Non-alcoholic fatty liver disease and diabetes

Metabolism: Clinical and Experimental

Volumn 65, Issue 8, 2016, Pages 1096-1108

  Hazlehurst, Jonathan M ^a   Woods, Conor ^a   Marjot, Thomas ^b   Cobbold, Jeremy F ^b   Tomlinson, Jeremy W ^a  

^a UNIVERSITY OF OXFORD   (United Kingdom)

^b OXFORD UNIVERSITY HOSPITALS NHS FOUNDATION TRUST   (United Kingdom)

Author keywords

Diabetes; Diabetes complications; Insulin resistance; NAFLD; NASH

Indexed keywords

2,4 THIAZOLIDINEDIONE DERIVATIVE; DIPEPTIDYL PEPTIDASE IV INHIBITOR; FAT; GLUCAGON LIKE PEPTIDE 1 RECEPTOR AGONIST; INSULIN; METFORMIN; ORAL ANTIDIABETIC AGENT; SODIUM GLUCOSE COTRANSPORTER 2 INHIBITOR; SULFONYLUREA;

ARTICLE; BARIATRIC SURGERY; DEATH; DECOMPENSATED LIVER CIRRHOSIS; DIABETES MELLITUS; DISEASE COURSE; DRUG EFFICACY; EVIDENCE BASED PRACTICE; FOLLOW UP; GLYCEMIC CONTROL; HUMAN; INSULIN RESISTANCE; LIVER CELL CARCINOMA; NON INSULIN DEPENDENT DIABETES MELLITUS; NONALCOHOLIC FATTY LIVER; NONHUMAN; OUTCOME ASSESSMENT; PATHOGENESIS; PHASE 3 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL (TOPIC); RISK; WEIGHT GAIN; WEIGHT REDUCTION; COMPLICATION; DIABETIC COMPLICATION; METABOLISM; PATHOLOGY; PHYSIOLOGY;

DIABETES COMPLICATIONS; DIABETES MELLITUS, TYPE 2; DISEASE PROGRESSION; HUMANS; INSULIN RESISTANCE; NON-ALCOHOLIC FATTY LIVER DISEASE;

EID: 84978842582     PISSN: 00260495     EISSN: 15328600     Source Type: Journal    
DOI: 10.1016/j.metabol.2016.01.001     Document Type: Article

References (134)

1. [1] Williamson, R.M., Price, J.F., Glancy, S., Perry, E., Nee, L.D., Hayes, P.C., 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 34 (2011), 1139–1144, 10.2337/dc10-2229.
2. [2] Targher, G., Bertolini, L., Padovani, R., Rodella, S., Tessari, R., Zenari, L., et al. Prevalence of nonalcoholic fatty liver disease and its association with cardiovascular disease among type 2 diabetic patients. Diabetes Care 30 (2007), 1212–1218, 10.2337/dc06-2247.
3. [3] Sanchez, P.P., Bril, F., Maximos, M., Lomonaco, R., Biernacki, D., Orsak, B., et al. High prevalence of nonalcoholic fatty liver disease in patients with type 2 diabetes mellitus and normal plasma aminotransferase levels. J Clin Endocrinol Metab, 2015, jc20151966, 10.1210/jc.2015–1966.
4. [4] Armstrong, M.J., Hazlehurst, J.M., Parker, R., Koushiappi, E., Mann, J., Khan, S., et al. Severe asymptomatic non-alcoholic fatty liver disease in routine diabetes care; a multi-disciplinary team approach to diagnosis and management. QJM 107 (2014), 33–41, 10.1093/qjmed/hct198.
5. [5] Williamson, R.M., Price, J.F., Hayes, P.C., Glancy, S., Frier, B.M., Johnston, G.I., et al. Prevalence and markers of advanced liver disease in type 2 diabetes. QJM 105 (2012), 425–432, 10.1093/qjmed/hcr233.
6. [6] Ryu, S., Chang, Y., Jung, H.-S., Yun, K.E., Kwon, M.-J., Choi, Y., et al. Relationship of sitting time and physical activity with non-alcoholic fatty liver disease. J Hepatol, 2015, 10.1016/j.jhep.2015.07.010.
7. [7] Hillenbrand, A., Kiebler, B., Schwab, C., Scheja, L., Xu, P., Henne-Bruns, D., et al. Prevalence of non-alcoholic fatty liver disease in four different weight related patient groups: association with small bowel length and risk factors. BMC Res Notes, 8, 2015, 290, 10.1186/s13104-015-1224-7.
8. [8] Margariti, A., Kontogianni, M.D., Tileli, N., Georgoulis, M., Deutsch, M., Zafeiropoulou, R., et al. Increased abdominal fat levels measured by bioelectrical impedance are associated with histological lesions of nonalcoholic steatohepatitis. Eur J Gastroenterol Hepatol 27 (2015), 907–913, 10.1097/MEG.0000000000000381.
9. [9] Shibata, M., Kihara, Y., Taguchi, M., Tashiro, M., Otsuki, M., Nonalcoholic fatty liver disease is a risk factor for type 2 diabetes in middle-aged Japanese men. Diabetes Care 30 (2007), 2940–2944, 10.2337/dc07-0792.
10. [10] Kim, C.-H., Park, J.-Y., Lee, K.-U., Kim, J.-H., Kim, H.-K., Fatty liver is an independent risk factor for the development of type 2 diabetes in Korean adults. Diabet Med 25 (2008), 476–481, 10.1111/j.1464-5491.2008.02410.x.
