Duodenal-jejunal Bypass Liner Research Articles

A duodenal sleeve bypass device added to intensive medical therapy for obesity with type 2 diabetes: a RCT

BackgroundThe EndoBarrier®(GI Dynamics Inc., Boston, MA, USA) is an endoluminal duodenal–jejunal bypass liner developed for the treatment of patients with obesity and type 2 diabetes mellitus. Meta-analyses of its effects on glycaemia and weight have called for larger randomised controlled trials with longer follow-up.ObjectivesThe primary objective was to compare intensive medical therapy with a duodenal–jejunal bypass liner with intensive medical therapy without a duodenal–jejunal bypass liner, comparing effectiveness on the metabolic state as defined by the International Diabetes Federation as a glycated haemoglobin level reduction of ≥ 20%. The secondary objectives were to compare intensive medical therapy with a duodenal–jejunal bypass liner with intensive medical therapy without a duodenal–jejunal bypass liner, comparing effectiveness on the metabolic state as defined by the International Diabetes Federation as a glycated haemoglobin level of < 42 mmol/mol, blood pressure of < 135/85 mmHg, and the effectiveness on total body weight loss. Additional secondary outcomes were to investigate the cost-effectiveness and mechanism of action of the effect of a duodenal–jejunal bypass liner on brain reward system responses, insulin sensitivity, eating behaviour and metabonomics.DesignA multicentre, open-label, randomised controlled trial.SettingImperial College Healthcare NHS Trust and University Hospital Southampton NHS Foundation Trust.ParticipantsPatients aged 18–65 years with a body mass index of 30–50 kg/m2and with inadequately controlled type 2 diabetes mellitus who were on oral glucose-lowering medications.InterventionsParticipants were randomised equally to receive intensive medical therapy alongside a duodenal–jejunal bypass liner device (n = 85) or intensive medical therapy alone for 12 months (n = 85), and were followed up for a further 12 months.ResultsThere was no significant difference between groups in the percentage of patients achieving the glycaemic primary or secondary outcomes [primary outcome at 12 months: duodenal–jejunal bypass liner group 54.5% vs. control group 55.2% (odds ratio 0.93, 95% confidence interval 0.44 to 1.98;p = 0.85); primary outcome at 24 months: duodenal–jejunal bypass liner group 39.7% vs. control group 36.5% (odds ratio 1.13, 95% confidence interval 0.52 to 2.47;p = 0.75)]. Significantly more patients in the duodenal–jejunal bypass liner group than in the control group lost > 15% of their total body weight (duodenal–jejunal bypass liner group 24.2% vs. control group 3.7%; odds ratio 8.33, 95% confidence interval 1.78 to 39.0;p = 0.007) and achieved blood pressure targets (duodenal–jejunal bypass liner group 68.2% vs. control group 44.4%; odds ratio 2.57, 95% confidence interval 1.21 to 5.48;p = 0.014). These differences were observed at 12 months but not at 24 months. There were more adverse events in the duodenal–jejunal bypass liner group, including one liver abscess. The increase in peripheral insulin sensitivity was superior in the duodenal–jejunal bypass liner group. Spectroscopic analyses of plasma, urine and faeces revealed several distinct metabolic perturbations in the duodenal–jejunal bypass liner group but not in the control group. Brain reward responses to food cues were not different between groups. The number of mean quality-adjusted life-years gained was similar in both groups and the additional costs of the duodenal–jejunal bypass liner may outweigh the value of the health benefits by £2560 per patient treated.ConclusionsThe results show that the endoluminal duodenal–jejunal bypass liner was not superior to intensive medical therapy for glycaemic control and was associated with more adverse events. The duodenal–jejunal bypass liner was associated with significant weight loss and improvement in cardiometabolic parameters at 12 months but not at 24 months. Economic evaluation showed that the bypass liner was not cost-effective for glycaemic control or for weight loss.Trial registrationCurrent Controlled Trials ISRCTN30845205.FundingThis project was funded by the Efficacy and Mechanism Evaluation (EME) Programme, a Medical Research Council (MRC) and National Institute for Health Research (NIHR) partnership. This will be published in full inEfficacy and Mechanism Evaluation; Vol. 7, No. 6. See the NIHR Journals Library website for further project information. This study was executed with the support of GI Dynamics Inc. and with the kind support of Nutricia Advanced Medical Nutrition for providing oral nutritional supplements.

