非诺贝特与阿托伐他汀对2型糖尿病合并混合型高脂血症患者E-选择素和血管细胞黏附分子-1浓度的不同影响：一项随机交叉试验。
Differential effects of fenofibrate versus atorvastatin on the concentrations of E-selectin and vascular cellular adhesion molecule-1 in patients with type 2 diabetes mellitus and mixed hyperlipoproteinemia: a randomized cross-over trial.
作者信息
Empen Klaus, Frost Robert J A, Geiss H Christian, Otto Carsten, Parhofer Klaus G
机构信息
Department of Internal Medicine B, University of Greifswald, Germany.
出版信息
Cardiovasc Diabetol. 2003 Dec 8;2:17. doi: 10.1186/1475-2840-2-17.
BACKGROUND
Diabetic dyslipoproteinemia is characterized by hypertriglyceridemia, low HDL-cholesterol and often elevated LDL-cholesterol and is a strong risk factor for atherosclerosis. Adhesion molecule levels are elevated both in hyperlipoproteinemia and diabetes mellitus. It is unclear whether fibrate or statin therapy has more beneficial effects on adhesion molecule concentrations.
METHODS
Atorvastatin (10 mg/d) was compared to fenofibrate (200 mg/d) each for 6 weeks separated by a 6 week washout period in 11 patients (6 male, 5 female; 61.8 +/- 8.2 years; body mass index 29.8 +/- 3.1 kg/m2) with type 2 diabetes mellitus (HbA1c 7.3 +/- 1.1%) and mixed hyperlipoproteinemia using a randomized, cross-over design. Fasting blood glucose, HbA1c, lipid parameters, E-selectin, ICAM-1, VCAM-1, and fibrinogen concentrations were determined before and after each drug.
RESULTS
Glucose and HbA1c concentrations remained unchanged during the whole study period. LDL cholesterol was reduced during atorvastatin therapy, triglycerides were lowered more effectively with fenofibrate. Comparison of pre- and postreatment concentrations of E-selectin showed a reduction during atorvastatin (-7%, p = 0.11) and fenofibrate (-10%, p < 0.05) therapy. Atorvastatin treatment reduced VCAM-1 levels by 4% (p < 0.05), while VCAM-1 concentrations remained unchanged (+1%, ns) during fenofibate therapy. However, direct comparisons of post-treatment levels during both forms of therapy were not of statistical significance. ICAM-1 levels were not influenced by either form of therapy.
CONCLUSIONS
In addition to the different beneficial effects on lipid metabolism, both drugs appear to lower adhesion molecule plasma concentrations in a different manner in patients with type 2 diabetes and mixed hyperlipoproteinemia. Our observations should be confirmed in a larger cohort of such patients.
背景
糖尿病血脂异常血症的特征为高甘油三酯血症、低高密度脂蛋白胆固醇，且常常伴有低密度脂蛋白胆固醇升高，是动脉粥样硬化的一个重要危险因素。在高脂血症和糖尿病中，黏附分子水平均会升高。目前尚不清楚贝特类药物或他汀类药物治疗对黏附分子浓度是否具有更有益的影响。
方法
采用随机交叉设计，对11例2型糖尿病（糖化血红蛋白7.3±1.1%）合并混合性高脂血症患者（6例男性，5例女性；年龄61.8±8.2岁；体重指数29.8±3.1kg/m²）进行研究，将阿托伐他汀（10mg/d）与非诺贝特（200mg/d）各治疗6周，中间间隔6周的洗脱期。在每种药物治疗前后分别测定空腹血糖、糖化血红蛋白、血脂参数、E选择素、细胞间黏附分子-1（ICAM-1）、血管细胞黏附分子-1（VCAM-1）和纤维蛋白原浓度。
结果
在整个研究期间，血糖和糖化血红蛋白浓度保持不变。阿托伐他汀治疗期间低密度脂蛋白胆固醇降低，非诺贝特降低甘油三酯的效果更显著。比较治疗前后E选择素的浓度，阿托伐他汀治疗期间降低了7%（p=0.11），非诺贝特治疗期间降低了10%（p<0.05）。阿托伐他汀治疗使VCAM-1水平降低了4%（p<0.05），而非诺贝特治疗期间VCAM-1浓度保持不变（升高1%，无统计学意义）。然而，两种治疗方式治疗后水平的直接比较无统计学意义。两种治疗方式均未影响ICAM-1水平。
结论
除了对脂质代谢有不同的有益作用外，两种药物似乎以不同方式降低2型糖尿病合并混合性高脂血症患者血浆中黏附分子的浓度。我们的观察结果应在更大规模的此类患者队列中得到证实。
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