Myocardial Function & FFA Metabolism in HIV Metabolic Syndrome

Inclusion Criteria: All participants both with and without metabolic syndrome:

• 28-50 years old.
• Plasma HIV RNA less than 5, 000 copies/mL for previous 3 months OR CD4 count greater than 100 cells/µL for previous 3 months.
• Stable for at least the past 3 months on any HAART regimen.
• "Normal" blood chemistries for at least 1 month prior to enrollment: platelet count >50,000/mm3, absolute neutrophil count >750/mm3, liver transaminases 30g/L, creatine kinase 35kg/m2).
• Chronic hepatitis B infection (HB surface antigen positive). Active hepatitis C infection (detectable Hep C RNA). Those who have cleared hepatitis B or C infection are eligible.
• Diabetes [fasting glucose >125 mg/dL, or fasting insulin >45 µU/mL, or 2-hr glucose >200mg/dL].
• Medications or agents that regulate glucose metabolism (e.g., insulin-sensitizers, insulin-secretagogues). Lipid lowering agents that regulate lipid metabolism (i.e. fibrate, statin).
• Gestational diabetes, pregnancy, or nursing mothers.
• Serum triglycerides ≥ 500 mg/dL.
• Hypogonadism [total testosterone 12µIU/mL]; hypercortisolemia [morning cortisol >22µg/dL]. Replacement testosterone or thyroid hormones to normalize abnormal levels is acceptable, as long as treatment and blood levels have been stable for at least 3 months.
• Use of human growth hormone (hGH) or GH-secretagogues (GH-releasing hormone-peptides) within the previous 3 months.
• History of serious cardiovascular disease; MI, angina pectoris, heart failure, congenital heart disease, coronary artery disease, coronary artery bypass graft, stroke. Bundle branch block is exclusionary because it limits the interpretability of the resting/exercise ECG. Cardiovascular or physical contraindications to maximal exercise testing on a cycle ergometer.
• Uncontrolled hypertension (>140/90 mmHg). Certain antihypertensive medications will be permitted (diuretics, ACE inhibitors) as long as the medication, dose, and blood pressure have been stable for at least 3 months.
• Well-trained athletes (defined as >3 exercise training exposures/week; >30min regimented exercise/exposure maintained for at least the prior 4 weeks).
• History of or active substance abuse (eg, alcoholism, cocaine, heroin, crack, methamphetamine, phencyclidine).
• Active secondary infection. Any significant change in chronic suppressive therapy for an opportunistic infection during 1 month prior to enrollment.
• New serious systemic infection during the 3 weeks prior to enrollment.
• History of hyperlactatemia or lactic acidosis, esp. with rapid weight loss.
• Debilitating-painful myopathy or neuropathy that requires 'assistance' to conduct normal activities of daily living (dressing, hygiene, preparing meals, operating a vehicle). These might affect peripheral substrate metabolism.
• Chronic renal insufficiency/failure or other comorbid conditions (eg. cancer, COPD) that alter metabolism.
• Pancreatitis, celiac disease, or cirrhosis.
• Inadequate macronutrient or energy intake, or malabsorptive disorder.
• Dementia or any condition that would prevent voluntary informed consent or compliance.
• Other compounds or blinded investigational new drugs that might affect metabolism or confound data interpretation (eg. RU486, interleukin therapy, or cytokine-receptor antagonist).
• Oral glucocorticoid or corticosteroid use within previous 3 months.