Advertisement

Digestive Diseases and Sciences

, Volume 61, Issue 2, pp 371–380 | Cite as

Current Concepts in Diabetes Mellitus and Chronic Liver Disease: Clinical Outcomes, Hepatitis C Virus Association, and Therapy

  • Diego García-CompeánEmail author
  • José Alberto González-González
  • Fernando Javier Lavalle-González
  • Emmanuel Irineo González-Moreno
  • Jesús Zacarías Villarreal-Pérez
  • Héctor J. Maldonado-Garza
Review

Abstract

Hereditary type 2 diabetes mellitus is a risk factor for chronic liver disease, and ~30 % of patients with liver cirrhosis develop diabetes. Diabetes mellitus has been associated with cirrhotic and non-cirrhotic hepatitis C virus liver infection, can aggravate the course the liver infection, and can induce a lower sustained response to antiviral treatment. Evidences that HCV may induce metabolic and autoimmune disturbances leading to hypobetalipoproteinemia, steatosis, insulin resistance, impaired glucose tolerance, thyroid disease, and gonadal dysfunction have been found. Prospective studies have demonstrated that diabetes increases the risk of liver complications and death in patients with cirrhosis. However, treatment of diabetes in these patients is complex, as antidiabetic drugs can promote hypoglycemia and lactic acidosis. There have been few therapeutic studies evaluating antidiabetic treatments in patients with liver cirrhosis published to date; thus, the optimal treatment for diabetes and the impact of treatment on morbidity and mortality are not clearly known. As numbers of patients with chronic liver disease and diabetes mellitus are increasing, largely because of the global epidemics of obesity and nonalcoholic fatty liver disease, evaluation of treatment options is becoming more important. This review discusses new concepts on hepatogenous diabetes, the diabetes mellitus–hepatitis C virus association, and clinical implications of diabetes mellitus in patients with chronic liver disease. In addition, the effectiveness and safety of old and new antidiabetic drugs, including incretin-based therapies, will be described.

Keywords

Chronic C hepatitis Diabetes mellitus Hepatogenous diabetes Liver cirrhosis Therapy 

Notes

Acknowledgments

This study was supported by Gastroenterology and Endocrinology Services of the University Hospital, Universidad Autónoma de Nuevo León, Monterrey, México.

Compliance with ethical standards

Conflict of interest

All authors who have participated in preparation of this manuscript declare not to have conflict of interests.

