Diabetes CentreIsala Clinics, PO Box 10400, 8000 G.K. Zwolle, The Netherlands Departments of Internal Medicine General PracticeUniversity Medical Center Groningen, Groningen, The Netherlands Langerhans Medical Research GroupZwolle, The Netherlands Department of Internal MedicineIsala Clinics, Zwolle, The Netherlands Division of Cell BiologyDepartment of Clinical and Experimental Medicine and Faculty of Health SciencesDiabetes Research Centre, Linköping University, Linköping, Sweden.
Endocr Connect. 2014 Jan 21;3(1):17-23. doi: 10.1530/EC-13-0089. Print 2014.
In type 1 diabetes mellitus (T1DM), low concentrations of IGF1 and high concentrations of IGF-binding protein 1 (IGFBP1) have been reported. It has been suggested that these abnormalities in the GH-IGF1 axis are due to low insulin concentrations in the portal vein. We hypothesized that the i.p. route of insulin administration increases IGF1 concentrations when compared with the s.c. route of insulin administration. IGF1 and IGFBP1 concentrations in samples derived from an open-label, randomized cross-over trial comparing the effects of s.c. and i.p. insulin delivery on glycaemia were determined. T1DM patients were randomized to receive either 6 months of continuous i.p. insulin infusion (CIPII) through an implantable pump (MIP 2007C, Medtronic) followed by 6 months of s.c. insulin infusion or vice versa with a washout phase in between. Data from 16 patients who had complete measurements during both treatment phases were analysed. The change in IGF1 concentrations during CIPII treatment was 10.4 μg/l (95% CI -0.94, 21.7 μg/l; P=0.06) and during s.c. insulin treatment was -2.2 μg/l (95% CI -13.5, 9.2 μg/l; P=0.69). When taking the effect of treatment order into account, the estimated change in IGF1 concentrations was found to be 12.6 μg/l (95% CI -3.1, 28.5 μg/l; P=0.11) with CIPII treatment compared with that with s.c. insulin treatment. IGFBP1 concentrations decreased to -100.7 μg/l (95% CI -143.0, -58.3 μg/l; P<0.01) with CIPII treatment. During CIPII treatment, parts of the GH-IGF1 axis changed compared with that observed during s.c. insulin treatment. This supports the hypothesis that the i.p. route of insulin administration is of importance in the IGF1 system.
在 1 型糖尿病(T1DM)中,已报道 IGF1 浓度降低和 IGF 结合蛋白 1(IGFBP1)浓度升高。据推测,GH-IGF1 轴的这些异常是由于门静脉中胰岛素浓度低所致。我们假设,与皮下注射胰岛素相比,腹腔内注射胰岛素可增加 IGF1 浓度。通过开放标签、随机交叉试验比较皮下和腹腔内胰岛素给药对血糖的影响,确定了来自该试验的样本中 IGF1 和 IGFBP1 浓度。将 T1DM 患者随机分为两组,一组接受 6 个月的连续腹腔内胰岛素输注(CIPII),通过植入式输液泵(MIP 2007C,Medtronic)进行,随后进行 6 个月的皮下胰岛素输注;另一组相反,两组之间有洗脱期。分析了在两种治疗阶段均完成测量的 16 例患者的数据。CIPII 治疗期间 IGF1 浓度的变化为 10.4μg/l(95%CI-0.94,21.7μg/l;P=0.06),皮下胰岛素治疗期间为-2.2μg/l(95%CI-13.5,9.2μg/l;P=0.69)。考虑到治疗顺序的影响,发现与皮下胰岛素治疗相比,CIPII 治疗时 IGF1 浓度的估计变化为 12.6μg/l(95%CI-3.1,28.5μg/l;P=0.11)。CIPII 治疗时 IGFBP1 浓度下降至-100.7μg/l(95%CI-143.0,-58.3μg/l;P<0.01)。与皮下胰岛素治疗相比,CIPII 治疗时部分 GH-IGF1 轴发生改变。这支持了腹腔内注射胰岛素给药在 IGF1 系统中很重要的假设。