Post-transplant Diabetes Mellitus Research Articles

Fast Tacrolimus Metabolism Does Not Promote Post-Transplant Diabetes Mellitus after Kidney Transplantation.

Post-transplant diabetes mellitus (PTDM) after kidney transplantation induced by tacrolimus is an important issue. Fast tacrolimus metabolism, which can be estimated by concentration-to-dose (C/D) ratio, is associated with increased nephrotoxicity and unfavorable outcomes after kidney transplantation. Herein, we elucidate whether fast tacrolimus metabolism also increases the risk for PTDM. Data from 596 non-diabetic patients treated with tacrolimus-based immunosuppression at the time of kidney transplantation between 2007 and 2015 were retrospectively analyzed. The median follow-up time after kidney transplantation was 4.7 years (IQR 4.2 years). Our analysis was complemented by experimental modeling of fast and slow tacrolimus metabolism kinetics in cultured insulin-producing pancreatic cells (INS-1 cells). During the follow-up period, 117 (19.6%) patients developed PTDM. Of all patients, 210 (35.2%) were classified as fast metabolizers (C/D ratio < 1.05 ng/mL × 1/mg). Fast tacrolimus metabolizers did not have a higher incidence of PTDM than slow tacrolimus metabolizers (p = 0.496). Consistent with this, insulin secretion and the viability of tacrolimus-treated INS-1 cells exposed to 12 h of tacrolimus concentrations analogous to the serum profiles of fast or slow tacrolimus metabolizers or to continuous exposure did not differ (p = 0.286). In conclusion, fast tacrolimus metabolism is not associated with increased incidence of PTDM after kidney transplantation, either in vitro or in vivo. A short period of incubation of INS-1 cells with tacrolimus using different concentration profiles led to comparable effects on cell viability and insulin secretion in vitro. Consistent with this, in our patient, collective fast Tac metabolizers did not show a higher PTDM incidence compared to slow metabolizers.

Is Intestinal Dysbiosis-Associated With Immunosuppressive Therapy a Key Factor in the Pathophysiology of Post-Transplant Diabetes Mellitus?

Post-transplant diabetes mellitus (PTDM) is one of the most common and deleterious comorbidities after solid organ transplantation (SOT). Its incidence varies depending on the organs transplanted and can affect up to 40% of patients. Current research indicates that PTDM shares several common features with type 2 diabetes mellitus (T2DM) in non-transplant populations. However, the pathophysiology of PTDM is still poorly characterized. Therefore, ways should be sought to improve its diagnosis and therapeutic management. A clear correlation has been made between PTDM and the use of immunosuppressants. Moreover, immunosuppressants are known to induce gut microbiota alterations, also called intestinal dysbiosis. Whereas the role of intestinal dysbiosis in the development of T2DM has been well documented, little is known about its impacts on PTDM. Functional alterations associated with intestinal dysbiosis, especially defects in pathways generating physiologically active bacterial metabolites (e.g., short-chain fatty acids, trimethylamine N-oxide, indole and kynurenine) are known to favour several metabolic disorders. This publication aims at discussing the potential role of intestinal dysbiosis and dysregulation of bacterial metabolites associated with immunosuppressive therapy in the occurrence of PTDM.

Post-transplant Diabetes Mellitus: What Physicians Need to Know.

Post-transplant diabetes mellitus (PTDM) is a common problem among solid organ transplant recipients contributing to morbidity and affecting patient as well as graft survival adversely. It can occur at any period following transplantation, but maximum incidence is observed in the first few months, with a second peak after a few years after transplantation. The pathogenesis is complex and poorly understood, however, it is associated with both dysfunctional beta-cells and insulin resistance. Both nonpharmacologic and antidiabetic therapies are important for adequate glycemic control. This point of view article provides a short review on PTDM in solid organ transplantation (SOT) recipients from a general physician's perspective.

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.

New-onset Obesity After Lung Transplantation: Incidence, Risk Factors, and Clinical Outcomes.

