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1 San Raffaele Scientific
Institute,
The classic (hereafter cold) and the labeled
(hereafter hot) minimal models are powerful tools to investigate
glucose metabolism. The cold model provides, from intravenous glucose
tolerance test (IVGTT) data, indexes of glucose effectiveness
(SG) and insulin sensitivity
(SI) that measure the effect of
glucose and insulin, respectively, to enhance glucose disappearance and
inhibit endogenous glucose production. The hot model provides, from hot
IVGTT data, indexes of glucose effectiveness
(
) and insulin sensitivity (
) that, respectively, measure the
effects of glucose and insulin on glucose disappearance only. Recent
reports call for a reexamination of some of the assumptions of the
minimal models. We have previously pointed out the criticality of the
single-compartment description of glucose kinetics on which both the
minimal models are founded. In this paper we evaluate the impact of
single-compartment undermodeling on
SG,
SI,
, and
by using a two-compartment model
to describe the glucose system. The relationships of the minimal model
indexes to the analogous indexes measured with the glucose clamp
technique are also examined. Theoretical analysis and simulation
studies indicate that cold indexes are more affected than hot indexes
by undermodeling. In particular, care must be exercised in the
physiological interpretation of
SG, because this index is a local
descriptor of events taking place in the initial portion of the IVGTT.
As a consequence, SG not only
reflects glucose effect on glucose uptake and production but also the
rapid exchange of glucose between the accessible and nonaccessible
glucose pools that occurs in the early part of the test.
insulin sensitivity; glucose effectiveness; mathematical model; intravenous glucose tolerance test; glucose clamp
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