Endocrine Abstracts

Introduction: Type 1 diabetes (T1D) is characterized by primary insulin insufficiency and secondary disruption of GH–IGF–IGFBP axis. S.c. insulin therapy is necessary to normalize this axis. This study aimed to investigate whether the distinct insulin profiles obtained with insulin aspart and human insulin preparations, respectively, affect IGF1 concentration and bioactivity and IGFBP levels differently.

Methods: In a randomized, four-period crossover study, 19 patients with T1D received identical doses (0.2 U/kg s.c.) of insulin aspart, BIAsp70, or BIAsp50 immediately before a standardized meal, or human insulin 30 min before meal. Serum total IGF1, bioactive IGF1 and IGFBP-1 to -3 were measured for 9 h postprandially.

Results: After equipotent doses, IGFBP-1 levels decreased significantly during the first 3 h with all insulin treatments, but the AUC of IGFBP-1 was significantly higher in the BIAsp50 group (mean (range) 351, 312–396 μg h/l) as compared to insulin aspart (262, 233–294 μg h/l) and human insulin (256, 228–288 μg h/l, P=0.001). Human insulin showed lower AUC of IGFBP-1 than insulin aspart preparations during 0–3, 0–6, 6–9 and 0–9 h. During the first 6 h, the four insulin preparations resulted in similar profiles and AUCs of total IGF1, bioactive IGF1, IGFBP-2 and IGFBP-3. Whereas total IGF1 remained constant, bioactive IGF-I fell at the end of the study (6–9 h), concomitant with the increase in IGFBP-1.

Conclusions: Despite distinct pharmacokinetic properties, the insulin aspart preparations had similar effects on IGF1 concentration and bioactivity, IGFBP-2 and IGFBP-3 as compared to those of human insulin, but differed in respect to IGFBP-1. Further, bioactive IGF-I appeared to be more sensitive to insulin exposure than total IGF1.