Lung transplant (LTx) recipients who gain weight after transplantation may experience an upward shift in body mass index (BMI) that places them in the obese category. The incidence, risk factors, and impact on metabolic health and mortality of new-onset obesity have not been documented in the LTx setting. This single-center retrospective study included 564 LTx recipients. Individuals were stratified according to their BMI trajectories from pretransplant evaluation up to 10 y posttransplant. New-onset obesity was defined as a pretransplant BMI <30 kg/m 2 and posttransplant BMI >30 kg/m 2 . The incidence, risk factors, and posttransplant diabetes mellitus, metabolic syndrome, and mortality of recipients with new-onset obesity were compared with those of nonobese (BMI <30 kg/m 2 , pre/post-LTx), consistently obese (BMI >30 kg/m 2 , pre/post-LTx), and obese recipients with weight loss (BMI >30 kg/m 2 pre-LTx, BMI <30 kg/m 2 post-LTx). We found that 14% of recipients developed obesity after transplantation. Overweight individuals (odds ratio [OR]: 9.01; 95% confidence interval [CI] [4.86-16.69]; P < 0.001) and candidates with chronic obstructive pulmonary disease (OR: 6.93; 95% CI [2.30-20.85]; P = 0.001) and other diagnoses (OR: 4.28; 95% CI [1.22-14.98]; P = 0.023) were at greater risk. Multivariable regression analysis showed that new-onset obesity was associated with a greater risk of metabolic syndrome (hazard ratio: 1.70; 95% CI [1.17-2.46]; P = 0.005), but not of posttransplant diabetes mellitus, than nonobesity. Recipients with new-onset obesity had a survival comparable to that of consistently obese individuals. A greater understanding of the multifaceted nature of post-LTx obesity may lead to interventions that are better tailored to the characteristics of these individuals.

Post-transplant diabetes mellitus in Canadian liver and renal transplant recipients.

BACKGROUND: Post-transplant diabetes mellitus (PTDM) occurs in 10%-40% of liver and renal transplant recipients. Whether the risk factors for PTDM in liver and renal transplant recipients are similar and whether Indigenous Canadians, who have a high underlying prevalence of diabetes mellitus (DM), are at increased risk of developing PTDM have yet to be determined. OBJECTIVE: To describe and compare those variables associated with PTDM in adult Canadian liver and renal transplant recipients. METHODS: A retrospective chart review of adult liver and renal transplant recipients attending four transplant follow-up clinics in three Canadian provinces was undertaken. RESULTS: De novo PTDM was diagnosed in 184/905 (20.3%) liver and 179/390 (45.9%) renal transplant recipients. Older age, higher pre-transplant BMI, underlying immune-mediated liver disease, lower trough tacrolimus levels and longer duration of follow-up were independently associated with PTDM in liver transplant recipients and non-Caucasian race, higher pre-transplant BMI, and incidence of organ rejection in renal transplant recipients. Compared with Caucasians, Indigenous Canadians who had undergone renal transplantation had a significantly increased prevalence of PTDM (56.5% versus 40.0%, p = 0.035). The prevalence of PTDM in liver transplant recipients was similar in Indigenous Canadians and Caucasians (27.9% versus 20.1%, p = 0.215). CONCLUSIONS: The variables associated with PTDM differ in liver and renal transplant recipients. Compared with Caucasians, Indigenous Canadians undergoing renal transplantation are at increased risk of developing PTDM.

Analysis of risk factors and establishment of a risk prediction model for post-transplant diabetes mellitus after kidney transplantation

IntroductionPost-transplant diabetes mellitus (PTDM) is a known side effect in transplant recipients administered immunosuppressant drugs, such as tacrolimus. This study aimed to investigate the risk factors related to PTDM, and establish a risk prediction model for PTDM. In addition, we explored the effect of PTDM on the graft survival rate of kidney transplantation recipients. MethodsPatients with pre-diabetes mellitus before kidney transplant were excluded, and 495 kidney transplant recipients were included in our study, who were assigned to the non-PTDM and PTDM groups. The cumulative incidence was calculated at 3 months, 6 months, 1 year, 2 years, and 3 years post-transplantation. Laboratory tests were performed and the tacrolimus concentration, clinical prognosis, and adverse reactions were analyzed. Furthermore, binary logistic regression analysis was used to identify the independent risk factors of PTDM. ResultsAge ≥ 45 years (adjusted odds ratio [aOR] 2.25, 95% confidence interval [CI] 1.14–3.92; P = 0.015), body mass index (BMI) > 25 kg/m2 (aOR 3.12, 95% CI 2.29–5.43, P < 0.001), tacrolimus concentration > 10 ng/mL during the first 3 months post-transplantation (aOR 2.46, 95%CI 1.41–7.38; P < 0.001), transient hyperglycemia (aOR 4.53, 95% CI 1.86–8.03; P < 0.001), delayed graft function (DGF) (aOR 1.31, 95% CI 1.05–2.39; P = 0.019) and acute rejection (aOR 2.16, 95% CI 1.79–4.69; P = 0.005) were identified as independent risk factors of PTDM. The PTDM risk prediction model was developed by including the above six risk factors, and the area under the receiver operating characteristic curve was 0.916 (95% CI 0.862–0.954, P < 0.001). Furthermore, the cumulative graft survival rate was significantly higher in the non- PTDM group than in the PTDM group. ConclusionsRisk factors related to PTDM were age ≥ 45 years, BMI > 25 kg/m2, tacrolimus concentration > 10 ng/mL during the first 3 months post-transplantation, transient hyperglycemia, DGF and acute rejection.

