Neuroendocrine Unit, Department of Medicine, Massachusetts General Hospital/Harvard Medical School, Boston, MA 02114, USA.
Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital/Harvard Medical School, Boston, MA 02114, USA.
J Clin Endocrinol Metab. 2023 Nov 17;108(12):e1542-e1550. doi: 10.1210/clinem/dgad375.
Overweight and obesity are associated with relative growth hormone (GH) deficiency, which has been implicated in the development of nonalcoholic fatty liver disease (NAFLD). NAFLD is a progressive disease without effective treatments.
We hypothesized that GH administration would reduce hepatic steatosis in individuals with overweight/obesity and NAFLD.
In this 6-month randomized, double-blind, placebo-controlled trial of low-dose GH administration, 53 adults aged 18 to 65 years with BMI ≥25 kg/m2 and NAFLD without diabetes were randomized to daily subcutaneous GH or placebo, targeting insulin-like growth factor 1 (IGF-1) to the upper normal quartile. The primary endpoint was intrahepatic lipid content (IHL) by proton magnetic resonance spectroscopy (1H-MRS) assessed before treatment and at 6 months.
Subjects were randomly assigned to a treatment group (27 GH; 26 placebo), with 41 completers (20 GH and 21 placebo) at 6 months. Reduction in absolute % IHL by 1H-MRS was significantly greater in the GH vs placebo group (mean ± SD: -5.2 ± 10.5% vs 3.8 ± 6.9%; P = .009), resulting in a net mean treatment effect of -8.9% (95% CI, -14.5 to -3.3%). All side effects were similar between groups, except for non-clinically significant lower extremity edema, which was more frequent in the GH vs placebo group (21% vs 0%, P = .02). There were no study discontinuations due to worsening of glycemic status, and there were no significant differences in change in glycemic measures or insulin resistance between the GH and placebo groups.
GH administration reduces hepatic steatosis in adults with overweight/obesity and NAFLD without worsening glycemic measures. The GH/IGF-1 axis may lead to future therapeutic targets for NAFLD.
超重和肥胖与相对生长激素（GH）缺乏有关，而后者与非酒精性脂肪性肝病（NAFLD）的发生有关。NAFLD 是一种进展性疾病，目前尚无有效的治疗方法。
我们假设生长激素（GH）治疗可减少超重/肥胖伴 NAFLD 患者的肝内脂肪沉积。
在这项为期 6 个月的低剂量 GH 给药、随机、双盲、安慰剂对照试验中，53 名年龄在 18 至 65 岁之间、BMI≥25kg/m2 且无糖尿病的 NAFLD 患者被随机分配至每日皮下 GH 或安慰剂组，以将胰岛素样生长因子 1（IGF-1）靶向至正常上限四分位区间。主要终点为质子磁共振波谱（1H-MRS）检测的肝内脂质含量（IHL），在治疗前和 6 个月时进行评估。
受试者被随机分配至治疗组（27 名 GH；26 名安慰剂），6 个月时共有 41 名患者完成试验（20 名 GH，21 名安慰剂）。与安慰剂组相比，GH 组 IHL 绝对值降低（1H-MRS 评估）更显著（平均 ± SD：-5.2±10.5%比 3.8±6.9%；P=.009），治疗效果的净均值差异为-8.9%（95%CI，-14.5 至-3.3%）。除下肢非临床显著水肿外，两组的所有不良反应均相似（GH 组发生率为 21%，安慰剂组为 0%，P=.02）。没有因血糖状态恶化而停止研究的情况，且 GH 组和安慰剂组的血糖和胰岛素抵抗的变化没有显著差异。
GH 治疗可减少超重/肥胖伴 NAFLD 成人的肝内脂肪沉积，且不会恶化血糖指标。GH/IGF-1 轴可能成为 NAFLD 的未来治疗靶点。
