Effects of Hyperglycemia on Myocardial Perfusion in Humans With and Without Type 2 Diabetes
| Status: | Completed |
|---|---|
| Conditions: | Peripheral Vascular Disease, Cardiology, Diabetes |
| Therapuetic Areas: | Cardiology / Vascular Diseases, Endocrinology |
| Healthy: | No |
| Age Range: | 40 - 60 |
| Updated: | 4/21/2016 |
| Start Date: | February 2010 |
| End Date: | July 2014 |
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.
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.
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.
We found this trial at
1
site
Click here to add this to my saved trials
