Key findings demonstrated that (1) HMGCS2 overexpression effectively normalized aberrant ketone body production in NASH-T2DM mice; (2) this intervention significantly attenuated hepatocyte senescence, as evidenced by reduced SA-β-gal-positive cells and downregulated senescence-associated proteins; and (3) a concomitant amelioration of histopathological injury and inflammatory infiltration was observed. This evidence concerns the gene HMGCS2 and type 2 diabetes mellitus.