According to clinical measurements, kratio was also correlated with ipeak calculated directly from the serum insulin concentration measured during the first-phase secretion in hyperglycemic clamp (Supplementary Figure S8a, r = 0.423, P < 0.001), indicating that hepatic insulin clearance is pathologically correlated with the peak amplitude in the first-phase secretion from NGT to borderline type and T2DM. This evidence concerns the gene INS and type 2 diabetes mellitus.