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

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). 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 30-50kg/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. 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. 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. ClinicalTrials.gov Identifier NCT02459561.

A Preclinical Animal Study of Combined Intragastric Balloon and Duodenal-Jejunal Bypass Liner for Obesity and Metabolic Disease.

INTRODUCTION:Endoscopic bariatric and metabolic therapies can potentially reproduce similar gastric and small intestinal anatomic and physiologic manipulations as Roux-en-Y gastric bypass. This proof of concept animal study was aimed to assess the feasibility, safety, efficacy, and impact on gastrointestinal physiology of combined intragastric balloons (IGB) and duodenal-jejunal bypass liner (DJBL) for the treatment of obesity.METHODS:Five Ossabaw pigs were fed a high-calorie diet to develop obesity and were randomly assigned to receive IGB or DJBL in sequence. The weight gain rate was calculated. Fasting and postprandial blood samples were drawn before any intervention (serving as the baseline group) and 1 month after second device insertion (serving as the combination group) to measure gut neurohormonal changes and metabolic parameters.RESULTS:Four pigs successfully received a sequential device insertion. One pig developed duodenal sleeve prolapse that was spontaneously resolved. One pig was early terminated because of developing a central line infection. The rate of weight gain in the combination group (0.63 ± 1.3 kg/wk) was significantly lower than the baseline group (1.96 ± 2.17 kg/wk) and numerically lower than after insertion of the IGB (1.00 ± 1.40 kg/wk) or the DJBL (0.75 ± 2.27 kg/wk) alone. A trend of higher postprandial glucagon-like peptide-1 was observed in the combination group compared with the baseline group.DISCUSSION:A combination of IGB and DJBL is feasible and well tolerated. A strategy of sequential use of these devices might offer a synergistic approach that can enhance weight loss and metabolic outcomes.

Comparative efficacy of bariatric endoscopic procedures in the treatment of morbid obesity: a systematic review and network meta-analysis.

The comparative efficacy of bariatric endoscopic procedures has not been completely elucidated. We aimed to comprehensively evaluate the efficacy of bariatric endoscopic procedures. We searched for randomized controlled trials investigating the efficacy of bariatric endoscopic procedures, including the use of an intragastric balloon, duodenal-jejunal bypass liner (DJBL), aspiration therapy, primary obesity surgery endoluminal (POSE) procedure, and botulinum toxin injection to the stomach. Network meta-analyses were performed to determine the percentage of weight loss (%weight loss) and percentage of excess weight loss (%EWL). 22 studies with 2141 patients were included in the meta-analysis. Most endoscopic procedures showed superior efficacy in terms of %weight loss compared with the control (mean difference [MD] [95 % confidence interval (CI)]: aspiration therapy 10.4 % [7.0 % to 13.7 %]; fluid-filled balloon 5.3 % [3.4 % to 7.2 %]; POSE 4.9 % [1.7 % to 8.2 %]; and DJBL 4.5 % [1.4 % to 7.7 %]). In terms of %EWL, aspiration therapy, fluid-filled balloon, POSE, and DJBL were superior to the control (MD [95 %CI]: 27.3 % [15.3 % to 39.3 %]; 22.4 % [15.4 % to 29.4 %]; 15.3 % [2.5 % to 28.0 %]; and 13.0 % [4.9 % to 21.2], respectively). The gas-filled balloon and botulinum toxin injection did not show a significant difference in %weight loss or %EWL compared with the control. For the fluid-filled balloon, the %EWL and %weight loss tended to decrease after balloon removal at 6 months after the procedure. All bariatric endoscopic procedures, except for gas-filled balloon and botulinum toxin injection to the stomach, showed superior short-term efficacy in terms of %weight loss or %EWL compared with lifestyle modification.

Effect of bariatric surgery on circulating FGF-19: A systematic review and meta-analysis.

