The DIAGRAM+ consortium observed that three loci (TCF7L2, ARAP1 and CDKAL1) were associated with reduced fasting insulin also suggestive of β-cell dysfunction, whereas the T2D risk alleles at PPARG, FTO, IRS1 and KLF14 were associated with higher fasting insulin, indicating a primary effect on insulin action [25]. This evidence concerns the gene INS and type 2 diabetes mellitus.