Moreover, HOMA-IR was only reflective of organ-level dysfunction in HepGluc[+]+mIR, which was the most at-risk phenotype in terms of systemic and tissue-specific metabolic impairment, including higher inflammation, IR, liver fat, CACs, and biomarkers of MASLD and CVD.<h4>Conclusions/interpretation</h4>This study explores a potential liver-heart metabolic axis in T2D, linked to insulin-mediated dysfunction that may originate in the heart and extend to the liver. This evidence concerns the gene INS and type 2 diabetes mellitus.