J Korean Diabetes.  2016 Sep;17(3):159-163. 10.4093/jkd.2016.17.3.159.

Management of Diabetes in Liver Cirrhosis

• Kim JH

• KMID: 2354279
• DOI: http://doi.org/10.4093/jkd.2016.17.3.159

Abstract

Diabetes mellitus (DM) is common in patients with liver cirrhosis, indicating a bidirectional relationship between DM and liver cirrhosis. Type 2 DM is a risk factor for development and progression of chronic liver disease including liver cirrhosis, and DM may occur as a complication of liver cirrhosis. Hyperglycemia and hyperinsulinemia have profibrogenic properties on hepatic stellate cells, and contribute to liver damage by promoting inflammation and fibrosis through an increase in mitochodrial oxidative stress mediated by adipokines. The presence of DM in patients with liver cirrhosis is not only related to the poor survival rate but also associated with major complications of cirrhosis. This suggests that optimal management of DM could be beneficial in patients with liver cirrhosis. However, the management of DM in patients with liver cirrhosis is complex because of impaired liver function and of the potential hepatotoxicity of oral hypoglycemic agents. We review the clinical implications and the therapeutic management of DM in patients with liver cirrhosis.

Keyword

Diabetes mellitus; Glucose control; Liver cirrhosis

MeSH Terms

Adipokines
Diabetes Mellitus
Fibrosis
Hepatic Stellate Cells
Humans
Hyperglycemia
Hyperinsulinism
Hypoglycemic Agents
Inflammation
Liver Cirrhosis*
Liver Diseases
Liver*
Oxidative Stress
Risk Factors
Survival Rate
Adipokines
Hypoglycemic Agents

Reference

References

1. García-Compeán D, Jáquez-Quintana JO, Lavalle-González FJ, Reyes-Cabello E, González-González JA, Muñoz-Espinosa LE, Vázquez-Elizondo G, Villarreal-Pérez JZ, Maldonado-Garza HJ. The prevalence and clinical characteristics of glucose metabolism disorders in patients with liver cirrhosis. A prospective study. Ann Hepatol. 2012; 11:240–8.

2. García-Compean D, Jaquez-Quintana JO, Maldonado-Garza H. Hepatogenous diabetes. Current views of an ancient problem. Ann Hepatol. 2009; 8:13–20.

3. Harrison SA. Liver disease in patients with diabetes mellitus. J Clin Gastroenterol. 2006; 40:68–76.

4. Butt Z, Jadoon NA, Salaria ON, Mushtaq K, Riaz IB, Shahzad A, Hashmi AM, Sarwar S. Diabetes mellitus and decompensated cirrhosis: risk of hepatic encephalopathy in different age groups. J Diabetes. 2013; 5:449–55.

5. Bertolani C, Marra F. The role of adipokines in liver fibrosis. Pathophysiology. 2008; 15:91–101.

6. Paradis V, Perlemuter G, Bonvoust F, Dargere D, Parfait B, Vidaud M, Conti M, Huet S, Ba N, Buffet C, Bedossa P. High glucose and hyperinsulinemia stimulate connective tissue growth factor expression: a potential mechanism involved in progression to fibrosis in nonalcoholic steatohepatitis. Hepatology. 2001; 34:738–44.

7. Fehrenbach H, Weiskirchen R, Kasper M, Gressner AM. Up-regulated expression of the receptor for advanced glycation end products in cultured rat hepatic stellate cells during transdifferentiation to myofibroblasts. Hepatology. 2001; 34:943–52.

8. Arvaniti V, D'Amico G, Fede G, Manousou P, Tsochatzis E, Pleguezuelo M, Burroughs AK. Infections in patients with cirrhosis increase mortality four-fold and should be used in determining prognosis. Gastroenterology. 2010; 139:1246–56. 1256.e1–5.

9. Sigal SH, Stanca CM, Kontorinis N, Bodian C, Ryan E. Diabetes mellitus is associated with hepatic encephalopathy in patients with HCV cirrhosis. Am J Gastroenterol. 2006; 101:1490–6.

10. 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; 30:734–43.

11. Chan NN, Brain HP, Feher MD. Metformin-associated lactic acidosis: a rare or very rare clinical entity? Diabet Med. 1999; 16:273–81.

12. Nkontchou G, Cosson E, Aout M, Mahmoudi A, Bourcier V, Charif I, Ganne-Carrie N, Grando-Lemaire V, Vicaut E, Trinchet JC, Beaugrand M. Impact of metformin on the prognosis of cirrhosis induced by viral hepatitis C in diabetic patients. J Clin Endocrinol Metab. 2011; 96:2601–8.

13. Marks V, Teale JD. Drug-induced hypoglycemia. Endocrinol Metab Clin North Am. 1999; 28:555–77.

14. Ampuero J, Ranchal I, Nuñez D, Díaz-Herrero Mdel M, Maraver M, del Campo JA, Rojas Á, Camacho I, Figueruela B, Bautista JD, Romero-Gómez M. Metformin inhibits glutaminase activity and protects against hepatic encephalopathy. PLoS One. 2012; 7:e49279.

15. Gentile S, Turco S, Guarino G, Oliviero B, Annunziata S, Cozzolino D, Sasso FC, Turco A, Salvatore T, Torella R. Effect of treatment with acarbose and insulin in patients with non-insulindependent diabetes mellitus associated with nonalcoholic liver cirrhosis. Diabetes Obes Metab. 2001; 3:33–40.

16. Jaakkola T, Laitila J, Neuvonen PJ, Backman JT. Pioglitazone is metabolised by CYP2C8 and CYP3A4 in vitro: potential for interactions with CYP2C8 inhibitors. Basic Clin Pharmacol Toxicol. 2006; 99:44–51.

17. Chitturi S, Le V, Kench J, Loh C, George J. Gliclazide-induced acute hepatitis with hypersensitivity features. Dig Dis Sci. 2002; 47:1107–10.

18. Hatorp V. Clinical pharmacokinetics and pharmacodynamics of repaglinide. Clin Pharmacokinet. 2002; 41:471–83.

19. Giorda CB, Nada E, Tartaglino B. Pharmacokinetics, safety, and efficacy of DPP-4 inhibitors and GLP-1 receptor agonists in patients with type 2 diabetes mellitus and renal or hepatic impairment. A systematic review of the literature. Endocrine. 2014; 46:406–19.

20. Golightly LK, Drayna CC, McDermott MT. Comparative clinical pharmacokinetics of dipeptidyl peptidase-4 inhibitors. Clin Pharmacokinet. 2012; 51:501–14.

21. Kasichayanula S, Liu X, Zhang W, Pfister M, LaCreta FP, Boulton DW. Influence of hepatic impairment on the pharmacokinetics and safety profile of dapagliflozin: an open-label, parallel-group, single-dose study. Clin Ther. 2011; 33:1798–808.

22. Nigro SC, Riche DM, Pheng M, Baker WL. Canagliflozin, a novel SGLT2 inhibitor for treatment of type 2 diabetes. Ann Pharmacother. 2013; 47:1301–11.

23. Macha S, Rose P, Mattheus M, Cinca R, Pinnetti S, Broedl UC, Woerle HJ. Pharmacokinetics, safety and tolerability of empagliflozin, a sodium glucose cotransporter 2 inhibitor, in patients with hepatic impairment. Diabetes Obes Metab. 2014; 16:118–23.

24. Holmes G, Galitz L, Hu P, Lyness W. Pharmacokinetics of insulin aspart in obesity, renal impairment, or hepatic impairment. Br J Clin Pharmacol. 2005; 60:469–76.