Effects of micronized fenofibrate and vitamin E on in vitro oxidation of lipoproteins in patients with type 1 diabetes mellitus.
OBJECTIVE
The primary objective was to compare the antioxidant activity of micronised fenofibrate 200 mg to 400 IU of vitamin E and placebo, on the LDL and VLDL particles of patients with type 1 diabetes. The secondary objective was to investigate the possible synergy between micronized fenofibrate and vitamin E and to compare the efficacy of these treatments on lipids.


METHODS
A double-blind, placebo-controlled trial in which patients were randomised into three treatment groups after a wash-out period of 8 weeks: the placebo group (Pla/Pla-group) in which patients received placebo during two consecutive periods of 8 weeks, the vitamin E group (Vit E/Vit E-group) in which patients received Vitamin E during two consecutive periods, and the fenofibrate/Vitamin E group (Fen/Fen + Vit E-group) in which patients received fenofibrate during the first period, followed by fenofibrate and vitamin E during the consecutive period. Blood samples taken at each visit, were analysed for routine biochemistry, blood lipids and copper mediated lipid peroxidation in vitro.


RESULTS
The lag time of the non-HDL lipoprotein oxidation increased in the group given fenofibrate. The lag-time increased further when fenofibrate and vitamin E were given in association. (This reached significance in the intention-to-treat population, P = 0.034). The AUC of TBARS formation in the Vit E/Vit E group decreased after the first period, but this effect was not enhanced by continuing vitamin E for another 8 weeks. The AUC of TBARS formation did not change significantly after the administration of fenofibrate. Only after the second period, when vit E was given in association, the AUC of TBARS formation decreased significantly (P = 0.004). Fenofibrate caused a significant decrease in total and LDL-cholesterol and triglycerides (P < 0.05). In contrast, vitamin E had no effect on lipids.


CONCLUSIONS
The combination of micronized fenofibrate 200 mg/day and vitamin E 400 IU/day tended to increase the resistance of non-HDL lipoproteins to copper-mediated oxidation, shown by a prolongation of the lag-time. Vitamin E administration only, decreased the oxidation of non-HDL lipoproteins shown by a reduction of TBARS formation. This protective effect of vitamin E tended to be amplified by micronized fenofibrate.
Engelen
W
W
Department of Diabetology, Metabolism and Clinical Nutrition, Faculty of Medicine, University Hospital of Antwerp, UZA, Wilrijkstraat 10, 2650 Edegem, Antwerp, Belgium.
Manuel-y-Keenoy
B
B
Vertommen
J
J
De Leeuw
I
I
Van Gaal
L
L
D000328:Adult; D001794:Blood Pressure; D015992:Body Mass Index; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000503:physiopathology; D004304:Dosage Forms; D004311:Double-Blind Method; D005260:Female; D011345:Fenofibrate / Q000627:therapeutic use*; D006801:Humans; D000960:Hypolipidemic Agents / Q000627:therapeutic use; D008074:Lipoproteins / Q000097:blood* / Q000187:drug effects; D008297:Male; D018579:Patient Selection; D010919:Placebos; D014810:Vitamin E / Q000627:therapeutic use*
D004304:Dosage Forms; D000960:Hypolipidemic Agents; D008074:Lipoproteins; D010919:Placebos; D014810:Vitamin E; D011345:Fenofibrate