Interplay of childhood metabolic dysfunction-associated steatotic liver disease and obesity in the development of youth-onset type 2 diabetes.

BACKGROUND: The global increase in childhood and adolescent obesity has significantly contributed to the rising prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) - a condition now recognized as a key metabolic complication in youth. MASLD significantly increases the risk of youth-onset type 2 diabetes (T2D), particularly among obese individuals. Its asymptomatic progression presents considerable challenges for timely diagnosis and intervention. AIM: To review epidemiology, pathophysiological mechanisms, and management strategies related to pediatric MASLD, exploring its interaction with obesity and youth-onset T2D. METHODS: A comprehensive literature search was conducted using PubMed, Scopus, and Google Scholar to identify peer-reviewed studies published between 2015 and 2025. Keywords included "pediatric MASLD", "childhood obesity", "youth-onset type 2 diabetes", "hepatic insulin resistance", and "noninvasive biomarkers". Articles were selected based on relevance, methodological quality, and focus on human pediatric populations. RESULTS: MASLD affects approximately 13% of children globally and up to 47% of those with obesity, with the highest prevalence reported in urban areas of the United States, China, and India. In children and adolescents, excess adiposity is the leading contributor to hepatic steatosis and metabolic dysfunction, particularly when body mass exceeds standard growth benchmarks for age and sex. MASLD increases the risk of adolescent T2D by approximately 2.7-fold. Key pathophysiological mechanisms include hepatic insulin resistance, mitochondrial dysfunction, and chronic inflammation, driven by lipotoxic metabolites such as ceramides and pro-inflammatory cytokines. Lifestyle modifications - particularly low free-sugar diets and structured physical activity - have demonstrated moderate efficacy in reducing hepatic fat and improving metabolic outcomes. Pharmacologic interventions, including glucagon-like peptide-1 receptor agonists such as liraglutide and semaglutide, show potential for weight reduction and glycemic control, though their effects on hepatic histology remain under investigation. CONCLUSION: MASLD represents a critical metabolic threat in pediatric populations, strongly influenced by obesity and closely associated with increased risk of youth-onset T2D. Effective management requires early detection, multidisciplinary interventions, and equitable access to care. Future research should prioritize the validation of noninvasive diagnostic tools, development of targeted therapies, and reduction of socioeconomic and ethnic disparities in disease burden and treatment outcomes.