阿托伐他汀和ω-3 乙酯 90 对 2 型糖尿病患者血浆植物固醇浓度和胆固醇合成的影响：一项随机安慰剂对照析因试验。
Impact of atorvastatin and omega-3 ethyl esters 90 on plasma plant sterol concentrations and cholesterol synthesis in type 2 diabetes: a randomised placebo controlled factorial trial.
机构信息
NIHR School of Primary Care Research, Division of Public Health & Primary Health Care, University of Oxford, Old Road Campus, Headington, Oxford OX3 7LF, UK.
出版信息
Atherosclerosis. 2010 Dec;213(2):512-7. doi: 10.1016/j.atherosclerosis.2010.09.013. Epub 2010 Sep 18.
OBJECTIVE
To determine the effects of statin treatment and omega-3 polyunsaturated fatty acid supplementation on plasma plant sterol concentrations and cholesterol synthesis in patients with type 2 diabetes.
METHODS
Plant sterol concentrations and lanosterol (a marker of cholesterol synthesis) were measured using a high sensitivity assay to assess the effect of double-blind daily treatment for 4 months with atorvastatin 20mg or placebo and, in a 2 × 2 factorial design, omega-3 ethyl esters 90 2g or placebo.
RESULTS
658 patients were included in a per protocol analysis. The 4 treatment groups had similar mean [SD] age (63.5 years [11.7]), HbA(1c) (6.9% [1.1]) and diabetes duration (median 4 years [inter-quartile range 2, 8]). Atorvastatin treatment alone reduced low density lipoprotein (LDL) cholesterol by 1.4 mmol/l (44%, p<0.001), triglycerides by 0.3 mmol/l (20%, p<0.0001) and lanosterol by 0.36 μmol/l (72%, p<0.001). There was no significant placebo adjusted change in median [95% confidence intervals] total plant sterol concentrations (-0.77 μmol/l [inter-quartile range -2.13, 0.59]), although they were increased significantly with omega-3-acid EE90 treatment (3.23 μmol/l [1.28, 5.17]). There was a 27% smaller reduction in LDL cholesterol with atorvastatin treatment in low cholesterol synthesisers with high absorption, defined by changes at or above the median lanosterol and campesterol levels, respectively, compared with the obverse group (difference 0.42 mmol/l [0.21, 0.62]).
CONCLUSION
Treatment with atorvastatin in type 2 diabetes did not change median total plasma plant sterol concentrations, but LDL cholesterol was reduced most efficaciously in high cholesterol synthesisers with low intestinal cholesterol absorption.
CLINICAL TRIAL REGISTRATION INFORMATION
Current controlled trials number ISRCTN: 76737502 (http://isrctn.org).
目的
确定他汀类药物治疗和 ω-3 多不饱和脂肪酸补充对 2 型糖尿病患者血浆植物固醇浓度和胆固醇合成的影响。
方法
使用高灵敏度测定法测量植物固醇浓度和羊毛甾醇（胆固醇合成的标志物），以评估阿托伐他汀 20mg 或安慰剂每日双盲治疗 4 个月的效果，并采用 2×2 析因设计评估 ω-3 乙酯 90 2g 或安慰剂的效果。
结果
658 例患者纳入方案分析。4 个治疗组的平均[标准差]年龄（63.5 岁[11.7]）、HbA1c（6.9%[1.1]）和糖尿病病程（中位数 4 年[四分位距 2，8]）相似。阿托伐他汀单独治疗可使低密度脂蛋白（LDL）胆固醇降低 1.4mmol/L（44%，p<0.001）、甘油三酯降低 0.3mmol/L（20%，p<0.0001）和羊毛甾醇降低 0.36μmol/L（72%，p<0.001）。总植物固醇浓度的中位数[95%置信区间]无显著安慰剂调整变化（-0.77μmol/L[-2.13，0.59]），尽管 ω-3-酸 EE90 治疗后总植物固醇浓度显著升高（3.23μmol/L[1.28，5.17]）。在胆固醇合成较高、肠道胆固醇吸收较高的患者中，与相反组相比，阿托伐他汀治疗的 LDL 胆固醇降低幅度较小（差异 0.42mmol/L[0.21，0.62]），定义为羊毛甾醇和菜油固醇水平分别等于或高于中位数。
结论
在 2 型糖尿病患者中，阿托伐他汀治疗并未改变血浆总植物固醇浓度的中位数，但在胆固醇合成较高、肠道胆固醇吸收较低的患者中，LDL 胆固醇的降低效果最为显著。
临床试验注册信息
当前对照试验编号 ISRCTN：76737502（http://isrctn.org）。
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