Is non-alcoholic fatty liver disease a consequence of obesity and a predictor of diabetes?


Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

Abstract

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease that tends to annually increase in incidence along with obesity. The presence of NAFLD is associated with the development of fibrosis, cirrhosis, liver cancer, as well as a high incidence of cardiovascular diseases. At the same time, the occurrence of type 2 diabetes mellitus (DM2) is certainly associated with NAFLD; moreover, the combination of these diseases contributes to their accelerated progressive course. This review was aimed to the evaluation of the pathogenetic relationship of NAFLD, DM2 and obesity in order to develop the most appropriate tactics for the treatment of comorbidity.

Full Text

Restricted Access

About the authors

N. I Volkova

Rostov State Medical University

Rostov-on-Don, Russia

Stanislav O. Panenko

Rostov State Medical University

Email: stasrostov555@gmail.com
Postgraduate Student at the Department of Internal Medicine № 3 Rostov-on-Don, Russia

A. O Golubeva

Rostov State Medical University

Rostov-on-Don, Russia

References

  1. Hardy Т., Oakley F., Anstee Q.M., Day C.P Nonalcoholic Fatty Liver Disease: Pathogenesis and Disease Spectrum. Annu Rev Pathol. 2016;11:451-96. doi: 10.1146/annurev-pathol-012615-044224.
  2. Younossi Z.M., Koenig A.B., Abdelatif D., et al. Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology. 2016;64(1):73-84. doi: 10.1002/hep.28431.
  3. Katsiki N., Perez-Martinez P, Anagnostis P, et al. Is Nonalcoholic Fatty Liver Disease Indeed the Hepatic Manifestation of Metabolic Syndrome? Curr Vasc Pharmacol. 2018;16(3):219-27. Doi:10.2174/I 570161115666170621075619/
  4. Taylor R.S., Taylor R.J., Bayliss S., et al. Association Between Fibrosis Stage and Outcomes of Patients With Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis. Gastroenterology. 2020;158(6):1611-25.e12. Doi:10.1053/j. gastro.2020.01.043.
  5. Baratta F, Pastori D., Angelico F, et al. Nonalcoholic Fatty Liver Disease and Fibrosis Associated With Increased Risk of Cardiovascular Events in a Prospective Study. Clin Gastroenterol Hepatol. 2020;18(10):2324-31.e4. Doi:10.1016/j. cgh.2019.12.026.
  6. Sheka A.C., Adeyi O., Thompson J., et al. Nonalcoholic Steatohepatitis: A Review [published correction appears in JAMA. 2020;323(16):1619]. JAMA. 2020;323(12):1175-83. Doi:10.1001/ jama.2020.2298.
  7. 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. doi: 10.1016/j.jhep.2019.06.021
  8. Jarvis H, Craig D., Barker R., et al. Metabolic risk factors and incident advanced liver disease in non-alcoholic fatty liver disease (NAFLD): A systematic review and meta-analysis of population-based observational studies. PLoS Med. 2020;17(4):e1003100. doi: 10.1371/journal. pmed.1003100.
  9. Chun H.S., Lee J.S., Lee H.W., et al. Association between the severity of liver fibrosis and cardiovascular outcomes in patients with type 2 diabetes. J Gastroenterol Hepatol. 2021;36(6):1703-13. doi: 10.1111/jgh.15387.
  10. Ichikawa K., Miyoshi T., Osawa K., et al. Prognostic value of non-alcoholic fatty liver disease for predicting cardiovascular events in patients with diabetes mellitus with suspected coronary artery disease: a prospective cohort study. Cardiovasc Diabetol. 2021;20(1):8. doi: 10.1186/s12933-020-01192-4.
  11. Targher G. Is it time for non-alcoholic fatty liver disease screening in patients with type 2 diabetes mellitus? HepatobiliarySurg Nutr. 2020;9(2):239-41. doi: 10.21037/hbsn.2019.10.21.
  12. Mantovani A., Petracca G., Beatrice G., et al. Nonalcoholic fatty liver disease and risk of incident diabetes mellitus: an updated meta-analysis of 501 022 adult individuals. Gut. 2021;70(5):962-69. doi: 10.1136/gutjnl-2020-322572.
  13. Lu F.B., Zheng K.I., Rios R.S., et al. Global epidemiology of lean non-alcoholic fatty liver disease: A systematic review and meta-analysis. J Gastroenterol Hepatol. 2020;35(12):2041-50. doi: 10.1111/jgh.15156.
