Translation Between Two Models; Application with Integrated Glucose Homeostasis Models.

Pharm Res

Department of Pharmaceutical Biosciences, Uppsala University, Box 591, 751 23, Uppsala, Sweden.

Published: April 2019

Purpose: For some biological systems, there exist several models with somewhat different features and perspectives. We propose an evaluation method for NLME models by analyzing real and simulated data from the model of main interest using a structurally different, but similar, NLME model. We showcase this method using the Integrated Glucose Insulin (IGI) model and the Integrated Minimal Model (IMM). Additionally, we try to map parameters carrying similar information between the two models.

Methods: A bootstrap of real data and simulated datasets from both the IMM and IGI models were analyzed with the two models. Important parameters of the IMM were mapped to IGI parameters using a large IMM simulated dataset analyzed under the IGI model.

Results: Comparison of the parameters estimated from real data and data simulated with the IMM and analyzed with the IGI model demonstrated differences between real and IMM-simulated data. Comparison of the parameters estimated from real data and data simulated with the IGI model and analyzed with the IMM also demonstrated differences but to a lower extent. The strongest parameter correlations were found for: insulin-dependent glucose clearance (IGI) ~ insulin sensitivity (IMM); insulin-independent glucose clearance (IGI) ~ glucose effectiveness (IMM); and insulin effect parameter (IGI) ~ insulin action (IMM).

Conclusions: We demonstrated a new approach to investigate models' ability to simulate real-life-like data, and the information captured in each model in comparison to real data, and the IMM clinically used parameters were successfully mapped to their corresponding IGI parameters.

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Source
http://dx.doi.org/10.1007/s11095-019-2592-9DOI Listing

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