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ENDOCRINE AND DIABETES MELLITUS

The Effects of Different Doses of Atorvastatin on Plasma Endothelin-1 Levels in Type 2 Diabetic Patients with Dyslipidemia

Hing-Chung Lam^*,,1, Chih-Hsun Chu^,, Mei-Chih Wei, Hsiu-Man Keng, Chih-Chen Lu^,, Chun-Chin Sun, Jenn-Kuen Lee^,, Ming-Ju Chuang, Mei-Chun Wang and Ming-Hong Tai^*

^* Department of Medical Education and Research, and Department of Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, ROC; and National Yang-Ming University School of Medicine, Taipei, Taiwan, ROC

To whom requests for reprints should be addressed at ¹ Division of Medical Research, Department of Medical Education and Research, Kaohsiung Veterans General Hospital, 386, Ta-Chung 1st Rd., Kaohsiung, Taiwan 813, Republic of China. E-mail: hclam{at}isca.vghks.gov.tw

Abstract

We investigated the effects of three different daily doses (10 mg, 20 mg, and 40 mg) of atorvastatin, a relatively new and potent statin, on plasma endothelin (ET)-1 and highly sensitive C-reactive protein (CRP) levels in type 2 diabetic subjects. Twenty-nine type 2 diabetic patients with dyslipidemia were enrolled and randomly assigned to receive atorvastatin orally at 10 mg (A10; n = 10), 20 mg (A20; n = 10), or 40 mg (A40; n = 9) daily for 12 weeks. Levels of plasma total cholesterol and low-density lipoprotein (LDL)-cholesterol (C) in all three studied groups were significantly decreased after treatment with atorvastatin for 12 weeks (all groups, P < 0.001). However, the greatest LDL-C lowering effect and the highest percentage of subjects achieving the National Cholesterol Education Program’s Adult Treatment Panel III (NCEP-ATP III) LDL-C goal were observed in the A20 group. All diabetic subjects had a higher plasma ET-1 concentration (A10, 1.02 ± 0.37 pg/ml, mean ± SD; A20, 1.17 ± 0.55 pg/ml; and A40, 0.87 ± 0.45 pg/ml) than that of age- and sex-matched normal control subjects (0.64 ± 0.15 pg/ml; all groups, P < 0.001). Plasma ET-1 levels showed a borderline significant decrease at the end of study, by 22% in diabetic subjects treated with 10 mg atorvastatin (P=0.05 compared with baseline), and by 30% in subjects treated with 20 mg atorvastatin (P = 0.06, compared with baseline). Paradoxically, the 40-mg dose of atorvastatin provided an increase of 2% in plasma ET-1 levels at the end of study, which is significantly different (P < 0.05) and marginally significant (P = 0.057) from the levels of the 10- and 20-mg doses, respectively. Similarly, although insignificantly, plasma concentrations of CRP also tended to decrease by 12% and 48%, and paradoxically increased by 18% in diabetic patients treated with 10 mg, 20 mg, and 40 mg atorvastatin, respectively. The clinical significance of these biphasic lipid-independent statin effects is unknown and the present study suggests that 20 mg atorvastatin may have the best benefits in treating diabetic patients with dyslipidemia.

Key Words: atorvastatin • CRP • dyslipidemia • endothelin-1 • type 2 diabetes