In recent years, an increasing amount of experimental and clinical evidence indicates that proinsulin and proinsulin-like compounds (mainly des-31,32 proinsulin) in serum have a close relationship with T2DM, whereas hyperinsulinemia in the early and intermediate disease stages is due to cross-reactivity between insulin and its precursors (Pfutzner et al., 2004). This evidence concerns the gene INS and hyperinsulinism.