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High Incidence of Early Posttransplantation Diabetes Mellitus in an Eastern Population
Metabolic
High Incidence of Early Posttransplantation Diabetes Mellitus in an Eastern Population N. Mohsin, M. Budruddin, A. Pakkyara, A. Kumar, S. Kalankara, S. Malvathu, J. Amitabh, and A. Daar ABSTRACT The prevalence of diabetes mellitus (DM) in the Gulf region is among the highest in the world. In the general population of Oman, the rate is approximately 11.7% with an additional 6.1% of the population having an abnormal glucose tolerance. This study reviewed the data for 162 adults who received kidney transplants between 2001 and 2004. The immunosuppression regimen was cyclosporine, mycophenolate mofetil (MMF), and steroids. The mean age of the group was 40.2 years. Twenty-two patients (13.6%) had DM prior to transplantation. Within the first 2 months after transplantation, 45 (32%) of the remaining 140 patients required insulin, and 10 (7.1%) required oral agents. A further 16 patients (11.4%) displayed blood glucose levels ⬎11 mmol/L, but required only a special diet for control. The data indicate that 50% of recent adult kidney recipients in Oman receiving cyclosporine develop posttransplantation DM. This major problem in our transplant population requires special attention. Protocols with minimal steroid use and/or steroid withdrawal may be beneficial for the Oman kidney recipient population.
D
IABETES mellitus (DM) is a relatively common, serious complication after organ transplantation, which is associated with both short- and long-term complications. Diabetes is a major public health problem in the Gulf region. The objective of this study was to determine the incidence of posttransplantation diabetes mellitus (PTDM).
PATIENTS AND METHODS We retrospectively examined data from 162 adult kidney transplant recipients who were followed at our center between 2001 and 2004. The period of interest was the initial 2 months after transplantation using cyclosporine, mycophenolate mofetil (MMF), and prednisolone. Cyclosporine was monitored based on C2 levels (cyclosporine blood level 2 hours after the ingestion of the oral dose)
with target levels dependent on the time posttransplantation. The MMF dose was 1 g twice daily. In most cases, prednisolone started at a dose of 20 mg once daily and was tapered to 10 mg at 3 months. All of the transplants came from living donors. In each case, blood glucose levels were monitored in capillary blood samples at least 3 times daily during the initial admission (average duration roughly 2 weeks), and thereafter at least 3 times monthly for the first 2 months postsurgery. World Health Organization (WHO) criteria were used to diagnose DM.
From the Department of Nephrology, Royal Hospital, Muscat, Oman. Address reprint requests to Nabil Mohsin, MD, Department of Nephrology, Royal Hospital, P.O. Box 1331, PC 111 Muscat, Oman. E-mail: [email protected]
© 2005 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
0041-1345/05/$–see front matter doi:10.1016/j.transproceed.2005.07.037
Transplantation Proceedings, 37, 3093–3094 (2005)
3093
3094
RESULTS
The mean age of the 162 recipients at the time of transplantation was 42 years. Twenty-two patients (13.6%) already had DM prior to transplantation. Of the remaining 140 individuals, 45 (32.1%) developed insulin-requiring DM within the first 2 months after transplantation, and 10 (7.1%) were diagnosed with DM that could be controlled with oral antidiabetic agents and diet. A further 16 recipients (11.4%) had blood glucose levels ⬎11 mmol/L but their DM was controlled with diet alone. Overall, PTDM developed in 50% of the recipients who were not already diabetic at the time of transplantation. DISCUSSION
The onset of DM after transplantation is associated with a negative effect on graft and patient survival.1 Research has also shown that PTDM is associated with significantly higher rates of infection and hospital admissions.2 It is likely that this problem is greater than current reports indicate, because of inadequate definitions and lack of standardized screening.3 Several risk factors for PTDM have been identified, but reported findings have not been consistent. The factors identified to date include deceased donors transplantation, hepatitis C virus infection, tacrolimus, occurrence of at least 1 rejection episode, family history of DM, and possibly operative time. In addition, it appears that obesity is fairly consistently associated with PTDM.1,4,5 Steroids are known to be diabetogenic; most studies indicate an association between steroid administration and development of PTDM.4,5 Calcineurins also have a diabetogenic effect, which seems to be due to a direct effect on pancreatic beta cells, in particular via intracellular calcium.6 Impaired insulin secretion seems to play a major role in PTDM.7 The reported incidence rates of PTDM vary, ranging from 5% to 40%.4 Our data in this series of kidney recipients from Oman reveal one of the highest rates of PTDM ever reported worldwide (50%). Part of the explanation for this could be the frequent monitoring of our