Fibroblast growth factor-19 (FGF-19) is a gut hormone which interacts with metabolism and is depleted in obesity. There is some indication that the hormone undergoes a resurgence following bariatric surgery (BS), an effect which may contribute to the beneficial outcomes of such procedures. This systematic review and meta-analysis aims to synthesize the available literature on FGF-19 levels before and after BS. MEDLINE, Scopus and Web of Science databases were searched, and the effect of different surgical procedures and degrees of body mass index (BMI) reduction on FGF-19 levels was assessed by DerSimonian and Laird random-effects model in meta-analysis and dose-response analyses. This meta-analysis, which included 474 patients from 25 arms undergoing one of five BS procedures, revealed a significant increase in the levels of circulating FGF-19 following all-type BS. Vertical sleeve gastrectomy, duodenal-jejunal bypass liner and Roux-en-Y gastric bypass all significantly increased circulating FGF-19 levels from baseline. However, gastric banding failed to achieve the same, and in fact, biliopancreatic diversion was associated with decreased circulating FGF-19. Finally, an inverse association between FGF-19 and the degree of BMI-reduction post-operatively was noted. FGF-19 is increased by BS and may represent a pharmaceutical target in efforts to reproduce the beneficial effects of BS in a medical setting.

Influence of glucometric 'dynamical' variables on duodenal-jejunal bypass liner (DJBL) anthropometric and metabolic outcomes.

The endoscopically implanted duodenal-jejunal bypass liner (DJBL) is an attractive alternative to bariatric surgery for obese diabetic patients. This article aims to study dynamical aspects of the glycaemic profile that may influence DJBL effects. Thirty patients underwent DJBL implantation and were followed for 10 months. Continuous glucose monitoring (CGM) was performed before implantation and at month 10. Dynamical variables from CGM were measured: coefficient of variation of glycaemia, mean amplitude of glycaemic excursions (MAGE), detrended fluctuation analysis (DFA), % of time with glycaemia under 6.1 mmol/L (TU6.1), area over 7.8 mmol/L (AO7.8) and time in range. We analysed the correlation between changes in both anthropometric (body mass index, BMI and waist circumference) and metabolic (fasting blood glucose, FBG and HbA1c) variables and dynamical CGM-derived metrics and searched for variables in the basal CGM that could predict successful outcomes. There was a poor correlation between anthropometric and metabolic outcomes. There was a strong correlation between anthropometric changes and changes in glycaemic tonic control (∆BMI-∆TU6.1: rho = - 0.67, P < .01) and between metabolic outcomes and glycaemic phasic control (∆FBG-∆AO7.8: r = .60, P < .01). Basal AO7.8 was a powerful predictor of successful metabolic outcome (0.85 in patients with AO7.8 above the median vs 0.31 in patients with AO7.8 below the median: Chi-squared = 5.67, P = .02). In our population, anthropometric outcomes of DJBL correlate with improvement in tonic control of glycaemia, while metabolic outcomes correlate preferentially with improvement in phasic control. Assessment of basal phasic control may help in candidate profiling for DJBL implantation.

Duodenal-Jejunal Bypass Liner (DJBL) Improves Cardiovascular Risk Biomarkers and Predicted 4-Year Risk of Major CV Events in Patients with Type 2 Diabetes and Metabolic Syndrome.

The duodenal-jejunal bypass liner (DJBL) represents a novel endoscopic minimally invasive treatment option for obesity-associated type 2 diabetes (T2D), affecting body weight and metabolic control. Until now, the effects of DJBL on cardiovascular risk have never been investigated. Between 2012 and 2017, 71 patients with T2D and metabolic syndrome (MS) were recruited for implantation of DJBL for 9-12months. Within DJBL treatment and a follow-up period of 6months, patients were analysed for dynamics of cardiovascular biomarkers. Overall cardiovascular risk was estimated by the ADVANCE Risk Engine at time of implantation, explantation and 6months after explantation of DJBL. DJBL-induced weight loss and improvements in blood sugar control were accompanied by significant decreases of the cardiovascular biomarkers high-sensitive CRP, lipoprotein-associated phospholipase A2 and small dense lipoprotein fraction LDL-4 (p = 0.001, p < 0.001 and p = 0.04, respectively). Estimated overall cardiovascular risk decreased significantly after DJBL implantation and remained stable within 6months after explantation. In addition to beneficial effects of DJBL on weight loss, glycaemic control and lipid parameters in patients with MS, this is the first study that could further reveal significant impact on serological cardiovascular biomarkers and estimated CV risk, suggesting putative protective effects of DJBL on CV outcome.

