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/m(2)) with type 2 diabetes mellitus (hemoglobin A(1c) 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 con improve lipoprotein metabolism in type 2 diabetes. However, the medications affect different aspects of lipoprotein metabolism. (C) 2001 by Excerpta Medico, Inc.