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BACKGROUND: Newonset diabetes after transplantation (NODAT) is a serious complicatin of kidney transplantation (KT) with adverse impacts on graft and patient survivals. This study aims assess potential risk factors for development of NODAT and compare clinical outcomes of KT recipients with versus without NODAT.METHODS: We retrospectively evaluated 648 patients who underwent KT between 2005 and 2009. From the 83 (12.8%) subjects who developed NODAT, we selected 47 for comparison with controls free of diabetes.RESULTS: The diagnosis of NODAT was made at 4.3 ± 8.5 months after transplantation in 47 patients, including 76.6% males, with an overall mean age of 54.5 ± 10.8 years. Patients with NODAT presented higher pretransplantation fasting plasma glucose levels (P < .001) as well as cyclosporine and tacrolimus trough levels (P = .003 and P < .001, respectively). On multivariate analysis, higher pretransplantation fasting plasma glucose and higher tacrolimus, but not cyclosporine concentrations were independent predictors of NODAT. No differences were found for other potential risk factors. Upon followup at 6, 12, 24, 36, 48, and 60 months, renal function (estimated Glomerular Filtration Rate using Modification of Diet in Renal Disease), 24 hour proteinuria and proportions of patients with hypertension were similar between groups. Patients with NODAT showed comparable numbers of hospitalizations and infections, as well as acute rejection episodes and acute cardiovascular events as their counterparts. Eventfree survival (loss of graft functiondeath with functioning graft) was similar between the groups (P = .418; KM).DISCUSSION: In our population, higher pretransplantation fasting plasma glucose levels and higher tacrolimus concentrations were independent predictors of NODAT. During a mean followup of 3 years, NODAT was not associated with worse clinical outcomes.
New-Onset Diabetes After Transplantation: Assessment of Risk Factors and Clinical Outcomes P Cotovio, M Neves, L Rodrigues, R Alves, M Bastos, C Baptista, F Macário, and A Mota ABSTRACT Background New-onset diabetes after transplantation (NODAT) is a serious complicatin of kidney transplantation (KT) with adverse impacts on graft and patient survivals This study aims assess potential risk factors for development of NODAT and compare clinical outcomes of KT recipients with versus without NODAT Methods We retrospectively evaluated 648 patients who underwent KT between 2005 and 2009 From the 83 (12.8%) subjects who developed NODAT, we selected 47 for comparison with controls free of diabetes Results The diagnosis of NODAT was made at 4.3 Ϯ 8.5 months after transplantation in 47 patients, including 76.6% males, with an overall mean age of 54.5 Ϯ 10.8 years Patients with NODAT presented higher pretransplantation fasting plasma glucose levels (P Ͻ 001) as well as cyclosporine and tacrolimus trough levels (P ϭ 003 and P Ͻ 001, respectively) On multivariate analysis, higher pretransplantation fasting plasma glucose and higher tacrolimus, but not cyclosporine concentrations were independent predictors of NODAT No differences were found for other potential risk factors Upon follow-up at 6, 12, 24, 36, 48, and 60 months, renal function (estimated Glomerular Filtration Rate using Modification of Diet in Renal Disease), 24 hour proteinuria and proportions of patients with hypertension were similar between groups Patients with NODAT showed comparable numbers of hospitalizations and infections, as well as acute rejection episodes and acute cardiovascular events as their counterparts Event-free survival (loss of graft function/death with functioning graft) was similar between the groups (P ϭ 418; K-M) Discussion In our population, higher pretransplantation fasting plasma glucose levels and higher tacrolimus concentrations were independent predictors of NODAT During a mean follow-up of years, NODAT was not associated with worse clinical outcomes EW-ONSET diabetes after transplantation (NODAT) is a multifactorial, complex metabolic disorder that has been reported to occur in 2% to 53% of all organ transplant