References

  1. 1.
    El-Serag HB, Tran T, Everhart JE. Diabetes increases the risk of chronic liver disease and hepatocellular carcinoma. Gastroenterology. 2004;126:460–468.PubMedCrossRefGoogle Scholar
  2. 2.
    Tolman KG, Fonseca V, Dalpiaz A, Tan MH. Spectrum of liver disease in type 2 diabetes and management of patients with diabetes and liver disease. Diabetes Care. 2007;30:734–743.PubMedCrossRefGoogle Scholar
  3. 3.
    El-Serag HB, Everhart JE. Diabetes increases the risk of acute hepatic failure. Gastroenterology. 2002;122:1822–1828.PubMedCrossRefGoogle Scholar
  4. 4.
    Garcia-Compean D, Jaquez-Quintana JO, Gonzalez-Gonzalez JA, Maldonado-Garza H. Liver cirrhosis and diabetes: Risk factors, pathophysiology, clinical implications and management. World J Gastroenterol. 2009;15:280–288.PubMedCentralPubMedCrossRefGoogle Scholar
  5. 5.
    Hickman IJ, Macdonald GA. Impact of diabetes on the severity of liver disease. Am J Med. 2007;120:829–834.PubMedCrossRefGoogle Scholar
  6. 6.
    Garcia-Compean D, Jaquez-Quintana JO, Lavalle-Gonzalez FJ, et al. The prevalence and clinical characteristics of glucose metabolism disorders in patients with liver cirrhosis: A prospective study. Ann Hepatol. 2012;11:240–248.PubMedGoogle Scholar
  7. 7.
    Tappy L, Minehira K. New data and new concepts on the role of the liver in glucose homeostasis. Curr Opin Clin Nutr Metab Care. 2001;4:273–277.PubMedCrossRefGoogle Scholar
  8. 8.
    Petrides AS, Stanley T, Matthews DE, Vogt C, Bush AJ, Lambeth H. Insulin resistance in cirrhosis: Prolonged reduction of hyperinsulinemia normalizes insulin sensitivity. Hepatology. 1998;28:141–149.PubMedCrossRefGoogle Scholar
  9. 9.
    Petrides AS, Groop LC, Riely CA, DeFronzo RA. Effect of physiologic hyperinsulinemia on glucose and lipid metabolism in cirrhosis. J Clin Investig. 1991;88:561–570.PubMedCentralPubMedCrossRefGoogle Scholar
  10. 10.
    Petrides AS, Vogt C, Schulze-berge D, Matthews D, Strohmeyer G. Pathogenesis of glucose intolerance and diabetes mellitus in cirrhosis. Hepatology. 1994;19:616–627.PubMedCrossRefGoogle Scholar
  11. 11.
    American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2012;35:S64–S71.PubMedCentralCrossRefGoogle Scholar
  12. 12.
    Gundling F, Schepp W, Schumm-Draeger PM. Hepatogenous diabetes in cirrhosis: Academic sport or a neglected disease? Exp Clin Endocrinol Diabetes. 2012;120:469–471.PubMedCrossRefGoogle Scholar
  13. 13.
    Buzzelli G, Chiarantini E, Cotrozzi G, et al. Estimate of prevalence of glucose intolerance in chronic liver disease. Degree of agreement among some diagnostic criteria. Liver. 1988;8:354–359.PubMedCrossRefGoogle Scholar
  14. 14.
    Niederau C, Fischer R, Pürschel A, Stremmel W, Häussinger D, Strohmeyer G. Long-term survival in patients with hereditary hemochromatosis. Gastroenterology. 1996;110:1107–1119.PubMedCrossRefGoogle Scholar
  15. 15.
    Del Vecchio Blanco C, Gentile S, Marmo R, Carbone L, Coltorti M. Alterations of glucose metabolism in chronic liver disease. Diabetes Res Clin Pract. 1990;8:29–36.PubMedCrossRefGoogle Scholar
  16. 16.
    Matsumoto N, Arase Y, Seko Y, et al. Prevalence and predictive factors of diabetes in hepatitis virus positive liver cirrhosis with fasting plasma glucose level of <126 mg/dL. Hepatol Res. 2012;42:558–563.PubMedCrossRefGoogle Scholar
