Effect of Demographic and Clinical Factors on New- Onset Diabetes Mellitus after Liver Transplantation in Iranian Patients
Abstract
Backgrounds: New- onset diabetes after transplantation (NODAT) is a serious complication which runs the risk of infections, morbidity and mortality. Older age, male sex, immunosuppressive agents and hepatitis C are reported as risk factors. The focus of this research is evaluating some demographic and clinical factors in development of NODAT in hepatic transplanted patients. This study aims to help identifying high risk recipients in order to prevent NODAT and improve transplantation prognosis.
Methods: In this study 134 liver recipients without pre- transplantation diabetes were investigated; 70 euglycemic and 64 with NODAT within 2 years after transplantation. All the patients were on tacrolimus- based immunosuppressive regimen. The role of recipients’ age, sex, body mass index (BMI), model for end- stage liver disease (MELD) score, blood group, diseases leading to transplantation, tacrolimus dose and serum level, mycophenolate mofetil (MMF) and prednisolone dose in the incidence of NODAT were assessed.
Results: The prevalence of NODAT in this study was 17.92%. The means of duration after transplantation that NODAT occurred, was 98.36± 21.62 days. The mean age of all patients was 37.83±16.26 years and 60.40% were females. Two groups were similar in terms of pre- transplantation fasting blood sugar (FBS) (P=0.091). Age (P=0.001,OR=1.063,CI:1.025-1.102) and prednisolone dose (P<0.0001,OR=1.270,CI:1.163-1.388) the only independent predictors of NODAT, while tacrolimus daily dose and plasma level, MMF daily dose, sex, BMI and underlying diseases were not risk factors for NODAT.
Conclusions: Recipients with older age and higher prednisolone dose are more prone to NODAT and need more accurate monitoring.
Chamberlain JJ, Rhinehart AS, Shaefer CF Jr, Neuman A. Diagnosis and Management of Diabetes: Synopsis of the 2016 American Diabetes Association Standards of Medical Care in Diabetes. Ann Intern Med 2016; 164(8):542-52.
Krentz AJ, Wheeler DC. New-onset diabetes after transplantation: a threat to graft and patient survival. Lancet 2005;365(9460):640-2.
Lee, Sr, Moon JY, Lee SH, et al. Angiotensinogen polymorphisms and post-transplantation diabetes mellitus in Korean renal transplant subjects. Kidney Blood Press Res 2013;37(2-3):95-102.
Kesiraju S, Paritala P, Rao Ch UM, Sahariah S. New onset of diabetes after transplantation - an overview of epidemiology, mechanism of development and diagnosis. Transpl Immunol 2014;30(1):52-8.
Parvizi Z, Azarpira N, Kohan L, Darai M, Kazemi K, Parvizi MM. Association between E23K variant in KCNJ11 gene and new-onset diabetes after liver transplantation. Mol Biol Rep 2014;41(9):6063-9.
Ling Q, Xu X, Xie H, et al. New-onset diabetes after liver transplantation: a national report from China Liver Transplant Registry. Liver Int 2016; 35:705-12.
Rodrigo E, Fernandez-Fresnedo G, Valero R, et al. New-onset diabetes after kidney transplantation: risk factors. J Am Soc Nephrol 2006;17(12 Suppl 3):S291-5.
Saliba F, Lakehal M, Pageaux GP, et al. Risk factors for new-onset diabetes mellitus following liver transplantation and impact of hepatitis C infection: an observational multicenter study. Liver Transpl 2007;13(1):136-44.
Ghisdal L, Van Laecke S, Abramowicz MJ, Vanholder R, Abramowicz D. New-Onset Diabetes After Renal Transplantation: Risk assessment and management. Diabetes Care 2012; 35(1):181-8.
Benson KA, Maxwell AP, McKnight AJ. A HuGE Review and Meta- Analyses of Genetic Associations in New Onset Diabetes after Kidney Transplantation. PLoS ONE 2016; 11(1):e0147323.
Palepu S, Prasad GVR. New-onset diabetes mellitus after kidney transplantation: Current status and future directions. World J Diabetes 2015; 6(3):445-55.
Van Laecke S, Desideri F, Geerts A, et al. Hypomagnesemia and the risk of new-onset diabetes after liver transplantation. Liver Transpl 2010; 16(11):1278-87.
Van Laecke S, Van Biesen W, Verbeke F, De Bacquer D, Peeters P, Vanholder R. Posttransplantation hypomagnesemia and its relation with immunosuppression as predictors of new-onset diabetes after transplantation. Am J Transplant 2009; 9(9):2140-9.
