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Duodenal-Jejunal Bypass Liner for the management of Type 2 Diabetes Mellitus and Obesity: A Multicenter Randomized Controlled Trial.
Ruban, A, Miras, AD, Glaysher, MA, Goldstone, AP, Prechtl, CG, Johnson, N, Chhina, N, Al-Najim, W, Aldhwayan, M, Klimowska-Nassar, N, et al
Annals of surgery. 2022;(3):440-447
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Abstract
OBJECTIVE The aim of this study was to examine the clinical efficacy and safety of the duodenal-jejunal bypass liner (DJBL) while in situ for 12 months and for 12 months after explantation. SUMMARY BACKGROUND DATA This is the largest randomized controlled trial (RCT) of the DJBL, a medical device used for the treatment of people with type 2 diabetes mellitus (T2DM) and obesity. Endoscopic interventions have been developed as potential alternatives to those not eligible or fearful of the risks of metabolic surgery. METHODS In this multicenter open-label RCT, 170 adults with inadequately controlled T2DM and obesity were randomized to intensive medical care with or without the DJBL. Primary outcome was the percentage of participants achieving a glycated hemoglobin reduction of ≥20% at 12 months. Secondary outcomes included weight loss and cardiometabolic risk factors at 12 and 24 months. RESULTS There were no significant differences in the percentage of patients achieving the primary outcome between both groups at 12 months [DJBL 54.6% (n = 30) vs control 55.2% (n = 32); odds ratio (OR) 0.93, 95% confidence interval (CI): 0.44-2.0; P = 0.85]. Twenty-four percent (n = 16) patients achieved ≥15% weight loss in the DJBL group compared to 4% (n = 2) in the controls at 12 months (OR 8.3, 95% CI: 1.8-39; P = .007). The DJBL group experienced superior reductions in systolic blood pressure, serum cholesterol, and alanine transaminase at 12 months. There were more adverse events in the DJBL group. CONCLUSIONS The addition of the DJBL to intensive medical care was associated with superior weight loss, improvements in cardiometabolic risk factors, and fatty liver disease markers, but not glycemia, only while the device was in situ. The benefits of the devices need to be balanced against the higher rate of adverse events when making clinical decisions. TRIAL REGISTRATION ISRCTN30845205. isrctn.org; Efficacy and Mechanism Evaluation Programme, a Medical Research Council and National Institute for Health Research (NIHR) partnership reference 12/10/04.
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The effect of a duodenal-jejunal bypass liner on lipid profile and blood concentrations of long chain polyunsaturated fatty acids.
Glaysher, MA, Ward, J, Aldhwayan, M, Ruban, A, Prechtl, CG, Fisk, HL, Chhina, N, Al-Najim, W, Smith, C, Klimowska-Nassar, N, et al
Clinical nutrition (Edinburgh, Scotland). 2021;(4):2343-2354
Abstract
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.
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Type 2 diabetes is associated with impaired jejunal enteroendocrine GLP-1 cell lineage in human obesity.
Osinski, C, Le Gléau, L, Poitou, C, de Toro-Martin, J, Genser, L, Fradet, M, Soula, HA, Leturque, A, Blugeon, C, Jourdren, L, et al
International journal of obesity (2005). 2021;(1):170-183
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Abstract
OBJECTIVES Altered enteroendocrine cell (EEC) function in obesity and type 2 diabetes is not fully understood. Understanding the transcriptional program that controls EEC differentiation is important because some EEC types harbor significant therapeutic potential for type 2 diabetes. METHODS EEC isolation from jejunum of obese individuals with (ObD) or without (Ob) type 2 diabetes was obtained with a new method of cell sorting. EEC transcriptional profiles were established by RNA-sequencing in a first group of 14 Ob and 13 ObD individuals. EEC lineage and densities were studied in the jejunum of a second independent group of 37 Ob, 21 ObD and 22 non obese (NOb) individuals. RESULTS The RNA seq analysis revealed a distinctive transcriptomic signature and a decreased differentiation program in isolated EEC from ObD compared to Ob individuals. In the second independent group of ObD, Ob and NOb individuals a decreased GLP-1 cell lineage and GLP-1 maturation from proglucagon, were observed in ObD compared to Ob individuals. Furthermore, jejunal density of GLP-1-positive cells was significantly reduced in ObD compared to Ob individuals. CONCLUSIONS These results highlight that the transcriptomic signature of EEC discriminate obese subjects according to their diabetic status. Furthermore, type 2 diabetes is associated with reduced GLP-1 cell differentiation and proglucagon maturation leading to low GLP-1-cell density in human obesity. These mechanisms could account for the decrease plasma GLP-1 observed in metabolic diseases.