IMPACT OF BODY FAT DISTRIBUTION, ADIPOCYTOKINES AND VARIABILITY IN ASSOCIATED GENES ON KIDNEY TRANSPLANT OUTCOMES

Objective: Adiposity distribution contributes to a number of pathologies. We aimed to assess whether this distribution was associated with clinical outcomes and to identify its relationship with leptin and adiponectin gene variants and plasma concentrations in renal transplant recipients (RTR). Design and method: Anthropometric parameters were measured in 236 RTR by bioelectrical impedance analysis, allograft function and post-transplant complications were retrieved from records. Blood samples were drawn to measure plasma leptin/adiponectin levels and to seek for polymorphisms in the leptin receptor (LEPR) and adiponectin (ADIPOQ) genes. Logistic regression models were applied to identify associations. Results: The waist-to-height ratio (WHr) displayed a significant association with delayed graft function (DGF), acute rejection (AR) and post-transplant diabetes mellitus, with OR values of 2.04 (1.02–4.08) p = 0.045; 3.08 (1.22–7.79) p = 0.017 and 2.79 (1.16–6.74) p = 0.022, respectively. Waist circumference was linked to DGF [OR = 1.03 (1.01 – 1.053), p = 0.025] and AR [OR = 1.041 (1.01 – 1.073), p = 0.009]. Leptin levels were significantly higher in patients who experienced AR [19.91 ± 23.72 vs. 11.22 ± 16.42 ng/ml; OR = 1.021 (1.01–1.04), p = 0.017]. The ADIPOQ rs1501299TT genotype showed a significant association with higher WHr (0.63 ± 0.11 vs. 0.59 ± 0.87 for GG/GT genotypes; p = 0.015) and WC values (102.3 ± 14.12 vs. 96.38 ± 14.65 for GG/GT genotypes; p = 0.021). Conclusions: We have shown that WC, and especially WHr, are associated with adverse outcomes in renal transplant and hence may be useful parameters in RTR monitoring. In turn, these anthropometric parameters were affected by variability in the ADIPOQ gene, suggesting this polymorphism could be a useful marker of transplanted patients at risk.

194-LB: Tacrolimus-Induced Hyperglycemic Emergencies in Posttransplant Patients—A Case Series

Introduction: Tacrolimus is effective immunosuppressant in posttransplant patients. It inhibits calcineurin and prevents T cell activation. Post-transplantation diabetes mellitus (PTDM) is a well-established adverse effect of tacrolimus. We report the rare occurrences of DKA and hyperosmolar hyperglycemia syndrome respectively in 2 patients on tacrolimus after renal transplants. Description Case 1: A 25 year old obese (BMI 37.7 kg/m2) black female with no history of DM received a live donor kidney transplant. She was on mycophenolate 720 mg po bid, tacrolimus 7 mg po bid, and prednisone 5 mg daily. Eleven weeks after transplant she presented with polyuria and polydipsia and was admitted for DKA. Labs revealed glucose 1000 mg/dL (74-106) , HCO3 7.0 meq/L (21-32) , beta-hydroxybutyric acid 8.4 mg/dL (0.2 - 2.8) , tacrolimus trough levels 19.6 ng/mL (4.1 - 10.7) . Her A1c was 10.6% compared to 5.3% pre-transplant. Case 2: A 50 year old obese (BMI 35.6 kg/m2) black female with no prior history of DM received a cadaveric kidney transplant due to ESRD. Patient was on mycophenolate 360 mg bid, and tacrolimus 8 mg bid. She was admitted to hospital for HHS 9 weeks later. Labs revealed a glucose 940 mg/dL, serum osmolality 341 msom/kg (275-295) , HCO3 22 mmol/L, tacrolimus trough levels 12.1 ng/mL. Her A1c was 8.7% compared to 5.3% pre-transplant. Discussion: Our 2 patients with no history of DM developed hyperglycemic emergencies within 3 months of receiving kidney transplants and initiating tacrolimus. Both responded well to IV fluids and insulin and were transitioned to SQ insulin by discharge. Risk factors for post-transplant de novo DKA and HHS common to both patients were African American ethnicity, high BMI, and tacrolimus treatment with elevated trough levels. Tacrolimus inhibits insulin secretion and is linked to increased rates of PTDM, which is often reversible with tacrolimus dosage reduction. Both of our patients were prescribed tacrolimus at reduced dosage and were scheduled for outpatient Endocrine clinic evaluation to determine whether they should continue insulin treatment. Disclosure S. Gupta: None. D. Lovre: Other Relationship; AstraZeneca, Bayer AG, Novo Nordisk. R. Galagan: None.

