Incretin Hormone Antagonism After Bariatric Surgery

Study Overview
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Brief Summary
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Using the glucagon-like peptide-1 (GLP-1) antagonist exendin(9-39) and the glucose-dependent insulinotropic peptide (GIP) antagonist GIP(3-30), the purpose of this study is to clarify the importance of endogenous GLP-1 and GIP for postprandial glucose metabolism after RYGB and SG in subjects with normal glucose tolerance. We hypothesize that GLP-1 is more important after RYGB, and GIP is more important after SG, for postprandial glucose tolerance and beta-cell function. A group of un-operated subjects with normal glucose tolerance will serve as controls.

Official Title
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Importance of Endogenous Glucagon-like Peptide-1 and Glucose-dependent Insulinotropic Polypeptide for Postprandial Glucose Metabolism After Roux-en-Y Gastric Bypass and Sleeve Gastrectomy Surgery

Conditions
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Bariatric Surgery

Intervention / Treatment
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* Other: Placebo
* Other: GLP-1 antagonism
* Other: GIP antagonism
* Other: GLP-1 and GIP antagonism


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria, surgery groups: Age > 18 years RYGB or SG operation > 12 months prior to inclusion Weight stable (± 3 kg during the last month) HbA1c < 48 mmol/mol before surgery, and no history of diabetes HbA1c < 48 mmol/mol and fasting plasma glucose < 6.1 mmol/l at inclusion Inclusion Criteria, control group: Age > 18 years no former RYGB- or SG operation Weight stable (± 3 kg during the last month) HbA1c < 48 mmol/mol, fasting plasma glucose < 6.1 mmol/l and no history of diabetes Exclusion Criteria: Thyrotoxicosis or inadequately treated hypothyreosis Hemoglobin < 6.5 mmol/l at inclusion Pregnancy or breast feeding Medication affecting the planned examinations Matching between groups Age Sex BMI at inclusion and for surgery groups also pre-surgery BMI

Ages Eligible for Study
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Minimum Age: 18 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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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Gastric bypass operated patients<br>Four test days in a randomized, patient-blinded, cross-over design | Other: Placebo<br>* Four-hour liquid mixed meal tests and a subsequent ad libitum meal during saline infusion.<br>Other: GLP-1 antagonism<br>* Four-hour liquid mixed meal tests and a subsequent ad libitum meal during exendin 9-39 and saline infusion.<br>Other: GIP antagonism<br>* Four-hour liquid mixed meal tests and a subsequent ad libitum meal during GIP(3-30) and saline infusion.<br>Other: GLP-1 and GIP antagonism<br>* Four-hour liquid mixed meal tests and a subsequent ad libitum meal during exendin and GIP(3-30) infusion.<br>|
| Other: Sleeve gastrectomy operated patients<br>Four test days in a randomized, patient-blinded cross-over, design | Other: Placebo<br>* Four-hour liquid mixed meal tests and a subsequent ad libitum meal during saline infusion.<br>Other: GLP-1 antagonism<br>* Four-hour liquid mixed meal tests and a subsequent ad libitum meal during exendin 9-39 and saline infusion.<br>Other: GIP antagonism<br>* Four-hour liquid mixed meal tests and a subsequent ad libitum meal during GIP(3-30) and saline infusion.<br>Other: GLP-1 and GIP antagonism<br>* Four-hour liquid mixed meal tests and a subsequent ad libitum meal during exendin and GIP(3-30) infusion.<br>|
| Other: Un-operated controls<br>Four test days in a randomized, patient-blinded cross-over, design | Other: Placebo<br>* Four-hour liquid mixed meal tests and a subsequent ad libitum meal during saline infusion.<br>Other: GLP-1 antagonism<br>* Four-hour liquid mixed meal tests and a subsequent ad libitum meal during exendin 9-39 and saline infusion.<br>Other: GIP antagonism<br>* Four-hour liquid mixed meal tests and a subsequent ad libitum meal during GIP(3-30) and saline infusion.<br>Other: GLP-1 and GIP antagonism<br>* Four-hour liquid mixed meal tests and a subsequent ad libitum meal during exendin and GIP(3-30) infusion.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| iAUC glucose | Main comparison between groups: delta iAUC glucose (iAUC exendin(9-39) test day - iAUC GIP(3-30) test day) in the RYGB group compared to the SG group | 240 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Beta-cell glucose sensitivity (β-GS) | Main comparison between groups: delta β-GS (β-GS exendin(9-39) test day - β-GS GIP(3-30) test day) in the RYGB group compared to the SG group | 240 minutes | 

 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 polypeptide, Roux-en-Y gastric bypass, sleeve gastrectomy, gastric bypass, bariatric surgery, glucose, diabetes, exendin(9-39), GIP(3-30)