Effect of Gastric Bypass Surgery on Pancreatic Islets and Incretin Function

Study Overview
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Brief Summary
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The study aims at describing the acute and subacute changes after Roux-en-Y (RYGB) gastric bypass in insulin secretion from the beta cell and glucagon secretion from the alpha cell as well as the stimulatory effect of the incretins on the pancreatic islets. RYGB is a bariatric procedure that changes the gastrointestinal anatomy and has been demonstrated to cause remission of type 2 diabetes shortly after the operation, before any significant weight loss. The altered transit of nutrient through the gastrointestinal tract after the operation is thought to play a key role in this remission and studies have shown significant changes in the secretion of gut hormones, namely the incretin hormone glucagon-like peptide-1 (GLP-1). However it is unknown whether the secretory function of the pancreatic islets as well as the stimulatory effect of the incretin hormones is changes postoperatively.

Official Title
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The Effect of Gastric Bypass Surgery on the Beta- and Alpha Cells Secretory Function and the Insulinotropic Effect of the Incretin Hormones

Conditions
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Obesity

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Normal glucose tolerance Age > 18 years BMI > 40 or > 35 if combined with hypertension or obstructive sleep apnoea Caucasian Normal hemoglobinaemia Signed informed consent Exclusion Criteria: Major psychiatric disorder Alcohol or drug abuse Major hearth or pulmonary disease Previous major abdominal disease (e.g. peritonitis, large hernia) Pregnancy/lactation Treatment with GLP-1 analogs

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 |
| --- | --- |
| Normal glucose tolerance<br>Morbidly obese subjects with normal glucose tolerance undergoing gastric bypass surgery | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in beta cell function | Change in first and second phase insulin response, disposition index, and acute insulin secretion in response to a non-glucose stimulus | Before and 1 week and 3 months after surgery | 
| Insulinotropic effect of incretin hormones | Change in first and second phase insulin response during GLP-1 and GIP infusion compared to saline | Before and 1 week and 3 months after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in alpha cell function | Change in glucagon secretion in response to glucose and non-glucose stimuli | Before and 1 week and 3 months after surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Obesity, Roux-en-Y gastric bypass, Beta cell function, Incretin hormones