Skip to main content
SpringerLink
Log in

Non-alcoholic Fatty Liver in the Pathogenesis of Diabetes

  • Chapter
  • First Online:
The Diabetes Textbook

  • 3877 Accesses

Abstract

Non-alcoholic fatty liver disease [1] is prevalent worldwide and is recently one of the leading causes of chronic liver disease in the occident due to obesity-related epidemic and metabolic syndrome [2]. NAFLD presents with different phenotypes and may progress to cirrhosis and hepatocellular carcinoma. Moreover, it may be the leading cause for liver transplant in the next decade [3]. NAFLD was formerly identified in 1980, when Ludwig et al. described a small series of patients with liver histology characterized by fat accumulation, hepatic necroinflammation, and, in most cases, fibrosis, in the absence of a history of excessive alcohol consumption [4].

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 79.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Piscaglia F, Svegliati-Baroni G, Barchetti A, et al. Clinical patterns of hepatocellular carcinoma in nonalcoholic fatty liver disease: a multicenter prospective study. Hepatology (Baltimore, Md). 2016;63:827–38.

    Article  Google Scholar 

  2. Rinella ME. Nonalcoholic fatty liver disease: a systematic review. JAMA. 2015;313:2263–73.

    Article  CAS  Google Scholar 

  3. Wong RJ, Aguilar M, Cheung R, et al. Nonalcoholic steatohepatitis is the second leading etiology of liver disease among adults awaiting liver transplantation in the United States. Gastroenterology. 2015;148:547–55.

    Article  Google Scholar 

  4. Ludwig J, Viggiano TR, McGill DB, Oh BJ. Nonalcoholic steatohepatitis: Mayo Clinic experiences with a hitherto unnamed disease. Mayo Clin Proc. 1980;55:434–8.

    CAS  PubMed  Google Scholar 

  5. Kleiner D, Brunt E. Nonalcoholic fatty liver disease: pathologic patterns and biopsy evaluation in clinical research. Semin Liver Dis. 2012;32:3–13.

    Article  CAS  Google Scholar 

  6. Browning JD, Szczepaniak LS, Dobbins R, et al. Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity. Hepatology (Baltimore, Md). 2004;40:1387–95.

    Article  Google Scholar 

  7. Loomba R, Sanyal AJ. The global NAFLD epidemic. Nat Rev Gastroenterol Hepatol. 2013;10:686.

    Article  CAS  Google Scholar 

  8. Hoofnagle JH, Van Natta ML, Kleiner DE, et al. Vitamin E and changes in serum alanine aminotransferase levels in patients with non-alcoholic steatohepatitis. Aliment Pharmacol Ther. 2013;38:134–43.

    Article  CAS  Google Scholar 

  9. Babusik P, Bilal M, Duris I. Nonalcoholic fatty liver disease of two ethnic groups in Kuwait: comparison of prevalence and risk factors. Med Princ Pract. 2012;21:56–62.

    Article  Google Scholar 

  10. Mendez-Sanchez N. Non alcoholic fatty liver disease. Ann Hepatol. 2009;8(Suppl 1):S3.

    Article  Google Scholar 

  11. Onyekwere CA, Ogbera AO, Balogun BO. Non-alcoholic fatty liver disease and the metabolic syndrome in an urban hospital serving an African community. Ann Hepatol. 2011;10:119–24.

    Article  Google Scholar 

  12. Bellentani S, Scaglioni F, Marino M, Bedogni G. Epidemiology of non-alcoholic fatty liver disease. Dig Dis. 2010;28:155–61.

    Article  Google Scholar 

  13. Leite N, Salles G, Araujo A, Villela-Nogueira C, Cardoso C. Prevalence and associated factors of non-alcoholic fatty liver disease in patients with type-2 diabetes mellitus. Liver Int. 2009;29:113–9.

    Article  CAS  Google Scholar 

  14. Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Report of the expert committee on the diagnosis and classification of diabetes mellitus. Diabetes Care. 2003;26(Suppl 1):S5–20.

    Google Scholar 

  15. Williamson RM, Price JF, Glancy S, et al. Prevalence of and risk factors for hepatic steatosis and nonalcoholic fatty liver disease in people with type 2 diabetes: the Edinburgh type 2 diabetes study. Diabetes Care. 2011;34:1139–44.

    Article  Google Scholar 

  16. Sanyal A, Poklepovic A, Moyneur E, Barghout V. Population-based risk factors and resource utilization for HCC: US perspective. Curr Med Res Opin. 2010;26:2183–91.

