Effects of Atorvastatin on LDL sub-fractions and peroxidation in type 1 diabetic patients: a randomised double-blind placebo-controlled study.
BACKGROUND
Patients with diabetes have an increased risk of both developing and dying from cardiovascular disease, and, currently, more aggressive lipid-lowering targets are being recommended for these patients. Statins are widely and successfully used to correct dyslipidemia and prevent acute coronary episodes, but their effects on lipoprotein composition and peroxidation have not been fully investigated. We aimed to address this issue in type 1 diabetes mellitus.


METHODS
T1DM patients with atherogenic index (total/HDL-cholesterol > 4) were randomised double-blindly to group A (n = 12) that received Atorvastatin 40 mg/day and group P (n = 12) that received placebo. They were monitored for blood biochemistry, LDL sub-fractions and lipid peroxidation at inclusion, after 6 and after 12 weeks.


RESULTS
In group A, the 40% decrease in serum total and LDL cholesterol and 20% decrease in triglycerides was accompanied by a decrease in serum alpha-tocopherol from 46.4 +/- 16.3 (mean +/- SD) at inclusion to 32.2 +/- 11.8 and 32.6 +/- 14.0 micromol/L after 6 and 12 weeks respectively (p < 0.001 compared to group P by repeated-measures ANOVA). Relative to LDL + VLDL cholesterol, alpha-tocopherol increased by 40% (p < 0.001). Copper-induced LDL + VLDL peroxidation increased from 4891 +/- 1325 at inclusion to 6821 +/- 2291 and 7040 +/- 1712 nmol TBARS/mg LDL + VLDL cholesterol produced in 3 h (p = 0.004). LDL sub-fractions shifted towards the less dense regions (p = 0.03).


CONCLUSIONS
These results suggest that Atorvastatin lowers the antioxidant capacity of LDL and VLDL in T1DM. The mechanisms underlying these changes merit further investigation and should be taken into account when planning long-term primary prevention of CHD in diabetes.
Manuel-Y-Keenoy
Begoña
B
Laboratory of Endocrinology, University of Antwerp, Belgium. begona@uia.ua.ac.be
Van Campenhout
Christel
C
Vertommen
Jan
J
De Leeuw
Ivo
I
D000328:Adult; D017668:Age of Onset; D000368:Aged; D000069059:Atorvastatin; D015992:Body Mass Index; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000503:physiopathology*; D004311:Double-Blind Method; D005215:Fasting; D005260:Female; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D015227:Lipid Peroxidation / Q000187:drug effects*; D008055:Lipids / Q000097:blood*; D008077:Lipoproteins, LDL / Q000097:blood* / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D010919:Placebos; D011758:Pyrroles / Q000627:therapeutic use*; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis
D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008055:Lipids; D008077:Lipoproteins, LDL; D010919:Placebos; D011758:Pyrroles; D017392:Thiobarbituric Acid Reactive Substances; D000069059:Atorvastatin