Skip to main content
Top
Published in: Endocrine 3/2014

01-04-2014 | Review

Non-alcoholic fatty liver disease: a diabetologist’s perspective

Authors: Joseph M. Pappachan, Farrah A. Antonio, Mahamood Edavalath, Arjun Mukherjee

Published in: Endocrine | Issue 3/2014

Login to get access

Abstract

In the recent years, non-alcoholic fatty liver disease (NAFLD) has emerged as the commonest cause of chronic liver disease in the developed world. The global epidemic of obesity secondary to physical inactivity and adverse food habits accounts for the alarming rise in NAFLD. Metabolic syndrome plays a major role in the pathogenesis of both NAFLD and type 2 diabetes mellitus (T2DM). Whilst most cases of NAFLD remain asymptomatic with only hepatic steatosis, about 30 % progress to non-alcoholic steatohepatitis with chronic liver inflammation that can lead on to fibrosis, cirrhosis, liver failure, and hepatocellular carcinoma. Because of the similar pathogenesis shared between T2DM and NAFLD, T2DM occurs as an important complication in many cases of NAFLD, and many cases of T2DM are further complicated by NAFLD. Rapid progression and increased complications of the individual diseases is the end result of this dual coexistence. Diagnosis of NAFLD relies upon hepatic imaging, serum biochemical markers, and liver biopsy. As in T2DM, the most important management option for patients with NAFLD is lifestyle changes targeted at weight reduction. Other treatment options include insulin sensitizers (metformin and pioglitazone), vitamin E, incretin mimetics, omega-3 fatty acids, cholesterol lowering agents, orlistat, and bariatric surgery. The clinical spectrum, patho-physiological features and therapeutic options of NAFLD share many things in common with T2DM and therefore, this review is to highlight the diabetologist’s perspective of the disease.
Literature
1.
go back to reference P. Angulo, GI epidemiology: non-alcoholic fatty liver disease. Aliment. Pharmacol. Ther. 25, 883–889 (2007)PubMedCrossRef P. Angulo, GI epidemiology: non-alcoholic fatty liver disease. Aliment. Pharmacol. Ther. 25, 883–889 (2007)PubMedCrossRef
2.
go back to reference M.M. Finucane, G.A. Stevens, M.J. Cowan, G. Danaei, J.K. Lin, C.J. Paciorek et al., National, regional, and global trends in body-mass index since 1980: systematic analysis of health examination surveys and epidemiological studies with 960 country-years and 9.1 million participants. Lancet. 377(9765), 557–567 (1980). (2011)CrossRef M.M. Finucane, G.A. Stevens, M.J. Cowan, G. Danaei, J.K. Lin, C.J. Paciorek et al., National, regional, and global trends in body-mass index since 1980: systematic analysis of health examination surveys and epidemiological studies with 960 country-years and 9.1 million participants. Lancet. 377(9765), 557–567 (1980). (2011)CrossRef
3.
go back to reference M.J. Pappachan, Increasing prevalence of lifestyle diseases: high time for action. Indian J. Med. Res. 134, 143–145 (2011)PubMedCentralPubMed M.J. Pappachan, Increasing prevalence of lifestyle diseases: high time for action. Indian J. Med. Res. 134, 143–145 (2011)PubMedCentralPubMed
4.
go back to reference S. Bellentani, M. Marino, Epidemiology and natural history of non-alcoholic fatty liver disease (NAFLD). Ann. Hepatol. 8(Suppl 1), S4–S8 (2009)PubMed S. Bellentani, M. Marino, Epidemiology and natural history of non-alcoholic fatty liver disease (NAFLD). Ann. Hepatol. 8(Suppl 1), S4–S8 (2009)PubMed
5.
go back to reference N. Chalasani, Z. Younossi, J.E. Lavine, A.M. Diehl, E.M. Brunt, K. Cusi 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. Hepatology 55, 2005–2023 (2012)PubMedCrossRef N. Chalasani, Z. Younossi, J.E. Lavine, A.M. Diehl, E.M. Brunt, K. Cusi 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. Hepatology 55, 2005–2023 (2012)PubMedCrossRef
6.
7.
go back to reference C.M. Leevy, Fatty liver: a study of 270 patients with biopsy proven fatty liver and review of the literature. Medicine 41, 249–276 (1962)PubMedCrossRef C.M. Leevy, Fatty liver: a study of 270 patients with biopsy proven fatty liver and review of the literature. Medicine 41, 249–276 (1962)PubMedCrossRef
8.
go back to reference J. Ludwig, T.R. Viggiano, D.B. McGill, Nonalcoholic steatohepatitis: Mayo Clinic experiences with a hitherto unnamed disease. Mayo Clin. Proc. 55, 434–438 (1980)PubMed J. Ludwig, T.R. Viggiano, D.B. McGill, Nonalcoholic steatohepatitis: Mayo Clinic experiences with a hitherto unnamed disease. Mayo Clin. Proc. 55, 434–438 (1980)PubMed
9.
go back to reference H. Lu, H. Liu, F. Hu, L. Zou, S. Luo, L. Sun, Independent Association between nonalcoholic fatty liver disease and cardiovascular disease: a systematic review and meta-analysis. Int. J. Endocrinol. 2013, 124958 (2013)PubMedCentralPubMedCrossRef H. Lu, H. Liu, F. Hu, L. Zou, S. Luo, L. Sun, Independent Association between nonalcoholic fatty liver disease and cardiovascular disease: a systematic review and meta-analysis. Int. J. Endocrinol. 2013, 124958 (2013)PubMedCentralPubMedCrossRef
10.
