Given that the role of FAP in T2DM-induced HFpEF is unclear, the signaling pathways implicated in myocardial hypertrophy, fibrosis, inflammation, oxidative stress, apoptosis, and energy metabolism dysfunction such as the p-mTOR, p-ERK1/2, TGF-β1, p-Smad2/3, NOX1, NOX2, and NOX4 were explored. Here, NOX4 is linked to type 2 diabetes mellitus.