Method to generate a large cohort in-silico for type 1 diabetes

In the last decade, several technological solutions have been proposed as artificial pancreas systems able to treat type 1 diabetes; most often they are built based on a control algorithm that needs to be validated before it is used with real patients. Control algorithms are usually tested with simulation tools that integrate mathematical models related mainly to the glucose-insulin dynamics, but other variables can be considered as well. In general, the simulators have a limited set of subjects. The main goal of this paper is to propose a new computational method to increase the number of virtual subjects, with physiological characteristics, included in the original mathematical models.

A subject is defined by a set of parameters given by a mathematical model. From the available reduced number of subjects in the model, the covariance of each parameter of every subject is obtained to establish a mathematical relationship. Then, new sets of parameters are calculated using linear regression methods; this generates larger cohorts, which allows for testing insulin therapies in open-loop or closed-loop scenarios. The new method proposed here increases the number of subjects in a virtual cohort using two versions of Hovorka's mathematical model.

Two covariant cohorts are obtained with linear regression. Both cohorts are clustered to avoid overlapping in the glucose-insulin dynamics and are compared in terms of their qualitative and quantitative behaviours in the normoglycemic range. As a result, there have been generated two larger cohorts (256 subjects) than the original population, which contributes to improving the variability in in-silico tests. In addition, for analysing the characteristics of the covariant generation method, two random cohorts have been generated, where the parameters are obtained individually and independently from each other, exhibiting only distribution limitations so that these cohorts do not have physiological subjects.

The proposed methodology has enabled the generation of a large cohort of 256 subjects, with different characteristics that are plausible in the T1DM population, significantly increasing the number of available subjects in existing mathematical models. The proposed methodology does not limit the number of subjects that can be generated and thus, it can be used to increase the number of cohorts provided by other mathematical models in diabetes, or even other scientific problems.