MOHSIN, BUDRUDDIN, PAKKYARA ET AL
patients and the stringent criteria used for diagnosis. We used WHO criteria, whereas others have reported the incidence of only insulin-dependent DM or DM requiring pharmacological treatment.1,3,4,7 Nevertheless, we believe that use of less rigorous criteria results in underdiagnosis of this important form of morbidity. In addition to the high rate of PTDM, DM is also a major health problem in the general population of Oman, prevalence 11.7% with an additional 6% with abnormal glucose tolerance. The high incidence of PTDM in our kidney recipients and the high prevalence of DM in the general population of our country suggest that genetic, dietary, and lifestyle factors contribute to this disease. In conclusion, in Oman PTDM is a major problem in renal transplant recipients that requires special attention. Immunosuppressive protocols that eliminate or minimize risk factors for the development of DM, such as minimal steroid use and/or withdrawal, may be of special benefit for our country’s kidney recipient population. REFERENCES 1. Gourishankar S, Jhangri GS, Tonelli M, et al: Development of diabetes mellitus following kidney transplantation: a Canadian experience. Am J Transplant 4:1876, 2004 2. Saleem TF, Cunningham KE, Hollenbeak CS, et al: Development of diabetes mellitus post-renal transplantation is associated with poor short-term clinical outcomes. Transplant Proc 35:2916, 2003 3. Moore R, Boucher A, Carter J, et al: Post-transplant diabetes mellitus advisory board. Transplant Proc 35:1265, 2003 4. Foo SM, Wong HS, Morad Z: Risk factors and incidence of post transplant diabetes mellitus in renal transplant recipients. Transplant Proc 36:2139, 2004 5. Secchi A: The incidence, clinical implications and risk factors of diabetes mellitus. G Ital Nefrol 20 (suppl 25):S7, 2003 6. Ippoliti GB, Vigano M: Calcineurin inhibitors and mechanisms that are responsible in the appearance of post-transplant diabetes mellitus. G Ital Nefrol 20(suppl 25):S11, 2003 7. Hagen M, Hjelmesaeth J, Jenssen T, et al: A 6-year prospective study on new onset diabetes mellitus, insulin release and insulin sensitivity in renal transplant recipients. Nephrol Dial Transpl 18:2154, 2003
High Incidence of Early Posttransplantation Diabetes Mellitus in an Eastern Population N. Mohsin, M. Budruddin, A. Pakkyara, A. Kumar, S. Kalankara, S. Malvathu, J. Amitabh, and A. Daar ABSTRACT The prevalence of diabetes mellitus (DM) in the Gulf region is among the highest in the world. In the general population of Oman, the rate is approximately 11.7% with an additional 6.1% of the population having an abnormal glucose tolerance. This study reviewed the data for 162 adults who received kidney transplants between 2001 and 2004. The immunosuppression regimen was cyclosporine, mycophenolate mofetil (MMF), and steroids. The mean age of the group was 40.2 years. Twenty-two patients (13.6%) had DM prior to transplantation. Within the first 2 months after transplantation, 45 (32%) of the remaining 140 patients required insulin, and 10 (7.1%) required oral agents. A further 16 patients (11.4%) displayed blood glucose levels ⬎11 mmol/L, but required only a special diet for control. The data indicate that 50% of recent adult kidney recipients in Oman receiving cyclosporine develop posttransplantation DM. This major problem in our transplant population requires special attention. Protocols with minimal steroid use and/or steroid withdrawal may be beneficial for the Oman kidney recipient population.
D
IABETES mellitus (DM) is a relatively common, serious complication after organ transplantation, which is associated with both short- and long-term complications. Diabetes is a major public health problem in the Gulf region. The objective of this study was to determine the incidence of posttransplantation diabetes mellitus (PTDM).
PATIENTS AND METHODS We retrospectively examined data from 162 adult kidney transplant recipients who were followed at our center between 2001 and 2004. The period of interest was the initial 2 months after transplantation using cyclosporine, mycophenolate mofetil (MMF), and prednisolone. Cyclosporine was monitored based on C2 levels (cyclosporine blood level 2 hours after the ingestion of the oral dose)
with target levels dependent on the time posttransplantation. The MMF dose was 1 g twice daily. In most cases, prednisolone started at a dose of 20 mg once daily and was tapered to 10 mg at 3 months. All of the transplants came from living donors. In each case, blood glucose levels were monitored in capillary blood samples at least 3 times daily during the initial admission (average duration roughly 2 weeks), and thereafter at least 3 times monthly for the first 2 months postsurgery. World Health Organization (WHO) criteria were used to diagnose DM.