  17. 17.
    Thuluvath PJ, John PR. Association between hepatitis C, diabetes mellitus, and race: A case–control study. Am J Gastroenterol. 2003;98:438–441.PubMedGoogle Scholar
  18. 18.
    Montenegro L, De Michina A, Misciagna G, Guerra V, Di Leo A. Virus C hepatitis and type 2 diabetes: A cohort study in southern Italy. Am J Gastroenterol. 2013;108:1108–1111.PubMedCrossRefGoogle Scholar
  19. 19.
    Mehta SH, Brancati FL, Sulkowski MS, Strathdee SA, Szklo M, Thomas DL. Prevalence of type 2 diabetes mellitus among persons with hepatitis C virus infection in the United States. Ann Intern Med. 2000;133:592–599.PubMedCrossRefGoogle Scholar
  20. 20.
    Romero-Gómez M. Insulin resistance and hepatitis C. World J Gastroenterol. 2006;12:7075–7080.PubMedCentralPubMedGoogle Scholar
  21. 21.
    Antonelli A, Ferri C, Fallahi P, et al. Hepatitis C virus infection. Evidence for an association with type 2 diabetes. Diabetes Care. 2005;28:2548–2550.PubMedCrossRefGoogle Scholar
  22. 22.
    Lecube A, Hernandez C, Genesca J, Esteban JI, Jardi R, Simo R. High prevalence of glucose abnormalities in patients with hepatitis C virus infection: A multivariate analysis considering the liver injury. Diabetes Care. 2004;27:1171–1175.PubMedCrossRefGoogle Scholar
  23. 23.
    Serfaty L, Andreani T, Giral P, Carbonell N, Chazouilleres O, Poupon R. Hepatitis C virus induced hypobetalipoproteinemia: A possible mechanism for steatosis in chronic hepatitis C. J Hepatol. 2001;34:428–434.PubMedCrossRefGoogle Scholar
  24. 24.
    Anty R, Gelsi E, Giudicelli J, et al. Glucose intolerance and hypoadiponectinemia are already present in lean patients with chronic hepatitis C infected with genotype non-3 viruses. Eur J Gastroenterol Hepatol. 2007;19:671–677.PubMedCrossRefGoogle Scholar
  25. 25.
    Custro N, Carroccio A, Ganci A, et al. Glicemic homeostasis in chronic viral hepatitis and liver cirrhosis. Diabetes Metab. 2001;27:476–481.PubMedGoogle Scholar
  26. 26.
    Lecube A, Hernández C, Genescà J, Simó R. Proinflammatory cytokines, insulin resistance, and insulin secretion in chronic hepatitis C patients: A case–control study. Diabetes Care. 2006;29:1096–1101.PubMedCrossRefGoogle Scholar
  27. 27.
    Moucari R, Asselah T, Cazals-Hatem D, et al. Insulin resistance in chronic hepatitis C: Association with genotypes 1 and 4, serum HCV RNA level, and liver fibrosis. Gastroenterology. 2008;134:416–423.PubMedCrossRefGoogle Scholar
  28. 28.
    Hui JM, Sud A, Farrell GC, et al. Insulin resistance is associated with chronic hepatitis C virus infection and fibrosis progression. Gastroenterology. 2003;125:1695–1704.PubMedCrossRefGoogle Scholar
  29. 29.
    Antonelli A, Ferri C, Ferrari SM, Colaci M, Sansonno D, Fallahi P. Endocrine manifestations of hepatitis C virus infection. Nat Clin Pract Endocrinol Metab. 2009;5:26–34.PubMedCrossRefGoogle Scholar
  30. 30.
    Antonelli A, Ferri C, Fallahi P, et al. Type 2 diabetes in hepatitis C-related mixed cryoglobulinaemia patients. Rheumatology (Oxford). 2004;43:238–240.CrossRefGoogle Scholar
  31. 31.
    Masini M, Campani D, Boggi U, et al. Hepatitis C virus infection and human pancreatic β-cell dysfunction. Diabetes Care. 2005;28:940–941.PubMedCrossRefGoogle Scholar
  32. 32.
