Efficacy and safety of duodenal-jejunal bypass liner for obesity and type 2 diabetes: A systematic review and meta-analysis.

This study aimed to evaluate the efficacy and safety of duodenal-jejunal bypass liner (DJBL) for obesity and type 2 diabetes mellitus. A comprehensive search of electronic databases was conducted up to September 15, 2022. Thirty studies involving 1751 patients were included. At 12 months post-implantation, the reduction in body mass index (BMI) was 4.8 kg/m2 (95% CI 4.1, 5.5), with an excess weight loss of 41.3% (95% CI 33.4%,49.2%) and a total weight loss of 13.1% (95% CI 10.1%, 16.0%). Significant decrease was observed in HbA1c and fasting glucose, with a standardized mean difference of - 0.72 (95% CI - 0.95, - 0.48) and - 0.62 (95% CI - 0.82, - 0.42), respectively. However, these improvements in weight loss and glycemic control were only partially sustained after explantation. In situ, DJBL significantly improves blood pressure and lipid levels. The pooled early removal rate was 19%, and the incidence of severe adverse events was 17%, including device migration (6%), gastrointestinal hemorrhage (4%), device obstruction (4%), and hepatic abscess (2%). DJBL offers significant improvement in weight loss and glycemic control, as well as cardiovascular parameters while in situ. Further studies are warranted to better understand the long-term efficacy and safety of DJBL. The benefits of DJBL need to be carefully weighed against the risks in clinical decision-making.

Endoscopic duodenal-jejunal bypass liner treatment of moderate obstructive sleep apnoea-A pilot study.

We aimed to assess the extent to which people with type 2 diabetes or pre-diabetes, obesity (BMI 30-45 kg/m2) and moderate obstructive sleep apnoea (OSA) requiring continuous positive airway pressure ventilation (CPAP) were able to discontinue CPAP following EndoBarrier-related weight loss. We assessed sleep and metabolic parameters before, during and after EndoBarrier in 12 participants with moderate OSA requiring CPAP (75% female, 8/12 [66%] type 2 diabetes, 4/12 [34%] prediabetes, mean ± SD age 52.6 ± 9.7 years, BMI 37.4 ± 3.5 kg/m2, median duration of OSA while on CPAP 9.0 [7.0-15.0] months). With EndoBarrier in-situ, mean ± SD Apnoea Hypopnoea Index (AHI) fell by 9.1 ± 5.0 events/h from 18.9 ± 3.8 to 9.7 ± 3.0 events/h (p < .001) with an associated reduction in symptoms of daytime sleepiness (mean Epworth Sleepiness Score) such that all the 12 participants no longer required CPAP according to National Institute for Health and Care Excellence criteria. After EndoBarrier removal, 10/12 (83%) patients attended follow-up and at 12 months after removal, AHI remained below 15 in 5/10 (50%) patients but in other five the AHI rose above 15 such that restarting CPAP was recommended as justified by their symptoms. Rather than restart CPAP, two patients lost the regained weight and their AHI dropped below 15 again. Thus, 7/10 (70%) of patients were able to remain off CPAP 12 or more months after EndoBarrier removal. These results demonstrate major benefit of EndoBarrier in moderate OSA, allowing all patients to discontinue CPAP during treatment, and with maintenance of improvement at follow-up in 70%. They confirm previously demonstrated metabolic improvements in diabetes and obesity.

Endoscopic Bariatric Treatment with Duodenal-Jejunal Bypass Liner Improves Non-invasive Markers of Non-alcoholic Steatohepatitis.

