A simulator with realistic and challenging scenarios for virtual T1D patients undergoing CSII and MDI therapy

Abstract

In silico simulations have become essential for the development of diabetes treatments. However, currently available simulators are not challenging enough and often suffer from limitations in insulin and meal absorption variability, which is unable to realistically reflect the dynamics of people with type 1 diabetes (T1D). Additionally, T1D simulators are mainly designed for the testing of continuous subcutaneous insulin infusion (CSII) therapies. In this work, a simulator is presented that includes a generated virtual patient (VP) cohort and both fast- and long-acting Glargine-100 U/ml (Gla-100), Glargine-300 U/ml (Gla-300), and Degludec-100 U/ml (Deg-100) insulin models. Therefore, in addition to CSII therapies, multiple daily injections (MDI) therapies can also be tested. The Hovorka model and its published parameter probability distributions were used to generate cohorts of VPs that represent a T1D population. Valid patients are filtered through restrictions that guarantee that they are physiologically acceptable. To obtain more realistic scenarios, basal insulin profile patterns from the literature have been used to identify variability in insulin sensitivity. A library of mixed meals identified from real data has also been included. This work presents and validates a methodology for the creation of realistic VP cohorts that include physiological variability and a simulator that includes challenging and realistic scenarios for in silico testing. A cohort of 47 VPs has been generated and in silico simulations of both CSII and MDI therapies were performed in open-loop. The simulation outcome metrics were contrasted with literature results

This work was partially supported by the Spanish Ministry of Science and Innovation through grant PID2019-107722RB-C22, in part by the Autonomous Government of Catalonia, Spain under Grant 2017 SGR 1551, and program for researchers in training at the University of Girona (IFUdG2019)

Open Access funding provided thanks to the CRUE-CSIC agreement with Elsevier