Pioglitazone improves myocardial blood flow and glucose utilization in nondiabetic patients with combined hypedipidemia - A randomized, double-blind, placebo-controlled study
Pioglitazone improves myocardial blood flow and glucose utilization in nondiabetic patients with combined hypedipidemia - A randomized, double-blind, placebo-controlled study
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DOI：
10.1016/j.jacc.2007.07.070
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发表时间：
2007-11-20
影响因子：
24
通讯作者：
Camici, Paolo G.
中科院分区：
文献类型：
--
作者：
Naoumova, Rossi P.;Kindler, Heiko;Camici, Paolo G.
目的本研究的目的是检测在常规降脂治疗基础上加用吡格列酮是否能改善非糖尿病家族性混合型高脂血症（FCHL）患者的心肌葡萄糖利用率（MGU）和血流量（MBF）。家族性混合型高脂血症是一种复杂的遗传性疾病，具有早发冠心病的高风险，其特征是高血清胆固醇和/或甘油三酯，低高密度脂蛋白（HDL）胆固醇，和insulinresistance.Methods我们对26例FCHL患者进行了随机，双盲，安慰剂对照研究，用吡格列酮或匹配的安慰剂每天30 mg治疗4周，随后每天45 mg，持续12周。正电子发射断层扫描被用来测量MBF在休息和腺苷诱导充血和MGU在正常血糖高胰岛素钳夹在基线和治疗后。结果而没有变化，在安慰剂组治疗后观察到，患者接受吡格列酮显示全身葡萄糖处置显着增加（3.93 +/- 1.59 mg/kg/min至5.24 +/- 1.65 mg/kg/min; p = 0.004）和MGU（0.62 ± 0.26 μ mol/g/min至0.81 ± 0.14 μ mol/g/min; p = 0.0007），同时伴有静息MBF的显著改善（1.11 +/- 0.20 ml/min/g至1.25 +/- 0.21 ml/min/g; p = 0.008）。此外，吡格列酮组HDL胆固醇（+28%; p = 0.003）和脂联素（+156.2%; p = 0.0001）升高，血浆胰岛素（-35%;结论在接受常规降脂治疗的FCHL患者中，加入吡格列酮可显著改善MGIJ和MBF，对血脂和代谢参数具有良好的效果。（一项研究探讨吡格列酮对家族性混合高脂血症患者全身和心肌葡萄糖摄入以及心肌血流量/冠状动脉血管扩张储备的影响; http：//www.controlledtrials.com/mrct/trial/230761/ISRCTN78563659; ISRCTN 78563659）。
Objectives This study's aim was to examine whether treatment with pioglitazone, added to conventional lipid-lowering therapy, would improve myocardial glucose utilization (MGU) and blood flow (MBF) in nondiabetic patients with familial combined hyperlipidemia (FCHL).Background Thiazolidinediones were found to improve insulin sensitivity and MGU in type 2 diabetes and MBF in Mexican Americans with insulin resistance. Familial combined hyperlipidemia is a complex genetic disorder conferring a high risk of premature coronary artery disease, characterized by high serum cholesterol and/or triglyceride, low high-density lipoprotein (HDL) cholesterol, and insulin resistance.Methods We undertook a randomized, double-blind, placebo-controlled study in 26 patients with FCHL, treated with pioglitazone or matching placebo 30 mg daily for 4 weeks, followed by 45 mg daily for 12 weeks. Positron emission tomography was used to measure MBF at rest and during adenosine-induced hyperemia and MGU during euglycemic hyperinsulinemic clamp at baseline and after treatment.Results Whereas no change was observed in the placebo group after treatment, patients receiving pioglitazone showed a significant increase in whole body glucose disposal (3.93 +/- 1.59 mg,/kg/min to 5.24 +/- 1.65 mg/kg/min; p = 0.004) and MGU (0.62 +/- 0.26 mu mol/g/min to 0.81 +/- 0.14 mu mol/g/min; p = 0.0007), accompanied by a significant improvement in resting MBF (1.11 +/- 0.20 ml/min/g to 1.25 +/- 0.21 ml/min/g; p = 0.008). Furthermore, in the pioglitazone group HDL cholesterol (+28%; p = 0.003) and adiponectin (+156.2%; p = 0.0001) were increased and plasma insulin (-35%; p = 0.017) was reduced.Conclusions In patients with FCHL treated with conventional lipid-lowering therapy, the addition of pioglitazone led to significant improvements in MGIJ and MBF, with a favorable effect on blood lipid and metabolic parameters. (A study to investigate the effect of pioglitazone on whole body and myocardial glucose uptake and myocardial blood flow/coronary vasodilator reserve in patients with familial combined hyperlipidaemia; http://www.controlledtrials.com/mrct/trial/230761/ISRCTN78563659; ISRCTN78563659).