Development Of New-onset Diabetes After Transplantation Research Articles

Risk of New-Onset Diabetes after Transplantation among Kidney Transplant Recipients with Cytomegalovirus Infection: A Retrospective Analysis

Background: New-onset diabetes after transplantation (NODAT) is one of the common complications reported in patients with kidney transplant and is associated with risk of infection, poor allograft and patient survival. There is conflicting research literature regarding the role of cytomegalovirus (CMV) infection in increasing the risk of NODAT development. Objective: To assess the risk of development of NODAT in kidney transplant patients with CMV infection Methods: A total of 59 kidney transplant patients were studied from March 2017 to February 2019. NODAT was defined as two readings of fasting plasma glucose of ≥126 mg/dL at three months post-transplant. CMV viral load was also documented. The 12 months post-transplant allograft and patient survival outcomes were also measured. Results: Mean age was 43.4 ± 6.2 years. Nearly one-fourth, 14 (23.7%), of the patients had NODAT. CMV viral load and viremia were high in NODAT group; however, the result did not reach statistical significance. CMV DNA replication was statistically high during 1-6 months post-transplant for NODAT group (P<0.001). Only 7 (11.9%) recipients advanced to symptomatic CMV infection. Also, we found that high CMV viremia load was associated with poor kidney allograft function at 12 months. Conclusions: In summary, this study showed that infection with CMV may not be a risk factor to develop NODAT in patients transplanted with kidney. An elevated CMV viral load may decrease the post-transplant allograft function at 12 months. The prompt diagnosis and timely management of CMV infection could substantially lessen the risk to develop NODAT subsequent worsening of allograft and patient survival. Keywords: Kidney; Transplant; NODAT; New-onset Diabetes; Cytomegalovirus

Early Steroid Withdrawal After Kidney Transplantation in Patients at Risk for New-Onset Diabetes After Transplantation

New-onset diabetes after transplantation (NODAT) is a serious complication after kidney transplantation because of worse graft survival and increased risk of cardiovascular events. It is partly induced by immunosuppressive therapies such as corticosteroids. This study aimed to assess whether early corticosteroid withdrawal on day 4 (early steroid withdrawal [ESW] group) could prevent the development of NODAT within 2 years posttransplantation while maintaining good graft and patient survival rates. This was an observational, single-center, retrospective study. All patients received an induction therapy of antithymocyte globulin or basiliximab and maintenance therapy of tacrolimus/mycophenolate mofetil/corticosteroids. Patients were either weaned off corticosteroids on day 4 (ESW group) or were maintained on corticosteroids for at least 3 months (standard group). NODAT was defined as the initiation of any oral hypoglycemic agent or insulin at 3 months and up to 2 years posttransplantation in previously nondiabetic recipients. Between January, 1, 2010, and December 14, 2014, 492 recipients were included in this study; 88 received the ESW strategy, and 404 received the standard strategy. Age and body mass index (BMI) were significantly higher in the ESW group. The incidence of NODAT was 36.8% in the ESW group and 8.8% in the standard group (odds ratio [OR], 47.5; P < .001). Compared with a matched sample from the standard group that had the same probability to benefit from ESW at baseline, ESW was still associated with a significantly increased risk of NODAT (OR, 4.41; P=.018). Among recipients with a BMI >25 kg/m2, the ESW strategy significantly decreased the risk of NODAT compared with the standard strategy (OR, 0.07; P=.013). Safety endpoints (eg, acute rejection, de novo-specific antibodies, graft function/survival) did not differ between groups. Despite a reassuring safety profile, ESW on day 4 after kidney transplantation only had a marginal effect on the incidence of NODAT.