    Article  CAS  Google Scholar 

  17. Charlton M, Burns J, Pedersen R, Watt K, Heimbach J, Dierkhising R. Frequency and outcomes of liver transplantation for nonalcoholic steatohepatitis in the United States. Gastroenterology. 2011;141:1249–53.

    Article  Google Scholar 

  18. Saadeh S, Younossi ZM, Remer EM, et al. The utility of radiological imaging in nonalcoholic fatty liver disease. Gastroenterology. 2002;123:745–50.

    Article  Google Scholar 

  19. Alberti KG, Zimmet P, Shaw J, IDF Epidemiology Task Force Consensus Group. The metabolic syndrome--a new worldwide definition. Lancet. 2005;366:1059–62.

    Article  Google Scholar 

  20. Jeanes YM, Reeves S. Metabolic consequences of obesity and insulin resistance in polycystic ovary syndrome: diagnostic and methodological challenges. Nutr Res Rev. 2017;30(1):97–105.

    Article  Google Scholar 

  21. Angulo P. Nonalcoholic fatty liver disease. N Engl J Med. 2002;346:1221–31.

    Article  CAS  Google Scholar 

  22. Osman KA, Osman MM, Ahmed MH. Tamoxifen-induced non-alcoholic steatohepatitis: where are we now and where are we going? Expert Opin Drug Saf. 2007;6:1–4.

    Article  CAS  Google Scholar 

  23. Farrell GC. Drugs and steatohepatitis. Semin Liver Dis. 2002;22:185–94.

    Article  CAS  Google Scholar 

  24. Debongnie JC, Pauls C, Fievez M, Wibin E. Prospective evaluation of the diagnostic accuracy of liver ultrasonography. Gut. 1981;22:130–5.

    Article  CAS  Google Scholar 

  25. Scaglioni F, Ciccia S, Marino M, Bedogni G, Bellentani S. ASH and NASH. Dig Dis. 2011;29:202–10.

    Article  CAS  Google Scholar 

  26. Liangpunsakul S, Chalasani N. What should we recommend to our patients with NAFLD regarding alcohol use? Am J Gastroenterol. 2012;107:976–8.

    Article  Google Scholar 

  27. Pendino GM, Mariano A, Surace P, et al. Prevalence and etiology of altered liver tests: a population-based survey in a Mediterranean town. Hepatology (Baltimore, Md). 2005;41:1151–9.

    Article  Google Scholar 

  28. Abdelmalek MF, Sanderson SO, Angulo P, et al. Betaine for nonalcoholic fatty liver disease: results of a randomized placebo-controlled trial. Hepatology. 2009;50:1818–26.

    Article  CAS  Google Scholar 

  29. Sorrentino P, Tarantino G, Conca P, et al. Silent non-alcoholic fatty liver disease-a clinical-histological study. J Hepatol. 2004;41:751–7.

    Article  CAS  Google Scholar 

  30. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998;352:854–65.

    Google Scholar 

  31. McPherson S, Stewart SF, Henderson E, Burt AD, Day CP. Simple non-invasive fibrosis scoring systems can reliably exclude advanced fibrosis in patients with non-alcoholic fatty liver disease. Gut. 2010;59:1265–9.

    Article  Google Scholar 

  32. Bedossa P. Pathology of non-alcoholic fatty liver disease. Liver Int. 2017;37(Suppl 1):85–9.

    Article  Google Scholar 

  33. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive summary of the third report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III). JAMA. 2001;285:2486–97.

    Article  Google Scholar 

  34. de Ledinghen V, Wong VW, Vergniol J, et al. Diagnosis of liver fibrosis and cirrhosis using liver stiffness measurement: comparison between M and XL probe of FibroScan(R). J Hepatol. 2012;56:833–9.

    Article  Google Scholar 

  35. Wong VW, Vergniol J, Wong GL, et al. Diagnosis of fibrosis and cirrhosis using liver stiffness measurement in nonalcoholic fatty liver disease. Hepatology (Baltimore, Md). 2010;51:454–62.

    Article  CAS  Google Scholar 

  36. Samir AE, Dhyani M, Vij A, et al. Shear-wave elastography for the estimation of liver fibrosis in chronic liver disease: determining accuracy and ideal site for measurement. Radiology. 2015;274:888–96.

    Article  Google Scholar 

  37. Cassinotto C, Lapuyade B, Mouries A, et al. Non-invasive assessment of liver fibrosis with impulse elastography: comparison of Supersonic Shear Imaging with ARFI and FibroScan(R). J Hepatol. 2014;61:550–7.