1155-P: Effect of Endoscopic Duodenal-Jejunal Bypass Liner on Parameters of Insulin Sensitivity and Secretion in Subjects with Type 2 Diabetes Mellitus and Obesity

Duodenal-jejunal by-pass liner (DJBL) is an endoscopically implantable device designed to non-invasively mimic the effects of surgical gastric by-pass. However, the exact mechanisms responsible for improved glucose control associated with DJBL are still unclear. The aim of our study was to assess the effect of DJBL on insulin sensitivity and secretion in subjects with type 2 diabetes mellitus (T2DM) and obesity. Twenty-one obese subjects with T2DM (15 males, age 52.3 ± 11.2 years) underwent the implantation of the EndoBarrier DJBL (GI Dynamics, U.S.). Anthropometric, biochemical and hormonal parameters were measured before and 10 months after the implantation of DJBL. Insulin sensitivity was assessed using euglycemic-hyperinsulinemic clamp. Standard parameters including glucose disposal rate (M) and metabolic clearance rate of glucose (MCG) were calculated based on clamp results. Over 10 months the implantation of DJBL decreased body weight (body mass index 41.6 ± 6.1 vs. 37.5 ± 4.2 kg/m2, p&amp;lt;0.001) and improved glucose control (fasting blood glucose 10.5 ± 2.5 vs. 8.4 ± 2.4 mmol/l, p&amp;lt;0.001; HbA1C 74.7 ± 17.8 vs. 55.6 ± 12.4 mmol/mol, p&amp;lt;0.001). These improvements were accompanied by a marked increase in insulin sensitivity as shown by the results of the euglycemic-hyperinsulinemic clamp (M 1.5 ± 0.8 vs. 2.6 ± 1.0 mg.kg-1.min-1, p&amp;lt;0.001; MCG 1.4 ± 0.7 vs. 2.6 ± 0.2 mg.kg-1.min-1, p&amp;lt;0.001). In contrast, insulin secretion was not affected by DJBL (fasting insulin 21.8 ± 13.0 vs. 18.5 ± 9.5 mIU/l, p=0.312; C-peptide 2.7 ± 1.1 vs. 2.4 ± 1.1 nmol/l, p=0.172). To conclude the improvement in glucose control associated with the implantation of Endobarrier DJBL is primarily caused by increased insulin sensitivity rather than augmented insulin secretion. Disclosure M. Kudlackova: None. M. Mraz: None. M. Haluzik: None. T. Pelikanova: None. M. Benes: None. D. Lapesova: None. D. Kobrova: None. Z. Vlasakova: None. O. Brizova: None. Z. Lacinova: None. Funding Institute for Clinical and Experimental Medicine (IN00023001)

1-OR: Effect of Duodenal-Jejunal Bypass Liner on Cardiovascular Risk in Patients with Type 2 Diabetes and Metabolic Syndrome

Introduction: The duodenal-jejunal bypass liner (DJBL) is an antiresorptive endoscopic treatment option for type 2 diabetes (T2DM) and obesity. The effects of DJBL on cardiovascular risk parameters remain elusive. Methods: We implanted in 71 patients with T2DM and metabolic syndrome a DJBL for 9-12 months. At implantation, 3 months, explantation, 3 and 6 months follow-up, data on blood sugar, body weight, blood pressure and lipid status were collected. Serum samples were analysed for dynamics of cardiovascular biomarkers: high sensitive CRP (HsCRP); lipoprotein-associated phospholipase A2 (Lp-PLA2); Homoarginine; symmetrical dimethylarginin (SDMA), assymetrical dimethylarginine (ADMA), and low densitiy lipoprotein (LDL) subfractions. Overall cardiovascular risk was estimated by Advanced-Risk-Engine at time of implantation, explantation and after 6 months of follow-up. Results: Implantation of DJBL was accompanied by significant decrease of body weight and improvement of blood sugar. We observed decrements of systolic blood pressure, LDL and triglyceride levels in the course of DJBL implantation (p=1x10-3, p=2x10-3, p=0.01). hsCRP, Lp-PLA2 and small dense lipoprotein fraction LDL-4 showed significant decreases after implantation (hsCRP: V1 vs. V6, p=1x10-3, Lp-PLA2: V1 vs. V5, p&amp;lt;1x10-3, LDL-4: V1 vs. V5, p=0.04). Unexpectedly, decreased homoarginine levels after DJBL-implantation correlated with body weight reduction, possibly reflecting catabolic metabolism. Estimated overall cardiovascular risk by Advanced-Risk-Engine decreased after implantation and remained stable within 6 months of follow-up. Discussion: Above recent reports of beneficial effects of DJBL on weight loss, glycemic control and lipid parameters in patients with metabolic syndrome, this is the first study that revealed significant impact on serological cardiovascular biomarkers, indicating possible protective effects of DJBL on cardiovascular outcome. Disclosure K. Laubner: Research Support; Self; Boehringer Ingelheim International GmbH, GI Dynamics, Inc. Speaker's Bureau; Self; AstraZeneca, Berlin-Chemie AG, Boehringer Ingelheim International GmbH, Merck Sharp &amp; Dohme Corp., Novartis AG. N. Röhlen: None. D. Bettinger: None. H. Hilger: None. C. König: None. A. Krebs: None. J. Seufert: None. Funding GI Dynamics

