New-onset Diabetes After Transplantation Research Articles

6984 New Onset Diabetes After Transplant: Need for Strict Glucose Monitoring

Abstract Disclosure: T. Chaudhary: None. O. Syed: None. M. Nawaz: None. R. Kaur: None. Introduction: Immunosuppressant use comes at a cost of challenging side effects, which are being discovered more as its use increases. One such example is our case of new-onset diabetes after transplant (NODAT).Patient presentation: A 36-year-old male with a past medical history of end-stage renal disease status post renal transplant (6/2023), hypertension, and hyperlipidemia who presented to the hospital in 10/2023 with fever, chills, and diarrhea. His vitals at that time were as follows: temperature 36.1C, blood pressure 148/84 mmHg, pulse 87 bpm, and a respiratory rate of 22. Lab work was significant for blood glucose 1144, anion gap 22, bicarbonate 13, potassium 7.3, Sodium 135, lipase 427, pH 7.3, urine ketones 80, HbA1C 11.5 %. CT scan of the abdomen revealed loss of peripancreatic fat and inflammatory changes surrounding the pancreas. His medication review included Tacrolimus 12 mg daily, Mycophenolate 500 mg BID, Valtrex 500mg daily, and fluconazole 200mg every other day. He was treated with 2 liters of normal saline bolus and started on maintenance fluid, and insulin drip as per DKA protocol. Calcium gluconate and an albuterol nebulizer were given for hyperkalemia. Tacrolimus and prednisone were held. Endocrinology and Nephrology were consulted. The patient was thought to have diabetes due to steroid use which were discontinued and the patient was discharged on subcutaneous insulin regimen and lower dose of tacrolimus. Despite discontinuation of steroids, patients continued to have raised glucose readings confirming the causative agent as tacrolimus. Conclusion: The current guidelines for post-kidney transplant patients recommend checking fasting blood glucose weekly for the first four weeks, then biweekly for two months, and then monthly thereafter. HbA1C should be checked every 3 months and if it is >6% then home glucose monitoring should be done as well. Although the frequency of these check-ups decreases, it is imperative for physicians to remember that patients can still develop NODAT months post-transplant. It is also essential to reinforce the importance of these glucose checks for the patient as missed diagnosis can lead to dangerous complications such as DKA. Presentation: 6/2/2024

Safety of SGLT2 Inhibitors in Kidney Transplant Recipients with Type 2 Diabetes Mellitus (T2DM) or New-Onset Diabetes after Transplant (NODAT): A Single-Centre Experience

Safety of SGLT2 Inhibitors in Kidney Transplant Recipients with Type 2 Diabetes Mellitus (T2DM) or New-Onset Diabetes after Transplant (NODAT): A Single-Centre Experience

Impact of New-Onset Diabetes after Transplantation on Cardiovascular Risk and Mortality in Korea: A Nationwide Population-Based Study.

Limited data are available on the adverse effects of new-onset diabetes after transplantation (NODAT) in solid organ transplantation (TPL) other than kidney. This study aimed to identify the risk of complications associated with NODAT in recipients of kidney, liver, or heart TPL. Using the Korean National Health Insurance Service database, recipients of kidney, liver, or heart TPL between 2009 and 2015 were identified. The incidence of coronary artery disease (CAD), cerebrovascular accident (CVA), and malignancy was compared across groups with NODAT, pretransplant diabetes mellitus (DM), and without DM using Cox regression analysis. A total of 9,632 kidney, liver, or heart TPL recipients were included. During the median follow-up of 5.9 years, NODAT independently increased the incidence of CAD (hazard ratio [HR], 2.46; 95% confidence interval [CI], 1.39 to 4.30) and overall mortality (HR, 1.48; 95% CI, 1.14 to 1.95) compared to the reference group even after adjustment for confounders; this was more prominent in kidney TPL than in liver TPL. The risk of CVA was significantly increased by pretransplant DM but not by NODAT in both kidney and liver TPL (HR, 2.47; 95% CI, 1.68 to 3.65; and HR, 3.18; 95% CI, 1.07 to 9.48, respectively). NODAT increased the risk of malignancy in the crude model, which lost its statistical significance after confounder adjustment. NODAT independently increases the risk of CAD and mortality after TPL, which is more evident in kidney recipients. There was no additional increased risk of CVA or malignancy with NODAT in solid organ TPL.

