However, it is worthy to note that: 1) the consistency of the results observed both as risk of type 2 diabetes in the DIAGRAM+ meta-analysis and as intermediate phenotype such as insulin resistance argues against a chance finding; 2) the hypotheses in this study were defined a priori, are biologically plausible and the “in vitro" results are consistent with the “in vivo" data. The gene discussed is INS; the disease is type 2 diabetes mellitus.