Glucagon-like Peptide 1 (GLP-1) and Endothelial Dysfunction in Metabolic Syndrome

December 10, 2013 updated by: Manfredi Tesauro, University of Rome Tor Vergata

Effect of GLP-1 on Endothelial Function and Glucose Uptake in Patients With Metabolic Syndrome

Glucagon-like peptide 1 (GLP-1) is an intestinal peptide hormone secreted in a nutrient-dependent manner that stimulates the pancreatic beta cells to secrete more insulin in response to the same amount of blood glucose. In patients with Type 2 diabetes, GLP-1 secretion is lower than normal, thus suggesting that the hormone may contribute to the pathogenesis of the disease. Whether infusion of GLP-1 affects endothelial function and glucose uptake in humans has never been investigated. In the current proposal, the investigators hypothesize that GLP-1 administration might ameliorate endothelial dysfunction in patients with metabolic syndrome. To test this hypothesis, the investigators will evaluate the acute effects of GLP-1 in the forearm circulation of patients with metabolic syndrome during local hyperinsulinemia by use of the forearm perfusion technique.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Subjects meeting the entrance criteria will be studied in a quiet room with a temperature of approximately 22°C. While the participants are supine, a 20-gauge Teflon catheter will be inserted into the brachial artery of the nondominant arm under local anesthesia. This arm will be slightly elevated above the level of the heart, and a mercury-filled Silastic strain gauge will be placed on the widest part of the forearm. The strain gauge will be connected to a plethysmography calibrated to measure the percent change in volume; the plethysmograph in turn will be connected to a chart recorder to record the forearm flow measurements. For each measurement, a cuff placed on the upper arm will be inflated to 40 mmHg with a rapid cuff inflator to occlude venous outflow from the extremity. A wrist cuff will be inflated to suprasystolic pressures l min before each measurement to exclude the hand circulation. Flow measurements will be recorded for approximately 7 seconds every 15 seconds; 7 readings will be obtained for each value.

The intraarterial catheter will be connected by a 3-way stopcock to both a pressure transducer (to measure intraarterial blood pressure) and an infusion pump. Saline or drugs then will be infused at the rate of 0.5-1ml per minute. Another 20-gauge Teflon catheter will be inserted in a homolateral antecubital vein for blood sampling.

To assess the effects of GLP-1 on insulin stimulated vasodilation, after the forearm will be instrumented, patients with metabolic syndrome will receive intraarterial infusion of saline for 15 minutes; blood samples will be collected and baseline flow will be measured. Then infusion of regular insulin (Humulin, Eli Lilly, Indianapolis, IN; 0.1 mU per kg of body weight per minute) will be started. Next, forearm blood flow will be measured after infusion of Ach, a vasodilator whose effect is predominantly related to nitric oxide (NO), and sodium nitroprusside (SNP), an exogenous NO donor.

After 20 min of insulin infusion, another baseline measurement will be obtained and continuous intraarterial infusion of GLP-1 will be started at 20 pmol/min infusion rate. This dose has been chosen in order to achieve intravascular GLP-1 concentrations within the infused forearm in a range (approximately 0.50 pmol/mL) previously shown effective to improve insulin sensitivity. GLP-1 infusion will be continued for 60 minutes, and forearm blood flow will be measured every 30 minutes; venous blood samples will be obtained at the end of this infusion period. Then, while maintaining GLP-1 infusion unchanged, dose-response curves to ACh and SNP will be repeated, at the same doses and following the same protocol as before.

Study Type

Interventional

Enrollment (Actual)

20

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Rome, Italy, 90100
        • Tor Vergata University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

20 years to 60 years (Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Otherwise healthy individuals aged between 20 and 60 years
  • Must satisfy 3 out of the 5 listed criteria for the diagnosis of the metabolic syndrome (ATP III) will be included

Exclusion Criteria:

  • Pregnancy
  • Liver disease
  • Pulmonary disease
  • Renal insufficiency
  • Coronary heart disease
  • Heart failure
  • Peripheral vascular disease
  • Coagulopathy
  • Any disease predisposing to vasculitis or Raynaud's phenomenon
  • Bleeding disorders
  • Kidney stones
  • Platelet count < 150,000/ml blood
  • Prothrombin time/partial thromboplastin time (PT/PTT) > 1 second above the normal range, and positive tests for HIV, or hepatitis B or C
  • Subjects who are taking any kind of medication will not be included in this study; therefore, antihypertensive and/or lipid-lowering drugs will be discontinued at least 2 weeks before enrollment into this study
  • All subjects will be told to refrain from alcohol, beverages containing caffeine, or smoking for at least 24 hours before the study is performed

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: GLP-1 infusion
Patients with metabolic syndrome
Participants will receive intraarterial infusion of GLP-1 (20 pmol/ml solution) for 100 min.
Other Names:
  • Incretins

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Endothelium-dependent vasodilation capacity
Time Frame: 60 minutes
60 minutes

Secondary Outcome Measures

Outcome Measure
Time Frame
Insulin-mediated glucose uptake
Time Frame: 100 minutes
100 minutes

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Collaborators

Investigators

  • Principal Investigator: Manfredi Tesauro, MD, Internal Medicine Department, Tor Vergata University, Rome

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2008

Primary Completion (Actual)

June 1, 2012

Study Completion (Actual)

June 1, 2012

Study Registration Dates

First Submitted

March 5, 2009

First Submitted That Met QC Criteria

March 5, 2009

First Posted (Estimate)

March 6, 2009

Study Record Updates

Last Update Posted (Estimate)

December 11, 2013

Last Update Submitted That Met QC Criteria

December 10, 2013

Last Verified

December 1, 2013

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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