    Article  Google Scholar 

  38. Younossi Z, Gramlich T, Matteoni C, Boparai N, Mccullough A. Nonalcoholic fatty liver disease in patients with type 2 diabetes. Clin Gastroenterol Hepatol. 2004;2:262–5.

    Article  Google Scholar 

  39. Prashanth M, Ganesh HK, Vima MV, et al. Prevalence of nonalcoholic fatty liver disease in patients with type 2 diabetes mellitus. J Assoc Physicians India. 2009;57:205–10.

    CAS  PubMed  Google Scholar 

  40. Leite N, Villela-Nogueira C, Pannain V, et al. Histopathological stages of nonalcoholic fatty liver disease in type 2 diabetes: prevalences and correlated factors. Liver Int. 2011;31:700–6.

    Article  Google Scholar 

  41. Loomba R, Abraham M, Unalp A, et al. Association between diabetes, family history of diabetes, and risk of nonalcoholic steatohepatitis and fibrosis. Hepatology (Baltimore, Md). 2012;56:943–51.

    Article  Google Scholar 

  42. 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;30:1212–8.

    Article  Google Scholar 

  43. Targher G, Bertolini L, Padovani R, et al. Prevalence of non-alcoholic fatty liver disease and its association with cardiovascular disease in patients with type 1 diabetes. J Hepatol. 2010;53:713–8.

    Article  CAS  Google Scholar 

  44. Targher G, Bertolini L, Rodella S, Lippi G, Zoppini G, Chonchol M. Relationship between kidney function and liver histology in subjects with nonalcoholic steatohepatitis. Clin J Am Soc Nephrol. 2010;5:2166–71.

    Article  CAS  Google Scholar 

  45. Targher G, Chonchol M, Pichiri I, Zoppini G. Risk of cardiovascular disease and chronic kidney disease in diabetic patients with non-alcoholic fatty liver disease: just a coincidence? J Endocrinol Investig. 2011;34:544–51.

    CAS  Google Scholar 

  46. 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;35:873–8.

    Article  CAS  Google Scholar 

  47. Willner I, Waters B, Patil S, Reuben A, Morelli J, Riely C. Ninety patients with nonalcoholic steatohepatitis: insulin resistance, familial tendency, and severity of disease. Am J Gastroenterol. 2001;96:2957–61.

    Article  CAS  Google Scholar 

  48. Kasturiratne A, Weerasinghe S, Dassanayake AS, et al. Influence of non-alcoholic fatty liver disease on the development of diabetes mellitus. J Gastroenterol Hepatol. 2013;28:142–7.

    Article  Google Scholar 

  49. Choi JH, Rhee EJ, Bae JC, et al. Increased risk of type 2 diabetes in subjects with both elevated liver enzymes and ultrasonographically diagnosed nonalcoholic fatty liver disease: a 4-year longitudinal study. Arch Med Res. 2013;44:115–20.

    Article  CAS  Google Scholar 

  50. Shah RV, Allison MA, Lima JA, et al. Liver fat, statin use, and incident diabetes: the multi-ethnic study of atherosclerosis. Atherosclerosis. 2015;242:211–7.

    Article  CAS  Google Scholar 

  51. Musso G, Gambino R, Cassader M, Pagano G. Meta-analysis: natural history of non-alcoholic fatty liver disease (NAFLD) and diagnostic accuracy of non-invasive tests for liver disease severity. Ann Med. 2011;43:617–49.

    Article  Google Scholar 

  52. Ballestri S, Zona S, Targher G, et al. Nonalcoholic fatty liver disease is associated with an almost twofold increased risk of incident type 2 diabetes and metabolic syndrome. Evidence from a systematic review and meta-analysis. J Gastroenterol Hepatol. 2016;31:936–44.

    Article  CAS  Google Scholar 

  53. 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;48:634–42.

    Article  CAS  Google Scholar 

  54. Cusi K. Role of obesity and lipotoxicity in the development of nonalcoholic steatohepatitis: pathophysiology and clinical implications. Gastroenterology. 2012;142:711–25.e6.

    Article  CAS  Google Scholar 

  55. 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;55:1389–97.

    Article  CAS  Google Scholar 

  56. Fain JN, Bahouth SW, Madan AK. TNF alpha release by the nonfat cells of human adipose tissue. Int J Obes Relat Metab Disord. 2004;28:616–22.

    Article  CAS  Google Scholar 

  57. Sabio G, Das M, Mora A, et al. A stress signaling pathway in adipose tissue regulates hepatic insulin resistance. Science. 2008;322:1539–43.