  14. Sookoian S., Pirola C.J. Systematic review with meta-analysis: risk factors for non-alcoholic fatty liver disease suggest a shared altered metabolic and cardiovascular profile between lean and obese patients. Aliment Pharmacol Ther 2017;46(2):85-95. doi: 10.1111/apt.14112.
  15. Xing J., Guan X., Zhang Q., et al. Triglycerides Mediate Body Mass Index and Nonalcoholic Fatty Liver Disease: A Population-Based Study Obes Facts. 2021;14(2):190-96. doi: 10.1159/000514848.
  16. Li M., Shu W, Zunong J., et al. Predictors of nonalcoholic fatty liver disease in children. Pediatr Res. 2021. doi: 10.1038/s41390-021-01754-6.
  17. Suzuki A., Angulo P, Lymp J., et al. Chronological development of elevated aminotransferases in a nonalcoholic population. Hepatology. 2005;41(1):64-71. doi: 10.1002/hep.20543.
  18. Cree-Green M., Ravi S., Carreau A.M., et al. Nonalcoholic fatty liver disease in obese adolescent females is associated with multi-tissue insulin resistance and visceral adiposity markers. Metabol Open. 2019;2:100011. Doi:10.1016/j. metop.2019.100011.
  19. Deivanayagam S., Mohammed B.S., Vitola B.E., et al. Nonalcoholic fatty liver disease is associated with hepatic and skeletal muscle insulin resistance in overweight adolescents. Am J Clin Nutr 2008;88(2):257-62. Doi:10.1093/ ajcn/88.2.257.
  20. Marchesini G., Brizi M., Bianchi G., et al. Nonalcoholic fatty liver disease: a feature of the metabolic syndrome. Diabetes. 2001;50(8):1844-doi: 10.2337/diabetes.50.8.1844.
  21. Lee S., Rivera-Vega M., Alsayed H.M., et al. Metabolic inflexibility and insulin resistance in obese adolescents with non-alcoholic fatty liver disease. Pediatr Diabetes. 2015;16(3):211-18. doi: 10.1111/pedi.12141.
  22. Bugianesi E., Gastaldelli A., Vanni E., et al. Insulin resistance in non-diabetic patients with non-alcoholic fatty liver disease: sites and mechanisms. Diabetologia. 2005;48(4):634-42. doi: 10.1007/s00125-005-1682-x.
  23. Eshraghian A, Nikeghbalian S, Shamsaeefar A, et al. Hepatic steatosis and liver fat contents in liver transplant recipients are associated with serum adipokines and insulin resistance. Sci Rep. 2020;10(1):12701. doi: 10.1038/s41598-020-69571-1.
  24. Wu H., Ballantyne C.M. Metabolic Inflammation and Insulin Resistance in Obesity. Circ Res. 2020;126(11):1549- 64. Doi:10.1161/ CIRCRESAHA.119.315896.
  25. Zhang J., Zhao Y, Xu C., et al. Association between serum free fatty acid levels and nonalcoholic fatty liver disease: a cross-sectional study. Sci Rep. 2014;4:5832. doi: 10.1038/srep05832.
  26. lomonaco R., Ortiz-Lopez C., Orsak B., et al. Effect of adipose tissue insulin resistance on metabolic parameters and liver histology in obese patients with nonalcoholic fatty liver disease. Hepatology. 2012;55(5):1389-97. Doi:10.1002/ hep.25539.
  27. omonaco R., Bril F, Portillo-Sanchez P, et al. Metabolic Impact of Nonalcoholic Steatohepatitis in Obese Patients With Type 2 Diabetes. Diabetes Care. 2016;39(4):632-38. doi: 10.2337/dc15-1876.
  28. Musso G, Cassader M., De Michieli F., et al. Nonalcoholic steatohepatitis versus steatosis: adipose tissue insulin resistance and dysfunctional response to fat ingestion predict liver injury and altered glucose and lipoprotein metabolism. Hepatology. 2012;56(3):933-42. Doi: 10.1002/ hep.25 739.
  29. London A., Lundsgaard A.M., Kiens B., Bojsen-Mller K.N. The Role of Hepatic Fat Accumulation in Glucose and Insulin Homeostasis-Dysregulation by the Liver. J Clin Med. 2021;10(3):390. doi: 10.3390/jcm10030390.
  30. Donnelly K.L., Smith C.I., Schwarzenberg S.J., et al. Sources of fatty acids stored in liver and secreted via lipoproteins in patients with nonalcoholic fatty liver disease. J Clin Invest. 2005;115(5):1343-51. doi: 10.1172/J023621.
  31. Handa Ft, Vemulakonda A.L., Maliken B.D., et al. Differences in hepatic expression of iron, inflammation and stress-related genes in patients with nonalcoholic steatohepatitis. Ann Hepatol. 2017;16(1):77-85. doi: 10.5604/16652681.1226818.
  32. Abiru S., Migita K., Maeda Y, et al. Serum cytokine and soluble cytokine receptor levels in patients with non-alcoholic steatohepatitis. Liver Int. 2006;26(1):39-45. doi: 10.1111/j.1478-3231.2005.01191.x.
