Risk Of New-onset Diabetes After Transplantation Research Articles

#1992 Triglyceride-glucose index and risk of cardiovascular events, graft loss and new onset diabetes after transplantation in renal transplant recipients

Abstract Background and Aims Insulin resistance is prevalent disorder, but its clinical significance remains undetermined in renal transplant recipients. We explored the clinical implication of triglyceride-glucose (TyG) index in renal transplant recipients, recognizing it as a valuable marker for insulin resistance. Method A total of 6354 renal transplant recipients were enrolled from a nationwide, prospective cohort between May 2014 and December 2022. The TyG index was assessed between 6- and 12-months post-transplantation. We evaluated the association between TyG index and the risk of composite of cardiovascular events and death, renal allograft loss, and new onset diabetes after transplantation (NODAT). Results During the mean follow-up period of 39.2 ± 26.1 months, a total of 106 composite events of cardiovascular events and death, 174 events of renal allograft loss, and 438 events of NODAT were observed. The cumulative rate for composite events, graft loss, and NODAT was greater in patients with higher TyG quartile (all P < 0.001). In multivariate analysis, higher quartile of TyG was associated with an increased risk of composite events (HR 1.81, 95% CI 1.14–2.86), renal allograft loss (HR 2.13, 95% CI 1.28–3.55), and NODAT (HR 2.52, 95% CI 1.90–3.34). Higher quartile of TyG was associated with future graft dysfunction (adjusted mean eGFR differences of −4.72, 95% CI −7.39 – −2.04). There was a linear escalation in the risk of composite events and graft loss with the incremental rise in the TyG index, concomitant with an exponential augmentation in the risk of NODAT. Conclusion Renal transplant recipients with higher TyG index are associated with higher risk of composite of cardiovascular event and death, renal allograft loss, and NODAT.

Genetic variations in a Sestrin2/Sestrin3/mTOR Axis and development of new-onset diabetes after kidney transplantation

BackgroundGenetic variations in Sestrin2/Sestrin3/ mTOR axis may cause obesity-associated metabolic syndrome, including lipid accumulation and insulin resistance thereby increasing individual's risk of diabetes. In this study, we explored the association between single nucleotide polymorphisms (SNPs) of these genes and new onset diabetes after transplantation in Hispanic renal transplant recipients (RTRs). MethodsNine potential functional polymorphisms in Sestrin2, Sestrin3 and mTOR genes were genotyped using the Taqman qPCR method in this study. We compared 160 Hispanic RTRs with no evidence of pre-existing diabetes, who developed new onset diabetes after transplantation (NODAT) with 152 controls with no history of diabetes. The logistic proportional hazard model was used to examine risks for NODAT. Nongenetic and genetic characteristics were included in the multivariate risk model. ResultsSignificant associations were observed between NODAT and mTOR TT (rs2295080 OR = 1.79, 95% CI =1.14–2.82, p = 0.01), Sestrin2 AA (rs580800, OR = 0.42, 95% CI =0.27–0.67, p = 0.002), and Sestrin3 AA (rs684856, OR = 0.45, 95% CI = 0.27–0.75, p = 0.001). Sestrin2 AA (rs580800), Sestrin3 AA (rs684856) and mTOR TT (rs2295080) remained significantly associated with NODAT after adjusting for acute rejection and sirolimus use. No interactions observed between the mTOR rs2295080 and Sestrin3 rs684856 and risk of NODAT (mTOR rs2295080 and Sestrin3 rs684856, p = 0.123 and mTOR rs2295080 and Sestrin2 rs580800, p = 0.167). Of the nongenetic factors, use of sirolimus and older age were associated with an increased risk for NODAT. ConclusionPolymorphisms in the Sestrin2/Sestrin3/ mTOR gene may confer certain protection/predisposition for NODAT.

