The purpose of this study is to investigate the extent to which diet and exercise may improve PAH through the modulation of insulin sensitivity. The central hypothesis is that dysregulated glucose metabolism elicits a response in PAH patients that can be modified by exercise and diet, thereby leading to improvements in pulmonary vascular disease.

Pulmonary arterial hypertension (PAH) leads to premature death as a consequence of increased pulmonary vascular resistance and right heart failure. PAH-targeted therapies developed over the past 20 years target excessive vasoconstriction. However, the pathobiology of PAH is more complicated, and includes dysregulated vascular cell proliferation, cellular metabolic abnormalities, and inflammation. Even with modern PAH therapies, current outcomes remain poor, with an estimated 3-year survival rate of only 55%. Thus, there is a clear need for more effective therapies, based on better understanding of the pathobiology of the disease.

Insulin resistance has emerged as a potential new mechanism in PAH. Animal models of insulin resistance are associated with PAH, which reverses with the administration of insulin sensitizing drugs. Over the past decade there has been an epidemiologic shift in PAH, where the disease is increasingly observed in older, obese, and diabetic subjects. Low levels of high-density lipoprotein cholesterol in PAH, a feature of insulin resistance, have been observed and found to be a strong independent predictor of PAH mortality. Elevated glycosylated hemoglobin (HbA1c) also correlates with PAH diagnosis and severity. As measured by the OGTT, idiopathic PAH patients have not only insulin resistance, but also an inability to mount an appropriate insulin response to a glucose challenge. These data point to dysfunction in the pancreatic beta cells of PAH patients. It is known that an exercise and low glycemic index diet intervention improves insulin sensitivity in pre-diabetic subjects.

Inclusion Criteria:

• Age range between 18-75 years old
• Group 1 PAH, including idiopathic, heritable, drugs and toxin induced, and PAH associated with connective tissue disease, HIV infection and congenital heart disease
• NYHA Class II or III
• ≥ 1 PAH-targeted therapy with a stable dose for ≥ 2 months
• Stable dose of diuretics and rate of supplemental oxygen for the preceding 2 months

Exclusion Criteria:

• Decompensated Right Heart Failure
• NYHA Class IV
• Syncope within the previous 3 months
• Cardiac Arrhythmia (except for controlled atrial fibrillation or flutter)
• Baseline supplemental O2 > 4 LPM
• Portal Hypertension
• Pulmonary hypertension due to Lung Disease and Hypoxia
• Pulmonary Hypertension due to Left Heart Disease
• Chronic Thromboembolic Pulmonary Hypertension
• Pulmonary Hypertension associated with systemic diseases such as hematological disorders and sarcoidosis
• Type 2 Diabetes
• Evidence of cardiac ischemia on a graded exercise test