Serum paraoxonase-I activity is unaffected by short-term administration of simvastatin, bezafibrate, and their combination in type 2 diabetes mellitus

Background: The high-density lipoprotein (HDL)-associated anti-oxidative and anti-inflammatory enzyme, paraoxonase-I, has been found previously to be lower in type 2 diabetes mellitus. We studied whether statin and fibrate treatment, alone and in combination, affect serum paraoxonase-I activity in conjunction with changes in HDL cholesterol in diabetic patients. Subjects and methods: A placebo-controlled crossover study was carried out in 14 type 2 diabetic patients to test the effect of 8 weeks of active treatment with simvastatin (40 mg daily), bezafibrate (400 mg daily), and their combination on serum paraoxonase-I activity, measured as its activity towards arylesterase and paraoxon. Serum paraoxonase-I activity was also compared between these diabetic patients and 49 non-diabetic control subjects. Results: Serum arylesterase activity was lower in type 2 diabetic patients compared to control subjects (P < 0·001), but the difference in paraoxonase activity was not significant (P = 0·22). Neither arylesterase (P = 0·24) nor paraoxonase activity (P = 0·37) was increased in response to treatment, despite higher HDL cholesterol and apolipoprotein A-I during combination therapy (P < 0·05 for both). Conclusion: Short-term administration of simvastatin and bezafibrate, even when combined, is ineffective in raising serum paraoxonase-I activity in type 2 diabetes.