#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.

#2586 Time to event prediction of new-onset diabetes after transplantation in kidney transplant recipients using machine learning models

Abstract Background and Aims New-onset diabetes after transplantation (NODAT) is a common and serious complication of kidney transplantation that contributes to long-term morbidity and mortality after the transplant procedure. Conventional methods may predict the risk of, but not time to developing NODAT. We aimed to develop a machine learning model that predicts the time to NODAT in kidney transplant recipients (KTR). Method Two large prospective cohort studies of stable KTR (inclusion >1 year after transplantation) from the University Medical Center Groningen were combined. Data collection took place between 2001 and 2003 for cohort A, and between 2008 and 2011 for cohort B, resulting in the inclusion of 750 KTR free of NODAT at baseline. To predict absolute time to NODAT, a bootstrap aggregating (bagging) approach was utilized which consisted of several extreme gradient boosting (XGBoost) models with the accelerated failure time (AFT) objective. The performance of the resulting bagging model was internally evaluated by assessing the concordance index (c-index) in 20% of the dataset not used for training. Results From the 750 KTR included, 76 (10.1%) developed NODAT during a median (interquartile range [IQR]) follow-up of 5.8 (4.7 to 9.2) years. The median (IQR) age was 51.2 (40.5 to 60.7) years and 342 (45.6%) of the KTR were female. During feature engineering, 18 features from 53 were selected. After hyperparameter tuning, model performance during internal validation was 0.84. Furthermore, SHapley Additive exPlanations (SHAP) values were used to estimate feature importance, which revealed that glucose, HbA1c, mean arterial pressure, cyclosporine concentrations and daily vegetable intake were the most important features. Conclusion The developed machine learning model shows good discriminative ability of time to NODAT prediction. Due to the methodology used, the model allows for flexible incremental learning, meaning that the bagging model can be retrained with additional data without compromising on performance.

#97 Study of association between post transplant diabetes mellitus (PTDM) and hypomagnesemia

Abstract Background and Aims New onset diabetes after transplantation (NODAT) or PTDM (Post-transplant Diabetes Mellitus) is associated with increased morbidity, renal graft loss, cardiovascular complications, mortality and increased health care costs. It has been shown that incidence of NODAT is rising in recent years. It is suggested that there is more prominent role of beta cell dysfunction rather than insulin resistance in patients with PTDM. Hypomagnesemia which is commonly seen in post-transplant patients is suggested to have a role in promoting beta cell dysfunction. Emerging modifiable risk factors for PTDM like hypomagnesemia need to be studied which may help to improve its prevalence and outcomes. Method This study was single centre study to assess association of PTDM or NODAT with hypomagnesemia. Other risk factors like body mass index (BMI) >25 kg/m2, higher age and sex of the recipient were also studied. This study was a prospective, non-randomised, comparative, observational study. Duration of the study was from 1st October 2016 to 28th February 2018. Recipients with age > 18 years with at least 2 fasting blood sugar readings of >126 mg/dl or 2 post prandial readings of >200 mg/dl or need for antidiabetic medications beyond 1-month post-transplant were studied as PTDM or NODAT. Patients with deceased donor transplant, second kidney transplant, simultaneous other organ transplant, active Hepatitis C infection, active cytomegalovirus infection, patients with acute rejection, patients with polycystic kidney disease and patients with basiliximab induction were excluded. Results After applying exclusion and exclusion criteria, 98 patients were studied in total. Among 98 patients around 40 patients developed PTDM. When assessed independently higher age of the patient (age more than 50 years) was associated with PTDM (p = .030) while sex of the recipient was not associated with PTDM (P = .188). BMI >25 kg/m2 was significantly associated with PTDM at 1 month (p = .0001), 2 month (p < .0001), 3 month (p < .0001), 6 month (p < .0001), 9 month (p = .0001) and 12 month (p = .003) post-transplant. No statistical difference between doses of steroids were seen in patients with or without PTDM. All 98 patients received tacrolimus as part of their immunosuppressant regime. Time varying serum tacrolimus trough levels were not associated with PTDM and was removed as confounder by using univariate cox proportional hazard model (p = 0.691). After univariate and subsequently multivariate logistic regression analysis only hypomagnesemia was significantly associated with PTDM (p = .0001). After using univariate and subsequently multivariate cox proportional hazard model to study time varying risk factors, both hypomagnesemia (HR, 0.099; 95% CI, 0.016-0.624, p = .014) and BMI >25 kg/m2 (HR, 3.435; 95% CI, 1.657-7.119, p = .001) were associated with PTDM. Significantly a greater number of patients with lower magnesium levels developed PTDM early as compared to patients with normal magnesium levels (Spearman's coefficient of rank correlation (rho) = 0.53; 95% CI, 0.261-0.722, p = .0004). Conclusion Hypomagnesemia and overweight are modifiable risk factors significantly associated with PTDM even after removing confounding factors. Early development of PTDM in patient with hypomagnesemia further corroborates its role. Active interventions should be sought to control hypomagnesemia and overweight which may improve the morbidity and mortality of kidney transplant patients in long run.

