We hypothesize that the hearts of HIV+ people with The Metabolic Syndrome use and oxidize fats and sugars inappropriately, and that this may impair the heart's ability to pump blood. We hypothesize that exercise training or pioglitazone (Actos) will improve fat and sugar metabolism in the hearts of HIV+ people with The Metabolic Syndrome. This study will advance our understanding of cardiovascular disease in HIV+ people, and will test the efficacy of exercise training and pioglitazone for improving insulin resistance, heart metabolism and heart function in this at risk population.
We hypothesize that myocardial free fatty acid and glucose utilization and oxidation rates are dysregulated in HIV+ people with The Metabolic Syndrome in comparison to HIV+ people without The Metabolic Syndrome, and in comparison to HIV-seronegative people with and without The Metabolic Syndrome. We hypothesize that dysregulated myocardial fatty acid and glucose metabolism is associated with impaired heart function (diastolic dysfunction) in HIV+ people with The Metabolic Syndrome. We will use myocardial positron emission tomography, radioactive isotope tracers of palmitate and glucose, and echocardiography to evaluate myocardial metabolism and function. HIV+ people with The Metabolic Syndrome will receive 16wks of exercise training or pioglitazone (Actos), and we will evaluate their potential beneficial effects on myocardial metabolism and function.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
DIAGNOSTIC
Masking
NONE
Enrollment
24
30mg/day for 16 weeks
Cardiorespiratory and resistance exercise training 3days/wk for 16 weeks
Washington University School of Medicine
St Louis, Missouri, United States
Myocardial Glucose Utilization Rate
Radio-tracer (11C-glucose) and positron emission tomography quantification of myocardial glucose utilization rate. The rate at which glucose exits the blood, enters the muscle cells in the left ventricle, and is metabolized (ATP generation, glycolysis, glycogenolysis, or lactate production). Total glucose utilization rate in the left ventricle of the heart.
Time frame: Weeks 0 and 16
Myocardial Glucose Utilization Rate Per Unit Insulin
Radio-tracer (11C-glucose) and positron emission tomography quantification of myocardial glucose utilization rate per unit of plasma insulin. Total glucose utilization rate in the left ventricle of the heart expressed per unit of the circulating plasma insulin concentration.
Time frame: Weeks 0 and 16
Myocardial Fatty Acid Utilization Rate
Radio-tracer (11C-palmitate) and positron emission tomography quantification of myocardial fatty acid utilization rate. The rate at which palmitate exits the blood, enters the muscle cells in the left ventricle, and is metabolized (oxidation, re-esterification).
Time frame: Weeks 0 and 16
Myocardial Fatty Acid Oxidation Rate
Radio-tracer (11C-palmitate) and positron emission tomography quantification of myocardial fatty acid oxidation rate.
Time frame: Weeks 0 and 16
Myocardial Fatty Acid Esterification
Radio-tracer (11C-palmitate) and positron emission tomography quantification of myocardial fatty acid esterification as a % of total fatty acid extraction
Time frame: Weeks 0 and 16
Myocardial Contractile Function During Diastole
Echocardiographic quantification of (E/A) early to late diastolic filling velocity. Aria transfer blood to the ventricles in 2 steps: 1. blood collected in the atria falls into the ventricles when the atrioventricular valves opens. In the left heart, the velocity at which the blood moves during this initial action is called the early or "E" filling velocity. 2. residual blood in the atria, is emptied during diastole by atrial contraction. The velocity of the blood during atrial contraction is the "A" (for atrial) filling velocity. These are expressed as a ratio (E/A). If A exceeds E velocity (ratio \<1.0) this is a clinical marker of diastolic dysfunction. This can occur when the left ventricular wall becomes so stiff as to impair proper filling, which can lead to diastolic heart failure.
Time frame: Weeks 0 and 16
Myocardial Contractile Function During Systole
Echocardiographic quantification of E' wall velocity during systole averaged at the lateral wall and septum
Time frame: Weeks 0 and 16
Fasting Lipids and Lipoproteins
fasting serum triglycerides, LDL-, and HDL-cholesterol concentrations
Time frame: Week 0 and 16
Fasting Glucose Insulin and HOMA
fasting plasma glucose, insulin concentrations and HOMA-insulin resistance
Time frame: Week 0 and 16
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