Treatment with insulin glargine does not suppress serum IGF-1.
OBJECTIVE
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.


METHODS
In a crossover study, insulin glargine or NPH insulin, respectively, were used in identical doses as basal insulins in treatment periods of 3 weeks.


RESULTS
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).


CONCLUSIONS
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.
Slawik
M
M
Department of Internal Medicine II, Division of Diabetes/Endocrinology, University Hospital Freiburg, Germany. ms597@medschl@cam.ac.uk
Schories
M
M
Busse Grawitz
A
A
Reincke
M
M
Petersen
K-G
KG
D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000032:analysis; D018592:Cross-Over Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000188:drug therapy; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D007328:Insulin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000069036:Insulin Glargine; D007336:Insulin, Isophane / Q000494:pharmacology* / Q000627:therapeutic use; D049528:Insulin, Long-Acting; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008297:Male; D008875:Middle Aged
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D049528:Insulin, Long-Acting; D018970:Insulin-Like Growth Factor Binding Protein 1; D018972:Insulin-Like Growth Factor Binding Protein 3; D000069036:Insulin Glargine; D007336:Insulin, Isophane; D007334:Insulin-Like Growth Factor I