Intermittent Control for Safe Long-Acting Insulin Intensification for Type 2 Diabetes: In-Silico Experiment

TL;DR

This study introduces an adaptive control strategy for insulin titration in type 2 diabetes, demonstrating in-silico that it achieves faster and safer glycemic control compared to standard methods, with robustness to measurement variability.

Contribution

The paper presents a novel receding horizon control algorithm for insulin titration, improving speed and safety of glycemic management in T2D through in-silico validation.

Findings

Achieves target glucose levels faster (by week 8) than standard care.

Maintains safety with low hypoglycemia risk over 52 weeks.

Robust to missing fasting blood glucose measurements.

Abstract

Around a third of type 2 diabetes patients (T2D) are escalated to basal insulin injections. Basal insulin dose is titrated to achieve a tight glycemic target without undue hypoglycemic risk. In the standard of care (SoC), titration is based on intermittent fasting blood glucose (FBG) measurements. Lack of adherence and the day-to-day variabilities in FBG measurements are limiting factors to the existing insulin titration procedure. We propose an adaptive receding horizon control strategy where a glucose-insulin fasting model is identified and used to predict the optimal basal insulin dose. This algorithm is evaluated in \textit{in-silico} experiments using the new UVA virtual lab (UVlab) and a set of T2D avatars matched to clinical data (NCT01336023). Compared to SoC, we show that this control strategy can achieve the same glucose targets faster (as soon as week 8) and safer (increased hypoglycemia protection and robustness to missing FBG measurements). Specifically, when insulin is titrated daily, a time-in-range (TIR, 70--180 mg/dL) of 71.4$\pm$20.0\% can be achieved at week eight and maintained at week 52 (72.6$\pm$19.6%) without an increased hypoglycemia risk as measured by time under 70 mg/dL (TBR, week 8: 1.3$\pm$1.9% and week 52: 1.2$\pm$1.9%), when compared to the SoC (TIR at week 8: 59.3$\pm$28.0% and week:52 72.1$\pm$22.3%, TBR at week 8: 0.5$\pm$1.3% and week 52: 2.8$\pm$3.4%). Such an approach can potentially reduce treatment inertia and prescription complexity, resulting in improved glycemic outcomes for T2D using basal insulin injections.