Delay-induced uncertainty in the glucose-insulin system: Pathogenicity for obesity and type-2 diabetes mellitus.

We have recently shown that physiological delay can induce a novel form of sustained temporal chaos we call delay-induced uncertainty (DIU) (Karamched et al. (Chaos, 2021, 31, 023142)). This paper assesses the impact of DIU on the ability of the glucose-insulin system to maintain homeostasis when responding to the ingestion of meals. We address two questions. First, what is the nature of the DIU phenotype? That is, what physiological macrostates (as encoded by physiological parameters) allow for DIU onset? Second, how does DIU impact health? We find that the DIU phenotype is abundant in the space of intrinsic parameters for the Ultradian glucose-insulin model-a model that has been successfully used to predict glucose-insulin dynamics in humans. Configurations of intrinsic parameters that correspond to high characteristic glucose levels facilitate DIU onset. We argue that DIU is pathogenic for obesity and type-2 diabetes mellitus by linking the statistical profile of DIU to the glucostatic theory of hunger.