Close multilevel links between metabolic dysfunction-associated steatotic liver disease and type 2 diabetes mellitus

Since liver cirrhosis due to Metabolic Dysfunction Associated Steatotic Liver Disease (MASLD) was first described in patients with diabetes mellitus, the prevalence and severity of this liver disease have increased dramatically, driven by the increase in obesity and type 2 diabetes mellitus (T2DM). Strong epidemiological links between MASLD, insulin resistance and T2DM exist: T2DM is associated with higher prevalence and severity of MASLD, up to hepatic decompensation and hepatocellular carcinoma, and MASLD is in turn associated with incident T2DM Mechanistic studies support insulin resistance of metabolic tissues as the root cause of MASLD, whereas hepatic insulin resistance in turn contributes to hyperglycemia. Several pharmacological agents including incretin-based strategies, FGF21 analogues and the panPPAR agonist lanifibranor target the interface of MASLD and T2DM and have thereby shown promise to improve MASH and associated liver fibrosis. In light of the evident close multilevel links between MASLD and T2DM, care development efforts for MASLD in guidelines, local protocols and implementation strategies should aim to involve hepatologists, diabetologists, PCPs and their affiliated care teams in a joint effort to address the growing burden of fibrotic MASLD.