Award Title: Maximising the health benefits gained from bariatric surgery
Funder: Department of Health and Social Care

Abstract: 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 2013Roux-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. BenefitsThis 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.

Lay Abstract: Aim of this research To improve the treatment of obesity by Ensuring that obesity surgery is delivered in the best way possible to improve the health of obese patients Gaining new knowledge about obesity by studying people having obesity surgery. BackgroundOne quarter of UK adults are obese having an unhealthy amount of body fat. Obese people die at a younger age and are more likely to have type 2 diabetes (high blood sugar levels), high blood pressure, heart attacks, strokes and cancer. The National Health Service (NHS) costs of treating obese people are about 17 billion a year. The causes of obesity are complex but we know that genetic make-up plays a role. Losing weight by dieting and exercise improves health but staying at a lower weight is difficult because the body's weight-control systems try to return weight back to the higher level. There are no drugs available in the UK to help people lose weight in the long-term. Obesity surgery is the only treatment that causes long-term weight-loss. This surgery reduces the risk of obese people dying making them healthier by improving and preventing many of the illnesses linked to obesity. For patients with type 2 diabetes, 6 out of every 10 can stop all of their diabetes drugs after surgery. The National Institute of Health and Care Excellence (NICE) decides which treatments the NHS will offer based on health benefits and cost. Using their rules around 1.5 million UK people could have obesity surgery. However, only 6,000 operations were carried out in 2013 due to limited access. Obesity surgery alters the path that food takes through the gut. We do not know exactly how the surgery works but we know that it 'resets' how bodyweight is controlled. I have shown that hormones from the gut control eating and blood sugar. Obesity surgery alters the levels of these hormones and this contributes to the beneficial effects of obesity surgery. Unfortunately, around 1 in 5 people do not respond well to obesity surgery in terms of improved health. Given that access to obesity surgery is limited and that surgery itself carries a risk, although very small, of dying we need to maximise the health benefits obtained from this limited resource. The main ways of achieving this are to target obesity surgery to patients who will benefit most, ensure that after surgery patients receive support to maximise the effects of surgery and collect samples and information from patients undergoing surgery to increase knowledge about obesity. My new research suggests that we can increase the health benefits obtained from surgery by Using a person's genetic make-up to select which type of surgery they should have.Helping patients increase their exercise levels after surgeryUsing new drugs in patients with a poor weight loss after surgery to correct their gut hormone levels. We now plan to test if these approaches improve weight loss and health outcomes by carrying out studies (clinical trials) in patients. Design and methods An expert team of health care professionals and scientists will carry out the following studies in obese patients. 1) Patients will be invited to take part in a clinical trial where we will study two types of obesity surgery and determine if the patients' genetic make-up influences the effects of surgery by comparing health outcomes after two years. 2) After surgery patients will be randomly assigned to either standard care, (being told to exercise more) or to participate in a supervised 12-week exercise programme. We will compare health comes in these two groups at 1 year after surgery. 3) In patients with poor weight-loss following surgery we will test if giving drugs to correct their hormone levels reduces their appetite and helps them lose weight. 4) Blood and tissue samples will be collected in patients having obesity surgery and used to learn more about obesity. The results of these studies will lead to changes in how obese patients having obesity surgery are cared for and will improve the health of people with obesity. Patient and public involvement Obese patients and patients who had undergone obesity surgery have been involved in designing these studies. Patients/public members will be part of our research team and will contribute to the final design, write patient information sheets and summaries of our findings. DisseminationWe will publicise our findings using presentations at local groups, national and international meetings, via the web and social media, in the press and on radio and television.

Research Activity Codes: 6.1 PHARMACEUTICALS;6.4 SURGERY
Health Categories: CANCER AND NEOPLASMS;CARDIOVASCULAR;METABOLIC AND ENDOCRINE;ORAL AND GASTROINTESTINAL;STROKE