New onset diabetes after transplantation (NODAT) in kidney transplant recipient in Montenegro

New onset diabetes after transplantation (NODAT) in kidney transplant recipient in Montenegro

Safety and efficacy of early corticosteroid withdrawal in liver transplant recipients: A randomized controlled trial.

Prolonged use of steroids after liver transplantation (LT) significantly increases the risk of diabetes or cardiovascular disease, which can adversely affect patient outcomes. Our study evaluated the effectiveness and safety of early steroid withdrawal within the first year following LT. This study was conducted as an open-label, multicenter, randomized controlled trial. Liver transplant recipients were randomly assigned to one of the following two groups: Group 1, in which steroids were withdrawn two weeks posttransplantation, and Group 2, in which steroids were withdrawn three months posttransplantation. This study included participants aged 20 to 70 years who were scheduled to undergo a single-organ liver transplant from a living or deceased donor at one of the four participating centers. Between November 2012 and August 2020, 115 patients were selected and randomized into two groups, with 60 in Group 1 and 55 in Group 2. The incidence of new-onset diabetes after transplantation (NODAT) was notably higher in Group 1 (32.4%) than in Group 2 (10.0%) in the per-protocol set. Although biopsy-proven acute rejection, graft failure, and mortality did not occur, the median tacrolimus trough level/dose/weight in Group 1 exceeded that in Group 2. No significant differences in safety parameters, such as infection and recurrence of hepatocellular carcinoma, were observed between the two groups. The present study did not find a significant reduction in the incidence of NODAT in the early steroid withdrawal group. Our study suggests that steroid withdrawal three months posttransplantation is a standard and safe immunosuppressive strategy for LT patients.

Neutrophil: Lymphocyte and Platelet: Lymphocyte ratios measured before transplantation and their correlation with new-onset diabetes post-transplantation in renal transplant recipients