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

BackgroundThe 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.MethodsPatients 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.ResultsImplantation 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.ConclusionsDJBL 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.

Is Early Reimplantation of the Duodenal-Jejunal Bypass Liner Viable?

The endoscopically implanted duodenal-jejunal bypass liner (DJBL) is an impermeable fluoropolymer device which prevents food making contact with the proximal intestine, thus inducing weight loss and improvement of type 2 diabetes mellitus (T2DM). However, weight and HbA1c levels generally increase post explantation. This study investigated the safety and feasibility of early DJBL reimplantation in five patients with obesity whose glucose levels had relapsed post explantation, examining the effect of reimplantation on weight loss, BMI and T2DM management. All DJBL implantation and explantation procedures were performed without complications. Despite reduction of T2DM medications, reduction in body weight and HbA1c levels resumed after reimplantation. In conclusion, early reimplantation of DJBL appears feasible, safe and effective.

Neudesin in obesity and type 2 diabetes mellitus: the effect of acute fasting and weight reducing interventions.

ContextNeudesin has recently been identified as a novel regulator of energy expenditure in experimental animals; however, its role in humans remains unexplored.ObjectiveThe aim of this study was to assess the effects of obesity and type 2 diabetes mellitus (T2DM) along with selected weight reducing interventions on serum neudesin levels and adipose tissue mRNA expression.Patients and methodsFifteen obese subjects with T2DM undergoing endoscopic duodenal-jejunal bypass liner (DJBL) implantation, 17 obese subjects (11 with T2DM, 6 without T2DM) scheduled for gastric plication (GP), 15 subjects with functional hypoglycemia subjected to 72-hour acute fasting (AF), and 12 healthy controls were included in the study.ResultsBaseline neudesin levels were comparable between all groups. DJBL increased neudesin at 6 and 10 months after the procedure (1.77±0.86 vs 2.28±1.27 vs 2.13±1.02 ng/mL, P=0.001 for baseline vs 6 vs 10 months) along with reduction in body weight and improvement of HbA1c without any effect on neudesin mRNA expression in subcutaneous adipose tissue. Conversely, GP did not affect neudesin levels despite marked reduction in body weight and improvement of HbA1c. In contrast, AF decreased neudesin levels during the entire period (1.74±0.54 vs 1.46±0.48 ng/mL, P=0.001 for baseline vs 72 hours) with no impact of subsequent re-alimentation on neudesin concentrations.ConclusionNeudesin levels are differentially regulated during AF and chronic weight reduction induced by DJBL or GP. Further studies are needed to assess its possible significance in energy homeostasis regulation in humans.

Metabolic improvement in obese patients after duodenal-jejunal exclusion is associated with intestinal microbiota composition changes.

Intestinal microbiota have been suggested to play an important role in the pathogenesis of obesity and type 2 diabetes. Bariatric surgery improves both conditions and has been associated with changes in intestinal microbiota composition. We investigated the effect of a nonsurgical bariatric technique on intestinal microbiota composition in relation to metabolic improvement. Seventeen patients with obesity and type 2 diabetes were treated with the nonsurgical duodenal-jejunal bypass liner, which excludes the proximal 60 cm small intestine from food. Fecal samples as well as metabolic parameters reflecting obesity and type 2 diabetes were obtained from the patients at baseline, after 6 months with the device in situ, and 6 months after explantation. After 6 months of treatment, both obesity and type 2 diabetes had improved with a decrease in weight from 106.1 [99.4-123.5] to 97.4 [89.4-114.0] kg and a decrease in HbA1c from 8.5% [7.6-9.2] to 7.2% [6.3-8.1] (both p < 0.05). This was paralleled by an increased abundance of typical small intestinal bacteria such as Proteobacteria, Veillonella, and Lactobacillus spp. in feces. After removal of the duodenal-jejunal bypass liner, fecal microbiota composition was similar to that observed at baseline, despite persistent weight loss. Improvement of obesity and type 2 diabetes after exclusion of the proximal 60 cm small intestine by treatment with a nonsurgical duodenal-jejunal bypass liner may be promoted by changes in fecal microbiota composition.

