Effects of Hyperglycemia on Myocardial Perfusion in Humans With and Without Type 2 Diabetes (GLP-1)

July 3, 2015 updated by: Sharon Mulvagh, Mayo Clinic

Effects of Hyperglycemia on Myocardial Perfusion in Humans With and Without Type 2 Diabetes: Modulation by Glucagon-Like-Peptide-1

The overall goal of this proposal is to determine the effects of acute hyperglycemia and its modulation by Glucagon-like Peptide-1 (GLP-1) on myocardial perfusion in type 2 diabetes (DM). This study plan utilizes myocardial contrast echocardiography (MCE) to explore a) the effects of acute hyperglycemia on myocardial perfusion and coronary flow reserve in individuals with and without DM; and b) the effects of GLP-1 on myocardial perfusion and coronary flow reserve during euglycemia and hyperglycemia in DM. The investigators will recruit individuals with and without DM matched for age, gender and degree of obesity. The investigators will measure myocardial perfusion at rest and during vasodilator stress (to ascertain coronary flow reserve) while subjects are under controlled pancreatic clamp conditions during euglycemia (glucose ~100 mg/dl) and hyperglycemia (glucose ~250 mg/dl) in the presence and absence of concomitant GLP-1 infusion. The investigators believe that the translational significance of their studies is immense, impacting upon both acute and chronic cardiovascular disease manifestations. The effect of glycemic control on cardiovascular outcomes, morbidity and mortality remains an area of active investigation, fueled by the recent conflicting results of several large clinical trials (ACCORD, United Kingdom Prospective Diabetes Study (UKPDS), ADVANCE, VADT). If the investigators find that hyperglycemia is associated with altered myocardial perfusion, the mechanistic implications in the prevention and management of acute and chronic cardiovascular diseases in DM will be groundbreaking. Furthermore, if GLP-1 augments myocardial perfusion (as it does in the peripheral vasculature), the therapeutic benefits for prevention of cardiovascular events in this predisposed population are clear.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Observational

Enrollment (Actual)

33

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

  • United States
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic

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

40 years to 60 years (Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

25 subjects with type 2 diabetes and 25non-diabetic subjects matched for age, gender and degree of obesity will be studied.

The diabetic subjects will be between 40 and 60 years of age and will have a body mass index of < or =35 kg/m2. Diabetic subjects treated according to ADA guidelines will be eligible for study including a blood pressure < 140/90, LDL cholesterol < 130 mg/dl, HDL cholesterol >40 mg/dl and triglycerides <200 mg/dl.

All nondiabetic subjects will not have a history of diabetes in their first degree family members. None of the subjects will have any overt evidence of cardiac, renal, pulmonary or hepatic disorder nor will they be engaging in regular vigorous physical activities. All subjects will undergo a resting ECG and a treadmill ECG test to ensure that they do not have active or occult coronary artery disease unless such testing had been completed within six months of enrollment and reported as normal.

Description

Inclusion Criteria:

  • Males and females
  • Age 40-60 years
  • BMI< or = 35 kg/m2
  • Diabetic subjects with HbA1c concentrations of < or = 8%.
  • Diabetic subjects will be either on diet and lifestyle therapy alone, or monotherapy with metformin or sulphonylureas (except glyburide).
  • All diabetic subjects should be on stable dose oral agent therapy for 3 months prior to enrollment.

Exclusion Criteria:

  • Subjects with cerebrovascular or peripheral vascular disease.
  • Subjects with suspected or overt autonomic neuropathy.
  • Diabetic subject on thiazolidinediones, insulin, GLP-1 based therapies (exenatide or sitagliptin), alpha-glucosidase inhibitors, glyburide or combination antidiabetic drug therapies.
  • Diabetics with microalbuminuria.

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

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
With type 2 Diabetes
Drug: Glucagon-Like-Peptide-1/Regadenoson/Perflutren Lipid Microsphere

GLP-1 at a rate of 1.2 pmol/kg/min

Regadenoson as a stress agent 0.4mg IV given during MCE

Definity:0.6 ml of Definity diluted with 30ml of 0.9% saline infused by SYRINGE Infusion Pump

Other Names:
  • Definity
  • Lexiscan
Without type 2 diabetes
Drug: Glucagon-Like-Peptide-1/Regadenoson/Perflutren Lipid Microsphere

GLP-1 at a rate of 1.2 pmol/kg/min

Regadenoson as a stress agent 0.4mg IV given during MCE

Definity:0.6 ml of Definity diluted with 30ml of 0.9% saline infused by SYRINGE Infusion Pump

Other Names:
  • Definity
  • Lexiscan

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
To determine whether hyperglycemia alters myocardial perfusion in subjects with type 2 diabetes
Time Frame: Nov 2009-2011
Nov 2009-2011

Secondary Outcome Measures

Outcome Measure
Time Frame
To determine whether GLP-1 modulates myocardial perfusion in subjects with type 2 diabetes.
Time Frame: Nov 2009-2011
Nov 2009-2011

Collaborators and Investigators

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

Sponsor

Mayo Clinic

Collaborators

Astellas Pharma US, Inc.
University of Nebraska
Lantheus Medical Imaging

Investigators

  • Principal Investigator: Ananda Basu, MBBS, M.D., Mayo Clinic
  • Principal Investigator: Sharon L Mulvagh, M.D., Mayo Clinic

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.

General Publications

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

February 1, 2010

Primary Completion (Actual)

July 1, 2014

Study Completion (Actual)

July 1, 2014

Study Registration Dates

First Submitted

October 30, 2009

First Submitted That Met QC Criteria

November 25, 2009

First Posted (Estimate)

November 30, 2009

Study Record Updates

Last Update Posted (Estimate)

July 7, 2015

Last Update Submitted That Met QC Criteria

July 3, 2015

Last Verified

July 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 08-008750

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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