IRS1 and Insulin resistance: Key Findings: (1) Lactylation modulates core diabetic pathways by targeting IRS-1 (promoting insulin resistance), NLRP3 (amplifying inflammation), and FOXO1 (enhance oxidative stress); (2) Tissue-specific regulation is observed in complications: lactylation of LARS1 and ACSF2 exacerbates podocyte injury and mitochondrial dysfunction in nephropathy; the FTO-CDK2 axis drives vascular anomalies in retinopathy; and H4K12 lactylation activates Foxo1-mediated oxidative stress in cognitive impairment.