The hot IVGTT two-compartment minimal model: Indexes of glucose effectiveness and insulin sensitivity

A two-compartment minimal model (2CMM) has been proposed [A. Caumo and C. Cobelli. Am. J. Physiol. 264 (Endocrinol. Metab. 27): E829-E841, 1993] to describe intravenous glucose tolerance test (IVGTT) labeled (hereafter hot) glucose kinetics. This model, at variance with the one-compartment minimal model (1CMM), allows the estimation of a plausible profile of glucose production. The aim of this study is to show that the 2CMM also allows the assessment of insulin sensitivity (S(I)/(2*)), glucose effectiveness (S(G)/(2*)), and plasma clearance rate (PCR). The 2CMM was identified on stable-isotope IVGTTs performed in normal subjects (n = 14). Results were (means ± SE) S(G)/(2*) = 0.85 ± 0.14 ml · kg^-1 · min^-1, PCR = 2.02 ± 0.14 ml · kg^-1 · min^-1, and S(I)/(2*) = 13.83 ± 2.54 x 10^-2 ml · kg^-1 · min^-1 · μU^-1 · ml. The 1CMM was also identified; glucose effectiveness and insulin sensitivity indexes were S(G)/*V = 1.36 ± 0.08 ml · kg^-1 · min^-1 and S(I)/*V = 12.98 ± 2.21 x 10^-2 ml · kg^-1. min^-1 · μU^-1 · ml, respectively, where V is the 1CMM glucose distribution volume. S(G)/*V was lower than PCR and higher than S(G)/(2*) and did not correlate with either [r = 0.45 (NS) and r = 0.50 (NS), respectively], whereas S(I)/*V was not different from and was correlated with S(I)/(2*) (r = 0.95; P <0.001). S(G)/* compares well (r = 0.78; P <0.001) with PCR normalized by the 2CMM total glucose distribution volume. In conclusion, the 2CMM is a powerful tool to assess glucose metabolism in vivo.