ROSIGLITAZONE MODULATES FASTING AND POST-PRANDIAL PARAOXONASE 1 ACTIVITY IN TYPE 2 DIABETIC PATIENTS

In the present study, we have explored the effect of rosiglitazone on post-prandial paraoxonase (PON)-1, an enzyme with potent anti-oxidant properties that may protect against atherosclerosis because increased post-prandial lipaemia, although sometimes understated, is part of the diabetic dyslipidaemia.

A randomized, cross-over, placebo-controlled, double-blind clinical trial was performed. Participants (19 type 2 diabetic patients on oral antihyperglycaemic agents) were randomly assigned to receive either placebo or rosiglitazone 4 mg twice daily for 8 weeks. After a 6 week wash-out, the alternative treatment was implemented. Standardized 6 h oral fat-loading tests were performed after each treatment period.

Patients assigned to rosiglitazone had increased fasting PON-1 activity (from 331 ± 29 to 362 ± 32 U/L before treatment vs after treatment, respectively; P = 0.015), although the PON-1 mass did not change (68.8 ± 21.1 vs 64.2 ± 25.4 mg/L before treatment vs after treatment, respectively). In addition, rosiglitazone significantly decreased fasting plasma peroxides compared with placebo (162 ± 25 vs 214 ± 28 mmol/L, respectively; P = 0.019). The post-prandial fall in PON-1 activity, expressed as area under the curve, was attenuated by rosiglitazone (−97 ± 14 vs−161 ± 24 Uh/L for rosiglitazone vs placebo, respectively; P = 0.02) and the increase in PON-1 activity caused by rosiglitazone correlated with reductions in fasting plasma glucose (r = -0.42; P < 0.05), homeostatic model assessment index (r = -0.59; P < 0.01) and peroxides (r = -0.40; P = 0.07).

The present data indicate that rosiglitazone may convey increased protection against the oxidative modification that represents increased post-prandial lipaemia.