Analysis of the frequency of single nucleotide polymorphisms in cytokine genes in patients with New Onset Diabetes After Transplant

New Onset Diabetes After Transplantation (NODAT) is a serious metabolic complication. While β-cell dysfunction is considered the main contributing factor in the development of NODAT, the precise pathogenesis is not well understood. Cytokines are thought to be involved in the inflammation of islet β-cells in diabetes; however, few studies have investigated this hypothesis in NODAT. A total of 309 kidney transplant recipients (KTRs) were included in this study. An association between kidney transplants, and the development of diabetes after transplant (NODAT) was investigated. Comparison was made between KTRs who develop diabetes (NODAT cases) or did not develop diabetes (control), using key cytokines, IL-6 G (− 174)C, macrophage mediator; IL-4 C (− 490)T, T helper (Th)-2 cytokine profile initiator; Th-1 cytokine profile initiator interferon-γ T (+ 874) A gene and TGF β1 C (+ 869) T gene polymorphisms were investigated. The genes were amplified using well-established polymerase chain reaction (PCR) techniques in our laboratory. Compared to the AA and AT genotypes of interferon gamma (IFNG), there was a strong association between the TT genotype of IFNG and NODAT kidney transplant recipients (KTRs) versus non-NODAT KTRs (p = 0.005). The AA genotype of IFNG was found to be predominant in the control group (p = 0.004). Also, significant variations of IL6 G (− 174) C, IL-4 C (− 590) T, interferon-γ T (+ 874) A gene and transforming growth factor β1 C (+ 869) T may contribute to NODAT. Our data is consistent with theTh-1/T-reg pathway of immunity. Further larger pan Arab studies are required to confirm our findings.

Immunosuppressive therapy as a risk factor for new-onset diabetes after transplantation

To analyze the modes of immunosuppressive therapy as a risk factor for new-onset diabetes after transplantation (NODAT) in kidney recipients. The retrospective analysis included data from 1367 recipients (755 men and 612 women) who lived more than one year after NODAT and were observed at the Moscow City Nephrology Center from January 1989 to December 2018. NODAT was established for 178 (13%) patients based on criteria from the World Health Organization and the American Diabetes Association. The modes of immunosuppressive therapy using cyclosporin A (CSA), tacrolimus (Tac), mTOR inhibitors, glucocorticoids in patients with NODAT and without NODAT were evaluated. To assess the impact of risk factors, descriptive statistics methods were used, the odds ratio (OR) and the 95% confidence interval (CI) were calculated. NODAT was diagnosed in 105 men and 73 women. The OR for men was 1.19 (95% CI 0.871.64), the OR for women was 0.84 (95% CI 0.611.15). At the time of transplantation, the average age of the kidney recipients in the NODAT group was higher than in the group without NODAT: 51 [43; 57] and 43 [32; 52] years, respectively (p=0.0001). Most patients with NODAT (82%) were older than 50 years, while in the group without NODAT, the proportion of patients of the same age was 48.5% (p=0.0001). Among patients without NODAT, transplantation of a kidney from a living donor was significantly more often compared with the group with NODAT+ (7.1% vs 1.1%;p=0.001). Among the recipients who received the regimen with CSA, diabetes developed in 75 (42.1%), those who received Tac in 102 (57.3%;p0.05). The chance (risk of development) of NODAT in patients receiving i-mTOR + Tac was 3.2 (95% CI 1.476.78;p=0.032), and for patients receiving i-mTOR + cyclosporin A, the chance of development NODAT was 1.95 (95% CI 0.884.35;p=0.044). 13% of recipients developed de novo kidney diabetes after allograft. Age at the time of allotransplantation, gender, as well as the use of tacrolimus in combination with i-mTOR are the most significant risk factors for the development of NODAT.

Risk Factors Related to New-Onset Diabetes after Renal Transplantation in Patients of a High Complexity University Hospital in Colombia, 20 Years of Experience.

