The Effect of Different Macronutrients on Gastrointestinal Hormone Secretion After Gastric Bypass Operation

Study Overview
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Brief Summary
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The purpose of this study is to determine the type of macronutrient (carbohydrate, lipid or protein) that most potently stimulates the endogen secretion of different gut hormones (primary outcome = Glucagon-Like peptide-1) in gastric bypass operated patients. The study also includes a comparison of the secretion of gut hormones after oral intake of lipid with or without a pancreatic lipase inhibitor.

Official Title
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The Effect of Different Macronutrients on Gastrointestinal Hormone Secretion After Gastric Bypass Operation

Conditions
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Overweight, Bariatric Surgery (Gastric Bypass)

Intervention / Treatment
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* Other: Mealtest: High protein 200 kcal 200 ml liquid meal consumed during 10 minutes
* Other: Mealtest: High fat 200 kcal 200 ml liquid meal consumed during 10 minutes
* Other: Mealtest: High carbohydrate 200 kcal 200 ml liquid meal consumed during 10 minutes
* Other: Mealtest: High fat 200 kcal 200 ml liquid meal with pancreatic lipase inhibitor consumed during 10 minutes


Participation Criteria
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Eligibility Criteria
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RYGB Patients: Inclusion Criteria: Underwent RYGB surgery more than 18 months earlier, weight stabile (+/- 5 kg during 1 month) Exclusion Criteria: Inadequate thyroid substitution, undergoing treatment with drugs known to interact with Orlistat (such as cyclosporine, anticoagulating agents, amiodarone, amlodipine and epileptics), where pausing the treatment with these is not an option. Type 1 or 2 diabetes mellitus now or prior to RYGB operation. Serious heart or respiratory illness. Haemoglobin levels below 6,5 mM. Healthy control subjects: Inclusion Criteria: Have not underwent bariatric surgery. Exclusion Criteria: Inadequate thyroid substitution, undergoing treatment with drugs known to interact with Orlistat (such as cyclosporine, anticoagulating agents, amiodarone, amlodipine and epileptics), where pausing the treatment with these is not an option. Type 1 or 2 diabetes mellitus now or prior. Serious heart or respiratory illness. Haemoglobin levels below 6,5 mM.

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| 10 Roux-en-Y gastric bypass patients<br>Isocaloric amounts of specific macronutrients is mixed with 4 g vegetable bouillon and tested against each others ability to induce GLP-1 secretion. The mealtest takes place at 4 different days with 3-14 days separation. | Other: Mealtest: High protein 200 kcal 200 ml liquid meal consumed during 10 minutes<br> <br> * Other names: LACPRODAN SP-9225 INSTANT Whey Protein Isolate;Other: Mealtest: High fat 200 kcal 200 ml liquid meal consumed during 10 minutes<br> <br> * Other names: Lurpak® smør(butter) 81% fat;Other: Mealtest: High carbohydrate 200 kcal 200 ml liquid meal consumed during 10 minutes<br> <br> * Other names: Urtegaarden Druesukker (Dextrose monohydrat);Other: Mealtest: High fat 200 kcal 200 ml liquid meal with pancreatic lipase inhibitor consumed during 10 minutes<br> <br> * Other names: Lurpak® smør(butter) 81% fat with 120 mg Xenical® Orlistat;|
| 10 Healthy Control subjects<br>Isocaloric amounts of specific macronutrients is mixed with 4 g vegetable bouillon and tested against each others ability to induce GLP-1 secretion. The mealtest takes place at 4 different days with 3-14 days separation. | Other: Mealtest: High protein 200 kcal 200 ml liquid meal consumed during 10 minutes<br> <br> * Other names: LACPRODAN SP-9225 INSTANT Whey Protein Isolate;Other: Mealtest: High fat 200 kcal 200 ml liquid meal consumed during 10 minutes<br> <br> * Other names: Lurpak® smør(butter) 81% fat;Other: Mealtest: High carbohydrate 200 kcal 200 ml liquid meal consumed during 10 minutes<br> <br> * Other names: Urtegaarden Druesukker (Dextrose monohydrat);Other: Mealtest: High fat 200 kcal 200 ml liquid meal with pancreatic lipase inhibitor consumed during 10 minutes<br> <br> * Other names: Lurpak® smør(butter) 81% fat with 120 mg Xenical® Orlistat;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Within group difference in Glucagon-like Peptide 1 secretion (evaluated by iAUC). | I.e. Comparison of GLP-1 secretion (iAUC) as a result of intake of different macronutrients between a) gastric bypass patients only b) healthy volunteers only. | Basline, 0, 15, 30, 45, 60, 90, 120, 180, 240 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Within group difference in Glucagon secretion (evaluated by iAUC). |  | Basline, 0, 15, 30, 45, 60, 90, 120, 180, 240 | 
| Within group difference in Glucose-dependent insulinotropic peptide secretion (evaluated by iAUC). |  | Basline, 0, 15, 30, 45, 60, 90, 120, 180, 240 | 
| Within group difference in Cholecystokinin secretion (evaluated by iAUC). |  | Basline, 0, 15, 30, 45, 60, 90, 120, 180, 240 | 
| Within group difference in Peptide YY 3-36 secretion (evaluated by iAUC). |  | Basline, 0, 15, 30, 45, 60, 90, 120, 180, 240 | 
| Within group difference in Ghrelin secretion (evaluated by iAUC). |  | 0, 30, 45, 60, 120, 180, 240 | 
| Within group difference in Changes in bile acids. |  | 0, 30, 45, 60, 120, 180, 240 | 
| Within group difference in Changes in glycerol, triacylglycerol and free fatty acids. |  | 0, 30, 45, 60, 120, 180, 240 | 
| Within group difference in Insulin secretion (evaluated by iAUC). |  | 2xBasline, 0, 10, 15, 20, 30, 40, 45, 60, 90, 120, 180, 240 | 
| Within group difference in Plasma glucose concentration. |  | 2xBasline, 0, 5, 10, 15, 20, 25, 30, 40, 45, 60, 90, 120, 180, 240 | 
| Within group difference in Visual Analog Scale. | Hunger, satiety, abdominal pain and nausea measured by standard 10 cm Visual Analog Scale | 0, 30, 60, 90, 120, 180, 240 | 
| Within group difference in Ad libitum food intake (grams). |  | 240 | 
| Within group difference in Heart rate (bpm). |  | 2xBasline, 0, 5, 10, 15, 20, 25, 30, 40, 45, 60, 90, 120, 180, 240 | 
| Within group difference in Blood pressure (mmhg). |  | 0, 15, 30, 45, 60, 90, 120, 180, 240 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Glucagon-like Peptide-1, Glucose-dependent insulinotropic peptide, Glucagon, Peptide YY 3-36, Ghrelin, Body Weight, Obesity, Overnutrition, Overweight, Gastrointestinal Agents, GLP-1 secretagogue