Duodenal-jejunal lining increases postprandial unconjugated bile acid responses and disrupts the bile acid-FXR-FGF19 axis in humans

Background and AimsPlacement of the duodenal-jejunal bypass liner (DJBL) leads to rapid weight loss and restoration of insulin sensitivity in a similar fashion to bariatric surgery. Increased systemic bile acid levels are candidate effectors for these effects through postprandial activation of their receptors TGR5 and FXR. We aimed to quantify postprandial bile acid, GLP-1 and FGF19 responses and assess their temporal relation to the weight loss and metabolic and hormonal changes seen after DJBL placement. MethodsWe performed mixed meal testing in 17 obese patients with type 2 diabetes mellitus (DM2) directly before, one week after and 6 months after DJBL placement. ResultsBoth fasting and postprandial bile acid levels were unchanged at 1 week after implantation, and greatly increased 6 months after implantation. The increase consisted of unconjugated bile acid species. 3 hour-postprandial GLP-1 levels increased after 1 week and were sustained, whereas FGF19 levels and postprandial plasma courses were unaffected. ConclusionsDJBL placement leads to profound increases in unconjugated bile acid levels after 6 months, similar to the effects of bariatric surgery. The temporal dissociation between the changes in bile acids, GLP-1 and FGF19 and other gut hormone responses warrant caution about the beneficial role of bile acids after DJBL placement. This observational uncontrolled study emphasizes the need for future controlled studies.

Effect of the EndoBarrier Device: a 4-Year Follow-up of a Multicenter Randomized Clinical Trial.

To evaluate the long-term effect of the duodenal-jejunal bypass liner (DJBL) on weight loss and glycemic control. Data on the long-term effect of DJBL treatment is still missing. From 2010 to 2012, 29 patients were treated with the DJBL at center A and center B, as part of a multicenter randomized controlled trial. Prior to implantation and after removal of the DJBL, all patients underwent standardized physical examination and blood sampling. Four years after removal of the DJBL, included patients underwent standardized physical examination and blood sampling as previously performed during the initial study. Out of the 29 patients, 15 patients were eligible for follow-up with a median duration of 42months. Five patients had successfully received additional bariatric surgery. Four years after explantation of the DJBL, median weight in these 15 patients was 102.0kg (IQR 94.0-124.6), which was not statistically significantly different from the 106.1kg at baseline (IQR 99.0-128.4). Median BMI changed from 33.1kg/m2 (IQR 32.3-38.5) at baseline to 33.7kg/m2 (IQR 31.2-36.9) after follow-up. Patients had a TWL of 2.2% (IQR - 1.3-5.6) compared to baseline weight. None of the parameters were significantly different after follow-up compared to baseline. The effect of weight reduction of initial DJBL treatment seems to be diminished after 4years of follow-up. However, larger prospective studies with long-term follow-up need to be conducted in the future.

Influence of Duodenal–Jejunal Implantation on Glucose Dynamics: A Pilot Study Using Different Nonlinear Methods

Diabetes is a disease of great and rising prevalence, with the obesity epidemic being a significant contributing risk factor. Duodenal–jejunal bypass liner (DJBL) is a reversible implant that mimics the effects of more aggressive surgical procedures, such as gastric bypass, to induce weight loss. We hypothesized that DJBL also influences the glucose dynamics in type II diabetes, based on the induced changes already demonstrated in other physiological characteristics and parameters. In order to assess the validity of this assumption, we conducted a quantitative analysis based on several nonlinear algorithms (Lempel–Ziv Complexity, Sample Entropy, Permutation Entropy, and modified Permutation Entropy), well suited to the characterization of biomedical time series. We applied them to glucose records drawn from two extreme cases available of DJBL implantation: before and after 10 months. The results confirmed the hypothesis and an accuracy of 86.4% was achieved with modified Permutation Entropy. Other metrics also yielded significant classification accuracy results, all above 70%, provided a suitable parameter configuration was chosen. With the Leave–One–Out method, the results were very similar, between 72% and 82% classification accuracy. There was also a decrease in entropy of glycaemia records during the time interval studied. These findings provide a solid foundation to assess how glucose metabolism may be influenced by DJBL implantation and opens a new line of research in this field.

