About this Journal Submit a Manuscript Table of Contents
International Journal of Endocrinology
Volume 2013 (2013), Article ID 450639, 8 pages
http://dx.doi.org/10.1155/2013/450639
Review Article

Nonalcoholic Fatty Liver Disease, Diabetes Mellitus and Cardiovascular Disease: Newer Data

2nd Medical Department and Diabetes Center, NIMTS Hospital, 12 Monis Petraki, 11521 Athens, Greece

Received 9 March 2013; Accepted 12 March 2013

Academic Editor: Nikolaos Papanas

Copyright © 2013 A. N. Mavrogiannaki and I. N. Migdalis. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. P. M. Gholam, D. P. Kotler, and L. J. Flancbaum, “Liver pathology in morbidly obese patients undergoing Roux-en-Y gastric bypass surgery,” Obesity Surgery, vol. 12, no. 1, pp. 49–51, 2002. View at Publisher · View at Google Scholar · View at Scopus
  2. C. D. Williams, J. Stengel, M. I. Asike et al., “Prevalence of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis among a largely middle-aged population utilizing ultrasound and liver biopsy: a prospective study,” Gastroenterology, vol. 140, no. 1, pp. 124–131, 2011. View at Publisher · View at Google Scholar · View at Scopus
  3. G. Targher, L. Bertolini, R. Padovani et al., “Prevalence of non-alcoholic fatty liver disease and its association with cardiovascular disease in patients with type 1 diabetes,” Journal of Hepatology, vol. 53, no. 4, pp. 713–718, 2010. View at Publisher · View at Google Scholar · View at Scopus
  4. C. A. Caserta, G. M. Pendino, A. Amante et al., “Cardiovascular risk factors, nonalcoholic fatty liver disease, and carotid artery intima-media thickness in an adolescent population in southern Italy,” The American Journal of Epidemiology, vol. 171, no. 11, pp. 1195–1202, 2010. View at Publisher · View at Google Scholar · View at Scopus
  5. J. D. Browning, “Statins and hepatic steatosis: perspectives from the Dallas heart study,” Hepatology, vol. 44, no. 2, pp. 466–471, 2006. View at Publisher · View at Google Scholar · View at Scopus
  6. H. Malhi and G. J. Gores, “Molecular mechanisms of lipotoxicity in nonalcoholic fatty liver disease,” Seminars in Liver Disease, vol. 28, no. 4, pp. 360–369, 2008. View at Publisher · View at Google Scholar · View at Scopus
  7. G. Targher, C. P. Day, and E. Bonora, “Risk of cardiovascular disease in patients with nonalcoholic fatty liver disease,” The New England Journal of Medicine, vol. 363, no. 14, pp. 1341–1350, 2010. View at Publisher · View at Google Scholar · View at Scopus
  8. G. Targher, F. Marra, and G. Marchesini, “Increased risk of cardiovascular disease in non-alcoholic fatty liver disease: causal effect or epiphenomenon?” Diabetologia, vol. 51, no. 11, pp. 1947–1953, 2008. View at Publisher · View at Google Scholar · View at Scopus
  9. S. E. Baumeister, H. Völzke, P. Marschall et al., “Impact of fatty liver disease on health care utilization and costs in a general population: a 5-year observation,” Gastroenterology, vol. 134, no. 1, pp. 85–94, 2008. View at Publisher · View at Google Scholar · View at Scopus
  10. N. C. Leite, G. F. Salles, A. L. E. Araujo, C. A. Villela-Nogueira, and C. R. L. Cardoso, “Prevalence and associated factors of non-alcoholic fatty liver disease in patients with type-2 diabetes mellitus,” Liver International, vol. 29, no. 1, pp. 113–119, 2009. View at Publisher · View at Google Scholar · View at Scopus
  11. A. Kotronen, L. Juurinen, A. Hakkarainen et al., “Liver fat is increased in type 2 diabetic patients and underestimated by serum alanine aminotransferase compared with equally obese nondiabetic subjects,” Diabetes Care, vol. 31, no. 1, pp. 165–169, 2008. View at Publisher · View at Google Scholar · View at Scopus
  12. E. K. Speliotes, J. M. Massaro, U. Hoffmann et al., “Fatty liver is associated with dyslipidemia and dysglycemia independent of visceral fat: the Framingham heart study,” Hepatology, vol. 51, no. 6, pp. 1979–1987, 2010. View at Publisher · View at Google Scholar · View at Scopus
