Insulin resistance as a trigger for hepatocellular injury and inflammation in metabolic dysfunction–associated steatotic liver disease

Introduction . MASLD is currently a significant public health problem, affecting more than 30% of the world's population, and is associated with premature mortality from many causes. Insulin resistance (IR) is one of the leading pathogenetic links in MASLD. According to various authors, there is a direct relationship between the occurrence of lobular inflammation, ballooning degeneration and the level of IR in MASLD in individuals with type 2 diabetes mellitus (DM2), which is due to the inducing effect of IR on unflammation. In patients with MASLD without DM2, the effect of IR on the inflammatory process in the liver still unclear. The aim of the study was to assess the relationship between the degree of IR and indicators of the necrotic-inflammatory process in patients with MASLD without DM2. Materials and methods . A total of 110 patients with MASBP were examined: 68 men (61.8%) and 42 women (38.2%), aged 50.5±10.8 years. Traditional liver tests and cytokines TNF-α, IL-1β, IL-6 and IL-8, and cytokeratin fragments-18 (CK-18) were determined. The HOMA-IR index was calculated using the formula (fasting glucose, mmol/l) x (fasting insulin, μIU/ ml)/22.5. Results . Insulin resistance according to HOMA-IR ≥2.6 was detected in 55 (50.0%) patients and was not detected in 55 (50.0%) patients. When comparing laboratory parameters in MASLD with normal and elevated HOMA-IR, significantly higher levels of FCK-18, ALT, AST, IL-1β and IL-6 were detected in patients with IR. The same pattern was observed for carbohydrate and lipid metabolism parameters. HOMA-IR demonstrated reliable correlations with FCK-18, AST, and the number of lymphocytes and monocytes of peripheral blood. Conclusion . In 50.0% of patients with MASLD, prior to the development of overt clinical type 2 diabetes mellitus, there was a high level of HOMA-IR, confirming insulin resistance. Its presence was accompanied by a significant increase in biomarkers of hepatocellular death and inflammation, which predicted a more severe course of MASLD.