11. [11] Adams, L.A., Waters, O.R., Knuiman, M.W., Elliott, R.R., Olynyk, J.K., NAFLD as a risk factor for the development of diabetes and the metabolic syndrome: an eleven-year follow-up study. Am J Gastroenterol 104 (2009), 861–867, 10.1038/ajg.2009.67.
12. [12] Balkau, B., Lange, C., Vol, S., Fumeron, F., Bonnet, F., Nine-year incident diabetes is predicted by fatty liver indices: the French D.E.S.I.R. study. BMC Gastroenterol, 10, 2010, 56, 10.1186/1471-230X-10-56.
13. [13] Yamada, T., Fukatsu, M., Suzuki, S., Wada, T., Yoshida, T., Joh, T., Fatty liver predicts impaired fasting glucose and type 2 diabetes mellitus in Japanese undergoing a health checkup. J Gastroenterol Hepatol 25 (2010), 352–356, 10.1111/j.1440-1746.2009.05998.x.
14. [14] Sung, K.-C., Kim, S.H., Interrelationship between fatty liver and insulin resistance in the development of type 2 diabetes. J Clin Endocrinol Metab 96 (2011), 1093–1097, 10.1210/jc.2010-2190.
15. [15] Bae, J.C., Rhee, E.J., Lee, W.Y., Park, S.E., Park, C.Y., Oh, K.W., et al. Combined effect of nonalcoholic fatty liver disease and impaired fasting glucose on the development of type 2 diabetes: a 4-year retrospective longitudinal study. Diabetes Care 34 (2011), 727–729, 10.2337/dc10-1991.
16. [16] Chon, C.W., Kim, B.S., Cho, Y.K., Sung, K.C., Bae, J.C., Kim, T.W., et al. Effect of nonalcoholic fatty liver disease on the development of type 2 diabetes in nonobese, nondiabetic Korean men. Gut Liver 6 (2012), 368–373, 10.5009/gnl.2012.6.3.368.
17. [17] Sung, K.-C., Jeong, W.-S., Wild, S.H., Byrne, C.D., Combined influence of insulin resistance, overweight/obesity, and fatty liver as risk factors for type 2 diabetes. Diabetes Care 35 (2012), 717–722, 10.2337/dc11-1853.
18. [18] Choi, J.H., Rhee, E.J., Bae, J.C., Park, S.E., Park, C.Y., Cho, Y.K., 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 (2013), 115–120, 10.1016/j.arcmed.2013.01.007.
19. [19] Kotronen, A., Laaksonen, M.A., Heliövaara, M., Reunanen, A., Tuomilehto, J., Yki-Järvinen, H., et al. Fatty liver score and 15-year incidence of type 2 diabetes. Hepatol Int 7 (2013), 610–621, 10.1007/s12072-013-9430-7.
20. [20] Park, S.K., Seo, M.H., Shin, H.C., Ryoo, J.-H., Clinical availability of nonalcoholic fatty liver disease as an early predictor of type 2 diabetes mellitus in Korean men: 5-year prospective cohort study. Hepatology 57 (2013), 1378–1383, 10.1002/hep.26183.
21. [21] Zelber-Sagi, S., Lotan, R., Shibolet, O., Webb, M., Buch, A., Nitzan-Kaluski, D., et al. Non-alcoholic fatty liver disease independently predicts prediabetes during a 7-year prospective follow-up. Liver Int 33 (2013), 1406–1412, 10.1111/liv.12200.
22. [22] Ming, J., Xu, S., Gao, B., Liu, G., Ji, Y., Yang, F., et al. Non-alcoholic fatty liver disease predicts type 2 diabetes mellitus, but not prediabetes, in Xi'an, China: a five-year cohort study. Liver Int, 2015, 10.1111/liv.12851.
23. [23] Jäger, S., Jacobs, S., Kröger, J., Stefan, N., Fritsche, A., Weikert, C., et al. Association between the fatty liver index and risk of type 2 diabetes in the EPIC-potsdam study. PLoS One, 10, 2015, e0124749, 10.1371/journal.pone.0124749.
24. [24] Adams, L.A., Harmsen, S., St Sauver, J.L., Charatcharoenwitthaya, P., Enders, F.B., Therneau, T., et al. Nonalcoholic fatty liver disease increases risk of death among patients with diabetes: a community-based cohort study. Am J Gastroenterol 105 (2010), 1567–1573, 10.1038/ajg.2010.18.
25. [25] Yamazaki, H., Tsuboya, T., Tsuji, K., Dohke, M., Maguchi, H., Independent association between improvement of nonalcoholic fatty liver disease and reduced incidence of type 2 diabetes mellitus. Diabetes Care, 2015, 10.2337/dc15-0140.
26. [26] Matsumoto, N., Arase, Y., Kawamura, Y., Ohmoto-Sekine, M., Amakawa, K., Ogawa, K., et al. Significance of oral glucose tolerance tests in non-alcoholic fatty liver disease patients with a fasting plasma glucose level of < 126 mg/dL and HbA1c level of ≤ 6.4% in Japan. Intern Med 54 (2015), 875–880, 10.2169/internalmedicine.54.3437.
27. [27] Jun, D.W., Kim, H.J., Bae, J.H., Lee, O.Y., The clinical significance of HbA1c as a predictive factor for abnormal postprandial glucose metabolism in NAFLD patients with an elevated liver chemistry. Hepato-Gastroenterology 58 (2011), 1274–1279.
28. [28] Kotronen, A., Juurinen, L., Hakkarainen, A., Westerbacka, J., Cornér, A., Bergholm, R., 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 31 (2008), 165–169, 10.2337/dc07-1463.