  13. A. L. Fracanzani, L. Valenti, E. Bugianesi et al., “Risk of severe liver disease in nonalcoholic fatty liver disease with normal aminotransferase levels: a role for insulin resistance and diabetes,” Hepatology, vol. 48, no. 3, pp. 792–798, 2008. View at Publisher · View at Google Scholar · View at Scopus
  14. S. A. Harrison, D. Oliver, H. L. Arnold, S. Gogia, and B. A. Neuschwander-Tetri, “Development and validation of a simple NAFLD clinical scoring system for identifying patients without advanced disease,” Gut, vol. 57, no. 10, pp. 1441–1447, 2008. View at Publisher · View at Google Scholar · View at Scopus
  15. K. Cusi, “The role of adipose tissue and lipotoxicity in the pathogenesis of type 2 diabetes,” Current Diabetes Reports, vol. 10, no. 4, pp. 306–315, 2010. View at Publisher · View at Google Scholar · View at Scopus
  16. A. Kotronen and H. Yki-Järvinen, “Fatty liver: a novel component of the metabolic syndrome,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 28, no. 1, pp. 27–38, 2008. View at Publisher · View at Google Scholar
  17. N. Sattar, A. McConnachie, I. Ford et al., “Serial metabolic measurements and conversion to type 2 diabetes in the West of Scotland Coronary Prevention Study: specific elevations in alanine aminotransferase and triglycerides suggest hepatic fat accumulation as a potential contributing factor,” Diabetes, vol. 56, no. 4, pp. 984–991, 2007. View at Publisher · View at Google Scholar · View at Scopus
  18. R. K. Schindhelm, J. M. Dekker, G. Nijpels et al., “Alanine aminotransferase predicts coronary heart disease events: a 10-year follow-up of the Hoorn Study,” Atherosclerosis, vol. 191, no. 2, pp. 391–396, 2007. View at Publisher · View at Google Scholar · View at Scopus
  19. M. Hamaguchi, N. Takeda, C. Nagata et al., “Nonalcolholic fatty liver disease is a novel predictor cardiovascular disease,” World Journal of Gastroenterology, vol. 13, no. 10, pp. 1579–1584, 2007.
  20. G. N. Ioannou, N. S. Weiss, E. J. Boyko, D. Mozaffarian, and S. P. Lee, “Elevated serum alanine aminotransferase activity and calculated risk of coronary heart disease in the United States,” Hepatology, vol. 43, no. 5, pp. 1145–1151, 2006. View at Publisher · View at Google Scholar · View at Scopus
  21. M. Ekstedt, L. E. Franzén, U. L. Mathiesen et al., “Long-term follow-up of patients with NAFLD and elevated liver enzymes,” Hepatology, vol. 44, no. 4, pp. 865–873, 2006. View at Publisher · View at Google Scholar · View at Scopus
  22. S. Treeprasertsuk, F. Lopez-Jimenez, and K. D. Lindor, “Nonalcoholic fatty liver disease and the coronary artery disease,” Digestive Diseases and Sciences, vol. 56, no. 1, pp. 35–45, 2011. View at Publisher · View at Google Scholar · View at Scopus
  23. G. Targher, L. Bertolini, R. Padovani et al., “Relations between carotid artery wall thickness and liver histology in subjects with nonalcoholic fatty liver disease,” Diabetes Care, vol. 29, no. 6, pp. 1325–1330, 2006. View at Publisher · View at Google Scholar · View at Scopus
  24. N. Villanova, S. Moscatiello, S. Ramilli et al., “Endothelial dysfunction and cardiovascular risk profile in nonalcoholic fatty liver disease,” Hepatology, vol. 42, no. 2, pp. 473–480, 2005. View at Publisher · View at Google Scholar · View at Scopus
  25. G. Targher, L. Bertolini, S. Rodella et al., “NASH predicts plasma inflammatory biomarkers independently of visceral fat in men,” Obesity, vol. 16, no. 6, pp. 1394–1399, 2008. View at Publisher · View at Google Scholar · View at Scopus
  26. G. Donati, B. Stagni, F. Piscaglia et al., “Increased prevalence of fatty liver in arterial hypertensive patients with normal liver enzymes: role of insulin resistance,” Gut, vol. 53, no. 7, pp. 1020–1023, 2004. View at Publisher · View at Google Scholar · View at Scopus
  27. G. Perseghin, G. Lattuada, F. De Cobelli et al., “Increased mediastinal fat and impaired left ventricular energy metabolism in young men with newly found fatty liver,” Hepatology, vol. 47, no. 1, pp. 51–58, 2008. View at Publisher · View at Google Scholar · View at Scopus
