Incorporating bolus and infusion pharmacokinetics into the ICING insulin model

Abstract

The ICING model has been successfully used to guide clinical decisions on insulin administration in critical illness. However, insulin pharmacokinetics in the ICING model can be improved to better describe both intravenous (IV) bolus and infusion insulin administration. Patient data from 217 Dynamic Insulin Sensitivity and Secretion Tests (DISST) and 36 Intravenous Glucose Tolerance Tests (IVGTT) from independent dietary intervention studies was used to fit model parameters to a model structure that conforms to known behaviour. The DISST tests measured both endogenous and exogenous IV insulin bolus responses, while the IVGTT measured exogenous IV insulin infusion dynamics. Unidentifiable parameters were given physiologically justified values, with knowledge on relative insulin clearance rates used to constrain parameter values. The resulting whole-cohort description was able to simultaneously describe both IV bolus and infusion dynamics, and improves ICING model descriptive capability. Improved infusion dynamics will allow better description of subcutaneous insulin, the insulin administration route favoured in outpatient care of diabetes.