Pretransplant and Posttransplant Alcohol Consumption and Outcomes in Kidney Transplantation: A Prospective Multicenter Cohort Study.

The impact of pretransplant and posttransplant alcohol consumption on outcomes in kidney transplant recipients (KTRs) is uncertain. Self-reported alcohol consumption was obtained at the time of transplant and 2 years after transplant in a prospective cohort study. Among 907 KTRs, 368 (40.6%) were drinkers at the time of transplant. Compared to non-drinkers, alcohol consumption did not affect the risk of death-censored graft failure (DCGF), biopsy-proven acute rejection (BPAR), cardiovascular events, or all-cause mortality. Compared to persistent non-drinkers, the development of DCGF, BPAR, cardiovascular events, all-cause mortality, or posttransplant diabetes mellitus was not affected by the alcohol consumption pattern (persistent, de novo, or stopped drinking) over time. However, de novo drinkers had a significantly higher total cholesterol (p < 0.001) and low-density lipoprotein cholesterol levels (p = 0.005) compared to persistent non-drinkers 5 years after transplant, and had significantly higher total cholesterol levels (p = 0.002) compared to the stopped drinking group 7 years after transplant, even after adjusting for the use of lipid-lowering agents, age, sex, and body mass index. Although pretransplant and posttransplant alcohol consumption were not associated with major outcomes in KTRs during the median follow-up of 6.0 years, a new start of alcohol use after KT results in a relatively poor lipid profile. Clinical Trial Registration: clinicaltrials.gov, identifier NCT02042963.

COVID-19 in Kidney Transplant Recipients: A Multicenter Experience from the First Two Waves of Pandemic

BackgroundKidney transplant recipients have an increased risk of complications from COVID-19. However, data on the risk of allograft damage or death in kidney transplant recipients recovering from COVID-19 is limited. In addition, the first and second waves of the pandemic occurred at different times all over the world. In Turkey, the Health Minister confirmed the first case in March 2020; after that, the first wave occurred between March and August 2020; afterward, the second wave began in September 2020. This study aims to demonstrate the clinical presentations of kidney transplant recipients in the first two waves of the pandemic in Turkey and explore the impact of COVID-19 on clinical outcomes after the initial episode.MethodsPatients with COVID-19 from seven centers were included in this retrospective cohort study. Initially, four hundred and eighty-eight kidney transplant recipients diagnosed with COVID-19 between 1 March 2020 to 28 February 2021 were enrolled. The endpoints were the occurrence of all-cause mortality, acute kidney injury, cytokine storm, and acute respiratory distress syndrome. In addition, longer-term outcomes such as mortality, need for dialysis, and allograft function of the surviving patients was analyzed.ResultsFour hundred seventy-five patients were followed up for a median of 132 days after COVID-19. Forty-seven patients (9.9%) died after a median length of hospitalization of 15 days. Although the mortality rate (10.1% vs. 9.8%) and intensive care unit admission (14.5% vs. 14.5%) were similar in the first two waves, hospitalization (68.8% vs. 29.7%; p < 0.001), acute kidney injury (44.2% vs. 31.8%; p = 0.009), acute respiratory distress syndrome (18.8% vs. 16%; p = 0.456), and cytokine storm rate (15.9% vs. 10.1%; p = 0.072) were higher in first wave compared to the second wave. These 47 patients died within the first month of COVID-19. Six (1.4%) of the surviving patients lost allografts during treatment. There was no difference in the median serum creatinine clearance of the surviving patients at baseline (52 mL/min [IQR, 47–66]), first- (56 mL/min [IQR, 51–68]), third- (51 mL/min [IQR,48–67]) and sixth-months (52 mL/min [IQR, 48–81]). Development of cytokine storm and posttransplant diabetes mellitus were independent predictors for mortality.ConclusionsMortality remains a problem in COVID-19. All the deaths occur in the first month of COVID-19. Also, acute kidney injury is common in hospitalized patients, and some of the patients suffer from graft loss after the initial episode.