recipients1,2 and 4% to 25% of kidney transplantation (KT) cases.2 The variation in this incidence may be due in part to the lack of a standard definition, the follow-up duration, the presence of modifiable and nonmodifiable risk factors, as well as the type of organ transplantation.2 Although most patients develop diabetes with in the first months after transplantation, the incidence of NODAT increases with follow-up period.3,4 NODAT has been associated with impaired long-term graft function, reduced recipient survival, increased risk of cardiovascular disease (CVD), and infectious complications.5 KT recipients who develop NODAT are at a two- to N three-fold increased risk of fatal and nonfatal cardiovascular events compared with nondiabetics.2,6 Several risk factors have been shown to independently predict NODAT Nonmodifiable risk factors include older age, nonwhite ethnicity, male gender, family history of diabetes, presence From the Department of Nephrology (P.C., M.N., L.R., R.A., F.M.), Department of Endocrinology, Diabetes and Metabolism (M.B., C.B.), and Department of Urology and Renal Transplantation (A.M.), Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal Address reprint requests to Partrớcia Cotovio, Serviỗo de Nefrologia, Centro Hospitalar e Universitário de Coimbra - HG, Quinta dos Vales, 3041-801 São Martinho Bispo, Coimbra, Portugal E-mail: patriciacotovio@gmail.com © 2013 by Elsevier Inc All rights reserved 360 Park Avenue South, New York, NY 10010-1710 0041-1345/–see front matter http://dx.doi.org/10.1016/j.transproceed.2013.03.009 Transplantation Proceedings, 45, 1079 –1083 (2013) 1079 1080 of HLA A30, B27, and B42, male donor, deceased donor, increased HLA mismatches, and acute rejection episodes The modifiable (or potentially modifiable) risk factors comprise obesity and other components of the metabolic syndrome, previous glucose intolerance, hepatitis C virus (HCV) and cytomegalovirus infections, as well as immunosuppressive drugs.2 Identifying high-risk patients may improve long-term outcomes by allowing tailoring of immunosuppression and early institution of lifestyle modifications The purpose of our study was to evaluate the potential risk factors associated with the development of NODAT in KT recipients and to compare clinical outcomes of patients with NODAT to their paired recipients without diabetes METHODS We developed a single-center retrospective registry-based study of all 648 KT recipients, between 2005 and 2009 among whom 83 developed NODAT (12.8%) The occurrence of disease was defined according to the NODAT 2003 International Consensus Guidelines2 as symptoms of diabetes mellitus and casual plasma glucose concentrations Ն 200 mg/dL (11.1 mmol/L) or fasting plasma glucose Ն 126 mg/dL (7.0 mmol/L) or 2-hour plasma glucose Ն 200 mg/dL (11.1 mmol/L) during an oral glucose tolerance test Among those 83 patients, we excluded 36 recipients whose recipient pair also developed NODAT or for whom only one kidney was available for transplantation We included 47 patients with a diagnosis of NODAT and 47 corresponding paires control recipients who did not develop the disorder, thereby seeking to eliminate potential effects deriving from the donor We only included the 45 pairs who had a minimum follow-up of months (mean, 36.6 Ϯ 17.2 (34.5) months; range, to 79.2 months) Gathered demographic and clinical data included age at transplantation, gender, race, smoking history, body mass index (BMI), arterial hypertension, dyslipidemia and CVD (coronary, cerebrovascular, peripheral artery disease and/or congestive heart failure), pretransplantation fasting plasma glucose, HCV serology, chronic kidney disease etiology (undetermined, glomerular, tubulointerstitial, hypertension/renal vascular, polycystic) and previous renal replacement therapy (RRT) Arterial hypertension was defined as systolic blood pressure (BP) Ն 140 mm Hg and/or diastolic BP Ն 90 mm Hg and/or antihypertensive drug use Dyslipidemia was defined as total cholesterol Ն 220 mg/dL, triglyceride levels Ն 150 mg/dL and/or need for specific lipid-decreasing therapy Recorded transplantation-specific data included