PURPOSE: People with obesity often develop non-alcoholic fatty liver disease (NAFLD) and are at high risk of progression to non-alcoholic steatohepatitis (NASH). Few therapies are effective other than bariatric surgery. We therefore analyzed data from duodenal-jejunal bypass liner (DJBL) patients regarding steatosis, fibrosis, and NASH. METHODS: Consecutive DJBL patients with type 2 diabetes underwent standardized assessments up to device removal at 48 weeks. These included aspartate and alanine transaminase (AST, ALT), controlled attenuation parameter (CAP, for steatosis), and liver stiffness measurement (LSM, for fibrosis). The NAFLD fibrosis score (NFS), fibrosis-4 score (FIB4), and enhanced liver fibrosis (ELF) test were also used to assess fibrosis and the Fibroscan-AST (FAST) score to assess NASH. Mixed models were used and missing data were accounted for with multiple imputation. RESULTS: Thirty-two patients (18 female, mean age 55.1, mean BMI 40.2 kg/m2) were included. After 48 weeks, the change compared to baseline with 95% CI was a factor 0.74 (0.65 to 0.84) for AST, 0.63 (0.53 to 0.75) for ALT, and a difference of - 0.21 (- 0.28 to - 0.13) for FAST, all with p < 0.001. Fibrosis based on LSM, NFS, and ELF did not change whereas FIB4 exhibited slight improvement. Eight DJBL were explanted early due to device-related complications and eight complications led to hospitalization. CONCLUSIONS: One year of DJBL therapy is associated with relevant improvements in non-invasive markers of steatosis and NASH, but not fibrosis, and is accompanied by a substantial number of complications. Given the lack of alternatives, DJBL deserves further attention.

Does Bypass of the Proximal Small Intestine Impact Food Intake, Preference, and Taste Function in Humans? An Experimental Medicine Study Using the Duodenal-Jejunal Bypass Liner.

The duodenal-jejunal bypass liner (Endobarrier) is an endoscopic treatment for obesity and type 2 diabetes mellitus (T2DM). It creates exclusion of the proximal small intestine similar to that after Roux-en-Y Gastric Bypass (RYGB) surgery. The objective of this study was to employ a reductionist approach to determine whether bypass of the proximal intestine is the component conferring the effects of RYGB on food intake and sweet taste preference using the Endobarrier as a research tool. A nested mechanistic study within a large randomised controlled trial compared the impact of lifestyle modification with vs. without Endobarrier insertion in patients with obesity and T2DM. Forty-seven participants were randomised and assessed at several timepoints using direct and indirect assessments of food intake, food preference and taste function. Patients within the Endobarrier group lost numerically more weight compared to the control group. Using food diaries, our results demonstrated similar reductions of food intake in both groups. There were no significant differences in food preference and sensory, appetitive reward, or consummatory reward domain of sweet taste function between groups or changes within groups. In conclusion, the superior weight loss seen in patients with obesity and T2DM who underwent the Endobarrier insertion was not due to a reduction in energy intake or change in food preferences.

Endoscopic bariatrics: current therapies and future directions.

Endoscopic bariatric therapies (EBTs) are endoscopic procedures indicated for weight loss in the obese population. They are shown to be safe and effective for patients who do not quality for bariatric surgery. There are currently no randomized controlled studies comparing bariatric surgery with EBTs. However, EBTs are more cost effective and have fewer complications. This review will examine currently available EBTs with published data.

EndoBarrier™ Implantation Rapidly Improves Insulin Sensitivity in Obese Individuals with Type 2 Diabetes Mellitus.

The EndoBarrier™ medical device is a duodenal-jejunal bypass liner designed to mimic the effects of gastric bypass surgery to induce weight loss and glycaemic improvement. In this study, 10 participants with type 2 diabetes mellitus (T2DM), a mean body mass index (BMI) of 43.3 ± 5.0 (kg/m2) and a mean glycated haemoglobin A1c (HbA1c) of 60.6 ± 8.6 mmol/mol were examined at baseline (before implantation of EndoBarrier™), 4 weeks after implantation, at 36 weeks (right before explantation) and 24 weeks after the removal of the device to explore the short and long-term effects on glucose metabolism. Besides a significant reduction in body weight and fat mass, EndoBarrier™ treatment significantly improved insulin sensitivity during Botnia clamp investigations after four weeks of implantation. The beneficial effects decreased over time but remained significant 24 weeks after removal of the device.

