Targeting pathophysiological hallmark genes and pathways in diabesotension to advance personalized therapeutic interventions

Abstract Diabesotension refers to the pathophysiological association between diabetes mellitus, obesity, and hypertension. Despite their frequent coexistence, the underlying molecular mechanisms driving this triad remain poorly understood, and current therapeutic strategies typically address each condition in isolation rather than targeting their shared pathophysiological pathways. To identify potential hallmark genes underlying diabesotension, we mined gene associations with the triad from the NCBI database. Our analysis revealed that AKT1 and NF-κB1 are implicated in four major hallmarks of diabesotension, such as insulin resistance, inflammation, neurohormonal regulation, and oxidative stress. Collectively, these findings highlight the PI3K/Akt and NF-κB pathways as potential molecular drivers in the pathogenesis of diabesotension. This commentary will provide a comprehensive discussion of these findings within the broader context of current knowledge on the role of PI3K/Akt and NF-κB signaling in diabesotension.