Centre for Bioengineering, Department of Mechanical Engineering, University of Canterbury, Christchurch, New Zealand.
J Diabetes Sci Technol. 2023 Jul;17(4):1016-1028. doi: 10.1177/19322968221085032. Epub 2022 Mar 26.
Accurate, safe glycemic management requires reliable delivery of insulin doses. Insulin can be delivered subcutaneously for action over a longer period of time. Needle-free jet injectors provide subcutaneous (SC) delivery without requiring needle use, but the volume of insulin absorbed varies due to losses associated with the delivery method. This study employs model-based methods to determine the expected proportion of active insulin present from a needle-free SC dose.
Insulin, C-peptide, and glucose assay data from a frequently sampled insulin-modified oral glucose tolerance test trial with 2U SC insulin delivery, paired with a well-validated metabolic model, predict metabolic outcomes for = 7 healthy adults. Subject-specific nonlinear hepatic clearance profiles are modeled over time using third-order basis splines with knots located at assay times. Hepatic clearance profiles are constrained within a physiological rate of change, and relative to plasma glucose profiles. Insulin loss proportions yielding optimal insulin predictions are then identified, quantifying delivery losses.
Optimal parameter identification suggests losses of up to 22% of the nominal 2U SC dose. The degree of loss varies between subjects and between trials on the same subject. Insulin fit accuracy improves where loss greater than 5% is identified, relative to where delivery loss is not modeled.
Modeling shows needle-free SC jet injection of a nominal dose of insulin does not necessarily provide metabolic action equivalent to total dose, and this availability significantly varies between trials. By quantifying and accounting for variability of jet injection insulin doses, better glycemic management outcomes using SC jet injection may be achieved.
准确、安全的血糖管理需要可靠地输送胰岛素剂量。胰岛素可以通过皮下注射来实现更长时间的作用。无针喷射注射器提供了无需使用针头的皮下（SC）输送，但由于输送方法相关的损失，吸收的胰岛素量会有所不同。本研究采用基于模型的方法来确定无针 SC 剂量下存在的有效胰岛素的预期比例。
使用经过良好验证的代谢模型，对 2U SC 胰岛素输送的频繁采样胰岛素改良口服葡萄糖耐量试验试验中的胰岛素、C 肽和葡萄糖检测数据进行分析，以预测 7 名健康成年人的代谢结果。使用位于检测时间的三阶基样条对随时间变化的个体特异性非线性肝清除率曲线进行建模。肝清除率曲线受到生理变化率和相对于血浆葡萄糖曲线的限制。然后确定产生最佳胰岛素预测的胰岛素损失比例，从而量化输送损失。
最佳参数识别表明，名义 2U SC 剂量的损失高达 22%。损失程度在个体之间和同一个体的不同试验之间有所不同。与不进行输送损失建模相比，当确定损失大于 5%时，胰岛素拟合精度会提高。
模型表明，名义剂量的无针 SC 喷射注射不一定能提供与总剂量相当的代谢作用，而且这种可及性在不同试验之间存在显著差异。通过量化和考虑喷射注射胰岛素剂量的变异性，可能会实现使用 SC 喷射注射更好的血糖管理效果。