PurposeOur goal was to evaluate the neutrophil:lymphocyte (NLR) and platelet:lymphocyte (PLR) ratios measured before transplantation and their correlation with new-onset diabetes after transplantation (NODAT) in renal transplant recipients. Patients and methodsWe conducted our study in 324 adult patients consecutively admitted to Military Hospital 103, Ha Noi, Viet Nam, who received kidney allografts from living donors. These patients were followed-up during the first 2 years post-transplantation for NODAT. We examined the association between NLR and PLR measured prior to transplantation in patients with NODAT: NLR and PLR were calculated based on the results of the complete blood count. The criteria for diagnosis of a fully symptomatic NODAT case were based on the guidelines established by the American Diabetes Association and included fasting venous blood glucose and glycosylated hemoglobin A1c (HbA1c) levels, with or without an oral glucose tolerance test. ResultsThe overall rate of NODAT during the two years after kidney transplantation was 13.6%. We found mean values of age and body mass index (BMI), and median values of NLR, PLR, high sensitivity C-reactive protein (hs-CRP) levels, and the arteriosclerosis ratio in the NODAT group to be significantly higher than those of the non-NODAT group (all p < 0.05). Furthermore, an adjusted multivariate regression analysis showed that age (area under the curve [AUC] = 0.727, p < 0.001), BMI (AUC = 0.846, p < 0.001), serum hs-CRP levels (AUC = 0.884, p < 0.001), NLR (AUC = 0.888; p < 0.001), and PLR (AUC = 0.818; p < 0.001) had predictive value for NODAT. ConclusionNLR and PLR measured before transplantation were good predictors for NODAT in the first 2 years post-renal transplantation.

Single Center Experience With Sodium-Glucose Co-Transporter-2 Inhibitors (SGLT2i) in Kidney Transplant Recipients With Diabetes.

Sodium-glucose co-tranporter-2 inhibitors have been shown to be safe and effective in patients with type 2 diabetes for improving glycemia. Furthermore large, randomized control trials have shown cardiovascular and renal benefits. However, limited safety and efficacy data is available in kidney transplant patients with diabetes. To investigate the safety and efficacy of SGLT2i use on stability of renal function in adult kidney transplant recipients (KTR) with type 2 diabetes mellitus (DM2) or New Onset Diabetes After Transplantation (NODAT). We performed a single center, retrospective cohort study pre- and post-SGLT2i exposure. Adults with DM2 or NODAT who received a living or deceased kidney transplant (Tx) and started on an SGLT2i post-Tx were reviewed. Patients who had type 1 diabetes were excluded. The baseline was the SGLT2i start date. We reviewed available data from 24 months (M) before and after SGLT2i initiation. The primary endpoints were the effects of SGLT2i use on stability of renal function using serum creatinine and eGFR, change in urine albumin excretion(uACR), and glycosylated hemoglobin (A1C). Secondary endpoints compared blood pressure, body mass index and adverse reactions at baseline and quarterly after SGLT2i initiation. 125 KTRs were included in cohort: NODAT (52, 42%), DM2 (73, 58%); female (33, 27%); mean age at Tx 55 years (25-75); LD (56, 45%), DD (69, 55%); mean duration of Tx (6.8 years, 0.1-42.5); study follow-up (1.8 years, 0.3-4.9).The mean eGFR remained stable pre-SGLT2i at 64.6 mL/min/1.73m2, vs post at 64.3 mL/min/1.73m2. There was no difference in mean A1C after SGLT2i initiation. The slope of uACR using natural log transformation pre-SGLT2i compared with post-SGLT2i slope reduced from +0.7 (0.03, 0.11) to -0.04 (-0.01, -0.35) mg/mmol/3mths (P = .002). The risk of developing new genital mycotic infections among all patients was 4% (95% CI 1.3%-9.1%) While there was no significant difference in UTI before (13.6%) and after (12%) SGLT2i use (P = .68), there was a higher risk of UTI seen in patients with a previous history of UTI (23.5%) vs no previous history (10.2%) post initiation. There was no significant increase in AKI pre 8%, post 10.4%, P = .51. There was a single DKA event pre- and post-SGLT2. The limitations of this study include its retrospective nonrandomized nature. In this retrospective analysis, SGLT2i use in KTR appears to be safe and efficacious with stable renal function and glycemic control, alongside improvements in uACR. There was a low risk of new genital yeast infections after SGLT2i start. UTI occurrence was higher in patients with a previous history of UTI compared with those with no previous history.

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.

