[A relationship between insulin resistance and reduction in oxidative stress in vivo by atorvastatin].
OBJECTIVE
To examine the relationship between insulin resistance (IR) and the reduction of oxidative stress in vivo by the statin atorvastatin.


METHODS
This study included 40 patients with hypercholesterolemia without a history of diabetes mellitus (21 males, 19 females, mean age 62 +/- 11 years). Homeostasis assessment insulin resistance (HOMA-IR) was used as a marker for insulin resistance. The patients were divided into two groups [IR group (n = 24) and non-IR group (n = 16), using the cut off level of 1.73]. Urinary 8-iso-prostaglandin F2alpha (U-8-iso) excretion was used as an oxidative stress marker. The subjects were treated with atorvastatin (10 mg/day) for 12 weeks.


RESULTS
The IR group had significantly higher U-8-iso levels than the non-IR group before atorvastatin administration (211 +/- 112 vs 137 +/- 33 pg/mg Cr, p = 0.01). Low-density lipoprotein cholesterol, triglyceride, and 8-iso levels were significantly reduced in both groups after 12 weeks, U-8-iso levels were significantly higher in the IR group than the non-IR group (178 +/- 61 vs 110 +/- 38 pg/mg Cr, p = 0.003), and HOMA-IR showed no significant change. Multiple regression analysis after 12 weeks showed that HOMA-IR and triglyceride levels were independent variables for U-8-iso levels (standard regression coefficient = 0.60, 0.59, p < 0.0001, p = 0.0002).


CONCLUSIONS
Insulin resistance is important in the occurrence of oxidative stress in patients with hypercholesterolemia. Since atorvastatin does not reduce insulin resistance, further therapy to reduce insulin resistance is necessary for early prevention of cardiovascular events during atorvastatin treatment.
Hitsumoto
Takashi
T
Department of Cardiovascular Center, Sakura Hospital, Toho University School of Medicine, Chiba. ddda@cc.rim.or.jp
Iizuka
Takuo
T
Takahashi
Mao
M
Nakamura
Keijirou
K
Shimizu
Kazuhiro
K
Satoh
Shin
S
Sugiyama
Yuko
Y
Sakurai
Takeshi
T
Noike
Hirofumi
H
Ohsawa
Hidefumi
H
Watanabe
Hitoshi
H
Shirai
Kohji
K
D000368:Aged; D000069059:Atorvastatin; D015237:Dinoprost / Q000031:analogs & derivatives* / Q000652:urine; D005260:Female; D006538:Heptanoic Acids / Q000494:pharmacology* / Q000627:therapeutic use; D006706:Homeostasis; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D006937:Hypercholesterolemia / Q000097:blood / Q000503:physiopathology*; D007333:Insulin Resistance; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects*; D011758:Pyrroles / Q000494:pharmacology* / Q000627:therapeutic use
D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008055:Lipids; D011758:Pyrroles; C075750:8-epi-prostaglandin F2alpha; D000069059:Atorvastatin; D015237:Dinoprost