    Elkrief L, Chouinard P, Bendersky N, et al. Diabetes mellitus is an independent prognostic factor for major liver-related outcomes in patients with cirrhosis and chronic hepatitis C. Hepatology. 2014;60:823–831.PubMedCrossRefGoogle Scholar
  33. 33.
    Romero-Gomez M, Del Mar Viloria M, Andrade RJ, et al. Insulin resistance impairs sustained response rate to peginterferon plus ribavirin in chronic hepatitis C patients. Gastroenterology. 2005;128:636–641.PubMedCrossRefGoogle Scholar
  34. 34.
    Khattab M, Emad M, Abdelaleem A, et al. Pioglitazone improves virological response to peginterferon alpha-2b/ribavirin combination therapy in hepatitis C genotype 4 patients with insulin resistance. Liver Int. 2010;3:447–454.CrossRefGoogle Scholar
  35. 35.
    Harrison SA, Hamzeh FM, Han J, Pandya PK, Sheikh MY, Vierling JM. Chronic hepatitis C genotype 1 patients with insulin resistance treated with pioglitazone and peginterferon alpha-2a plus ribavirin. Hepatology. 2012;56:464–473.PubMedCrossRefGoogle Scholar
  36. 36.
    Romero-Gómez M, Diago M, Andrade RJ, et al. Treatment of insulin resistance with metformin in naïve genotype 1 chronic hepatitis C patients receiving peginterferon alfa-2a plus ribavirin. Hepatology. 2009;50:1702–1708.PubMedCrossRefGoogle Scholar
  37. 37.
    Sanyal AJ, Chand N, Comar K, Mirshahi F. Hyperinsulinemia blocks the inhibition of hepatitis C virus (HCV) replication by interferon: A potential mechanism for failure of interferon therapy in subjects with HCV and nonalcoholic liver disease (Abstract). Hepatology. 2004;40:179A.CrossRefGoogle Scholar
  38. 38.
    Simó R, Lecube A, Genescà J, Esteban JI, Hernández C. Sustained virological response correlates with reduction in the incidence of glucose abnormalities in patients with chronic hepatitis C virus infection. Diabetes Care. 2006;29:2462–2466.PubMedCrossRefGoogle Scholar
  39. 39.
    Giordanino C, Bugianesi E, Smedile A, et al. Incidence of type 2 diabetes mellitus and glucose abnormalities in patients with chronic hepatitis C infection by response to treatment: Results of a cohort study. Am J Gastroenterol. 2008;103:2481–2487.PubMedCrossRefGoogle Scholar
  40. 40.
    Ruhl CE, Menke A, Cowie CC, Everhart JE. The relationship of hepatitis C virus infection with diabetes in the United States population. Hepatology. 2014;60:1139–1149.PubMedCentralPubMedCrossRefGoogle Scholar
  41. 41.
    Cusi K. The relationship between hepatitis C Virus infection and diabetes: Time for a Divorce? Hepatology. 2014;60:1121–1123.PubMedCrossRefGoogle Scholar
  42. 42.
    Trombetta M, Spiazzi G, Zoppini G, Muggeo M. Review article: Type 2 diabetes and chronic liver disease in the Verona diabetes study. Aliment Pharmacol Ther. 2005;22:24–27.PubMedCrossRefGoogle Scholar
  43. 43.
    Harrison SA. Liver disease in patients with diabetes mellitus. J Clin Gastroenterol. 2006;40:68–76.PubMedCrossRefGoogle Scholar
  44. 44.
    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. 1999;22:756–761.PubMedCrossRefGoogle Scholar
  45. 45.
    Bianchi G, Marchesini G, Zoli M, Bugianesi E, Fabbri A, Pisi E. Prognostic significance of diabetes in patients with cirrhosis. Hepatology. 1994;20:119–125.PubMedGoogle Scholar
  46. 46.
    Quintana JO, García-Compean D, González JA, et al. The impact of diabetes mellitus in mortality of patients with compensated liver cirrhosis—A prospective study. Ann Hepatol. 2011;10:56–62.PubMedGoogle Scholar