Introduction New-onset diabetes after transplantation (NODAT) is associated with immunosuppression. Its complications can negatively influence patients' quality of life, which is why it is important to study the associated risk factors and expand the possible therapies in this particular group of patients. Materials and methods. Case-control study nested in a retrospective cohort. It included patients who received kidney transplantation at the high complexity University Hospital Fundación Valle del Lili in Cali, Colombia, between 1995 and 2014. Two controls were assigned for each case, depending on the type of donor and the date of the surgery. Information was collected from clinical records and the institutional TRENAL registry. We carried out a descriptive analysis of the selected variables and identified the risk factors with conditional logistic regression. Results 122 cases were identified to which 224 controls were assigned. The median age was 44 years (IQR: 34–55), and 54% were men. Having >50 years of age at the time of transplantation (OR: 3.18, 95% CI: 1.6−6.3, p = 0.001), body mass index >30 kg/m2 (OR: 3.6, 95% CI: 1.3−9.7, p = 0.010) and being afro-descendant (OR: 2.74, 95% CI: 1.1−6.5, p = 0.023) were identified as risk factors for the development of NODAT. Pretransplant fasting plasma glucose >100 mg/dl (OR: 2.9, 95% CI: 1.4−6.4, p = 0.005) and serum triglycerides >200 mg/dl (OR: 2.5, 95% CI: 1.4−4.4, p = 0.002) were also reported as independent risk factors.Conclusion We ratify some risk factors for the development of this important disease, which include certain modifiable characteristics. Interventions aimed at changes in lifestyle could be established in a timely manner before transplant surgery.

A new scoring system to predict the incidence of new onset diabetes after transplantation (NODAT)

Background. We performed this study to develop a new scoring system to stratify different levels of risk of developing new onset diabetes after transplantation (NODAT) in patients who underwent renal transplantation. Many prognostic variables have been previously described but few efforts have been made to group them in order to enhance their individual predictive power. Material and methods. In a first phase, 100 patients were prospectively analysed to determine which factors were significantly associated with the development of NODAT. A risk score ranging from 0 to 10 points was developed using a multivariate analysis. In a second phase, such score was validated in a new sample of 100 patients. Results. BMI ≥ 23.5 kg/m 2 , age ≥ 38.5 years, fasting blood sugar at 1 st post-operative day ≥ 159.5 mg/dL, fasting blood sugar at 5th post-operative day ≥ 122.5 mg/dL and HOMA-IR ≥ 2.5 were found as independent prognostic variables. A clear distinction was shown among categories of low, intermediate and high risk, defined according to the risk score. Conclusion. This new scoring framework is basic and simple to accomplish. It permits a generally excellent stratification of risk of developing NODAT in patients undergoing renal transplantation. They might be separated in three risk stratification cohorts, which could be of help in early identification of NODAT.

Prevalence and Risk Factors of New-Onset Diabetes After Transplantation (NODAT).

BackgroundNew-onset diabetes after transplantation (NODAT) is a serious complication after a solid organ transplant. NODAT occurs in 2% to 53% of all solid organ transplant recipients. The identification of high-risk patients and the implementation of measures to limit the development of NODAT can improve the long-term patient prognosis.Material/MethodsOur study group consisted of 336 patients undergoing heart transplant. Patients with prior diabetes (60 patients) were excluded from analysis. The remaining 276 patients were divided in 2 groups: with NODAT (n=109) and without NODAT (n=167). Logistic regression analysis was used for NODAT risk factor assessment.ResultsNODAT occurred in 109 (32%) out of 336 patients without diagnosed diabetes before heart transplantation. Risk factors for post-transplant diabetes mellitus, which was shown by the analysis of the collected data, were BMI at discharge (OR=1.082, CI 1.011–1.158, p=0.0233), history of diagnosed CMV infection (OR=1.464, CI 1.068–2.007, p=0.0179), and age over 51 years (OR=1.634, CI 1.274–2.095, p=0.0001).Conclusions1. New-onset diabetes after transplantation (NODAT) or long-lasting hypoglycemia (over 2 years after transplantation) was diagnosed in 32% patients after heart transplantation developed. 2. The risk factors of NODAT were BMI at discharge and history of diagnosed CMV infection, and age over 51 years was an independent risk factor.

