Different Effects of Intraperitoneal and Subcutaneous Insulin Administration on the GH-IGF-1 Axis in Type 1 Diabetes

Peter R van Dijk, Susan J J Logtenberg, Simona I Chisalita, Christina A Hedman, Klaas H Groenier, Reinold O B Gans, Nanne Kleefstra, Hans J Arnqvist, Henk J G Bilo

In type 1 diabetes mellitus (T1DM), low levels of insulin-like growth factor -1 (IGF-1) and IGF binding protein-3 (IGFBP-3) and high levels of growth hormone (GH) and IGFBP-1 are present, probably due to portal vein insulinopenia. To test the hypothesis that continuous intraperitoneal insulin infusion (CIPII) has a more pronounced effect than subcutaneous (SC) insulin therapy on regulation of the GH-IGF-1 axis. Prospective, observational case-control study. Measurements were performed twice at a 26-week interval. Two secondary care hospitals in the Netherlands. A total of 184 patients, age and gender matched, of which 39 used CIPII and 145 SC insulin therapy for the past 4 years. Primary endpoint included differences in IGF-1. Secondary outcomes were differences in GH, IGFBP-1 and IGFBP-3. IGF-1 was higher with CIPII as compared to SC insulin therapy: 124 μg/l (95% CI 111, 138) versus 108 μg/l (95% CI 102, 115) (p=0.035). Additionally, IGFBP-3 concentrations were higher and IGFBP-1 and GH concentrations were lower with CIPII as compared to SC insulin therapy: 3.78 mg/l (95% CI 3.49, 4.10) versus 3.31 mg/l (95% CI 3.17, 3.47) for IGFBP-3, 50.9 μg/l (95% CI 37.9, 68.2) versus 102.6 μg/l (95% CI 87.8, 119.8) for IGFBP-1 and 0.68 μg/l (95% CI 0.44, 1.06) versus 1.21 μg/l (95% CI 0.95, 1.54) for GH, respectively. In multivariate analysis, IGF-1 had no significant association with HbA1c. The GH-IGF-1 axis may be affected by the route of insulin administration with CIPII counteracting dysregulation of the GH-IGF1 axis present during SC insulin therapy.