  47. 47.
    Holstein A, Hinze S, Thiessen E, Plaschke A, Egberts EH. Clinical implications of hepatogenous diabetes in liver cirrhosis. J Gastroenterol Hepatol. 2002;17:677–681.PubMedCrossRefGoogle Scholar
  48. 48.
    Nishida T, Tsuji S, Tsujii M, et al. Oral glucose tolerance test predicts prognosis of patients with liver cirrhosis. Am J Gastroenterol. 2006;101:70–75.PubMedCrossRefGoogle Scholar
  49. 49.
    García-Compeán D, Jáquez- Quintana JO, Lavalle-González FJ, et al. Subclinical abnormal glucose tolerance is a predictor of death in liver cirrhosis. World J Gastroenterol. 2014;20:7011–7018.PubMedCentralPubMedCrossRefGoogle Scholar
  50. 50.
    Hagel S, Bruns T, Herrmann A, Stallmach A, Schmidt C. Abnormal glucose tolerance: A predictor of 30-day mortality in patients with decompensated liver cirrhosis. Z Gastroenterol. 2011;49:331–334.PubMedCrossRefGoogle Scholar
  51. 51.
    Butt Z, Jadoon NA, Salaria ON, et al. Diabetes mellitus and decompensated cirrhosis: Risk of hepatic encephalopathy in different age groups. J Diabetes. 2013;5:449–455.PubMedCrossRefGoogle Scholar
  52. 52.
    Jeon HK, Kim MY, Baik SK, et al. Hepatogenous diabetes in cirrhosis is related to portal pressure and variceal hemorrhage. Dig Dis Sci. 2013;58:3335–3341.PubMedCrossRefGoogle Scholar
  53. 53.
    Huang YW, Wang TC, Lin SC, et al. Increased risk of cirrhosis and its decompensation in chronic hepatitis B patients with newly diagnosed diabetes: A nationwide cohort study. Clin Infect Dis. 2013;57:1695–1702.PubMedCrossRefGoogle Scholar
  54. 54.
    Hsiang JC, Gane EJ, Bai WW, Gerred SJ. Type 2 diabetes: A risk factor for liver mortality and complications in hepatitis B cirrhosis patients. J Gastroenterol Hepatol. 2015;30:591–599.PubMedCrossRefGoogle Scholar
  55. 55.
    Petta S, Torres D, Fazio G, et al. Carotid atherosclerosis and chronic hepatitis C: A prospective study of risk associations. Hepatology. 2012;55:1317–1323.PubMedCrossRefGoogle Scholar
  56. 56.
    Adinolfi LE, Restivo L, Zampino R, et al. Chronic HCV infection is a risk of atherosclerosis. Role of HCV and HCV related steatosis. Atherosclerosis. 2012;221:496–502.PubMedCrossRefGoogle Scholar
  57. 57.
    Amarapurkar DN, Patel ND, Kamani PM. Impact of diabetes mellitus on outcome of HCC. Ann Hepatol. 2008;7:148–151.PubMedGoogle Scholar
  58. 58.
    Marchesini G, Ronchi M, Forlani G, et al. Cardiovascular disease in cirrhosis—A point-prevalence study in relation to glucose tolerance. Am J Gastroenterol. 1999;94:655–662.PubMedGoogle Scholar
  59. 59.
    An J, Shim JH, Kim SO, et al. Prevalence and prediction of coronary artery disease in patients with liver cirrhosis: A registry-based matched case-control study. Circulation. 2014;130:1353–1362.PubMedCrossRefGoogle Scholar
  60. 60.
    Crespo J, Cayón A, Fernández-Gil P, et al. Gene expression of tumor necrosis factor alpha and TNF-receptors, p55 and p75, in nonalcoholic steatohepatitis patients. Hepatology. 2001;34:1158–1163.PubMedCrossRefGoogle Scholar
  61. 61.
    Anty R, Lemoine M. Liver fibrogenesis and metabolic factors. Clin Res Hepatol Gastroenterol. 2011;35:S10–S20.PubMedCrossRefGoogle Scholar
  62. 62.
    Bertolani C, Marra F. The role of adipokines in liver fibrosis. Pathophysiology. 2008;15:91–101.PubMedCrossRefGoogle Scholar
  63. 63.