Is duodeno-jejunal bypass liner superior to pylorus preserving bariatric surgery in terms of complications and efficacy?

PURPOSE: Based on recent scientific evidence, bariatric surgery is more effective in the management of morbid obesity and related comorbidities than conservative therapy. Pylorus preserving surgical procedures (PPBS) such as laparoscopic single-anastomosis duodeno-jejunal or duodeno-ileal bypass with sleeve gastrectomy are modified duodenal switch (DS) surgical techniques. The duodeno-jejunal bypass liner (DJBL) is a novel surgical method in the inventory of metabolism focused manual interventions that excludes duodeno-jejunal mucosa from digestion, mimicking DS procedures without the risk of surgical intervention. The aim of this article is to summarize and compare differences between safety-related features and weight loss outcomes of DJBL and PPBS. METHODS: A literature search was conducted in the PubMed database. Records of DJBL-related adverse events (AEs), occurrence of PPBS-related complications and reintervention rates were collected. Mean weight, mean body mass index (BMI), percent of excess of weight loss (EWL%), percent of total weight loss (TWL%) and BMI value alterations were recorded for weight loss outcomes. RESULTS: A total of 11 publications on DJBL and 6 publications on PPBS were included, involving 800 and 1462 patients, respectively. The baseline characteristics of the patients were matched. Comparison of DJBL-related AEs and PPBS-related severe complications showed an almost equal risk (risk difference (RD): -0.03 and confidence interval (CI): -0.27 to 0.21), despite higher rates among patients having received endoscopic treatment. Overall AE and complication rates classified by Clavien-Dindo showed that PPBS was superior to DJBL due to an excess risk level of 25% (RD: 0.25, CI: 0.01-0.49). Reintervention rates were more favourable in the PPBS group, without significant differences in risk (RD: -0.03, CI: -0.27 to 0.20). However, PPBS seemed more efficient regarding weight loss outcomes at 1-year follow-up according to raw data, while meta-analysis did not reveal any significant difference (odds ratio (OR): 1.08, CI: 0.74-1.59 for BMI changes). CONCLUSION: Only limited conclusions can be made based on our findings. PPBS was superior to DJBL with regard to safety outcomes (GRADE IIB), which failed to support the authors' hypothesis. Surgical procedures showed lower complication rates than the incidence of DJBL-related AEs, although it should be emphasized that the low number of PPBS-related mild to moderate complications reported could be the result of incomplete data recording from the analysed publications. Weight loss outcomes favoured bariatric surgery (GRADE IIB). As the DJBL is implanted into the upper gastrointestinal tract for 6 to 12 months, it seems a promising additional method in the inventory of metabolic interventions.

The effect of a duodenal-jejunal bypass liner on lipid profile and blood concentrations of long chain polyunsaturated fatty acids.

BACKGROUND & AIMS: Duodenal-jejunal bypass liners (DJBLs) prevent absorption in the proximal small intestine, the site of fatty acid absorption. We sought to investigate the effects of a DJBL on blood concentrations of essential fatty acids (EFAs) and bioactive polyunsaturated fatty acids (PUFAs). METHODS: Sub-study of a multicentre, randomised, controlled trial with two treatment groups. Patients aged 18-65 years with type-2 diabetes mellitus and body mass index 30-50 kg/m2 were randomised to receive a DJBL for 12 months or best medical therapy, diet and exercise. Whole plasma PUFA concentrations were determined at baseline, 10 days, 6 and 11.5 months; data were available for n = 70 patients per group. RESULTS: Weight loss was significantly greater in the DJBL group compared to controls after 11.5 months: total body weight loss 11.3 ± 5.3% versus 6.0 ± 5.7% (mean difference [95% CI] = 5.27% [3.75, 6.80], p < 0.001). Absolute concentrations of both EFAs, linoleic acid and α-linolenic acid, and their bioactive derivatives, arachidonic acid, eicosapentaenoic acid, docosapentaenoic acid and docosahexaenoic acid, were significantly lower in the DJBL group than in the control group at 6 and 11.5 months follow-up. Total serum cholesterol, LDL-cholesterol and HDL-cholesterol were also significantly lower in the DJBL group. CONCLUSION: One year of DJBL therapy is associated with superior weight loss and greater reductions in total serum cholesterol and LDL-cholesterol, but also depletion of EFAs and their longer chain derivatives. DJBL therapy may need to be offset by maintaining an adequate dietary intake of PUFAs or by supplementation. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT02459561.

