Features of Early Diagnosis of Non-Alcoholic Fatty Liver Disease in Patients with Type 2 Diabetes Mellitus
Abstract
Non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) are interrelated pathologies forming the basis of metabolic syndrome. These conditions significantly increase the risk of severe complications, such as fibrosis, cirrhosis, and hepatocellular carcinoma. This article explores the primary pathogenesis theories of NAFLD, including alimentary and metabolic theories, and introduces the novel concept of metabolic dysfunction-associated fatty liver disease (MAFLD). Modern diagnostic approaches, such as ultrasound techniques and biochemical markers, along with the prospects of genetic testing, are discussed in detail. Molecular genetic determination of the I148M polymorphism in the PNPLA3 gene can be recommended for patients with non-alcoholic fatty liver disease (NAFLD) at any stage of disease progression, regardless of the presence or absence of other risk factors for the transition from simple steatosis to non-alcoholic steatohepatitis (NASH). Further studies on larger patient cohorts and in various populations will help refine these findings and potentially develop screening methods for the timely identification of individuals at high risk for adverse NAFLD outcomes.
References
Babenko A.Yu., Laevskaya M.Yu. Non-Alcoholic Fatty Liver Disease – Links with Metabolic Syndrome // Russian Medical Journal. – 2018. – Vol. 1. – No. I. – P. 34–40.
Bakulin I.G., Sandler Yu.G., Vinnitskaya E.V., et al. Type 2 Diabetes Mellitus and Non-Alcoholic Fatty Liver Disease: Facets of Association // Therapeutic Archive. – 2017. – Vol. 89. – No. 2. – P. 59–65.
Drapkina O.M., Korneyeva O.N., Ivashkin V.T. Therapy of Non-Alcoholic Steatohepatitis in Metabolic Syndrome: Focus on Essential Phospholipids // Attending Physician. – 2010. – No. 2. – P. 18–24.
Ivashkin V.T., Maevskaya M.V., Pavlov Ch.S., et al. Clinical Guidelines for the Diagnosis and Treatment of Non-Alcoholic Fatty Liver Disease by the Russian Society for the Study of the Liver and the Russian Gastroenterological Association // Russian Journal of Gastroenterology, Hepatology, Coloproctology. – 2016. – Vol. 26. – No. 2. – P. 24–42.
Kiseleva E.V., Demidova T.Yu. Non-Alcoholic Fatty Liver Disease and Type 2 Diabetes Mellitus: The Problem of Association and Development Stages // Obesity and Metabolism. – 2021. – Vol. 18. – No. 3. – P. 313–319.
Lazabnik L.B., Golovanova E.V., Turkina S.V., et al. Non-Alcoholic Fatty Liver Disease in Adults: Clinical Features, Diagnosis, Treatment. Recommendations for Physicians, Third Version // Experimental and Clinical Gastroenterology. – 2021. – Vol. 1. – No. 1. – P. 4–52.
Mishina E.E., Mayorov A.Yu., Bogomolov P.O., et al. Non-Alcoholic Fatty Liver Disease: Cause or Consequence of Insulin Resistance? // Diabetes Mellitus. – 2017. – Vol. 20. – No. 5. – P. 335–342.
Shagazatova B., Vafoyev Sh. Non-Alcoholic Fatty Liver Disease in the Formation of Insulin Resistance and Correction Pathways. – 2022.
Alkhouri N, et al. Noninvasive diagnosis of NASH and liver fibrosis within the spectrum of NAFLD. Gastroenterology & Hepatology. 2018;14(6):348-358.
Allen A.M., Therneau T.M., Larson J.J. et al. Nonalcoholic fatty liver disease incidence and impact on metabolic burden and death: a 20 year-community study. Hepatology. 2018. Vol. 67. № 5. P. 1726–1736.
Angulo P., KleineAr D.E., Dam-Larsen S., et al. Liver fibrosis, but no other histologic features, is associated with long-term outcomes of patients with nonalcoholic fatty liver disease. Gastroenterology. 2015. Vol. 149. № 2. P. 389–397.e10.
Anstee Q.M., Reeves H.L., Kotsiliti E., et al. From NASH to HCC: Current Concepts and Future Challenges. Nat Rev Gastroenterol Hepatol. 2019. Vol. 16. № 7. P. 411-428.
Asrih M, Jornayvaz FR. Metabolic syndrome and nonalcoholic fatty liver disease: Is insulin resistance the link? Molecular and Cellular Endocrinology. 2015;418:55-65.
