Gastroenterologie
a hepatologie

Hepatogenous diabetes in liver transplant candidates: prevalence, risk factors and posttransplant outcome – prospective study

Irena Míková¹, Denisa Kyselová¹, Kateřina Dvořáková¹, Monika Dezortová ^{Orcid.org  2}, Milan Hájek ^{Orcid.org  2}, Věra Lánská³, Julius Špičák ^{Orcid.org  1}, Pavel Trunečka¹

+ Affiliation
¹ Klinika hepatogastroenterologie, Transplantcentrum, IKEM, Praha
² Pracoviště radiodiagnostiky a intervenční radiologie, Komplement, IKEM, Praha
³ Oddělení datových analýz, statistik a umělé inteligence OI, IKEM, Praha

Summary

Introduction: Diabetes mellitus (DM) associated with liver cirrhosis (hepatogenous DM) has several differences from classical DM type 2 (T2DM), data about its prevalence, risk factors and outcome after liver transplantation (LT) are limited. The aim of this study was to evaluate the prevalence, risk factors and posttransplant outcome of DM diagnosed during the pretransplant investigation in a prospectively followed cohort of LT candidates. Methods: The study included 122 adult patients who were listed for LT in the period from 5/2015 to 4/2017. Presence of DM was evaluated by standard criteria including oral glucose tolerance test (OGTT). Results: DM was present in 54 patients (44.3%) pretransplant, of whom 26 patients (21.3%) had long-term history of DM before they were listed for LT (classical T2DM), and in other 28 patients (23.0%) DM was diagnosed during the pretransplant investigation based on pathological results of OGTT (hepatogenous DM). In 13 patients, de novo DM after LT was diagnosed. On the multivariate analysis, patients with hepatogenous DM had significantly lower BMI (P = 0.015), lower fasting glucose (P = 0.002) and lower glycated hemoglobin (P = 0.010), compared to classical T2DM. In comparison to patients without DM, patients with hepatogenous DM had more frequent occurrence of metabolic syndrome (P = 0.033). Patients with hepatogenous DM were less frequently treated with insulin at 1 month (32.0% vs. 76.2%; P = 0.002), 6 months (20.0% vs. 76.2%; P <0.001), 1 year (20.0% vs. 75.0%; P <0.001) and 2 years after LT (23.8% vs. 66.7%; P = 0.007) than patients with classical T2DM; but they were more frequently treated with insulin than patients without pretransplant DM 1 month after LT (32.0% vs. 7.7%; P = 0.015) and 2 years after LT (23.8% vs. 9.1%; P = 0.029). Conclusion: Hepatogenous DM is frequent in LT candidates (23.0%), it regresses in the majority of patients after LT unlike the classical T2DM, however, insulinotherapy is still necessary up to one quarter of patients even 2 years after LT.

Keywords

hepatogenous diabetes, type 2 diabetes mellitus, liver transplantation, insulinotherapy