Minireview: Current status of endoscopic duodenal mucosal resurfacing.

Several strategies are being pursued to overcome the alarming pandemics of obesity and type 2 diabetes (T2D). In recent years, duodenal mucosal resurfacing (DMR) has shown its potential to improve glycemic indices. Following animal studies, which demonstrated feasibility and safety, the procedure has been applied in two human studies. The DMR procedure has been considered feasible and safe in humans with a limited occurrence of complications and adverse events. Reductions in glycated haemoglobin, weight, fasting plasma glucose, and alanine transaminase have been proven at different follow-up time-points. The length of the ablation may induce different outcomes, having the patients with long duodenal segment ablated showed greater beneficial effects. The current evidence does not still prove the apparent insulin-sensitizing mechanism explaining the impact of the DMR procedure on hepatic glucose production. However, the initial findings have demonstrated a positive risk-benefit ratio and an effect on the treatment of metabolic diseases, such as T2D. Future studies should clarify the mechanisms underlying the positive effects and durability of the treatment using controlled trial conditions on larger number of patients.

Clinical follow-up on weight loss, glycemic control, and safety aspects of 24 months of duodenal-jejunal bypass liner implantation.

BACKGROUND: The duodenal-jejunal bypass liner (DJBL) is an endoscopic device designed to induce weight loss and improve glycemic control. The liner is licensed for a maximum implant duration of 12 months. It might be hypothesized that extension of the dwelling time results in added value. The goals of our study were to determine weight change, change in glycemic control, and safety in patients with an intended 24 months of DJBL dwelling time. METHODS: Patients were initially selected for a 12-month implantation period. When no physical complaints or adverse events (AEs) occurred, motivated patients who responded well were selected for extension of dwelling time to 24 months. Patients underwent a control endoscopy 12 months after implantation and visited the out-patient clinic every 3 months up to explantation. Patients agreed to remove the DJBL when complaints or AEs occurred that could not be treated conservatively. RESULTS: Implantation was extended in 44 patients, and 24 (55%) patients completed the full 24 months. Twenty patients required early removal due to AEs. During dwelling time, body weight decreased significantly (15.9 kg; TBWL 14.6%). HbA1c decreased non-significantly (4.9 mmol/mol). The number of insulin users and daily dose of insulin both decreased significantly. At 24 months after removal, glycemic control had worsened, while body weight was still significantly lower compared to baseline. In total, 68% of the patients experienced at least one AE. Two patients developed a hepatic abscess. CONCLUSIONS: DJBL treatment results in significant weight loss and improves glycemic control during implantation. The largest beneficial effects occur during the first 9-12 months after implantation. Extension of dwelling time to 24 months results only in stabilization of body weight and glycemic control. After explantation, weight improvements are maintained, but glycemic control worsens. As the cumulative risk of AEs increases with time, a maximal dwelling time of 12 months is advisable.

Endoscopic Management of Anchor Erosion Adjacent to the Pylorus Following Duodenal-Jejunal Bypass Sleeve.

