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

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

This study will test the hypothesis that reducing the release of free fatty acids (FFA) from fat cells will restore insulin-mediated, endothelium-dependent vasodilation in people with 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