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
File(s)
Author(s)
Ruban, Aruchuna
Type
Thesis or dissertation
Abstract
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.
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.
Version
Open Access
Date Issued
2019-10
Online Publication Date
2021-05-30T23:01:15Z
2021-08-17T13:49:03Z
Date Awarded
2019-12
Copyright Statement
Creative Commons Attribution NonCommercial Licence
Advisor
Teare, Julian
Ashrafian, Hutan
Li, Jia
Sponsor
National Institute for Health Research
Publisher Department
Department of Surgery & Cancer
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)