donor demographics histocompatibility (number of HLA matches), immunization (peak serum panel reactive antibody [PRA]) cold ischemic time, antibody induction therapy, maintenance immunosuppressive regimens, incidence of delayed graft function, and number of acute rejection episodes treated with pulse steroids up to the time of the diagnosis of NODAT To compare groups regarding the evolution of estimated glomerular filtration rate (eGFR) calculated by the Modification of Diet in Renal Disease (MDRD) formula, proteinuria and prevalence of arterial hypertension at 6, 12, 24, 36, 48, and 60 months after NODAT diagnosis, we collected serum creatinine and 24-hour proteinuria values Hospitalizations, infections, acute rejection episodes, and acute cardiovascular events (acute myocardial infarction, stroke and acute heart failure) were registered for each patient Survival analysis focused on graft loss or death with a functioning graft COTOVIO, NEVES, RODRIGUES ET AL Statistical analysis was performed using SPSS 17.0 Continuous variables are shown as mean values and standard deviations or a medians with minimums and maximums Categorical variables are shown as numbers and percentages Quantitative variables were compared using the Student t and Mann-Whitney U tests; nominal variables, chi-square tests Binary logistic regression models analyzed potential risk factors for development of NODAT For survival analysis we used the Kaplan-Meier method with log-rank tests for significance P values Ͻ 05 are reported as statistically significant RESULTS The diagnosis of NODAT was made at 4.3 Ϯ 8.5 months after transplantation (median, 1.4 months) including 87.2% of cases within the first months The general characteristics and statistical comparisons between patients who developed NODAT and the control cohort are presented in Table Baseline recipient characteristics were similar between the groups with regard to age, gender, race, smoking history, BMI, dyslipidemia, hypertension, CVD, HCV serology, chronic kidney disease etiology, as well as modality and duration of previous RRT All patients received a deceased donor graft No significant differences were observed regarding the proportion of extended criteria donors, peak serum PRA level, number of HLA matches, cold ischemic time, use of mono/polyclonal antibodies for induction therapy, maintenance immunosuppression therapy (all treated with calcineurin inhibitors at the time of diagnosis) and incidence of delayed graft function or number of acute rejection episodes treated with pulse steroids (P ϭ not significant) Patients who developed NODAT showed significantly higher pretransplantation fasting plasma glucose (P Ͻ 001) and both cyclosporine and tacrolimus concentrations (P ϭ 003 and P Ͻ 001, respectively) Logistic regression analysis revealed pretransplantation fasting plasma glucose (odds ratio [OR] 1.1, 95% confidence interval [IC] 1.02 to 1.14, P ϭ 014) and tacrolimus concentrations (OR 1.5, 95% CI 1.19 to 1.90, P ϭ 001) to act as independent predictors of NODAT, whereas cyclosporine content lost significance The 45 recipient-pairs for follow-up comparisons showed comparable evolution of renal function with eGFR-MDRD values (mL/min/1.73 m2) among NODAT versus controls of 53 Ϯ 26 versus 52 Ϯ 44 (P ϭ 84), 61 Ϯ 21 versus 58 Ϯ 22 (P ϭ 48), 62 Ϯ 21 versus 56 Ϯ 21 (P ϭ 16), 62 Ϯ 19 versus 56 Ϯ 20 (P ϭ 20), 63 Ϯ 22 versus 58 Ϯ 26 (P ϭ 45), 64 Ϯ 24 versus 58 Ϯ 29 (P ϭ 65), and 58 Ϯ 10 versus 58 Ϯ 18 (P ϭ 98) at 0, 6, 12, 24, 36, 48, and 60 months, respectively Similarly, recipients with NODAT did not display increased 24-hour proteinuria (g): 0.13 Ϯ 0.3 versus 0.13 Ϯ 0.5 (P ϭ 47), 0.31 Ϯ 0.8 versus 0.12 Ϯ 0.2 (P ϭ 33), 0.44 Ϯ 0.7 versus 0.42 Ϯ 0.9 (P ϭ 92), 0.48 Ϯ 0.9 versus 0.31 Ϯ 0.4 (P ϭ 86), 0.23 Ϯ 0.3 versus 0.69 Ϯ 1.8 (P ϭ 38), and 0.16 Ϯ 0.2 versus 0.11 Ϯ 0.1 (P ϭ 86) at 6, 12, 24, 36, 48, and 60 months, respectively The proportion of patients with hypertension was similar between groups at 76% versus 61% (P ϭ 15), 82% versus 71% (P ϭ 21), 86% versus 73% (P ϭ NEW-ONSET DIABETES AFTER TRANSPLANTATION 1081 Table Characteristics of Patients With NODAT versus the