J Korean Endocr Soc.  2006 Oct;21(5):373-381. 10.3803/jkes.2006.21.5.373.

Contributing Factors to Different Natural Courses of Posttansplantation Diabetes Mellitus in Renal Allograft Recipients

• Hur KY
• Kim MS
• Nam JH
• Kang ES
• Lee HJ
• Kim SH
• Cha BS
• Ahn CW
• Kim SI
• Kim YS
• Lee HC

• KMID: 1511986
• DOI: http://doi.org/10.3803/jkes.2006.21.5.373

Abstract

BACKGROUND: New onset diabetes is a major complication after kidney transplantation. However, the natural course of posttransplantation diabetes mellitus (PTDM) remains unclear. The aim of this study was to demonstrate the detailed natural courses of PTDM according to the onset and persistency of hyperglycemia, and to investigate risk factors for development of different courses of PTDM in renal allograft recipients.
METHODS
A total of 77 renal allograft recipients without previously known diabetes were enrolled and performed a serial 75 g oral glucose tolerance test at 0, 1, and 7 years after kidney transplantation. Patients were classified according to the onset and persistency of PTDM: early PTMD (E-PTDM), late PTDM (L-PTDM), persistent PTDM (P-PTDM), transient PTMD (T-PTDM), and non-PTDN (N-PTDM).
RESULTS
The incidence of each group was as follows: E-PTDM, 39%; L-PTDM, 11.7%; P-PTDM, 23.4% T-PTDM, 15.6%; N-PTDM, 49.3%. Tacrolimus and female gender were associated with the development of E-PTDM. Among E-PTDM, age at transplantation was a high risk factor for the development of P-PTDM. Higher BMI at year1 was associated with the development of L-PTDM.
CONCLUSION
Different risk factors were associated with various natural courses of PTDM. Since old age and female gender are not modifiable risk factors, it may be important to modify immunosuppressive therapy regimens for the prevention of E-PTDM and control of body weight for L-PTDM.

Keyword

Natural courses; Posttransplantation diabetes mellitus; Risk factors

MeSH Terms

Allografts*
Body Weight
Diabetes Mellitus*
Female
Glucose Tolerance Test
Humans
Hyperglycemia
Incidence
Kidney Transplantation
Risk Factors
Tacrolimus
Tacrolimus

Figure

• 

  Fig. 1 Different clinical courses of posttransplantation diabetes mellitus (PTDM) in renal allograft recipients. E-PTDM, early PTDM NGT; L-PTDM, late PTDM NGT, normal glucose tolerance; N-PTDM, non-PTDM until 7 year posttrnasplant; P-PTDM, persistent PTDM; T-PTDM, transient PTDM.

• 

  Fig. 2 Serial changes in insulin secretion, SecrAUC (A), insulin sensitivity (ISI) (B), ΔSecrAUC (C), and ΔISI (D). ISI, insulin sensitivity index (µmolkg-1ㆍmin-1pmol-1); ΔISI, ISI (at year 1 or 7) - ISI (at baseline); L-PTDM, late posttransplantation diabetes mellitus (PTDM); N-PTDM, non-PTDM until 7 year posttransplant; P-PTDM, persistent PTDM; SecrAUC, index of β-cell function (SecrAUCInsulin / SecrAUCGlucose); ΔSecrAUC, SecrAUC (at year 1 or 7) - SecrAUC (at baseline); T-PTDM, transient PTDM. *P < 0.05 compared with N-PTDM at each time point by the Kruskal-Wallis test. **P < 0.001 compared with N-PTDM at each time point by the Kruskal-Wallis test.

Reference

1. Montori VM, Basu A, Erwin PJ, Velosa JA, Gabriel SE, Kudva YC. Posttransplantation diabetes: a systematic review of the literature. Diabetes Care. 2002. 25:583–592.

2. Boudreaux JP, McHugh L, Canafax DM, Ascher N, Sutherland DE, Payne W, Simmons RL, Najarian JS, Fryd DS. The impact of cyclosporine and combination immunosuppression on the incidence of posttransplant diabetes in renal allograft recipients. Transplantation. 1987. 44:376–381.

3. Boudreaux JP, McHugh L, Canafax DM, Asher N, Sutherland DE, Payne W, Simmons RL, Najarian JS, Fryd DS. Cyclosporine, combination immunosuppression, and posttransplant diabetes mellitus. Transplant Proc. 1987. 19:1811–1813.

4. Vesco L, Busson M, Lang P. Characteristics of postrenal transplant diabetes mellitus. Transplant Proc. 1995. 27:2465–2466.

5. Vesco L, Busson M, Bedrossian J, Bitker MO, Hiesse C, Lang P. Diabetes mellitus after renal transplantation: characteristics, outcome, and risk factors. Transplantation. 1996. 61:1475–1478.

6. Wu CT, Wang WY, Lin SL, Lee CJ. Do immunosuppressants cause posttransplant diabetes mellitus? Zhonghua Yi Xue Za Zhi (Taipei). 1995. 55:37–41.

7. Lanerolle RD, de Abrew K, Fernando DJ, Sheriff MH. Post-renal transplant diabetes in Sri Lanka. Transplant Proc. 1996. 28:1945–1947.

8. Friedman EA, Shyh TP, Beyer MM, Manis T, Butt KM. Posttransplant diabetes in kidney transplant recipients. Am J Nephrol. 1985. 5:196–202.

9. Arner P, Gunnarsson R, Blomdahl S, Groth CG. Some characteristics of steroid diabetes: a study in renal -transplant recipients receiving high-dose corticosteroid therapy. Diabetes Care. 1983. 6:23–25.

