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Published July 2023 | Published
Journal Article Open

A simple modeling framework for prediction in the human glucose–insulin system

Abstract

Forecasting blood glucose (BG) levels with routinely collected data is useful for glycemic management. BG dynamics are nonlinear, complex, and nonstationary, which can be represented by nonlinear models. However, the sparsity of routinely collected data creates parameter identifiability issues when high-fidelity complex models are used, thereby resulting in inaccurate forecasts. One can use models with reduced physiological fidelity for robust and accurate parameter estimation and forecasting with sparse data. For this purpose, we approximate the nonlinear dynamics of BG regulation by a linear stochastic differential equation: we develop a linear stochastic model, which can be specialized to different settings: type 2 diabetes mellitus (T2DM) and intensive care unit (ICU), with different choices of appropriate model functions. The model includes deterministic terms quantifying glucose removal from the bloodstream through the glycemic regulation system and representing the effect of nutrition and externally delivered insulin. The stochastic term encapsulates the BG oscillations. The model output is in the form of an expected value accompanied by a band around this value. The model parameters are estimated patient-specifically, leading to personalized models. The forecasts consist of values for BG mean and variation, quantifying possible high and low BG levels. Such predictions have potential use for glycemic management as part of control systems. We present experimental results on parameter estimation and forecasting in T2DM and ICU settings. We compare the model's predictive capability with two different nonlinear models built for T2DM and ICU contexts to have a sense of the level of prediction achieved by this model.

Copyright and License

© 2023 Author(s). Published under an exclusive license by AIP Publishing.

Acknowledgement

We acknowledge financial support from NIH R01 LM012734 "Mechanistic Machine Learning." D.J.A. acknowledges helpful discussions with Bruce Gluckman, Rammah Abohtyra, Cecilia Diniz Behn, and Arthur Stewart Sherman.

Contributions

Melike Sirlanci: Formal analysis (lead); Methodology (lead); Software (lead); Visualization (lead); Writing – original draft (lead); Writing – review & editing (equal). Matthew E. Levine: Methodology (equal); Writing – review & editing (equal). Cecilia C. Low Wang: Writing – review & editing (equal). David J. Albers: Funding acquisition (equal); Supervision (equal); Writing – review & editing (equal). Andrew M. Stuart: Funding acquisition (equal); Supervision (equal); Writing – review & editing (equal).

Data Availability

The Columbia University IRB approved the collection of these T2DM data with the number AAAM0057. The ICU data were collected from the Columbia University Clinical Data Warehouse, are identified data, and can be made available upon request and approval of a data use agreement. We are currently working to make these data publicly available.

Ethics

Ethics approval for experiments reported in the submitted manuscript on animal or human subjects was granted. The Columbia University IRB approved the collection of these T2DM data with the number AAAM0057. The ICU data were collected from the Columbia University Clinical Data Warehouse. The consent was waved because it was secondary use of EHR data.

Conflict of Interest

The authors have no conflicts to disclose.

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Additional details

Created:
October 27, 2023
Modified:
July 10, 2024