4.7 Article

Generation of post-meal insulin correction boluses in type 1 diabetes simulation models for in-silico clinical trials: More realistic scenarios obtained using a decision tree approach

Journal

Publisher

ELSEVIER IRELAND LTD
DOI: 10.1016/j.cmpb.2022.106862

Keywords

Type 1 diabetes; Insulin bolus; Decision tree; lASSO; In-silico clinical trial

Funding

  1. Innovative Medicines Initiative 2 Joint Undertaking (JU) [777460]
  2. European Union
  3. EFPIA and T1D Exchange, JDRF
  4. Leona M. and Harry B. Helmsley Charitable Trust
  5. International Diabetes Federation (IDF)

Ask authors/readers for more resources

This study developed a simple and interpretable model to simulate the timing variability of correction boluses observed in real data, providing a more realistic representation of patient behavior in taking correction boluses and their post-prandial blood glucose response. The model showed better performance compared to traditional classifiers and exhibited good interpretability.
Background and objective: In type 1 diabetes (T1D) research, in-silico clinical trials (ISCTs) notably facilitate the design/testing of new therapies. Published simulation tools embed mathematical models of blood glucose (BG) and insulin dynamics, continuous glucose monitoring (CGM) sensors, and insulin treatments, but lack a realistic description of some aspects of patient lifestyle impacting on glucose control. Specifically, to effectively simulate insulin correction boluses, required to treat post-meal hyperglycemia (BG > 180 mg/dL), the timing of the bolus may be influenced by subjects' behavioral attitudes. In this work, we develop an easily interpretable model of the variability of correction bolus timing observed in real data, and embed it into a popular simulation tool for ISCTs. Methods: Using data collected in 196 adults with T1D monitored in free-living conditions, we trained a decision tree (DT) model to classify whether a correction bolus is injected in a future time window, based on predictors collected back in time, related to CGM data, previous insulin boluses and subject's characteristics. The performance was compared to that of a logistic regression classifier with LASSO regularization (LC), trained on the same dataset. After validation, the DT was embedded within a popular T1D simulation tool and an ISCT was performed to compare the simulated correction boluses against those observed in a subset of data not used for model training. Results: The DT provided better classification performance (accuracy: 0.792, sensitivity: 0.430, specificity: 0.878, precision: 0.455) than the LC and presented good interpretability. The most predictive features were related to CGM (and its temporal variations), time since the last insulin bolus, and time of the day. The correction boluses simulated by the DT, after implementation in the simulation tool, showed a good agreement with real-world data. Conclusions: The DT developed in this work represents a simple set of rules to mimic the same timing of correction boluses observed on real data. The inclusion of the model in simulation tools allows investigators to perform ISCTs that more realistically represent the patient behavior in taking correction boluses and the post-prandial BG response. In the future, more complex models can be investigated. (c) 2022 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ )

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.7
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available