INTRODUCTION: Obesity is a pandemic associated with significant comorbidities such as type 2 diabetes (T2DM). RYGB is an effective treatment modality for obesity and T2DM. However, bariatric surgery is currently limited to a relatively small population of patients. The duodenal-jejunal bypass sleeve (DJBS) has recently emerged as a promising therapy for obesity and T2DM by providing similar physiological effects to RYGB. We describe a case of a patient with a previously placed DJBS presenting with abdominal pain from anchor erosion managed with an endoscopic approach. METHODS: A 58-year-old man with obesity and T2DM who had failed prior medical therapy for obesity was referred for DJBS placement. This was placed without complications. At 8 weeks follow-up, he developed abdominal pain and vomiting prompting immediate endoscopic evaluation. RESULTS: EGD revealed an anchor erosion resulting in mild stenosis of the pylorus. Additionally, hyperplastic tissue was found to be adhered to the device in the duodenal bulb. Endoscopic removal with balloon dilation was unsuccessful, and a stent was placed in a "stent-in-stent" fashion through the sleeve to compress the area of tissue ingrowth encouraging local tissue necrosis and device extraction. At 15 days follow-up, the stent was removed; however, the DJBS remained adhered and immobile. Next, the ingrowing hyperplastic tissue was resected in a piecemeal fashion. This resulted in mobilization of the sleeve anchors in the duodenal bulb and successful removal of the DJBS. CONCLUSIONS: DJBS endoscopic removal is safe and effective even in challenging cases, thus preventing the need for surgical intervention.

Impact of Duodeno-Jejunal Bypass Liner (EndoBarrierTM) Implantation on Insulin Sensitivity in Patients with Type 2 Diabetes Mellitus (T2DM): A Study Protocol for a Pilot Trial.

INTRODUCTION: A 60-cm endoscopically implantable duodenal-jejunal bypass liner (Endobarrier™, GI Dynamics, Lexington, MA, USA) has been introduced as a therapeutic option to support weight loss for a selected group of obese subjects with type 2 diabetes mellitus (T2DM). The sleeve prevents contact between chyme and the intestinal mucosa of the upper gastrointestinal tract. The primary aim of this study is to elucidate the changes in insulin sensitivity and beta-cell function after EndoBarrier™ implantation in obese patients with T2DM; changes in gut permeability and gut microbiome are also to be examined. METHODS: This is an open, single-center, prospective trial in which ten obese subjects with T2DM and suboptimal glycemic control (glycosylated hemoglobin A1c (HbA1c) level > 48 mmol/mol) are investigated with regards to EndoBarrier™ implantation. The Endobarrier™ is implanted shortly after baseline and left in situ for a period of 36 weeks. Dual-energy X-ray absorptiometry measurement, assessment of beta-cell function and insulin sensitivity as measured by a Botnia clamp procedure, and a mixed-meal tolerance test are performed prior to implantation and at 4, 36, and 64 weeks after implantation. The composition of the gut microbiota is characterized from stool using 454 pyrosequencing of 16S rRNA genes. Gut permeability is assessed by a differential sugar absorption method. PLANNED OUTCOME: This study will give mechanistic insights in particulr into changes of insulin sensitivity, beta-cell function or microbiome changes over time in subjects implanted with an EndobarrierTM device. TRIAL REGISTRATION: NCT02769728, Registered 12 May 2016. Current Protocol Date/Version: 04 September 2017/Version 1.9.

Non-pharmacological Treatment Options in the Management of Diabetes Mellitus.

The global prevalence of diabetes, especially type 2 diabetes mellitus, has reached epidemic proportions in the last few decades of the 20th century because of the obesity pandemic resulting from adverse lifestyles. Diabetes as a consequence of obesity (diabesity), continues to increase exponentially in the 21st century. Although there are a multitude of drugs for the effective management of diabesity with modest benefits, most patients will require insulin for control of diabetes at some stage that would worsen obesity, and thereby diabesity. Therefore, effective non-pharmacological therapy needs to be expedited in all patients with diabesity. These measures include medical nutrition interventions, change of lifestyles and bariatric surgery. Non-pharmacological interventions are also useful for the effective management of even type 1 diabetes mellitus when used along with insulin therapy especially in those with obesity. This review summarises the current evidence base for the non-pharmacological interventions in the management of diabetes.