MO952: Risk Factors of Post Transplantation Diabetes Mellitus After Kidney Transplantation

Abstract BACKGROUND AND AIMS Between 10 and 30% of kidney transplant recipients develop post-transplant diabetes mellitus (PTDM). PTDM is a major risk factor for cardiovascular events and death in kidney transplant recipients. At our center prednisolone doses are tapered to a low maintenance dose eight weeks after transplantation. In a retrospective single-center cohort study, we investigated risk factors for development of de novo PTDM from 8 weeks after kidney transplantation. METHOD Inclusion criteria were kidney transplantation, age &amp;gt; 18 years, no known diabetes prior to, or at the 8-week control after transplantation and with at least one year of follow up. At the 8-week control an oral glucose tolerance test (OGTT) was performed for PTDM diagnosis. De novo PTDM was defined as fasting glucose ≥7 mmol/L, 2-h glucose ≥11.1 mmol/L at OGTT performed routinely at the one-year visit, or at least two registered dispensations of glucose lowering medication in the Norwegian Prescription Database (NorPD). RESULTS In total 632 patients (median age 53 years, 62% males) with a median follow-up of 2.7 years [1–4] were included of which 54 (8.5%) developed de novo PTDM (31 diagnosed by the OGTT at 1 year and 23 identified by glucose lowering dispensation). De novo PTDM patients were older than non-PTDM patients at transplantation (median age 63 versus 52 years), were more often males (81% versus 61%), and had higher fasting blood glucose (mean 5.8 versus 5.3 mmol/L), 2-h glucose (mean 8.3 versus 6.6 mmol/L) and HbA1c (median 38 versus 32 mmol/mol) at the 8-week post-transplantation control. In a multiple logistic regression analysis, significant associated factors of PTDM were age (years), OR 1.04 (CI 95%: 1.01;1.06), triglycerides (mmol/L), OR 1.42 (CI 95%: 1.10;1.81) and tacrolimus (µg/L) OR 1.23 (CI 95%: 1.03;1.46) concentrations measured at the one-year control visits, and CMV serostatus (positive donor to negative recipient), OR 2.12 (CI 95%: 1.04;4.28). Plasma magnesium, gender, BMI and plasma creatinine were not associated with development of PTDM. CONCLUSION Development of de novo PTDM from 8 weeks after kidney transplantation was associated with increased age, higher triglycerides, higher tacrolimus concentrations and D+/R- CMV-serostatus.

MO958: Hyperleptinemia as A Risk Factor for Post-Transplant Diabetes Mellitus Development After Kidney Transplantation

Abstract BACKGROUND AND AIMS Adipose tissue, as an endocrine organ, is involved in the synthesis of hormones that are involved in several processes, including the regulation of food intake, the control of insulin sensitivity or as mediators of inflammatory processes. The aim of this study was to determine the importance of leptin, adiponectin, interleukin 6 and interleukin 10 levels for the development of post-transplant diabetes mellitus (PTDM) 1 year after kidney transplantation (KT). METHOD In the prospective analysis, the studied sample (n = 104) was divided into three groups: (1) control group, (2) patients who developed a pre-diabetic condition after KT (impaired glucose tolerance, fasting hyperglycemia) and (3) patients who developed de novo PTDM. Pre-transplantation and subsequently at 3, 6 and 12 months after KT, we recorded the basic characteristics of the donor and recipient, including parameters reflecting graft function, metabolic (lipid profile, glucose metabolism parameters) and anthropometric parameters. At the same time, we monitored the levels of adipocytokines (adiponectin, leptin) and interleukins (IL-6, IL-10) during the monitored period (Table 1). RESULTS The level of leptin in the post-transplant period had a continuously decreasing tendency in the control group with a significantly lower level 12 months after KT (P = 0.0078). On the other hand, after transient decrease, leptin level remained high in 12 months after KT in the group with prediabetes (P = 0.0343) and PTDM (insignificant). In contrast, adiponectin levels showed a significant decrease after 12 months in the group with prediabetes (P = 0.0009) and PTDM (P &amp;lt;0.0001), while it increased in the control group. IL-6 decreased significantly in the control group (P = 0.0023), with prediabetes (P = 0.0061) and PTDM (P = 0.0499). After adjusting for differences in the baseline donor and recipient characteristics, we found risk factors for PTDM 12 months after KT in a univariate analysis: baseline hyperleptinemia (P = 0.0458) and at 12 months (P = 0.0464), low adiponectin levels at 12 months (P = 0.0108), low IL-6 baseline (P = 0.0180), IL10 at 6 months (P = 0.0271) and 12 months (P = 0.0397). Using multivariate analysis, we identified hyperleptinemia 12 months after KT as an independent risk factor for PTDM development 1 year after KT [OR: 1.0320; 95% Cl: 0.9785–1.0884 (P = 0.0038)] (Table 2). CONCLUSION We confirmed that elevated leptin level 12 months after KT is associated with the development of PTDM. Levels of inflammatory process mediators (IL-6 and IL-10) did not correlate with an increased incidence of metabolic complications. Their importance seems to apply in the event of acute rejection, which requires further investigation.