From the Department of Nephrology, Royal Hospital, Muscat, Oman. Address reprint requests to Nabil Mohsin, MD, Department of Nephrology, Royal Hospital, P.O. Box 1331, PC 111 Muscat, Oman. E-mail: [email protected]
© 2005 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
0041-1345/05/$–see front matter doi:10.1016/j.transproceed.2005.07.037
Transplantation Proceedings, 37, 3093–3094 (2005)
3093
3094
RESULTS
The mean age of the 162 recipients at the time of transplantation was 42 years. Twenty-two patients (13.6%) already had DM prior to transplantation. Of the remaining 140 individuals, 45 (32.1%) developed insulin-requiring DM within the first 2 months after transplantation, and 10 (7.1%) were diagnosed with DM that could be controlled with oral antidiabetic agents and diet. A further 16 recipients (11.4%) had blood glucose levels ⬎11 mmol/L but their DM was controlled with diet alone. Overall, PTDM developed in 50% of the recipients who were not already diabetic at the time of transplantation. DISCUSSION
The onset of DM after transplantation is associated with a negative effect on graft and patient survival.1 Research has also shown that PTDM is associated with significantly higher rates of infection and hospital admissions.2 It is likely that this problem is greater than current reports indicate, because of inadequate definitions and lack of standardized screening.3 Several risk factors for PTDM have been identified, but reported findings have not been consistent. The factors identified to date include deceased donors transplantation, hepatitis C virus infection, tacrolimus, occurrence of at least 1 rejection episode, family history of DM, and possibly operative time. In addition, it appears that obesity is fairly consistently associated with PTDM.1,4,5 Steroids are known to be diabetogenic; most studies indicate an association between steroid administration and development of PTDM.4,5 Calcineurins also have a diabetogenic effect, which seems to be due to a direct effect on pancreatic beta cells, in particular via intracellular calcium.6 Impaired insulin secretion seems to play a major role in PTDM.7 The reported incidence rates of PTDM vary, ranging from 5% to 40%.4 Our data in this series of kidney recipients from Oman reveal one of the highest rates of PTDM ever reported worldwide (50%). Part of the explanation for this could be the frequent monitoring of our
MOHSIN, BUDRUDDIN, PAKKYARA ET AL
patients and the stringent criteria used for diagnosis. We used WHO criteria, whereas others have reported the incidence of only insulin-dependent DM or DM requiring pharmacological treatment.1,3,4,7 Nevertheless, we believe that use of less rigorous criteria results in underdiagnosis of this important form of morbidity. In addition to the high rate of PTDM, DM is also a major health problem in the general population of Oman, prevalence 11.7% with an additional 6% with abnormal glucose tolerance. The high incidence of PTDM in our kidney recipients and the high prevalence of DM in the general population of our country suggest that genetic, dietary, and lifestyle factors contribute to this disease. In conclusion, in Oman PTDM is a major problem in renal transplant recipients that requires special attention. Immunosuppressive protocols that eliminate or minimize risk factors for the development of DM, such as minimal steroid use and/or withdrawal, may be of special benefit for our country’s kidney recipient population. REFERENCES 1. Gourishankar S, Jhangri GS, Tonelli M, et al: Development of diabetes mellitus following kidney transplantation: a Canadian experience. Am J Transplant 4:1876, 2004 2. Saleem TF, Cunningham KE, Hollenbeak CS, et al: Development of diabetes mellitus post-renal transplantation is associated with poor short-term clinical outcomes. Transplant Proc 35:2916, 2003 3. Moore R, Boucher A, Carter J, et al: Post-transplant diabetes mellitus advisory board. Transplant Proc 35:1265, 2003 4. Foo SM, Wong HS, Morad Z: Risk factors and incidence of post transplant diabetes mellitus in renal transplant recipients. Transplant Proc 36:2139, 2004 5. Secchi A: The incidence, clinical implications and risk factors of diabetes mellitus. G Ital Nefrol 20 (suppl 25):S7, 2003 6. Ippoliti GB, Vigano M: Calcineurin inhibitors and mechanisms that are responsible in the appearance of post-transplant diabetes mellitus. G Ital Nefrol 20(suppl 25):S11, 2003 7. Hagen M, Hjelmesaeth J, Jenssen T, et al: A 6-year prospective study on new onset diabetes mellitus, insulin release and insulin sensitivity in renal transplant recipients. Nephrol Dial Transpl 18:2154, 2003