No uniformly established cut-off values for glucose concentrations are defined in the literature for the diagnosis of post-gastric bypass hypoglycaemia. For establishing an accurate diagnosis of post-gastric bypass hypoglycaemia, a validated questionnaire, in connection with the diagnostic performance of provocation tests, is the most important thing missing. Given these shortcomings, we provide recommendations based upon the current literature.

Bariatric surgery rapidly improves Type 2 diabetes mellitus (T2DM). Our objective was to profile and compare the extent and duration of improved glycemic control following Roux-en-Y gastric (RYGB) bypass surgery and vertical sleeve gastrectomy (SG) and compare against calorie restriction/weight loss and medical combination therapy-based approaches using the Zucker diabetic fatty rat (ZDF) rodent model of advanced T2DM. Male ZDF rats underwent RYGB (n = 15) or SG surgery (n = 10) at 18 wk of age and received postsurgical insulin treatment, as required to maintain mid-light-phase glycemia within a predefined range (10-15 mmol/l). In parallel, other groups of animals underwent sham surgery with ad libitum feeding (n = 6), with body weight (n = 8), or glycemic matching (n = 8) to the RYGB group, using food restriction or a combination of insulin, metformin, and liraglutide, respectively. Both bariatric procedures decreased the daily insulin dose required to maintain mid-light-phase blood glucose levels below 15 mmol/l, compared with those required by body weight or glycemia-matched rats (P < 0.001). No difference was noted between RYGB and SG with regard to initial efficacy. SG was, however, associated with higher food intake, weight regain, and higher insulin requirements vs. RYGB at study end (P < 0.05). Severe hypoglycemia occurred in several rats after RYGB. RYGB and SG significantly improved glycemic control in a rodent model of advanced T2DM. While short-term outcomes are similar, long-term efficacy appears marginally better after RYGB, although this is tempered by the increased risk of hypoglycemia.