MO637: Effectiveness and Safety of Glucagon-Like Peptide-1 Receptor Agonist in a Cohort of Kidney Transplant Recipients

Abstract BACKGROUND AND AIMS Diabetes mellitus (DM) is a complication in kidney transplant (KT). Therapies such as glucagon-like peptide-1 receptor agonist analogs (GLP-1RA) have been incorporated that could have benefits in KT, although experience is limited [1, 2]. The objective of our study is to describe the effectiveness and safety of GLP-1RA in KT patients. METHOD Retrospective cohort study of KT with DM who started GLP-1RA between February 2016 and December 2021. Clinical and demographic variables were analyzed. We collected GLP-1RA type and dose. Glomerular filtration rate (eGFR), proteinuria and weight were collected at the start of treatment and after 6 and 12 months. We analyze glycemic control, blood pressure and lipid profile. Acute rejections (AR), de novo donor-specific antibodies (DSA) and adverse effects were documented. A descriptive analysis was performed and the variables described before and after the start of treatment were compared. Parametric and non-parametric tests were performed according to the normality of the sample. RESULTS In this period, 50 KT with DM treated with GLP-1RA in our center from 1 March 2016 to 15 December 2021. Sixteen patients (32%) had developed post-transplant diabetes mellitus (PTDM). The mean age was 62.8 years and 52.5% were men. Mean baseline estimated glomerular filtration rate (eGFR) was 46.1 mL/min/1.73 m2 and the time post-KT was 38 months. The GLP-1RA mostly prescribed was semaglutide (47.5%), followed by liraglutide (32.5%) and dulaglutide (20%). Twenty-nine patients (58%) reached the maximum recommended dose of the drug. All patients received steroids, tacrolimus and mycophenolate. Forty KT recipients had a minimum follow-up of 6 months and 26 were followed for 12 months. Values of variables compared during the follow-up are shown in Table 1. We observed an improvement in eGFR (+3.5 mL/min/1.73 m2 at 12 months, P = 0.030) and a reduction in proteinuria (−59.1 mg/g at 6 months, P = 0.009 and −48.5 mg/g at 12 months, P = 0.021) during all the follow-up. Additionally, we found a significant reduction in systolic blood pressure (−9.2 mmHg at 12 months, P = 0.022) despite the number of patients receiving angiotensin receptor blockers, angiotensin-converting enzyme and other antihypertensive therapies as well as their doses that did not change during the period of the study. In our cohort, body weight significantly reduced (−2.4 Kg at 6 months, P = 0.006 and −3 Kg at 12 months, P = 0.041). Furthermore, HbA1c decreased (−9 mmol/mol at 6 months, P &amp;lt;0.001 and −5 mmol/mol at 12 months, P = 0.018). Notably, insulin dose was also reduced (−4 UI/day at 6 months, P = 0.003 and −4 UI/day at 12 months, P = 0.036) and the rest of antidiabetic treatment did not significantly change. Finally, we observed a reduction in total cholesterol (−14 mg/dL at 6 months, P = 0.015 and −6.3 mg/dL at 12 months, P = 0.344) and LDL-c (−8.8 mg/dL at 6 months, P = 0.49 and −4.9 mg/dL at 12 months, P = 0.384) during the follow-up. Twelve patients (24%) suffered from side effects, mainly nausea and vomiting, and only two patients (4%) discontinued the treatment. One patient discontinued the treatment due to the diagnosis of pancreatic cancer 8 months after starting the drug. We did not find differences in the levels or in the dose of tacrolimus. Neither AR episodes nor de novo DSAs’ development was notified. CONCLUSION In conclusion, this is one of the largest series reporting the effectiveness and safety of GLP-1RA in a cohort of KT. Our results support that it can be an option for the management of DM in these patients. Its use is safe and it does not seem to alter tacrolimus trough levels, to induce AR episodes or de novo DSAs development.

