Overview

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.

Eligibility

Inclusion Criteria:

• Aged 18 -70 years.
• Male or female.
• Previous bariatric surgery for obesity and/or diabetes (studies 1 and 2).
• ≥1 year interval after bariatric surgery (studies 1 and 2).
• Awaiting bariatric surgery at the Imperial Weight Centre (study 3)
• Able to give informed consent.

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.
• 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.
• Any other co-morbidity that would compromise the validity of the study or the safety of the participant such as heart failure or clinically apparent cardiovascular disease.
• Anatomical or endocrinological pathology causing poor weight loss or weight regain
• Uncontrolled hypertension (systolic blood pressure of 160 mmHg or above and/or diastolic blood pressure of 100 mmHg or above)
• Participation in a research study within the last two months.
• Unable to speak English (this is relevant to answering the psychological questionnaires)