Treatment with insulin glargine does not suppress serum IGF-1

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.