The effect of tenofovir disoproxil fumarate on whole-body insulin sensitivity, lipids and adipokines in healthy volunteers
The effect of tenofovir disoproxil fumarate on whole-body insulin sensitivity, lipids and adipokines in healthy volunteers
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DOI：
10.3851/imp1518
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发表时间：
2010-01-01
影响因子：
1.2
通讯作者：
Moyle, Graeme J.
中科院分区：
文献类型：
--
作者：
Randell, Paul A.;Jackson, Akil G.;Moyle, Graeme J.
背景：已知某些抗逆转录病毒药物会影响脂质和葡萄糖稳态。本研究的目的是评估在 HIV-1 血清阴性健康男性志愿者中，与安慰剂相比，富马酸替诺福韦二吡呋酯 (TDF) 给药两周对胰岛素敏感性（通过使用高胰岛素正常血糖钳测定外周葡萄糖摄取来确定）的影响。还评估了脂质、脂联素、瘦素、纤溶酶原激活剂抑制剂 1 (PAI-1) 以及粘附分子 E-选择素和 P-选择素的变化。 方法：这是一项单中心、随机、双盲、安慰剂对照研究，采用两序列、两阶段交叉设计。该研究共招募了 19 名 HIV 阴性男性，并以 1:1 的比例随机分组，接受 2 周的 TDF（300 毫克，每天一次），然后接受 2 周的安慰剂治疗，或者先接受安慰剂，然后接受替诺福韦治疗。在基线、2 周后和 4 周后进行钳夹。结果：所有 3 次钳夹均由 16 名参与者完成。在正常血糖钳夹期间，与安慰剂或基线相比，TDF 给药 2 周后胰岛素敏感性没有显着变化。与安慰剂相比，服用 2 周 TDF 后，平均总胆固醇 (9.4%) 和低密度脂蛋白 (LDL；8.1%) 胆固醇显着降低。脂联素、瘦素、PAI-1、P-选择素和E-选择素的水平没有显着改变。结论：根据 HIV 阴性男性志愿者的高胰岛素正常血糖钳夹评估，使用 TDF 2 周不会影响胰岛素敏感性。 TOE 的使用导致总胆固醇和低密度脂蛋白胆固醇适度降低，但具有统计学意义。
Background: Certain antiretrovirals are known to affect lipid and glucose homeostasis. The aim of this study was to assess the effect on insulin sensitivity (determined by peripheral glucose uptake using a hyperinsulinaemic euglycaemic clamp) of tenofovir disoproxil fumarate (TDF) administration compared with placebo for 2 weeks in HIV-1-seronegative healthy male volunteers. Changes in lipids, adiponectin, leptin, plasminogen activator inhibitor 1 (PAI-1) and the adhesion molecules E-selectin and P-selectin were also assessed.Methods: This was a single-centre, randomized, double-blinded, placebo-controlled study that used a two-sequence, two-period cross-over design. A total of 19 HIV-negative males were recruited to the study and randomized 1:1 to receive either 2 weeks of TDF (300 mg once daily) followed by 2 weeks of placebo or placebo initially followed by tenofovir. Clamps were performed at baseline, after 2 weeks and after 4 weeks.Results: All three clamps were completed by 16 participants. During the euglycaemic clamp, there were no significant changes in insulin sensitivity after 2 weeks of TDF administration compared with placebo or baseline. There was a significant reduction in the mean total cholesterol (9.4%) and low-density lipoprotein (LDL; 8.1%) cholesterol following 2 weeks of TDF compared with placebo. Levels of adiponectin, leptin, PAI-1, P-selectin and E-selectin were not significantly altered.Conclusions: TDF use for 2 weeks does not affect insulin sensitivity, as assessed by the hyperinsulinaemic euglycaemic clamp in HIV-negative male volunteers. TOE use resulted in modest, but statistically significant, reductions in total and LDL cholesterol.