go back to reference C. Flannery, S. Dufour, R. Rabøl, G.I. Shulman, K.F. Petersen, Skeletal muscle insulin resistance promotes increased hepatic de novo lipogenesis, hyperlipidemia, and hepatic steatosis in the elderly. Diabetes 61, 2711–2717 (2012)PubMedCentralPubMedCrossRef C. Flannery, S. Dufour, R. Rabøl, G.I. Shulman, K.F. Petersen, Skeletal muscle insulin resistance promotes increased hepatic de novo lipogenesis, hyperlipidemia, and hepatic steatosis in the elderly. Diabetes 61, 2711–2717 (2012)PubMedCentralPubMedCrossRef
11.
go back to reference G. Targher, C.D. Byrne, Clinical Review: nonalcoholic fatty liver disease: a novel cardiometabolic risk factor for type 2 diabetes and its complications. J. Clin. Endocrinol. Metab. 98, 483–495 (2013)PubMedCrossRef G. Targher, C.D. Byrne, Clinical Review: nonalcoholic fatty liver disease: a novel cardiometabolic risk factor for type 2 diabetes and its complications. J. Clin. Endocrinol. Metab. 98, 483–495 (2013)PubMedCrossRef
12.
go back to reference E. Scorletti, P.C. Calder, C.D. Byrne, Non-alcoholic fatty liver disease and cardiovascular risk: metabolic aspects and novel treatments. Endocrine 40, 332–343 (2011)PubMedCrossRef E. Scorletti, P.C. Calder, C.D. Byrne, Non-alcoholic fatty liver disease and cardiovascular risk: metabolic aspects and novel treatments. Endocrine 40, 332–343 (2011)PubMedCrossRef
13.
go back to reference K.G. Alberti, P. Zimmet, J. Shaw, Metabolic syndrome–a new world-wide definition. A Consensus Statement from the International Diabetes Federation. Diabetes Med. 23, 469–480 (2006)CrossRef K.G. Alberti, P. Zimmet, J. Shaw, Metabolic syndrome–a new world-wide definition. A Consensus Statement from the International Diabetes Federation. Diabetes Med. 23, 469–480 (2006)CrossRef
14.
go back to reference A.B. Ross, J.P. Godin, K. Minehira, J.P. Kirwan, Increasing whole grain intake as part of prevention and treatment of nonalcoholic Fatty liver disease. Int. J. Endocrinol. 2013, 585876 (2013)PubMedCentralPubMedCrossRef A.B. Ross, J.P. Godin, K. Minehira, J.P. Kirwan, Increasing whole grain intake as part of prevention and treatment of nonalcoholic Fatty liver disease. Int. J. Endocrinol. 2013, 585876 (2013)PubMedCentralPubMedCrossRef
15.
go back to reference D.N. Amarapurkar, E. Hashimoto, L.A. Lesmana, J.D. Sollano, P.J. Chen, K.L. Goh, How common is non-alcoholic fatty liver disease in the Asia-Pacific region and are there local differences? J. Gastroenterol. Hepatol. 22, 788–793 (2007)PubMedCrossRef D.N. Amarapurkar, E. Hashimoto, L.A. Lesmana, J.D. Sollano, P.J. Chen, K.L. Goh, How common is non-alcoholic fatty liver disease in the Asia-Pacific region and are there local differences? J. Gastroenterol. Hepatol. 22, 788–793 (2007)PubMedCrossRef
16.
go back to reference J.D. Browning, L.S. Szczepaniak, R. Dobbins, P. Nuremberg, J.D. Horton, J.C. Cohen et al., Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity. Hepatology 40, 1387–1395 (2004)PubMedCrossRef J.D. Browning, L.S. Szczepaniak, R. Dobbins, P. Nuremberg, J.D. Horton, J.C. Cohen et al., Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity. Hepatology 40, 1387–1395 (2004)PubMedCrossRef
17.
18.
go back to reference M.C. Brindisi, B. Guiu, L. Duvillard, A. Athias, F. Rollot, B. Bouillet et al., Liver fat content is associated with an increase in cholesterol synthesis independent of statin therapy use in patients with type 2 diabetes. Atherosclerosis 224, 465–468 (2012)PubMedCrossRef M.C. Brindisi, B. Guiu, L. Duvillard, A. Athias, F. Rollot, B. Bouillet et al., Liver fat content is associated with an increase in cholesterol synthesis independent of statin therapy use in patients with type 2 diabetes. Atherosclerosis 224, 465–468 (2012)PubMedCrossRef
19.
go back to reference A. Kotronen, L. Juurinen, M. Tiikkainen, S. Vehkavaara, H. Yki-Järvinen, Increased liver fat, impaired insulin clearance, and hepatic and adipose tissue insulin resistance in type 2 diabetes. Gastroenterology 135, 122–130 (2008)PubMedCrossRef A. Kotronen, L. Juurinen, M. Tiikkainen, S. Vehkavaara, H. Yki-Järvinen, Increased liver fat, impaired insulin clearance, and hepatic and adipose tissue insulin resistance in type 2 diabetes. Gastroenterology 135, 122–130 (2008)PubMedCrossRef
20.
go back to reference C.P. Day, O.F. James, Steatohepatitis: a tale of two “hits”? Gastroenterology 114, 842–845 (1998)PubMedCrossRef C.P. Day, O.F. James, Steatohepatitis: a tale of two “hits”? Gastroenterology 114, 842–845 (1998)PubMedCrossRef
21.