    García-Compeán D, Jáquez-Quintana JO, Lavalle-González FJ, González-González JA, Maldonado-Garza HJ, Villarreal-Pérez JZ. Plasma cytokine levels imbalance in cirrhotic patients with impaired glucose tolerance and diabetes mellitus. A prospective study. Ann Hepatol. 2014;13:403–410.PubMedGoogle Scholar
  64. 64.
    Cheruvattath R, Balan V. Infections in patients with end-stage liver disease. J Clin Gastroenterol. 2007;41:403–411.PubMedCrossRefGoogle Scholar
  65. 65.
    Sorrentino P, Tarantino G, Conca P, Perrella A, Perella O. Clinical presentation and prevalence of spontaneous bacterial peritonitis in patients with cryptogenic cirrhosis and features of metabolic syndrome. Can J Gastroenterol. 2004;18:381–386.PubMedGoogle Scholar
  66. 66.
    Ahmadieh H, Samir ST. Liver disease and diabetes: Association, pathophysiology and management. Diabetes Res Clin Pract. 2014;104:53–62.PubMedCrossRefGoogle Scholar
  67. 67.
    Gundling F, Seidl H, Strassen I, et al. Clinical manifestations and treatment options in patients with cirrhosis and diabetes mellitus. Digestion. 2013;87:75–84.PubMedCrossRefGoogle Scholar
  68. 68.
    Kwon SY, Kim SS, Kwon OS, et al. Prognostic significance of glycaemic control in patients with HBV and HCV-related cirrhosis and diabetes mellitus. Diabet Med. 2005;22:1530–1535.PubMedCrossRefGoogle Scholar
  69. 69.
    Gentile S, Turco S, Guarino G, et al. Effect of treatment with acarbose and insulin in patients with non-insulin-dependent diabetes mellitus associated with non-alcoholic liver cirrhosis. Diabetes Obes Metab. 2001;3:33–40.PubMedCrossRefGoogle Scholar
  70. 70.
    Nkontchou G, Cosson E, Aout M, et al. Impact of metformin on the prognosis of cirrhosis induced by viral hepatitis C in diabetic patients. J Clin Endocrinol Metab. 2011;96:2601–2608.PubMedCrossRefGoogle Scholar
  71. 71.
    Zhang X, Harmsen WS, Mettler TA, et al. Continuation of metformin use after a diagnosis of cirrhosis significantly improves survival of patients with diabetes. Hepatology. 2014;60:2008–2016.PubMedCentralPubMedCrossRefGoogle Scholar
  72. 72.
    Scheen AJ. Pharmacokinetic and toxicological considerations for the treatment of diabetes in patients with liver disease. Expert Opin Drug Metab Toxicol. 2014;10:839–857.PubMedCrossRefGoogle Scholar
  73. 73.
    Marks V, Teale JD. Drug-induced hypoglycemia. Endocrinol Metab Clin N Am. 1999;28:555–577.CrossRefGoogle Scholar
  74. 74.
    Loomba R, Lutchman G, Kleiner DE, et al. Clinical trial: Pilot study of metformin for the treatment of non-alcoholic steatohepatitis. Aliment Pharmacol Ther. 2009;29:172–182.PubMedCentralPubMedCrossRefGoogle Scholar
  75. 75.
    Bugianesi E, Gentilcore E, Manini R, et al. A randomized controlled trial of metformin versus vitamin E or prescriptive diet in nonalcoholic fatty liver disease. Am J Gastroenterol. 2005;100:1082–1090.PubMedCrossRefGoogle Scholar
  76. 76.
    de Oliveira CP, Stefano JT, de Siqueira ER, et al. Combination of N-acetylcysteine and metformin improves histological steatosis and fibrosis in patients with non-alcoholic steatohepatitis. Hepatol Res. 2008;38:159–165.PubMedGoogle Scholar
  77. 77.
    Chan NN, Brain HP, Feher MD. Metformin-associated lactic acidosis: A rare or very rare clinical entity? Diabet Med. 1999;16:273–281.PubMedCrossRefGoogle Scholar
  78. 78.
