Few attempts have been made to model mathematically the progression of type 2 diabetes. A realistic representation of the long-term physiological adaptation to developing insulin resistance is necessary for effectively designing clinical trials and evaluating diabetes prevention or disease modification therapies. Writing a good model for diabetes progression is difficult because the long time span of the disease makes experimental verification of modeling hypotheses extremely awkward. In this context, it is of primary importance that the assumptions underlying the model equations properly reflect established physiology and that the mathematical formulation of the model give rise only to physically plausible behavior of the solutions. In the present work, a model of the pancreatic islet compensation is formulated, its physiological assumptions are presented, some fundamental qualitative characteristics of its solutions are established, the numerical values assigned to its parameters are extensively discussed (also with reference to available cross-sectional epidemiologic data), and its performance over the span of a lifetime is simulated under various conditions, including worsening insulin resistance and primary replication defects. The differences with respect to two previously proposed models of diabetes progression are highlighted, and therefore, the model is proposed as a realistic, robust description of the evolution of the compensation of the glucose-insulin system in healthy and diabetic individuals. Model simulations can be run from the authors' web page.

Due to the increasing importance of identifying insulin resistance, a need exists to have a reliable mathematical model representing the glucose/insulin control system. Such a model should be simple enough to allow precise estimation of insulin sensitivity on a single patient, yet exhibit stable dynamics and reproduce accepted physiological behavior.

This work presents a polynomial version of the well-known extended Kalman filter (EKF) for the state estimation of nonlinear discrete-time stochastic systems. The proposed filter, denoted polynomial EKF (PEKF), consists in the application of the optimal polynomial filter of a chosen degree /spl mu/ to the Carleman approximation of a nonlinear system. When /spl mu/=1 the PEKF algorithm coincides with the standard EKF. For the filter implementation the moments of the state and output noises up to order 2/spl mu/ are required. Numerical simulations compare the performances of the PEKF with those of some other existing filters, showing significant improvements.

A family of delay-differential models of the glucose-insulin system is introduced, whose members represent adequately the Intra-Venous Glucose Tolerance Test and allied experimental procedures of diabetological interest. All the models in the family admit positive bounded unique solutions for any positive initial condition and are persistent. The models agree with the physics underlying the experiments, and they all present a unique positive equilibrium point.   Local stability is investigated in a pair of interesting member models: one, a discrete-delays differential system; the other, a distributed-delay system reducing to an ordinary differential system evolving on a suitably defined extended state space. In both cases conditions are given on the physical parameters in order to ensure the local asymptotic stability of the equilibrium point. These conditions are always satisfied, given the actual parameter estimates obtained experimentally. A study of the global stability properties is performed, but while from simulations it could be conjectured that the models considered are globally asymptotically stable, sufficient stability criteria, formally derived, are not actually satisfied for physiological parameters values. Given the practical importance of the models studied, further analytical work may be of interest to conclusively characterize their behavior.

This paper deals with the state estimation problem for stochastic nonlinear differential systems, driven by standard Wiener processes, and presents a filter that is a generalization of the classical extended kalman-bucy filter (EKBF). While the EKBF is designed on the basis of a first order approximation of the system around the current estimate, the proposed filter exploits a Carleman-like approximation of a chosen degree v ges 1. The approximation procedure, applied to both the state and the measurement equations, allows to define an approximate representation of the system by means of a bilinear system, for which a filtering algorithm is available from the literature. Numerical simulations on an example show the improvement, in terms of sample error covariance, of the filter based on the first-order, second-order and third-order system approximations (v = 1,2,3).