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Atorvastatin Therapy May Cause Increased Lipid Peroxidation in Patients with Type 1 Diabetes

LDL-cholesterol lowering treatment with atorvastatin may lead to an increase in lipid peroxidation in patients with type 1 diabetes, according to new research.

Individuals with diabetes have a 2- to 4-fold increased risk of morbidity and mortality from cardiovascular disease. Several studies have shown that aggressive LDL-lowering therapy with statins can reduce recurrent coronary heart disease events in patients with diabetes. However, most of these trials were conducted with type 2 diabetes patients, and less information is available on the effects of statins in type 1 diabetes.

"It is not totally known how the properties and composition of lipoproteins are affected and how these can affect lipid peroxidation, foam cell accumulation and eventually atheroma-plaque formation in type 1 diabetes mellitus," writes Begona Manuel-y-Keenoy, of the University of Antwerp, Belgium.

To address this concern, Dr. Manuel-y-Keenoy and colleagues performed a randomised, double-blind study to examine the effects of Atorvastatin on lipoprotein composition, LDL sub-fractions and peroxidation in type 1 diabetes patients with high serum levels of cholesterol.

The study included 24 patients with an atherogenic index (total cholesterol/HDL cholesterol) > 4. The patients were randomised, with 12 to receive 40 mg atorvastatin (mean age, 44; 9 males) and 12 to receive placebo (mean age, 44; 9 males) daily. They were monitored at inclusion and after 6 and 12 weeks of treatment.

Patients treated with atorvastatin experienced a 40%-50% decrease in total and LDL cholesterol, apolipoprotein B and atherogenic index, and a 20% decrease in serum triglycerides compared with the placebo group. LDL subfractions shifted towards the VLDL region with atorvastatin, whereas the pattern of change in the placebo group occurred in the opposite direction.

Vitamin E also decreased significantly in the atorvastatin group compared with the placebo groups (30%, P < .001). However, it increased by 40% when expressed relative to LDL + VLDL. Furthermore, in vitro peroxidation of LDL+VLDL increased by 40% (P = .004) with atorvastatin therapy.

The researchers emphasise that lipid peroxidation can play a fundamental role in the early stages of atheroma-plaque formation, and this may take place many years before the manifestation of clinical episodes.

"The increase in in vitro peroxidation induced by atorvastatin merits further investigation and should be taken into account when planning the primary prevention of the dyslipidaemia in diabetes," the researchers conclude.

Diabetes Metab Res Rev 2003 Nov-Dec;19:6:478-86. "Effects of Atorvastatin on LDL sub-fractions and peroxidation in type 1 diabetic patients: a randomised double-blind placebo-controlled study"

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