Kinetic Modeling of the Glucoregulatory System to Improve Insulin Therapy

Abstract

For simulating glucose-insulin control systems with respect to application in an optimized therapy of insulin-dependent diabetes, a global transfer model was generated and supplemented with a structural model of the opened control circuit. The transfer characteristics within the established linear range of the intact system, which is identical with the range of euglycaemia, can be described by a 4th-order differential equation. A test strategy was developed to identify the state variables of the opened, i. e., of the diabetic, system and to determine by pole assignment those control constants of glucose-controlled insulin provision that are optimally adapted to a given set of state variables. The model system was verified by the prediction of plasma insulin and blood glucose reponses to various loads of glucose and/or insulin, by isotopic studies (U-14C-glucose) of glucose turnover, and by predicting the rates of absorption (i. e., of appearance within the distribution space) of orally administered glucose. The latter situations provide fields of application for this model strategy in addition to the main goal, namely, the individual optimization of control parameters for open-loop or closed-loop insulin therapy.