  33. Zang M. The Molecular Basis of Hepatic De Novo Lipogenesis in Insulin Resistance. In: Ntambi J. (eds) Hepatic De Novo Lipogenesis and Regulation of Metabolism. Springer, Cham. 2016. doi: 10.1007/978-3-319-25065-6_2.
  34. Gastaldelli A. NAFLD and Insulin Resistance: A Multisystemic Disease. In: Bugianesi E. (eds) NonAlcoholic Fatty Liver Disease. Springer, Cham. 2020. doi: 10.1007/978-3-319-95828-6_4
  35. Lambert J.E., Ramos-Roman M.A., Browning J.D., et al. Increased de novo lipogenesis is a distinct characteristic of individuals with nonalcoholic fatty liver disease. Gastroenterology. 2014;146(3):726-35. Doi: 10.1053/j. gastro.2013.11.049.
  36. Pierantonelli I., Svegliati-Baroni G. Nonalcoholic Fatty Liver Disease: Basic Pathogenetic Mechanisms in the Progression From NAFLD to NASH. Transplantation. 2019;103(1):e1-e13. doi: 10.1097/TP0000000000002480.
  37. Ipsen D.H., Lykkesfeldt J., Tveden-Nyborg P Molecular mechanisms of hepatic lipid accumulation in non-alcoholic fatty liver disease. Cell Mol Life Sci. 2018;75(18):3313-27. doi: 10.1007/s00018-018-2860-6.
  38. Kohjima M., Higuchi N., Kato M., et al. SREBP-1c, regulated by the insulin and AMPK signaling pathways, plays a role in nonalcoholic fatty liver disease. Int J Mol Med. 2008;21(4):507-11.
  39. Smith G.I., Shankaran M., Yoshino M., et al. Insulin resistance drives hepatic de novo lipogenesis in nonalcoholic fatty liver disease. J Clin Invest. 2020;130(3):1453-60. Doi:10.1172/ JCI134165.
  40. Siddiqui M.S., Fuchs M., Idowu M.O., et al. Severity of nonalcoholic fatty liver disease and progression to cirrhosis are associated with atherogenic lipoprotein profile. Clin Gastroenterol Hepatol. 2015;13(5):1000-8.e3. Doi:10.1016/j. cgh.2014.10.008.
  41. Ter Horst K.W., Vatner D.F., Zhang D., et al. Hepatic Insulin Resistance Is Not Pathway Selective in Humans With Nonalcoholic Fatty Liver Disease. Diabetes Care. 2021;44(2):489-98. doi: 10.2337/dc20-1644.
  42. Brouwers B., Schrauwen-Hinderling V.B., Jelenik T., et al. Metabolic disturbances of non-alcoholic fatty liver resemble the alterations typical for type 2 diabetes. Clin Sci (Lond). 2017;131(15):1905-17. doi: 10.1042/CS20170261.
  43. Ohmi S, Ono M, Takata H., et al. Analysis of factors influencing glucose tolerance in Japanese patients with non-alcoholic fatty liver disease. Diabetol Metab Syndr. 2017;9:65. doi: 10.1186/s13098-017-0264-7.
  44. Oh Y.S., Bae G.D., Baek D.J., et al. Fatty Acid-Induced Lipotoxicity in Pancreatic Beta-Cells During Development of Type 2 Diabetes. Front Endocrinol (Lausanne). 2018;9:384. Doi:10.3389/ fendo.2018.00384.
  45. Li F, Ye J., Sun Y, et al. Distinct Dose-Dependent Association of Free Fatty Acids with Diabetes Development in Nonalcoholic Fatty Liver Disease Patients. Diabetes Metab J. 2021;45(3):417-29. doi: 10.4093/dmj.2020.0039.
  46. Wysham C., Shubrook J. Beta-cell failure in type 2 diabetes: mechanisms, markers, and clinical implications. Postgrad Med. 2020;132(8):676-86. doi: 10.1080/00325481.2020.1771047.
  47. Kawahito S., Kitahata H., Oshita S. Problems associated with glucose toxicity: role of hyperglycemia-induced oxidative stress. World J Gastroenterol. 2009;15(33):4137-42. doi: 10.3748/wjg.15.4137.
  48. Ortiz-Lopez C., Lomonaco R., Orsak B., et al. Prevalence of prediabetes and diabetes and metabolic profile of patients with nonalcoholic fatty liver disease (NAFLD). Diabetes Care. 2012;35(4):873-878. dc11-1849.
  49. Qureshi K., Clements R.H., Saeed F, Abrams G.A. Comparative evaluation of whole body and hepatic insulin resistance using indices from oral glucose tolerance test in morbidly obese subjects with nonalcoholic Fatty liver disease. J Obes. 2010;2010:741521. doi: 10.1155/2010/741521.
  50. Pan X., Kaminga A.C., Chen J., Luo M., Luo J. Fetuin-A and Fetuin-B. Non-Alcoholic Fatty Liver Disease: A Meta-Analysis and Meta-Regression. Int J Environ Res Public Health. 2020;17(8):2735. doi: 10.3390/ijerph17082735.
  51. Meex R.C.R., Watt M.J. Hepatokines: linking nonalcoholic fatty liver disease and insulin resistance. Nat Rev Endocrinol. 2017;13(9):509-doi: 10.1038/nrendo.2017.56.

Supplementary files

Supplementary Files
Action
1. JATS XML

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies