Acromegaly is a disease characterized by overproduction of growth hormone (GH). As a consequence of excessive GH secretion, circulating insulin-like growth factor-I (IGF-I) is elevated in active (untreated) acromegaly. IGF-I is often used as a marker of disease activity and growth hormone status in acromegaly. Although IGF-I can directly improve insulin sensitivity and glucose uptake in muscles, the excessive GH secretion in active acromegaly frequently leads to insulin resistance, glucose intolerance and even diabetes. In this review evidence will be discussed that in active acromegaly chronically elevated IGF-I, insulin and soluble Klotho (S-Klotho) levels play a pathophysiological role in the development of IGF-I receptor (IGF-IR) resistance. It is postulated that as soon as circulating IGF-I, insulin and S-Klotho rise above a certain level the IGF-IR becomes relatively resistant to actions of IGF-I. The development of a degree of IGF-IR resistance for metabolic actions may help to explain why in active acromegaly diabetogenic effects of GH predominate and are not completely counteracted and neutralized by elevated circulating levels of IGF-I. Further studies are necessary in order to support this hypothesis.

肢端肥大症是以生长激素（GH）过量产生为特征的疾病。由于过量的GH分泌，在活跃的（未治疗的）肢端肥大症中循环胰岛素样生长因子-1（IGF-1）升高。IGF-I通常用作肢端肥大症疾病活动和生长激素状态的标志物。尽管IGF-I可以直接改善肌肉的胰岛素敏感性和葡萄糖吸收，但是活跃的肢端肥大症中GH的过度分泌经常导致胰岛素抵抗，葡萄糖耐受不良甚至糖尿病。在这篇综述中，将讨论证据，即在肢端肥大症的慢性IGF-I慢性升高中，胰岛素和可溶性Klotho（S-Klotho）水平在IGF-I受体（IGF-IR）耐药性的发展中起着病理生理作用。据推测，一旦IGF-I发行，胰岛素和S-Klotho升高到一定水平以上，IGF-1R相对变得对IGF-1的作用具有抗性。对代谢作用的一定程度的IGF-IR抵抗力的发展可能有助于解释为什么GH在活跃的肢端肥大性糖尿病中起主要作用，而不能被升高的IGF-I循环水平完全抵消和抵消。为了支持该假设，需要进一步的研究。