ASSOCIATION BETWEEN TYPE 2 DIABETES MELLITUS AND NAFLD PROGRESSION: A COMPREHENSIVE NARRATIVE REVIEW
Keywords:
NAFLD, Type 2 Diabetes Mellitus, NASH, Fibrosis, Insulin Resistance, MASLD, Resmetirom, GLP-1 Receptor Agonists, Non-invasive Testing.Abstract
Non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) represent two intertwined epidemics of the modern era, sharing common pathophysiological roots in insulin resistance and metabolic dysfunction. This comprehensive narrative review examines the bidirectional relationship between T2DM and NAFLD progression, exploring the epidemiological burden, molecular mechanisms, clinical implications, and emerging therapeutic strategies. The global prevalence of NAFLD has risen dramatically to approximately 38% among adults, with T2DM present in up to 70% of NAFLD patients. Conversely, 55-70% of T2DM patients develop NAFLD, and 20-40% progress to non-alcoholic steatohepatitis (NASH). Multiple meta-analyses have confirmed that T2DM doubles the risk of severe liver disease events and increases the risk of hepatocellular carcinoma by 2.0-2.5 fold. The pathophysiological nexus centers on insulin resistance-driven lipotoxicity, chronic low-grade inflammation, and oxidative stress, perpetuating a vicious cycle of metabolic deterioration. Recent advances in pharmacotherapy, including the FDA approval of resmetirom in March 2024 as the first targeted treatment for NASH with fibrosis, combined with the established benefits of GLP-1 receptor agonists, SGLT2 inhibitors, and pioglitazone, have transformed the therapeutic landscape. Early identification through non-invasive screening algorithms and integrated management approaches targeting both metabolic and hepatic endpoints are essential for improving outcomes in this high-risk population.
References
1. Younossi ZM, et al. The global epidemiology of NAFLD and NASH in patients with type 2 diabetes: A systematic review and meta-analysis. J Hepatol. 2019;71(4):793-801.
2. Cernea S. NAFLD Fibrosis Progression and Type 2 Diabetes: The Hepatic-Metabolic Interplay. Life (Basel). 2024;14(2):272.
3. Jarvis H, et al. Type 2 diabetes and severe liver disease: A nationwide cohort study. Diabetes Care. 2020;43(2):e30-e32.
4. Alexander M, et al. Risks and clinical predictors of cirrhosis and hepatocellular carcinoma diagnoses in adults with diagnosed NAFLD. J Hepatol. 2019;71(2):278-286.
5. Kanwal F, et al. Risk of hepatocellular cancer in patients with non-alcoholic fatty liver disease. Gastroenterology. 2018;155(6):1828-1837.
6. Targher G, Corey KE, Byrne CD. The complex link between NAFLD and type 2 diabetes mellitus: Mechanisms and treatments. Nat Rev Gastroenterol Hepatol. 2021;18(9):599-612.
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