Measurement of selective effect of insulin on glucose disposal from labeled glucose oral test minimal model

The oral glucose minimal model (OMM) measures insulin sensitivity (S _I) and the glucose rate of appearance (R_a) of ingested glucose in the presence of physiological changes of insulin and glucose concentrations. However, S_I of OMM measures the overall effect of insulin on glucose utilization and glucose production. In this study we show that, by adding a tracer to the oral dose, e.g., of a meal, and by using the labeled version of OMM, OMM* to interpret the data, one can measure the selective effect of insulin on glucose disposal, S*_I Eighty-eight individuals underwent both a triple-tracer meal with the tracer-to-tracee clamp technique, providing a model-independent reference of the R_a of ingested glucose (R_{a meal}^ref) and an insulin-modified labeled intravenous glucose tolerance test (IVGTT*). We show that OMM* provides not only a reliable means of tracing the R _a of ingested glucose (R_{a meal}) but also accurately measures S*_I. We do so by comparing OMM* R _{a meal} with the model-independent R_{a meal}^ref provided by the tracer-to-tracee clamp technique, while OMM* S*_I is compared with both S*_I^ref, obtained by using as known input R_{a meal}^ref and with S*_I measured during IVGTT*.