Pioglitazone added to conventional lipid-lowering treatment in familial combined hyperlipidaemia improves parameters of metabolic control: relation to liver, muscle and regional body fat content.
Pioglitazone added to conventional lipid-lowering treatment in familial combined hyperlipidaemia improves parameters of metabolic control: relation to liver, muscle and regional body fat content.
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DOI：
10.1016/j.atherosclerosis.2007.03.043
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发表时间：
2007-11-01
期刊：
影响因子：
5.3
通讯作者：
Naoumova, Rossi P
中科院分区：
文献类型：
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作者：
Thomas, E Louise;Potter, Elizabeth;Naoumova, Rossi P
家族性混合性高脂血症(FCHL)是一种复杂的遗传性疾病，具有早期动脉粥样硬化的高风险，其特征是高胆固醇和/或甘油三酯，低高密度脂蛋白胆固醇和胰岛素抵抗。我们研究了在常规降脂治疗的基础上加用吡格列酮是否会有利地影响代谢参数和改变体内脂肪含量。我们对22名男性FCHL患者进行了一项随机、双盲、安慰剂对照研究，他们每天服用30毫克的吡格列酮或服用相应的安慰剂，疗程为4周，12周后增至45毫克。分别于治疗前和治疗后进行磁共振成像和质子磁共振波谱检测脂肪组织(AT)、体含量以及肝细胞内脂质(IHCL)和心肌细胞内脂质(IMCL)。吡格列酮组治疗后甘油三酯/高密度脂蛋白下降32.3%(p=0.002)，血糖下降4.4%(p=0.03)，丙氨酸氨基转移酶下降7.7%(p=0.005)，脂联素下降130.1%(p=0.001)。吡格列酮治疗组大鼠总脂肪组织(5.3%，p=0.02)、皮下脂肪组织(7.1%，p=0.003)和比目鱼肌-IMCL水平(47.4%，p=0.02)显著增加，而腹内AT和IHCl水平无明显变化。ALT、AST与IHCL呈显著正相关(r=0.72，p
Familial combined hyperlipidaemia (FCHL) is a complex genetic disorder conferring high risk of premature atherosclerosis, characterized by high cholesterol and/or triglyceride, low high density lipoprotein (HDL) cholesterol and insulin resistance. We examined whether pioglitazone, added to conventional lipid-lowering therapy, would favourably affect metabolic parameters and alter body fat content. We undertook a randomized, double blind, placebo-controlled study in 22 male patients with FCHL treated with pioglitazone or matching placebo 30 mg daily for 4 weeks, increasing to 45 mg for 12 weeks. Magnetic resonance imaging and proton magnetic resonance spectroscopy were performed to measure adipose tissue (AT) body content as well as intrahepatocellular lipids (IHCL) and intramyocellular lipids (IMCL) at baseline and after treatment. Significantly improved in the pioglitazone group were: triglyceride/HDL (atherogenic index of plasma) -32.3% (p=0.002), plasma glucose -4.4% (p=0.03), alanine-aminotransferase (ALT) -7.7% (p=0.005) and adiponectin 130.1% (p=0.001). Pioglitazone treatment resulted in a significant increase in total (5.3%, p=0.02) and subcutaneous (7.1%, p=0.003) adipose tissue as well as in soleus-IMCL levels (47.4%, p=0.02) without alteration in intra-abdominal AT or IHCL. Changes in ALT and AST and IHCL were strongly correlated (r=0.72, p