Effects of atorvastatin versus fenofibrate on lipoprotein profiles, low-density lipoprotein subfraction distribution, and hemorheologic parameters in type 2 diabetes mellitus with mixed hyperlipoproteinemia

Diabetic dyslipoproteinemia characterized by hypertriglyceridemia, low high-density lipoprotein (HDL) cholesterol, and often elevated low-density lipoprotein (LDL) cholesterol with predominance of small, dense LDL is a strong risk factor for atherosclerosis. It is unclear whether fibrate or statin therapy is more effective in these patients. We compared atorvastatin (10 mg/day) with fenofibrate (200 mg/day), each for 6 weeks separated by a 6-week washout period in 13 patients (5 men and 8 women; mean age 60.0 ± 6.8 years; body mass index 30.0 ± 3.0 kg/m2) with type 2 diabetes mellitus (hemoglobin A1c 7.3 ± 1.1%) and mixed hyperlipoproteinemia (LDL cholesterol 164.0 ± 37.8 mg/dl, triglycerides 259.7 ± 107 mg/dl, HDL cholesterol 48.7 ± 11.0 mg/dl) using a randomized, crossover design. Lipid profiles, LDL subfraction distribution, fasting plasma viscosity, red cell aggregation, and fibrinogen concentrations were determined before and after each drug. Atorvastatin decreased all LDL subfractions (LDL cholesterol, −29%; p <0.01) including small, dense LDL. Fenofibrate predominantly decreased triglyceride concentrations (triglycerides, −39%; p <0.005) and induced a shift in LDL subtype distribution from small, dense LDL (−31%) to intermediate-dense LDL (+36%). The concentration of small, dense LDL was comparable during therapy to both drugs (atorvastatin 62.8 ± 19.5 mg/dl, fenofibrate 63.0 ± 18.1 mg/dl). Both drugs induced an increase in HDL cholesterol (atorvastatin +10%, p <0.05; fenofibrate +11%, p = 0.06). In addition, fenofibrate decreased fibrinogen concentration (−15%, p <0.01) associated with a decrease in plasma viscosity by 3% (p <0.01) and improved red cell aggregation by 15% (p <0.05), whereas atorvastatin did not affect any hemorheologic parameter. We conclude that atorvastatin and fenofibrate can improve lipoprotein metabolism in type 2 diabetes. However, the medications affect different aspects of lipoprotein metabolism.