Li D-W, Lu T-F, Hua X-W, et al. Risk factors for new onset diabetes mellitus after liver transplantation: A meta-analysis. World J Gastroenterol 2015; 21(20):6329-40.
Marchetti P. New-onset diabetes after liver transplantation: from pathogenesis to management. Liver Transpl 2005; 11(6):612-20.
Haddad EM, McAlister VC, Renouf E, Malthaner R, Kjaer MS, Gluud LL. Cyclosporin versus tacrolimus for liver transplanted patients. Cochrane Database Syst Rev 2006; (4):Cd005161.
Pham PT, Pham PM, Pham SV, Pham PA, Pham PC. New onset diabetes after transplantation (NODAT): an overview. Diabetes Metab Syndr Obes 2011; 4:175-86.
Tueche SG. Diabetes mellitus after liver transplant new etiologic clues and cornerstones for understanding. Transplant Proc 2003; 35(4):1466-8.
Ling Q, Xie H, Lu D, et al. Association between donor and recipient TCF7L2 gene polymorphisms and the risk of new-onset diabetes mellitus after liver transplantation in a Han Chinese population. J Hepatol 2013; 58(2):271-7.
Musavi Z, Azarpira N, Sangtarash MH, et al. Polymorphism of Transcription Factor-7-Like 2 (TCF7L2) Gene and New-Onset Diabetes after Liver Transplantation. Int J Organ Transplant Med 2015; 6(1):14-22.
Davidson JA, Wilkinson A. New-Onset Diabetes After Transplantation 2003 International Consensus Guidelines. Diabetes Care 2004 ;27(3):805-12.
Eghtesad Online. [updated 8/15/2016; cited 2016 8/20]. Available from: URL: http://www.en.eghtesadonline.com/Section-news-2/1617-iranian-hospital-achieves-global-first-rank-for-liver transplant.
Kamath PS, Kim WR. The model for end-stage liver disease (MELD). Hepatology 2007;45(3):797-805.
Backman LA. Post-transplant diabetes mellitus: the last 10 years with tacrolimus. Nephrol Dial Transplant 2004;19 Suppl 6:vi13-vi6.
Cho YM, Park KS, Jung HS, et al. High incidence of tacrolimus-associated posttransplantation diabetes in the Korean renal allograft recipients according to American Diabetes Association criteria. Diabetes Care 2003;26(4):1123-8.
Kasiske BL, Snyder JJ, Gilbertson D, Matas AJ. Diabetes mellitus after kidney transplantation in the United States. Am J Transplant 2003;3(2):178-85.
Hornum M, Jorgensen KA, Hansen JM, et al. New-onset diabetes mellitus after kidney transplantation in Denmark. Clin J Am Soc Nephrol 2010;5(4):709-16.
Vaughn VM, Cron DC, Terjimanian MN, et al. Analytic morphomics identifies predictors of new-onset diabetes after liver transplantation. Clin Transplant 2015;29(5):458-64.
Bodziak KA, Hricik DE. New-onset diabetes mellitus after solid organ transplantation. Transpl Int 2009;22(5):519-30.
Cullen TJ, McCarthy MP, Lasarev MR, Barry JM, Stadler DD. Body mass index and the development of new-onset diabetes mellitus or the worsening of pre-existing diabetes mellitus in adult kidney transplant patients. J Ren Nutr 2014;24(2):116-22.
Stepanova M, Henry L, Garg R, Kalwaney S, Saab S, Younossi Z. Risk of de novo post-transplant type 2 diabetes in patients undergoing liver transplant for non-alcoholic steatohepatitis. BMC Gastroenterol 2015;15:175.
Yadav AD, Chang Y-H, Aqel BA, et al. New Onset Diabetes Mellitus in Living Donor versus Deceased Donor Liver Transplant Recipients: Analysis of the UNOS/OPTN Database. J Transplant 2013;2013:269096.
Bays HE, Chapman RH, Grandy S. The relationship of body mass index to diabetes mellitus, hypertension and dyslipidaemia: comparison of data from two national surveys. Int J Clin Pract 2007; 61(5):737-47.
Gray N, Picone G, Sloan F, Yashkin A. The Relationship between BMI and Onset of Diabetes Mellitus and its Complications. South Med J 2015;108(1):29-36.
Gomes MB, Cobas RA. Post-transplant diabetes mellitus. Diabetol Metab Syndr 2009;1(1):1-4.
