Minimal model S(G) overestimation and S(I) underestimation: Improved accuracy by a Bayesian two-compartment model

The intravenous glucose tolerance test (IVGTT) single-compartment minimal model (1CMM) method has recently been shown to overestimate glucose effectiveness and underestimate insulin sensitivity. Undermodeling, i.e., use of single- instead of two-compartment description of glucose kinetics, has been advocated to explain these limitations. We describe a new two- compartment minimal model (2CMM) into which we incorporate certain available knowledge on glucose kinetics. 2CMM is numerically identified using a Bayesian approach. Twenty-two standard IVGTT (0.30 g/kg) in normal humans were analyzed. In six subjects, the clamp-based index of insulin sensitivity (S(I)/(c)) was also measured. 2CMM glucose effectiveness (S(G)/²) and insulin sensitivity (S(I)/²) were, respectively, 60% lower (P <0.0001) and 35% higher (P <0.0001) than the corresponding 1CMM S(G)/¹ and S(I)/¹ indexes: 2.81 ± 0.29 (SE) vs. S(G)/¹ = 4.27 ± 0.33 ml·min^-1·kg^-1 and S(I)/² = 11.67 ± 1.71 vs. S(I)/¹ = 8.68 ± 1.62 10² ml·min^-1·kg^-1 per μU/ml. S(I)/² was not different from S(I)/(c) = 12.61 ± 2.13 10² ml·min^-1·kg^-1 per μU/ml (nonsignificant), whereas S(I)/¹ was 60% lower (P <0.02). In conclusion, a new 2CMM has been presented that improves the accuracy of glucose effectiveness and insulin sensitivity estimates of the classic 1CMM from a standard IVGTT in normal humans.