go back to reference H. Tilg, A.R. Moschen, Evolution of inflammation in nonalcoholic fatty liver disease: the multiple parallel hits hypothesis. Hepatology 52, 1836–1846 (2010)PubMedCrossRef H. Tilg, A.R. Moschen, Evolution of inflammation in nonalcoholic fatty liver disease: the multiple parallel hits hypothesis. Hepatology 52, 1836–1846 (2010)PubMedCrossRef
22.
go back to reference A. Kotronen, L. Juurinen, M. Tiikkainen, S. Vehkavaara, H. Yki-Järvinen, Increased liver fat, impaired insulin clearance, and hepatic and adipose tissue insulin resistance in type 2 diabetes. Gastroenterology 135, 122–130 (2008)PubMedCrossRef A. Kotronen, L. Juurinen, M. Tiikkainen, S. Vehkavaara, H. Yki-Järvinen, Increased liver fat, impaired insulin clearance, and hepatic and adipose tissue insulin resistance in type 2 diabetes. Gastroenterology 135, 122–130 (2008)PubMedCrossRef
23.
go back to reference H. Rodríguez-Hernández, L.E. Simental-Mendía, G. Rodríguez-Ramírez, M.A. Reyes-Romero, Obesity and inflammation: epidemiology, risk factors, and markers of inflammation. Int. J. Endocrinol. 2013, 678159 (2013)PubMedCentralPubMedCrossRef H. Rodríguez-Hernández, L.E. Simental-Mendía, G. Rodríguez-Ramírez, M.A. Reyes-Romero, Obesity and inflammation: epidemiology, risk factors, and markers of inflammation. Int. J. Endocrinol. 2013, 678159 (2013)PubMedCentralPubMedCrossRef
24.
go back to reference O. James, C. Day, Non-alcoholic steatohepatitis: another disease of affluence. Lancet 353, 1634–1636 (1999)PubMedCrossRef O. James, C. Day, Non-alcoholic steatohepatitis: another disease of affluence. Lancet 353, 1634–1636 (1999)PubMedCrossRef
26.
go back to reference E.M. Brunt, Nonalcoholic steatohepatitis: definition and pathology. Semin. Liver Dis. 21, 3–16 (2001)PubMedCrossRef E.M. Brunt, Nonalcoholic steatohepatitis: definition and pathology. Semin. Liver Dis. 21, 3–16 (2001)PubMedCrossRef
27.
go back to reference L. Abenavoli, N. Milic, A. De Lorenzo, F. Luzza, A pathogenetic link between non-alcoholic fatty liver disease and celiac disease. Endocrine 43, 65–67 (2013)PubMedCrossRef L. Abenavoli, N. Milic, A. De Lorenzo, F. Luzza, A pathogenetic link between non-alcoholic fatty liver disease and celiac disease. Endocrine 43, 65–67 (2013)PubMedCrossRef
28.
go back to reference M. Civera, A. Urios, M.L. Garcia-Torres, J. Ortega, J. Martinez-Valls, N. Cassinello et al., Relationship between insulin resistance, inflammation and liver cell apoptosis in patients with severe obesity. Diabetes Metab. Res. Rev. 26, 187–192 (2010)PubMedCrossRef M. Civera, A. Urios, M.L. Garcia-Torres, J. Ortega, J. Martinez-Valls, N. Cassinello et al., Relationship between insulin resistance, inflammation and liver cell apoptosis in patients with severe obesity. Diabetes Metab. Res. Rev. 26, 187–192 (2010)PubMedCrossRef
29.
go back to reference V. Ratziu, S. Bellentani, H. Cortez-Pinto, C. Day, G. Marchesini, A position statement on NAFLD/NASH based on the EASL 2009 special conference. J. Hepatol. 53, 372–384 (2010)PubMedCrossRef V. Ratziu, S. Bellentani, H. Cortez-Pinto, C. Day, G. Marchesini, A position statement on NAFLD/NASH based on the EASL 2009 special conference. J. Hepatol. 53, 372–384 (2010)PubMedCrossRef
30.
go back to reference H. Kang, J.K. Greenson, J.T. Omo, C. Chao, D. Peterman, L. Anderson et al., Metabolic syndrome is associated with greater histologic severity, higher carbohydrate, and lower fat diet in patients with NAFLD. Am. J. Gastroenterol. 101, 2247–2253 (2006)PubMedCrossRef H. Kang, J.K. Greenson, J.T. Omo, C. Chao, D. Peterman, L. Anderson et al., Metabolic syndrome is associated with greater histologic severity, higher carbohydrate, and lower fat diet in patients with NAFLD. Am. J. Gastroenterol. 101, 2247–2253 (2006)PubMedCrossRef
31.
go back to reference M.C. Ryan, A.M. Wilson, J. Slavin, J.D. Best, A.J. Jenkins, P.V. Desmond, Associations between liver histology and severity of the metabolic syndrome in subjects with nonalcoholic fatty liver disease. Diabetes Care 28, 1222–1224 (2005)PubMedCrossRef M.C. Ryan, A.M. Wilson, J. Slavin, J.D. Best, A.J. Jenkins, P.V. Desmond, Associations between liver histology and severity of the metabolic syndrome in subjects with nonalcoholic fatty liver disease. Diabetes Care 28, 1222–1224 (2005)PubMedCrossRef
32.
go back to reference B.A. Neuschwander-Tetri, J.M. Clark, N.M. Bass, M.L. Van Natta, A. Unalp-Arida, J. Tonascia et al., Clinical, laboratory and histological associations in adults with nonalcoholic fatty liver disease. Hepatology 52, 913–924 (2010)PubMedCentralPubMedCrossRef B.A. Neuschwander-Tetri, J.M. Clark, N.M. Bass, M.L. Van Natta, A. Unalp-Arida, J. Tonascia et al., Clinical, laboratory and histological associations in adults with nonalcoholic fatty liver disease. Hepatology 52, 913–924 (2010)PubMedCentralPubMedCrossRef
33.
