Short-term effects of NPH insulin, insulin detemir, and insulin glargine on the GH-IGF1-IGFBP axis in patients with type 1 diabetes

Abstract

Objective: Insulin regulates the GH-IGF1 axis. Insulin analogs differ from human insulin in receptor affinity and possibly liver accessibility. Therefore, we compared the GH-IGF1 axis response with human NPH insulin, insulin detemir, and insulin glargine in patients with type 1 diabetes (T1D). Methods: A total of 17 patients (seven were women) with T1D (age of 42 (24-63) years (mean and range), BMI of 24.7 (19.5-28.3) kg/m2, HbA1c of 7.2 (6.3-8.0) % (55 (45-64) mmol/mol), T1D duration of 26 (8-45) years) were studied using a randomized, three-period crossover design. Patients received s.c. injections of equal, individual doses of NPH, detemir, and glargine at 1800 h. Plasma glucose, serum total IGF1, bioactive IGF, IGF-binding protein (IGFBPs), and GH were measured hourly for 14 h post-injection. Results: When compared with the area under the curve (AUC) following NPH and glargine, detemir resulted in the lowest 6-14 h AUC (mean and range) of IGFBP1 (1518 (1280-1800)) vs 1621 (1367-1922) vs 1020 (860-1210) mg/l!h) and GH (17.1 (14.1-20.6) vs 15.4 (12.7-18.6) vs 10.2 (8.5-12.3) mg/l!h), but in the highest AUC of bioactive IGF (3.8 (3.5-4.2) vs 3.7 (3.4-4.0) vs 4.4 (4.1-4.8) mg/l!h) (all P!0.01). These differences were unrelated to plasma glucose. By contrast, profiles of total IGF1, IGFBP2, and IGFBP3 were comparable. Conclusions: Independent of plasma glucose, a single dose of detemir caused larger suppression in serum IGFBP1 than NPH and glargine, whereas bioactive IGF was higher, thereby explaining the lower GH levels. Thus, detemir appears to be more liver specific than NPH insulin and glargine.