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


R.P.F. Dullaart, Department of Endocrinology, University Medical Centre Groningen, University of Groningen, PO Box 30·001, Groningen, 9700 RB, the Netherlands. Tel.: +31 503613731; Fax: +31 503619392; E-mail: r.p.f.dullaart@int.umcg.nl


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 (β = –0·15, P = 0·028) and adiponectin (β = –0·18, P = 0·009), and positively to leptin (β = 0·33, P < 0·001) and BMI (β = 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.