Effects of human insulin and insulin aspart preparations on levels of IGF-I, IGFBPs and IGF bioactivity in patients with type 1 diabetes

摘要

Background Insulin aspart (IAsp) and its biphasic preparations BIAsp50 and BIAsp70 (containing 50% and 70% IAsp, respectively) have distinct glucose-lowering properties as compared to human insulin (HI). We investigated whether this affected the circulating IGF-system which depends on the hepatic insulin exposure. Methods In a randomized, four-period crossover study, 19 patients with type 1 diabetes received identical doses (0.2 U/kg sc) of IAsp, BIAsp70, BIAsp50 and HI together with a standardized meal. Serum total IGF-I and IGFBP-1 to -3 were measured by immunoassays for nine hours post-prandially. Bioactive IGF was determined by an in-house, cell-based IGF-I receptor kinase activation (KIRA) assay. Results Despite marked differences in peripheral insulin concentrations and plasma glucose, the four insulin preparations resulted in parallel decreases in IGFBP-1 levels during the first 3?hours, and parallel increases during the last part of the study (3–9?hours). Thus, only minor significances were seen. Insulin aspart and human insulin resulted in a lower area under the curve (AUC) during the first 3?hours as compared to BIAsp70 (p?=?0.009), and overall, human insulin resulted in a lower IGFBP-1 AUC than BIAsp70 (p?=?0.025). Nevertheless, responses and AUCs of bioactive IGF were similar for all four insulin preparations. Changes in levels of bioactive IGF were inversely correlated to those of IGFBP-1, increasing during the first 3?hours, whereafter levels declined (-0.83?≤?r?≤?-0.30; all p-values Total IGF-I and IGFBP-3 remained stable during the 9?hours, whereas IGFBP-2 changed opposite of IGFBP-1, increasing after 3–4?hours whereafter levels gradually declined. The four insulin preparations resulted in similar profiles and AUCs of total IGF-I, IGFBP-2 and IGFBP-3. Conclusions Despite distinct glucose-lowering properties, the tested insulin preparations had similar effects on IGF-I concentration and IGF bioactivity, IGFBP-2 and IGFBP-3 as compared to HI; only small differences in IGFBP-1 were seen and they did not affect bioactive IGF. Thus, insulin aspart containing preparation behaves as HI in regards to the circulating IGF-system. However, bioactive IGF appeared to be more sensitive to insulin exposure than total IGF-I. The physiological significance of this finding remains to be determined. Trial registration NCT00888732