Post-transplant diabetes mellitus (PTDM) is a well-known solid organ transplant complication, which can be related to immunosuppressants, particularly tacrolimus. We report an unusual presentation of PTDM with diabetic ketoacidosis (DKA). This is unique as PTDM typically resembles Type 2 DM, whereas DKA is associated with Type 1 DM and has rarely been reported as a complication of tacrolimus. A 38-year-old African American male on LCP-tacrolimus presented four months post kidney transplant with vomiting, weakness, poor appetite, and polyuria. Labs demonstrated hyperglycemia, ketonuria, and high anion gap metabolic acidosis. He was nonobese and had no personal or family history of Type 2 DM. DKA was suspected to be secondary to tacrolimus-induced pancreatic beta cell damage worsened by supratherapeutic tacrolimus levels. Latent autoimmune diabetes in adults (LADA) was diagnosed when further testing showed insulinopenia, low C-peptide, and anti-glutamic acid decarboxylase (GAD) autoantibodies. He required 120-units of subcutaneous insulin daily. Our literature review revealed only 16 other tacrolimus-induced DKA cases. No cases reported anti-GAD positivity and most showed beta cell toxicity reversibility with tacrolimus tapering or substitution. Our patient was early post-transplant with leukocytopenia, so tacrolimus was not exchanged. This unusual PTDM case may have resulted from both autoimmune and tacrolimus-induced beta cell destruction. Physicians should be aware of new onset LADA post-transplantation and tacrolimus toxicity leading to DKA, even in patients without traditional risk factors. Anti-GAD antibody screening in patients on tacrolimus who develop PTDM may identify patients less likely to recover beta cell function with immunosuppression augmentation which requires careful monitoring.

Organ transplantation is the treatment of choice for individuals with kidney failure requiring kidney replacement therapy, as well as for those with end-stage liver disease. Despite the significant reduction in long-term morbidity and mortality with transplantation, kidney and liver allograft recipients remain at high risk for cardiovascular disease (CVD) and premature death from cardiovascular causes. This heightened risk is represented across all phenotypes of CVD, including coronary heart disease, heart failure, arrhythmias, valvulopathies and pulmonary hypertension. Pre-existing vascular risk factors for CVD, coupled with superimposed cardiovascular-kidney-metabolic derangements after transplantation, driven at least in part by post-transplant weight gain, immunosuppressive therapies and de novo risk factors such as dyslipidaemia and diabetes, coalesce to increase total CVD risk. In this review, we summarise pathophysiological considerations for both the short- and long-term increase in CVD risk following kidney/liver transplantation. We review the different phenotypes of CVD, with unique considerations for post-transplant care in this patient population. Finally, we highlight the need for awareness about long-term CVD risk and a multidisciplinary approach to managing organ-specific CVD risk in kidney and liver transplant patients.

This investigation sought to examine the clinical and pathological characteristics, outcomes, and risk factors linked to the progression of renal function in adult-onset immunoglobulin A (IgA) vasculitis within a single center in northwest China.

Data were retrospectively gathered from cases of adult-onset IgA vasculitis recorded at a tertiary hospital in northwest China, covering the period from January 2013 to August 2024. During the follow-up, clinical information was compared between patients who advanced to chronic kidney disease (CKD) stage 3 and those who did not.

A sum of 1082 adult-onset IgA vasculitis patients (632 men; median age of 37 years) were included. Among patients with baseline proteinuria >0.5 g/24h (43.9%), 40.7% progressed to chronic kidney disease (CKD) stage 3, while 5.1% developed end-stage renal disease (ESRD). COX regression analysis indicated that older age, renal pathological grade IV, hypertension (HTN), diabetes, hyperlipidemia, and hyperuricemia were independent risk factors for CKD stage 3 progression in individuals with adult-onset IgA vasculitis.

Older age and comorbidities such as hypertension and diabetes significantly increase the risk of renal progression in adult-onset IgAV. Early management of these comorbidities may mitigate the risk of CKD progression.

Direct-acting antivirals (DAAs) have revolutionized hepatitis C virus (HCV) treatment. The changing landscape of hepatocellular carcinoma (HCC) in liver transplant (LT) recipients lacks a thorough description of the outcomes of HCC based on etiology.

To assess the waitlist (WL) dropout and graft survival in HCC LT candidates based on the etiology of HCC in the post-DAA era.

This retrospective cohort study analyzed United Network Organ Sharing/Organ Procurement Transplant Network data from 2015 to 2022. Graft survival was analyzed using Kaplan-Meier curves, and predictors of WL dropout and graft failure were assessed using multivariate analysis.

