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Abstract
New onset diabetes after transplantation (NODAT) is a common complication after solid-organ transplantation and is associated with increased cardiovascular morbidity, mortality, and graft loss. The risk factors for NODAT include older age, ethnicity, genetic factors, obesity, family history of diabetes, hepatitis C virus infection, and immunosuppressant use (corticosteroids, calcineurin inhibitors, and mTOR inhibitor). Management of NODAT must be considered at the pre-transplantation stage in order to properly screen high-risk patients. Although NODAT management is similar to that of general type 2 diabetes, some specific considerations must be made in NODAT management, including the interactions between anti-diabetes medication and immunosuppressive agents.
REFERENCES
1. Ducloux D, Kazory A, Chalopin JM. Posttransplant diabetes mellitus and atherosclerotic events in renal transplant recipients: a prospective study. Transplantation. 2005; 79:438–43.
2. Rodrigo E, Fernandez-Fresnedo G, Valero R, Ruiz JC, Pinera C, Palomar R, Gonzalez-Cotorruelo J, Gomez-Alamillo C, Arias M. New-onset diabetes after kidney transplantation: risk factors. J Am Soc Nephrol. 2006; 17:S291–5.
3. Fernández-Fresnedo G, Escallada R, de Francisco AL, Rodrigo E, Zubimendi JA, Ruiz JC, Piñera C, Herraez I, Arias M. Posttransplant diabetes is a cardiovascular risk factor in renal transplant patients. Transplant Proc. 2003; 35:700.
4. Wauters RP, Cosio FG, Suarez Fernandez ML, Kudva Y, Shah P, Torres VE. Cardiovascular consequences of new-onset hyperglycemia after kidney transplantation. Transplantation. 2012; 94:377–82.
5. Tsai JP, Lian JD, Wu SW, Hung TW, Tsai HC, Chang HR. Long-term impact of pretransplant and posttransplant diabetes mellitus on kidney transplant outcomes. World J Surg. 2011; 35:2818–25.
6. Hjelmesaeth J, Hartmann A, Leivestad T, Holdaas H, Sagedal S, Olstad M, Jenssen T. The impact of early-diagnosed new-onset posttransplantation diabetes mellitus on survival and major cardiac events. Kidney Int. 2006; 69:588–95.
7. Crutchlow MF, Bloom RD. Transplant-associated hyperglycemia: a new look at an old problem. Clin J Am Soc Nephrol. 2007; 2:343–55.
8. Sumrani NB, Delaney V, Ding ZK, Davis R, Daskalakis P, Friedman EA, Butt KM, Hong JH. Diabetes mellitus after renal transplantation in the cyclosporine era -an analysis of risk factors. Transplantation. 1991; 51:343–7.
9. Al-Uzri A, Stablein DM, A Cohn R. Posttransplant diabetes mellitus in pediatric renal transplant recipients: a report of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS). Transplantation. 2001; 72:1020–4.
10. Kasiske BL, Snyder JJ, Gilbertson D, Matas AJ. Diabetes mellitus after kidney transplantation in the United States. Am J Transplant. 2003; 3:178–85.
11. Hur KY, Kim MS, Kim YS, Kang ES, Nam JH, Kim SH, Nam CM, Ahn CW, Cha BS, Kim SI, Lee HC. Risk factors associated with the onset and progression of posttransplantation diabetes in renal allograft recipients. Diabetes Care. 2007; 30:609–15.
12. Sumrani N, Delaney V, Ding Z, Davis R, Daskalakis P, Friedman EA, Butt KM, Hong JH. Posttransplant diabetes mellitus in cyclosporine-treated renal transplant recipients. Transplant Proc. 1991; 23:1249–50.
13. Sulanc E, Lane JT, Puumala SE, Groggel GC, Wrenshall LE, Stevens RB. New-onset diabetes after kidney transplantation: an application of 2003 International Guidelines. Transplantation. 2005; 80:945–52.
14. Kang ES, Kim MS, Kim CH, Nam CM, Han SJ, Hur KY, Ahn CW, Cha BS, Kim SI, Lee HC, Kim YS. Association of common type 2 diabetes risk gene variants and posttransplantation diabetes mellitus in renal allograft recipients in Korea. Transplantation. 2009; 88:693–8.
