Given that (1 − kratio), corresponding to hepatic insulin clearance, increases as the kratio decreases, our finding strongly suggests that, from NGT to borderline type and T2DM, the peak amplitude of serum insulin concentration decreases due to the increase in hepatic insulin clearance and the temporal pattern changes from transient to sustained occur because of a decrease in peripheral insulin clearance (Fig. 5). Here, INS is linked to type 2 diabetes mellitus.