  28. I. Zib, A. N. Jacob, I. Lingvay et al., “Effect of pioglitazone therapy on myocardial and hepatic steatosis in insulin-treated patients with type 2 diabetes,” Journal of Investigative Medicine, vol. 55, no. 5, pp. 230–236, 2007. View at Publisher · View at Google Scholar · View at Scopus
  29. G. Targher, L. Bertolini, F. Poli et al., “Nonalcoholic fatty liver disease and risk of future cardiovascular events among type 2 diabetic patients,” Diabetes, vol. 54, no. 12, pp. 3541–3546, 2005. View at Publisher · View at Google Scholar · View at Scopus
  30. G. Targher, L. Bertolini, S. Rodella et al., “Nonalcoholic fatty liver disease is independently associated with an increased incidence of cardiovascular events in type 2 diabetic patients,” Diabetes Care, vol. 30, no. 8, pp. 2119–2121, 2007. View at Publisher · View at Google Scholar · View at Scopus
  31. K. Cusi, “Nonalcoholic fatty liver disease in type 2 diabetes mellitus,” Current Opinion in Endocrinology, Diabetes and Obesity, vol. 16, no. 2, pp. 141–149, 2009. View at Publisher · View at Google Scholar · View at Scopus
  32. P. Angulo, “Medical progress: nonalcoholic fatty liver disease,” The New England Journal of Medicine, vol. 346, no. 16, pp. 1221–1231, 2002. View at Publisher · View at Google Scholar · View at Scopus
  33. C. P. Day, “Natural history of NAFLD: remarkably benign in the absence of cirrhosis,” Gastroenterology, vol. 129, no. 1, pp. 375–378, 2005. View at Publisher · View at Google Scholar · View at Scopus
  34. K. F. Petersen, S. Dufour, A. Hariri et al., “Apolipoprotein C3 gene variants in nonalcoholic fatty liver disease,” The New England Journal of Medicine, vol. 362, no. 12, pp. 1082–1089, 2010. View at Publisher · View at Google Scholar · View at Scopus
  35. N. M. W. de Alwis and C. P. Day, “Genetics of alcoholic liver disease and nonalcoholic fatty liver disease,” Seminars in Liver Disease, vol. 27, no. 1, pp. 44–54, 2007. View at Publisher · View at Google Scholar · View at Scopus
  36. N. M. W. de Alwis and C. P. Day, “Genes and nonalcoholic fatty liver disease,” Current Diabetes Reports, vol. 8, no. 2, pp. 156–163, 2008. View at Publisher · View at Google Scholar · View at Scopus
  37. G. Musso, R. Gambino, F. De Michieli et al., “Dietary habits and their relations to insulin resistance and postprandial lipemia in nonalcoholic steatohepatitis,” Hepatology, vol. 37, no. 4, pp. 909–916, 2003. View at Publisher · View at Google Scholar · View at Scopus
  38. S. Zelber-Sagi, D. Nitzan-Kaluski, R. Goldsmith et al., “Long term nutritional intake and the risk for non-alcoholic fatty liver disease (NAFLD): a population based study,” Journal of Hepatology, vol. 47, no. 5, pp. 711–717, 2007. View at Publisher · View at Google Scholar · View at Scopus
  39. N. Chalasani, Z. Younossi, J. E. Lavine et al., “The diagnosis and management of non-alcoholic fatty liver disease: practice guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association,” The American Journal of Gastroenterology, vol. 107, no. 6, pp. 811–826, 2012. View at Publisher · View at Google Scholar
  40. B. Taouli, R. L. Ehman, and S. B. Reeder, “Advanced MRI methods for assessment of chronic liver disease,” The American Journal of Roentgenology, vol. 193, no. 1, pp. 14–27, 2009. View at Publisher · View at Google Scholar · View at Scopus
  41. A. Wieckowska, A. J. McCullough, and A. E. Feldstein, “Noninvasive diagnosis and monitoring of nonalcoholic steatohepatitis: present and future,” Hepatology, vol. 46, no. 2, pp. 582–589, 2007. View at Publisher · View at Google Scholar · View at Scopus
  42. S. F. Solga, A. Alkhuraishe, K. Cope et al., “Breath biomarkers and non-alcoholic fatty liver disease: preliminary observations,” Biomarkers, vol. 11, no. 2, pp. 174–183, 2006. View at Publisher · View at Google Scholar · View at Scopus
  43. S. C. Kalhan, L. Guo, J. Edmison et al., “Plasma metabolomic profile in nonalcoholic fatty liver disease,” Metabolism, vol. 60, no. 3, pp. 404–413, 2011. View at Publisher · View at Google Scholar · View at Scopus
