Metabolic Dysfunction-Associated Steatotic Liver Disease: Heterogeneity of Its Pathophysiology and Its Relationship with Type 2 Diabetes Mellitus

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the leading cause of chronic liver disease worldwide. People with MASLD can progress to cirrhosis and have an increased risk of developing hepatic decompensation and hepatocellular carcinoma. People with MASLD are also at increased risk of type 2 diabetes mellitus (T2DM), cardiovascular disease (CVD), chronic kidney disease, and extrahepatic cancers and most people with MASLD die from CVD. With a prevalence of about 65%, MASLD is very common among adults with T2DM. This close link between MASLD and cardiometabolic diseases suggests that the conditions share common causes, e.g., insulin resistance, hyperglycaemia, subclinical inflammation, and dysfunctional adipose tissue, and that they also influence each other. In this respect, important insights have been gained in recent years, particularly regarding the heterogeneity of MASLD pathophysiology. In this review we address this heterogeneity and discuss its impact on MASLD-related outcomes. Since successful treatment of MASLD often resembles an effective treatment regimen for T2DM, we discuss how metabolism-based treatment approaches, accounting for the heterogeneity of the pathogenesis of MASLD, might enable personalized treatment of this disease in the future.