Maximising the health benefits gained from bariatric surgery

Background Bariatric surgery is the only effective treatment for patients with severe obesity, producing sustained weight-loss, amelioration of obesity-associated co-morbidities, reduced mortality and economic savings. In the UK ~1.5 million people fulfill the National Institute for Health and Care Excellence bariatric surgery eligibility criteria. However, in 2013 Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG), the most common bariatric procedures undertaken, produce comparable weight-loss and resolution of co-morbidities, with ~60% of T2D patients being in 'remission' 2 years post-surgery. However, at an individual level, post-surgery health benefits, in terms of weight-loss and improvement in obesity-associated co-morbidities, are highly variable. Up to 20% of patients derive little post-operative clinical benefit in the long-term. RYGB and SG are different anatomically and differentially alter circulating gut hormones, key regulators of energy homeostasis. However, there are no criteria to determine whether a patient would derive most benefit from RYGB or SG. Given the severely limited access to bariatric surgery the key question that needs to be addressed is 'How do we maximize the health benefits obtained from bariatric surgery?' I am ideally placed to address this question. My research is at the forefront of international research efforts focused on understanding how bariatric surgery mediates its beneficial effects. Using experimental medicine approaches, my work has identified gut hormones as key regulators of energy homeostasis. I lead the University College London Hospitals (UCLH) Bariatric Centre for Weight Management and Metabolic Surgery, one of the largest UK bariatric centres with an embedded translational research programme. My new data suggest that post-operative health outcomes can be improved by utilizing genetics to optimize bariatric procedure selection and by implementation of post-operative strategies. Aims My overall aim is to maximize the health benefits obtained from bariatric surgery by utilizing the following inter-related strategies: Genotype-based bariatric procedure selection. Implementation of an early post-operative exercise-behavioural programme. Post-operative pharmacological interventions tailored to the patients' post-operative biology. Establishment of a bariatric biobank to facilitate reverse translational studies to gain further mechanistic insights into the variability in response to surgery. Plan of investigation in order to achieve my aims 1) Establish a multi-disciplinary obesity clinical trials team, within a research framework that integrates patient/public involvement, to allow effective translation of my research findings into clinical practice. 2) Undertake a randomized-controlled trial to evaluate whether an early post-operative exercise-behavioural intervention improves post-operative weight-loss, metabolic outcomes and functional activity. 3) Establish a bariatric biobank (serum, DNA and tissues obtained at the time of surgery, including gut, liver, subcutaneous and visceral fat and muscle) to facilitate reverse translation. 4) Determine whether allocation of surgical procedure (RYGB or SG) based upon the FTO-linked SNP rs9939609 improves post-surgical weight loss and metabolic outcomes by undertaking a randomized trial. 5) Investigate whether 'poor' post-operative weight-loss response can be improved using personalized pharmaceutical interventions tailored to the patients' post-surgery biology. 6) Collaborate with and attract other investigators to translational obesity research to complement existing research in this focus area and establish inter-institutional translational research networks. Benefits This project will bring immediate benefits to patients and the NHS by identifying strategies that maximize the health benefits obtained from bariatric surgery. By establishing a multi-disciplinary obesity translational research team, together with mechanisms for training these individuals in a range of obesity research methods, I will increase capacity for the delivery of broad ranging obesity research within the UK. This will benefit patients and the NHS by allowing the effective translation of research findings into clinical practice, bringing health benefits to patients and reducing the health burden of obesity.