Among LT recipients, etiologies were HCV (53.6%), alcohol-associated liver disease (ALD) (12.0%), metabolic dysfunction-associated steatotic liver disease (MASLD) (16.6%), hepatitis B virus (HBV) (5.6%), and other (12.1%). MASLD and ALD had the highest dropout rates (1-year: 20.4%, 21.7%; 3-year: 58.2%, 51.1%; P  < 0.001). Dropout was linked to diabetes, low albumin, high Model of End-Stage Liver Disease, high alpha-fetoprotein, tumor number, and size. MASLD had the worst 1-, 3-, and 5-year graft survival (89.8%, 81.8%, and 74.1%) and higher failure risk than HCV (hazard ratio: 1.143, 95% CI: 1.021-1.281). Diabetes negated MASLD's impact on graft failure but worsened survival for MASLD-HCC compared with HBV and ALD, matching HCV.

MASLD has the highest WL dropout and post-LT graft failure among HCC LT candidates, surpassing HCV in the post-DAA era. The worst graft survival in MASLD-HCC is associated with pre-LT diabetes.

Post-transplant diabetes mellitus (PTDM) is a common complication following heart transplantation (HT). The purpose of this study was to investigate sex differences in risk factors for the development of PTDM after HT, as well as in PTDM-related post-transplant outcomes, including acute cellular rejection (ACR), antibody-mediated rejection (AMR), cardiac allograft vasculopathy (CAV), and death.

A retrospective review of patients who underwent HT at a large-volume center between January 1, 2010 and December 31, 2019 was performed. PTDM was defined as hemoglobin A1C ≥ 6.5% or a random glucose >200 after HT among patients with no prior history of DM. Predictors of PTDM and post-HT outcomes were analyzed by sex.

A total of 533 patients were transplanted during the study period and screened for inclusion. Among the 317 HT patients without pre-transplant DM, 71 (22.4%) developed PTDM: 24 women (33.7%), 47 men (66.2%). Baseline hypertension (OR 2.9, [1.3, 6.7], p = 0.009) and mean steroid dose over the first 2 years post-transplant (OR 1.2, [1.0, 1.3], p = 0.006) were predictors of PTDM in women but not in men, and mean tacrolimus dose was a predictor in men (OR 1.1, [1.0, 1.2], p = 0.001) but not in women while mean tacrolimus level was a predictor in women (OR 1.2, [1.0, 1.2], p = 0.034) but not in men. Post-transplant outcomes, including ACR, AMR, CAV, and death, did not differ between men with and without PTDM. However, women with PTDM had a higher rate of AMR (38% vs. 18%, p = 0.04) as compared to women without PTDM. There were no significant differences in rates of ACR, CAV, infection requiring hospitalization, or death among women.

PTDM is a common complication of HT. Our study suggests that risk factors for PTDM and outcomes among HT patients differ by sex.

Heart transplant (HT) recipients experience high rates of cardiometabolic disease. Novel therapies targeting hyperlipidemia, diabetes, and obesity, including proprotein convertase subtilisin/kexin inhibitors, sodium-glucose cotransporter-2 inhibitors, and glucagon-like peptide-1 agonists, are increasingly used for cardiometabolic risk mitigation in the general population. However, limited data exist to support the use of these agents in patients who have undergone heart transplantation. Herein, we describe the mechanisms of action and emerging evidence supporting the use of novel pharmacologic agents in the post-HT setting for cardiometabolic risk mitigation and review evidence supporting their ability to modulate immune pathways associated with atherogenesis, epicardial adipose tissue, and coronary allograft vasculopathy.

Kidney transplantation (KT) represents a pivotal intervention for patients with chronic kidney disease (CKD), significantly improving survival and quality of life. However, KT recipients face an array of non-immunological complications, collectively amplifying cardiovascular (CV) and metabolic risks. This review explores the intersection of cardio-metabolic syndrome and KT, emphasizing the recently introduced cardiovascular-kidney-metabolic (CKM) syndrome. CKM syndrome integrates metabolic risk factors, CKD, and CV disease, with KT recipients uniquely predisposed due to immunosuppressive therapies and pre-existing CKD-related risks. Key issues include post-transplant hypertension, obesity, dyslipidemia, post-transplant diabetes mellitus (PTDM), and anemia. Immunosuppressive agents such as corticosteroids, calcineurin inhibitors, and mTOR inhibitors contribute significantly to these complications, exacerbating metabolic dysfunction, insulin resistance, and lipid abnormalities. For instance, corticosteroids and calcineurin inhibitors heighten the risk of PTDM, while mTOR inhibitors are strongly associated with dyslipidemia. These pharmacologic effects underscore the need for tailored immunosuppressive strategies. The management of these conditions requires a multifaceted approach, including lifestyle interventions, pharmacological therapies like SGLT2 inhibitors and GLP-1 receptor agonists, and close monitoring. Additionally, emerging therapies hold promise in addressing metabolic complications in KT recipients. Proactive risk stratification and early intervention are essential to mitigating CKM syndrome and improving outcomes. This comprehensive review highlights the importance of integrating cardio-metabolic considerations into KT management, offering insights into optimizing long-term recipient health and graft survival.