Control group Characteristic Age (years) Age Ͼ 50 years (n, %) Black race (n, %) Male gender (n, %) History of smoking (n, %) BMI (kg/m2) Dyslipidemia (n, %) Arterial hypertension (n, %) History of CVD (n, %) Pretransplantation fasting plasma glucose (mg/dL) Chronic HCV infection (n) Chronic kidney disease etiology Undetermined Glomerular Tubulointestitial Hypertension/renal vascular Polycystic Previous RRT (n HD) Time on dialysis (mo) Previous renal transplantation (n) Graft type (n cadaveric) Extended criteria donor (n) PRA level before transplantation (n) 0% to 24% Ն25% Number of HLA matches Cold ischemic time (hours) Induction therapy (n, %) Maintenance immunosuppression with cyclosporine/tacrolimus (n) Serum cyclosporine trough level (ng/mL) Serum tacrolimus trough level (ng/mL) Delayed graft function (n) Antirejection therapy with steroids* (n) NODAT (n ϭ 47) Control Group (n ϭ 47) P Value 54.5 Ϯ 10.8 34 (72.3%) (14.9%) 36 (76.6%) (17%) 24.5 Ϯ 3.7 29 (61.7%) 35 (74.5%) (21.3%) 102.9 Ϯ 16.1 (4.3%) 49.3 Ϯ 14.5 26 (55.3%) (4.3%) 31 (66.0%) (6.4%) 24.0 Ϯ 4.2 27 (57.4%) 28 (59.6%) 10 (21.3%) 91.4 Ϯ 13.3 (10.6%) 18 086 08 254 109 536 674 125 60 Ͻ.001 239 746 19 (40.4%) 10 (21.3%) (17.0%) (10.6%) (10.6%) 47 (100%) 68.0 Ϯ 38.6 (6.4%) 47 (100%) 29 (61.7%) 19 (40.4%) 10 (21.3%) (10.6%) (19.1%) (8.5%) 46 (97.9%) 79.3 Ϯ 67.5 (14.9%) 47 (100%) 26 (55.3%) 43 (91.5%) (8.5%) 2.3 Ϯ 1.0 17.5 Ϯ 4.7 32 (68.1%) 10/57 383.5 Ϯ 124.0 11.9 Ϯ 2.9 12 (25.5%) (19.1%) 44 (93.6%) (6.4%) 2.1 Ϯ 1.2 18.0 Ϯ 5.4 33 (70.2%) 13/34 226.8 Ϯ 66.8 8.5 Ϯ 2.5 16 (34.1%) (17.0) 29 324 177 N/A 53 694 607 67 823 472 003 Ͻ.001 367 789 Abbreviations: NODAT, new onset diabetes after transplantation BMI, body mass index; CVD, cardiovascular disease; HCV, hepatitis C virus; RRT, renal replacement therapy; HD, hemodialysis; PRA, panel reactive antibody *Methylprednisone 500 mg on consecutive days .14), 89% versus 82% (P ϭ 44), 91% versus 79% (P ϭ 31), 89% versus 91% (P ϭ 31), 75% versus 100% (P ϭ 35), in patients with NODAT versus nondiabetics at 0, 6, 12, 24, 36, 48, and 60 months, respectively Recipients with NODAT required comparable numbers of hospitalizations (0.57 versus 0.64 ep./y, P ϭ 69) and experienced similar infection (0.33 versus 0.47 ep./y, P ϭ 32) as their counterparts Rate of acute rejection episodes (4.4% versus 17.1%, P ϭ 056) and acute cardiovascular events (17.8% versus 12.2%, P ϭ 47) were not greater among the NODAT versus control group During follow-up, 21 patients were transferred to other transplantation units, including NODAT (20%) and 12 nondiabetic (29%) Only recipients without diabetes (7.3% versus 0%, P ϭ 07) lost their grafts Death with a functioning graft occurred in NODAT recipients (2 CVD and infections) and nondiabetics (infections) (8.9% versus 7.3%, P ϭ 79) Kaplan-Meier analysis showed similar event-free survial (loss of graft function/death with functioning graft) between NODAT and nondiabetic groups at 12, 24, 36, 48, and 60 months to be 100% 97%, 94%, 85% and 85% versus 100%, 95%, 89%, 82%, and 74%, respectively (P ϭ 418; KaplanMeier; Fig 1) DISCUSSION Evidence suggests that NODAT is associated with impaired long-term patient survival, partly owing to the increased risks of CVD and infectious complications, as well as acute rejection episodes.1,5–10 Although NODAT clearly contributes to overall graft failure rates, the direct effects of NODAT on allograft survival are difficult to ascertain.11 United States Renal Data System (USRDS) analysis showed that compared to “no diabetes,” NODAT was associated with a 63% increased risk of graft failure (P Ͻ 0001), a 46% increased risk of death-censored graft failure (P Ͻ 0001) and a 85% increased risk of mortality (P Ͻ 0001).6 In other studies, when death-censored graft loss is 1082 COTOVIO, NEVES, RODRIGUES ET AL Fig Kaplan-Meier curve by NODAT status for event-free survival (log rank P ϭ 418) accounted for, NODAT was no longer a significant risk for graft loss.11–13 During a mean follow-up of years of our population, NODAT was not associated with worse renal function, 24-hour proteinuria, prevalence of hypertension, acute rejection episodes, acute cardiovascular