Is the minimal model too minimal?

The intravenous glucose tolerance test (IVGTT: standard or modified with a tolbutamide or insulin injection) interpreted with the classic minimal model of glucose disappearance [1, 2] is a powerful non-invasire tool with which to investigate glucose metabolism in physiopathology studies. The model provides two metabolic indices measuring glucose effectiveness, Sc~ and insulin sensitivity, SI, in a single individual. S c and S I are composite parameters, i.e. they measure the net effect of glucose and insulin, respectively, to p romote glucose disappearance and inhibit endogenous glucose production. The minimal model me thod has gained increasing populari ty (approximately 250 papers appeared before 1995) and is used by investigators around the world because it is simple and non-invasive. Unfortunately several reports in the last few years have indicated that some assumptions of the minimal model me thod may not be entirely correct [3-7]. In particular, Quon et al. [6] have shown in a study on insulindependent diabetic patients that the decay of glucose during an IV G TT in which insulin is maintained at the basal level is not monoexponent ia l as predicted by the minimal model and that S G is overestimated. More recently, Saad et al. [7] have shown that in normotolerant subjects S~ obtained from an insulin-modified IVGTT is underes t imated when compared to insulin sensitivity obtained with the glucose clamp technique and that in non-insul in-dependent diabetic (NIDDM) patients SI is both inaccurate and imprecise. However, no clear explanation has been offered as to why S c is overest imated and S I underest imated.