Effects of Hyperglycemia on Myocardial Perfusion in Humans With and Without Type 2 Diabetes - Full Text View

Purpose

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.

Condition	Intervention
Coronary Artery Disease Diabetes Mellitus Type 2	Drug: Glucagon-Like-Peptide-1/Regadenoson/Perflutren Lipid Microsphere


Study Type:	Observational
Study Design:	Observational Model: Case Control Time Perspective: Prospective
Official Title:	Effects of Hyperglycemia on Myocardial Perfusion in Humans With and Without Type 2 Diabetes: Modulation by Glucagon-Like-Peptide-1

Resource links provided by NLM:

MedlinePlus related topics: Diabetes Type 2 Hyperglycemia

Drug Information available for: Perflutren Glucagon Regadenoson

U.S. FDA Resources

Further study details as provided by Mayo Clinic:

Primary Outcome Measures:

To determine whether hyperglycemia alters myocardial perfusion in subjects with type 2 diabetes [ Time Frame: Nov 2009-2011 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

To determine whether GLP-1 modulates myocardial perfusion in subjects with type 2 diabetes. [ Time Frame: Nov 2009-2011 ] [ Designated as safety issue: No ]


Enrollment:	33
Study Start Date:	February 2010
Study Completion Date:	July 2014
Primary Completion Date:	July 2014 (Final data collection date for primary outcome measure)

Groups/Cohorts	Assigned Interventions
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: Lexiscan Definity
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: Lexiscan Definity

Eligibility


Ages Eligible for Study:	40 Years to 60 Years (Adult)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes
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.

Criteria

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.

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01021865

Locations


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

Sponsors and Collaborators

Mayo Clinic

University of Nebraska

Astellas Pharma US, Inc.

Lantheus Medical Imaging

Investigators


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

More Information

Publications:

Abdelmoneim SS, Hagen ME, Mendrick E, Pattan V, Wong B, Norby B, Roberson T, Szydel T, Basu R, Basu A, Mulvagh SL. Acute hyperglycemia reduces myocardial blood flow reserve and the magnitude of reduction is associated with insulin resistance: a study in nondiabetic humans using contrast echocardiography. Heart Vessels. 2013 Nov;28(6):757-68. doi: 10.1007/s00380-012-0305-y. Epub 2012 Nov 23.


Responsible Party:	Sharon Mulvagh, PI, Mayo Clinic
ClinicalTrials.gov Identifier:	NCT01021865 History of Changes
Other Study ID Numbers:	08-008750
Study First Received:	October 30, 2009
Last Updated:	July 3, 2015
Health Authority:	United States: Food and Drug Administration

Keywords provided by Mayo Clinic:


GLP-1 Myocardial contrast echocardiography Myocardial perfusion

Additional relevant MeSH terms:


Diabetes Mellitus Coronary Artery Disease Myocardial Ischemia Coronary Disease Hyperglycemia Diabetes Mellitus, Type 2 Glucose Metabolism Disorders Metabolic Diseases Endocrine System Diseases Heart Diseases Cardiovascular Diseases Arteriosclerosis Arterial Occlusive Diseases Vascular Diseases	Glucagon Glucagon-Like Peptide 1 Regadenoson Gastrointestinal Agents Hormones Hormones, Hormone Substitutes, and Hormone Antagonists Physiological Effects of Drugs Incretins Adenosine A2 Receptor Agonists Purinergic P1 Receptor Agonists Purinergic Agonists Purinergic Agents Neurotransmitter Agents Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 23, 2016

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