10. Gunnarsson R, Arner P, Lundgren G, Magnusson G, Ostman J, Groth CG. Diabetes mellitus--a more-common-than-believed complication of renal transplantation. Transplant Proc. 1979. 11:1280–1281.

11. McIntyre EA, Walker M. Genetics of type 2 diabetes and insulin resistance: knowledge from human studies. Clin Endocrinol (Oxf). 2002. 57:303–311.

12. 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. 51:343–347.

13. Kasiske BL, Snyder JJ, Gilbertson D, Matas AJ. Diabetes mellitus after kidney transplantation in the United States. Am J Transplant. 2003. 3:178–185.

14. Neylan JF. Racial differences in renal transplantation after immunosuppression with tacrolimus versus cyclosporine. FK506 Kidney Transplant Study Group. Transplantation. 1998. 65:515–523.

15. Reisaeter AV, Hartmann A. Risk factors and incidence of posttransplant diabetes mellitus. Transplant Proc. 2001. 33:suppl 5A. 8S–18S.

16. David DS, Cheigh JS, Braun DW Jr, Fotino M, Stenzel KH, Rubin AL. HLA-A28 and steroid-induced diabetes in renal transplant patients. JAMA. 1980. 243:532–533.

17. Starzl TE, Marchioro TL, Rifkind D, Holmes JH, Rowlands DT Jr, Waddell WR. Factors in successful renal transplantation. Surgery. 1964. 56:296–318.

18. Vincenti F, Jensik SC, Filo RS, Miller J, Pirsch J. A long-term comparison of tacrolimus (FK506) and cyclosporine in kidney transplantation: evidence for improved allograft survival at five years. Transplantation. 2002. 73:775–782.

19. Mayer AD, Dmitrewski J, Squifflet JP, Besse T, Grabensee B, Klein B, Eigler FW, Heemann U, Pichlmayr R, Behrend M, Vanrenterghem Y, Donck J, van Hooff J, Christiaans M, Morales JM, Andres A, Johnson RW, Short C, Buchholz B, Rehmert N, Land W, Schleibner S, Forsythe JL, Talbot D, Pohanka E. Multicenter randomized trial comparing tacrolimus (FK506) and cyclosporine in the prevention of renal allograft rejection: a report of the European Tacrolimus Multicenter Renal Study Group. Transplantation. 1997. 64:436–443.

20. Pirsch JD, Miller J, Deierhoi MH, Vincenti F, Filo RS. A comparison of tacrolimus (FK506) and cyclosporine for immunosuppression after cadaveric renal transplantation. FK506 Kidney Transplant Study Group. Transplantation. 1997. 63:977–983.

21. Knoll GA, Bell RC. Tacrolimus versus cyclosporin for immunosuppression in renal transplantation: meta-analysis of randomised trials. BMJ. 1999. 318:1104–1107.

22. Hjelmesaeth J, Hartmann A, Kofstad J, Stenstrom J, Leivestad T, Egeland T, Fauchald P. Glucose intolerance after renal transplantation depends upon prednisolone dose and recipient age. Transplantation. 1997. 64:979–983.

23. Miles AM, Sumrani N, Horowitz R, Homel P, Maursky V, Markell MS, Distant DA, Hong JH, Sommer BG, Friedman EA. Diabetes mellitus after renal transplantation: as deleterious as non-transplant-associated diabetes? Transplantation. 1998. 65:380–384.

24. 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. 13:1374–1380.

25. American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2004. 27:suppl 1. S5–S10.

26. Stumvoll M, Mitrakou A, Pimenta W, Jenssen T, Yki-Jarvinen H, Van Haeften T, Renn W, Gerich J. Use of the oral glucose tolerance test to assess insulin release and insulin sensitivity. Diabetes Care. 2000. 23:295–301.

27. Davidson J, Wilkinson A, Dantal J, Dotta F, Haller H, Hernandez D, Kasiske BL, Kiberd B, Krentz A, Legendre C, Marchetti P, Markell M, van der Woude FJ, Wheeler DC. New-onset diabetes after transplantation: 2003 International consensus guidelines. Proceedings of an international expert panel meeting. Barcelona, Spain, 19 February 2003. Transplantation. 2003. 75:suppl 10. S3–S24.

28. Weir MR, Fink JC. Risk for posttransplant diabetes mellitus with current immunosuppressive medications. Am J Kidney Dis. 1999. 34:1–13.

29. Jindal RM, Hjelmesaeth J. Impact and management of posttransplant diabetes mellitus. Transplantation. 2000. 70:suppl 11. S58–S63.

30. Nam JH, Mun JI, Kim SI, Kang SW, Choi KH, Park K, Ahn CW, Cha BS, Song YD, Lim SK, Kim KR, Lee HC, Huh KB. Beta-Cell dysfunction rather than insulin resistance is the main contributing factor for the development of postrenal transplantation diabetes mellitus. Transplantation. 2001. 71:1417–1423.

31. Uchizono Y, Iwase M, Nakamura U, Sasaki N, Goto D, Iida M. Tacrolimus impairment of insulin secretion in isolated rat islets occurs at multiple distal sites in stimulus-secretion coupling. Endocrinology. 2004. 145:2264–2272.

32. Cho YM, Park KS, Jung HS, Jeon HJ, Ahn C, Ha J, Kim SJ, Rhee BD, Kim SY, Lee HK. High incidence of tacrolimus-associated posttransplantation diabetes in the Korean renal allograft recipients according to American Diabetes Association criteria. Diabetes Care. 2003. 26:1123–1128.