Correlations between the Index and G provide tests of the validity of this model. And in fact, the close relationships between the Index and G0 and G120 (r2=83%) reported by Gastaldelli et al. support this strongly. The unexplained variance in these relationships (17%) is consistent with the likely measurement errors in the Index (10–15%) and G (~3%). Other factors which could contribute to error variance include: (i) variations within subjects in insulin secretory sensitivity to glucose and index of whole-body insulin resistance across the different conditions (fasting, OGTT, glucose clamp); (ii) independent (of β and IR) variations in Rin between subjects during fasting or OGTT; and (iii) the many physiological complexities excluded from the model. The very good fits obtained by Gastaldelli’s team suggest that all of these factors have little influence on the responses observed. The model appears equally valid across the ranges of glucose tolerance, measurement conditions and adiposity in the sample. In this model, the Index or other Disposition Indices provide no information on the causes of variations in glucose tolerance apart from apparently negligible effects of variations in Rin. Measures of any two of G, IR and β are sufficient to calculate the third. In summary, the strong fits to this model obtained by Gastaldelli et al. do not address any effects that obesity may have on underlying β or IR. We suggest that any attempt to relate between subject variations in indices of the type used in the study in question (Disposition Indices) and glycaemia with the aim of investigating the pathogenesis of glucose intolerance will be similarly invalid.