A three-compartment model of the C-peptide-insulin dynamic during the DIST test

Dynamic insulin sensitivity (SI) tests often utilise model-based parameter estimation. This research analyses the impact of expanding the typically used two-compartment model of insulin and C-peptide kinetics to incorporate a hepatic third compartment. The proposed model requires only four C-peptide assays to simulate endogenous insulin production (uen), greatly reducing the cost and clinical burden. Sixteen subjects participated in 46 dynamic insulin sensitivity tests (DIST). Population kinetic parameters are identified for the new compartment. Results are assessed by model error versus measured data and repeatability of the identified SI. The median C-peptide error was 0% (IQR: -7.3, 6.7)%. Median insulin error was 7% (IQR: -28.7, 6.3)%. Strong correlation (r=0.92) existed between the SI values of the new model and those from the original two-compartment model. Repeatability in SI was similar between models (new model inter/intra-dose variability 3.6/12.3% original model -8.5/11.3%). When frequent C-peptide samples may be available, the added hepatic compartment does not offer significant diagnostic, repeatability improvement over the two-compartment model. However, a novel and successful three-compartment modelling strategy was developed which provided accurate estimation of endogenous insulin production and the subsequent SI identification from sparse C-peptide data.