P0701LONG-TERM RETROSPECTIVE OBSERVATION STUDY TO EVALUATE EFFECTS OF ADIPONECTIN ON SKELETAL MUSCLE IN KIDNEY TRANSPLANT RECIPIENTS

Abstract Background and Aims Although it is reported that chronic kidney disease participates some roles in progression of sarcopenia, mechanisms of the progression of sarcopenia are unclear so far. In this observational study, we focused on serum adiponectin levels, that is a marker of metabolic syndrome, cardiovascular disease, and skeletal muscle mass in patients with kidney transplantation. Method Fifty-one patients who underwent renal transplantation at our hospital in and after 1998 (31 males and 20 females; aged 29-52 years at the time of transplantation) were retrospectively examined the relationships between the psoas muscle index (PMI), intramuscular adipose tissue content (IMAC), serum adiponectin fractions (high-/low-molecular-weight), and new-onset diabetes after transplantation (NODAT). Results Age at kidney transplantation negatively correlated with PMI before transplantation and positively correlated with IMAC before transplantation (rS=-0.427, p&amp;lt;0.01; rS=0.501, p&amp;lt;0.01, respectively). Both in one and five years after transplantation, PMI was higher than before transplantation (p&amp;lt;0.01). In contrast, IMAC transiently decreased one year after kidney transplantation, but subsequently recovered five years after kidney transplantation. Multivariate analyses identified that the mean increases of high-molecular-weight adiponectin concentrations was exacerbating factor for the mean change in PMI (p=0.003). Moreover, the mean increases of PMI and IMAC were exacerbating factors for the newly development of post-transplantation diabetes mellitus. Conclusion PMI increased associated with high-molecular-weight adiponectin levels after renal transplantation. In addition, PMI increased suppressed the development of NODAT.

Statin Use Is Prospectively Associated With New-Onset Diabetes After Transplantation in Renal Transplant Recipients.

New-onset diabetes after transplantation (NODAT) is frequent and worsens graft and patient outcomes in renal transplant recipients (RTRs). In the general population, statins are diabetogenic. This study investigated whether statins also increase NODAT risk in RTRs. From a prospective longitudinal study of 606 RTRs (functioning allograft >1 year, single academic center, follow-up: median 9.6 [range, 6.6-10.2] years), 95 patients using statins were age- and sex-matched to RTRs not on statins (all diabetes-free at inclusion). NODAT incidence was 7.2% (73.3% of these on statins). In Kaplan-Meier (log-rank test, P = 0.017) and Cox regression analyses (HR 3.86 [95% CI 1.21-12.27]; P = 0.022), statins were prospectively associated with incident NODAT, even independent of several relevant confounders including immunosuppressive medication and biomarkers of glucose homeostasis. This study demonstrates that statin use is prospectively associated with the development of NODAT in RTRs independent of other recognized risk factors.

A retrospective cohort study of preoperative lipid indices and their impact on new-onset diabetes after liver transplantation.

BackgroundThe correlation between preoperative lipid profiles and new‐onset diabetes after transplantation (NODAT) remains relatively unexplored in liver transplant recipients (LTRs). Thus, we aimed to investigate the preoperative lipid profiles in Chinese LTRs and evaluate the different influences of preoperative total cholesterol, total triglycerides (TG), high‐density lipoprotein cholesterol, and low‐density lipoprotein cholesterol on the development of NODAT in both sexes.MethodsA total of 767 Chinese LTRs from Zhongshan Hospital were retrospectively evaluated. NODAT was defined according to the American Diabetes Association guidelines; the relationship between each preoperative lipid index and NODAT development was analyzed separately in men and women.ResultsPretransplant hypotriglyceridemia was observed in 35.72% of the total LTRs. In men, only the preoperative TG level was significantly associated with incident NODAT after adjusting for potential confounders (hazard ratio 1.37, 95% confidence interval 1.13‐1.66, P = .001). There was a nonlinear relationship between the preoperative TG level and NODAT risk. The risk of NODAT significantly increased with preoperative a TG level above 0.54 mmol/L (log‐likelihood ratio test, P = .043). In women, no significant association was observed.ConclusionAmong male LTRs, a higher preoperative TG level, even at a low level within the normal range, was significantly and nonlinearly associated with an increased risk of NODAT.

Incidence of New-Onset Diabetes and PostTransplant Metabolic Syndrome after Liver Transplantation - A Prospective Study from South India.