Kidney transplantation was an effective method for treating chronic kidney failure via transplanting a healthy kidney from a donor to a patient with the loss of kidney function. However, clinical studies revealed that the posttransplantation status of patients was associated with a substantial aggregation of risk factors contributing to metabolic syndrome.

This article provided a comprehensive review of the current researches on metabolic syndrome after kidney transplantation, and the latest advances in the interaction between metabolism and immune cells were also covered.

Our aim was to identify and intervene high-risk recipients in time and thus improving the prognosis of recipients.

Sodium-glucose cotransporter-2 inhibitors (SGLT2i) improve cardiovascular prognosis in patients with chronic kidney disease (CKD), diabetes, and heart failure; and slow the decline of kidney dysfunction in patients with albuminuria. Although safety and efficacy of SGLT2i have not been investigated in kidney transplant recipients (KTRs), their marketing authorization leaves the possibility of their use in these patients in France.

This was a prospective multicenter real-life study including all consecutive KTRs treated with SGLT2i.

We identified 347 KTRs treated with SGLT2i (97% with dapagliflozin), with an initiation of treatment most often beyond the first year after transplantation (87%). Importantly, 226 (65.1%) were diabetic and 245 (70.6%) were treated with angiotensin-converting enzyme (ACE) inhibitors or angiotensin-receptor blockers (ARBs). We found a low incidence of urinary tract infections (UTIs) (6.6%) and genital mycosis (0.6%), without any serious adverse event. Overall, SGLT2i were stopped in 54 patients (15.6%). The causes of SGLT2i discontinuations were very diverse. The main causes were graft dysfunction (32%), intercurrent infections (17%), urinary infections (11%), and digestive symptoms (9%). KTRs with a low estimated glomerular filtration rate (eGFR), especially those with eGFR < 30 ml/min per 1.73 m2, presented with the highest incidence of SGLT2i discontinuation (P = 0.003). SGLT2i were associated with a reduction in proteinuria, found in both diabetic and nondiabetic KTRs. In addition, they had an antihypertensive effect restricted to uncontrolled-hypertensive patients.

SGLT2i have been used in KTRs since their authorization in France. They were discontinued more frequently in patients with impaired graft function; however, the expected side effects were infrequent and not life-threatening. The short-term antiproteinuric and antihypertensive effects are promising.

Iron is known to play a role in glucose homeostasis, and diabetes is highly prevalent in patients with iron overload. Here, we investigated whether ferritin and hepcidin (as parameters of iron status) are associated with the development of post-transplant diabetes in kidney transplant recipients, a population in which around 10 % is known to have high iron status.

Prospective data from the TransplantLines Insulin Resistance and Inflammation Biobank and Cohort Study from the University Medical Center Groningen, the Netherlands were evaluated, involving stable adult kidney transplant recipients > 1 year after transplantation. Associations between ferritin and hepcidin levels, as markers of iron status, and incident post-transplant diabetes were analyzed by multivariable Cox regression models, followed by the exploration of potential clinical cut-offs of ferritin levels related to the risk of post-transplant diabetes.

Of the included 443 kidney transplant recipients (age 50 ± 12 years, 44 % women, median 6.1 [3.0 - 12.1] years after transplantation), 65 kidney transplant recipients (15 %) developed post-transplant diabetes during a median follow-up of 9.6 [6.3 - 10.2] years. In contrast to hepcidin levels, ferritin levels were significantly associated with incident post-transplant diabetes, independent of adjustment for potential confounders (HR per 50 µg/l, 1.08; 95 % CI 1.02 - 1.14). When analyzing specific clinical cut-offs of ferritin levels, kidney transplant recipients with a ferritin > 500 µg/l (n=40) had more than twice the risk of developing post-transplant diabetes, compared to kidney transplant recipients with ferritin < 100 µg/l (HR, 2.81; 95 % CI 1.04 - 7.55).

Increased levels of ferritin are independently associated with a higher risk of post-transplant diabetes in kidney transplant recipients. Especially, kidney transplant recipients with ferritin levels > 500 µg/l, seem susceptible to the development of post-transplant diabetes over time.

Posttransplantation diabetes mellitus (PTDM) is a form of diabetes developed after solid organ or stem cell transplantation. This condition shares physiopathological traits with type 2 diabetes, including insulin resistance and β-cells dysfunction and its prevalence varies significantly based on the diagnostic criteria used. Immunosuppressive drugs directly contribute to PTDM risk through intricate impacts on glucose regulation, insulin secretion, and inflammation. In addition, modifiable and non-modifiable environmental risk factors are associated with the onset of this condition. This review aims to provide a comprehensive overview of the multifactorial nature of PTDM in order to highlight candidate genes and variants for pharmacogenetic research. An extensive literature search was conducted to identify studies on pharmacological and genetic factors influencing PTDM development. This review stresses the importance of understanding these interactions for improving PTDM management and underscores the need for further research to refine preventive approaches, ultimately enhancing patient outcomes post-transplantation.

