• The effect of treatment on Peak LDL particle size
  

• The effect of treatment on:
  
• traditional lipid parameters (LDL-C, HDL-C, triglycerides)
  
• % of lipids in regions IIIa+IIIb of a gradient gel electrophoresis
  
• LDL phenotype
  
• fasting glucose
  
• Hemoglobin A1c
  

The Metabolic Syndrome is characterized by an atherogenic dyslipidemia consisting of hypertriglyceridemia, modest elevations of LDL cholesterol, low levels of HDL cholesterol, and LDL phenotype pattern B (small, dense LDL particles). Statins are first line therapy, and reduce LDL cholesterol levels without affecting LDL particle size. Fenofibrate addresses the triglycerides, HDL cholesterol levels, and LDL phenotype, so is recommended as second level therapy. The third element is niacin, but for insulin resistant patients, a question has been whether niacin might be exacerbating the underlying pathophysiology of Metabolic Syndrome patients. In SNARED, niacin was compared to the insulin sensitizer rosiglitazone in study subjects already on statin and fenofibrate.

All volunteers participating in SNARED exhibit LDL phenotype pattern B despite statin therapy at the time of recruitment. Comparisons of LDL phenotype at baseline are to be compared to measurements made after 4 months of statin + fenofibrate. If the LDL phenotype converts to pattern A (large LDL particles), this is a study endpoint. Otherwise, study subjcts are randomized to receive statin+fenofibrate+niacin, or statin+fenofibrate+rosiglitazone for six months, at which time lipid phenotype will again be determined..