Kraegen E W, Chisholm D J
Diabetologia. 1984 Mar;26(3):208-13. doi: 10.1007/BF00252409.
Refinement of continuous subcutaneous insulin infusion for diabetes therapy requires improved knowledge of subcutaneous insulin absorption kinetics. We have used kinetic modelling to quantitate systemic insulin delivery produced by subcutaneously-infused insulin (i.e. simulated meal and basal delivery). Profiles were studied in normal subjects, with endogenous insulin suppressed. Paired studies of intravenous insulin infusion enabled systemic insulin delivery to be quantitated. High rate subcutaneous delivery (10 U in 5 min) resulted in a systemic delivery of approximately 8 U in 4 h. Increasing infused insulin concentration delayed systemic delivery (p less than 0.025). Both continuous and pulsatile low-rate infusions (2.4 U/h) gave similar slow increases in systemic delivery to 1 U after 4 h. Computer fitting to a two-pool model of the subcutaneous space suggested a low rate of insulin degradation for all profiles (rate constant less than 10%/h). We conclude that: systemic insulin delivery following subcutaneous infusion conforms reasonably to a two-pool model, subcutaneous insulin degradation is low regardless of input profile, a long delay in basal systemic delivery should be taken into account when initiating or resuming interrupted subcutaneous insulin infusion. Kinetic modelling of subcutaneous insulin absorption should be useful to predict the impact of programming strategies for continuous subcutaneous insulin infusion therapy.
优化糖尿病治疗中的持续皮下胰岛素输注需要更好地了解皮下胰岛素吸收动力学。我们采用动力学建模来定量皮下输注胰岛素产生的全身胰岛素输送量（即模拟进餐和基础输送量）。在正常受试者中进行研究，抑制内源性胰岛素分泌。通过静脉输注胰岛素的配对研究来定量全身胰岛素输送量。高剂量皮下注射（5分钟内注射10单位）在4小时内产生的全身输送量约为8单位。增加输注胰岛素浓度会延迟全身输送（p<0.025）。持续和脉冲式低剂量输注（2.4单位/小时）在4小时后全身输送量均缓慢增加至1单位，且二者相似。对皮下空间的双池模型进行计算机拟合表明，所有输注模式下胰岛素降解率均较低（速率常数<10%/小时）。我们得出以下结论：皮下输注后的全身胰岛素输送量合理符合双池模型；无论输入模式如何，皮下胰岛素降解率均较低；在开始或恢复中断的皮下胰岛素输注时，应考虑基础全身输送的长时间延迟。皮下胰岛素吸收的动力学建模对于预测持续皮下胰岛素输注治疗的编程策略的影响应该是有用的。