15. Kang ES, Kim MS, Kim YS, Hur KY, Han SJ, Nam CM, Ahn CW, Cha BS, Kim SI, Lee HC. A variant of the transcription factor 7-like 2 (TCF7L2) gene and the risk of posttransplantation diabetes mellitus in renal allograft recipients. Diabetes Care. 2008; 31:63–8.
16. Kang ES, Kim MS, Kim YS, Kim CH, Han SJ, Chun SW, Hur KY, Nam CM, Ahn CW, Cha BS, Kim SI, Lee HC. A polymorphism in the zinc transporter gene SLC30A8 confers resistance against posttransplantation diabetes mellitus in renal allograft recipients. Diabetes. 2008; 57:1043–7.
17. Lee YH, Kang ES, Kim SH, Han SJ, Kim CH, Kim HJ, Ahn CW, Cha BS, Nam M, Nam CM, Lee HC. Association between polymorphisms in SLC30A8, HHEX, CDKN2A/B, IGF2BP2, FTO, WFS1, CDKAL1, KCNQ1 and type 2 diabetes in the Korean population. J Hum Genet. 2008; 53:991–8.
18. Kang ES, Magkos F, Kim BS, Zhai R, Su L, Kim YS, Christiani DC, Lee HC, Mantzoros CS. Variants of the adiponectin and adiponectin receptor-1 genes and posttransplantation diabetes mellitus in renal allograft recipients. J Clin Endocrinol Metab. 2012; 97:E129–35.
19. Kim I, Kang ES, Yim YS, Ko SJ, Jeong SH, Rim JH, Kim YS, Ahn CW, Cha BS, Lee HC, Kim CH. A low-risk ZnT-8 allele (W325) for posttransplantation diabetes mellitus is protective against cyclosporin A-induced impairment of insulin secretion. Pharmacogenomics J. 2011; 11:191–8.
20. Bamoulid J, Courivaud C, Deschamps M, Mercier P, Ferrand C, Penfornis A, Tiberghien P, Chalopin JM, Saas P, Ducloux D. IL-6 promoter polymorphism-174 is associated with new-onset diabetes after transplantation. J Am Soc Nephrol. 2006; 17:2333–40.
21. Numakura K, Satoh S, Tsuchiya N, Horikawa Y, Inoue T, Kakinuma H, Matsuura S, Saito M, Tada H, Suzuki T, Habuchi T. Clinical and genetic risk factors for posttransplant diabetes mellitus in adult renal transplant recipients treated with tacrolimus. Transplantation. 2005; 80:1419–24.
22. Ogunkolade BW, Boucher BJ, Prahl JM, Bustin SA, Burrin JM, Noonan K, North BV, Mannan N, McDermott MF, DeLuca HF, Hitman GA. Vitamin D receptor (VDR) mRNA and VDR protein levels in relation to vitamin D status, insulin secretory capacity, and VDR genotype in Bangladeshi Asians. Diabetes. 2002; 51:2294–300.
23. Hitman GA, Mannan N, McDermott MF, Aganna E, Ogunkolade BW, Hales CN, Boucher BJ. Vitamin D receptor gene polymorphisms influence insulin secretion in Bangladeshi Asians. Diabetes. 1998; 47:688–90.
24. Armstrong KA, Campbell SB, Hawley CM, Nicol DL, Johnson DW, Isbel NM. Obesity is associated with worsening cardiovascular risk factor profiles and proteinuria progression in renal transplant recipients. Am J Transplant. 2005; 5:2710–8.
25. Cosio FG, Pesavento TE, Osei K, Henry ML, Ferguson RM. Posttransplant diabetes mellitus: increasing incidence in renal allograft recipients transplanted in recent years. Kidney Int. 2001; 59:732–7.
26. Gursoy M, Guvener N, Koksal R, Karavelioglu D, Baysal C, Ozdemir N, Boyacioglu S, Bilgin N, Erdal R. Impact of HCV infection on development of posttransplantation diabetes mellitus in renal allograft recipients. Transplant Proc. 2000; 32:561–2.