Background and Aims:Liver transplantation has become an effective therapy for patients with end-stage liver disease. The risk of new-onset diabetes after transplantation (NODAT) and posttransplant metabolic syndrome (PTMS) is high among patients after liver transplantation. These are thought to be associated with increased risks of graft rejection, infection, cardiovascular disease, and death. Our study aimed to document the incidence of NODAT and PTMS and analyze pre and posttransplant predictive factors for their development in patients undergoing a liver transplant.Methods:This was a prospective comparative study on 51 patients who underwent live donor liver transplantation. They were evaluated at baseline, 3 and 6 months after transplantation with fasting glucose, lipids, serum insulin levels, C-peptide, and HbA1C. They were followed up at 5 years to document any cardiovascular events or rejection.Results:The incidence of preoperative diabetes mellitus (DM) in the study group was 25/51 (49%). The incidence of NODAT was 38.5% (10/26 patients) and PTMS 29% (10/35), respectively. Age (47.7 ± 5.4 vs 41.5 ± 12.7 years), HOMA2 - IR (2.3 ± 1.8 vs 2.1 ± 1.6), serum insulin (16.1 ± 12.0 vs 17.9 ± 14.5), and C-peptide (4.6 ± 0.5 vs 4.8 ± 0.7) were similar at baseline in the NODAT group compared to those who did not develop it. Mean tacrolimus levels were higher in PTMS group (6.8 ± 2.9 vs 5.0. ± 2.0 P value = 0.042). By the end of 5 years, 7 patients expired; 6 due to rejection and one due to cardiovascular disease. Moreover, 2 of these patients had preexisting DM and 2 had NODAT.Conclusions:None of the baseline metabolic factors in patients undergoing liver transplant were predictive of the development of NODAT or PTMS. Mean tacrolimus levels were significantly higher in the PTMS group. A 5-year follow-up showed no excess risk of cardiovascular events or rejection in those with preexisting DM or in those who developed NODAT.

Immune phenotype predicts new onset diabetes after kidney transplantation

Few data are available concerning immune factors involved in the occurrence of new onset diabetes after transplantation (NODAT). Our objective was to determine an immune profile associated with the subsequent development of NODAT. The secondary objective was to build a predictive model of NODAT. We studied a prospective cohort of incident kidney transplant patients to determine whether pre-transplant immune characteristics could be associated with the occurrence of NODAT. 818 patients were included. We observed a significant inverse correlation between BMI and recent thymic emigrants (RTE) % at transplant time (p < 0.001). 177 (17.3%) of 677 non-diabetic patients experienced NODAT in the first year post-transplant. In multivariate analysis, age, body mass index (BMI), use of Tacrolimus, use of anti-thymocyte globulins (ATG), higher B cell count, and lower recent thymic emigrants (RTE) % were associated with NODAT. A differential effect of immune profile was observed in ATG-treated patients and non-ATG-treated patients. B cell count predicts NODAT only in non-ATG-treated patients whereas lower RTE% was associated with NODAT only in ATG-treated patients. Tacrolimus sparing and B cell depletion may efficiently prevent NODAT in selected patients. We identified an immune profile associated with the occurrence of post-transplant diabetes. Further studies should better precise the exact mechanisms involved in this association. Trial registration NCT02843867, registered July 8, 2016 – retrospectively registered https://clinicaltrials.gov/ct2/show/record/NCT02843867.

Immunogenetics of new onset diabetes after transplantation in Kuwait.

Introduction and aim: New onset diabetes after transplantation (NODAT) is a serious metabolic complication following kidney transplantation. Although beta-cell dysfunction is considered the main contributing factor in the development of this complication, its exact etiology is yet to be identified. We aimed to investigate NODAT among kidney transplant cohort in Kuwait with special stress on correlation between its risk factors and interferon gamma genotyping.Materials and methods: We surveyed 309 kidney transplant recipients from Hamed Al Essa Transplantation Centre, Kuwait. The participants were categorized into cohorts according to the development of NODAT diagnosed based on the American Diabetes Association guidelines. Statistical analyses were performed using SPSS software. We genotyped interferon gamma as the leading immunosignature for T lymphocyte.Results: No relationship between ethnicity and the development of NODAT was identified. However, there was a significant difference in age between cohorts. Younger patients demonstrated a lower rate of NODAT while, NODAT reached its maximum in 40–60-year age group. IFNG TT genotype was significantly associated with NODAT (p=0.005), while IFNG AA was considerably higher in the non-NODAT group.Conclusion: Beside the conventional contributing factors of NODAT, our results might represent a suitable platform for a larger cytokine and chemokine spectrum genotyping.