Adverse Events of the Duodenal-Jejunal Bypass Liner: a Systematic Review.

A systematic review was conducted on adverse events (AEs) associated with the use of the duodenal-jejunal bypass liner (DJBL). PubMed, EMBASE, and Cochrane library were searched up to January 2018. The quality of reporting AEs was determined by the McHarm questionnaire and the risk of bias by the Newcastle-Ottawa scale. Thirty-eight studies were included. The comparability of the studies was low and the McHarm questionnaire showed incompleteness for most parameters in all studies. A total of 891 AEs were reported in 1056 patients. Thirty-three AEs (3.7%) were classified as severe, including hepatic abscess and esophageal perforation. The anchor of the DJBL caused or likely caused 85% of the SAEs. To improve the safety margin of the DJBL, adjustments to the anchoring system are needed.

Endobarrier as a Pre Bariatric Surgical Intervention in High-Risk Patients: a Feasibility Study.

BACKGROUND: Obesity surgery mortality risk scoring system (OS-MRS) classifies patients into high, intermediate and low risk, based on age, body mass index, sex and other comorbidities such as hypertension and history of pulmonary embolism. High-risk patients not only have a higher mortality but are more likely to develop post-operative complications necessitating intervention or prolonged hospital stay following bariatric surgery. Endoscopically placed duodenal-jejunal bypass sleeve (Endobarrier) has been designed to achieve weight loss and improve glycaemic control in morbidly obese patients with clinically proven effectiveness. The aim of this study was to assess if pre-operative insertion of endobarrier in high-risk patients can decrease morbidity and length of stay after bariatric surgery. MATERIALS AND METHODS: Between 2012 and 2014, a cohort of 11 high-risk patients had an Endobarrier inserted (E&BS group) for 1 year prior to definitive bariatric surgery. These patients were compared against a similar group undergoing primary bariatric surgery (PBS group) during same duration. The two groups were matched for age, gender, body mass index, comorbidities, surgical procedure and OS-MRS using propensity score matching. Outcome measures included operative time, morbidity, length of stay, intensive therapy unit (ITU) stay, readmission rate, percentage excess weight loss (%EWL) and percentage total weight loss (%TWL). RESULTS: Patient characteristics and OS-MRS were similar in both groups (match tolerance 0.1). There was no significant difference in total length of stay, readmission rate, %EWL and %TWL. Operative time, ITU stay, post-operative complications and severity of complications were significantly less in the E&BS group (p < 0.05) with significant likelihood of planned ITU admissions in the PBS group (p < 0.05). CONCLUSION: Endobarrier could be considered as a pre bariatric surgical intervention in high-risk patients. It may result in improved post-operative outcomes in high-risk bariatric patients.

Safety and efficacy of the endoscopic duodenal-jejunal bypass liner prototype in severe or morbidly obese subjects implanted for up to 3 years.