27. Bloom RD, Rao V, Weng F, Grossman RA, Cohen D, Mange KC. Association of hepatitis C with posttransplant diabetes in renal transplant patients on tacrolimus. J Am Soc Nephrol. 2002; 13:1374–80.
28. Baid S, Cosimi AB, Farrell ML, Schoenfeld DA, Feng S, Chung RT, Tolkoff-Rubin N, Pascual M. Posttransplant diabetes mellitus in liver transplant recipients: risk factors, temporal relationship with hepatitis C virus allograft hepatitis, and impact on mortality. Transplantation. 2001; 72:1066–72.
29. Fabrizi F, Martin P, Dixit V, Bunnapradist S, Kanwal F, Dulai G. Posttransplant diabetes mellitus and HCV seropositive status after renal transplantation: meta-analysis of clinical studies. Am J Transplant. 2005; 5:2433–40.
30. Woodward RS, Schnitzler MA, Baty J, Lowell JA, Lopez-Rocafort L, Haider S, Woodworth TG, Brennan DC. Incidence and cost of new onset diabetes mellitus among U.S. wait-listed and transplanted renal allograft recipients. Am J Transplant. 2003; 3:590–8.
31. Ozbay LA, Smidt K, Mortensen DM, Carstens J, Jorgensen KA, Rungby J. Cyclosporin and tacrolimus impair insulin secretion and transcriptional regulation in INS-1E beta-cells. Br J Pharmacol. 2011; 162:136–46.
32. Prokai A, Fekete A, Pasti K, Rusai K, Banki NF, Reusz G, Szabo AJ. The importance of different immunosuppressive regimens in the development of posttransplant diabetes mellitus. Pediatr Diabetes. 2012; 13:81–91.
33. Wissing KM, Unger P, Ghisdal L, Broeders N, Berkenboom G, Carpentier Y, Abramowicz D. Effect of atorvastatin therapy and conversion to tacrolimus on hypercholesterolemia and endothelial dysfunction after renal transplantation. Transplantation. 2006; 82:771–8.
34. McCune TR, Thacker LR II, Peters TG, Mulloy L, Rohr MS, Adams PA, Yium J, Light JA, Pruett T, Gaber AO, Selman SH, Jonsson J, Hayes JM, Wright FH Jr., Armata T, Blanton J, Burdick JF. Effects of tacrolimus on hyperlipidemia after successful renal transplantation: a Southeastern Organ Procurement Foundation multicenter clinical study. Transplantation. 1998; 65:87–92.
35. Ligtenberg G, Hene RJ, Blankestijn PJ, Koomans HA. Cardiovascular risk factors in renal transplant patients: cyclosporin A versus tacrolimus. J Am Soc Nephrol. 2001; 12:368–73.
36. Pereira MJ, Palming J, Rizell M, Aureliano M, Carvalho E, Svensson MK, Eriksson JW. The immunosuppressive agents rapamycin, cyclosporin A and tacrolimus increase lipolysis, inhibit lipid storage and alter expression of genes involved in lipid metabolism in human adipose tissue. Mol Cell Endocrinol. 2013; 365:260–9.
37. Kasiske B, Cosio FG, Beto J, Bolton K, Chavers BM, Grimm R Jr., Levin A, Masri B, Parekh R, Wanner C, Wheeler DC, Wilson PW. Clinical practice guidelines for managing dyslipidemias in kidney transplant patients: a report from the Managing Dyslipidemias in Chronic Kidney Disease Work Group of the National Kidney Foundation Kidney Disease Outcomes Quality Initiative. Am J Transplant. 2004; 4(Suppl 7):13–53.
38. Ridker PM, Pradhan A, MacFadyen JG, Libby P, Glynn RJ. Cardiovascular benefits and diabetes risks of statin therapy in primary prevention: an analysis from the JUPITER trial. Lancet. 2012; 380:565–71.
39. Ridker PM, Danielson E, Fonseca FA, Genest J, Gotto AM Jr., Kastelein JJ, Koenig W, Libby P, Lorenzatti AJ, MacFadyen JG, Nordestgaard BG, Shepherd J, Willerson JT, Glynn RJ. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med. 2008; 359:2195–207.
