Glucagon-like Peptide 1, Glucose Metabolism and Gastric Bypass

Study Overview
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Brief Summary
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The overall goal of this project is to understand the mechanisms by which gastric bypass surgery improves glucose metabolism. The central hypothesis guiding this project is that the reconfiguration of intestinal transit with the Roux-en-Y will increase the release of insulinotropic GI hormones, termed incretins that improve insulin secretion and glucose metabolism. The study is divided into three specific aims. To determine the role of incretin hormones on insulin secretion in patients with gastric bypass surgery using intravenous-oral hyperglycemic clamp. To compare incretin effect and glucose tolerance among patient who suffer from hypoglycemia after RYGB and asymptomatic surgical and non-surgical individuals. To quantify the contribution of GLP-1 to incretin effect enhancement following surgery.

Detailed Description
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The overall goal of this project is to understand the mechanisms by which gastric bypass surgery improves glucose metabolism. The central hypothesis guiding this project is that the reconfiguration of intestinal transit with the Roux-en-Y will increase the release of insulinotropic GI hormones, termed incretins that improve insulin secretion and glucose metabolism. The study is divided into three specific aims. To determine the role of incretin hormones on insulin secretion in patients with gastric bypass surgery using intravenous-oral hyperglycemic clamp. To compare incretin effect and glucose tolerance among patient who suffer from hypoglycemia after RYGB and asymptomatic surgical and non-surgical individuals. To quantify the contribution of GLP-1 to incretin effect enhancement following surgery.

Official Title
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The Role of Glucagon Like Peptide-1 in Glucose Metabolism and Weight Loss Following Gastric Bypass Surgery

Conditions
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Post-bariatric Surgery

Intervention / Treatment
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* Drug: exendin-(9-39)
* Drug: exendin -(9-39)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age 18-65 healthy control without diabetes or active organ disease Individuals with bariatric surgery recurrent hypoglycemia post gastric bypass Exclusion Criteria: pregnancy significant anemia diabetes currently unless pre-op for bariatric surgery procedure GI obstruction

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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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Non-Randomized
Intervention Model: Factorial Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: hyperglycemic clamp-Meal tolerance test<br>these studies are to evaluate the effect of exendin-9 on insulin secretion before and after meal ingestion in patients after bariatric surgeries compared to non-surgical controls | Drug: exendin-(9-39)<br>* hyperglycemic clamp-meal tolerance test is designed to assess insulin secretion before and after meal ingestion<br>* Other names: no other name for exendin-(9-39);|
| Experimental: Labeled meal tolerance test<br>The effect of GLP-1 receptor blockade on glucose tolerance and glucose kinetics are evaluated in the group patients with bariatric surgery vs. nonsurgical using exendin-9-39 infusion during one of the the 2-day dual tracer studies of meal tolerance test | Drug: exendin -(9-39)<br>* 2-day meal tolerance tests with labeled oral and IV glucose using exendin-(9-39) infusion are designed to evaluate the role of GLP-1 signaling on glucose tolerance and glucose kinetics.<br>* Other names: no other name for exendin-(9-39);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The investigator measure glucose, islet and GI hormonal levels in response to meal ingestion as a composite measure and the percentage of contribution of GLP-1 contribution to postprandial insulin levels will also be calculated |  | up to 1 year (10 sessions) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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gastric bypass, glucose metabolism, hypoglycemia