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Title: The role of gut hormones in mediating the beneficial effects of RYGB on glycaemia and energy balance
Author: Behary, Preeshila
ISNI:       0000 0004 7232 707X
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2018
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Obesity and type 2 diabetes are both on the rise. Bariatric surgery is currently the most efficient treatment for obesity. Early weight-loss-independent improvement in glycaemia and longer-term ‘remission’ of type 2 diabetes are typically observed post-RYGB. The Gut hormones, GLP-1, OXM and PYY (GOP), are augmented post-prandially after RYGB. They are anorectic and have the potential to enhance beta cell function and increase energy expenditure. We hypothesized that the elevation in GOP levels, mediate the beneficial metabolic effects of RYGB. GOP infused subcutaneously at combined doses of 4/4/0.4 pmol/kg/min, successfully, replicated the peak post-prandial circulating levels of the individual hormone post-RYGB. Subsequently, GOP at 4/4/0.4 pmol/kg/min was infused chronically for 28 days in obese volunteers with type 2 diabetes, in a randomised single-blinded placebo-controlled study. Effects of GOP on Energy Intake (EI), Appetite ratings, Energy Expenditure, Anthropometrics and Glycaemia were assessed and compared to the effects of RYGB on similar parameters. Both an acute and chronic GOP infusion led to a significant reduction in EI, comparable to the effect of RYGB. A similar enhancement in satiety and decrease in ‘prospective food intake’ were observed following GOP and RYGB. However, only RYGB volunteers displayed a significant increase in Diet-induced-Thermogenesis. Weight loss was superior following RYGB compared to GOP at a similar time-frame. Nonetheless, a comparable and significant improvement in Fructosamine, HbA1c, Fasting and Post-prandial Glucose, was generated following both interventions at 4 weeks. Enhancement in beta cell function and insulin sensitivity appeared to be important. In summary, the gut hormones - GOP, are the likely candidates mediating 1) the reduction in EI post-RYGB by promoting satiety and contributing to weight loss 2) the improvement in glycaemia, early after surgery, irrespective of weight loss. Other mechanisms appear to be responsible for the increase in EE and the majority of weight loss, post-RYGB.
Supervisor: Tan, Tricia ; Bloom, Steve ; Dhillo, Waljit Sponsor: Medical Research Council
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral