Effects of Hyperglycemia on Myocardial Perfusion in Humans With and Without Type 2 Diabetes
Status:
Completed
Trial end date:
2014-07-01
Target enrollment:
Participant gender:
Summary
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.
Details
Lead Sponsor:
Mayo Clinic
Collaborators:
Astellas Pharma US, Inc. Lantheus Medical Imaging University of Nebraska