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[HIV 诱发疾病患者的脂质紊乱]

[Lipid disorders in patients with HIV-induced diseases].

作者信息

Chanu B, Valensi P

机构信息

Service d'endocrinologie, de diabétologie et de nutrition, Hôpital Jean Verdier, Bondy (93).

出版信息

Presse Med. 2005 Sep 10;34(15):1087-94. doi: 10.1016/s0755-4982(05)84124-7.

Abstract

Before the availability of protease inhibitors, elevated triglyceride levels were frequently observed in patients with advanced-stage HIV infection. Since the addition of protease inhibitors to combination treatments, metabolic side effects (alterations in distribution of adipose tissue and metabolic disorders combining dyslipidemia, insulin-resistance and glucose intolerance) have been observed in HIV-positive patients receiving these treatments. Reverse transcriptase nucleoside inhibitors also provoke metabolic disorders. Dyslipidemia is defined by an increase in triglyceride levels of varying and sometimes major intensity, either isolated or combined with a more moderate increase in LDL-cholesterol, while HDL-cholesterol levels may decrease or remain unchanged. These metabolic alterations are potentially atherogenic and may explain these patients' increased risk of cardiovascular disorders. Their mechanism is complex and not yet clearly elucidated. The infection, the improvement in patients' general health and immune status, and individual predisposing factors are probably involved. Treatment probably plays a major role, since the different drugs in these two classes show effects of clearly different intensity. In vitro and ex vivo studies suggest that protease inhibitors alter adipocyte differentiation and induce insulin resistance. Reverse transcriptase nucleoside inhibitors modify adipocyte metabolism too, promoting tissue atrophy. Endocrine factors (cortisol and growth hormones) are also likely to have a role in this hypertrophy of adipose, especially visceral, tissue. These metabolic abnormalities result mainly from the effects of the antiretroviral drugs, notably protease inhibitors, on the hepatic lipid metabolism and on tissue sensitivity to insulin. Lipodystrophy contributes to these abnormalities, as does the reduction in cytokine secretion by adipose tissue. Management of these metabolic disorders is based primarily on a change in the drug regimen (administration of the least deleterious combinations), followed by standard dietary measures and, when necessary, lipid-lowering agents.

摘要

在蛋白酶抑制剂问世之前,晚期HIV感染患者中经常观察到甘油三酯水平升高。自从在联合治疗中加入蛋白酶抑制剂以来,接受这些治疗的HIV阳性患者出现了代谢副作用(脂肪组织分布改变以及合并血脂异常、胰岛素抵抗和葡萄糖耐受不良的代谢紊乱)。逆转录酶核苷抑制剂也会引发代谢紊乱。血脂异常的定义是甘油三酯水平有不同程度(有时是显著)的升高,可单独出现或伴有低密度脂蛋白胆固醇较中度升高,而高密度脂蛋白胆固醇水平可能降低或保持不变。这些代谢改变具有潜在的致动脉粥样硬化作用,可能解释了这些患者心血管疾病风险增加的原因。其机制复杂,尚未完全阐明。感染、患者总体健康状况和免疫状态的改善以及个体易感因素可能都与之有关。治疗可能起主要作用,因为这两类不同药物显示出强度明显不同的作用。体外和离体研究表明,蛋白酶抑制剂会改变脂肪细胞分化并诱导胰岛素抵抗。逆转录酶核苷抑制剂也会改变脂肪细胞代谢,促进组织萎缩。内分泌因素(皮质醇和生长激素)也可能在这种脂肪组织(尤其是内脏组织)肥大中起作用。这些代谢异常主要是抗逆转录病毒药物,尤其是蛋白酶抑制剂,对肝脏脂质代谢和组织对胰岛素的敏感性产生影响的结果。脂肪营养不良以及脂肪组织细胞因子分泌减少也促成了这些异常情况。这些代谢紊乱的管理主要基于改变药物治疗方案(使用危害最小的联合用药),其次是采取标准饮食措施,必要时使用降脂药物。

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