1398-P: Contribution of New-Onset Diabetes after Organ Transplantation on the Incident Cardiovascular Disease and Malignancy in Korea—A Nationwide Population-Based Study

Background: In Korea, the number of solid organ transplantation (TPL) has been markedly increased; however, there has been limited data on the adverse effect on the cardiovascular disease and malignancy of new onset diabetes after transplantation (NODAT) in solid organ TPL other than kidney. Methods: Using the National Health Insurance Service (NHIS) database which covers the claims of 97.0% of the population in Korea, the recipients of kidney, liver, and heart TPL in 2009-2015 were identified and categorized into 3 groups: without NODAT (reference), with NODAT, and pre-existing diabetes mellitus (DM). The incidence of myocardial infarction (MI), stroke, and malignancy till December 2018 in each group were compared using Cox-regression analysis. Results: Among the entire 18,763 cases of TPL identified, NODAT was detected in 29.8% (27.2% [2,903 out of 10,687], 43.4% [3,247 out of 7,747], and 41.5% [250 out of 602] in kidney, liver, and heart TPL, respectively); and 77.3% of NODAT cases were detected within 3 months after TPL. NODAT increased the risk of MI, but not of stoke, by 2.3 times compared to the reference group after adjustment for age, sex, hypertension, dyslipidemia, and immunosuppressants (hazard ratio [HR], 2.34; 95% CI, 1.61-3.51), which was observed only in kidney TPL (HR, 2.44; 95% CI, 1.52-3.91) but not in liver TPL. A significant increment of the risk of malignancy by NODAT was found only in kidney TPL (HR, 1.30; 95% CI, 1.04-1.64), whose statistical significance was lost after adjusting confounders. During the same period, no association between pre-existing DM and malignancy was found, neither. Conclusion: NODAT independently increased the risk of MI after organ transplantation, which was more evident in the recipient of kidney TPL. There was no additional increased risk of stroke or malignancy by NODAT in solid-organ TPL. Disclosure B.Koo: None. M.Moon: None. S.Park: None. K.Han: None.

CARDIOVASCULAR COMPLICATIONS AFTER CADAVERIC RENAL TRANSPLANTATION

Objective: Renal transplantation is the treatment for end-stage renal disease. Cadaveric donor renal transplantation (CDRT) is still uncommon in Tunisia, constituting less than 20% of total renal transplants. The aim of our study was to evaluate the results and cardiovascular complications in our center Design and method: A retrospective analysis of 30 CDRT was performed between November 1995 and December 2018. Data analysis included. age, gender, cold ischemia time, graft function graft function, dialysis requirements dialysis requirements, rejection episodes rejection, infectious episodes, new onset diabetes after transplantation (NODAT), hypertension and cardiovascular events Results: Thirty patients underwent CDRT among 172 renal transplants performed in our unit. Among the donors, there were 23 males and 7 females, with a mean age of 32 ± 9 years. All transplants were blood group compatible with 3 HLA matches in the majority of cases (45%). The mean age of the recipients was 34 ± 9 years. Chronic glomerulonephritis (40%) and chronic chronic interstitial nephropathy (32%) represented the main type of native renal disease. 88.5% of the patients were hemodialysis before transplantation and the median time to transplantation on dialysis was dialysis was eight years. The mean nadir of creatinine was 108 ± 27 μmol/l. Two biopsies showed acute tubular injury, four patients had acute rejection and two patients had allograft nephropathy allograft nephropathy with one case of segmental and focal hyalinosis. segmental and focal hyalinosis. The major infectious complication was a cytomegalovirus cytomegalovirus infection (33.3%) followed by a urinary tract infection (23.8%). Regarding metabolic complications metabolic complications, NODAT and hypertension were observed in three and four patients respectively. Two patients presented an acute coronary syndrome treated with medical therapy. Five patients returned to dialysis. The rest (57.7%) have been followed up regularly in our consultation so far over a period of 87 months (range 16-209 months). Conclusions: CDRT is not common in our center, but the analysis shows good results and provides encouraging data that support broadening the criteria for potential donors eligible for organ donation especially in the face of increasing organ shortages. Cardiovascular complications are not as common

Endoplasmic reticulum stress in the adipose tissue and monocyte chemoattractant protein-1 are involved in tacrolimus-induced diabetes mellitus.

