Metabolic dysfunction-associated steatotic liver disease and type 2 diabetes: Pathophysiology, diagnosis, and emerging therapeutic strategies

Table 2 Risk factors for metabolic dysfunction-associated steatotic liver disease progression in patients with type 2 diabetes

Risk factor	Mechanism	Associated outcome
Insulin resistance	Promotes de novo lipogenesis and reduces fatty acid oxidation	Steatosis, progression to MASH
Visceral obesity	Pro-inflammatory adipokine secretion, lipotoxicity	Fibrosis progression, inflammation
Poor glycemic control	Increases oxidative stress, mitochondrial dysfunction	Fibrosis, hepatocellular injury
Dyslipidemia	Elevated triglycerides and LDL lead to hepatocyte stress	Lipotoxicity, NASH progression
Hypertension	Induces endothelial dysfunction and chronic inflammation	Increased risk of fibrosis
Sedentary lifestyle	Reduces insulin sensitivity and promotes weight gain	Increased steatosis and metabolic burden
Genetic variants (e.g., PNPLA3, TM6SF2)	Impaired lipid export and processing	Accelerated fibrosis progression
Gut microbiota dysbiosis	Increased endotoxin (LPS) translocation and inflammation	Worsening hepatic inflammation and fibrosis
Advanced age	Reduced hepatic regeneration capacity, cumulative metabolic injury	Greater risk of advanced fibrosis
Diet high in saturated fats/fructose	Increases hepatic fat accumulation and lipotoxic intermediates	Steatohepatitis and fibrosis
Smoking	Oxidative stress and impaired insulin sensitivity	Fibrosis and cardiovascular risk

This table outlines the key clinical, metabolic, genetic, and lifestyle-related factors that contribute to the progression of metabolic dysfunction-associated steatotic liver disease in individuals with type 2 diabetes. Insulin resistance, visceral adiposity, dyslipidemia, and poor glycemic control are core drivers that promote hepatic steatosis, inflammation, and fibrosis. Additionally, environmental and genetic influences such as sedentary behavior, dietary composition, gut microbiota alterations, and PNPLA3 variants can further accelerate disease severity. Recognizing these risk factors is essential for targeted intervention and prevention of progression to advanced liver disease. LPS: Lipopolysaccharide; LDL: Low density lipoprotein; NASH: Nonalcoholic fatty liver disease; MASH: Metabolic dysfunction-associated steatohepatitis.