    Edwards CM, Barton MA, Snook J, David M, Mak VH, Chowdhury TA. Metformin-associated lactic acidosis in a patient with liver disease. QJM. 2003;96:315–316.PubMedCrossRefGoogle Scholar
  79. 79.
    Donadon V, Balbi M, Mas MD, Casarin P, Zanette G. Metformin and reduced risk of hepatocellular carcinoma in diabetic patients with chronic liver disease. Liver Int. 2010;30:750–758.PubMedCrossRefGoogle Scholar
  80. 80.
    Inkster B, Zammitt NN, Frier BM. Drug-induced hypoglycaemia in type 2 diabetes. Expert Opin Drug Saf. 2012;11:597–614.PubMedCrossRefGoogle Scholar
  81. 81.
    Chitturi S, Le V, Kench J, Loh C, George J. Gliclazide-induced acute hepatitis with hypersensitivity features. Dig Dis Sci. 2002;47:1107–1110.PubMedCrossRefGoogle Scholar
  82. 82.
    Choudhury S, Hirschberg Y, Filipek R, Lasseter K, McLeod JF. Single-dose pharmacokinetics of nateglinide in subjects with hepatic cirrhosis. J Clin Pharmacol. 2000;40:634–640.PubMedCrossRefGoogle Scholar
  83. 83.
    Scott LJ. Repaglinide: A review of its use in type 2 diabetes mellitus. Drugs. 2012;72:249–272.PubMedCrossRefGoogle Scholar
  84. 84.
    Hatorp V. Clinical pharmacokinetics and pharmacodynamics of repaglinide. Clin Pharmacokinet. 2002;41:471–483.PubMedCrossRefGoogle Scholar
  85. 85.
    Rosenson RS, Reasner CA. Therapeutic approaches in the prevention of cardiovascular disease in metabolic syndrome and in patients with type 2 diabetes. Curr Opin Cardiol. 2004;19:480–487.PubMedCrossRefGoogle Scholar
  86. 86.
    Lebovitz HE, Kreider M, Freed MI. Evaluation of liver function in type 2 diabetic patients during clinical trials: evidence that rosiglitazone does not cause hepatic dysfunction. Diabetes Care. 2002;25:815–821.PubMedCrossRefGoogle Scholar
  87. 87.
    Ratziu V, Giral P, Jacqueminet S, LIDO Study Group, et al. Rosiglitazone for nonalcoholic steatohepatitis: One-year results of the randomized placebo-controlled Fatty Liver Improvement with Rosiglitazone Therapy (FLIRT) Trial. Gastroenterology. 2008;135:100–110.PubMedCrossRefGoogle Scholar
  88. 88.
    Neuschwander-Tetri BA, Brunt EM, Wehmeier KR, Sponseller CA, Hampton K, Bacon BR. Interim results of a pilot study demonstrating the early effects of the PPAR-gamma ligand rosiglitazone on insulin sensitivity, aminotransferases, hepatic steatosis and body weight in patients with non-alcoholic steatohepatitis. J Hepatol. 2003;38:434–440.PubMedCrossRefGoogle Scholar
  89. 89.
    Sanyal AJ, Mofrad PS, Contos MJ, et al. A pilot study of vitamin E versus vitamin E and pioglitazone for the treatment of nonalcoholic steatohepatitis. Clin Gastroenterol Hepatol. 2004;2:1107–1115.PubMedCrossRefGoogle Scholar
  90. 90.
    Jespersen MJ, Knop FK, Christensen M. GLP-1 agonists for type 2 diabetes:pharmacokinetic and toxicological considerations. Expert Opin Drug Metab Toxicol. 2013;9:17–29.PubMedCrossRefGoogle Scholar
  91. 91.
    Ohki T, Isogawa A, Iwamoto M, et al. The effectiveness of liraglutide in nonalcoholic fatty liver disease patients with type 2 diabetes mellitus compared to sitagliptin and pioglitazone. Sci World J. 2012;2012:496453.CrossRefGoogle Scholar
  92. 92.
    Scheen AJ. A review of gliptins in 2011. Expert Opin Pharmacother. 2012;13:81–99.PubMedCrossRefGoogle Scholar
  93. 93.
    Graefe-Mody U, Rose P, Retlich S, et al. Pharmacokinetics of linagliptin in subjects with hepatic impairment. Br J Clin Pharmacol. 2012;74:75–85.PubMedCentralPubMedCrossRefGoogle Scholar
