SERUM PARAOXONASE ACTIVITY, CONCENTRATION, AND PHENOTYPE DISTRIBUTIONIN DIABETES-MELLITUS AND ITS RELATIONSHIP TO SERUM-LIPIDS AND LIPOPROTEINS

Human serum paraoxonase is physically associated with HDL and has been implicated in the detoxification of organophosphates and possibly in the prevention of LDL lipid peroxidation. We investigated the serum ac tivity and concentration of paraoxonase in 78 patients with type 1 dia betes mellitus, 92 with type 2 diabetes, and 82 nondiabetic control su bjects. Paraoxonase activity was generally lower in diabetics than in control subjects. This decrease was unrelated to differences in paraox onase phenotype distribution or its serum concentration. Rather, the d ifference in paraoxonase activity was explained by its specific activi ty, which was lower in diabetics, indicating either the presence of a circulating inhibitor or disturbance of the interaction of paraoxonase with HDL affecting its activity. Paraoxonase specific activity was lo west in patients with peripheral neuropathy, suggesting an association of paraoxonase with neuropathy. In control subjects but not patients with diabetes, paraoxonase correlated with HDL cholesterol and apolipo protein A-1. Our results indicate that the low paraoxonase activity in diabetes is due to decreased specific activity. In other studies low serum paraoxonase activity has been associated with increased suscepti bility to atherosclerosis, and the present results also suggest an ass ociation with peripheral neuropathy, which could be due to reduced cap acity to detoxify lipid peroxides in diabetes.