29. [29] Bae, J.C., Cho, Y.K., Lee, W.Y., Seo, H. II, EJ, Rhee, SE, Park, et al. Impact of nonalcoholic fatty liver disease on insulin resistance in relation to HbA1c levels in nondiabetic subjects. Am J Gastroenterol 105 (2010), 2389–2395, 10.1038/ajg.2010.275.
30. [30] Wong, V.W.S., Hui, A.Y., Tsang, S.W.C., Chan, J.L.Y., Wong, G.L.H., Chan, A.W.H., et al. Prevalence of undiagnosed diabetes and postchallenge hyperglycaemia in Chinese patients with non-alcoholic fatty liver disease. Aliment Pharmacol Ther 24 (2006), 1215–1222, 10.1111/j.1365-2036.2006.03112.x.
31. [31] McPherson, S., Hardy, T., Henderson, E., Burt, A.D., Day, C.P., Anstee, Q.M., Evidence of NAFLD progression from steatosis to fibrosing-steatohepatitis using paired biopsies: implications for prognosis & clinical management. J Hepatol, 2014, 10.1016/j.jhep.2014.11.034.
32. [32] Vanni, E., Bugianesi, E., Kotronen, A., De Minicis, S., Yki-Järvinen, H., Svegliati-Baroni, G., From the metabolic syndrome to NAFLD or vice versa?. Dig Liver Dis 42 (2010), 320–330, 10.1016/j.dld.2010.01.016.
33. [33] Llauradó, G., Sevastianova, K., Sädevirta, S., Hakkarainen, A., Lundbom, N., Orho-Melander, M., et al. Liver fat content and hepatic insulin sensitivity in overweight patients with type 1 diabetes. J Clin Endocrinol Metab 100 (2015), 607–616, 10.1210/jc.2014-3050.
34. [34] Petit, J.M., Pedro, L., Guiu, B., Duvillard, L., Bouillet, B., Jooste, V., et al. Type 1 diabetes is not associated with an increased prevalence of hepatic steatosis. Diabet Med, 2015, 10.1111/dme.12805.
35. [35] Regnell, S.E., Peterson, P., Trinh, L., Broberg, P., Leander, P., Lernmark, Å., et al. Magnetic resonance imaging reveals altered distribution of hepatic fat in children with type 1 diabetes compared to controls. Metabolism 64 (2015), 872–878, 10.1016/j.metabol.2015.04.002.
36. [36] Targher, G., Bertolini, L., Rodella, S., Tessari, R., Zenari, L., Lippi, G., et al. Nonalcoholic fatty liver disease is independently associated with an increased incidence of cardiovascular events in type 2 diabetic patients. Diabetes Care 30 (2007), 2119–2121, 10.2337/dc07-0349.
37. [37] Dunn, M.A., Behari, J., Rogal, S.S., O'Connell, M.R., Furlan, A., Aghayev, A., et al. Hepatic steatosis in diabetic patients does not predict adverse liver-related or cardiovascular outcomes. Liver Int 33 (2013), 1575–1582, 10.1111/liv.12285.
38. [38] Athyros, V.G., Tziomalos, K., Katsiki, N., Doumas, M., Karagiannis, A., Mikhailidis, D.P., Cardiovascular risk across the histological spectrum and the clinical manifestations of non-alcoholic fatty liver disease: an update. World J Gastroenterol 21 (2015), 6820–6834, 10.3748/wjg.v21.i22.6820.
39. [39] Targher, G., Bertolini, L., Rodella, S., Zoppini, G., Lippi, G., Day, C., et al. Non-alcoholic fatty liver disease is independently associated with an increased prevalence of chronic kidney disease and proliferative/laser-treated retinopathy in type 2 diabetic patients. Diabetologia 51 (2008), 444–450, 10.1007/s00125-007-0897-4.
40. [40] Ryysy, L., Häkkinen, A.M., Goto, T., Vehkavaara, S., Westerbacka, J., Halavaara, J., et al. Hepatic fat content and insulin action on free fatty acids and glucose metabolism rather than insulin absorption are associated with insulin requirements during insulin therapy in type 2 diabetic patients. Diabetes 49 (2000), 749–758.
41. [41] De Marco, R., Locatelli, F., Zoppini, G., Verlato, G., Bonora, E., Muggeo, M., Cause-specific mortality in type 2 diabetes. The Verona Diabetes Study. Diabetes Care 22 (1999), 756–761.
42. [42] Hossain, N., Afendy, A., Stepanova, M., Nader, F., Srishord, M., Rafiq, N., et al. Independent predictors of fibrosis in patients with nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol 7 (2009), 1224–1229, 10.1016/j.cgh.2009.06.007 [1229.e1–2].
43. [43] Younossi, Z.M., Gramlich, T., Matteoni, C.A., Boparai, N., McCullough, A.J., Nonalcoholic fatty liver disease in patients with type 2 diabetes. Clin Gastroenterol Hepatol 2 (2004), 262–265.
44. [44] Gramlich, T., Kleiner, D.E., McCullough, A.J., Matteoni, C.A., Boparai, N., Younossi, Z.M., Pathologic features associated with fibrosis in nonalcoholic fatty liver disease. Hum Pathol 35 (2004), 196–199, 10.1016/j.humpath.2003.09.018.
45. [45] Adams, L.A., Sanderson, S., Lindor, K.D., Angulo, P., The histological course of nonalcoholic fatty liver disease: a longitudinal study of 103 patients with sequential liver biopsies. J Hepatol 42 (2005), 132–138, 10.1016/j.jhep.2004.09.012.
