In summary, the AMPK/SIRT1-PGC-1α-SIRT3 pathway and miR-421, miR-34a, miR-200a, and miR-206 were studied for the first time in penile tissue from diabetic middle-aged men, demonstrating that CVDRF additional to DM have a major impact in the response to oxidative damage. This evidence concerns the gene PPARGC1A and diabetes mellitus.