Rosiglitazone modulates fasting and post-prandial paraoxonase 1 activity in type 2 diabetic patients.
1. 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. 2. 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. 3. 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). 4. The present data indicate that rosiglitazone may convey increased protection against the oxidative modification that represents increased post-prandial lipaemia.
van Wijk
Jeroen
J
Department of Internal Medicine, University Medical Center, Utrecht, The Netherlands.
Coll
Blai
B
Cabezas
Manuel Castro
MC
Koning
Eelco
E
Camps
Jordi
J
Mackness
Bharti
B
Joven
Jorge
J
D000328:Adult; D043303:Aryldialkylphosphatase / Q000378:metabolism*; D008076:Cholesterol, HDL / Q000097:blood; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000201:enzymology*; D004041:Dietary Fats; D004311:Double-Blind Method; D005215:Fasting / Q000378:metabolism*; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D008054:Lipid Peroxides / Q000378:metabolism; D008297:Male; D047495:PPAR gamma / Q000819:agonists; D019518:Postprandial Period / Q000502:physiology*; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology*
D008076:Cholesterol, HDL; D004041:Dietary Fats; D007004:Hypoglycemic Agents; D008054:Lipid Peroxides; D047495:PPAR gamma; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D043303:Aryldialkylphosphatase