Analysis of glucocorticoid receptor gene polymorphisms in kidney recipients with post-transplant diabetes

Introduction: Post-transplant diabetes mellitus (PTDM) is a severe and common metabolic problem after transplantation. Glucocorticoid receptor (GR) is encoded by the NR3C1 gene and it seems that polymorphisms in this gene lead to altering insulin sensitivity. Objectives: This study aimed to evaluate the frequency of four common polymorphisms in the NR3C1 gene of renal recipients with and without PTDM. Patients and Methods: Blood samples were collected from 32 PTDM and 59 non-diabetic renal-transplanted patients. After DNA extraction, DNA fragments were amplified and directly sequenced using specific primers. Data analysis was performed with SPSS 22.0 software. Results: There was no significant correlation between diabetes incidence and the four investigated polymorphisms of the GR gene. Nevertheless, diabetic patients’ age was higher than non-diabetic patients. Additionally, transplant acute rejection (AR) in diabetic patients was found to be more than non-diabetic patients. Conclusion: Based on gathered information in this research, none of the studied polymorphisms affected the development of PTDM. Further investigations should be conducted in a large sample size.

Oral Glucose Tolerance Test for the Screening of Glucose Intolerance Long Term Post-Heart Transplantation.

Post-transplant diabetes mellitus (PTDM) is a frequent complication post-heart transplantation (HT), however long-term prevalence studies are missing. The aim of this study was to determine the prevalence and determinants of PTDM as well as prediabetes long-term post-HT using oral glucose tolerance tests (OGTT). Also, the additional value of OGTT compared to fasting glucose and glycated hemoglobin (HbA1c) was investigated. All patients > 1 year post-HT seen at the outpatient clinic between August 2018 and April 2021 were screened with an OGTT. Patients with known diabetes, an active infection/rejection/malignancy or patients unwilling or unable to undergo OGTT were excluded. In total, 263 patients were screened, 108 were excluded. The included 155 patients had a median age of 54.3 [42.2–64.3] years, and 63 (41%) were female. Median time since HT was 8.5 [4.8–14.5] years. Overall, 51 (33%) had a normal range, 85 (55%) had a prediabetes range and 19 (12%) had a PTDM range test. OGTT identified prediabetes and PTDM in more patients (18% and 50%, respectively), than fasting glucose levels and HbA1c. Age at HT (OR 1.03 (1.00–1.06), p = 0.044) was a significant determinant of an abnormal OGTT. Prediabetes as well as PTDM are frequently seen long-term post-HT. OGTT is the preferred screening method.

Donor and recipient polygenic risk scores influence the risk of post-transplant diabetes.

Post-transplant diabetes mellitus (PTDM) reduces allograft and recipient life span. Polygenic risk scores (PRSs) show robust association with greater risk of developing type 2 diabetes (T2D). We examined the association of PTDM with T2D PRS in liver recipients (n = 1,581) and their donors (n = 1,555), and kidney recipients (n = 2,062) and their donors (n = 533). Recipient T2D PRS was associated with pre-transplant T2D and the development of PTDM. T2D PRS in liver donors, but not in kidney donors, was an independent risk factor for PTDM development. The inclusion of a combined liver donor and recipient T2D PRS significantly improved PTDM prediction compared with a model that included only clinical characteristics: the area under the curve (AUC) was 67.6% (95% confidence interval (CI) 64.1-71.1%) for the combined T2D PRS versus 62.3% (95% CI 58.8-65.8%) for the clinical characteristics model (P = 0.0001). Liver recipients in the highest quintile of combined donor and recipient T2D PRS had the greatest risk of PTDM, with an odds ratio of 3.22 (95% CI 2.07-5.00) (P = 1.92 × 10-7) compared with those in the lowest quintile. In conclusion, T2D PRS identifies transplant candidates with high risk of PTDM for which pre-emptive diabetes management and donor selection may be warranted.

Posttransplantation Diabetes Mellitus Among Solid Organ Recipients in a Danish Cohort.

Post-transplant diabetes mellitus (PTDM) is associated with a higher risk of adverse outcomes. We aimed to describe the proportion of patients with diabetes prior to solid organ transplantation (SOT) and post-transplant diabetes mellitus (PTDM) in three time periods (early-likely PTDM: 0–45 days; 46–365 days and >365 days) post-transplant and to estimate possible risk factors associated with PTDM in each time-period. Additionally, we compared the risk of death and causes of death in patients with diabetes prior to transplant, PTDM, and non-diabetes patients. A total of 959 SOT recipients (heart, lung, liver, and kidney) transplanted at University Hospital of Copenhagen between 2010 and 2015 were included. The highest PTDM incidence was observed at 46–365 days after transplant in all SOT recipients. Age and the Charlson Comorbidity Index (CCI Score) in all time periods were the two most important risk factors for PTDM. Compared to non-diabetes patients, SOT recipients with pre-transplant diabetes and PTDM patients had a higher risk of all-cause mortality death (aHR: 1.77, 95% CI: 1.16–2.69 and aHR: 1.89, 95% CI: 1.17–3.06 respectively). Pre-transplant diabetes and PTDM patients had a higher risk of death due to cardiovascular diseases and cancer, respectively, when compared to non-diabetes patients.