46. [46] Wang, C., Wang, X., Gong, G., Ben, Q., Qiu, W., Chen, Y., et al. Increased risk of hepatocellular carcinoma in patients with diabetes mellitus: a systematic review and meta-analysis of cohort studies. Int J Cancer 130 (2012), 1639–1648, 10.1002/ijc.26165.
47. [47] Day, C.P., James, O.F.W., Steatohepatitis: a tale of two “hits”?. Gastroenterology 114 (1998), 842–845, 10.1016/S0016-5085(98)70599-2.
48. [48] Dowman, J.K., Tomlinson, J.W., Newsome, P.N., Pathogenesis of non-alcoholic fatty liver disease. QJM 103 (2010), 71–83, 10.1093/qjmed/hcp158.
49. [49] Cusi, K., Role of obesity and lipotoxicity in the development of nonalcoholic steatohepatitis: pathophysiology and clinical implications. Gastroenterology 142 (2012), 711–725.e6, 10.1053/j.gastro.2012.02.003.
50. [50] Zarrinpar, A., Loomba, R., Review article: the emerging interplay among the gastrointestinal tract, bile acids and incretins in the pathogenesis of diabetes and non-alcoholic fatty liver disease. Aliment Pharmacol Ther 36 (2012), 909–921, 10.1111/apt.12084.
51. [51] Abdul-Hai, A., Abdallah, A., Malnick, S.D., Influence of gut bacteria on development and progression of non-alcoholic fatty liver disease. World J Hepatol 7 (2015), 1679–1684, 10.4254/wjh.v7.i12.1679.
52. [52] Kantartzis, K., Peter, A., Machicao, F., Machann, J., Wagner, S., Königsrainer, I., et al. Dissociation between fatty liver and insulin resistance in humans carrying a variant of the patatin-like phospholipase 3 gene. Diabetes 58 (2009), 2616–2623, 10.2337/db09-0279.
53. [53] Donnelly, K.L., Smith, C.I., Schwarzenberg, S.J., Jessurun, J., Boldt, M.D., Parks, E.J., Sources of fatty acids stored in liver and secreted via lipoproteins in patients with nonalcoholic fatty liver disease. J Clin Invest 115 (2005), 1343–1351, 10.1172/JCI23621.
54. [54] Schwarz, J.-M., Linfoot, P., Dare, D., Aghajanian, K., Hepatic de novo lipogenesis in normoinsulinemic and hyperinsulinemic subjects consuming high-fat, low-carbohydrate and low-fat, high-carbohydrate isoenergetic diets. Am J Clin Nutr 77 (2003), 43–50.
55. [55] Sunny, N.E., Parks, E.J., Browning, J.D., Burgess, S.C., Excessive hepatic mitochondrial TCA cycle and gluconeogenesis in humans with nonalcoholic fatty liver disease. Cell Metab 14 (2011), 804–810, 10.1016/j.cmet.2011.11.004.
56. [56] Wei, Y., Rector, R.S., Thyfault, J.P., Ibdah, J.A., Nonalcoholic fatty liver disease and mitochondrial dysfunction. World J Gastroenterol 14 (2008), 193–199.
57. [57] Wong, V.W.-S., Wong, G.L.-H., Choi, P.C.-L., Chan, A.W.-H., Li, M.K.-P., Chan, H.-Y., et al. Disease progression of non-alcoholic fatty liver disease: a prospective study with paired liver biopsies at 3 years. Gut 59 (2010), 969–974, 10.1136/gut.2009.205088.
58. [58] Sharma, M., Mitnala, S., Vishnubhotla, R.K., Mukherjee, R., Reddy, D.N., Rao, P.N., The riddle of nonalcoholic fatty liver disease: progression from nonalcoholic fatty liver to nonalcoholic steatohepatitis. J Clin Exp Hepatol 5 (2015), 147–158, 10.1016/j.jceh.2015.02.002.
59. [59] Garcia-Monzón, C., Martín-Pérez, E., Iacono, O.L., Fernández-Bermejo, M., Majano, P.L., Apolinario, A., et al. Characterization of pathogenic and prognostic factors of nonalcoholic steatohepatitis associated with obesity. J Hepatol 33 (2000), 716–724, 10.1016/S0168-8278(00)80301-3.
60. [60] Du Plessis, J., van Pelt, J., Korf, H., Mathieu, C., van der Schueren, B., Lannoo, M., et al. Association of adipose tissue inflammation with histological severity of Non-alcoholic fatty liver disease. Gastroenterology, 2015, 10.1053/j.gastro.2015.05.044.
61. [61] Choudhary, N.S., Saraf, N., Saigal, S., Gautam, D., Lipi, L., Rastogi, A., et al. Rapid reversal of liver steatosis with life style modification in highly motivated liver donors. J Clin Exp Hepatol 5 (2015), 123–126, 10.1016/j.jceh.2015.04.002.
62. [62] Hallsworth, K., Thoma, C., Hollingsworth, K.G., Cassidy, S., Anstee, Q.M., Day, C.P., et al. Modified high-intensity interval training reduces liver fat and improves cardiac function in non-alcoholic fatty liver disease: a randomised controlled trial. Clin Sci (Lond), 2015, 10.1042/CS20150308.
63. [63] Vilar-Gomez, E., Martinez-Perez, Y., Calzadilla-Bertot, L., Torres-Gonzalez, A., Gra-Oramas, B., Gonzalez-Fabian, L., et al. Weight loss via lifestyle modification significantly reduces features of nonalcoholic steatohepatitis. Gastroenterology 149 (2015), 367–378.e5, 10.1053/j.gastro.2015.04.005.
