The Impact of Free Fatty Acid Reduction on Vascular Function in the Metabolic Syndrome

We hypothesize that acipimox, by decreasing plasma FFA concentrations, will augment
endothelium-dependent vasodilation in conduit vessels and insulin-mediated vasodilation in
forearm resistance arterioles in vivo, whole-body insulin sensitivity, and AKT (also known as
Protein Kinase B) and endothelial nitric oxide synthase (eNOS) phosphorylation in skin biopsy
specimens ex vivo, when compared with placebo.

Inclusion Criteria:

- Adults with metabolic syndrome, defined as the presence of 3 of 5 components of the
syndrome as defined by the National Cholesterol Education Program including:

- abdominal obesity

- elevated fasting blood sugar (110 mg/dL< glucose < 126 mg/dL)

- low HDL

- elevated fasting blood triglycerides (> 150 mg/dL)

- hypertension (BP > 140/90 mm HG)

- Normal cardiovascular examination

Exclusion Criteria:

- Diabetes mellitus

- Untreated hypercholesterolemia (LDL > 75th percentile for age)

- Cigarette smoking within 1 year

- Renal insufficiency (creatinine > 1.4 mg/dl)

- Blood dyscrasia

- Hepatic dysfunction (ALT > 2x normal)

- Evident coronary/peripheral atherosclerosis