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In Search of the Optimal Reconstruction Method after Total Gastrectomy. Is Roux-en-Y the Best? A Review of the Randomized Clinical Trials.
Naum, C, Bîrlă, R, Marica, DC, Constantinoiu, S
Chirurgia (Bucharest, Romania : 1990). 2020;(1):12-22
Abstract
Background: Numerous procedures for reconstruction after total gastrectomy have been proposed in order to achieve the lowest postoperative morbidity. Roux-en-Y esojejunostomy is widely accepted as a standard reconstruction technique due to its simplicity and its satisfactory nutritional outcomes. The construction of a gastric pouch and the maintenance of the duodenal transit have been proposed to ameliorate the quality of life of patients with gastric cancer. The aim of this study is to assess the quality of life of patients with different types of reconstruction after total gastrectomy. Material and Method: A systematic literature search was performed in PubMed, Science Direct, Wiley Online, Springer Link, up to December 1, 2019. Only original articles published in English were included. Quality of life was measured using different instruments. Postoperative aspects of reflux oesophagitis, dumping syndrome, food intake and weight status were evaluated. Results: 15 studies were included in this research. Three techniques for restoring the digestive tract continuity were compared: Roux-en-Y eso-jejunostomy, jejunal interposition and gastric pouch construction. The statistical results of the included studies were evaluated in terms of quality of life or weight status. Conclusions: The length of the alimentary limb for prophylaxis of eso-jejunal reflux should be at least 50 cm, but not more than 60 cm for the prevention of malabsorption. The quality of life was significantly better in patients with gastric pouch. Maintaining the duodenal transit does not seem to bring any benefit in quality of life or weight status, even if this is a physiological way.
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Efficacy and Safety of the Duodeno-Jejunal Bypass Liner in Patients With Metabolic Syndrome: A Multicenter Randomized Controlled Trial (ENDOMETAB).
Caiazzo, R, Branche, J, Raverdy, V, Czernichow, S, Carette, C, Robert, M, Disse, E, Barthet, M, Cariou, B, Msika, S, et al
Annals of surgery. 2020;(5):696-702
Abstract
OBJECTIVE The aim of this study was to compare the efficacy and safety of 12-month implantation of a duodeno-jejunal bypass liner (DJBL) with conventional medical care in patients with metabolic syndrome (MS). SUMMARY BACKGROUND DATA DJBL is an endoscopic device for treating obesity and related disorders. The persistence of favorable results after 6 months has not been tested in a controlled study. METHODS We conducted a multicenter randomized controlled trial, stratified by center and diabetes status. The primary endpoint was the remission of MS at 12 months. The secondary endpoints included body mass index (BMI), glucose control, blood pressure, and lipids, assessed at 12 months after implantation, and again, at 12 months after the removal of the DJBL. Up to 174 subjects were planned to be randomized into either the DJBL or the control arm at a 2:1 ratio, respectively. Study enrollment was discontinued by the Scientific Monitoring Committee due to the early termination of the ENDO trial (NCT01728116) by the US Food and Drug Administration. The study was terminated after withdrawal of the device's European Conformity marking by the European Medicines Agency, and an interim analysis was performed. RESULTS A total of 82 patients were enrolled (67.5% female, 48.8% with diabetes). At 12 months after randomization, the primary endpoint was met in 6 (12%) DJBL patients and 3 (10%) controls (P = 0.72). Patients in the DJBL group experienced greater BMI loss [mean adjusted difference (95% confidence interval, CI) -3.1 kg/m (-4.4 to -1.9) kg/m, P < 0.001] and HbA1c change [mean adjusted difference -0.5% (95% CI -0.9 to -0.2); P < 0.001] than those in the control group. No difference remained statistically significant at 12 months after the removal of the DJBL. In the DJBL group, 39% of patients experienced at least one device-related serious adverse event, which was classified as Grade III Dindo-Clavien in 22%, and required premature device explantation in 16%. CONCLUSIONS The present study showed a transient clinical benefit of DJBL, which was only apparent at 1 year, when the device was still in situ, and was obtained at the risk of serious device-related adverse events in 39% of patients. These results do not support the routine use of DJBL for weight loss and glucose control in patients with MS.
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Manometric demonstration of duodenal/jejunal motor function consistent with the duodenal brake mechanism.
