A Novel Method for Generation of in Silico Subjects with Type 2 Diabetes

A type 2 diabetes (T2D) simulator has been recently proposed for supporting drug development and treatment optimization. This tool consists of a physiological model of glucose/insulin/C-peptide dynamics and a virtual cohort of T2D subjects (i.e., random extractions of model parameterizations from a joint parameter distribution) well describing both average and variability realistic T2D dynamics. However, the state-of-art procedure to get a reliable virtual population requires some post-processing after subject extraction, in order to discard implausible behaviors. We propose an improved method for virtual subjects\u27 generation to overcome this burdensome task. To do so, we first assessed a refined joint parameter distribution, from which extracting a number of subjects, greater than the target population size. Then, target-size subsets are undersampled from the large cohort. The final virtual population is selected among the subsets as the one maximizing the similarity with T2D data and model parameter distribution, by means of measurement\u27 outcome metrics and Euclidian distance (Δ), respectively. In the final population, almost all the outcome metrics are statistically identical to the clinical counterparts (p-value>0.05) and model parameters\u27 distribution differs by ~5-10% from that derived from data. The methodology described here is flexible, thus resulting suitable for different T2D stages and type 1 diabetes, as well.Clinical Relevance - A straightforward subjects\u27 generation would ease the availability of tailored in silico trials for testing diabetes treatment in a specific population