  94. 94.
    Scheen AJ. Pharmacokinetics in patients with chronic liver disease and hepatic safety of incretin-based therapies for the management of type 2 diabetes mellitus. Clin Pharmacokinet. 2014;53:773–785.PubMedCrossRefGoogle Scholar
  95. 95.
    Golightly LK, Drayna CC, McDermott MT. Comparative clinical pharmacokinetics of dipeptidyl peptidase-4 inhibitors. Clin Pharmacokinet. 2012;51:501–514.PubMedCrossRefGoogle Scholar
  96. 96.
    Itou M, Kawaguchi T, Taniguchi E, Sata M. Dipeptidyl peptidase-4: A key player in chronic liver disease. World J Gastroenterol. 2013;19:2298–2306.PubMedCentralPubMedCrossRefGoogle Scholar
  97. 97.
    Letiexhe MR, Scheen AJ, Gerard PL, et al. Insulin secretion, clearance, and action on glucose metabolism in cirrhotic patients. J Clin Endocrinol Metab. 1993;77:1263–1268.PubMedGoogle Scholar
  98. 98.
    Petrides AS. Hepatogenic diabetes: Pathophysiology, therapeutic options and prognosis. Z Gastroenterol. 1999;16:15–21.Google Scholar
  99. 99.
    Holmes G, Galitz L, Hu P, Lyness W. Pharmacokinetics of insulin aspart in obesity, renal impairment, or hepatic impairment. Br J Clin Pharmacol. 2005;60:469–476.PubMedCentralPubMedCrossRefGoogle Scholar
  100. 100.
    Kupčová V, Arold G, Roepstorff C, Højbjerre M, Klim S, Haahr H. Insulin degludec: Pharmacokinetic properties in subjects with hepatic impairment. Clin Drug Investig. 2014;34:127–133.PubMedCentralPubMedCrossRefGoogle Scholar
  101. 101.
    Merli M, Leonetti F, Riggio O, et al. Glucose intolerance and insulin resistance in cirrhosis are normalized alter liver transplantation. Hepatology. 1999;30:649–654.PubMedCrossRefGoogle Scholar
  102. 102.
    Blanco JJ, Herrero JI, Quiroga J, et al. Liver transplantation in cirrhotic patients with diabetes mellitus: Midterm results, survival, and adverse events. Liver Transpl. 2001;7:226–233.PubMedCrossRefGoogle Scholar
  103. 103.
    Perseghin G, Mazzaferro V, Sereni LP, et al. Contribution of reduced insulin sensitivity and secretion to the pathogenesis of hepatogenous diabetes: Effect of liver transplantation. Hepatology. 2000;31:694–703.PubMedCrossRefGoogle Scholar
  104. 104.
    Younossi ZM, Stepanova M, Saab S, et al. The impact of type 2 diabetes and obesity on the long-term outcomes of more than 85,000 liver transplant recipients in the US. Aliment Pharmacol Ther. 2014;40:686–694.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Diego García-Compeán
    • 1
    • 3
    Email author
  • José Alberto González-González
    • 1
  • Fernando Javier Lavalle-González
    • 2
  • Emmanuel Irineo González-Moreno
    • 1
  • Jesús Zacarías Villarreal-Pérez
    • 2
  • Héctor J. Maldonado-Garza
    • 1
  1. 1.Gastroenterology Service and Department of Internal Medicine, University Hospital “Dr. José E. González” and Medical SchoolUniversidad Autónoma de Nuevo LeónMonterreyMexico
  2. 2.Endocrinology Service and Department of Internal Medicine, University Hospital “Dr. José E. González” and Medical SchoolUniversidad Autónoma de Nuevo LeónMonterreyMexico
  3. 3.Gastroenterology Service and Department of Internal Medicine, University Hospital “Dr. José E. González” and Faculty of MedicineUniversidad Autónoma de Nuevo LeónMonterreyMexico

Personalised recommendations