go back to reference N. Baršić, I. Lerotić, L. Smirčić-Duvnjak, V. Tomašić, M. Duvnjak, Overview and developments in noninvasive diagnosis of nonalcoholic fatty liver disease. World J. Gastroenterol. 18, 3945–3954 (2012)PubMedCentralPubMedCrossRef N. Baršić, I. Lerotić, L. Smirčić-Duvnjak, V. Tomašić, M. Duvnjak, Overview and developments in noninvasive diagnosis of nonalcoholic fatty liver disease. World J. Gastroenterol. 18, 3945–3954 (2012)PubMedCentralPubMedCrossRef
35.
go back to reference L.A. Adams, P. Angulo, Role of liver biopsy and serum markers of liver fibrosis in non-alcoholic fatty liver disease. Clin. Liver Dis. 11, 25–35 (2007). viiiPubMedCrossRef L.A. Adams, P. Angulo, Role of liver biopsy and serum markers of liver fibrosis in non-alcoholic fatty liver disease. Clin. Liver Dis. 11, 25–35 (2007). viiiPubMedCrossRef
36.
go back to reference P. Angulo, J.C. Keach, K.P. Batts, K.D. Lindor, Independent predictors of liver fibrosis in patients with nonalcoholic steatohepatitis. Hepatology 30, 1356–1362 (1999)PubMedCrossRef P. Angulo, J.C. Keach, K.P. Batts, K.D. Lindor, Independent predictors of liver fibrosis in patients with nonalcoholic steatohepatitis. Hepatology 30, 1356–1362 (1999)PubMedCrossRef
37.
go back to reference P. Sorrentino, G. Tarantino, P. Conca, A. Perrella, M.L. Terracciano, R. Vecchione et al., Silent non-alcoholic fatty liver disease-a clinical-histological study. J. Hepatol. 41, 751–757 (2004)PubMedCrossRef P. Sorrentino, G. Tarantino, P. Conca, A. Perrella, M.L. Terracciano, R. Vecchione et al., Silent non-alcoholic fatty liver disease-a clinical-histological study. J. Hepatol. 41, 751–757 (2004)PubMedCrossRef
38.
go back to reference H. Osawa, Y. Mori, Sonographic diagnosis of fatty liver using a histogram technique that compares liver and renal cortical echo amplitudes. J. Clin. Ultrasound 24, 25–29 (1996)PubMedCrossRef H. Osawa, Y. Mori, Sonographic diagnosis of fatty liver using a histogram technique that compares liver and renal cortical echo amplitudes. J. Clin. Ultrasound 24, 25–29 (1996)PubMedCrossRef
39.
go back to reference S.M. Mazhar, M. Shiehmorteza, C.B. Sirlin, Noninvasive assessment of hepatic steatosis. Clin. Gastroenterol. Hepatol. 7, 135–140 (2009)PubMedCrossRef S.M. Mazhar, M. Shiehmorteza, C.B. Sirlin, Noninvasive assessment of hepatic steatosis. Clin. Gastroenterol. Hepatol. 7, 135–140 (2009)PubMedCrossRef
40.
go back to reference M. Fishbein, F. Castro, S. Cheruku, S. Jain, B. Webb, T. Gleason, W.R. Stevens, Hepatic MRI for fat quantitation: its relationship to fat morphology, diagnosis, and ultrasound. J. Clin. Gastroenterol. 39, 619–625 (2005)PubMedCrossRef M. Fishbein, F. Castro, S. Cheruku, S. Jain, B. Webb, T. Gleason, W.R. Stevens, Hepatic MRI for fat quantitation: its relationship to fat morphology, diagnosis, and ultrasound. J. Clin. Gastroenterol. 39, 619–625 (2005)PubMedCrossRef
41.
go back to reference R. Longo, P. Pollesello, C. Ricci, F. Masutti, B.J. Kvam, L. Bercich et al., Proton MR spectroscopy in quantitative in vivo determination of fat content in human liver steatosis. J. Magn. Reson. Imaging 5, 281–285 (1995)PubMedCrossRef R. Longo, P. Pollesello, C. Ricci, F. Masutti, B.J. Kvam, L. Bercich et al., Proton MR spectroscopy in quantitative in vivo determination of fat content in human liver steatosis. J. Magn. Reson. Imaging 5, 281–285 (1995)PubMedCrossRef
42.
go back to reference S. Saadeh, Z.M. Younossi, E.M. Remer, T. Gramlich, J.P. Ong, M. Hurley et al., The utility of radiological imaging in nonalcoholic fatty liver disease. Gastroenterology 123, 745–750 (2002)PubMedCrossRef S. Saadeh, Z.M. Younossi, E.M. Remer, T. Gramlich, J.P. Ong, M. Hurley et al., The utility of radiological imaging in nonalcoholic fatty liver disease. Gastroenterology 123, 745–750 (2002)PubMedCrossRef
43.
go back to reference V.W.S. Wong, J. Vergniol, G.L. Wong, J. Foucher, H.L. Chan, B. Le Bail et al., Diagnosis of fibrosis and cirrhosis using liver stiffness measurement in nonalcoholic fatty liver disease. Hepatology 51, 454–462 (2010)PubMedCrossRef V.W.S. Wong, J. Vergniol, G.L. Wong, J. Foucher, H.L. Chan, B. Le Bail et al., Diagnosis of fibrosis and cirrhosis using liver stiffness measurement in nonalcoholic fatty liver disease. Hepatology 51, 454–462 (2010)PubMedCrossRef
44.
