Gut Hormones and Roux en Y Gastric Bypass

This study is designed to investigate whether chronic elevation of glucagon-like peptide-1 (GLP-1), oxyntomodulin and peptide YY (PYY) in combination is responsible for the majority of the metabolic effects of Roux-en-Y gastric bypass (RYGB) including improved glycaemia, increased energy expenditure, reduced food intake, weight loss, reduced preference for high calorie foods and reduced activation in brain reward areas in response to visual food cues.

Inclusion criteria

• Aged 18 - 70 years.
• Male or female.
• Eligible for bariatric surgery under the NHS.
• Diagnosed with impaired glucose regulation or type 2 diabetes, according to WHO 2011 criteria.
• Those with diabetes should be stable and well controlled with either diet or one oral hypoglycaemic agent.
• HbA1c ≤9.0% or 74.9 mmol/mol.

Exclusion criteria

• History of any medical, psychological or other condition, or use of any medications, including over-the-counter products, which, in the opinion of the investigators, would either interfere with the study or potentially cause harm to the volunteer.
• Without access at home to a telephone or other factor likely to interfere with ability to participate reliably in the study.
• Pregnancy or breastfeeding.
• Smokers.
• Unable to maintain adequate contraception for the duration of the study and for one month afterwards.
• History of hypersensitivity to any of the components of the subcutaneous infusions.
• Donated blood during the preceding 3 months or intention to do so before the end of the study.
• Insulin treatment.
• Uncontrolled hypertension.
• Any other co-morbidity that would compromise the validity of the study or the safety of the participant such as heart failure, clinically apparent cardiovascular disease.
• Volunteers on anti-coagulants such as warfarin and factor Xa inhibitors will not undergo adipose tissue biopsy.
• Unable to give informed consent.
• Previous bariatric surgery.
• Unable to undergo fMRI due to:

• Claustrophobia.
• Pacemaker, metal implant, clips, implanted device, shrapnel or bullet, metal in eyes that precludes magnetic resonance imaging.
• Significant structural abnormality on magnetic resonance brain scan