Interestingly, the loss of HDL’s ability to stimulate eNOS activity was correlated with a decrease of sphingosine-1-phosphate (S1P) levels in the plasma of T2DM; the authors suggested that the loss of S1P is a possible mechanism to explain the inability of HDL to exert its protective functions, contributing to the generation of vascular complications in diabetes [66]. The gene discussed is NOS3; the disease is type 2 diabetes mellitus.