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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:
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:
In addition, the study team hypothesizes that poor responders exhibit:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Gut hormone secretion study | No Intervention | This will be a retrospective study of participants who have undergone bariatric surgery. On the day of the visit participants will undergo comprehensive physiological profiling which will include the following tests:
| |
| Gut hormone sensitivity study | Placebo Comparator | This will be a single blinded study with participants attending three visits. 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. Occasionally some volunteers are more sensitive to the gut hormone infusion and the doses needs to be titrated down. The doses used will be established doses of the gut hormones infused previously and which have been shown to be safe and tolerated, and to reduce appetite (In house data). |
|
| Prospective assessment of gut hormone response pre and post-surgery | No Intervention | This will be a prospective study assessing the gut hormone response pre and post bariatric surgery. On the day of the visit participants will undergo comprehensive physiological profiling which will include the following tests:
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Gut hormones | Other | 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:
|
| Measure | Description | Time Frame |
|---|---|---|
| Gut 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. | 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. | 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. | During two study visits (Mixed Meal Test), one before and one 1 year after surgery. |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Resting Energy Expenditure | Resting energy expenditure assessment via indirect calorimetry. | 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Kleopatra Alexiadou, PhD | Contact | +442033138038 | 38038 | k.alexiadou@imperial.ac.uk |
| Name | Affiliation | Role |
|---|---|---|
| Tricia M Tan, PhD | Imperial College London | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Imperial College London | Recruiting | London | W120NN | United Kingdom |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 25585572 | Background | Aasheim ET, Aylwin SJ, Radhakrishnan ST, Sood AS, Jovanovic A, Olbers T, le Roux CW. Assessment of obesity beyond body mass index to determine benefit of treatment. Clin Obes. 2011 Apr;1(2-3):77-84. doi: 10.1111/j.1758-8111.2011.00017.x. Epub 2011 Jul 5. | |
| 12167864 | Background | Batterham RL, Cowley MA, Small CJ, Herzog H, Cohen MA, Dakin CL, Wren AM, Brynes AE, Low MJ, Ghatei MA, Cone RD, Bloom SR. Gut hormone PYY(3-36) physiologically inhibits food intake. Nature. 2002 Aug 8;418(6898):650-4. doi: 10.1038/nature00887. |
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| ID | Term |
|---|---|
| D009767 | Obesity, Morbid |
| D003924 | Diabetes Mellitus, Type 2 |
| ID | Term |
|---|---|
| D009765 | Obesity |
| D050177 | Overweight |
| D044343 | Overnutrition |
| D009748 | Nutrition Disorders |
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|
Diet induced thermogenesis assessment via indirect calorimetry. |
| 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. | Change between two visits: Before and 1 year after bariatric surgery. |
| 22000927 | Background | De Silva A, Salem V, Long CJ, Makwana A, Newbould RD, Rabiner EA, Ghatei MA, Bloom SR, Matthews PM, Beaver JD, Dhillo WS. The gut hormones PYY 3-36 and GLP-1 7-36 amide reduce food intake and modulate brain activity in appetite centers in humans. Cell Metab. 2011 Nov 2;14(5):700-6. doi: 10.1016/j.cmet.2011.09.010. Epub 2011 Oct 13. |
| 20501690 | Background | Laferrere B, Swerdlow N, Bawa B, Arias S, Bose M, Olivan B, Teixeira J, McGinty J, Rother KI. Rise of oxyntomodulin in response to oral glucose after gastric bypass surgery in patients with type 2 diabetes. J Clin Endocrinol Metab. 2010 Aug;95(8):4072-6. doi: 10.1210/jc.2009-2767. Epub 2010 May 25. |
| 23248172 | Background | Tan TM, Field BC, McCullough KA, Troke RC, Chambers ES, Salem V, Gonzalez Maffe J, Baynes KC, De Silva A, Viardot A, Alsafi A, Frost GS, Ghatei MA, Bloom SR. Coadministration of glucagon-like peptide-1 during glucagon infusion in humans results in increased energy expenditure and amelioration of hyperglycemia. Diabetes. 2013 Apr;62(4):1131-8. doi: 10.2337/db12-0797. Epub 2012 Dec 17. |
| D009750 |
| Nutritional and Metabolic Diseases |
| D001835 | Body Weight |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D004700 | Endocrine System Diseases |