Search

We present a method to estimate parameters in pharmacokinetic (PK) and pharmacodynamic (PD) models for glucose insulin dynamics in humans. The method combines 1) experimental glucose infusion rate (GIR) data from glucose clamp studies and 2) a PK-PD model to estimate parameters such that the model fits the data. Assuming that the glucose clamp is perfect, we do not need to know the details of the controller in the clamp, and the GIR can be computed directly from the PK-PD model. To illustrate the procedure, we use the glucoregulatory model developed by Hovorka and modify it to have a smooth non-negative endogeneous glucose production (EGP) term. We estimate PK-PD parameters for rapid-acting insulin analogs (Fiasp and NovoRapid). We use these PK-PD parameters to illustrate GIR for insulin analogs with 30% and 50% faster absorption time than currently available rapid-acting insulin analogs. We discuss the role of system identification using GIR data from glucose clamp studies and how such identified models can be used in automated insulin dosing (AID) systems with ultra rapid-acting insulin., Comment: Submitted to be presented at a conference, 6 pages, 10 figures, 1 table

In type 2 diabetes (T2D) treatment, finding a safe and effective basal insulin dose is a challenge. The dose-response is highly individual and to ensure safety, people with T2D titrate by slowly increasing the daily insulin dose to meet treatment targets. This titration can take months. To ease and accelerate the process, we use short-term artificial pancreas (AP) treatment tailored for initial titration and apply it as a diagnostic tool. Specifically, we present a method to automatically estimate a personalized daily dose of basal insulin from closed-loop data collected with an AP. Based on AP-data from a stochastic simulation model, we employ the continuous-discrete extended Kalman filter and a maximum likelihood approach to estimate parameters in a simple dose-response model for 100 virtual people. With the identified model, we compute a daily dose of basal insulin to meet treatment targets for each individual. We test the personalized dose and evaluate the treatment outcomes against clinical reference values. In the tested simulation setup, the proposed method is feasible. However, more extensive tests will reveal whether it can be deemed safe for clinical implementation., Comment: 6 pages, 4 figures, 1 table. Accepted for publication in Proceedings of the 2022 61st IEEE Conference on Decision and Control (CDC)