Obesity and type 2 diabetes are major causes of illness and premature death worldwide and their incidence is increasing rapidly. Bariatric surgery is considered as the "gold-standard" surgical treatment for both conditions. However, not all patients do equally well after surgery and indeed the weight loss experienced by patients undergoing bariatric surgery can vary. As such when patients are seen after bariatric surgery in clinic they fall in one of the following two categories: 1. Good responders: this is the majority of patients who lose the expected amount of weight based on the published studies. 2. Poor responders: this is a small group of patients who either lose less than the expected amount of weight after bariatric surgery or lose the expected amounts of weight early after surgery but then regain a substantial proportion of the weight they have lost. The so-called "poor responders" are exposed to all the risks of the operation and do not benefit from the weight loss as much as good responders. This study would therefore like to investigate the physiological factors that distinguish poor from good responders before, and after bariatric surgery. The study team hypothesizes that compared to good responders, poor responders exhibit: 1. a smaller degree of fullness sensation after a meal, 2. a lower energy expenditure after a meal, and 3. genetic changes (single nucleotide polymorphisms) that predispose the poor responder to development of obesity. In addition, the study team hypothesizes that poor responders exhibit: 1. lower gut hormone secretion after a meal and 2. are less sensitive to the physiological action of gut hormones compared to good responders and that this difference in gut hormone secretion and response to gut hormones prior to bariatric surgery can be helpful to predict response to bariatric surgery.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
SINGLE
Enrollment
220
Their first visit will act as an acclimatisation visit and participants will be infused subcutaneously with a triple gut hormone infusion (GLP-1, PYY and OXM). This will not only allow us to acclimatise the study volunteer to the study visits, but also allow us to test for subject tolerability of the gut hormones. For the next two visits participants will be randomised in a single-blinded fashion to a subcutaneous infusion of either: 1. 0.9% saline, 2. GLP-1
Imperial College London
London, United Kingdom
RECRUITINGGut hormone secretion study: Peak plasma level of gut hormones after meal ingestion
A standardized mixed-meal tolerance test. Blood samples will be taken at intervals over four hours. These will be analysed for gut hormones.
Time frame: During one study visit (Mixed Meal Test), at least 1 year post-surgery.
Gut hormone sensitivity study: Change in Food intake following gut hormone infusion compared to placebo.
Ad libitum meal test. A meal will be served to participants and they will be allowed 20 minutes to eat until they feel comfortably full. Food intake will be measured at the end of the meal.
Time frame: During three study visits (gut hormone infusion visits), at least 1 year post-surgery.
Prospective assessment of gut hormone response pre and post-surgery: Change in Peak plasma level of gut hormones after meal ingestion.
A standardized mixed-meal tolerance test. Blood samples will be taken at intervals over four hours. These will be analysed for gut hormones.
Time frame: During two study visits (Mixed Meal Test), one before and one 1 year after surgery.
Change in Resting Energy Expenditure
Resting energy expenditure assessment via indirect calorimetry.
Time frame: Change between two visits: before and 1 year after bariatric surgery (Prospective assessment of gut hormone response pre and post-surgery).
Change in Diet Induced Thermogenesis
Diet induced thermogenesis assessment via indirect calorimetry.
Time frame: Change between two visits: before and 1 year after bariatric surgery (Prospective assessment of gut hormone response pre and post-surgery).
Change in Genetic factors
Change in genetic factors assessed by collection of plasma DNA samples.
Time frame: Change between two visits: Before and 1 year after bariatric surgery.
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