events, infections and hospitalizations, as well as event-free survival In fact, some published studies corroborate our results An analysis by the Organ Procurement Transplant Network/Scientific Registry of Transplant Recipient (OPTN/SRTS) database showed pretransplantation diabetes but not NODAT to be associated with all-cause and cardiovascular mortality during a median follow-up of 548 days.8 In a single-center study, patients with NODAT displayed similar KaplanMeier survival curves to nondiabetic KT recipients for up to 96 months after which the plots began to diverge as survival in patients with NODAT suddently deteriorated Interestingly, a Kaplan-Meier survival plot constructed in the NODAT group, starting from the time of diagnosis, was similar to that for transplant recipients who had pre-existing diabetes when the two plots were superimposed.9 This finding suggested that KT recipients who developed NODAT may experience accelerated progression of diabetes-related complications that affect patient survival.11 To improve the outcomes of KT recipients, it is of great interest to know risk factors that contribute to NODAT development Among our population, higher pretransplantation fasting plasma glucose values were an independent predictor of NODAT In fact, abnormal glucose metabolism has been reported to be a risk factor for NODAT in some but not all studies Examing 490 KT recipients Cosio et al reported that higher pretransplantation glucose values were a risk factor for NODAT at year after transplanta- tion.14 In another study, random blood glucose values greater than mmol/L portended a greater than 25% independent risk to develop NODAT.15 In our study, higher levels of calcineurin inhibitors showed significant association with NODAT Multivariate analysis revealed tacrolimus concentrations to act as an independent predictive risk factor, whereas those of cyclosporine lost significance Calcineurin inhibitors have been associated with an increased risk of NODAT Although clinical trials comparing the incidence of NODAT in cyclosporine- versus tacrolimus–treated recipients have produced mixed results—, more consistently tacrolimus shows greater diabetogenic effect.16 –18 We recognize limitations of out study It was a retrospective and single-center analysis; therefore, the results may not be able to be generalized Our sample was small and the follow-up short, namely, a median of 34.5 months, which may not be long enough to manifest the detrimental clinical effects of NODAT The association between NODAT and adverse recipient outcomes suggests that treatment of hyperglycemia may enhance patient and graft survival Therefore, screening for glucose dysregulation and for risk factors with subsequent lifestyle interventions (diet, weight loss, and exercise) should be systematic in all phases of the transplantation process, commencing at evaluation.1,19,20 Among high-risk patients, one must consider carefully the appropriate immunosuppressive regimen.1,19 After transplantation, screening for the development of diabetes should include monitoring of fasting plasma glucose at least weekly in the first weeks, then at 3-, 6-, and 12-month intervals, and annually thereafter.20 Management of NODAT should follow a stepwise approach, beginning with nonpharmacologic therapy and progression, if necessary, to NEW-ONSET DIABETES AFTER TRANSPLANTATION oral agents either alone or in combination with other oral agents or insulin A review and dose adjustment of the immunosuppressive should be undertaken to improve glucose homeostasis.5,20 Self-monitoring of blood glucose, evaluation of glycated hemoglobin (HbA1c) levels every months, screening, and treatment of other components of metabolic syndrome, as well as annual screening for diabetic complications are integral parts of NODAT care A multifaceted team-oriented approach, including physicians, nurse-educators, and nutritionists, has the greatest chance of successfully and safety diagnosing and treating NODAT, thereby optimizing the health of affected recipients.19 In conclusion, higher pretransplantation fasting plasma glucose levels and higher tacrolimus concentrations