The interplay of insulin resistance, glycemic variability, and metabolic dysfunction-associated steatotic liver disease

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a systemic metabolic disorder closely related to insulin resistance, obesity, and type 2 diabetes mellitus. While sustained hyperglycemia and insulin resistance are central to the pathogenesis of MASLD, there is growing evidence suggesting that glucose dysregulation in this condition is heterogeneous and dynamic. Glycemic variability (GV), which reflects fluctuations in glucose levels over time, has emerged as a complementary dimension of glucose homeostasis and has been increasingly explored in relation to hepatic steatosis, fibrosis, and cardiometabolic risk. Experimental data indicate that recurrent glucose oscillations promote oxidative stress, inflammatory signaling, and fibrogenic activation, while observational studies have reported associations between short- and long-term GV and MASLD-related phenotypes in diverse populations. The aim of this review is to describe the mechanistic links between insulin resistance, GV, and MASLD, summarize the current clinical and population evidence evaluating GV in this context, and identify key methodological and conceptual gaps that should inform future research.