go back to reference L. Abenavoli, M. Beaugrand, Transient elastography in non-alcoholic fatty liver disease. Ann. Hepatol. 11, 172–178 (2012)PubMed L. Abenavoli, M. Beaugrand, Transient elastography in non-alcoholic fatty liver disease. Ann. Hepatol. 11, 172–178 (2012)PubMed
46.
go back to reference G. Musso, R. Gambino, M. Cassader, G. Pagano, Meta-analysis: natural history of non-alcoholic fatty liver disease (NAFLD) and diagnostic accuracy of non-invasive tests for liver disease severity. Ann. Med. 43, 617–649 (2011)PubMedCrossRef G. Musso, R. Gambino, M. Cassader, G. Pagano, Meta-analysis: natural history of non-alcoholic fatty liver disease (NAFLD) and diagnostic accuracy of non-invasive tests for liver disease severity. Ann. Med. 43, 617–649 (2011)PubMedCrossRef
47.
go back to reference E.M. Brunt, D.E. Kleiner, L.A. Wilson, P. Belt, B.A. Neuschwander-Tetri, NASH Clinical Research Network (CRN). The NAS and the histopathologic diagnosis in NAFLD: distinct clinicopathologic meanings. Hepatology 53, 810–820 (2011)PubMedCentralPubMedCrossRef E.M. Brunt, D.E. Kleiner, L.A. Wilson, P. Belt, B.A. Neuschwander-Tetri, NASH Clinical Research Network (CRN). The NAS and the histopathologic diagnosis in NAFLD: distinct clinicopathologic meanings. Hepatology 53, 810–820 (2011)PubMedCentralPubMedCrossRef
48.
go back to reference L.A. Adams, S. Sanderson, K.D. Lindor, P. Angulo, The histological course of nonalcoholic fatty liver disease: a longitudinal study of 103 patients with sequential liver biopsies. J. Hepatol. 42, 132–138 (2005)PubMedCrossRef L.A. Adams, S. Sanderson, K.D. Lindor, P. Angulo, The histological course of nonalcoholic fatty liver disease: a longitudinal study of 103 patients with sequential liver biopsies. J. Hepatol. 42, 132–138 (2005)PubMedCrossRef
49.
go back to reference J.H. Choi, E.J. Rhee, J.C. Bae, S.E. Park, C.Y. Park, Y.K. Cho 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. 44, 115–120 (2013)PubMedCrossRef J.H. Choi, E.J. Rhee, J.C. Bae, S.E. Park, C.Y. Park, Y.K. Cho 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. 44, 115–120 (2013)PubMedCrossRef
50.
go back to reference M. Ekstedt, L.E. Franzén, U.L. Mathiesen, L. Thorelius, M. Holmqvist, G. Bodemar, S. Kechagias, Long-term follow-up of patients with NAFLD and elevated liver enzymes. Hepatology 44, 865–873 (2006)PubMedCrossRef M. Ekstedt, L.E. Franzén, U.L. Mathiesen, L. Thorelius, M. Holmqvist, G. Bodemar, S. Kechagias, Long-term follow-up of patients with NAFLD and elevated liver enzymes. Hepatology 44, 865–873 (2006)PubMedCrossRef
51.
go back to reference Y. Colak, E. Senates, A. Yesil, Y. Yilmaz, O. Ozturk, L. Doganay et al., Assessment of endothelial function in patients with nonalcoholic fatty liver disease. Endocrine 43, 100–107 (2013)PubMedCrossRef Y. Colak, E. Senates, A. Yesil, Y. Yilmaz, O. Ozturk, L. Doganay et al., Assessment of endothelial function in patients with nonalcoholic fatty liver disease. Endocrine 43, 100–107 (2013)PubMedCrossRef
52.
go back to reference A. Suzuki, K. Lindor, J. St Saver, J. Lymp, F. Mendes, A. Muto et al., Effect of changes on body weight and lifestyle in nonalcoholic fatty liver disease. J. Hepatol. 43, 1060–1066 (2005)PubMedCrossRef A. Suzuki, K. Lindor, J. St Saver, J. Lymp, F. Mendes, A. Muto et al., Effect of changes on body weight and lifestyle in nonalcoholic fatty liver disease. J. Hepatol. 43, 1060–1066 (2005)PubMedCrossRef
53.
go back to reference J.A. Davila, R.O. Morgan, Y. Shaib, K.A. McGlynn, H.B. El-Serag, Diabetes increases the risk of hepatocellular carcinoma in the United States: a population based case control study. Gut 54, 533–539 (2005)PubMedCentralPubMedCrossRef J.A. Davila, R.O. Morgan, Y. Shaib, K.A. McGlynn, H.B. El-Serag, Diabetes increases the risk of hepatocellular carcinoma in the United States: a population based case control study. Gut 54, 533–539 (2005)PubMedCentralPubMedCrossRef
55.
go back to reference M.J. Contos, W. Cales, R.K. Sterling, V.A. Luketic, M.L. Shiffman, A.S. Mills et al., Development of nonalcoholic fatty liver disease after orthotopic liver transplantation for cryptogenic cirrhosis. Liver Transpl. 7, 363–373 (2001)PubMedCrossRef M.J. Contos, W. Cales, R.K. Sterling, V.A. Luketic, M.L. Shiffman, A.S. Mills et al., Development of nonalcoholic fatty liver disease after orthotopic liver transplantation for cryptogenic cirrhosis. Liver Transpl. 7, 363–373 (2001)PubMedCrossRef
56.