    Article  CAS  Google Scholar 

  58. Polyzos SA, Toulis KA, Goulis DG, Zavos C, Kountouras J. Serum total adiponectin in nonalcoholic fatty liver disease: a systematic review and meta-analysis. Metabolism. 2011;60:313–26.

    Article  CAS  Google Scholar 

  59. Cnop M, Welsh N, Jonas JC, Jorns A, Lenzen S, Eizirik DL. Mechanisms of pancreatic beta-cell death in type 1 and type 2 diabetes: many differences, few similarities. Diabetes. 2005;54(Suppl 2):S97–107.

    Article  CAS  Google Scholar 

  60. Horton JD, Goldstein JL, Brown MS. SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver. J Clin Invest. 2002;109:1125–31.

    Article  CAS  Google Scholar 

  61. Postic C, Girard J. The role of the lipogenic pathway in the development of hepatic steatosis. Diabetes Metab. 2008;34:643–8.

    Article  CAS  Google Scholar 

  62. Ferre P, Foufelle F. Hepatic steatosis: a role for de novo lipogenesis and the transcription factor SREBP-1c. Diabetes Obes Metab. 2010;12(Suppl 2):83–92.

    Article  CAS  Google Scholar 

  63. Birkenfeld AL, Shulman GI. Nonalcoholic fatty liver disease, hepatic insulin resistance, and type 2 diabetes. Hepatology. 2014;59:713–23.

    Article  Google Scholar 

  64. Kumashiro N, Erion DM, Zhang D, et al. Cellular mechanism of insulin resistance in nonalcoholic fatty liver disease. Proc Natl Acad Sci U S A. 2011;108:16381–5.

    Article  CAS  Google Scholar 

  65. Cook JR, Langlet F, Kido Y, Accili D. Pathogenesis of selective insulin resistance in isolated hepatocytes. J Biol Chem. 2015;290:13972–80.

    Article  CAS  Google Scholar 

  66. Pirola CJ, Sookoian S. The dual and opposite role of the TM6SF2-rs58542926 variant in protecting against cardiovascular disease and conferring risk for nonalcoholic fatty liver: a meta-analysis. Hepatology. 2015;62:1742–56.

    Article  CAS  Google Scholar 

  67. Sookoian S, Pirola CJ. Meta-analysis of the influence of I148M variant of patatin-like phospholipase domain containing 3 gene (PNPLA3) on the susceptibility and histological severity of nonalcoholic fatty liver disease. Hepatology. 2011;53:1883–94.

    Article  CAS  Google Scholar 

  68. Czupryniak L. Guidelines for the management of type 2 diabetes: is ADA and EASD consensus more clinically relevant than the IDF recommendations? Diabetes Res Clin Pract. 2009;86(Suppl 1):S22–5.

    Article  Google Scholar 

  69. Konner AC, Bruning JC. Toll-like receptors: linking inflammation to metabolism. Trends Endocrinol Metab. 2011;22:16–23.

    Article  Google Scholar 

  70. Cani PD, Amar J, Iglesias MA, et al. Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes. 2007;56:1761–72.

    Article  CAS  Google Scholar 

  71. Miele L, Valenza V, La Torre G, et al. Increased intestinal permeability and tight junction alterations in nonalcoholic fatty liver disease. Hepatology. 2009;49:1877–87.

    Article  CAS  Google Scholar 

  72. Ruiz AG, Casafont F, Crespo J, et al. Lipopolysaccharide-binding protein plasma levels and liver TNF-alpha gene expression in obese patients: evidence for the potential role of endotoxin in the pathogenesis of non-alcoholic steatohepatitis. Obes Surg. 2007;17:1374–80.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. School of Medicine, Internal Medicine Department, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil

    Cristiane A. Villela Nogueira

  2. Clementino Fraga Filho University Hospital, Internal Medicine Division, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil

    Nathalie Carvalho Leite

Authors
  1. Cristiane A. Villela Nogueira
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nathalie Carvalho Leite
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Multidisciplinary Diabetes Center, Mexico City, Mexico

    Joel Rodriguez-Saldana

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Villela Nogueira, C.A., Leite, N.C. (2019). Non-alcoholic Fatty Liver in the Pathogenesis of Diabetes. In: Rodriguez-Saldana, J. (eds) The Diabetes Textbook. Springer, Cham. https://doi.org/10.1007/978-3-030-11815-0_15

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-11815-0_15

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-11814-3

  • Online ISBN: 978-3-030-11815-0

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation