Recombinant leptin for weight loss in obese and lean adults - A randomized, controlled, dose-escalation trial
Recombinant leptin for weight loss in obese and lean adults - A randomized, controlled, dose-escalation trial
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DOI：
10.1001/jama.282.16.1568
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发表时间：
1999-10-27
影响因子：
120.7
通讯作者：
McCamish, M
中科院分区：
文献类型：
--
作者：
Heymsfield, SB;Greenberg, AS;McCamish, M
研究背景瘦素是一种重要的蛋白质激素，对体重的稳态调节起着重要作用。外源性瘦素治疗可能影响体重减轻。目的确定增加外源性瘦素剂量与瘦和肥胖成人体重减轻之间的关系。设计一个随机、双盲、安慰剂对照、多中心、从1997年4月到1998年10月进行的剂量递增队列试验。设置4个大学营养和肥胖诊所和2个合同临床研究诊所。参与者五十四度倾斜（体重指数，20.0-27.5 kg/m2;平均[SD]体重，72.0 [9.7] kg）和73例肥胖体重指数27.6- 36.0kg/m2;平均[SD]体重，89.8 [11.4] kg），主要为白色（80%）男性（n = 67）和女性（n = 60），平均（SD）年龄为39岁通过每天早晨皮下注射（0 [安慰剂]、0.01、0.03、0.10或0.30 mg/kg）自我施用重组甲硫氨酰人瘦素。在A部分中，瘦型和肥胖型受试者接受4周治疗;在B部分中，肥胖型受试者再接受20周治疗。瘦的受试者食用合理热量的饮食以维持当前的体重值，肥胖的受试者被规定每日减少2100千焦/天的能量摄入（500-kcal/d）从维持稳定体重所需的量。主要结果测量体重，体脂肪，结果在所有受试者中，在4周时，随着瘦素剂量的增加，体重从基线下降（P = 0.02）和肥胖受试者在治疗24周时（P = 0.01）。第4周时的平均（SD）体重变化范围为安慰剂组（n = 36）-0.4（2.0）kg至0.1 mg/kg剂量组（n = 29）-1.9 kg（1.6）kg。第24周时的平均（SD）体重变化范围为0.01 mg/kg剂量组（n = 6）-0.7（5.4）kg至0.30 mg/kg剂量组（n = 8）-7.1（8.5）kg。第4周时，所有受试者的脂肪量随着剂量增加而较基线下降（P = 0.002），治疗24周时肥胖受试者中（P = .004）;在24周时，在2个最高剂量组中超过95%的体重减轻是脂肪减轻，基线血清瘦素浓度与第4周（P = 0.88）或第24周（P = 0.76）的体重减轻无关。未观察到对主要器官系统的临床显著不良反应。注射部位的轻度至中度反应是最常见的不良反应。结论瘦型和肥胖型受试者皮下注射重组瘦素与体重和脂肪减少存在剂量反应关系。进一步研究瘦素和相关激素在治疗人类肥胖中的潜在作用是必要的。
Context The protein hormone leptin is important to the homeostatic regulation of body weight. Treatment with exogenous leptin may affect weight loss,Objective To determine the relationship between increasing doses of exogenous leptin administration and weight loss in both lean and obese adults.Design A randomized, double-blind, placebo-controlled, multicenter, escalating dose cohort trial conducted from April 1997 to October 1998.Setting Four university nutrition and obesity clinics and 2 contract clinical research clinics.Participants Fifty-four lean (body mass index, 20.0-27.5 kg/m(2); mean [SD] body weight, 72.0 [9.7] kg) and 73 obese (body mass index, 27.6-36.0 kg/m(2); mean [SD] body weight, 89.8 [11.4] kg) predominantly white (80%) men (n = 67) and women (n = 60) with mean (SD) age of 39 (10.3) years.Interventions Recombinant methionyl human leptin self-administered by daily morning subcutaneous injection (0 [placebo], 0.01, 0,03, 0.10, or 0.30 mg/kg). In part A, lean and obese subjects were treated for 4 weeks; in part B, obese subjects were treated for an additional 20 weeks. Lean subjects consumed a eucaloric diet to maintain body weight at the current value, and obese subjects were prescribed a diet that reduced their daily energy intake by 2100 kJ/d (500-kcal/d) from the amount needed to maintain a stable weight.Main Outcome Measures Body weight, body fat, and incidence of adverse events.Results Weight loss from baseline increased with increasing dose of leptin among all subjects at 4 weeks (P = .02) and among obese subjects at 24 weeks (P = .01) of treatment. Mean (SD) weight changes at 4 weeks ranged from -0.4 (2.0) kg for placebo (n = 36) to -1.9 kg (1.6) kg for the 0.1 mg/kg dose (n = 29). Mean (SD) weight changes at 24 weeks ranged from -0.7 (5.4) kg for the 0.01 mg/kg dose (n = 6) to -7.1 (8.5) kg for the 0.30 mg/kg dose (n = 8). Fat mass declined from baseline as dose increased among all subjects at 4 weeks (P = .002) and among obese subjects at 24 weeks of treatment (P = .004); more than 95% of weight loss was fat loss in the 2 highest dose cohorts at 24 weeks, Baseline serum leptin concentrations were not related to weight loss at week 4 (P = .88) or at week 24 (P = .76). No clinically significant adverse effects were observed on major organ systems. Mild-to-moderate reactions at the injection site were the most commonly reported adverse effects.Conclusions A dose-response relationship with weight and fat loss was observed with subcutaneous recombinant leptin injections in both lean and obese subjects, Based on this study, administration of exogenous leptin appears to induce weight loss in some obese subjects with elevated endogenous serum leptin concentrations. Additional research into the potential role for leptin and related hormones in the treatment of human obesity is warranted.