Dent, J, Deloose, E, Dinning, P, Corsetti, M, Rommel, N, Tack, J, Wiklendt, L, Papageorgiou, AW, Arkwright, JW
Neurogastroenterology and motility. 2020;(10):e13835
Abstract
BACKGROUND High-resolution manometric studies below the stomach are rare due to technical limitations of traditional manometry catheters. Consequently, specific motor patterns and their impact on gastric and small bowel function are not well understood. High-resolution manometry was used to record fed-state motor patterns in the antro-jejunal segment and relate these to fasting motor function. METHODS Antro-jejunal pressures were monitored in 15 healthy females using fiber-optic manometry (72 sensors at 1 cm intervals) before and after a high-nutrient drink. KEY RESULTS Postprandial motility showed a previously unreported transition point 18.8 cm (range 13-28 cm) beyond the antro-pyloric junction. Distal to the transition, a zone of non-propagating, repetitive pressure events (11.5 ± 0.5 cpm) were dominant in the fed state. We have named this activity, the duodeno-jejunal complex (DJC). Continuous DJC activity predominated, but nine subjects also exhibited intermittent clusters of DJC activity, 7.4 ± 4.9/h, lasting 1.4 ± 0.55 minutes, and 3.8 ± 1.2 minutes apart. DJC activity was less prevalent during fasting (3.6 ± 3.3/h; P = .04). 78% of fed and fasting state propagating antro-duodenal pressure events terminated proximally or at the transition point and were closely associated with DJC clusters. CONCLUSIONS AND INFERENCES High-resolution duodeno-jejunal manometry revealed a previously unrecognized transition point and associated motor pattern extending into the jejunum, consistent with the duodenal brake previously identified fluoroscopically. Timing suggests DJC activity is driven by chyme stimulating duodenal mucosal chemosensors. These findings indicate that the duodenum and proximal jejunum consists of two major functional motor regions.
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Is Early Reimplantation of the Duodenal-Jejunal Bypass Liner Viable?
Leventi, E, Günthert, SJ, Stier, C, Staikov, P, Stein, J, Farrag, K
Obesity surgery. 2019;(5):1690-1693
Abstract
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.
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The Regional-Specific Relative and Absolute Expression of Gut Transporters in Adult Caucasians: A Meta-Analysis.
Harwood, MD, Zhang, M, Pathak, SM, Neuhoff, S
Drug metabolism and disposition: the biological fate of chemicals. 2019;(8):854-864
Abstract
The aim of this study was to derive region-specific transporter expression data suitable for in vitro-to-in vivo extrapolation (IVIVE) within a physiologically based pharmacokinetic (PBPK) modeling framework. A meta-analysis was performed whereby literary sources reporting region-specific transporter expression obtained via absolute and relative quantification approaches were considered in healthy adult Caucasian individuals. Furthermore, intestinal total membrane protein yield was calculated to enable mechanistic IVIVE via absolute transporter abundances. Where required, authors were contacted for additional information. A refined database was constructed where samples were excluded based on quantification in, non-Caucasian subjects, disease tissue, subjects <18 years old, duplicated samples, non-total membrane matrix, pooled matrices, or cDNA. Demographic data were collected where available. The weighted and geometric mean, coefficient of variation, and between-study homogeneity was calculated in each of eight gut segments (duodenum, two jejunum, four ileum, and colon) for 16 transporters. Expression data were normalized to that in the proximal jejunum. From a total of 47 articles, the final database consisted of 2238 measurements for 16 transporters. The solute carrier peptide transporter 1 (PepT1) showed the highest jejunal abundance, while multidrug resistance-associated protein (MRP) 2 was the highest abundance ATP-binding cassette transporter. Transporters displaying significant region-specific expression included the ileal bile acid transporter, which showed 18-fold greater terminal ileum expression compared with the proximal jejunum, while MRP3, organic cation transporter type 1 (OCTN1), and OCT1 showed >2-fold higher expression in other regions compared with the proximal jejunum. This is the first systematic analysis incorporating absolute quantification methodology to determine region-specific intestinal transporter expression. It is expected to be beneficial for mechanistic transporter IVIVE in healthy adult Caucasians. SIGNIFICANCE STATEMENT Given the burgeoning reports of absolute transporter abundances in the human intestine, the incorporation of such information into mechanistic IVIVE-PBPK models could offer a distinct advantage in facilitating the robust assessment of the impact of gut transporters on drug disposition. The systematic and formal assessment via a literature meta-analysis described herein, enables assignment of the regional-specific expression, absolute transporter abundances, interindividual variability, and other associated scaling factors to healthy Caucasian populations within PBPK models. The resulting values are available to incorporate into PBPK models, and offer a verifiable account describing intestinal transporter expression within PBPK models for persons wishing to utilize them. Furthermore, these data facilitate the development of appropriate IVIVE scaling strategies using absolute transporter abundances.
