GLP1R Polymorphisms and Response to GLP1

Study Overview
=================
Brief Summary
-----------------
Glucagon-like Peptide-1 (GLP-1) is an important incretin hormone which acts as a powerful insulin secretagogue. Defects in GLP-1 synthesis and secretion are thought to be part of the pathogenesis of type 2 diabetes. Furthermore GLP-1 based therapy is an important part of the therapeutic armamentarium for the treatment of type 2 diabetes. The GLP-1 receptor (GLP1R) is the principal site of action of GLP-1 and GLP-1 receptor agonists like exenatide and liraglutide. The gene coding for this receptor, GLP1R, is highly polymorphic and contains numerous non-synonymous Single Nucleotide Polymorphisms (nsSNPs) which could potentially alter response to endogenous or exogenous GLP-1 or GLP-1R agonists. Indeed there is some in vitro data to support this concept. We propose to utilize a hyperglycemic clamp to test the insulin secretory response to infused GLP-1 in healthy volunteers to determine the effect of genetic variation in GLP1R on response to GLP-1.

Official Title
-----------------
A Pilot Study Examining How Common Genetic Variation in GLP1R Alters Response to GLP1 Infusion

Conditions
-----------------
Diabetes

Intervention / Treatment
-----------------
* Drug: GLP-1


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Aged 18-40 fasting glucose concentration of less than 95 mg/dl. Exclusion Criteria: Individuals with a BMI < 19 or > 40 kg/m^2 active systemic illness medication that can alter gastric emptying, insulin secretion & action history of abdominal surgery (other than appendectomy or tubal ligation).

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GLP-1<br>All participants recieved GLP-1 intravenously at 0.75 pmol/kg/min for the first hour and then at 1.5 pmol/kg/min for the next hour | Drug: GLP-1<br>* GLP-1 infused at 0.75 pmol/kg/min from 121-180 minutes, GLP-1 infused at 1.55 pmol/kg/min from 181-240 minutes,<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Insulin Secretion at 150-180 Minutes. | The 180 minute value represents the mean of the values obtained at 150, 160, 170, and 180 minutes. | 150 - 180 minutes after GLP-1 infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Insulin Secretion at 210-240 Minutes | The 240 minute value represents the mean of values obtained at 210, 220, 230, and 240 minutes. | 210 - 240 minutes after GLP-1 infusion | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
GLP-1, Insulin Secretion