Lee Jennifer H, Chan Jean L, Sourlas Epaminondas, Raptopoulos Vassilios, Mantzoros Christos S
Division of Endocrinology, Diabetes, and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Stoneman 816, Boston, Massachusetts 02215, USA.
J Clin Endocrinol Metab. 2006 Jul;91(7):2605-11. doi: 10.1210/jc.2005-1545. Epub 2006 Apr 24.
Highly active antiretroviral therapy (HAART) for HIV-1 infection has been associated with a metabolic syndrome characterized by insulin resistance, hyperlipidemia, and redistribution of body fat (lipodystrophy). A subset of patients with predominant lipoatrophy has low levels of the adipocyte-secreted hormone leptin.
The objective of the study was to assess whether administration of recombinant methionyl human leptin (r-metHuLeptin) improves insulin resistance and other metabolic abnormalities in HIV+ leptin-deficient subjects with HAART-induced lipoatrophy.
DESIGN, SETTING, PATIENTS, AND INTERVENTION: We conducted a randomized, placebo-controlled, double-blinded, crossover study from 2002 to 2004 in seven HIV+ men with HAART-induced lipoatrophy, serum leptin level less than 3 ng/ml, and fasting triglyceride level greater than 300 mg/dl, who were administered placebo for 2 months before or after administration of r-metHuLeptin at physiological doses for an additional 2 months.
Insulin resistance, lipid levels, inflammatory markers, body composition, and HIV control were measured.
Compared with placebo, r-metHuLeptin therapy improved fasting insulin levels, insulin resistance (as expressed by the homeostasis model assessment index and an insulin suppression test), and high-density lipoprotein. Body weight and fat mass decreased on r-metHuLeptin, mainly due to a decrease in truncal fat but not peripheral fat or lean body mass. r-metHuLeptin was well tolerated, and HIV control was not adversely affected.
r-metHuLeptin replacement at physiological doses in HIV+ leptin-deficient patients with HAART-induced lipoatrophy improves insulin resistance, high-density lipoprotein, and truncal fat mass. Future larger and more long-term studies in HAART-induced lipoatrophy, including patients with more severe metabolic abnormalities, are warranted to evaluate the physiological and potentially therapeutic role of r-metHuLeptin for this condition and to fully clarify the underlying mechanisms of action.
用于治疗HIV-1感染的高效抗逆转录病毒疗法（HAART）与一种代谢综合征相关，该综合征的特征为胰岛素抵抗、高脂血症和身体脂肪重新分布（脂肪代谢障碍）。一部分以脂肪萎缩为主的患者脂肪细胞分泌的激素瘦素水平较低。
本研究的目的是评估给予重组甲硫氨酰人瘦素（r-metHuLeptin）是否能改善因HAART导致脂肪萎缩的HIV阳性且瘦素缺乏患者的胰岛素抵抗及其他代谢异常。
设计、地点、患者和干预措施：2002年至2004年，我们对7名因HAART导致脂肪萎缩、血清瘦素水平低于3 ng/ml且空腹甘油三酯水平高于300 mg/dl的HIV阳性男性进行了一项随机、安慰剂对照、双盲、交叉研究，在给予生理剂量的r-metHuLeptin治疗2个月之前或之后，先给予安慰剂治疗2个月。
测量胰岛素抵抗、血脂水平、炎症标志物、身体组成和HIV控制情况。
与安慰剂相比，r-metHuLeptin治疗改善了空腹胰岛素水平、胰岛素抵抗（以稳态模型评估指数和胰岛素抑制试验表示）以及高密度脂蛋白水平。接受r-metHuLeptin治疗后体重和脂肪量下降，主要是由于躯干脂肪减少，而非外周脂肪或去脂体重减少。r-metHuLeptin耐受性良好，且对HIV控制没有不利影响。
对于因HAART导致脂肪萎缩的HIV阳性且瘦素缺乏患者，给予生理剂量的r-metHuLeptin替代治疗可改善胰岛素抵抗、高密度脂蛋白水平和躯干脂肪量。未来有必要针对HAART导致的脂肪萎缩开展更大规模、更长期的研究，纳入代谢异常更严重的患者，以评估r-metHuLeptin对这种情况的生理及潜在治疗作用，并充分阐明其潜在作用机制。
