Low human paraoxonase predicts cardiovascular events in Japanese patients with type 2 diabetes.

Human serum paraoxonase (PON1) is associated with HDL and inhibits oxidative modification of LDL. PON1 enzymatic activity has been shown to decrease in diabetic patients; however, the effect of PON1 status on long-term outcome has not been reported. In this study, we examined the association between baseline PON1 status and the development of cardiovascular disease (CVD) during 10 years of follow-up in 88 type 2 diabetic patients whose enzymatic activities, concentrations, and genetic polymorphisms of PON1 had been determined. A total of 20 CVD events were recorded during the follow-up period. Using Kaplan-Meier survival curves, we found a significantly increased incidence of CVD in patients with a lower concentration or paraoxonase activity of PON1 than each median value (log-rank 7.460; P < 0.01, and log-rank 4.187; P < 0.05, respectively). By Cox regression analysis, both concentration and paraoxonase activity were significantly associated with the development of CVD, even after correction for gender, age, and preexisting CVD (P < 0.05). Low concentration and enzymatic activity of PON1 may be an independent predictor of cardiovascular events in diabetic patients.