Remnant lipoprotein cholesterol is associated with incident new onset diabetes after transplantation (NODAT) in renal transplant recipients: results of the TransplantLines Biobank and cohort Studies

BackgroundNew onset diabetes after transplantation (NODAT) is a frequent and serious complication of renal transplantation resulting in worse graft and patient outcomes. The pathophysiology of NODAT is incompletely understood, and no prospective biomarkers have been established to predict NODAT risk in renal transplant recipients (RTR). The present work aimed to determine whether remnant lipoprotein (RLP) cholesterol could serve as such a biomarker that would also provide a novel target for therapeutic intervention.MethodsThis longitudinal cohort study included 480 RTR free of diabetes at baseline. 53 patients (11%) were diagnosed with NODAT during a median [interquartile range, IQR] follow-up of 5.2 [4.1–5.8] years. RLP cholesterol was calculated by subtracting HDL and LDL cholesterol from total cholesterol values (all directly measured).ResultsBaseline remnant cholesterol values were significantly higher in RTR who subsequently developed NODAT (0.9 [0.5–1.2] mmol/L vs. 0.6 [0.4–0.9] mmol/L, p = 0.001). Kaplan-Meier analysis showed that higher RLP cholesterol values were associated with an increased risk of incident NODAT (log rank test, p < 0.001). Cox regression demonstrated a significant longitudinal association between baseline RLP cholesterol levels and NODAT (HR, 2.27 [1.64–3.14] per 1 SD increase, p < 0.001) that remained after adjusting for plasma glucose and HbA1c (p = 0.002), HDL and LDL cholesterol (p = 0.008) and use of immunosuppressive medication (p < 0.001), among others. Adding baseline remnant cholesterol to the Framingham Diabetes Risk Score significantly improved NODAT prediction (change in C-statistic, p = 0.01).ConclusionsThis study demonstrates that baseline RLP cholesterol levels strongly associate with incident NODAT independent of several other recognized risk factors.

TCF7L2 rs7903146 Is Associated With Increased Risk of New-Onset Diabetes After Transplant: A Meta-analysis of Literature

Single nucleotide polymorphisms may influence the risk of development of new-onset diabetes after transplant (NODAT), a post-transplant clinical complication that is often implicated in allograft rejection and mortality. We performed a meta-analysis of association between transcription factor 7-like-2 (TCF7L2) rs7903146 and risk of NODAT. A systematic search was conducted using PubMed and ScienceDirect electronic databases for studies published between January 2001 and January 2021. Case-control or cohort studies reporting association between NODAT (diagnosis based on American Diabetes Association criteria) and TCF7L2 rs7903146 were included. MetaGenyo was used for meta-analysis (random-effects model). Pooled odds ratios with 95% confidence intervals were reported to evaluate the strength of association. Two reviewers independently screened for articles. A total of 6 case-control studies were included for full-text review and quantitative analysis after screening for eligibility. Genotypic distributions were in Hardy-Weinberg equilibrium for included studies. All articles reported statistically significant association of TCF7L2 rs7903146 for risk of NODAT except for 1 study. There was moderate heterogeneity among studies (I2=60.6%). Pooled analysis revealed 51% odds of developing NODAT with TCF7L2 rs7903146 T allele (allele contrast model: odds ratio, 1.51; 95% confidence interval, 1.13-2.02; P=.005). The present meta-analysis demonstrated association between TCF7L2 variant rs7903146 and risk of developing NODAT. This finding suggest clinical implications for individuals undergoing kidney transplant.

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.

Predictive Value of Triglyceride Glucose Index for the Development of New-Onset Diabetes Mellitus Following Heart Transplantation