BACKGROUND: The duodenal-jejunal bypass liner (DJBL) is an endoscopic device that mimics the duodenal-jejunal exclusion component of the Roux-en-Y gastric bypass. Previous studies assessing the efficacy of the DJBL have shown 10-40% excess weight loss (%EWL) and improvements in obesity-associated comorbidities. The aim of this study was to evaluate the safety and efficacy of a new DJBL prototype over a 3-year period. METHODS: Morbidly obese subjects were enrolled in a single-arm, open-label, prospective trial. The subjects were offered the opportunity to continue with the trial annually and signed a new consent form. The primary endpoint was safety. The secondary endpoints were changes in weight and biochemical parameters from baseline. RESULTS: The DJBL was implanted endoscopically in 80 subjects (age: 35±10 years; 69% female; weight: 109±17 kg; BMI: 42±5.4 kg/m2). Seventy-two severe adverse events (AEs) were observed in 55 patients (68%), of which nine subjects required a prolonged hospital stay and three subjects required major interventions. Overall, 23 subjects (29%) underwent early device removal due to AEs. Additionally, 95% of the patients experienced mild AEs that mainly consisted of abdominal pain. The severe AEs included a liver abscess (3), upper GI bleeding (4), cholangitis (1), and acute pancreatitis (1) and mostly occurred after 12 months of follow-up. Two patients presented a short esophageal perforation during explantation. These perforations were successfully managed with endoscopic closure in one subject and medical treatment in the other subject. In the completer population at 52 weeks (71 patients), 104 weeks (40 patients), and 156 weeks (11 patients), the mean %EWL were 44 ± 16, 40 ± 22, and 39 ± 20, respectively (p < 0.001). CONCLUSION: This study shows significant and sustained weight loss after 3 years of treatment with the new DJBL. However, the high frequency and severity of AEs preclude the use of this prototype for periods longer than 1 year.

A randomised controlled trial of a duodenal-jejunal bypass sleeve device (EndoBarrier) compared with standard medical therapy for the management of obese subjects with type 2 diabetes mellitus.

INTRODUCTION: The prevalence of obesity and obesity-related diseases, including type 2 diabetes mellitus (T2DM), is increasing. Exclusion of the foregut, as occurs in Roux-en-Y gastric bypass, has a key role in the metabolic improvements that occur following bariatric surgery, which are independent of weight loss. Endoscopically placed duodenal-jejunal bypass sleeve devices, such as the EndoBarrier (GI Dynamics, Lexington, Massachusetts, USA), have been designed to create an impermeable barrier between chyme exiting the stomach and the mucosa of the duodenum and proximal jejunum. The non-surgical and reversible nature of these devices represents an attractive therapeutic option for patients with obesity and T2DM by potentially improving glycaemic control and reducing their weight. METHODS AND ANALYSIS: In this multicentre, randomised, controlled, non-blinded trial, male and female patients aged 18-65 years with a body mass index 30-50 kg/m2 and inadequately controlled T2DM on oral antihyperglycaemic medications (glycosylated haemoglobin (HbA1c) 58-97 mmol/mol) will be randomised in a 1:1 ratio to receive either the EndoBarrier device (n=80) for 12 months or conventional medical therapy, diet and exercise (n=80). The primary outcome measure will be a reduction in HbA1c by 20% at 12 months. Secondary outcome measures will include percentage weight loss, change in cardiovascular risk factors and medications, quality of life, cost, quality-adjusted life years accrued and adverse events. Three additional subgroups will investigate the mechanisms behind the effect of the EndoBarrier device, looking at changes in gut hormones, metabolites, bile acids, microbiome, food hedonics and preferences, taste, brain reward system responses to food, eating and addictive behaviours, body fat content, insulin sensitivity, and intestinal tissue gene expression. TRIAL REGISTRATION NUMBER: ISRCTN30845205, ClinicalTrials.gov Identifier NCT02459561.

For Debate: Should Bariatric Surgery be Performed in Children and Adolescents with Hypothalamic Obesity?

Hypothalamic dysfunction leading to severe obesity is a serious long-term consequence of paediatric craniopharyngioma. It compromises quality of life, leads to long-term metabolic hazards, and may shorten life expectancy. Therefore, a proactive approach is required. Conventional treatment of hypothalamic obesity is difficult and hardly successful. Experience with bariatric surgery is limited, especially in younger patients. Two retrospective studies recently reported on classic bariatric surgery in a small series of individuals after craniopharyngioma. Of these, one included nine paediatric patients who underwent laparoscopic adjustable gastric banding (LAGB), sleeve gastrectomy (SG), Roux-en-Y gastric bypass (RYGB) or biliopancreatic diversion (BPD). The immediate effects were promising: The mean weight loss was 20.9 kilograms at 6 months and 15.1 kilograms at 12 months. A duodenal-jejunal bypass sleeve (DBJS; EndoBarrier) is a mini-invasive, endoscopically placed and fully reversible bariatric procedure. We reported a boy diagnosed with craniopharyngioma at 10 years old who underwent surgery and radiotherapy. His body weight increased to 139 kilograms and body mass index (BMI) to 46.1 kg/m2 (+4.0 SD) within the subsequent 4.5 years. Fifteen months after DJBS placement, he lost 32.8 kilograms, and his BMI dropped to 32.7 kg/m2 (+2.9 SD). Thus, DJBS proved to be a promising procedure in the treatment of hypothalamic obesity. We suggest performing it in children and adolescents with hypothalamic obesity to prevent or attenuate its devastating long-term sequelae.