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Roux-en-Y or Billroth II Reconstruction After Radical Distal Gastrectomy for Gastric Cancer: A Multicenter Randomized Controlled Trial.
So, JB, Rao, J, Wong, AS, Chan, YH, Pang, NQ, Tay, AYL, Yung, MY, Su, Z, Phua, JNS, Shabbir, A, et al
Annals of surgery. 2018;(2):236-242
Abstract
OBJECTIVE The aim of the study was to compare the clinical symptoms between Billroth II (B-II) and Roux-en-Y (R-Y) reconstruction after distal subtotal gastrectomy (DG) for gastric cancer. BACKGROUND Surgery is the mainstay of curative treatment for gastric cancer. The technique for reconstruction after DG remains controversial. Both B-II and R-Y are popular methods. METHODS This is a prospective multicenter randomized controlled trial. From October 2008 to October 2014, 162 patients who underwent DG were randomly allocated to B-II (n = 81) and R-Y (n = 81) groups. The primary endpoint is Gastrointestinal (GI) Symptoms Score 1 year after surgery. We also compared the nutritional status, extent of gastritis on endoscopy, and quality of life after surgery between the 2 procedures at 1 year. RESULTS Operative time was significantly shorter for B-II than for R-Y [mean difference 21.5 minutes, 95% confidence interval (95% CI) 3.8-39.3, P = 0.019]. The B-II and R-Y groups had a peri-operative morbidity of 28.4% and 33.8%, respectively (P = 0.500) and a 30-day mortality of 2.5% and 1.2%, respectively (P = 0.500). GI symptoms score did not differ between R-Y versus B-II reconstruction (mean difference -0.45, 95% CI -1.21 to 0.31, P = 0.232). R-Y resulted in a lower median endoscopic grade for gastritis versus B-II (mean difference -1.32, 95% CI -1.67 to -0.98, P < 0.001). We noted no difference in nutritional status (R-Y versus B-II mean difference -0.31, 95% CI -3.27 to 2.65, P = 0.837) and quality of life at 1 year between the 2 groups too. CONCLUSION Although BII is associated with a higher incidence of heartburn symptom and higher median endoscopic grade for gastritis, BII and RY are similar in terms of overall GI symptom score and nutritional status at 1 year after distal gastrectomy.
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Comparative efficacy and safety of the duodenal-jejunal bypass liner in obese patients with type 2 diabetes mellitus: A case control study.
Laubner, K, Riedel, N, Fink, K, Holl, RW, Welp, R, Kempe, HP, Lautenbach, A, Schlensak, M, Stengel, R, Eberl, T, et al
Diabetes, obesity & metabolism. 2018;(8):1868-1877
Abstract
AIMS: The duodenal-jejunal bypass liner (DJBL) is an endoscopic device mimicking surgical duodenal-jejunal bypass, and is indicated for the treatment of obesity-associated type 2 diabetes mellitus. This analysis was conducted to evaluate the efficacy and safety of the DJBL in comparison to lifestyle changes and antidiabetic drugs. MATERIALS AND METHODS To determine the efficacy and long-term safety of the DJBL, data concerning 235 obese patients with type 2 diabetes mellitus from the German DJBL registry were analysed. For comparison with standard treatment, propensity-score-matching with patients from the German DPV registry, including the matching parameters sex, age, diabetes duration, baseline BMI and baseline HbA1c, was applied. The final matched cohort consisted of 111 patients in the DJBL group and 222 matched control DPV patients. RESULTS Mean treatment time with the DJBL was 47.5 ± 12.2 weeks, mean BMI reduction was 5.0 kg/m2 (P < .001) and mean HbA1c reduction was 1.3% (11.9 mmol/mol) (P < .001). Reduction of antidiabetic medications and improvements in other metabolic and cardiovascular risk parameters was observed. In comparison to the matched control group, mean reductions in HbA1c (-1.37% vs -0.51% [12.6 vs 3.2 mmol/mol]; P < .0001) and BMI (-3.02 kg/m2 vs -0.39 kg/m2 ; P < .0001) were significantly higher. Total cholesterol, LDL cholesterol and blood pressure were also significantly better. CONCLUSION This study provides the largest, so far, hypothesis-generating evidence for a putative positive risk/benefit ratio for treatment of obese patients with type 2 diabetes mellitus with the DJBL as an alternative treatment option for this patient population.