Hyperinsulinemia, an overlooked clue, and potential way forward in metabolic dysfunction-associated steatotic liver disease

Metabolic dysfunction-associated steatotic liver disease (MASLD) is closely associated with other features of the metabolic syndrome such as type 2 diabetes. The progression of the disease may lead to liver fibrosis which is the main predictor of major adverse liver outcomes. Insulin resistance plays a major role in the pathogenesis of the disease. A component of the fasting hyperinsulinemia is a failure of the liver to adjust peripheral level of insulin due to reduced clearance. The associated fasting hyperinsulinemia has been independently associated as a predictor of major adverse liver outcomes and major adverse cardiovascular events. In this review, we discuss the potential mechanism and entanglement between liver fibrosis and hyperinsulinemia and we hypothesise that the measure of fasting insulin could become a hepatic functional test within the armamentarium of non-invasive tests for the assessment of MASLD.