go back to reference L.G. Lim, C.L. Cheng, A. Wee, S.G. Lim, Y.M. Lee, D.S. Sutedja et al., Prevalence and clinical associations of posttransplant fatty liver disease. Liver Int. 27, 76–80 (2007)PubMedCrossRef L.G. Lim, C.L. Cheng, A. Wee, S.G. Lim, Y.M. Lee, D.S. Sutedja et al., Prevalence and clinical associations of posttransplant fatty liver disease. Liver Int. 27, 76–80 (2007)PubMedCrossRef
57.
go back to reference L.A. Adams, J.F. Lymp, J. St Sauver, S.O. Sanderson, K.D. Lindor, A. Feldstein, P. Angulo, The natural history of nonalcoholic fatty liver disease: a population-based cohort study. Gastroenterology 129, 113–121 (2005)PubMedCrossRef L.A. Adams, J.F. Lymp, J. St Sauver, S.O. Sanderson, K.D. Lindor, A. Feldstein, P. Angulo, The natural history of nonalcoholic fatty liver disease: a population-based cohort study. Gastroenterology 129, 113–121 (2005)PubMedCrossRef
58.
go back to reference A. Fraser, R. Harris, N. Sattar, S. Ebrahim, G. Davey Smith, D.A. Lawlor, Alanine aminotransferase, gamma-glutamyltransferase, and incident diabetes: the British Women’s Heart and Health Study and meta-analysis. Diabetes Care 32, 741–750 (2009)PubMedCentralPubMedCrossRef A. Fraser, R. Harris, N. Sattar, S. Ebrahim, G. Davey Smith, D.A. Lawlor, Alanine aminotransferase, gamma-glutamyltransferase, and incident diabetes: the British Women’s Heart and Health Study and meta-analysis. Diabetes Care 32, 741–750 (2009)PubMedCentralPubMedCrossRef
59.
go back to reference C. Sreenivasa Baba, G. Alexander, B. Kalyani, R. Pandey, S. Rastogi, A. Pandey, G. Choudhuri, Effect of exercise and dietary modification on serum aminotransferase levels in patients with nonalcoholic steatohepatitis. J. Gastroenterol. Hepatol. 21, 191–198 (2006)PubMedCrossRef C. Sreenivasa Baba, G. Alexander, B. Kalyani, R. Pandey, S. Rastogi, A. Pandey, G. Choudhuri, Effect of exercise and dietary modification on serum aminotransferase levels in patients with nonalcoholic steatohepatitis. J. Gastroenterol. Hepatol. 21, 191–198 (2006)PubMedCrossRef
60.
go back to reference I.J. Hickman, J.R. Jonsson, J.B. Prins, S. Ash, D.M. Purdie, A.D. Clouston et al., Modest weight loss and physical activity in overweight patients with chronic liver disease results in sustained improvements in alanine aminotransferase, fasting insulin, and quality of life. Gut 53, 413–419 (2004)PubMedCentralPubMedCrossRef I.J. Hickman, J.R. Jonsson, J.B. Prins, S. Ash, D.M. Purdie, A.D. Clouston et al., Modest weight loss and physical activity in overweight patients with chronic liver disease results in sustained improvements in alanine aminotransferase, fasting insulin, and quality of life. Gut 53, 413–419 (2004)PubMedCentralPubMedCrossRef
61.
go back to reference K. Promrat, D.E. Kleiner, H.M. Niemeier, E. Jackvony, M. Kearns, J.R. Wands et al., Randomized controlled trial testing the effects of weight loss on nonalcoholic steatohepatitis. Hepatology 51, 121–129 (2010)PubMedCentralPubMedCrossRef K. Promrat, D.E. Kleiner, H.M. Niemeier, E. Jackvony, M. Kearns, J.R. Wands et al., Randomized controlled trial testing the effects of weight loss on nonalcoholic steatohepatitis. Hepatology 51, 121–129 (2010)PubMedCentralPubMedCrossRef
62.
go back to reference K. Hallsworth, G. Fattakhova, K.G. Hollingsworth, C. Thoma, S. Moore, R. Taylor et al., Resistance exercise reduces liver fat and its mediators innon-alcoholic fatty liver diseaseindependent of weight loss. Gut 60, 1278–1283 (2011)PubMedCentralPubMedCrossRef K. Hallsworth, G. Fattakhova, K.G. Hollingsworth, C. Thoma, S. Moore, R. Taylor et al., Resistance exercise reduces liver fat and its mediators innon-alcoholic fatty liver diseaseindependent of weight loss. Gut 60, 1278–1283 (2011)PubMedCentralPubMedCrossRef
63.
go back to reference B.A. Gordon, A.C. Benson, S.R. Bird, S.F. Fraser, Resistance training improves metabolic health in type 2 diabetes: a systematic review. Diabetes Res. Clin. Pract. 83, 157–175 (2009)PubMedCrossRef B.A. Gordon, A.C. Benson, S.R. Bird, S.F. Fraser, Resistance training improves metabolic health in type 2 diabetes: a systematic review. Diabetes Res. Clin. Pract. 83, 157–175 (2009)PubMedCrossRef
64.
go back to reference J.D. Browning, J.A. Baker, T. Rogers, J. Davis, S. Satapati, S.C. Burgess, Short-term weight loss and hepatic triglyceride reduction: evidence of a metabolic advantage with dietary carbohydrate restriction. Am. J. Clin. Nutr. 93, 1048–1052 (2011)PubMedCentralPubMedCrossRef J.D. Browning, J.A. Baker, T. Rogers, J. Davis, S. Satapati, S.C. Burgess, Short-term weight loss and hepatic triglyceride reduction: evidence of a metabolic advantage with dietary carbohydrate restriction. Am. J. Clin. Nutr. 93, 1048–1052 (2011)PubMedCentralPubMedCrossRef
65.
