In this longitudinal study, undertaken on 7098 participants of the PREDIMED trial, we have been able to demonstrate the relevance of the CLOCK-rs4580704 SNP in the incidence of T2D and related processes, which finally lead to a higher incidence of CVD in T2D subjects, strengthening the connection between genetic variants in core clock genes, metabolic alterations and CVD risk. This evidence concerns the gene CLOCK and type 2 diabetes mellitus.