Effects of Hyperglycemia on Myocardial Perfusion in Humans With and Without Type 2 Diabetes
Condition: Coronary Artery Disease; Diabetes Mellitus Type 2
MeSH terms: Coronary Artery Disease; Diabetes Mellitus; Hyperglycemia; Diabetes Mellitus, Type 2
Study type: Observational

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.
    


Intervention name(s): Glucagon-Like-Peptide-1/Regadenoson/Perflutren Lipid Microsphere
Intervention type(s): Drug
Intervention description(s): 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 intervention name(s): Lexiscan; Definity
Intervention MeSH terms: Glucagon; Glucagon-Like Peptide 1; Regadenoson
Observational model: Case-Control
Time perspective: Prospective
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.
      
Keywords: GLP-1; Myocardial contrast echocardiography; Myocardial perfusion