  44. P. Angulo, J. M. Hui, G. Marchesini et al., “The NAFLD fibrosis score: a noninvasive system that identifies liver fibrosis in patients with NAFLD,” Hepatology, vol. 45, no. 4, pp. 846–854, 2007. View at Publisher · View at Google Scholar · View at Scopus
  45. T. Ueno, H. Sugawara, K. Sujaku et al., “Therapeutic effects of restricted diet and exercise in obese patients with fatty liver,” Journal of Hepatology, vol. 27, no. 1, pp. 103–107, 1997. View at Publisher · View at Google Scholar · View at Scopus
  46. K. Promrat, D. E. Kleiner, H. M. Niemeier et al., “Randomized controlled trial testing the effects of weight loss on nonalcoholic steatohepatitis,” Hepatology, vol. 51, no. 1, pp. 121–129, 2010. View at Publisher · View at Google Scholar · View at Scopus
  47. F. H. Luyckx, C. Desaive, A. Thiry et al., “Liver abnormalities in severely obese subjects: effect of drastic weight loss after gastroplasty,” International Journal of Obesity, vol. 22, no. 3, pp. 222–226, 1998. View at Scopus
  48. S. A. Harrison, W. Fecht, E. M. Brunt, and B. A. Neuschwander-Tetri, “Orlistat for overweight subjects with nonalcoholic steatohepatitis: a randomized, prospective trial,” Hepatology, vol. 49, no. 1, pp. 80–86, 2009. View at Publisher · View at Google Scholar · View at Scopus
  49. J. R. van Werven, T. C. M. A. Schreuder, E. O. Aarts et al., “Hepatic steatosis in morbidly obese patients undergoing gastric bypass surgery: assessment with open-system 1H-MR spectroscopy,” The American Journal of Roentgenology, vol. 196, no. 6, pp. W736–W742, 2011. View at Publisher · View at Google Scholar
  50. L. Sjöström, K. Narbro, C. D. Sjöström et al., “Effects of bariatric surgery on mortality in Swedish obese subjects,” The New England Journal of Medicine, vol. 357, no. 8, pp. 741–752, 2007. View at Publisher · View at Google Scholar · View at Scopus
  51. J. B. Krasnoff, P. L. Painter, J. P. Wallace, N. M. Bass, and R. B. Merriman, “Health-related fitness and physical activity in patients with nonalcoholic fatty liver disease,” Hepatology, vol. 47, no. 4, pp. 1158–1165, 2008. View at Publisher · View at Google Scholar · View at Scopus
  52. N. A. Johnson, T. Sachinwalla, D. W. Walton et al., “Aerobic exercise training reduces hepatic and visceral lipids in obese individuals without weight loss,” Hepatology, vol. 50, no. 4, pp. 1105–1112, 2009. View at Publisher · View at Google Scholar · View at Scopus
  53. U. F. H. Leuschner, B. Lindenthal, G. Herrmann et al., “High-dose ursodeoxycholic acid therapy for nonalcoholic steatohepatitis: a double-blind, randomized, placebo-controlled trial,” Hepatology, vol. 52, no. 2, pp. 472–479, 2010. View at Publisher · View at Google Scholar · View at Scopus
  54. M. K. Chae, S. G. Park, S.-O. Song et al., “Pentoxifylline attenuates methionine- and choline-deficient-diet-induced steatohepatitis by suppressing TNF-α expression and endoplasmic reticulum stress,” Experimental Diabetes Research, vol. 2012, Article ID 762565, 8 pages, 2012. View at Publisher · View at Google Scholar
  55. L. A. Adams, C. O. Zein, P. Angulo, and K. D. Lindor, “A pilot trial of pentoxifylline in nonalcoholic steatohepatitis,” The American Journal of Gastroenterology, vol. 99, no. 12, pp. 2365–2368, 2004. View at Publisher · View at Google Scholar · View at Scopus
  56. A. J. Sanyal, N. Chalasani, K. V. Kowdley et al., “Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis,” The New England Journal of Medicine, vol. 362, no. 18, pp. 1675–1685, 2010. View at Publisher · View at Google Scholar · View at Scopus
  57. V. Nobili, M. Manco, R. Devito et al., “Lifestyle intervention and antioxidant therapy in children with nonalcoholic fatty liver disease: a randomized, controlled trial,” Hepatology, vol. 48, no. 1, pp. 119–128, 2008. View at Publisher · View at Google Scholar · View at Scopus
  58. J. E. Lavine, J. B. Schwimmer, M. L. Van Natta et al., “Nonalcoholic steatohepatitis clinical research network. Effect of vitamin E or metformin for treatment of nonalcoholic fatty liver disease in children and adolescents: the TONIC randomized controlled trial,” Journal of the American Medical Association, vol. 305, no. 16, pp. 1659–1668, 2011.