Tacrolimus is an independent risk factor for new-onset diabetes after transplantation (NODAT). This study aimed to identify the mechanisms underlying tacrolimus-induced NODAT. About 80 kidney-transplant patients receiving tacrolimus were divided into NODAT and non-NODAT groups after 1 year. Binary logistic regression was used to identify risk factors for NODAT. Insulin resistance indices were estimated using the homeostasis model assessment. The blood levels of 13 adipocytokines were measured 1 week after transplantation. A tacrolimus-induced diabetes mouse model was used to reveal the underlying mechanisms. The cumulative NODAT incidence was 12.7% at 1 year (median, 6 months; range, 3-12 months). Tacrolimus trough levels ≥10 ng/mL during the first 3 months (odds ratio: 2.54, p = .012) were related to NODAT. Insulin resistance indices were higher in NODAT patients than in non-NODAT patients at 3, 6, and 12 months. Monocyte chemoattractant protein (MCP)-1 was overexpressed in blood in NODAT patients. In the animal experiments, postprandial blood glucose and insulin levels, insulin pathway protein levels in adipose tissue, MCP-1 expression in blood and adipose tissue, and number of macrophages in adipose tissue were markedly higher in tacrolimus-treated mice than in control mice, and these increases were dose-dependent. The expression of endoplasmic reticulum (ER) stress proteins in adipose tissue was increased in a tacrolimus dose-dependent manner. In conclusion, tacrolimus-induced insulin resistance. Tacrolimus trough levels ≥10 ng/mL during the first 3 postoperative months were an independent risk factor for NODAT. ER stress and MCP-1 underlie tacrolimus-induced diabetes.

The effect of PINK1/Parkin pathway on glucose homeostasis imbalance induced by tacrolimus in mouse livers

Treatment using the immunosuppressive drug tacrolimus (TAC) is related to new-onset diabetes after transplantation (NODAT). Previous studies focused mainly on islet β cells in the diabetogenic effect of TAC. Herein, we revealed that NODAT was probably induced by TAC via hepatic insulin resistance. After daily injection of mice with TAC, a glucose metabolism disorder was induced. In addition, TAC decreased the mRNA and protein levels of insulin receptor substrate 2 (IRS2), glucose transporter type 2 (GLUT2), and the phosphorylation of protein kinase B beta (pAKT2), which indicated impaired hepatic insulin signaling. Furthermore, the PTEN-induced novel kinase 1(PINK1)/Parkin pathway was shown to have a key role in the TAC-induced imbalance of hepatic glucose homeostasis. Mechanistic investigations in human hepatic cell lines revealed that TAC stimulated PINK1/Parkin expression and inhibited the expression of insulin signaling related molecules (e.g., IRS2, GLUT2 and pAKT2). Knockdown of hepatic PINK1 regulated downstream molecules of the PINK1/Parkin pathway (GLUT2 and IRS2), which reversed TAC-induced insulin resistance. Thus, in the liver, PINK1/Parkin signaling plays an important role in the TAC-induced imbalance of glucose homeostasis. TAC-induced diabetes might be prevented using Targeted treatment.

Prevalence and Risk Factors of New-onset Diabetes after Transplant in East Africans.

Very little is known about the prevalence of new-onset diabetes after transplant (NODAT) in sub-Saharan and Eastern Africans. Most of the data are related to African Americans and to North and South Africans. The aims of this study were to examine the prevalence of NODAT in Sudanese renal transplant recipients, compare it with the published literature, and identify the risk factors for developing NODAT. In total, 150 patients who received a living-related kidney transplant between January 2015 and January 2016 were included in this study. Patients with diabetic nephropathy and pretransplant diabetes were excluded. Follow-up was for 2 years after the transplant. The variables studied were age, sex, body mass index, a family history of diabetes mellitus (DM), pretransplant steroid therapy, dyslipidemia, and hepatitis C virus infection. Twenty- three patients (15.3%) developed NODAT during the study period. The mean age of the patients who developed NODAT was 39 ± 14 years, and the mean time to develop NODAT was 5.78 ± 5.9 months. In the multivariate analysis, the risk factors for developing NODAT were a family history of DM (P = 0.01) and pretransplant steroid therapy (P = 0.01). The prevalence of NODAT in this study was 15.3%, which is in line with the reported literature from North Africa. However, it was significantly lower than the reported prevalence in African Americans.

