GLP1R Polymorphisms and Response to GLP1

Mayo Clinic

Status: Completed

Conditions: Diabetes

Treatments: Drug: GLP-1

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT00588380

07-004153

Details and patient eligibility

About

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.

Enrollment: 88 patients

Sex: All

Ages: 18 to 40 years old

Volunteers: Accepts Healthy Volunteers

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).

Trial design

Primary purpose: Basic Science

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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88 participants in 1 patient group

GLP-1

Experimental group

Description:

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

Treatment:

Drug: GLP-1