64. [64] Tang, A., Rabasa-Lhoret, R., Castel, H., Wartelle-Bladou, C., Gilbert, G., Massicotte-Tisluck, K., et al. Effects of insulin glargine and liraglutide therapy on liver fat as measured by magnetic resonance in patients with type 2 diabetes: a randomized trial. Diabetes Care 38 (2015), 1339–1346, 10.2337/dc14-2548.
65. [65] Lingvay, I., Raskin, P., Szczepaniak, L.S., Effect of insulin–metformin combination on hepatic steatosis in patients with type 2 diabetes. J Diabetes Complications 21 (2007), 137–142, 10.1016/j.jdiacomp.2007.02.005.
66. [66] Juurinen, L., Tiikkainen, M., Häkkinen, A.-M., Hakkarainen, A., Yki-Järvinen, H., Effects of insulin therapy on liver fat content and hepatic insulin sensitivity in patients with type 2 diabetes. Am J Physiol Endocrinol Metab 292 (2007), E829–E835, 10.1152/ajpendo.00133.2006.
67. [67] Topping, D.L., Mayes, P.A., The immediate effects of insulin and fructose on the metabolism of the perfused liver. Changes in lipoprotein secretion, fatty acid oxidation and esterification, lipogenesis and carbohydrate metabolism. Biochem J 126 (1972), 295–311.
68. [68] Zammit, V.A., Use of in vivo and in vitro techniques for the study of the effects of insulin on hepatic triacylglycerol secretion in different insulinaemic states. Biochem Soc Trans 28 (2000), 103–109.
69. [69] Goh, G., Pagadala, M., Diabetes mellitus, insulin, sulfonylurea and advanced fibrosis in non-alcoholic fatty liver disease. J Diabetes Metab 5 (2014), 1–5.
70. [70] Singh, S., Singh, P.P., Singh, A.G., Murad, M.H., Sanchez, W., Anti-diabetic medications and the risk of hepatocellular cancer: a systematic review and meta-analysis. Am J Gastroenterol 108 (2013), 881–891, 10.1038/ajg.2013.5 [quiz 892].
71. [71] Tiikkainen, M., Häkkinen, A.-M., Korsheninnikova, E., Nyman, T., Mäkimattila, S., Yki-Järvinen, H., Effects of rosiglitazone and metformin on liver fat content, hepatic insulin resistance, insulin clearance, and gene expression in adipose tissue in patients with type 2 diabetes. Diabetes 53 (2004), 2169–2176.
72. [72] Ford, R.J., Fullerton, M.D., Pinkosky, S.L., Day, E.A., Scott, J.W., Oakhill, J.S., et al. Metformin and salicylate synergistically activate liver AMPK, inhibit lipogenesis and improve insulin sensitivity. Biochem J 468 (2015), 125–132, 10.1042/BJ20150125.
73. [73] Zhou, G., Myers, R., Li, Y., Chen, Y., Shen, X., Fenyk-Melody, J., et al. Role of AMP-activated protein kinase in mechanism of metformin action. J Clin Invest 108 (2001), 1167–1174, 10.1172/JCI13505.
74. [74] Musso, G., Cassader, M., Rosina, F., Gambino, R., 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 (2012), 885–904, 10.1007/s00125-011-2446-4.
75. [75] Zhang, X., Harmsen, W.S., Mettler, T.A., Kim, W.R., Roberts, R.O., Therneau, T.M., et al. Continuation of metformin use after a diagnosis of cirrhosis significantly improves survival of patients with diabetes. Hepatology 60 (2014), 2008–2016, 10.1002/hep.27199.
76. [76] Chen, H.-P., Shieh, J.-J., Chang, C.-C., Chen, T.-T., Lin, J.-T., Wu, M.-S., et al. Metformin decreases hepatocellular carcinoma risk in a dose-dependent manner: population-based and in vitro studies. Gut 62 (2013), 606–615, 10.1136/gutjnl-2011-301708.
77. [77] Bhat, M., Chaiteerakij, R., Harmsen, W.S., Schleck, C.D., Yang, J.D., Giama, N.H., et al. Metformin does not improve survival in patients with hepatocellular carcinoma. World J Gastroenterol 20 (2014), 15750–15755, 10.3748/wjg.v20.i42.15750.
78. [78] Chen, T.-M., Lin, C.-C., Huang, P.-T., Wen, C.-F., Metformin associated with lower mortality in diabetic patients with early stage hepatocellular carcinoma after radiofrequency ablation. J Gastroenterol Hepatol 26 (2011), 858–865, 10.1111/j.1440-1746.2011.06664.x.
79. [79] Svegliati-Baroni, G., Ridolfi, F., Di Sario, A., Casini, A., Marucci, L., Gaggiotti, G., et al. Insulin and insulin-like growth factor-1 stimulate proliferation and type I collagen accumulation by human hepatic stellate cells: differential effects on signal transduction pathways. Hepatology 29 (1999), 1743–1751, 10.1002/hep.510290632.
80. [80] Belcher, G., Schernthaner, G., Changes in liver tests during 1-year treatment of patients with type 2 diabetes with pioglitazone, metformin or gliclazide. Diabet Med 22 (2005), 973–979, 10.1111/j.1464-5491.2005.01595.x.
81. [81] Dourakis, S., Tzemanakis, E., Gliclazide-induced acute hepatitis. Eur J Gastroenterol Hepatol 12 (2000), 119–121.