  59. A. Hirose, M. Ono, T. Saibara et al., “Angiotensin II type 1 receptor blocker inhibits fibrosis in rat nonalcoholic steatohepatitis,” Hepatology, vol. 45, no. 6, pp. 1375–1381, 2007. View at Publisher · View at Google Scholar · View at Scopus
  60. P. Riley, D. Sudarshi, M. Johal et al., “Weight loss, dietary advice and statin therapy in non-alcoholic fatty liver disease: a retrospective study,” International Journal of Clinical Practice, vol. 62, no. 3, pp. 374–381, 2008. View at Publisher · View at Google Scholar · View at Scopus
  61. H. Park, T. Shima, K. Yamaguchi et al., “Efficacy of long-term ezetimibe therapy in patients with nonalcoholic fatty liver disease,” Journal of Gastroenterology, vol. 46, no. 1, pp. 101–117, 2011. View at Publisher · View at Google Scholar · View at Scopus
  62. T. D. Filippatos and M. S. Elisaf, “Combination drug treatment in patients with non-alcoholic fatty liver disease,” World Journal of Hepatology, vol. 2, no. 4, pp. 139–142, 2010.
  63. G. L. Vega, M. Chandalia, L. S. Szczepaniak, and S. M. Grundy, “Effects of N-3 fatty acids on hepatic triglyceride content in humans,” Journal of Investigative Medicine, vol. 56, no. 5, pp. 780–785, 2008. View at Scopus
  64. L. Juurinen, M. Tiikkainen, A. M. Häkkinen, A. Hakkarainen, and H. Yki-Järvinen, “Effects of insulin therapy on liver fat content and hepatic insulin sensitivity in patients with type 2 diabetes,” The American Journal of Physiology, vol. 292, no. 3, pp. E829–E835, 2007. View at Publisher · View at Google Scholar · View at Scopus
  65. N. A. Gupta, J. Mells, R. M. Dunham et al., “Glucagon-like peptide-1 receptor is present on human hepatocytes and has a direct role in decreasing hepatic steatosis in vitro by modulating elements of the insulin signaling pathway,” Hepatology, vol. 51, no. 5, pp. 1584–1592, 2010. View at Publisher · View at Google Scholar · View at Scopus
  66. S. L. Samson and M. Bajaj, “Potential of incretin-based therapies for non-alcoholic fatty liver disease,” Journal of Diabetes and Its Complications. View at Publisher · View at Google Scholar
  67. V. G. Athyros, O. Giouleme, E. S. Ganotakis et al., “Safety and impact on cardiovascular events of long-term multifactorial treatment in patients with metabolic syndrome and abnormal liver function tests: a post hoc analysis of the randomised ATTEMPT study,” Archives of Medical Science, vol. 7, no. 5, pp. 796–805, 2011. View at Publisher · View at Google Scholar
  68. American Diabetes Association, “Clinical practice recommendations,” Diabetes Care, vol. 26, Suppl 1, pp. S11–S67, 2013.
  69. E. Fassio, E. Álvarez, N. Domínguez, G. Landeira, and C. Longo, “Natural history of nonalcoholic steatohepatitis: a longitudinal study of repeat liver biopsies,” Hepatology, vol. 40, no. 4, pp. 820–826, 2004. View at Publisher · View at Google Scholar · View at Scopus
  70. J. B. Dixon, P. S. Bhathal, and P. E. O'Brien, “Nonalcoholic fatty liver disease: predictors of nonalcoholic steatohepatitis and liver fibrosis in the severely obese,” Gastroenterology, vol. 121, no. 1, pp. 91–100, 2001. View at Scopus
  71. D. L. White, F. Kanwal, and H. B. El-Serag, “Association between nonalcoholic fatty liver disease and risk for hepatocellular cancer, based on systematic review,” Clinical Gastroenterology and Hepatology, vol. 10, no. 12, pp. 1342–1359, 2012. View at Publisher · View at Google Scholar
  72. C. Söderberg, P. Stål, J. Askling et al., “Decreased survival of subjects with elevated liver function tests during a 28-year follow-up,” Hepatology, vol. 51, no. 2, pp. 595–602, 2010. View at Publisher · View at Google Scholar · View at Scopus
  73. L. A. Adams, S. Harmsen, J. L. S. Sauver et al., “Nonalcoholic fatty liver disease increases risk of death among patients with diabetes: a community-based cohort study,” The American Journal of Gastroenterology, vol. 105, no. 7, pp. 1567–1573, 2010. View at Publisher · View at Google Scholar · View at Scopus