Pretransplant Homeostasis Model Assessment of Insulin Resistance and Fasting Plasma Glucose Predict New-Onset Diabetes After Renal Transplant in Chinese Patients

Background and AimThe present study aims to determine if homeostasis model assessment of insulin resistance (HOMA-IR) index, fasting plasma glucose (FPG), and plasma insulin (Ins) are able to predict development of new onset diabetes after transplant (NODAT) for kidney recipients. MethodsWe performed a single-center retrospective study of 123 nondiabetic patients receiving a first renal transplant. The NODAT was diagnosed between 1 month and 1 year post transplant. Both univariate and multivariable analyses, including logistic regression analysis and Cox proportional hazards model, were applied to dissect potential pretransplant risk factors of NODAT. ResultsA total of 26.8% (33/123) of recipients developed NODAT in the first year post transplant. The NODAT patients showed higher HOMA-IR index and increased levels of FPG and Ins than non-NODAT. Interestingly, we consistently revealed that both FPG (logistic: odds ratio [OR], 3.17 [1.41–6.45]; P = .01; Cox: OR, 2.75 [1.26–4.56]; P = .02) and HOMA-IR index (logistic: OR, 1.73 [1.21–2.87]; P = .02; Cox: OR, 1.72 [1.21–2.46]; P = .002) robustly predicted the development of NODAT. However, these analyses showed that neither plasma Ins nor hemoglobin A1c was associated with NODAT. ConclusionOur findings suggest that pretransplant HOMA-IR and FPG are independent predictors for the development of NODAT in Chinese nondiabetic patients receiving a first renal transplant.

Effects of preoperative hepatitis B virus infection, hepatitis C virus infection, and coinfection on the development of new-onset diabetes after kidney transplantation.

The effects of preoperative hepatitis B virus (HBV) infection, hepatitis C virus (HCV) infection, and HBV plus HCV coinfection on the development of new-onset diabetes after transplantation (NODAT) remain unexplored in kidney transplant recipients (KTRs). This study examined the association between preoperative viral status (i.e., HBV, HCV, and HBC + HCV infection) and incident NODAT in a large population of Chinese KTRs. This population-based retrospective cohort study enrolled 557 subjects who underwent kidney transplantation between 1993 and 2014 at Zhongshan Hospital. Pre-, peri-, and postoperative data were extracted and analyzed. Viral status was defined by serological results for hepatitis B surface antigen and anti-HCV antibody. The cumulative incidence of NODAT was compared across four groups of KTRs with different viral status. Multivariate Cox regression models were used to estimate the effects of HBV, HCV, and HBC + HCV infection on incident NODAT after adjusting for important confounders. Patients seropositive for HCV (both HCV monoinfection and HBC + HCV coinfection) had a significantly higher cumulative incidence of NODAT than KTRs who were not infected with HCV (P < 0.05 for both). However, only HCV infection alone was found to be a risk factor for NODAT, increasing the NODAT risk 3.03-fold (95% confidence interval 1.77-5.18; P < 0.001). There was no independent correlation between HBV infection (alone or combined with HCV) and incident NODAT in KTRs. Preoperative HCV infection significantly increased the risk of NODAT in Chinese KTRs, whereas HBV infection and HBC + HCV coinfection were not correlated with NODAT development.

New-onset diabetes after kidney transplantation: Incidence and associated factors.

