Addy Carol L, Gavrila Alina, Tsiodras Sotirios, Brodovicz Kimberly, Karchmer Adolf W, Mantzoros Christos S
Department of Internal Medicine, Endocrinology-Hypertension Division, Brigham and Women's Hospital, Boston, Massachusetts 02115,USA.
J Clin Endocrinol Metab. 2003 Feb;88(2):627-36. doi: 10.1210/jc.2002-020795.
A lipodystrophic syndrome and metabolic abnormalities have been observed in HIV-infected patients treated with highly active antiretroviral therapy (HAART). A murine model of lipodystrophy is associated with decreased levels of adiponectin, an adipocyte-secreted protein, the administration of which improves the metabolic syndrome in these mice. To investigate the association of adiponectin with metabolic changes in human lipodystrophy, we conducted a cross-sectional study of 112 HIV-infected patients treated with HAART. Mean adiponectin levels were higher in patients with no fat redistribution (FR) vs. FR (4.8 +/- 5.0 vs. 2.2 +/- 2.7 microg/ml, P < 0.01), but no significant differences in adiponectin levels were observed between FR subgroups. The difference in adiponectin levels between subjects with and without FR remained significant after adjusting for age, gender, leptin, HIV medication use, and CD4 count using logistic regression (odds ratio, 0.54, P = 0.008). Adiponectin was significantly correlated with triglycerides (r = -0.40), abdominal visceral fat (r = -0.35), extremity fat (r = 0.37), insulin resistance (HOMA-IR) (r = -0.28), nucleoside reverse transcriptase inhibitor (NRTI) use (r = -0.32), and high-density lipoprotein (HDL) (r = 0.41) using bivariate analysis (all P < 0.01). The association with HDL weakened but remained significant on multivariate analysis (standard beta = 0.29, P = 0.01). However, the association of adiponectin with HOMA-IR became nonsignificant after adjusting for NRTI use (standard beta = -0.15, P = 0.12), suggesting that changes in adiponectin levels may underlie the effect of NRTI use on insulin resistance. The associations of adiponectin with triglycerides and HOMA-IR were also slightly weakened after adjusting for visceral and extremity fat, indicating that adiponectin may, in part, mediate the effect of FR on triglycerides and insulin resistance. This study indicates that adiponectin is inversely correlated with abdominal visceral fat mass, serum triglycerides, and insulin resistance and is directly correlated with HDL and extremity fat in a sample of HIV-infected patients treated with HAART. The results also indicate that NRTI use may worsen insulin resistance by decreasing adiponectin levels. Thus, adiponectin replacement may be a potential treatment option to ameliorate the metabolic changes observed in this patient population.
在接受高效抗逆转录病毒治疗（HAART）的HIV感染患者中，已观察到脂肪营养不良综合征和代谢异常。脂肪营养不良的小鼠模型与脂联素水平降低有关，脂联素是一种脂肪细胞分泌的蛋白质，给予该蛋白质可改善这些小鼠的代谢综合征。为了研究脂联素与人类脂肪营养不良代谢变化的关系，我们对112例接受HAART治疗的HIV感染患者进行了一项横断面研究。无脂肪重新分布（FR）的患者与有FR的患者相比，平均脂联素水平更高（4.8±5.0 vs. 2.2±2.7μg/ml，P<0.01），但在FR亚组之间未观察到脂联素水平的显著差异。在使用逻辑回归对年龄、性别、瘦素、HIV药物使用和CD4计数进行调整后，有和没有FR的受试者之间脂联素水平的差异仍然显著（优势比，0.54，P = 0.008）。使用双变量分析，脂联素与甘油三酯（r = -0.40）、腹部内脏脂肪（r = -0.35）、四肢脂肪（r = 0.37）、胰岛素抵抗（HOMA-IR）（r = -0.28）、核苷类逆转录酶抑制剂（NRTI）使用（r = -0.32）和高密度脂蛋白（HDL）（r = 0.41）显著相关（所有P<0.01）。在多变量分析中，与HDL的关联减弱但仍然显著（标准β = 0.29，P = 0.01）。然而，在对NRTI使用进行调整后，脂联素与HOMA-IR的关联变得不显著（标准β = -0.15，P = 0.12），这表明脂联素水平的变化可能是NRTI使用对胰岛素抵抗产生影响的基础。在对内脏和四肢脂肪进行调整后，脂联素与甘油三酯和HOMA-IR的关联也略有减弱，表明脂联素可能部分介导FR对甘油三酯和胰岛素抵抗的影响。这项研究表明，在接受HAART治疗的HIV感染患者样本中，脂联素与腹部内脏脂肪量、血清甘油三酯和胰岛素抵抗呈负相关，与HDL和四肢脂肪呈正相关。结果还表明，使用NRTI可能通过降低脂联素水平而加重胰岛素抵抗。因此，补充脂联素可能是改善该患者群体中观察到的代谢变化的一种潜在治疗选择。
