Leptin-replacement therapy for lipodystrophy
Leptin-replacement therapy for lipodystrophy
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DOI：
10.1056/nejmoa012437
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发表时间：
2002-02-21
影响因子：
158.5
通讯作者：
Garg, A
中科院分区：
文献类型：
--
作者：
Oral, EA;Simha, V;Garg, A
背景：脂肪细胞激素瘦素在调节能量平衡中起重要作用。由于严重的脂肪代谢障碍与瘦素缺乏、胰岛素抵抗、高脂血症和肝脂肪变性有关，我们评估了瘦素替代是否会改善这种情况。（年龄范围：15至42岁; 8名患有糖尿病），他们患有脂肪代谢障碍，血清瘦素水平低于4 ng/ml（0.32nmol/ml）接受重组甲硫氨酰人瘦素（重组瘦素）。重组瘦素以递增剂量每天皮下给药两次，持续4个月，以达到低、中和高生理替代水平的瘦素。在用重组瘦素治疗期间，血清瘦素水平从1.3 ± 0.3ng/ml的平均值（± SE）增加到11.1 ± 2.5ng/ml（0.1 ± 0.02到0.9 ± 0.2nmol/ml）。在8名糖尿病患者中，糖化血红蛋白值的绝对下降为1.9%（95%置信区间，1.1%至2.7%; P=0.001）。四个月的治疗使平均甘油三酯水平降低了60%（95%置信区间，43%至77%; P
Background: The adipocyte hormone leptin is important in regulating energy homeostasis. Since severe lipodystrophy is associated with leptin deficiency, insulin resistance, hypertriglyceridemia, and hepatic steatosis, we assessed whether leptin replacement would ameliorate this condition.Methods: Nine female patients (age range, 15 to 42 years; eight with diabetes mellitus) who had lipodystrophy and serum leptin levels of less than 4 ng per milliliter (0.32 nmol per milliliter) received recombinant methionyl human leptin (recombinant leptin). Recombinant leptin was administered subcutaneously twice a day for four months at escalating doses to achieve low, intermediate, and high physiologic replacement levels of leptin.Results: During treatment with recombinant leptin, the serum leptin level increased from a mean (+/-SE) of 1.3+/-0.3 ng per milliliter to 11.1+/-2.5 ng per milliliter (0.1+/-0.02 to 0.9+/-0.2 nmol per milliliter). The absolute decrease in the glycosylated hemoglobin value was 1.9 percent (95 percent confidence interval, 1.1 to 2.7 percent; P=0.001) in the eight patients with diabetes. Four months of therapy decreased average triglyceride levels by 60 percent (95 percent confidence interval, 43 to 77 percent; P