Measurement of hepatic insulin sensitivity early after the bypass of the proximal small bowel in humans.

OBJECTIVE: Unlike gastric banding or sleeve gastrectomy procedures, intestinal bypass procedures, Roux-en-Y gastric bypass in particular, lead to rapid improvements in glycaemia early after surgery. The bypass of the proximal small bowel may have weight loss and even caloric restriction-independent glucose-lowering properties on hepatic insulin sensitivity. In this first human mechanistic study, we examined this hypothesis by investigating the early effects of the duodeno-jejunal bypass liner (DJBL; GI Dynamics, USA) on the hepatic insulin sensitivity by using the gold standard euglycaemic hyperinsulinaemic clamp methodology. METHOD: Seven patients with obesity underwent measurement of hepatic insulin sensitivity at baseline, 1 week after a low-calorie liquid diet and after a further 1 week following insertion of the DJBL whilst on the same diet. RESULTS: Duodeno-jejunal bypass liner did not improve the insulin sensitivity of hepatic glucose production beyond the improvements achieved with caloric restriction. CONCLUSIONS: Caloric restriction may be the predominant driver of early increases in hepatic insulin sensitivity after the endoscopic bypass of the proximal small bowel. The same mechanism may be at play after Roux-en-Y gastric bypass and explain, at least in part, the rapid improvements in glycaemia.

Endobarrier® in Grade I Obese Patients with Long-Standing Type 2 Diabetes: Role of Gastrointestinal Hormones in Glucose Metabolism.

BACKGROUND: The purpose of this study was to evaluate the efficacy and safety of Endobarrier® in grade 1 obese T2DM patients with poor metabolic control and the role of gastro-intestinal hormone changes on the metabolic outcomes. METHODS: Twenty-one patients aged 54.1 ± 9.5 years, diabetes duration 14.8 ± 8.5 years, BMI 33.4 ± 1.9 kg/m2, and HbA1c 9.1 ± 1.3 %, under insulin therapy, were implanted with Endobarrier®. Fasting concentrations of PYY, ghrelin and glucagon, and AUC for GLP-1 after a standard meal test were determined prior to and at months 1 and 12 after implantation. RESULTS: Patients lost 14.9 ± 5.7 % of their total body weight. HbA1c decreased 1.3 % in the first month, but at the end of the study, the reduction was 0.6 %. HbA1c ≤ 7 % was achieved in 26.3 % of patients. No differences in GLP-1 AUC values were found before and after implant. Fasting plasma ghrelin and PYY concentrations increased from month 1 to 12. Conversely, fasting plasma glucagon concentrations decreased at month 1 and increased thereafter. Weight (ß 0.152) and HbA1c decrease at month 1 (ß 0.176) were the only variables predictive of HbA1c values at 12 months (adjusted R 2 for the model 0.693, p = 0.001). Minor adverse events occurred in 14 % of patients and major events in 9.5 %. CONCLUSIONS: Endobarrier® in T2DM patients with grade I obesity and poor metabolic control is associated with significant weight decrease and moderate reduction in HbA1c at month 12. Our data do not support a role for GLP-1 in the metabolic improvement in this subset of patients.