AIMTo determine the incidence and associated factors of new-onset diabetes after transplantation (NODAT) in a Portuguese central hospital.METHODSThis single-center retrospective study involved consecutive adult nondiabetic transplant recipients, who had undergone kidney transplantation between January 2012 and March 2016. NODAT was diagnosed according to the criteria of the American Diabetes Association. Data were collected from an institutional database of the Nephrology and Kidney Transplantation Department (Santa Maria Hospital, Lisbon, Portugal) and augmented with data of laboratorial parameters collected from the corresponding patient electronic medical records. Exclusion criteria were preexisting diabetes mellitus, missing information and follow-up period of less than 12 mo. Data on demographic and clinical characteristics as well as anthropometric and laboratorial parameters were also collected. Patients were divided into two groups: With and without NODAT - for statistical comparison.RESULTSA total of 156 patients received kidney transplant during the study period, 125 of who were included in our analysis. NODAT was identified in 27.2% of the patients (n = 34; 53% female; mean age: 49.5 ± 10.8 years; median follow-up: 36.4 ± 2.5 mo). The incidence in the first year was 24.8%. The median time to diagnosis was 3.68 ± 5.7 mo after transplantation, and 76.5% of the patients developed NODAT in the first 3 mo. In the group that did not develop NODAT (n = 91), 47% were female, with mean age of 46.4 ± 13.5 years and median follow-up of 35.5 ± 1.6 mo. In the NODAT group, the pretransplant fasting plasma glucose (FPG) levels were significantly higher [101 (96.1-105.7) mg/dL vs 92 (91.4-95.8) mg/dL, P = 0.007] and pretransplant impaired fasting glucose (IFG) was significantly more frequent (51.5% vs 27.7%, P = 0.01). Higher pretransplant FPG levels and pretransplant IFG were found to be predictive risk factors for NODAT development [odds ratio (OR): 1.059, P = 0.003; OR: 2.772, P = 0.017, respectively].CONCLUSIONNODAT incidence was high in our renal transplant recipients, particularly in the first 3 mo posttransplant, and higher pretransplant FPG level and IFG were risk factors.

Interleukin-2 receptor antagonists: Protective factors against new-onset diabetes after renal transplantation.

The aim of the present study was to examine the association between interleukin-2 receptor antagonists (IL-2Ra) and new-onset diabetes after transplantation (NODAT) among renal transplant recipients (RTRs). Between January 1993 and March 2014, 915 patients underwent renal transplantation at Zhongshan Hospital. In all, 557 RTRs were included in the present retrospective cohort study. The incidence of NODAT in this cohort was determined and multivariate Cox regression analysis was used to evaluate the risk factors for NODAT and to show the association between IL-2Ra use and NODAT development among RTRs. The cumulative incidence of NODAT was compared between groups treated with or without IL-2Ra. The mean ±SD postoperative follow-up was 5.08 ±3.17 years. The incidence of NODAT at the end of follow-up was 20.3%. After adjusting for potential confounders in the multivariate logistic regression (i.e. age, sex, body mass index, history of smoking, family history of diabetes, duration of dialysis, type of dialysis, donor type, recovery of graft function, acute rejection, hepatitis B or C or cytomegalovirus infection, fasting plasma glucose levels before and 1 week after transplantation, preoperative total cholesterol and triglyceride levels, daily dose of glucocorticoid, immunosuppressive regimen type, and immunosuppressant concentration after transplantation), IL-2Ra use was found to be related to a reduced incidence of NODAT. Use of IL-2Ra is associated with protection against the development of NODAT in RTRs.

Influence of interleukin-2 receptor antagonists on the morbidity and prognosis of new-onset diabetes after liver transplantation