go back to reference J.E. Lavine, J.B. Schwimmer, M.L. Van Natta, J.P. Molleston, K.F. Murray, P. Rosenthal et al., Effect of vitamin E or metformin for treatment of nonalcoholic fatty liver disease in children and adolescents: the TONIC randomized controlled trial. JAMA 305, 1659–1668 (2011)PubMedCentralPubMedCrossRef J.E. Lavine, J.B. Schwimmer, M.L. Van Natta, J.P. Molleston, K.F. Murray, P. Rosenthal et al., Effect of vitamin E or metformin for treatment of nonalcoholic fatty liver disease in children and adolescents: the TONIC randomized controlled trial. JAMA 305, 1659–1668 (2011)PubMedCentralPubMedCrossRef
66.
go back to reference G. Musso, M. Cassader, F. Rosina, R. Gambino, Impact of current treatments on liver disease, glucose metabolism and cardiovascular risk in non-alcoholic fatty liver disease (NAFLD): a systematic review and meta-analysis of randomised trials. Diabetologia 55, 885–904 (2012)PubMedCrossRef G. Musso, M. Cassader, F. Rosina, R. Gambino, Impact of current treatments on liver disease, glucose metabolism and cardiovascular risk in non-alcoholic fatty liver disease (NAFLD): a systematic review and meta-analysis of randomised trials. Diabetologia 55, 885–904 (2012)PubMedCrossRef
67.
go back to reference A.J. Sanyal, N. Chalasani, K.V. Kowdley, A. McCullough, A.M. Diehl, N.M. Bass et al., Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis. N. Engl. J. Med. 362, 1675–1685 (2010)PubMedCentralPubMedCrossRef A.J. Sanyal, N. Chalasani, K.V. Kowdley, A. McCullough, A.M. Diehl, N.M. Bass et al., Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis. N. Engl. J. Med. 362, 1675–1685 (2010)PubMedCentralPubMedCrossRef
68.
go back to reference L. Abenavoli, N. Milic, F. Capasso, Anti-oxidant therapy in non-alcoholic fatty liver disease: the role of silymarin. Endocrine 42, 754–755 (2012)PubMedCrossRef L. Abenavoli, N. Milic, F. Capasso, Anti-oxidant therapy in non-alcoholic fatty liver disease: the role of silymarin. Endocrine 42, 754–755 (2012)PubMedCrossRef
69.
go back to reference T. Vilsbøll, M. Christensen, A.E. Junker, F.K. Knop, L.L. Gluud, Effects of glucagon-like peptide-1 receptor agonists on weight loss: systematic review and meta-analyses of randomised controlled trials. BMJ 344, d7771 (2012)PubMedCentralPubMedCrossRef T. Vilsbøll, M. Christensen, A.E. Junker, F.K. Knop, L.L. Gluud, Effects of glucagon-like peptide-1 receptor agonists on weight loss: systematic review and meta-analyses of randomised controlled trials. BMJ 344, d7771 (2012)PubMedCentralPubMedCrossRef
70.
go back to reference D.J. Cuthbertson, A. Irwin, C.J. Gardner, C. Daousi, T. Purewal, N. Furlong et al., Improved glycaemia correlates with liver fat reduction in obese, type 2 diabetes, patients givenglucagon-like peptide-1 (GLP-1) receptor agonists. PLoS One 7, e50117 (2012)PubMedCentralPubMedCrossRef D.J. Cuthbertson, A. Irwin, C.J. Gardner, C. Daousi, T. Purewal, N. Furlong et al., Improved glycaemia correlates with liver fat reduction in obese, type 2 diabetes, patients givenglucagon-like peptide-1 (GLP-1) receptor agonists. PLoS One 7, e50117 (2012)PubMedCentralPubMedCrossRef
71.
go back to reference Y. Yilmaz, O. Atug, O. Yonal, D. Duman, O. Ozdogan, N. Imeryuz et al., Dipeptidyl peptidase IV inhibitors: therapeutic potential in nonalcoholic fatty liver disease. Med. Sci. Monit. 15, HY1–HY5 (2009)PubMed Y. Yilmaz, O. Atug, O. Yonal, D. Duman, O. Ozdogan, N. Imeryuz et al., Dipeptidyl peptidase IV inhibitors: therapeutic potential in nonalcoholic fatty liver disease. Med. Sci. Monit. 15, HY1–HY5 (2009)PubMed
72.
go back to reference Y. Li, J. Hai, L. Li, X. Chen, H. Peng, M. Cao et al., Administration of ghrelin improves inflammation, oxidative stress, and apoptosis during and after non-alcoholic fatty liver disease development. Endocrine 43, 376–386 (2013)PubMedCrossRef Y. Li, J. Hai, L. Li, X. Chen, H. Peng, M. Cao et al., Administration of ghrelin improves inflammation, oxidative stress, and apoptosis during and after non-alcoholic fatty liver disease development. Endocrine 43, 376–386 (2013)PubMedCrossRef
73.
go back to reference P.J. Delhanty, A.J. van der Lely, Ghrelin: a new treatment for non-alcoholic fatty liver disease? Endocrine 43, 247–248 (2013)PubMedCrossRef P.J. Delhanty, A.J. van der Lely, Ghrelin: a new treatment for non-alcoholic fatty liver disease? Endocrine 43, 247–248 (2013)PubMedCrossRef
74.
