Effects of cilostazol on serum lipoprotein concentrations and particle size of low-density lipoproteins in patients with dyslipidemic NIDDM

Cilostazol is registered for the treatment of chronic atherosclerotic diseases such as arteriosclerosis obliterans and diabetes mellitus. Recently, the lipid lowering effects of cilostazol in hyperlipidemic subjects have also attracted attention. We investigated the effects of cilostazol on lipoprotein metabolism in 12 NIDDM subjects with dyslipoproteinemia. Eight NIDDM patients with dyslipoproteinemia were also investigated as control subjects. One hundred fifty mg per day of cilostazol was administered orally for three 4-week periods. Serum lipid and apolipoprotein concentrations were measured at the end of each 4-week period. Cholesterol content in the remnant-like particles (RLP-c) was measured by using monoclonal anti apo B-100 and anti apo A-I immunoaffinity mixed gels. LDL particle size was analyzed based on a new parameter, LDL-migration index (LDL-MI), which was calculated by dividing the distance from the VLDL peak to the LDL peak by the distance from the VLDL peak to the HDL peak on a PAGE densitogram. Serum concentrations of TC and LDL-c did not change, while the TG content in serum decreased significantly and the HDL-c content increased significantly. No significant changes of the lipid levels were found in the control subjects. Apo C-III and E decreased significantly. RLP-c also decreased from 11.4 to 5.1mg/dl. LDL-MI showed a significant decrease from 0.40 to 0.36, while LDL-MI showed no change in the control group. These results suggest that cilostazol may have some beneficial effects on lipoprotein metabolism by normalizing LDL particle size in NIDDM patients with dyslipoproteinemia.