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Literature

1. Grancini V, Trombetta M, Lunati ME et al. Contribution of ß-cell dysfunction and insulin resistance to cirrhosis-associated diabetes: Role of severity of liver disease. J Hepatol 2015; 63(6): 1484–1490. doi: 10.1016/j.jhep.2015.08.011.
2. Wlazlo N, Beijers HJBH, Schoon EJ et al. High prevalence of diabetes mellitus in patients with liver cirrhosis. Diabet Med 2010; 27(11): 1308–1311. doi: 10.1111/j.1464-5491.2010.03093.x.
3. Hosseini Z, Whiting SJ, Vatanparast H. Type 2 diabetes prevalence among Canadian adults – dietary habits and sociodemographic risk factors. Appl Physiol Nutr Metab 2019; 44(10): 1099–1104. doi: 10.1139/apnm-2018-0567.
4. Lee WG, Wells CI, McCall JL et al. Prevalence of diabetes in liver cirrhosis: A systematic review and meta-analysis. Diabetes Metab Res Rev 2019; 35(6): e3157. doi: 10.1002/dmrr.3157.
5. Nishida T, Tsuji S, Tsujii M et al. Oral glucose tolerance test predicts prognosis of patients with liver cirrhosis. Am J Gastroenterol 2006; 101(1): 70–75. doi: 10.1111/j.1572-0241.2005.00307.x.
6. Garcia-Compean D, Jaquez-Quintana JO, Gonzalez-Gonzalez JA et al. Liver cirrhosis and diabetes: risk factors, pathophysiology, clinical implications and management. World J Gastroenterol 2009; 15(3): 280–288. doi: 10.3748/wjg.15.280.
7. Elkrief L, Rautou P-E, Sarin S et al. Diabetes mellitus in patients with cirrhosis: clinical implications and management. Liver Int 2016; 36(7): 936–948. doi: 10.1111/liv.13115.
8. 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(11): 3335–3341. doi: 10.1007/s10 620-013-2802-y.
9. Holstein A, Hinze S, Thiessen E et al. Clinical implications of hepatogenous diabetes in liver cirrhosis. J Gastroenterol Hepatol 2002; 17(6): 677–681. doi: 10.1046/j.1440-1746.2002.02755.x.
10. Kuriyama S, Miwa Y, Fukushima H et al. Prevalence of diabetes and incidence of angiopathy in patients with chronic viral liver disease. J Clin Biochem Nutr 2007; 40(2): 116–122. doi: 10.3164/jcbn.40.116.
11. Imano E, Kanda T, Nakatani Y et al. Impaired splanchnic and peripheral glucose uptake in liver cirrhosis. J Hepatol 1999; 31(3): 469–473. doi: 10.1016/s0168-8278(99)80039-7.
12. Kim MG, Choi WC. Differential diagnosis of diabetes mellitus caused by liver cirrhosis and other type 2 diabetes mellitus. Korean J Hepatol 2006; 12(4): 524–529.
13. Merli M, Leonetti F, Riggio O et al. Glucose intolerance and insulin resistance in cirrhosis are normalized after liver transplantation. Hepatology 1999; 30(3): 649–654. doi: 10.1002/hep.510300306.
14. Grancini V, Trombetta M, Lunati ME et al. Central role of the ß-cell in driving regression of diabetes after liver transplantation in cirrhotic patients. J Hepatol 2019; 70(5): 954–962. doi: 10.1016/j.jhep.2019.01.015.
15. Pelaez-Jaramillo MJ, Cardenas-Mojica AA, Gaete P V et al. Post-Liver Transplantation Diabetes Mellitus: A Review of Relevance and Approach to Treatment. Diabetes Ther 2018; 9(2): 521–543. doi: 10.1007/s13300-018-03 74-8.
16. Muniyappa R, Lee S, Chen H, Quon MJ. Current approaches for assessing insulin sensitivity and resistance in vivo: advantages, limitations, and appropriate usage. Am J Physiol Endocrinol Metab 2008; 294(1): E15–E26. doi: 10.1152/ajpendo.00645.2007.
17. Brodosi L, Petta S, Petroni ML et al. Management of Diabetes in Candidates for Liver Transplantation and in Transplant Recipients. Transplantation 2022; 106(3): 462–478. doi: 10.1097/TP.0000000000003867.
18. McPherson S, Hardy T, Henderson E et al. Evidence of NAFLD progression from steatosis to fibrosing-steatohepatitis using paired biopsies: Implications for prognosis and clinical management. J Hepatol 2015; 62(5): 1148–1155. doi: 10.1016/j.jhep.2014.11.034.
19. Huang DQ, Wilson LA, Behling C et al. Fibrosis Progression Rate in Biopsy-Proven Nonalcoholic Fatty Liver Disease Among People With Diabetes Versus People Without Diabetes: A Multicenter Study. Gastroenterology 2023; 165(2): 463–472. doi: 10.1053/j.gastro.2023.04.025.
20. 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(12): 1695–1702. doi: 10.1093/ cid/cit603.
21. Huang YW, Yang SS, Fu SC et al. Increased risk of cirrhosis and its decompensation in chronic hepatitis C patients with new-onset diabetes: a nationwide cohort study. Hepatology 2014; 60(3): 807–814. doi: 10.1002/hep.27 212.
22. Kumar R, García-Compeán D, Maji T. Hepatogenous diabetes: Knowledge, evidence, and skepticism. World J Hepatol 2022; 14(7): 1291–1306. doi: 10.4254/wjh.v14.i7.1291.
23. Orsi E, Grancini V, Menini S, et al. Hepatogenous diabetes: Is it time to separate it from type 2 diabetes? Liver Int 2017; 37(7): 950–962. doi: 10.1111/liv.13337.
24. Andrade AR, Bittencourt PL, Codes L et al. New Onset Diabetes and Non-Alcoholic Fatty Liver Disease after Liver Transplantation. Ann Hepatol 2017; 16(6): 932–940. doi: 10.5604/01. 3001.0010.5285.
25. 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(3): 694–703. doi: 10.1002/ hep.510310320.
26. Aravinthan AD, Fateen W, Doyle AC et al. The Impact of Preexisting and Post-transplant Diabetes Mellitus on Outcomes Following Liver Transplantation. Transplantation 2019; 103(12): 2523–2530. doi: 10.1097/TP.0000000000002757.
27. Davies MJ, Aroda VR, Collins BS et al. Management of hyperglycaemia in type 2 diabetes, 2022. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetologia 2022; 65(12): 1925–1966. doi: 10.1007/s00125-022-05787-2.
28. EASL Clinical Practice Guidelines for the management of patients with decompensated cirrhosis. J Hepatol 2018; 69(2): 406–460. doi: 10.1016/j.jhep.2018.03.024.
29. EASL Clinical Practice Guidelines: Liver transplantation. J Hepatol 2016; 64(2): 433–485. doi: 10.1016/j.jhep.2015.10.006.
30. Rydén L, Grant PJ, Anker SD et al. ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD: the Task Force on diabetes, pre-diabetes, and cardiovascular diseases of the European Society of Cardiology (ESC) and developed in collaboration with the European Association for the Study of Diabetes (EASD). Eur Heart J 2013; 34(39): 3035–3087. doi: 10.1093/eurheartj/eht108.