Receptor-based Models of Insulin Saturation Dynamics

Abstract

Normalisation of blood glucose by intensive insulin therapy has beneficial effects on the mortality and morbidity of intensive care patients, but also increases the risk of life threatening hypoglycaemia. Attempts to improve the control of blood glucose with model based systems have shown promising results, but require that the saturation of the effect of insulin on glucose balance at high plasma insulin concentrations is modeled appropriately. This saturation is often ignored in commonly used models of glucose metabolism, such as the minimal model, but may be important in patients with reduced insulin sensitivity. In this paper three simple models of insulin saturation are explored, all of them ascribing saturation to properties of the binding between insulin and its receptor. The models can be fitted to data from patients with normal or near normal insulin sensitivity, and they all predict that the plasma concentration at which half-insulin effect is reached is about 50 mU/l, also in patients with reduced insulin sensitivity. This prediction can be tested against clinical data, and if true will lead to advice on insulin therapy that avoids infusions that exceed 8 U/hour, in order to avoid saturation and the associated risk of hypoglycaemia.