Maximizing the success rate of minimal model insulin sensitivity measurement in humans: the importance of basal glucose levels

Minimal model analysis of glucose and insulin concentrations in the intrave nous glucose tolerance test (IVGTT) has been widely used to obtain a measur e of insulin sensitivity in humans. Issues of model validity and IVGTT prot ocol have been explored extensively. Less attention has been paid, however, to the computer programming protocol for estimating the model parameters ( programming implementation). Minimal model analysis of data from an IVGTT p rotocol involving a high glucose dose (0.5 g/kg) and a reduced sample sched ule, employed in healthy pre- or post-menopausal women, healthy men or men with coronary heart disease or chronic heart failure (20 in each group), wa s undertaken according to 12 different programming implementations using a commercially available model-equation-solving program. The ability of the p rogram to arrive at an acceptable solution to the model equations gave a su ccess rate of between 39% and 96%, depending on the implementation. Variati on in basal glucose assignment significantly affected the magnitude of esti mates of insulin sensitivity. The maximum modelling success rare was achiev ed by introduction of an imputed glucose measurement at 360 min from the gl ucose injection, taking the basal glucose level as the fasting glucose conc entration, and overweighting the initial glucose measurement after a delay for mixing. Use of this implementation to analyse data from a study compari ng insulin sensitivities obtained using the minimal model and a euglycaemic clamp reference gave a correlation of 0.80 (P < 0.001) between the two met hods. Straightforward variations in programming implementation, involving a ppropriate assignment of the basal glucose concentration and use of an impu ted glucose measurement signifying re-establishment of basal glucose levels following the IVGTT, can considerably improve modelling success rate.