Objective To explore the influence of interleukin-2 receptor antagonists(IL-2Ra)on the morbidity and prognosis of new onset diabetes after transplantation(NODAT)in liver transplant recipients. Methods Pre- and post-operative clinical data of 879 nondiabetic patients who underwent a liver transplantation between April 2001 and December 2016 were retrospectively studied. All the enrolled patients were divided into IL-2Ra and non-IL-2Ra groups according to the use of IL-2Ra. Transient-NODAT(T-NODAT)and Persistent-NODAT(P-NODAT)were defined according to whether NODAT would be existed continuously. The impacts of IL-2Ra on the cumulative incidence as well as the risk of NODAT and T-NODAT were analyzed through comparison between patients who used IL-2Ra or not. And influence of IL-2Ra on the long-term survival of NODAT patients was further analyzed. Results Among 879 patients, 177(32.24%)from the IL-2Ra group(n=549)developed NODAT and 29.38%(n=52)of the NODAT reversed, while 131(39.70%)from the non-IL-2Ra group(n=330)developed NODAT and 26.72%(n=35)of the NODAT reversed. After adjusting for 18 possible confounding factors, the IL-2Ra group had significantly decreased cumulative incidence of NODAT over the non-IL-2Ra group(adjusted P=0.028). COX regression analyses showed that IL-2Ra was a protective factor against NODAT development(HR 0.774; 95%CI 0.616-0.973; P=0.028), while the use of IL-2Ra and the reverse of NODAT did not significantly related. In addition, long-term survival of the NODAT patients were far better in the IL-2Ra group(adjusted P=0.001). Conclusion IL-2Ra significantly reduces the risk of NODAT in liver transplant recipients and is beneficial to the long-term survival of NODAT patients. (Chin J Endocrinol Metab, 2018, 34: 121-128) Key words: Newly-onset diabetes after transplantation; Liver transplantation; Interleukin-2 receptor antagonists

Association between anemia at three different time points and new-onset diabetes after kidney transplantation––a retrospective cohort study

ABSTRACTPurpose: Anemia has been reported to be associated with diabetes, but the association between new-onset diabetes after transplantation (NODAT) and anemia has not been reported.Methods: Patients who underwent kidney transplantation and did not have diabetes prior to transplantation were included in this study. Hemoglobin levels and the prevalence of anemia (hemoglobin <12 g/dL in females and <13 g/dL in males) were evaluated at three time points (prior to transplantation, 6 months following transplantation or 1 month before the development of NODAT, 2 years following transplantation, or following the development of NODAT) and were compared between those who developed NODAT and those who did not. Variables associated with the development of anemia were compared between the two groups.Results: A total of 266 kidney transplant recipients were included, of which 71 (27%) developed NODAT during the time of the follow-up. Hemoglobin and hematocrit levels and the prevalence of anemia were similar in those with and without NODAT at all three time points evaluated. Ferritin levels, prior to transplantation and mean corpuscular volume (MCV) posttransplantation post-NODAT development, were slightly but significantly lower in those with NODAT, although both were within the normal range.Conclusions: Pretransplantation ferritin levels and posttransplantation post-NODAT development MCV are inversely associated with the development of NODAT in kidney transplants.

Genetic and clinic predictors of new onset diabetes mellitus after transplantation.

New Onset Diabetes after Transplantation (NODAT) is a frequent complication after solid organ transplantation, with higher incidence during the first year. Several clinical and genetic factors have been described as risk factors of Type 2 Diabetes (T2DM). Additionally, T2DM shares some genetic factors with NODAT. We investigated if three genetic risk scores (w-GRS) and clinical factors were associated with NODAT and how they predicted NODAT development 1 year after transplantation. In both main (n = 725) and replication (n = 156) samples the clinical risk score was significantly associated with NODAT (ORmain: 1.60 [1.36-1.90], p = 3.72*10-8 and ORreplication: 2.14 [1.39-3.41], p = 0.0008, respectively). Two w-GRS were significantly associated with NODAT in the main sample (ORw-GRS 2:1.09 [1.04-1.15], p = 0.001 and ORw-GRS 3:1.14 [1.01-1.29], p = 0.03) and a similar ORw-GRS 2 was found in the replication sample, although it did not reach significance probably due to a power issue. Despite the low OR of w-GRS on NODAT compared to clinical covariates, when integrating w-GRS 2 and w-GRS 3 in the clinical model, the Area under the Receiver Operating Characteristics curve (AUROC), specificity, sensitivity and accuracy were 0.69, 0.71, 0.58 and 0.68, respectively, with significant Likelihood Ratio test discrimination index (p-value 0.0004), performing better in NODAT discrimination than the clinical model alone. Twenty-five patients needed to be genotyped in order to detect one misclassified case that would have developed NODAT 1 year after transplantation if using only clinical covariates. To our knowledge, this is the first study extensively examining genetic risk scores contributing to NODAT development.