82. [82] Bowker, S.L., Majumdar, S.R., Veugelers, P., Johnson, J.A., Increased cancer-related mortality for patients with type 2 diabetes who use sulfonylureas or insulin. Diabetes Care 29 (2006), 254–258.
83. [83] Yki-Jävinen, H., Thiazolidinediones. N Engl J Med 351 (2004), 1106–1118, 10.1056/NEJMra041001.
84. [84] Yki-Järvinen, H., Thiazolidinediones and the liver in humans. Curr Opin Lipidol 20 (2009), 477–483, 10.1097/MOL.0b013e3283321d37.
85. [85] Pettinelli, P., Videla, L.A., Up-regulation of PPAR-gamma mRNA expression in the liver of obese patients: an additional reinforcing lipogenic mechanism to SREBP-1c induction. J Clin Endocrinol Metab 96 (2011), 1424–1430, 10.1210/jc.2010-2129.
86. [86] Souza-Mello, V., Peroxisome proliferator-activated receptors as targets to treat non-alcoholic fatty liver disease. World J Hepatol 7 (2015), 1012–1019, 10.4254/wjh.v7.i8.1012.
87. [87] Fernández-Miranda, C., Pérez-Carreras, M., Colina, F., López-Alonso, G., Vargas, C., Solís-Herruzo, J.A., A pilot trial of fenofibrate for the treatment of non-alcoholic fatty liver disease. Dig Liver Dis 40 (2008), 200–205, 10.1016/j.dld.2007.10.002.
88. [88] Yan, F., Wang, Q., Xu, C., Cao, M., Zhou, X., Wang, T., et al. Peroxisome proliferator-activated receptor α activation induces hepatic steatosis, suggesting an adverse effect. PLoS One, 9, 2014, e99245, 10.1371/journal.pone.0099245.
89. [89] Lewis, J.D., Habel, L.A., Quesenberry, C.P., Strom, B.L., Peng, T., Hedderson, M.M., et al. Pioglitazone use and risk of bladder cancer and other common cancers in persons with diabetes. JAMA 314 (2015), 265–277, 10.1001/jama.2015.7996.
90. [90] Aubert, R.E., Herrera, V., Chen, W., Haffner, S.M., Pendergrass, M., Rosiglitazone and pioglitazone increase fracture risk in women and men with type 2 diabetes. Diabetes Obes Metab 12 (2010), 716–721, 10.1111/j.1463-1326.2010.01225.x.
91. [91] Ratziu, V., Giral, P., Jacqueminet, S., Charlotte, F., Hartemann-Heurtier, A., Serfaty, L., et al. Rosiglitazone for nonalcoholic steatohepatitis: one-year results of the randomized placebo-controlled fatty liver improvement with rosiglitazone therapy (FLIRT) trial. Gastroenterology 135 (2008), 100–110, 10.1053/j.gastro.2008.03.078.
92. [92] Ratziu, V., Charlotte, F., Bernhardt, C., Giral, P., Halbron, M., Lenaour, G., et al. Long-term efficacy of rosiglitazone in nonalcoholic steatohepatitis: results of the Fatty Liver Improvement by Rosiglitazone Therapy (FLIRT 2) extension trial. Hepatology 51 (2010), 445–453, 10.1002/hep.23270.
93. [93] Belfort, R., Harrison, S.A., Brown, K., Darland, C., Finch, J., Hardies, J., et al. A placebo-controlled trial of pioglitazone in subjects with nonalcoholic steatohepatitis. N Engl J Med 355 (2006), 2297–2307, 10.1056/NEJMoa060326.
94. [94] Aithal, G.P., Thomas, J.A., Kaye, P.V., Lawson, A., Ryder, S.D., Spendlove, I., et al. Randomized, placebo-controlled trial of pioglitazone in nondiabetic subjects with nonalcoholic steatohepatitis. Gastroenterology 135 (2008), 1176–1184, 10.1053/j.gastro.2008.06.047.
95. [95] Sanyal, A.J., Chalasani, N., Kowdley, K.V., McCullough, A., Diehl, A.M., Bass, N.M., et al. Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis. N Engl J Med 362 (2010), 1675–1685, 10.1056/NEJMoa0907929.
96. [96] Polyzos, S.A., Kountouras, J., Zavos, C., Tsiaousi, E., The role of adiponectin in the pathogenesis and treatment of non-alcoholic fatty liver disease. Diabetes Obes Metab 12 (2010), 365–383, 10.1111/j.1463-1326.2009.01176.x.
97. [97] Balaban, Y.H., Korkusuz, P., Simsek, H., Gokcan, H., Gedikoglu, G., Pinar, A., et al. Dipeptidyl peptidase IV (DDP IV) in NASH patients. Ann Hepatol 6 (2007), 242–250.
98. [98] KH, Williams, AJ, Vieira De Ribeiro, Prakoso, E., A-S, Veillard, NA, Shackel, Brooks, B., et al. Circulating dipeptidyl peptidase-4 activity correlates with measures of hepatocyte apoptosis and fibrosis in non-alcoholic fatty liver disease in type 2 diabetes mellitus and obesity: a dual cohort cross-sectional study. J Diabetes, 2014, 10.1111/1753–0407.12237.
99. [99] Kern, M., Klöting, N., Niessen, H.G., Thomas, L., Stiller, D., Mark, M., et al. Linagliptin improves insulin sensitivity and hepatic steatosis in diet-induced obesity. PLoS One, 7, 2012, e38744, 10.1371/journal.pone.0038744.