PSUN228 Incidence and Predictors of New Onset Diabetes After Transplant (NODAT) in Liver Transplant recipients.

Abstract Background NODAT (New onset Diabetes after Transplant) is associated with multiple complications in liver transplant recipients which has to be diagnosed and treated early to prevent graft failure, cardiovascular morbidity and mortality. With improvement in the care of liver transplant recipients, post-transplant survival has significantly increased. With improved survival, incidence of chronic rejection, Diabetes, Hypertension, Dyslipidemia, etc. complications incidence also increasing. Aims and Objectives To know the incidence and predictors of NODAT. Methodology This was a prospective study of non-Diabetic recipients who underwent Liver Transplantation at Yashoda Hospital, Secunderabad from January 2020 to May 2021. The follow-up duration was 6 months. Total 65 patients were enrolled after excluding recipients who were &amp;lt;18 years of age, were already having diabetes, whose survival was less than 6 months of transplantation and who were not of an Indian origin. All the relevant clinical and biochemical data were collected. Appropriate statistical tests were applied to compare NODAT and Non-diabetes groups (recipients who did not develop diabetes after liver transplantation) to know the predictors of NODAT. Diagnosis of NODAT was be established by the standard ADA guidelines using Fasting blood sugar (FBS), Post prandial blood sugar(PPBS) or HbA1C. Diagnosis of NODAT required the presence of one of the four parameters: (i) fasting blood glucose levels ≥ 126 mg/dL on two occasions OR (ii) Insulin therapy requirement for &amp;gt;= 30 days OR (iii) oral hypoglycemic agent use for ≥ 30 consecutive days OR (iv) HbA1c ≥ 6.5. Transient NODAT was defined as the resolution of hyperglycemia within 6 months of transplantation. Results Total incidence of NODAT in our study was 29.2%. Among them 47.36% were transient NODAT and 52.67% were persistent NODAT. Factors significantly associated with occurrence of NODAT were: Type of Transplant (Living donor liver transplant v/s Deceased donor liver transplant), Presence of Impaired fasting glucose (IFG), presence of post-operative hyperglycemia, lower pre-transplant Magnesium &amp; Immediate post-operative Magnesium level, lower post-operative Albumin, higher trough Tacrolimus level at 3 Months, higher Tacrolimus and steroid dose at 3 months. Factors for which association with NODAT could not be found were: Age, Hepatitis C cirrhosis, alcoholic cirrhosis, pre-transplant BMI, baseline MELD score, pre-transplant FBS, donor age, donor gender, donor BMI, donor FBS &amp; Hba1c, donor CT LAI (Liver Attenuation Index, L-S) value, Steroid dose at discharge, immediate post-op trough Tacrolimus level and use of Everolimus. CONCLUSION: NODAT is the significant entity to be addressed. A robust strategy should be in place for the screening of NODAT. Lower Magnesium levels, presence of pre-transplant IFG and post-operative hyperglycemia give an early opportunity for detection of NODAT. Minimizing Tacrolimus level and steroid dose could be an effective strategy for the prevention of NODAT. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

Monitoring of blood glucose after pediatric kidney transplantation: a longitudinal cohort study

