Modeling Glucagon Action in Patients With Type 1 Diabetes
Abstract
The dual-hormone artificial pancreas is an emerging technology to treat type 1 diabetes (T1D). It consists of a glucose sensor, infusion pumps, and a dosing algorithm that directs hormonal delivery. Preclinical optimization of dosing algorithms using computer simulations has the potential to accelerate the pace of development for this technology. However, current simulation environments consider glucose regulation models that either do not include glucagon action submodels or include submodels that were proposed without comparison to other candidate models. We consider here nine candidate models of glucagon action featuring a number of possible characteristics: insulin-independent glucagon action, insulin/glucagon ratio effect on hepatic glucose production, insulin-dependent suppression of glucagon action, and the effect of rate of change of glucagon. To assess the models, we use measurements of plasma insulin, plasma glucagon, and endogenous glucose production collected from experiments involving eight subjects with T1D who receive four subcutaneous glucagon boluses. We estimate each model's parameters using a Bayesian approach, and the models are contrasted based on the deviance information criterion. The model achieving the best fit features insulin-dependent suppression of glucagon action and incorporates effects of both glucagon levels and its rate of change.
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Some mathematical models exist in the literature describing postprandial endogenous glucose production suppression as a function of plasma glucose, insulin, and glucagon.
“Some mathematical models exist in the literature describing the postprandial EGP suppression as a function of plasma glucose, insulin [10, 11], and glucagon [12–15].”
From Modeling the effect of glucagon on endogenous glucose production in healthy individuals under meal-like conditions (2025) · cites this paper as [14]
In these experimental conditions, this model and the other models of the literature are still suboptimal because they do not account for the glucagon evanescent effect visible in the data.
“Nonetheless, in our experimental conditions, this [11] and the other models of the literature [10, 12–15] are still suboptimal since they do not account for the glucagon evanescent effect visible in the data (Fig. 1, Panel D).”
From Modeling the effect of glucagon on endogenous glucose production in healthy individuals under meal-like conditions (2025) · cites this paper as [14]
Most existing mathematical models of postprandial endogenous glucose production suppression use plasma glucose and not endogenous glucose production as the variable to fit.
“However, most of them use plasma glucose and not EGP as a variable to fit.”
From Modeling the effect of glucagon on endogenous glucose production in healthy individuals under meal-like conditions (2025) · cites this paper as [14]
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Faggionato, E., Tonello, A., Laurenti, M. C., Vella, A., & Dalla Man, C. (2025) · American Journal of Physiology - Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00172.2025
- Authors
- Emami, A., Youssef, J. E., Rabasa-Lhoret, R., Pineau, J., Castle, J. R., & Haidar, A.
- Affiliations
- McGill University (CA)
- Oregon Health & Science University (US)
- Venue
- IEEE Journal of Biomedical and Health Informatics
- Published
- 2017-07
- Volume
- 21
- Issue
- 4
- Pages
- 1163-1171
- ISSN
- 2168-2194 (ISSN-L)
- 2168-2208
- OpenAlex
- W2484925680
- Cited by
- 20
- References
- 50
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 2 · 2023: 2 · 2022: 4 · 2021: 3 · 2020: 1 · 2019: 1 · 2017: 2
- FWCI
- 1.00
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- IEEE Journal of Biomedical and Health Informatics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- J.-A. DeSève Research Chair
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Keywords
- type 1 diabetes, dosing algorithm, hepatic glucose production, insulin/glucagon ratio, endogenous glucose production, Bayesian parameter estimation, model selection
- MeSH terms
- Algorithms, Bayes Theorem, Computer Simulation, Diabetes Mellitus, Type 1, Glucagon, Humans, Insulin, Insulin Infusion Systems, Models, Biological, Pancreas, Artificial
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