Statin action favors normalization of the plasma lipidome in the atherogenic mixed dyslipidemia of MetS: potential relevance to statin-associated dysglycemia.
Statin action favors normalization of the plasma lipidome in the atherogenic mixed dyslipidemia of MetS: potential relevance to statin-associated dysglycemia.
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DOI：
10.1194/jlr.p061143
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发表时间：
2015-12
影响因子：
6.5
通讯作者：
Chapman MJ
中科院分区：
文献类型：
--
作者：
Meikle PJ;Wong G;Tan R;Giral P;Robillard P;Orsoni A;Hounslow N;Magliano DJ;Shaw JE;Curran JE;Blangero J;Kingwell BA;Chapman MJ
评价他汀类药物治疗对代谢综合征混合型血脂异常患者血脂异常的影响，代谢综合征是糖尿病的高危人群。12例表现为蛋氨酸代谢综合征的胰岛素抵抗高甘油三酯血压性高血压肥胖男性患者接受匹伐他汀(4 mg/d)治疗180d，与年龄匹配的健康非肥胖男性患者(n=12)作为对照。他汀类药物治疗使甘油三酯(−41%)、残余胆固醇(−55%)和低密度脂蛋白胆固醇(−39%)显著正常化，对高密度脂蛋白胆固醇(+4%)影响不大。脂质组学分析归一化为非高密度脂蛋白-胆固醇，以探索他汀类药物诱导的分子组成差异，而不是血浆胆固醇的降低，结果显示，138种脂质物种中，132种在基线水平低于正常水平，并显著转向他汀类药物治疗的对照组。烷基和烯基磷脂(血浆原)的增加是显著的，与他汀类药物诱导的血浆多不饱和脂肪酸水平显著增加一致。在澳大利亚糖尿病、肥胖和生活方式研究和圣安东尼奥家庭心脏研究队列中，通过超几何分析将他汀类药物介导的脂组变化与糖尿病前期和T2D的异常血浆脂组特征进行比较，发现蛋氨酸介导的脂组显著转向对照组的脂组，表明有明显的正常血脂表型的趋势。匹伐他汀可减轻典型的糖尿病前期和T2D的甲硫氨酸患者的异常血脂。
The impact of statin treatment on the abnormal plasma lipidome of mixed dyslipidemic patients with metabolic syndrome (MetS), a group at increased risk of developing diabetes, was evaluated. Insulin-resistant hypertriglyceridemic hypertensive obese males (n = 12) displaying MetS were treated with pitavastatin (4 mg/day) for 180 days; healthy normolipidemic age-matched nonobese males (n = 12) acted as controls. Statin treatment substantially normalized triglyceride (−41%), remnant cholesterol (−55%), and LDL-cholesterol (−39%), with minor effect on HDL-cholesterol (+4%). Lipidomic analysis, normalized to nonHDL-cholesterol in order to probe statin-induced differences in molecular composition independently of reduction in plasma cholesterol, revealed increment in 132 of 138 lipid species that were subnormal at baseline and significantly shifted toward the control group on statin treatment. Increment in alkyl- and alkenylphospholipids (plasmalogens) was prominent, and consistent with significant statin-induced increase in plasma polyunsaturated fatty acid levels. Comparison of the statin-mediated lipidomic changes in MetS with the abnormal plasma lipidomic profile characteristic of prediabetes and T2D in the Australian Diabetes, Obesity, and Lifestyle Study and San Antonio Family Heart Study cohorts by hypergeometric analysis revealed a significant shift toward the lipid profile of controls, indicative of a marked trend toward a normolipidemic phenotype. Pitavastatin attenuated the abnormal plasma lipidome of MetS patients typical of prediabetes and T2D.