Vrablík Michal, Dobiásová Milada, Stulc Tomás, Kasalová Zdislava, Dolezalová Radka, Prázný Martin, Fait Tomas, Ceska Richard
3rd Department of Medicine, 1st Faculty of Medicine, Charles University, Czech Republic.
Neuro Endocrinol Lett. 2008 Feb;29(1):146-50.
Particle size distribution in both HDL and LDL is reflected in the fractional esterification rate of cholesterol by lecithin cholesterol acyltransferase (LCAT) in plasma depleted of apoB containing lipoproteins (FER(HDL)). We studied FER(HDL) in a group of patients with type 2 diabetes and determined the impact of two different PPAR agonists (fenofibrate and rosiglitazone) on this marker of lipoprotein particle quality.
66 patients with type 2 diabetes (26 women) and 32 control subjects (19 women) were included in the study. 33 patients received fenofibrate and 33 rosiglitazone as add on therapy. Average duration of treatment was 4 months. Plasma lipoprotein glucose levels were determined using an automated analyzer (COBAS Mira, Roche). LDL cholesterol concentrations were calculated by Friedewald formula. FER(HDL) was determined by a radioassay after precipitating apo-B containing particles of plasma. The assays were performed at baseline and at the end of each treatment. SPSS base program was used for statistical evaluation.
Both fenofibrate and rosiglitazone resulted in a significant decrease of FER(HDL) (24.62 +/- 11.27%/h vs. 19.93 +/- 10.34%/h; 20.0 +/- 6.1%/h vs. 15.8 +/- 5.8%/h, p < 0.001). Rosiglitazone was significantly more effective in FER(HDL) lowering than fenofibrate (p < 0,02)
Both fenofibrate and rosiglitazone improve FER(HDL) in patients with type 2 diabetes. The effect is more pronounced for rosiglitazone. Qualitative change of plasma lipoproteins reflected by FER(HDL) can contribute to antiatherogenic action of PPAR agonists. On contrary, changes of lipoprotein composition induced by PPAR agonists cannot explain adverse cardiovascular effects observed in some large clinical trials with PPAR agonists.
高密度脂蛋白(HDL)和低密度脂蛋白(LDL)中的颗粒大小分布反映在血浆中不含载脂蛋白B的脂蛋白(FER(HDL))的卵磷脂胆固醇酰基转移酶(LCAT)对胆固醇的酯化率上。我们研究了一组2型糖尿病患者的FER(HDL),并确定了两种不同的过氧化物酶体增殖物激活受体(PPAR)激动剂(非诺贝特和罗格列酮)对这种脂蛋白颗粒质量标志物的影响。
本研究纳入了66例2型糖尿病患者(26名女性)和32名对照受试者(19名女性)。33例患者接受非诺贝特,33例患者接受罗格列酮作为附加治疗。平均治疗持续时间为4个月。使用自动分析仪(COBAS Mira,罗氏公司)测定血浆脂蛋白葡萄糖水平。采用Friedewald公式计算低密度脂蛋白胆固醇浓度。在沉淀血浆中含载脂蛋白B的颗粒后,通过放射分析法测定FER(HDL)。在基线和每次治疗结束时进行检测。使用SPSS基础程序进行统计评估。
非诺贝特和罗格列酮均导致FER(HDL)显著降低(24.62±11.27%/小时对19.93±10.34%/小时;20.0±6.1%/小时对15.8±5.8%/小时,p<0.001)。罗格列酮在降低FER(HDL)方面比非诺贝特显著更有效(p<0.02)。
非诺贝特和罗格列酮均可改善2型糖尿病患者的FER(HDL)。罗格列酮的效果更显著。FER(HDL)反映的血浆脂蛋白的质量变化可能有助于PPAR激动剂的抗动脉粥样硬化作用。相反,PPAR激动剂引起的脂蛋白组成变化不能解释在一些使用PPAR激动剂的大型临床试验中观察到的不良心血管效应。