Muller A F, Leebeek F W, Janssen J A, Lamberts S W, Hofland L, van der Lely A J
Department of Internal Medicine, Erasmus University Medical Center, 3015 GD Rotterdam, The Netherlands.
J Clin Endocrinol Metab. 2001 Nov;86(11):5165-71. doi: 10.1210/jcem.86.11.7987.
Cardiovascular risk is increased in GH deficiency (GHD). GHD adults are frequently abdominally obese and display features of the metabolic syndrome. Otherwise healthy abdominally obese subjects have low GH levels and show features of the metabolic syndrome as well. We investigated in healthy nonobese males the effect of the GH receptor antagonist pegvisomant in different metabolic conditions. This is a model for acute GHD without the alterations in body composition associated with GHD. We compared the effect of pegvisomant with that of placebo before and after 3 d of fasting. In addition, we investigated the effect of pegvisomant under normal, i.e. fed, conditions. Three days of fasting as well as pegvisomant alone decreased serum free IGF-I levels (1.0 +/- 0.15 vs. 0.31 +/- 0.05 ng/ml and 0.86 +/- 0.23 vs. 0.46 +/- 0.23 ng/ml, respectively). Fasting in combination with pegvisomant also decreased serum free IGF-I levels (1.0 +/- 0.15 vs. 0.31 +/- 0.07 ng/ml). Treatment with pegvisomant had no additional influence on the decline of free IGF-I induced by fasting. Pegvisomant alone had no influence on insulin sensitivity. The increase in insulin sensitivity induced by fasting was comparable to the increase in insulin sensitivity induced by fasting combined with pegvisomant. Among serum lipid concentrations, only serum triglycerides increased significantly as a result of pegvisomant alone (1.0 +/- 0.2 vs. 1.6 +/- 0.4 mmol/liter). The changes in lipid concentrations induced by fasting alone or pegvisomant were not different from those induced by pegvisomant alone. von Willebrand factor antigen levels declined significantly under the influence of pegvisomant alone (1.1 +/- 0.07 vs. 0.8 +/- 0.06 U/ml). In conclusion, in different metabolic conditions the GH receptor antagonist pegvisomant induces no significant acute changes in the major risk markers for cardiovascular disease. These data suggest that the secondary metabolic changes, e.g. abdominal obesity or inflammatory factors, that develop as a result of long-standing GHD are of primary importance in the pathogenesis of atherosclerosis in patients with GHD.
生长激素缺乏症（GHD）患者心血管疾病风险增加。GHD成年患者常出现腹型肥胖，并表现出代谢综合征的特征。此外，健康的腹型肥胖受试者生长激素水平较低，也表现出代谢综合征的特征。我们研究了生长激素受体拮抗剂培维索孟对健康非肥胖男性在不同代谢状态下的影响。这是一个急性GHD模型，不存在与GHD相关的身体成分改变。我们比较了禁食3天前后培维索孟与安慰剂的效果。此外，我们还研究了培维索孟在正常即进食状态下的效果。禁食3天以及单独使用培维索孟均降低了血清游离胰岛素样生长因子-I水平（分别为1.0±0.15 vs. 0.31±0.05 ng/ml和0.86±0.23 vs. 0.46±0.23 ng/ml）。禁食联合培维索孟也降低了血清游离胰岛素样生长因子-I水平（1.0±0.15 vs. 0.31±0.07 ng/ml）。培维索孟治疗对禁食诱导的游离胰岛素样生长因子-I下降无额外影响。单独使用培维索孟对胰岛素敏感性无影响。禁食诱导的胰岛素敏感性增加与禁食联合培维索孟诱导的胰岛素敏感性增加相当。在血脂浓度中，仅单独使用培维索孟导致血清甘油三酯显著升高（1.0±0.2 vs. 1.6±0.4 mmol/L）。单独禁食或培维索孟诱导的血脂浓度变化与单独使用培维索孟诱导的变化无差异。在单独使用培维索孟的影响下，血管性血友病因子抗原水平显著下降（1.1±0.07 vs. 0.8±0.06 U/ml）。总之，在不同代谢状态下，生长激素受体拮抗剂培维索孟不会引起心血管疾病主要风险标志物的显著急性变化。这些数据表明，长期GHD导致的继发性代谢变化，如腹型肥胖或炎症因子，在GHD患者动脉粥样硬化的发病机制中起主要作用。
