High plasma C-reactive protein (CRP) is related to low paraoxonase-I (PON-I) activity independently of high leptin and low adiponectin in type 2 diabetes mellitus.

OBJECTIVES: In type 2 diabetes mellitus, circulating C-reactive protein (CRP) is increased, whereas the high density lipoprotein (HDL)-associated, anti-oxidative and anti-inflammatory enzyme, paraoxonase-I, is decreased. Both high CRP and low paraoxonase-I activity may predict cardiovascular disease. It is unknown whether lower paraoxonase-I activity contributes to higher CRP levels in diabetes. In type 2 diabetic and control subjects, we determined the relationship of CRP with paraoxonase-I when taking account of plasma levels of pro- and anti-inflammatory adipokines.

DESIGN AND PATIENTS: In 81 type 2 diabetic patients and 89 control subjects, plasma high-sensitive CRP, serum paraoxonase-I activity (arylesterase activity, assayed as the rate of hydrolysis of phenyl acetate into phenol), plasma leptin, adiponectin, resistin and lipids were determined.

RESULTS: Body mass index (BMI), waist, insulin resistance, triglycerides, CRP, leptin and resistin levels were higher (P < 0.05 to P < 0.001), whereas HDL cholesterol, paraoxonase-I activity and adiponectin levels were lower (P = 0.02 to P < 0.001) in diabetic compared to control subjects. Multiple linear regression analysis demonstrated that, after controlling for age and gender, CRP was inversely related to paraoxonase-I activity (beta = -0.15, P = 0.028) and adiponectin (beta = -0.18, P = 0.009), and positively to leptin (beta = 0.33, P < 0.001) and BMI (beta = 0.22, P = 0.007), independently of the diabetic state (or of fasting glucose or HbA1c), insulin resistance and lipids (P > 0.20 for all).

CONCLUSIONS: Low paraoxonase-I activity is related to higher CRP, independently of adipokines, as well as of obesity and lipids. Low paraoxonase-I activity in type 2 diabetes mellitus may contribute to increased cardiovascular risk via an effect on enhanced systemic low-grade inflammation.