100. [100] Kaji, K., Yoshiji, H., Ikenaka, Y., Noguchi, R., Aihara, Y., Douhara, A., et al. Dipeptidyl peptidase-4 inhibitor attenuates hepatic fibrosis via suppression of activated hepatic stellate cell in rats. J Gastroenterol 49 (2014), 481–491, 10.1007/s00535-013-0783-4.
101. [101] Arase, Y., Kawamura, Y., Seko, Y., Kobayashi, M., Suzuki, F., Suzuki, Y., et al. Efficacy and safety in sitagliptin therapy for diabetes complicated by non-alcoholic fatty liver disease. Hepatol Res 43 (2013), 1163–1168, 10.1111/hepr.12077.
102. [102] Iwasaki, T., Yoneda, M., Inamori, M., Shirakawa, J., Higurashi, T., Maeda, S., et al. Sitagliptin as a novel treatment agent for non-alcoholic fatty liver disease patients with type 2 diabetes mellitus. Hepatogastroenterology 58 (2011), 2103–2105, 10.5754/hge11263.
103. [103] Macauley, M., Hollingsworth, K.G., Smith, F.E., Thelwall, P.E., Al-Mrabeh, A., Schweizer, A., et al. Effect of vildagliptin on hepatic steatosis. J Clin Endocrinol Metab 100 (2015), 1578–1585, 10.1210/jc.2014-3794.
104. [104] Derosa, G., Bonaventura, A., Bianchi, L., Romano, D., Fogari, E., D'Angelo, A., et al. Vildagliptin compared to glimepiride on post-prandial lipemia and on insulin resistance in type 2 diabetic patients. Metabolism 63 (2014), 957–967, 10.1016/j.metabol.2014.04.008.
105. [105] Scheen, A.J., A review of gliptins for 2014. Expert Opin Pharmacother 16 (2015), 43–62, 10.1517/14656566.2015.978289.
106. [106] Baggio, L.L., Drucker, D.J., Biology of incretins: GLP-1 and GIP. Gastroenterology 132 (2007), 2131–2157, 10.1053/j.gastro.2007.03.054.
107. [107] Astrup, A., Rössner, S., Van Gaal, L., Rissanen, A., Niskanen, L., Al Hakim, M., et al. Effects of liraglutide in the treatment of obesity: a randomised, double-blind, placebo-controlled study. Lancet (Lond, Engl) 374 (2009), 1606–1616, 10.1016/S0140-6736(09)61375–1.
108. [108] Ding, X., Saxena, N.K., Lin, S., Gupta, N.A., Gupta, N., Anania, F.A., Exendin-4, a glucagon-like protein-1 (GLP-1) receptor agonist, reverses hepatic steatosis in ob/ob mice. Hepatology 43 (2006), 173–181, 10.1002/hep.21006.
109. [109] Trevaskis, J.L., Griffin, P.S., Wittmer, C., Neuschwander-Tetri, B.A., Brunt, E.M., Dolman, C.S., et al. Glucagon-like peptide-1 receptor agonism improves metabolic, biochemical, and histopathological indices of nonalcoholic steatohepatitis in mice. Am J Physiol Gastrointest Liver Physiol 302 (2012), G762–G772, 10.1152/ajpgi.00476.2011.
110. [110] Ben-Shlomo, S., Zvibel, I., Shnell, M., Shlomai, A., Chepurko, E., Halpern, Z., et al. Glucagon-like peptide-1 reduces hepatic lipogenesis via activation of AMP-activated protein kinase. J Hepatol 54 (2011), 1214–1223, 10.1016/j.jhep.2010.09.032.
111. [111] Körner, M., Stöckli, M., Waser, B., Reubi, J.C., GLP-1 receptor expression in human tumors and human normal tissues: potential for in vivo targeting. J Nucl Med 48 (2007), 736–743, 10.2967/jnumed.106.038679.
112. [112] Gupta, N.A., Mells, J., Dunham, R.M., Grakoui, A., Handy, J., Saxena, N.K., 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 51 (2010), 1584–1592, 10.1002/hep.23569.
113. [113] Armstrong, M.J., Houlihan, D.D., Rowe, I.A., Clausen, W.H.O., Elbrønd, B., Gough, S.C.L., et al. Safety and efficacy of liraglutide in patients with type 2 diabetes and elevated liver enzymes: individual patient data meta-analysis of the LEAD program. Aliment Pharmacol Ther 37 (2013), 234–242, 10.1111/apt.12149.
114. [114] Armstrong, M., Gaunt, P., Aithal, G., Parker, R., Liraglutide is effective in the histological clearance of non-alcoholic steatohepatitis in a multicentre, doubleblinded, randomised, placebocontrolled phase. Abstr G01, EASL, 2015.
115. [115] Armstrong, M.J., Hull, D., Guo, K., Barton, D., Hazlehurst, J.M., Gathercole, L.L., et al. Glucagon-like peptide 1 decreases lipotoxicity in non-alcoholic steatophepatitis. J Hepatol, 2015, 10.1016/j.jhep.2015.08.038.
116. [116] Whalen, K., Miller, S., Onge, E.S., The role of sodium-glucose co-transporter 2 inhibitors in the treatment of type 2 diabetes. Clin Ther 37 (2015), 1150–1166, 10.1016/j.clinthera.2015.03.004.
