The Effects of Additional Local-Mixing Compartments in the DISST Model-Based Assessment of Insulin Sensitivity

Abstract

Background: The identification of insulin sensitivity in glycemic modelling can be heavily obstructed by the presence of outlying data or unmodelled effects. The effect of data indicative of local mixing is especially problematic with models assuming rapid mixing of compartments. Methods such as manual removal of data and outlier detection methods have been used to improve parameter ID in these cases, but modelling data with more compartments is another potential approach. Methods: This research compares a mixing model with local depot site compartments with an existing, clinically validated insulin sensitivity test model. The Levenberg-Marquardt (LM) parameter identification method was implemented alongside a modified version (aLM) capable of operator-independent omission of outlier data in accordance with the 3 standard deviation rule. Three cases were tested: LM where data points suspected to be affected by incomplete mixing at the depot site were removed, aLM, and LM with the more complex mixing model. Results: While insulin parameters identified in the mixing model differed greatly from those in the DISST model, there were strong Spearman correlations of approximately 0.93 for the insulin sensitivity values identified across all 3 methods. The 2 models also showed comparable identification stability in insulin sensitivity estimation through a Monte Carlo analysis. However, the mixing model required modifications to the identification process to improve convergence, and still failed to converge to feasible parameters on 5 of the 212 trials. Conclusions: The mixing compartment model effectively captured the dynamics of mixing behavior, but with no significant improvement in insulin sensitivity identification.

Evolving Improved Sampling Protocols for Dose–Response Modelling Using Genetic Algorithms with a Profile-Likelihood Metric

“…A condition of minutes was imposed on samples to represent the limitation of practical sampling. Additionally, the 5 min of time following the bolus input at t = 60 min were set as infeasible sampling times, due to a practical consideration of local mixing effects being present immediately post-bolus (Lam et al 2021 ). In cases where the change would violate one of the constraints, the sampling point was shifted to the nearest valid location.…”