Effects of Hyperglycemia on Myocardial Perfusion in Humans With and Without Type 2 Diabetes (GLP-1)
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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, 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 |
- To determine whether hyperglycemia alters myocardial perfusion in subjects with type 2 diabetes [ Time Frame: Nov 2009-2011 ] [ Designated as safety issue: No ]
- 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:
|
| 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:
|
Eligibility| Ages Eligible for Study: | 40 Years to 60 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | Yes |
| Sampling Method: | Non-Probability Sample |
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.
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 LocationsPlease refer to this study by its ClinicalTrials.gov identifier: NCT01021865
| United States, Minnesota | |
| Mayo Clinic | |
| Rochester, Minnesota, United States, 55905 | |
| Principal Investigator: | Ananda Basu, MBBS, M.D. | Mayo Clinic | |
| Principal Investigator: | Sharon L Mulvagh, M.D. | Mayo Clinic |
More Information
Publications:
| 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: | October 20, 2014 |
| Health Authority: | United States: Food and Drug Administration |
Keywords provided by Mayo Clinic:
|
GLP-1 Myocardial contrast echocardiography Myocardial perfusion |
Additional relevant MeSH terms:
|
Coronary Artery Disease Coronary Disease Diabetes Mellitus Diabetes Mellitus, Type 2 Myocardial Ischemia Arterial Occlusive Diseases Arteriosclerosis Cardiovascular Diseases Endocrine System Diseases Glucose Metabolism Disorders Heart Diseases Metabolic Diseases Vascular Diseases |
Definity Glucagon Glucagon-Like Peptide 1 Perflutren Contrast Media Diagnostic Uses of Chemicals Gastrointestinal Agents Hormones Hormones, Hormone Substitutes, and Hormone Antagonists Incretins Pharmacologic Actions Physiological Effects of Drugs Therapeutic Uses |
ClinicalTrials.gov processed this record on February 27, 2015