40. Preiss D, Seshasai SR, Welsh P, Murphy SA, Ho JE, Waters DD, DeMicco DA, Barter P, Cannon CP, Sabatine MS, Braunwald E, Kastelein JJ, de Lemos JA, Blazing MA, Pedersen TR, Tikkanen MJ, Sattar N, Ray KK. Risk of incident diabetes with intensive-dose compared with moderate-dose statin therapy: a meta-analysis. Jama. 2011; 305:2556–64.
41. Choe EY, Wang HJ, Kwon O, Cho Y, Huh KH, Kim MS, Kim YS, Ahn CW, Cha BS, Lee HC, Kang ES. HMG CoA reductase inhibitor treatment induces dysglycemia in renal allograft recipients. Transplantation. 2014; 97:419–25.
42. Cho Y, Lee MJ, Choe EY, Jung CH, Joo DJ, Kim MS, Cha BS, Park JY, Kang ES. Statin therapy is associated with the development of new-onset diabetes after transplantation in liver recipients with high fasting plasma glucose levels. Liver Transpl. 2014; 20:557–63.
43. Wilkinson A, Davidson J, Dotta F, Home PD, Keown P, Kiberd B, Jardine A, Levitt N, Marchetti P, Markell M, Naicker S, O'Connell P, Schnitzler M, Standl E, Torregosa JV, Uchida K, Valantine H, Villamil F, Vincenti F, Wissing M. Guidelines for the treatment and management of new-onset diabetes after transplantation. Clin Transplant. 2005; 19:291–8.
44. Kamar N, Toupance O, Buchler M, Sandres-Saune K, Izopet J, Durand D, Rostaing L. Evidence that clearance of hepatitis C virus RNA after alpha-interferon therapy in dialysis patients is sustained after renal transplantation. J Am Soc Nephrol. 2003; 14:2092–8.
45. Cosio FG, Kudva Y, van der Velde M, Larson TS, Textor SC, Griffin MD, Stegall MD. New onset hyperglycemia and diabetes are associated with increased cardiovascular risk after kidney transplantation. Kidney Int. 2005; 67:2415–21.
46. Neuvonen PJ, Niemi M, Backman JT. Drug interactions with lipid-lowering drugs: mechanisms and clinical relevance. Clin Pharmacol Ther. 2006; 80:565–81.
47. American Diabetes Association. Standards of medical care in diabetes-2014. Diabetes Care. 2014; 37(Suppl 1):S14–80.
48. Lipska KJ, Bailey CJ, Inzucchi SE. Use of metformin in the setting of mild-to-moderate renal insufficiency. Diabetes Care. 2011; 34:1431–7.
49. Harrower AD. Pharmacokinetics of oral antihyperglycaemic agents in patients with renal insufficiency. Clin Pharmacokinet. 1996; 31:111–9.
50. Kajosaari LI, Niemi M, Neuvonen M, Laitila J, Neuvonen PJ, Backman JT. Cyclosporine markedly raises the plasma concentrations of repaglinide. Clin Pharmacol Ther. 2005; 78:388–99.
51. Saemann MD, Krebs M. Thiazolidinediones in the treatment of patients with Post-Transplant-Hyperglycemia or new-onset diabetes mellitus after renal transplantation (NODAT) - a new therapeutic option? Wien Klin Wochenschr. 2010; 122:198–202.
52. Str⊘m Halden TA, Åsberg A, Vik K, Hartmann A, Jenssen T. Short-term efficacy and safety of sitagliptin treatment in longterm stable renal recipients with new-onset diabetes after transplantation. Nephrol Dial Transplant. 2014; 29:926–33.
53. Lane JT, Odegaard DE, Haire CE, Collier DS, Wrenshall LE, Stevens RB. Sitagliptin therapy in kidney transplant recipients with new-onset diabetes after transplantation. Transplantation. 2011; 27(92):e56–7.
54. Haidinger M, Werzowa J, Hecking M, Antlanger M, Stemer G, Pleiner J, Kopecky C, Kovarik JJ, Döller D, Pacini G, Säemann MD. Efficacy and safety of vildagliptin in new-onset diabetes after kidney transplantation–a randomized, double-blind, placebo-controlled trial. Am J Transplant. 2014; 14:115–23.
Table 1.
Dosing of dipeptidyl peptidase-4 inhibitors in patients with renal insufficiency.
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