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

Context: In type 1 diabetes mellitus, low levels of insulin-like growth factor -1 (IGF-1) and IGF binding protein-3 (IGFBP-3) and high levels of GH and IGFBP-1 are present, probably due to portal vein insulinopenia. Objective: To test the hypothesis that continuous ip insulin infusion (CIPII) has a more pronounced effect than sc insulin therapy on regulation of the GH-IGF-1 axis. Design: This was a prospective, observational case-control study. Measurements were performed twice at a 26-week interval. Setting: Two secondary care hospitals in the Netherlands participated in the study. Patients: There were a total of 184 patients, age- and gender-matched, of which 39 used CIPII and 145 sc insulin therapy for the past 4 years. Outcomes: Primary endpoint included differences in IGF-1. Secondary outcomes were differences in GH, IGFBP-1, and IGFBP-3. Results: IGF-1 was higher with CIPII as compared to SC insulin therapy: 124 μg/liter (95% confidence interval [CI], 111–138) vs 108 μg/liter (95% CI 102–115) (P = .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/liter (95% CI, 3.49–4.10) vs 3.31 mg/liter (95% CI, 3.17–3.47) for IGFBP-3, 50.9 μg/liter (95% CI, 37.9–68.2) vs 102.6 μg/liter (95% CI, 87.8–119.8) for IGFBP-1 and 0.68 μg/liter (95% CI, 0.44–1.06) vs 1.21 μg/liter (95% CI, 0.95–1.54) for GH, respectively. In multivariate analysis, IGF-1 had no significant association with HbA1c. Conclusions: 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. “In this prospective case-control study among T1DM patients, we demonstrated that intraperitoneal insulin counteracts the dysregulation of the GH-IGF1 axis present during SC insulin therapy.”