Effects of fluvastatin in type 2 diabetic patients with hyperlipidemia: reduction in cholesterol oxidation products and VCAM-1.
The purpose of this study was to investigate the lipid-lowering and anti-oxidative effects of fluvastatin, a 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor, in type 2 diabetic patients. Six patients (3 men and 3 women, mean age = 56.2) took 20 mg of fluvastatin once daily (at night) for 12 weeks. Several markers of oxidative stress were then measured in these patients including plasma cholesterol oxidation products, i.e. oxysterols, and the levels of circulating adhesion molecules. Plasma total cholesterol levels were reduced by 12.3% in these individuals after 4 weeks of treatment, with levels remaining below 220 mg/dl for the entire treatment period. LDL levels were significantly reduced at 4 (18.1%) and 12 weeks (16.1%), and triglyceride levels were significantly reduced after 8 (22.5%) and 12 (37.7%) weeks of treatment. HDL-C levels increased from 50.7 +/- 15.4 prior to treatment to 63.8 +/- 24.3 mg/dl after 12 weeks of treatment, though this increase was not statistically significant. Lipid hydroperoxide, thiobarbituric acid-reactive substance (TBARS), and oxysterol levels were also reduced, suggesting that fluvastatin also had anti-oxidative effects. Finally, VCAM-1 levels were similarly reduced by fluvastatin treatment. We conclude that fluvastatin safely improves the plasma lipid profile in type 2 diabetic patients with hyperlipidemia. We speculate that this drug might be doubly effective in reducing atherosclerosis and cardiac events in these patients as a result of its demonstrated anti-oxidative effects and its ability to reduce VCAM-1 levels.
Guan
Jing-Zhi
JZ
Third Department of Internal Medicine, Hirosaki University School of Medicine, Zaifu 5, Hirosaki, Aomori 036-8562, Japan.
Murakami
Hiroshi
H
Yamato
Kazumi
K
Tanabe
Jutaro
J
Matsui
Jun
J
Tamasawa
Naoki
N
Suda
Toshihiro
T
D000975:Antioxidants / Q000627:therapeutic use; D002784:Cholesterol / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D005229:Fatty Acids, Monounsaturated / Q000627:therapeutic use*; D005260:Female; D000077340:Fluvastatin; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D006949:Hyperlipidemias / Q000150:complications / Q000188:drug therapy*; D007211:Indoles / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism*
D000975:Antioxidants; D005229:Fatty Acids, Monounsaturated; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles; D019010:Vascular Cell Adhesion Molecule-1; D000077340:Fluvastatin; D002784:Cholesterol