Minimal model estimation of glucose absorption and insulin sensitivity from oral test: Validation with a tracer method

Measuring insulin sensitivity during the physiological milieu of oral glucose perturbation, e.g., a meal or an oral glucose tolerance test, would be extremely valuable but difficult since the rate of appearance of absorbed glucose is unknown. The reference method is a tracer two-step one: first, the rate of appearance of glucose (R_{a meal}^ref) is reconstructed by employing the tracer-to-tracee ratio clamp technique with two tracers and a model of non-steady-state glucose kinetics; next, this R _{a meal}^ref K used as the known input of a model describing insulin action on glucose kinetics to estimate insulin sensitivity (S _I^ref). Recently, a nontracer method based on the oral minimal model (OMM) has been proposed to estimate simultaneously the above quantities, denoted R_{a meal} and S_I, respectively, from plasma glucose and insulin concentrations measured after an oral glucose perturbation. This last method has obvious advantages over the tracer method, but its domain of validity has never been assessed against a reference method. It is thus important to establish whether or not the "nontracer" R_{a meal} and S_I compare well with the "tracer" R_{a meal}^ref and S_I^ref. We do this comparison on a database of 88 subjects, and it is very satisfactory: R _{a meal} profiles agree well with the R_{a meal}^ref and correlation of S_I^ref with S_I is r = 0.86 (P < 0.0001). We conclude that OMM candidates as a reliable tool to measure both the rate of glucose absorption and insulin sensitivity from oral glucose tests without employing tracers.