Kotler Donald P, He Qing, Engelson Ellen S, Albu Jeanine B, Glesby Marshall J
Gastrointestinal Division, Department of Medicine, St Luke's-Roosevelt Hospital Center, Columbia University College of Physicians and Surgeons, New York, NY, USA.
Antivir Ther. 2016;21(2):107-16. doi: 10.3851/IMP2927. Epub 2014 Dec 23.
Hepatic fat is related to insulin resistance (IR) and visceral adipose tissue (VAT) in HIV+ and uninfected individuals. Growth hormone (GH) reduces VAT but increases IR. We evaluated the effects of recombinant human GH (rhGH) and rosiglitazone (Rosi) on hepatic fat in a substudy of a randomized controlled trial.
HIV+ subjects with abdominal obesity and IR (QUICKI≤0.33) were randomized to rhGH 3 mg daily, Rosi 4 mg twice daily, the combination or double placebo. Hepatic fat was measured by magnetic resonance spectroscopy, visceral fat by MRI and IR by frequently sampled intravenous glucose tolerance tests at baseline and week 12.
31 subjects were studied at both time points. Significant correlations between hepatic fat and VAT (r=0.41; P=0.02) and QUICKI (r=0.39; P<0.05) were seen at baseline. IR rose with rhGH but not Rosi. When rhGH treatment groups were combined, hepatic fat expressed as percentage change decreased significantly (P<0.05) but did not change in Rosi (P=0.71). There were no correlations between changes in hepatic fat and VAT (P=0.4) or QUICKI (P=0.6). In a substudy of 21 subjects, a trend was noticed between changes in hepatic fat and serum insulin-like growth factor-1 (IGF-1; P=0.09).
Hepatic fat correlates significantly with both VAT and IR, but changes in hepatic fat do not correlate with changes in VAT and glucose metabolism. Hepatic fat content is reduced by rhGH but Rosi has no effect. These results suggest an independent effect of GH or IGF-1 on hepatic fat. The study was registered at Clinicaltrials.gov (NCT00130286).
在HIV感染者和未感染者中,肝脏脂肪与胰岛素抵抗(IR)及内脏脂肪组织(VAT)相关。生长激素(GH)可减少VAT,但会增加IR。在一项随机对照试验的子研究中,我们评估了重组人生长激素(rhGH)和罗格列酮(Rosi)对肝脏脂肪的影响。
腹部肥胖且有IR(定量胰岛素敏感性检测指数≤0.33)的HIV感染者被随机分为每日3毫克rhGH组、每日两次4毫克Rosi组、联合用药组或双安慰剂组。通过磁共振波谱法测量肝脏脂肪,通过MRI测量内脏脂肪,并在基线和第12周时通过频繁采样静脉葡萄糖耐量试验测量IR。
在两个时间点对31名受试者进行了研究。基线时可见肝脏脂肪与VAT(r = 0.41;P = 0.02)及定量胰岛素敏感性检测指数(r = 0.39;P < 0.05)之间存在显著相关性。rhGH治疗后IR升高,但Rosi治疗后未升高。当rhGH治疗组合并后,以百分比变化表示的肝脏脂肪显著降低(P < 0.05),但Rosi治疗组未变化(P = 0.71)。肝脏脂肪变化与VAT(P = 0.4)或定量胰岛素敏感性检测指数(P = 0.6)之间无相关性。在一项21名受试者的子研究中,注意到肝脏脂肪变化与血清胰岛素样生长因子-1(IGF-1;P = 0.09)之间存在一种趋势。
肝脏脂肪与VAT和IR均显著相关,但肝脏脂肪变化与VAT变化及糖代谢变化无关。rhGH可降低肝脏脂肪含量,但Rosi无此作用。这些结果提示GH或IGF-1对肝脏脂肪有独立作用。该研究已在Clinicaltrials.gov注册(NCT00130286)。