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.

IntroductionA 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.MethodsThis 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 outcomeThis 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 registrationNCT02769728, Registered 12 May 2016. Current Protocol Date/Version: 04 September 2017/Version 1.9.

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.

Long-term effects of proximal small bowel exclusion by duodenal-jejunal bypass liner on weight reduction and glycemic control in diabetic patients

BackgroundExclusion of the proximal gut from nutrient absorption entails significant metabolic benefits. The duodenal-jejunal bypass liner (DJBL) is the first endoscopic device that excludes the first part of the gut by covering it. ObjectivesTo assess weight and glycemic control at the end of treatment and after 1 year of follow-up. SettingBariatric endoscopy service in a tertiary medical center. MethodsDiabetic patients were treated with DJBL and followed prospectively between 2013 and 2016. Data were collected during scheduled visits. ResultsOut of 51 patients treated, 39 completed at least 9 months with the device. Complications were recorded for the entire cohort. Percent of total weight loss was 15.05% ± 6.0% after 12 months of treatment (P < .001 versus baseline). Twelve months postretrieval, percent of total weight loss decreased to 8.75% ± 5.07% (P < .001 versus baseline). Patients with baseline body mass index ≥35 kg/m2 experienced greater percent total weight loss changes over time (P < .001). There was a significant effect on hemoglobin A1C levels over time (P = .003), and the nadir was reached at 9 months of treatment (median 6.05% versus 7.20% at baseline, P < .001). Insulin users had consistently higher median hemoglobin A1C values compared with insulin nonusers (P < .001). Adverse events were experienced by 12 of 51 patients (23.5%), of which 4 cases (7.8%) were severe. ConclusionsProximal bowel bypass by DJBL is an effective tool for weight reduction and glycemic control. Metabolic achievements are partially preserved at 1 year after device removal. Because DJBL entails a considerable rate of side effects, strategies to mitigate them are warranted.

Design of the Weight-loss Endoscopy Trial (WET): a multi-center, randomized, controlled trial comparing weight loss in endoscopically implanted duodenal-jejunal bypass liners vs. intragastric balloons vs. a sham procedure

BackgroundObesity is a global problem leading to reduced life expectancy, cardiovascular diseases, diabetes and many types of cancer. Even people willing to accept treatment only achieve a mean weight loss of about 5 kg using commercial weight loss programs. Surgical interventions, e.g. sleeve gastrectomy or gastric bypass are effective but accompanied by risk of serious complications and side effects. Less invasive endoscopic procedures mainly comprise the intragastric balloon (IB) and the duodenal-jejunal bypass liner (DJBL). To date, a randomized comparison between these devices has not been undertaken or shown to be superior to a sham procedure.MethodsWe designed a multi-center, randomized, patient and assessor-blinded, controlled trial comparing weight loss in endoscopically implanted IB vs. DJBL vs. a sham procedure. A total of 150 patients with a BMI > 35 kg/m2 or > 30 with obesity-related comorbidities and indication for proton pump inhibitors are randomized to receive either IB, DJBL or a sham gastroscopy (2:2:1 ratio). All participants undergo regular dietary consultation. The IB will be removed after 6 months, whereas the DJBL will be explanted after 12 months. All patients will receive gastroscopies at implantation and explantation of the devices or sedation without gastroscopy to maintain blinding. Main exclusion criteria are malignant diseases, peptic ulcer or previous bariatric intervention. Weight loss 12 months after explantation of the devices, changes in comorbidities, quality of life, complication rates and safety will be evaluated.DiscussionThis trial could help to identify the most effective and safest endoscopic device, thus determining the new standard procedure for endoscopic bariatric treatment.Trial registration16th January 2017. DRKS00011036. Funded by the German Research Foundation (DFG).