In order to study model behavior in case of extreme parameter estimates, Figure 5 panel A1 reports the predicted and observed plasma glucose concentrations obtained with the COMO model for one IFG patient whose insulin sensitivity index ISCOMO was estimated at the low limit of optimization (10−10), while Figure 5 panel B1 reports the predicted and observed plasma glucose concentrations obtained with the DMMO model for one T2DM patient whose insulin sensitivity index ISDMMO was estimated at 3.26×10−3 (very high). This evidence concerns the gene INS and type 2 diabetes mellitus.