Reuben A. Long-term management of the liver transplant patient: diabetes, hyperlipidemia, and obesity. Liver Transpl 2001;7(11 Suppl 1):S13-21.
Gourishankar S, Jhangri GS, Tonelli M, Wales LH, Cockfield SM. Development of diabetes mellitus following kidney transplantation: a Canadian experience. Am J Transplant 2004;4(11):1876-82.
Seifi S, Rahbar M, Lessan-Pezeshki M, et al. Posttransplant diabetes mellitus: incidence and risk factors. Transplant Proc 2009;41(7):2811-3.
Yang J, Hutchinson II, Shah T, Min DI. Genetic and clinical risk factors of new-onset diabetes after transplantation in Hispanic kidney transplant recipients. Transplantation 2011; 91(10):1114-9.
Hjelmesaeth J, Hartmann A, Kofstad J, et al. Glucose intolerance after renal transplantation depends upon prednisolone dose and recipient age. Transplantation 1997;64(7):979-83.
Hjelmesaeth J, Hartmann A, Kofstad J, Egeland T, Stenstrom J, Fauchald P. Tapering off prednisolone and cyclosporin the first year after renal transplantation: the effect on glucose tolerance. Nephrol Dial Transplant 2001;16(4):829-35.
Immunosuppression with Tacrolimus after Solid Organ Transplantation in Children. Pediatric Pharmacotherapy. 2003, Available from: URL: http:// www.medscape.com/viewarticle/457649, viewed at May 2016.
Jindal RM, Sidner RA, Milgrom ML. Post-transplant diabetes mellitus. The role of immunosuppression. Drug Saf 1997;16(4):242-57.
McAlister VC, Haddad E, Renouf E, Malthaner RA, Kjaer MS, Gluud LL. Cyclosporin versus tacrolimus as primary immunosuppressant after liver transplantation: a meta-analysis. Am J Transplant 2006;6(7):1578-85.
Neylan JF. Racial differences in renal transplantation after immunosuppression with tacrolimus versus cyclosporine. FK506 Kidney Transplant Study Group. Transplantation 1998; 65(4):515-23.
Weir MR, Fink JC. Risk for posttransplant Diabetes mellitus with current immunosuppressive medications. Am J Kidney Dis 1999;34(1):1-13.
Xu X, Ling Q, He ZL, Gao F, Zheng SS. Post-transplant diabetes mellitus in liver transplantation: Hangzhou experience. Hepatobiliary Pancreat Dis Int 2008;7(5):465-70.
Redmon JB, Olson LK, Armstrong MB, Greene MJ, Robertson RP. Effects of tacrolimus (FK506) on human insulin gene expression, insulin mRNA levels, and insulin secretion in HIT-T15 cells. J Clin Invest 1996;98(12):2786-93.
Tamura K, Fujimura T, Tsutsumi T, et al. Transcriptional inhibition of insulin by FK506 and possible involvement of FK506 binding protein-12 in pancreatic beta-cell. Transplantation 1995;59(11):1606-13.
Maes BD, Kuypers D, Messiaen T, et al. Posttransplantation diabetes mellitus in FK-506-treated renal transplant recipients: analysis of incidence and risk factors. Transplantation 2001; 72(10):1655-61.
Li CJ, Li L. Tacrolimus in preventing transplant rejection in Chinese patients--optimizing use. Drug Des Devel Ther 2015;9:473-85.
Johnson C, Ahsan N, Gonwa T, et al. Randomized trial of tacrolimus (Prograf) in combination with azathioprine or mycophenolate mofetil versus cyclosporine (Neoral) with mycophenolate mofetil after cadaveric kidney transplantation. Transplantation 2000; 69(5):834-41.
Cosio FG, Pesavento TE, Osei K, Henry ML, Ferguson RM. Post-transplant diabetes mellitus: increasing incidence in renal allograft recipients transplanted in recent years. Kidney Int 2001;59(2):732-7.
Montero N, Pascual J. Immunosuppression and Post-transplant Hyperglycemia. Curr Diabetes Rev 2015;11(3):144-54.
Lexi-Comp. Drug Information Handbook: A Clinically Relevant Resource for All Healthcare Professionals: Lexi-Comp, Incorporated .2014.
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| Issue | Vol 3, No 3-4 (Winter 2015) | |
| Section | Original Article(s) | |
| Keywords | ||
| Liver Transplantation Prednisolone Diabetes Mellitus | ||
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