The role of an endoscopic duodenal jejunal exclusion device on the metabolic profile, glycaemic control and weight loss in Type II Diabetes: a multi centred randomised control trial

The incidence and prevalence of Obesity and T2DM is increasing at an alarming rate and now poses a global threat to mankind. Bariatric surgery is now an established strategy for combating both these conditions but recent years have also seen the emergence of endoscopic treatments designed to mimic the effects of surgery. These devices have the added advantage of being minimally invasive and easily reversible. The Endobarrier (EB) is an endoluminal duodenal-jejunal bypass liner (DJBL) licensed for up to 12 months of treatment in patients with type 2 diabetes who are obese. In this thesis I explored the feasibility and safety of this device as an effective method of weight loss and glycaemic control in the setting of nationally funded multicenter randomised control trial. This clinical trial compared the device implanted for 1 year versus standard medical therapy (control) in a cohort of 170 obese patients with type 2 diabetes. Body weight decreased by 10.85.3kg in the EB group and 12.17.8kg at 6 and 12 months respectively. In comparison the control group lost 6.35.5kg at 6 months and 6.2 6.4kg at 12 months (P=<0.001). Significant improvements in fasting insulin levels, total cholesterol and liver biochemistry were also seen between both patient cohorts. Plasma, urine and stool from participants were also analysed using nuclear magnetic resonance to identify key metabolic perturbations between both patient cohorts. The metabolite trimethylamine N-oxide (TMAO) which is associated with the development of diabetes was found to reduce in the plasma of Endobarrier patients. Microbial derived metabolites phenylacetylglycine and 3-indoxylsulfate were found in increasing amounts in the urine whilst a reduction in tricarboxylic acid cycle intermediates fumarate and malate were seen in the stool. The results of this study help in defining the current role of the DJBL in the treatment algorithm of patients with diabetes and obesity but also identifies some of the devices similarities to gastric bypass surgery. Crucially this research provides a possible insight into the mechanisms of how this device may elicit its effect which may include altering the gut microbiome, reducing levels of TMAO and increasing anaerobic energy metabolism.Open Acces

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

Duodenal-Jejunal bypass liner for the management of Type 2 Diabetes mellitus and obesity - a multicenter randomized controlled trial

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

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

Background &amp; 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/m 2 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 &lt; 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. </p