Systemically modeling the dynamics of plasma insulin in subcutaneous injection of insulin analogues for type 1 diabetes

Abstract. Type 1 diabetics must inject exogenous insulin or insulin analogues one or more times daily. The timing and dosage of insulin administration have been a critical research area since the invention of insulin analogues. Several pharmacokinetical models have been proposed, and some are applied clinically in modeling various insulin therapies. However, their plasma insulin concen-tration must be computed separately from the models ’ output. Furthermore, minimal analytical study was performed in these existing models. We propose two systemic and simplified ordinary differential equation models to model the subcutaneous injection of rapid-acting insulin analogues and long-acting in-sulin analogues, respectively. Our models explicitly model the plasma insulin and hence have the advantage of computing the plasma insulin directly. The profiles of plasma insulin concentrations obtained from these two models are in good agreement with the experimental data. We also study the dynamics of insulin analogues, plasma insulin concentrations, and, in particular, the shape of the dynamics of plasma insulin concentrations