Bae J.C., Cho Y.K., Lee W.Y., et al. Impact of nonalcoholic fatty liver disease on insulin resistance in relation to HbA1c levels in nondiabetic subjects. Am J Gastroenterol. 2010;105(11):2389-2395. https://doi.org/10.1038/ajg.2010.275.
Browning J.D., Szczepaniak L.S., Dobbins R., et al. Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity. Hepatology. 2004. Vol. 40. № 6. P. 1387–1395.
Chalasani N, et al. The diagnosis and management of nonalcoholic fatty liver disease: Practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2018;67(1):328-357.
Chalasani N., Younossi Z., Lavine J.E., et al. The Diagnosis and Management of Nonalcoholic Fatty Liver Disease: Practice Guidance from the American Association for the Study of Liver Diseases. Hepatology. 2018;67(1):328-357.
Cusi K. Screening for Liver Disease in Patients with Type 2 Diabetes. Diabetes Care. 2020;43(2):399-402.
Cusi K. Treatment of type 2 diabetes mellitus and non-alcoholic fatty liver disease. Nature Reviews Endocrinology. 2016;12(5):266-278.
Dongiovanni P, et al. Transmembrane 6 superfamily member 2 gene variant disentangles nonalcoholic steatohepatitis from cardiovascular disease. Hepatology. 2015;61(2):506-514.
Eslam M, et al. A new definition for metabolic dysfunction-associated fatty liver disease: An international expert consensus statement. Journal of Hepatology. 2020;73(1):202-209.
International Diabetes Federation. IDF Diabetes Atlas. 9th ed. Brussels: IDF; 2022; 176 p.
Loomba R, et al. Advances in non-invasive assessment of hepatic fibrosis in NAFLD. Nature Reviews Gastroenterology & Hepatology. 2021;18(7):407-420.
Loomba R., Sanyal A. J. (2013). The global NAFLD epidemic. Nature Reviews Gastroenterology & Hepatology.
Loomba R., Schork N., Chen C.H. et al. Heritability of hepatic fibrosis and steatosis based on a prospective twin study // Gastroenterology. 2015. Vol. 149. № 7. P. 1784–1793.
Marchesini G., Brizi M., Morselli-Labate A.M., et al. Association of nonalcoholic fatty liver disease with insulin resistance. Am J Med. 1999;107(5):450-455. https://doi.org/10.1016/s0002-9343(99)00271-5.
Mitra S., De A., Chowdhury A. Epidemiology of non-alcoholic fatty liver diseases. Transl Gastroenterol Hepatol. 2020. Vol. 5. ID 16.
Noureddin M., Younossi Z.M., Loomba R., et al. Screening for Nonalcoholic Fatty Liver Disease in the Primary Care Clinic. Gastroenterol Hepatol (N Y). 2019;15(7):357-365.
Romeo S, et al. Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease. Nature Genetics. 2008;40(12):1461-1465.
Targher G. Is it time for non-alcoholic fatty liver disease screening in patients with type 2 diabetes mellitus? Hepatobiliary Surg Nutr. 2020;9(2):239-241. https://doi.org/10.21037/hbsn.2019.10.21.
Targher G., Bertolini L., Padovani R., et al. Prevalence of nonalcoholic fatty liver disease and its association with cardiovascular disease among type 2 diabetic patients. Diabetes Care. 2007;30(5):1212-1218. https://doi.org/10.2337/dc06-2247.
Vilar-Gomez E, et al. Weight loss through lifestyle modification significantly reduces features of nonalcoholic steatohepatitis. Gastroenterology. 2015;149(2):367-378.
Vilar-Gomez E., Calzadilla-Bertot L., Wong V.W., et al. Screening for Nonalcoholic Fatty Liver Disease in Persons with Type 2 Diabetes: Are Guidelines Cost-Effective. Gastroenterology. 2018;155(3):846-848.
Wang S.T., Zheng J., Peng H.W., et al. Physical activity intervention for non-diabetic patients with non-alcoholic fatty liver disease: a meta-analysis of randomized controlled trials. BMC Gastroenterol. 2020;20(1):66. https://doi.org/10.1186/s12876-020-01204-3.
Webb D.R., Yates T., Davies M.J. Pathophysiology of type 1 and type 2 diabetes mellitus: a 90-year perspective
Younossi Z.M., Golabi P., de Avila L., 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. https://doi.org/10.1016/j.jhep.2019.06.021.
Younossi ZM, et al. Global epidemiology of nonalcoholic fatty liver disease—Meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology. 2016;64(1):73-84.
