Slawik M, Schories M, Busse Grawitz A, Reincke M, Petersen K-G
Department of Internal Medicine II, Division of Diabetes/Endocrinology, University Hospital Freiburg, Germany. ms597@
Diabet Med. 2006 Jul;23(7):814-7. doi: 10.1111/j.1464-5491.2006.01863.x.
A 6-8-fold higher insulin-like growth factor 1 (IGF-1) receptor binding affinity in vitro is reported for the insulin analogue glargine compared with human insulin. This study evaluates the in vivo significance by exploring the growth hormone (GH)-IGF-1 axis. Assuming a higher binding affinity of insulin glargine to pituitary IGF-1 receptors, serum IGF-1 concentrations should decrease via negative feedback.
In a crossover study, insulin glargine or NPH insulin, respectively, were used in identical doses as basal insulins in treatment periods of 3 weeks.
Overall glycaemic control was not different between the treatment regimens. In contrast to the hypothesis, serum IGF-1 concentrations were higher during insulin glargine treatment compared with NPH insulin in patients with Type 1 diabetes (177 +/- 18 vs. 159 +/- 18 microg/l, P < 0.02, n = 17, age 28 +/- 2 years). The effect on IGF-1 was most pronounced in male patients with Type 1 diabetes (174 +/- 11 vs. 146 +/- 10 microg/l, P < 0.02, n = 10), but was not significant in patients with Type 2 diabetes (92 +/- 9 vs. 86 +/- 8 microg/l, NS, n = 25, age 66 +/- 2 years).
In contrast to our hypothesis, serum IGF-1 did not decrease, but rose during insulin glargine treatment, suggesting an absence of relevant IGF-1-like activity of glargine at the level of the pituitary. Improved plasma glucose at dawn during glargine treatment may intensify growth hormone surges and increase IGF-1 synthesis. Significant increases were seen in younger patients, compatible with the higher activity of the GH-IGF-1 axis in this age group.
据报道，与人类胰岛素相比，胰岛素类似物甘精胰岛素在体外对胰岛素样生长因子1（IGF-1）受体的结合亲和力高6至8倍。本研究通过探索生长激素（GH）-IGF-1轴来评估其体内意义。假设甘精胰岛素对垂体IGF-1受体具有更高的结合亲和力，血清IGF-1浓度应通过负反馈降低。
在一项交叉研究中，甘精胰岛素或中性鱼精蛋白锌胰岛素分别以相同剂量作为基础胰岛素，治疗周期为3周。
各治疗方案之间总体血糖控制无差异。与假设相反，1型糖尿病患者在甘精胰岛素治疗期间血清IGF-1浓度高于中性鱼精蛋白锌胰岛素治疗期间（177±18对159±18μg/l，P<0.02，n = 17，年龄28±2岁）。对IGF-1的影响在1型糖尿病男性患者中最为明显（174±11对146±10μg/l，P<0.02，n = 10）但在2型糖尿病患者中不显著（92±9对86±8μg/l，无显著性差异，n = 25，年龄66±2岁）。
与我们的假设相反，血清IGF-1在甘精胰岛素治疗期间没有降低，反而升高，这表明甘精胰岛素在垂体水平不存在相关的IGF-1样活性。甘精胰岛素治疗期间黎明时血糖改善可能会加剧生长激素激增并增加IGF-1合成。在年轻患者中观察到显著增加，这与该年龄组中GH-IGF-1轴的较高活性相符。