<h3>Purpose</h3> Diabetes mellitus (DM) is a major cause of morbidity and mortality following heart transplantation (HT), with 35% being affected within 5 years. Identification of patients at risk for the development of DM could enable prevention and proper intervention. The Triglyceride Glucose (TyG) index is considered a surrogate marker of insulin resistance and is an early indicator for developing type 2 DM in the non-transplant population. We investigated the association between the TyG index and new-onset diabetes after transplantation (NODAT). <h3>Methods</h3> A total of 158 non-DM HT patients were included in the study. The risk of NODAT was assessed according to the 3-month TyG index, calculated as ln[fasting triglycerides (mg/dL) × fasting plasma glucose (mg/dL)/2]. The endpoint was NODAT, defined according to the diagnostic criteria of the American Diabetes Association. <h3>Results</h3> The overall prevalence of NODAT was 20%. The TyG index in the NODAT group was significantly higher than that for the no-NODAT group (9.4 vs 8.7, p <0.001). A TyG index of 8.9 had a sensitivity of 78%, with a specificity of 70% for the prediction of NODAT. Kaplan-Meier survival analysis showed that NODAT rate was significantly higher for patients with a high vs a low TyG index (40 vs 8%, p >0.001, Fig.). Consistently, multivariable analysis, adjusted for age, gender, BMI, immunosuppression, hypertension, and dyslipidemia, showed that a high TyG index was independently associated with a significant 3.3-fold increased risk for NODAT (p = 0.03, Fig.). Patients with a high TyG index had significantly higher rates of peripheral vascular disease (21 vs 8%, p = 0.04) and allograft vasculopathy (48 vs 19%, p <0.001) than patients with a low TyG index. <h3>Conclusion</h3> The TyG index, a simple measure reflecting insulin resistance, might help identify individuals at high risk for developing NODAT. The implications of early interventions, using the TyG index as a marker, on the risk for NODAT and clinical outcomes, should be evaluated.

Use of Imputation and Decision Modeling to Improve Diagnosis and Management of Patients at Risk for New-Onset Diabetes After Transplantation.

BackgroundNew-onset diabetes after transplantation (NODAT) is a complication of solid organ transplantation. We sought to determine the extent to which NODAT goes undiagnosed over the course of 1 year following transplantation, analyze missed or later-diagnosed cases of NODAT due to poor hemoglobin A1c (HbA1c) and fasting blood glucose (FBG) collection, and to estimate the impact that improved NODAT screening metrics may have on long-term outcomes.Material/MethodsThis was a retrospective study utilizing 3 datasets from a single center on kidney, liver, and heart transplantation patients. Retrospective analysis was supplemented with an imputation procedure to account for missing data and project outcomes under perfect information. In addition, the data were used to inform a simulation model used to estimate life expectancy and cost-effectiveness of a hypothetical intervention.ResultsEstimates of NODAT incidence increased from 27% to 31% in kidney transplantation patients, from 31% to 40% in liver transplantation patients, and from 45% to 67% in heart transplantation patients, when HbA1c and FBG were assumed to be collected perfectly at all points. Perfect screening for kidney transplantation patients was cost-saving, while perfect screening for liver and heart transplantation patients was cost-effective at a willingness-to-pay threshold of $100 000 per life-year.ConclusionsImproved collection of HbA1c and FBG is a cost-effective method for detecting many additional cases of NODAT within the first year alone. Additional research into both improved glucometric monitoring as well as effective strategies for mitigating NODAT risk will become increasingly important to improve health in this population.

New-onset diabetes mellitus after liver transplantation in the patients with acute liver failure

To detect the frequency and possible risk factors of new-onset diabetes after liver transplantation in the patients with acute liver failure. The frequency of new-onset diabetes after transplant (NODAT) is 5–30% in liver transplant recipients. We aimed to analyze the frequency and predictors of NODAT in the patients undergoing liver transplantation due to acute liver failure. Adult patients undergoing liver transplantation due to acute liver failure were analyzed retrospectively. The patients with chronic liver failure or diabetes were excluded. We measured pretransplant random blood glucose and posttransplant fasting blood glucose. NODAT was diagnosed according to principally 1st month fasting blood glucose (group 1 125 mg/dL). The participants were subgrouped according to age, gender, body mass index, etiology, antiviral medication, thyroid function, pretransplant random blood glucose, donor type, immunosuppressive drug, common infection, and surgical complication. Mean age of total 91 patients was 33.48 (± 13.35), and 52.7% (n = 48) of them was female. The ratio of NODAT was 26.98% on the 1st month. NODAT group had a higher pretransplant random blood glucose than the others. Pretransplant hyperglycemia increased the risk of NODAT by 4.065 times (p = 0.018). We showed that pretransplant hyperglycemia increased NODAT risk by 4 times, but hypoglycemia did not affect. So, pretransplant hyperglycemia should be controlled also in the patients with acute liver failure as in the patients with chronic liver failure.

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.

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.

Risk factors and long-term consequences of new-onset diabetes after renal transplantation.