BackgroundGlucose metabolism after kidney transplantation (KT) is highly dynamic with the first post-transplantation year being the most critical period for new-onset diabetes after transplantation (NODAT) occurrence. The present study aimed to analyze dynamics of glucose metabolism and report incidence/risk factors of abnormal glycemic state during the first year after KT in children.MethodsTwenty-one consecutive freshly transplanted pediatric kidney transplant recipients (KTRs) were assessed for fasting plasma glucose (FPG) and oral glucose tolerance test (OGTT) weekly for 4 weeks, then every 3 months for 1 year.ResultsInterpretation of OGTT test showed normal glucose tolerance (NGT) in 6 patients (28.6%) while 15 (71.4%) experienced impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) at any time point of monitoring. Seven patients had NODAT, for which three needed insulin therapy. Hyperglycemia onset was 7.8 ± 13.12 weeks (median (range) = 1 (0–24) week) after KT. Percent of patients with abnormal OGTT was significantly more than that of IFG (38.1% vs. 71.4%, p = 0.029). Patients with abnormal glycemic state had significantly elevated trough tacrolimus levels at 6 months (p = 0.03). Glucose readings did not correlate with steroid doses nor rejection episodes while positively correlating with tacrolimus doses at 3 months (p = 0.02, CC = 0.73) and 6 months (p = 0.01, CC = 0.63), and negatively correlating with simultaneous GFR at 9 months (p = 0.04, CC = − 0.57).ConclusionsUp to two thirds of pediatric KTRs (71.4%) experienced abnormal glycemic state at some point with peak incidence within the first week up to 6 months after KT. OGTT was a better tool for monitoring of glucose metabolism than FPG. Abnormal glycemic state was induced by tacrolimus and adversely affected graft function.Graphical abstractA higher resolution version of the Graphicalabstract is available as Supplementary information.

Transplantation and new onset Diabetes Mellitus

Background: Single nucleotide polymorphisms may influence the risk of development of new-onset diabetes after transplantation (NODAT), a post-transplant clinical complication that is often implicated in allograft rejection and mortality. We performed a meta-analysis of association between TCF7L2 rs7903146 and risk of post-transplant diabetes mellitus.&#x0D; Methods: A systematic search was conducted using PubMed and ScienceDirect electronic databases for studies published between January 2001 to January 2021. Case-control or cohort studies reporting association between NODAT (diagnosis based on American Diabetes Association [ADA] 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 strengths of association.

Outcomes of Kidney Transplantation in Patients with Autosomal Dominant Polycystic Kidney Disease: Our Experience Based on 35-Years Follow-Up.

Background and objectives: For patients with end-stage renal disease (ESRD), the best replacement therapy is renal transplant (RTx) to ensure life with good quality. Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disorder and a common cause of ESRD. Different from ESRD of other causes, ADPKD patients need careful pre-RTx evaluations like detecting the presence of intracranial aneurisms, cardiac manifestations, and complications of liver and renal cysts. Materials: We retrieved a total of 1327 RTx patients receiving 1382 times RTx (two recipients with three times, 48 recipients with two times) over the last 35 years. Only 41 of these patients were diagnosed with ADPKD. Results: At the first RTx, patients’ ages were 42.9 ± 12.6 (mean ± SD) years. Ages of the ADPKD group (52.5 ± 10.1 years) were older than the non-ADPKD group (42.7 ± 12.7 years, p = 0.001). We found more cell mediated and antibody mediated rejection (29.3% vs. 26.0%, and 22.0% vs. 7.0%; both p < 0.001), new onset diabetes after transplant (NODAT) (21, 51.2% vs. 326, 25.3%; p = 0.005), and worse graft survival (p < 0.001) in the ADPKD group, and with the development of more malignancies (18; 43.9% vs. 360; 28.0%; p = 0.041). The long-term patient survivals were poorer in the ADPKD group (38.9% vs. 70.3%; p = 0.018). ADPKD was found as an independent risk factor for long-term patient survival (HR = 2.64, 95% CI 1.03–6.76, p = 0.04). Conclusions: Patients with ADPKD-related ESRD developed more NODAT, and also more malignancies if not aggressively surveyed before surgery. Due to poor long-term graft and patient survivals, regular careful examinations for NODAT and malignancies, even in the absence of related symptoms and signs, are highly recommended in the follow-ups.