Thus, while one would expect the hypoxic, I/R, inflammatory, and metabolic insults associated with CPB to normally upregulate enzymes such as SIRT1, the transcription factor FOXO3α, and the peroxisome proliferator-activated receptor gamma coactivator 1a (PGC1a) enzyme, involved in autophagy (SIRT1, FOXO3α) and fatty acid oxidation (PGC1a), these responses are all blunted in DM. The gene discussed is FOXO3; the disease is diabetes mellitus.