New-onset diabetes after transplant (NODAT) confers risk of diabetes-related complications as well as a threat to graft function and overall patient survival. The reported incidence of NODAT varies from 14 to 37% in renal transplant recipients worldwide; however, NODAT is yet to be studied in the Irish renal transplant population. Primary aims of this project were to estimate the incidence, to determine associated risk factors and to assess the long-term consequences of NODAT on graft survival and patient survival in the Irish renal transplant population. Retrospective data collection of 415 renal transplant recipients over a 12-year period was performed to record presence of NODAT, patient characteristics and perioperative management. Preoperative screening was reviewed in a subgroup of patients to determine concordance with the International Consensus Guidelines. Statistical analysis was performed using Kaplan-Meier survival functions estimating NODAT detection over time, graft and patient survival. Risk factor association was determined using Cox proportional-hazards models. NODAT incidence was 10.2% in the first 5years of post-transplant. Risk factors for developing NODAT were recipient age and body weight. Risk of NODAT was highest in the first year of post-transplant and conferred decreased patient survival; however, it did not significantly affect graft survival. Only seven patients of a subgroup of 21 patients who developed NODAT had preoperative testing for diabetes. NODAT incidence in the Irish renal transplant population is slightly below international figures. This project has highlighted current deficits in the national transplant guidelines for the detection of NODAT and NODAT-related risk factors.

Hypomagnesemia is associated with new-onset diabetes mellitus following heart transplantation

BackgroundDiabetes mellitus (DM) is a major cause of morbidity and mortality following heart transplantation (HT), with 21% and 35% of survivors being affected within 1 and 5 years following HT, respectively. Magnesium deficiency is common among HT patients treated with calcineurin inhibitors and is a known risk factor for DM in non-HT patients. We therefore investigated the association between serum Mg (s-Mg) levels and new-onset diabetes after transplantation (NODAT).MethodsBetween 2002 and 2017, 102 non-DM HT patients were assessed. In accordance with the mean value of all s-Mg levels recorded during the first year post-HT, patients were divided into high s-Mg (≥ 1.8 mg/dL) and low s-Mg (< 1.8 mg/dL) groups. The endpoint was NODAT, defined according to the diagnostic criteria of the American Diabetes Association.ResultsBaseline clinical and demographic characteristics for the high (n = 45) and low s-Mg (n = 57) groups were similar. Kaplan–Meier survival analysis showed that 15-year freedom from NODAT was significantly higher among patients with high vs low s-Mg (85% vs 46% log-rank test, p < 0.001). Consistently, multivariate analysis adjusted for age, gender, immunosuppression therapies, BMI and mean creatinine values in the first year post-HT, showed that low s-Mg was independently associated with a significant > 8-fold increased risk for NODAT (95% CI 2.15–32.63, p = 0.003). Stroke rate was significantly higher in patients with low s-Mg levels vs high s-Mg (14% vs 0, p = 0.025), as well as long term mortality (HR 2.6, 95% CI 1.02–6.77, p = 0.05).ConclusionsLow s-Mg level post-HT is an independent risk factor for NODAT in HT patients. The implications of interventions, focusing on preventing or correcting low s-Mg, for the risk of NODAT and for clinical outcomes should be evaluated.

Plasma Malondialdehyde and Risk of New-Onset Diabetes after Transplantation in Renal Transplant Recipients: A Prospective Cohort Study.

New-onset diabetes after transplantation (NODAT) is a frequent complication in renal transplant recipients (RTR). Although oxidative stress has been associated with diabetes mellitus, data regarding NODAT are limited. We aimed to prospectively investigate the long-term association between the oxidative stress biomarker malondialdehyde (measured by high-performance liquid chromatography) and NODAT in an extensively phenotyped cohort of non-diabetic RTR with a functioning graft ≥1 year. We included 516 RTR (51 ± 13 years-old, 57% male). Median plasma malondialdehyde (MDA) was 2.55 (IQR, 1.92–3.66) µmol/L. During a median follow-up of 5.3 (IQR, 4.6–6.0) years, 56 (11%) RTR developed NODAT. In Cox proportional-hazards regression analyses, MDA was inversely associated with NODAT, independent of immunosuppressive therapy, transplant-specific covariates, lifestyle, inflammation, and metabolism parameters (HR, 0.55; 95% CI, 0.36–0.83 per 1-SD increase; p < 0.01). Dietary antioxidants intake (e.g., vitamin E, α-lipoic acid, and linoleic acid) were effect-modifiers of the association between MDA and NODAT, with particularly strong inverse associations within the subgroup of RTR with relatively higher dietary antioxidants intake. In conclusion, plasma MDA concentration is inversely and independently associated with long-term risk of NODAT in RTR. Our findings support a potential underrecognized role of oxidative stress in post-transplantation glucose homeostasis.

