Long Term Effects of Weight Loss on Post-prandial Gut Hormone Responses and Meal Induced Thermogenesis

Study Overview
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Brief Summary
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A study to examine post-prandial gut-hormone secretion, meal-induced thermogenesis, fasting plasma metabolomic/lipidomic and cardiovascular indices among surgically managed obese individuals in the long term compared to conservatively managed obese patients.

Detailed Description
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This is a protocol for the study of post-prandial gut peptide response and meal-induced thermogenesis in a group of 15 conservatively managed (through diet and exercise) morbidly obese individuals. During two separate visits in the study site, anthropometric and bioelectric impendence data will be collected, resting metabolic rate will be measured, and the patients will undergo a panel of cardiovascular examinations (heart rate variability, baroreflex sensitivity, heart ultrasound). On a separate occasion, they will consume a standardized test mixed meal and complete visual analog scales for the subjective assessment of hunger and fullness every 30 minutes for 3 hours. At the same time points, blood samples will be collected for the consequent measurement of glucose, insulin, lipids, and gastrointestinal hormones. Additionally, immediately before and at 60', 120', 180' after the start of the consumption of the test meal, the resting metabolic rate of each participant will be assessed through indirect calorimetry, to quantify meal-induced thermogenesis. The observed induction of satiety and suppression of hunger, post prandial gut-peptide mobilization and change in metabolic rate will be compared to those of participants of trial no NCT03851874 (Morbidly obese patients that have undergone either Roux en Y gastric bypass or sleeve gastrectomy and participated in trial NCT03851874). Participants in the aforementioned cohort have been already followed-up during the first postoperative year and will attend the study site for another follow-up visit approximately 10 years postoperatively, whereby the same diagnostic evaluation described above will take place. Data analysis will take place within the bariatric cohort (longitudinal analysis of the effects of surgery and surgery types on anthropometric parameters, fasting and postprandial glycemia and lipemia, fasting NMR-Metabolomic/Lipidomic profiles, Indices of insulin resistance, echocardiography, energy expenditure) as well as between the two groups in a cross-sectional manner.

Official Title
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Postprandial Gut Hormone Responses and Meal-induced Thermogenesis After Non-surgical Long-term Weight Loss; Comparison With Surgically Treated Obese Individuals

Conditions
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Morbid Obesity

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: For the conservatively managed cohort: Morbid obesity based on BMI > 40kg/m2, managed exclusively with conservative measures (hypocaloric diet and/or increased physical activity and/or behavioral therapy) Age between 18 and 65 years For the bariatric cohort: Participation in NCT03851874 trial Exclusion Criteria: Serious and life threatening comorbidities (renal, cardiac, liver failure, or malignancy) Alcohol or other substance abuse Use of licenced or off-label weight loss medications during the past 6 months Concurrent psychiatric illness Known history of diabetes mellitus (remitted cases excluded)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Conservatively managed group<br>Individuals with conservatively managed obesity | |
| Surgically managed group<br>Individuals with a past history of bariatric surgery (Roux-en-Y gastric bypass/Sleeve gastrectomy) for the management of obesity | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in postprandial Gut peptide (ghrelin, Gastric Inhibitory Peptide, Secretin, Peptide Tyrosine-Tyrosine - , Glucagon-like peptide - 1, Oxyntomodulin, Glicentin) responses | Change in the cumulative postprandial response for the aforementioned gut hormones | 8-10 years following primary weight-loss intervention | 
| Change in weight, fat mass and lean body mass | Change in weight (percentage of weight following each intervention) | 8-10 years following primary weight-loss intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in postprandial glycemia | Change in postprandial glycemia | 8-10 years following primary weight-loss intervention | 
| Change in postprandial insulinemia | Change in the cumulative postprandial response for insulin | 8-10 years following primary weight-loss intervention | 
| Change in postprandial triglyceridemia | Change in the cumulative postprandial response for triglycerides | 8-10 years following primary weight-loss intervention | 
| Change in Insulin resistance | Change in Insulin resistance indices (HOMA-R, MMTT-derived Matsuda index) | 8-10 years following primary weight-loss intervention | 
| Change in serum metabolomic and lipidomic parameters | Change in levels of lipoprotein clusters, branched-chain amino-acids, LDL/HDL-Subtypes, Trimethylamine N-oxide assessed by NMR spectroscopy | 8-10 years following primary weight-loss intervention | 
| Change in resting metabolic rate following meal ingestion | Change in the cumulative postprandial thermogenesis | 8-10 years following primary weight-loss intervention | 
| Change in fasting serum adipokines | Change of fasting leptin, adiponektin concentrations | 8-10 years following primary weight-loss intervention | 
| Change in fasting plasma Activins and follistatins | Change in fasting plasma Activin A, B, AB, follistatin and follistatin-like 3 | 8-10 years following primary weight-loss intervention | 
| Change in postprandial Visual Analog Scale scores for hunger and satiety | Change in postprandial areas under the curve of subjective hunger and satiety expressed in Visual Analog Scales | 8-10 years following primary weight-loss intervention | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Weight loss, Gut peptides, Meal-induced thermogenesis, Glycemia