The identification of a missense variant (rs373863828, c.1370G>A, p.R457Q) in the CREB3 Regulatory Factor (CREBRF), which occurs at a relatively high frequency within Pacific Islander populations (minor allele frequency [MAF] range: 0.042–0.259) [6–14], suggests that genetic influences might mitigate type 2 diabetes mellitus risk for some in this population and may attenuate the overall population prevalence. This evidence concerns the gene CREBRF and type 2 diabetes mellitus.