Paragh_2006_Br.J.Clin.Pharmacol_61_694

AIMS: Diabetic dyslipidaemia with decreased high-density lipoprotein-cholesterol (HDL-C) concentration plays a key role in enhanced atherosclerosis. The antioxidant effect of HDL is due to the influence of human paraoxonase 1 (PON1) and several authors have described decreased activity of this enzyme in Type 2 diabetics and subjects with metabolic syndrome. The goal of this study was to examine the effect of daily ciprofibrate on serum PON1 and lipoprotein concentrations in patients with metabolic syndrome.
METHODS: Fifty-one patients with metabolic syndrome were enrolled into the study. We examined the effect of 100 mg day(-1) ciprofibrate treatment on lipid concentrations, oxidized low-density lipoprotein (LDL), PON1 concentrations and activity. We also investigated the calculated size of LDL-cholesterol (LDL-C).
RESULTS: During the 3-month study, it was observed that following treatment with ciprofibrate, the serum triglyceride concentration decreased significantly (from 2.76 +/- 0.9 mmol l(-1) to 2.27 +/- 1.6 mmol l(-1); -18%; P < 0.001), while HDL-C increased significantly (from 0.95 +/- 0.2 mmol l(-1) to 1.2 +/- 0.3 mmol l(-1); 26%; P < 0.001). The oxidatively modified LDL-C concentration decreased significantly (from 137 +/- 19 U l(-1) to 117 +/- 20 U l(-1); P < 0.001), while HDL-associated apolipoprotein A1 significantly increased (from 1.35 +/- 0.2 g l(-1) to 1.75 +/- 0.3 g l(-1); P < 0.001). The LDL-C/LDL-apoB ratio, which reflects the size of LDL, increased significantly (from 0.96 +/- 0.05 to 1.05 +/- 0.06; P < 0.05). Serum PON1 activity was significantly elevated (from 108 +/- 34 U l(-1) to 129 +/- 31 U l(-1); P < 0.05), while standardized values for HDL-C remained significantly unchanged (PON1/HDL-C) (from 114 +/- 21 to 107 +/- 20; NS). CONCLUSION: Three months of treatment with ciprofibrate favourably affected the lipid profile, increased LDL resistance to oxidation and improved antioxidant status by increasing serum paraoxonase activity in these patients.