Interstitial insulin kinetic parameters for a 2-compartment insulin model with saturable clearance

Glucose-insulin system models are commonly used for identifying insulin sensitivity, either for glycaemic control or diagnostic purposes. With physiological, 2-compartment insulin kinetics models, accurate kinetic parameter values are necessary to obtain reliable estimates of insulin sensitivity. This study combined data from 6 separate, published microdialysis studies to determine the best parameter values for the transcapillary diffusion rate (nI) and cellular insulin clearance rate (nC).The 6 studies (12 data sets) used microdialysis techniques to assay interstitial insulin concentrations simultaneously with plasma insulin concentration samples. The reported plasma insulin concentrations were used as input and interstitial insulin concentrations were simulated with the interstitial insulin kinetics sub-model. These simulated results were then compared to the reported interstitial measurements and an error value calculated as the mean absolute difference across the original measurement time points, normalised by the mean interstitial insulin concentration. The most appropriate set of parameter values was determined across the 12 data sets by combining the results.The results of this investigation suggest that the most appropriate values for the interstitial insulin kinetic parameters are nI = nC = 0.0060 min-1. These parameter values are associated with an effective, interstitial insulin half-life t1/2 = 58 mins, within the range of 25-130 mins reported by others.