Combined effect of coenzyme Q10 and fenofibrate on forearm microcirculatory function in type 2 diabetes.
Arteriopathy is the principal complication of type 2 diabetes mellitus. It develops from endothelial dysfunction, which we have hypothesised occurs in diabetes primarily as a consequence of dyslipidaemia and oxidative stress. Fenofibrate and CoQ may improve endothelial function by regulating dyslipidaemia and oxidative stress, respectively. We therefore aimed to assess the independent and combined effects of fenofibrate and coenzyme Q(10) (CoQ) on endothelium-dependent and endothelium-independent vasodilator function of the forearm microcirculation in type 2 diabetes. Eighty dyslipidaemic type 2 diabetics were randomized to receive fenofibrate (200 mg/daily), CoQ (200 mg/daily), fenofibrate plus CoQ (200+200 mg daily), or placebo for 12 weeks. Forearm microcirculatory function was assessed with venous occlusion plethysmography during the infusion of acetylcholine (ACh), bradykinin (BK), sodium nitroprusside (SNP) and N(G)-monomethyl-L-arginine (L-NMMA) into the brachial artery. Blood flow responses were calculated as area under the curve (AUC). Fenofibrate significantly lowered plasma cholesterol, triglyceride and fibrinogen (P<0.001), and elevated HDL-cholesterol and homocysteine (P<0.001). CoQ did not change plasma isoprostanes, but significantly lowered systolic blood pressure and HbA(1c) (P<0.05). Fenofibrate plus CoQ significantly improved (P<0.05) the AUC for ACh, BK and SNP without significantly altering basal responses to L-NMMA. Fenofibrate or CoQ alone did not significantly alter blood flow responses. Improvements in blood flow were independent of changes in plasma lipids, blood pressure, homocysteine and isoprostanes, but were correlated (P=0.013) with HbA(1c). In conclusion, in this factorial trial we found that only the combination of fenofibrate and CoQ markedly improved endothelial and non-endothelial forearm vasodilator function in dyslipidemic type 2 diabetic patients. The favourable vascular effect of this therapeutic combination could be due to increase in the bioactivity of and/or responses to endothelium-derived relaxing factors, including nitric oxide, and this may entail synergistic stimulation of peroxisome proliferator-activated receptors.
Playford
David A
DA
Department of Medicine, University of Western Australia, Royal Perth Hospital, GPO Box X2213, WA 6847, Australia.
Watts
Gerald F
GF
Croft
Kevin D
KD
Burke
Valerie
V
D000109:Acetylcholine / Q000008:administration & dosage; D000975:Antioxidants / Q000627:therapeutic use*; D016632:Apolipoprotein A-I / Q000097:blood / Q000187:drug effects; D019540:Area Under Curve; D001775:Blood Circulation / Q000187:drug effects*; D001794:Blood Pressure / Q000187:drug effects; D001920:Bradykinin / Q000008:administration & dosage; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003067:Coenzymes; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D004562:Electrocardiography; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D028441:F2-Isoprostanes / Q000097:blood; D005260:Female; D011345:Fenofibrate / Q000097:blood* / Q000627:therapeutic use*; D005542:Forearm / Q000098:blood supply*; D006442:Glycated Hemoglobin / Q000187:drug effects; D006710:Homocysteine / Q000097:blood / Q000187:drug effects; D006801:Humans; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009599:Nitroprusside / Q000008:administration & dosage; D012039:Regional Blood Flow / Q000187:drug effects; D013223:Statistics as Topic; D013599:Systole / Q000187:drug effects; D016896:Treatment Outcome; D014280:Triglycerides / Q000097:blood; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D014665:Vasodilator Agents / Q000008:administration & dosage; D019323:omega-N-Methylarginine / Q000008:administration & dosage
D000109:Acetylcholine; D000975:Antioxidants; D016632:Apolipoprotein A-I; D001920:Bradykinin; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D003067:Coenzymes; D004791:Enzyme Inhibitors; D028441:F2-Isoprostanes; D011345:Fenofibrate; D006442:Glycated Hemoglobin; D006710:Homocysteine; D000960:Hypolipidemic Agents; D009599:Nitroprusside; D014280:Triglycerides; D014451:Ubiquinone; D014665:Vasodilator Agents; D019323:omega-N-Methylarginine; C024989:coenzyme Q10