It is known that for a given
insulin level
glucose clearance depends on
glucose concentration. However, a quantitative representation of the concomitant effects of
hyperinsulinemia and
hyperglycemia on
glucose clearance, necessary to describe heterogeneous tests such as euglycemic and hyperglycemic clamps and oral tests, is lacking. Data from five studies (123 subjects) using a
glucose tracer and including all the above tests in normal and diabetic subjects were collected. A mathematical model was developed in which
glucose utilization was represented as a Michaelis-Menten function of
glucose with constant Km and
insulin-controlled Vmax, consistently with the basic notions of
glucose transport. Individual values for the model parameters were estimated using a population approach. Tracer data were accurately fitted in all tests. The estimated Km was 3.88 (2.83-5.32) mmol/l [median (interquartile range)]. Median model-derived
glucose clearance at 600 pmol/l
insulin was reduced from 246 to 158 ml·min(-1)·m(-2) when
glucose was raised from 5 to 10 mmol/l. The model reproduced the characteristic lack of increase in
glucose clearance when moderate
hyperinsulinemia was accompanied by
hyperglycemia. In all tests,
insulin sensitivity was inversely correlated with BMI, as expected (R(2) = 0.234, P = 0.0001). In conclusion,
glucose clearance in euglycemic and hyperglycemic clamps and oral tests can be described with a unifying model, consistent with the notions of
glucose transport and able to reproduce the suppression of
glucose clearance due to
hyperglycemia observed in previous studies. The model may be important for the design of reliable
glucose homeostasis simulators.