Liver transplantation and diabetes mellitus

Summary:

Post-transplant diabetes mellitus (PTDM) is a common complication after orthotopic liver transplantation (oLT). In our study, we investigated the prevalence and risk factors one year after transplantation in 618 patients who underwent oLT between 1990 and 1996 in a single center. The influence of steroid medication and hepatitis B or C (HBV/HCV) was also studied. Before oLT 66 of the 618 patients were diabetic. After transplantation 37 of these 66 (56%) patients showed no further signs of DM. Of the 552 patients without DM before transplantation 39 (7.2%) developed new onset PTDM. There was no influence of steroid medication on the presence of PTDM (steroids 10.4% PTDM, no steroids 12.5% PTDM). In addition we found no influence of HBV or HCV-infection on PTDM development. Analysis for risk factors showed no significant influence of the diagnosis leading to oLT, of FK506 or Cyclosorin A medication, age, gender or Child-Pugh class. Five year patient survival was not influenced by the presence of PTDM, especially patients with a preexisting DM showed no reduced survival. However, a subgroup of patients with new onset insulin-requiring PTDM showed significantly reduced 5 year survival (p < 0.05). In conclusion we found new onset PTDM in 7.2% of patients undergoing oLT one year after the operation. On the other hand in more than 50% of patients with preexisting DM, the disease was no longer present post-transplant. This could be an indication that DM is dependent on liver function in these patients. Patients with preexisting DM should not be excluded from transplantation if indicated. Development of new onset insulin-requiring PTDM could be an important prognostic factor for patient survival after oLT. Further investigations are necessary to evaluate the prognostic meaning of PTDM and the pathophysiologic mechanisms.

Key words:

Orthotopic liver transplantation - diabetes mellitus - post-transplant diabetes mellitus - corticosteroids - hepatitis B - hepatitis C

References

• 1 Alberti K G, Zimmet P Z. Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation.  Diabet Med. 15 539-553 1998; 
• 2 Assan R, Larger E, Samuel F, Saliba F, Castaing D, Bismuth H. Prevalence of diabetes mellitus in liver transplant patients (abstract).  J Hepatol. 18 S70 1993; 
• 3 Bosch J, Gomis R, Kravetz D, Casamitjana R, Terés J, Ribera F, Rodés J. Role of spontaneous portal-systemic shunting in hyperinsulinism in cirrhosis.  Am J Physiol. 247 G206-G212 1984; 
• 4 Boudreaux J P, McHugh L, Canafax D M. et al. . The impact of cyclosporine and combination immunosuppression on the incidence of posttransplant diabetes in renal allograft recipients.  Transplantation. 44 376-381 1987; 
• 5 Fraser G M, Grammoustianos K, Reddy J, Davidson B, Burroughs A K. Long-term immunosuppression without corticosteroids after orthotopic liver transplantation: a positive therapeutic aim.  Liver Transpl Surg. 2 411-417 1996; 
• 6 Hricik D E, Bartucci M R, Moir E J, Mayes J T, Schulak J A. Effects of steroid withdraw on posttransplant diabetes mellitus in cyclosporine-treated renal transplant recipients.  Transplantation. 51 374-377 1991; 
• 7 Jindal R M. Posttransplant diabetes mellitus - a review.  Transplantation. 58 1289-1298 1994; 
• 8 Jindal R M, Popescu I, Schwartz M E, Emre S, Boccagni P, Miller C M. Diabetogenicity of FK506 versus cyclosporine in liver transplant recipients.  Transplantation. 58 370-372 1994; 
• 9 Knobler H, Stagnaro-Green A, Wallenstein S, Schwartz M, Roman S H. Higher incidence of diabetes in liver transplant recipients with Hepatitis C.  J Clin Gastroenterol. 26 30-33 1998; 
• 10 Krentz A J, Dousset B, Mayer D, McMaster P, Buckels J, Cramb R, Smith J M, Nattrass M. Metabolic effects of cyclosporine A and FK506 in liver transplant recipients.  Diabetes. 42 1753-1759 1993; 
• 11 Ladowski J S, Kormos R L, Uretsky B F, Lee A, Cuuran M, Clark R, Armitage J M, Griffith B P, Hardesty R L. Posttransplantation diabetes mellitus in heart transplant recipients.  J Heart Transplant. 8 181-183 1989; 
• 12 Marchesini G, Pacini G, Bianchi G, Patrono D, Cobelli C. Glucose disposal, β-cell secretion, and hepatic insulin extraction in cirrosis: A minimal model assessment.  Gastroenterology. 99 1715-1722 1990; 
• 13 Megeysi C, Samols E, Marks V. Glucose tolerance and diabetes in chronic liver disease.  Lancet. 2 1051-1055 1967; 
• 14 Mieles L, Gordon R D, Mintz D. et al. . Glycemia and insulin need following FK 506 rescue therapy in liver transplant recipients.  Transplant Proc. 23 949-953 1991; 
• 15 Navasa M, Bustamante J, Marroni C. et al. . Diabetes mellitus after liver transplantation: prevalence and predictive factors.  J Hepatol. 25 64-71 1996; 
• 16 Petrides A S, Vogt C, Schulze-Berge D, Matthews D, Strohmeyer G. Pathogenesis of glucose intolerance and diabetes mellitus in cirrhosis.  Hepatology. 19 616-627 1994; 
• 17 Ruiz J O, Simmons R L, Callender C O, Kjellstrand C M, Buselmeier T J, Najarian J S. Steroid diabetes in renal transplant recipients: pathogenetic factors and prognosis.  Surgery. 73 759-765 1973; 
• 18 Starzl T E. Experience in renal transplantation. Philadelphia, Saunders 1964
• 19 Steinmüller T, Konrad T, Vicini P, Toffolo G, Jonas S, Tullius S, Bechstein W O, Cobelli C, Usadel K H, Neuhaus P. Effect of CsA versus FK 506 on insulin sensitivity and insulin response using a modeling technique.  Transplant Proc. 30 1452-1453 1998; 
• 20 Steinmüller T M, Gräf K J, Schleicher J. et al. . The effect of FK506 versus cyclosporine on glucose and lipid metabolism - a randomized trial.  Transplantation. 58 669-674 1994; 
• 21 Sumrani N B, Delaney V, Ding Z, Daskalakis P, Friedman E A, Butt K M, Hong J H. Diabetes mellitus after renal transplantation in the cyclosporine era - an analysis of risk factors.  Transplantation. 51 343-347 1991; 
• 22 Tabasco-Minguillan J, Mieles L, Carroll P, Gavaler J, Van Thiel D H, Starzl T E. Insulin requirements after liver transplantation and FK506 immunosuppression.  Transplantation. 56 862-867 1993; 
• 23 Todo S, Demetris A, Ueda Y. et al. . Renal transplantation in baboons under FK506.  Surgery. 106 444-450 1989;