Hypomagnesemia is Associated with New-Onset Diabetes Mellitus Following Heart Transplantation

Purpose Diabetes mellitus (DM) is a major cause of morbidity and mortality following heart transplantation (HT), with 21% and 35% of survivors being affected within 1 and 5 years following HT, respectively. Magnesium (Mg) deficiency is common among HT patients treated with calcineurin inhibitors and is a known risk factor for DM in non-HT patients. We therefore investigated the association between serum Mg (s-Mg) levels and new-onset diabetes after transplantation (NODAT). Methods Between 2002 and 2017 we assessed 101 non-DM HT patients. S-Mg levels were reviewed during the first year post-HT. In accordance with the mean value of all s-Mg levels recorded during the first year, patients were divided into high s-Mg (≥1.8 mg/dL) and low s-Mg ( hemoglobin A1c ≥6.5%; fasting plasma glucose ≥126 mg/dL; or random plasma glucose ≥200 mg/ dL. Results Baseline clinical and demographic characteristics for the high s-Mg (n=42) and low s-Mg (n=59) groups were similar. Kaplan-Meier survival analysis showed that 15-year freedom from NODAT was significantly higher among patients with high s-Mg vs low s-Mg (84% vs 22% log-rank test, p=0.003, Figure). Consistently, multivariate analysis adjusted for age, gender, immunosuppression therapies and mean creatinine values of the first year post-HT, showed that low s-Mg was independently associated with a significant >5-fold increased risk for NODAT (95% CI 1.35-21.04, p=0.02). Patients with low s-Mg levels had a significantly higher rate of cerebrovascular events than patients with high s-Mg (15.5% vs 0, p=0.02). Conclusion Low post-HT s-Mg level is an independent risk factor for NODAT in HT patients. The implications of interventions, focusing on preventing or correcting low s-Mg, on the risk for NODAT and on clinical outcomes should be evaluated.

New-Onset Diabetes and Preexisting Diabetes Are Associated With Comparable Reduction in Long-Term Survival After Liver Transplant: A Machine Learning Approach

ObjectiveTo identify key predictors and survival outcomes of new-onset diabetes after transplant (NODAT) in liver transplant (LT) recipients by using the Scientific Registry of Transplant Recipients. Patients and MethodsData of all adult LT recipients between October 1, 1987, and March 31, 2016, were analyzed using various machine learning methods. These data were divided into training (70%) and validation (30%) data sets to robustly determine predictors of NODAT. The long-term survival of patients with NODAT relative to transplant recipients with preexisting diabetes and those without diabetes was assessed. ResultsIncreasing age (odds ratio [OR], 1.01; 95% CI, 1.00-1.02; P≤.001), male sex (OR, 1.09; 95% CI, 1.05-1.13; P=.03), and obesity (OR, 1.13; 95% CI, 1.08-1.18; P<.001) were significantly associated with NODAT. Sirolimus as a primary immunosuppressant carried a 33% higher risk of NODAT than did tacrolimus (OR, 1.33; 95% CI, 1.22-1.45; P<.001) at 1 year after LT. Patients with NODAT had significantly decreased 10-year survival than did those without diabetes (63.0% vs 74.9%; P<.001), similar to survival in patients with diabetes before LT (58.9%). ConclusionUsing a machine learning approach, we found that older, male, and obese recipients are at especially higher risk of NODAT. Donor features do not affect risk. In addition, sirolimus-based immunosuppression is associated with a significantly higher risk of NODAT than other immunosuppressants. Most importantly, NODAT adversely affects long-term survival after LT in a manner similar to preexisting diabetes, indicating the need for more aggressive care and closer follow-up.