Association Between Transient Post-Transplantation Hyperglycemia and Long-Term Post-Transplantation Diabetes Mellitus in Lung Transplant Recipients

<h3>Purpose</h3> A 2014 International Consensus on Post-Transplantation Diabetes Mellitus (PTDM) states that Transient Post-Transplantation Hyperglycemia (TPTH) must be excluded before PTDM can be diagnosed. However, there is little evidence describing the long-term risk of PTDM in lung transplant recipients with TPTH. The purpose of this study was to characterize the risk of PTDM in lung transplant recipients who present with TPTH. <h3>Methods</h3> Pre-transplant diabetes was ascertained by chart review. Post-transplant diabetes status was ascertained retrospectively using plasma glucose values from a provincial transplant registry. TPTH was defined as ≥1 glucose value ≥11.1 mmol/L within the first 90 days post-transplant, followed by all glucose values <11.1 mmol/L on post-transplant days 91-365. Beyond the first year post-transplant, patients with "no diabetes" had all glucose values <11.1 mmol/L, while patients with "PTDM" had ≥1 glucose value ≥11.1 mmol/L. We fit regression models in our statistical analyses. <h3>Results</h3> 172 lung transplant recipients from 2010-2016 were followed until spring 2021. We excluded 6 patients because they died before post-transplant day 90. 33/131 (25%) without pre-transplant diabetes and 7/34 (21%) with pre-transplant diabetes had PTPH in the first year post-transplant. Amongst those with PTPH, 20/38 (53%) ended up in the "no diabetes" group and 18/38 (47%) ended up in the "PTDM" group beyond the first year post-transplant. TPTH was not associated with an increased odds of PTDM beyond the first year post-transplant compared to those without diabetes (OR 0.4, p=0.059) and with diabetes (OR 2.8, p=0.072) in the first year post-transplant, adjusted for age, sex, and pre-transplant diabetes. However, average glucose in the first 90 days post-transplant was associated with average glucose beyond the first year post-transplant (β=0.52, R²=0.41, p<0.001), adjusted for age, sex, and pre-transplant glucose. <h3>Conclusion</h3> A significant proportion of lung transplant recipients with TPTH end up with long-term diabetes beyond the first year post-transplant. These findings challenge the utility of the label "TPTH" and suggest that lung transplant recipients with high glucose values in the first 90 days post-transplant require close monitoring of glycemic indices even beyond the first year post-transplant.

Retrospective Analysis of the Risk Factors of Perioperative Bacterial Infection and Correlation with Clinical Prognosis in Kidney Transplant Recipients.

BackgroundInfection remains a leading cause of morbidity and mortality in kidney transplant patients. This study aimed to investigate the risk factors of bacterial infection during the perioperative period of transplantation and the effects of infection on long-term clinical outcomes.MethodsIn total, 295 kidney transplantation recipients were included in this retrospective study and assigned to two groups: non-infected and infected. The tacrolimus concentration, pharmacogenomics, laboratory parameters, and clinical outcomes of both groups were evaluated.ResultsA relatively low incidence of urinary tract infection was observed in our cohort, and lung was identified as the most frequent site of infection. Gram-negative bacteria, such as Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae, were the most common infecting strains in kidney transplant recipients. Patients with diabetes showed greater susceptibility to infection. Compared with the non-infected group, tacrolimus concentration was significantly lower on day 7 and 14 in the infected group. White blood cell count, neutrophil count, and C-reactive protein (CRP) in the infected group were markedly higher post-transplantation, while albumin levels were lower relative to the non-infected group. ABCB1 (rs2032582) genotype showed clear associations with infection. Furthermore, the incidence of delayed graft function (DGF) and early acute rejection (AR) before infection was significantly greater in the infected group. Finally, early post-transplant infection was associated with a marked increase in the incidence of AR, post-transplant diabetes mellitus (PTDM), and secondary infection.ConclusionPre-diabetes, longer duration of catheterization, lower albumin, higher CRP, tacrolimus concentration on the day 7 and 14, early AR before infection, and DGF were closely related to postoperative infection in kidney transplantation recipients. Moreover, bacterial infection during the perioperative period was closely associated with AR, PTDM and secondary infection.