were independent predictors of NODAT At a mean follow-up of years, NODAT was not associated with worse clinical outcomes, possibly related to systematic management and a multidisciplinary approach REFERENCES Davidson J, Wilkinson AH New-onset diabetes after transplantation 2003 International Consensus Guidelines: an endocrinologist’s view Diabetes Care 2004;27:805 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 Montori VM, Basu A, Erwin PJ, et al Posttransplantation diabetes: a systematic reivew of the literature Diabetes Care 2002;25:583 Allamani M, Sennesael J, Vendemeulenbroucke E Posttransplantation diabetes mellitus: a long-term retrospective cohort study Transplant Proc 2010;42:4378 Kaposztas Z, Gyurus E, Kahan BD New-onset diabetes after renal transplantation: diagnosis, incidence, risk factors, impact on outcomes, and novel implications Transplant Proc 2011;43:1375 Kasiske BL, Snyder JJ, Gilbertson D, et al Diabetes mellitus after kidney transplantation in the United States Am J Transplant 2003;3:178 Markell M Clinical impact of posttransplant diabetes mellitus Transplant Proc 2001;33 (suppl 5A):19S Kuo H-T, Sampaio MS, Vincenti F, et al Associations of pretransplant diabetes mellitus, new-onset diabetes mellitus after 1083 transplant, and acute rejection with transplant outcomes: an analysis of the Organ Procurement and Transplant Network/ United Network for Organ Sharing (OPTN/UNOS) database Am J Kidney Dis 2010;56(6):1026 Cosio FG, Pesavento TE, Kim S, Osei K, Henry M, Ferguson RM Patient survival after renal transplantation: IV Impact of post-transplant diabetes Kidney Int 2002;62:1440 –1446 10 Revanur VK, Jardine AG, Kingsmore DB, Jaques BC, Hamilton DH, Jindal RM Influence of diabetes mellitus on patient and graft survival in recipients of kidney transplantation Clin Transplant 2001;15:89 11 Sharif A, Baboolal K Complications associated with newonset diabetes after kidney transplantation Nat Rev Nephrol 2012;8:34 12 Matas AJ, Wilkinson A, Dantal J, et al Posttransplant diabetes mellitus and acute rejection: Impact on kidney transplant outcome Transplantation 2008;85:338 13 Cole EH, Johnston O, Rose CL, et al Impact of acute rejection and new-onset diabetes on long-term transplant graft and patient survival Clin J Am Soc Nephrol 2008;3:814 14 Cosio FG, Kudva Y, van der Velde M, et al New onset hyperglycemia and diabetes mellitus are associated with increased cardivascular risk after kidney transplantation Kidney Int 2005; 67(6):2415–2421 15 Ramesh Prasad GV, Huang M, Bandukwala F, et al Pretransplantation glucose testing for predicting new-onset diabetes mellitus after renal transplantation Clin Nephrol 2009;71(2): 140 –146 16 Woodward RS, Schnitzler MA, Baty J, et al Incidence and cost of new onset diabetes mellitus among US wait-listed and transplanted renal allograft recipients Am J Transplant 2005;3(5): 590 –598 17 Ekberg H, Tedesco-Silva H, Demirbas A, et al Reduced exposure to calcineurin inhibitors in renal transplantation N Engl J Med 2007;357(25):2562–2575 18 Vincenti F, Friman S, Sceuermann E, et al Results of an international, randomized trial comparing glucose metabolism disorders and outcome with cyclosporine versus tacrolimus Am J Transplant 2007;7(6):1506 –1514 19 Bloom RD, Crutchlow MF New-onset diabetes mellitus in the kidney recipient: diagnosis and management strategies Clin J Am Soc Nephrol 2008;3:S38 20 Davidson J, Wilkinson A, Dantal J, et al Diabetes after transplantation: 2003 International Consensus Guidelines Transplantation 2003;75:SS3–SS24 ... to “no diabetes, ” NODAT was associated with a 63% increased risk of graft failure (P Ͻ 0001), a 46% increased risk of death-censored graft failure (P Ͻ 0001) and a 85% increased risk of mortality... and 12-month intervals, and annually thereafter.20 Management of NODAT should follow a stepwise approach, beginning with nonpharmacologic therapy and progression, if necessary, to NEW- ONSET DIABETES. .. diabetes after transplantation 2003 International Consensus Guidelines: an endocrinologist’s view Diabetes Care 2004;27:805 Pham PT, Pham PM, Pham SV, Pham PA, Pham PC New onset diabetes after transplantation