Effect of Calcineurin Inhibitor on Blood Glucose Level in Non-Diabetic Kidney Transplant Patients

Background Calcineurin inhibitor (CNI) is a class of immunosuppressant agent used in kidney transplant management, known to pose risk for new-onset diabe­tes after transplant (NODAT). Tacrolimus and cyclo­sporine cause NODAT through multiple mechanisms, such as decreasing insulin secretion, increasing in­sulin resistance, and a direct effect on the pancreatic beta cell. Method This is a retrospective study on pa­tients receiving immunosuppressant agents for kidney transplant patients in Surabaya. The immunosuppres­sant agents studied were CNI (tacrolimus and cyclo­sporine) in combination with mycophenolate mofetil (MMF) or azathioprine (Aza) and steroid. The blood glucose measured were fasting blood glucose (FBD) and 2-hour postprandial blood glucose (2PPBG). Ob­jective Aim of this study is to determine the effect of calcineurin inhibitor (CNI) on glucose regulation in the nondiabetic renal transplant patient. Result Fifty-six subjects were included in the study, divided into two groups. One group of 28 patients (50%) received tac­rolimus-MMF-MP and the other group received cyc­losporine-MMF-MP. A significant increase in fasting blood glucose (pre-intervention level 86 ± 6 mg/dl vs post-intervention level 109 ± 34 mg/dl with p = 0.01) and 2-hour postprandial blood glucose (pre-interven­tion level 117 ± 20 mg/dl vs post-intervention level 150 ± 43 mg/dl with p &lt; 0.001) was found in the tacro­limus group. A significant increase was also found in the cyclosporine group, both in fasting blood glucose (pre-intervention value 85 ± 7 mg/dl vs post-interven­tion value 97 ± 22 mg/dl with p = 0.002) and 2-hour postprandial blood glucose (pre-intervention value 119 ± 18 mg/dl vs post-intervention value 148 ± 55 mg/dl with p = 0.001). Tacrolimus was found to have a relative risk of NODAT up to 1.2 fold compared to cy­closporine. Conclusion Tacrolimus poses 1.29 relative risk of NODAT compared to cyclosporine. However, both drugs significantly increase fasting blood glucose and 2-hour postprandial blood glucose in non-diabetic patients receiving kidney transplantation.

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.

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 ADIPOQ gene polymorphisms and the risk of new-onset diabetes mellitus after liver transplantation

New-onset diabetes after transplantation (NODAT) has become one of the major factors that affect the overall survival and long-term life quality in liver transplantation (LT) recipients. Previous studies found that the serum adiponectin concentration of diabetic patients is significantly lower than that of healthy subjects. Adiponectin regulates the blood glucose level by increasing body sensitivity to insulin through various mechanisms. In this study, we aimed to investigate the impact of diabetes related gene polymorphisms on the development of NODAT in liver recipients. A total of 256 LT patients in a single-center were selected retrospectively for the study. Genomic DNA was extracted from explanted liver tissues, and tested for twelve diabetes mellitus associated single nucleotide polymorphisms by Sequenom MassARRAY. Modified clinical models in predicting NODAT were established and evaluated. The GG genotype of ADIPOQ rs1501299 gene polymorphism was significantly more frequent in NODAT than non-NODAT LT patients (56% vs 39%, P=0.014). Dominant model (GG vs GT+TT, P=0.030) and recessive model (GT+GG vs TT, P=0.005) also confirmed the genotype distribution difference between NODAT and non-NODAT groups. Age (OR=1.048, P=0.004), BMI (OR=1.107, P=0.041), and blood tacrolimus level at 1-month LT (OR=1.170, P=0.003) were clinical independent risk factors of NODAT. Furthermore, rs1501299 could improve the ability of clinical model in predicting NODAT (AUROC=0.743, P<0.001). ADIPOQ rs1501299 gene polymorphism is associated with an increased risk of NODAT, which should be added to the clinical models in predicting the occurrence of NODAT in LT recipients.