go back to reference H.M. Parker, N.A. Johnson, C.A. Burdon, J.S. Cohn, H.T. O’Connor, J. George, Omega-3 supplementation and non-alcoholic fatty liver disease: a systematic review and meta-analysis. J. Hepatol. 56, 944–951 (2012)PubMedCrossRef H.M. Parker, N.A. Johnson, C.A. Burdon, J.S. Cohn, H.T. O’Connor, J. George, Omega-3 supplementation and non-alcoholic fatty liver disease: a systematic review and meta-analysis. J. Hepatol. 56, 944–951 (2012)PubMedCrossRef
75.
go back to reference M.N. Di Minno, A. Russolillo, R. Lupoli, P. Ambrosino, A. Di Minno, G. Tarantino, Omega-3 fatty acids for the treatment of non-alcoholic fatty liver disease. World J. Gastroenterol. 18, 5839–5847 (2012)PubMedCentralPubMedCrossRef M.N. Di Minno, A. Russolillo, R. Lupoli, P. Ambrosino, A. Di Minno, G. Tarantino, Omega-3 fatty acids for the treatment of non-alcoholic fatty liver disease. World J. Gastroenterol. 18, 5839–5847 (2012)PubMedCentralPubMedCrossRef
76.
go back to reference N. Chalasani, Z. Younossi, J.E. Lavine, A.M. Diehl, E.M. Brunt, K. Cusi 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. Hepatology 55, 2005–2023 (2012)PubMedCrossRef N. Chalasani, Z. Younossi, J.E. Lavine, A.M. Diehl, E.M. Brunt, K. Cusi 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. Hepatology 55, 2005–2023 (2012)PubMedCrossRef
77.
go back to reference M.H. Ahmed, C.D. Byrne, Current treatment of non-alcoholic fatty liver disease. Diabetes Obes. Metab. 11, 188–195 (2009)PubMedCrossRef M.H. Ahmed, C.D. Byrne, Current treatment of non-alcoholic fatty liver disease. Diabetes Obes. Metab. 11, 188–195 (2009)PubMedCrossRef
78.
go back to reference S. Fatani, I. Itua, P. Clark, C. Wong, E.K. Naderali, The effects of diet-induced obesity on hepatocyte insulin signaling pathways and induction of non-alcoholic liver damage. Int. J. Gen. Med. 4, 211–219 (2011)PubMedCentralPubMed S. Fatani, I. Itua, P. Clark, C. Wong, E.K. Naderali, The effects of diet-induced obesity on hepatocyte insulin signaling pathways and induction of non-alcoholic liver damage. Int. J. Gen. Med. 4, 211–219 (2011)PubMedCentralPubMed
79.
go back to reference H. Park, T. Shima, K. Yamaguchi, H. Mitsuyoshi, M. Minami, K. Yasui et al., Efficacy of long-term ezetimibe therapy in patients with nonalcoholic fatty liver disease. J. Gastroenterol. 46, 101–107 (2011)PubMedCrossRef H. Park, T. Shima, K. Yamaguchi, H. Mitsuyoshi, M. Minami, K. Yasui et al., Efficacy of long-term ezetimibe therapy in patients with nonalcoholic fatty liver disease. J. Gastroenterol. 46, 101–107 (2011)PubMedCrossRef
80.
go back to reference V.G. Athyros, O. Giouleme, E.S. Ganotakis, M. Elisaf, K. Tziomalos, T. Vassiliadis 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. Arch. Med. Sci. 7, 796–805 (2011)PubMedCentralPubMedCrossRef V.G. Athyros, O. Giouleme, E.S. Ganotakis, M. Elisaf, K. Tziomalos, T. Vassiliadis 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. Arch. Med. Sci. 7, 796–805 (2011)PubMedCentralPubMedCrossRef
81.
go back to reference T.D. Adams, L.E. Davidson, S.E. Litwin, R.L. Kolotkin, M.J. LaMonte, R.C. Pendleton et al., Health benefits of gastric bypass surgery after 6 years. JAMA 308, 1122–1131 (2012)PubMedCentralPubMedCrossRef T.D. Adams, L.E. Davidson, S.E. Litwin, R.L. Kolotkin, M.J. LaMonte, R.C. Pendleton et al., Health benefits of gastric bypass surgery after 6 years. JAMA 308, 1122–1131 (2012)PubMedCentralPubMedCrossRef
82.
go back to reference P. Mathurin, A. Hollebecque, L. Arnalsteen, D. Buob, E. Leteurtre, R. Caiazzo et al., Prospective study of the long-term effects of bariatric surgery on liver injury in patients without advanced disease. Gastroenterology 137, 532–540 (2009)PubMedCrossRef P. Mathurin, A. Hollebecque, L. Arnalsteen, D. Buob, E. Leteurtre, R. Caiazzo et al., Prospective study of the long-term effects of bariatric surgery on liver injury in patients without advanced disease. Gastroenterology 137, 532–540 (2009)PubMedCrossRef
Metadata
Title
Non-alcoholic fatty liver disease: a diabetologist’s perspective
Authors
Joseph M. Pappachan
Farrah A. Antonio
Mahamood Edavalath
Arjun Mukherjee
Publication date
01-04-2014
Publisher
Springer US
Published in
Endocrine / Issue 3/2014
Print ISSN: 1355-008X
Electronic ISSN: 1559-0100
DOI
https://doi.org/10.1007/s12020-013-0087-8

Other articles of this Issue 3/2014

Endocrine 3/2014 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.