117. [117] Hayashizaki-Someya, Y., Kurosaki, E., Takasu, T., Mitori, H., Yamazaki, S., Koide, K., et al. Ipragliflozin, an SGLT2 inhibitor, exhibits a prophylactic effect on hepatic steatosis and fibrosis induced by choline-deficient l-amino acid-defined diet in rats. Eur J Pharmacol 754 (2015), 19–24, 10.1016/j.ejphar.2015.02.009.
118. [118] Tahara, A., Kurosaki, E., Yokono, M., Yamajuku, D., Kihara, R., Hayashizaki, Y., et al. Effects of SGLT2 selective inhibitor ipragliflozin on hyperglycemia, hyperlipidemia, hepatic steatosis, oxidative stress, inflammation, and obesity in type 2 diabetic mice. Eur J Pharmacol 715 (2013), 246–255, 10.1016/j.ejphar.2013.05.014.
119. [119] Kern, M., Klöting, N., Grempler, R., Mayoux, E., Mark, M., Klein, T., et al. Tofogliflozin improves insulin resistance as well as glucose tolerance by ameliorating fatty liver and obesity. Diabetes, 62(Supp1), 2013, A285.
120. [120] Vasilakou, D., Karagiannis, T., Athanasiadou, E., Mainou, M., Liakos, A., Bekiari, E., et al. Sodium-glucose cotransporter 2 inhibitors for type 2 diabetes: a systematic review and meta-analysis. Ann Intern Med 159 (2013), 262–274, 10.7326/0003-4819-159-4-201308200-00007.
121. [121] Bolinder, J., Ljunggren, Ö., Kullberg, J., Johansson, L., Wilding, J., Langkilde, A.M., et al. Effects of dapagliflozin on body weight, total fat mass, and regional adipose tissue distribution in patients with type 2 diabetes mellitus with inadequate glycemic control on metformin. J Clin Endocrinol Metab 97 (2012), 1020–1031, 10.1210/jc.2011-2260.
122. [122] Courcoulas, A.P., Belle, S.H., Neiberg, R.H., Pierson, S.K., Eagleton, J.K., Kalarchian, M.A., et al. Three-year outcomes of bariatric surgery vs lifestyle intervention for type 2 diabetes mellitus treatment: a randomized clinical trial. JAMA Surg, 2015, 10.1001/jamasurg.2015.1534.
123. [123] Bower, G., Toma, T., Harling, L., Jiao, L.R., Efthimiou, E., Darzi, A., et al. Bariatric surgery and Non-alcoholic fatty liver disease: a systematic review of liver biochemistry and histology. Obes Surg, 2015, 10.1007/s11695-015-1691-x.
124. [124] Laferrère, B., Heshka, S., Wang, K., Khan, Y., McGinty, J., Teixeira, J., et al. Incretin levels and effect are markedly enhanced 1 month after Roux-en-Y gastric bypass surgery in obese patients with type 2 diabetes. Diabetes Care 30 (2007), 1709–1716, 10.2337/dc06-1549.
125. [125] Clark, J.M., Alkhuraishi, A.R.A., Solga, S.F., Alli, P., Diehl, A.M., Magnuson, T.H., Roux-en-Y gastric bypass improves liver histology in patients with non-alcoholic fatty liver disease. Obes Res 13 (2005), 1180–1186, 10.1038/oby.2005.140.
126. [126] Xourafas, D., Ardestani, A., Ashley, S.W., Tavakkoli, A., Impact of weight-loss surgery and diabetes status on serum ALT levels. Obes Surg 22 (2012), 1540–1547, 10.1007/s11695-012-0677-1.
127. [127] Pappachan, J.M., Viswanath, A.K., Metabolic surgery: a paradigm shift in type 2 diabetes management. World J Diabetes 6 (2015), 990–998, 10.4239/wjd.v6.i8.990.
128. [128] Obesity: identification, assessment and management of overweight and obesity in children, young people and adults. Guidance and guidelines. NICE, 2014.
129. [129] Ferslew, B.C., Xie, G., Johnston, C.K., Su, M., Stewart, P.W., Jia, W., et al. Altered bile acid metabolome in patients with nonalcoholic steatohepatitis. Dig Dis Sci, 2015, 10.1007/s10620-015-3776-8.
130. [130] Penney, N.C., Kinross, J., Newton, R.C., Purkayastha, S., The role of bile acids in reducing the metabolic complications of obesity after bariatric surgery: a systematic review. Int J Obes, 2015, 10.1038/ijo.2015.115.
131. [131] Cole, A.J., Teigen, L.M., Jahansouz, C., Earthman, C.P., Sibley, S.D., The influence of bariatric surgery on serum bile acids in humans and potential metabolic and hormonal implications: a systematic review. Curr Obes Rep, 2015, 10.1007/s13679-015-0171-x.
132. [132] Neuschwander-Tetri, B.A., Loomba, R., Sanyal, A.J., Lavine, J.E., Van Natta, M.L., Abdelmalek, M.F., et al. Farnesoid X nuclear receptor ligand obeticholic acid for non-cirrhotic, non-alcoholic steatohepatitis (FLINT): a multicentre, randomised, placebo-controlled trial. Lancet 385 (2015), 956–965, 10.1016/S0140-6736(14)61933-4.
133. [133] Quercia, I., Dutia, R., Kotler, D.P., Belsley, S., Laferrère, B., Gastrointestinal changes after bariatric surgery. Diabetes Metab 40 (2014), 87–94, 10.1016/j.diabet.2013.11.003.
134. [134] Troke, R.C., Tan, T.M., Bloom, S.R., The future role of gut hormones in the treatment of obesity. Ther Adv Chronic Dis 5 (2014), 4–14, 10.1177/2040622313506730.