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Am J Physiol Endocrinol Metab 276: E1171-E1193, 1999;
0193-1849/99 $5.00
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Vol. 276, Issue 6, E1171-E1193, June 1999

MODELING IN PHYSIOLOGY
Undermodeling affects minimal model indexes: insights from a two-compartment model

Andrea Caumo1, Paolo Vicini2, Jeffrey J. Zachwieja3, Angelo Avogaro4, Kevin Yarasheski5, Dennis M. Bier6, and Claudio Cobelli7

1 San Raffaele Scientific Institute, 20100 Milan; 4 Department of Metabolic Diseases and 7 Department of Electronics and Informatics, University of Padova, 35131 Padua, Italy; 2 Department of Bioengineering, University of Washington, Seattle, Washington 98195; 3 Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, Louisiana 70808; 5 Metabolism Division, Washington University School of Medicine, Saint Louis, Missouri 63110; and 6 Children's Nutrition Research Center, Baylor College of Medicine, Houston, Texas 77030-2600

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 (S*<SUB>G</SUB>) and insulin sensitivity (S*<SUB>I</SUB>) 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, S*<SUB>G</SUB>, and S*<SUB>I</SUB> 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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