Effects and Mechanisms of Action of an Endoscopically Placed Duodenal-Jejunal Sleeve Device (Endobarrier) in Obese Patients with Type II Diabetes

INTERVENTION: 40 patients will be recruited for this study. All patients will have an Endobarrier device inserted. Endobarrier insertion occurs endoscopically by trained endoscopists and is fluoroscopically assisted for delivery to just below the pyloric sphincter where the device will settle and attach to the mucosa. The procedure takes approximately 45 minutes. Following recruitment the patients will be randomised to either have an Endobarrier device inserted immediately (20 patients‐Group “ETG‐0”) or to be treated with standard, conservative weight loss management. Those that did not immediately have a device inserted will be randomised again after 6 months. Half of these patients will then have a device inserted immediately (10 patients‐Group “ETG‐6”) or continue with standard conservative management for a total of 12 months before the device is inserted (10 patients‐ Group “ETG‐12”) . The Endobarrier device will be removed after a maximum insertion period of 12 months. CONDITION: Obesity Type 2 Diabetes Mellitus PRIMARY OUTCOME: Weight loss ‐ assessed via weight on digital scales at each appointment. SECONDARY OUTCOME: Cardiopulmonary reserve and exercise capacity measured by a 6 minute walk test ‐ composite outcome Fasting blood glucose measured by blood assay Intraluminal digestion of triglycerides measure by a 13C labeled mixed triglyceride breath test Liver function ‐ measured via blood tests measuring liver fibrosis markers e.g. hyaluronic acid and a liver function panel including GGT, AST, ALT. ; ; Liver function will also be assessed by fibroscan to determine fibrosis Psychological wellbeing measured using hospital anxiety and depression scale Quality of life as measured by the SF‐36 v2 Stool microbiome ‐ Community profiling will enable characterisation of the bacterial diversity of the gastric and duodenal mucosa‐associated microbiome. Microbial DNA extractions from snap‐frozen samples will be undertaken using previously established methods. Extracted DNA will be amplified using barcoded primer sets that target one of the hypervariable regions of the gene encoding 16S ribosomal RNA (rRNA). Sequencing of these PCR products will allow identification of microbes to a genus/species level. fasting insulin measured via blood assay mucosal microbiome ‐ Community profiling will enable characterisation of the bacterial diversity of the gastric and duodenal mucosa‐associated microbiome. Microbial DNA extractions from snap‐frozen samples will be undertaken using previously established methods. Extracted DNA will be amplified using barcoded primer sets that target one of the hypervariable regions of the gene encoding 16S ribosomal RNA (rRNA). Sequencing of these PCR products will allow identification of microbes to a genus/species level. INCLUSION CRITERIA: 1. Aged between 18 and 65 years. 2. Functional level equivalent to an ECOG score of 2 or less. 3. Obese – BMI over 35. 4. Type II diabetes mellitus on oral hypoglycaemic agents but not insulin. 5. English speaking. 6. Willing to participate in a 3 year trial and with capacity to consent.