Post-transplant diabetes mellitus (PTDM) is a complex condition arising from various factors including immunosuppressive medications, insulin resistance, impaired insulin secretion and inflammatory processes. Its impact on patient and graft survival is a significant concern in kidney transplant recipients. PTDM's impact on kidney transplant recipients, including patient and graft survival and cardiovascular mortality, is a significant concern, given conflicting findings in previous studies. This meta-analysis was imperative not only to incorporate emerging evidence but also to delve into cause-specific mortality considerations. We aimed to comprehensively evaluate the association between PTDM and clinical outcomes, including all-cause and cardiovascular mortality, sepsis-related mortality, malignancy-related mortality and graft loss, in kidney transplant recipients.

PubMed, Ovid/Medline, Web of Science, Scopus and Cochrane Library databases were screened and studies evaluating the effect of PTDM on all-cause mortality, cardiovascular mortality, sepsis-related mortality, malignancy-related mortality and overall graft loss in adult kidney transplant recipients were included.

Fifty-three studies, encompassing a total of 138 917 patients, evaluating the association between PTDM and clinical outcomes were included. Our analysis revealed a significant increase in all-cause mortality [risk ratio (RR) 1.70, 95% confidence interval (CI) 1.53 to 1.89, P < .001] and cardiovascular mortality (RR 1.86, 95% CI 1.36 to 2.54, P < .001) among individuals with PTDM. Moreover, PTDM was associated with a higher risk of sepsis-related mortality (RR 1.96, 95% CI 1.51 to 2.54, P < .001) but showed no significant association with malignancy-related mortality (RR 1.20, 95% CI 0.76 to 1.88). Additionally, PTDM was linked to an increased risk of overall graft failure (RR 1.33, 95% CI 1.16 to 1.54, P < .001).

These findings underscore the importance of comprehensive management strategies and the need for research targeting PTDM to improve outcomes in kidney transplant recipients.

Background: Solid organ transplant (SOT) recipients have an elevated risk of diabetes mellitus (DM). This study investigated the risk of posttransplant DM (PTDM) in a retrospective cohort study. Methods: We analyzed patients aged over 18 years who received an SOT between 2002 and 2013. Each patient was matched with four control individuals by age, sex, insured salary, urbanization level, Charlson's comorbidity index (CCI), and year of inclusion in the study. After matching, the study comprised 6874 patients who underwent an SOT and 27,496 matched general patients as the comparison. The risk of DM among the SOT recipients was assessed using a Cox proportional hazards model after adjustment for all relevant variables. Results: The SOT cohort had a significantly higher risk of DM than general patients (adjusted hazard ratio [aHR], 1.61; 95% confidence interval [CI], 1.51-1.72). Kidney and liver recipients, respectively, had DM incidence rates 1.57 (95% CI, 1.46-1.70) and 1.73 (95% CI, 1.53-1.94) times that of the general patients. Conclusions: SOT recipients had an elevated risk of DM. Among various organ recipients, liver recipients had the highest PTDM risk. Kidney and liver recipients demonstrated the highest DM risk at 6 months after their SOT. The risk of PTDM following an SOT may result in long-term consequences. Hence, we advise the critical need for proper management to mitigate related complications after transplantation.

Diabetes mellitus (DM) in kidney transplant recipients (KTR) is a risk factor for mortality, increases the risk of infections and, in the long term, can lead to graft loss due to diabetic kidney disease. A preventive approach applied to those on the waiting list could decrease the incidence of post-transplant DM (PTDM) by detecting those patients at risk, thus allowing strategies to minimize the probability of developing a New Onset Diabetes After Transplant (NODAT). On the other hand, modifications of immunosuppressive therapy may improve glucose control in patients with KTR. In recent years, two new classes of antidiabetic drugs and non-steroidal mineralocorticoid receptor antagonists have demonstrated cardiovascular and renal benefits in randomized clinical trials where the transplant population has not been represented. Because of the potential benefit expected in this population, the clinical use of glucagon-like peptide-1 receptor agonists (GLP-1RA), sodium-glucose cotransporter 2 inhibitors (SGLT2i) and finerenone is increasing in the kidney transplant setting. This review focuses on comprehensive pharmacological interventions in KTR with glucose metabolism disorders. In-depth knowledge in this area will allow prevention and identification of potential adverse effects or drug interactions in the clinical course of KTR with DM.

The concept of pharmacokinetic (PK) boosting of calcineurin inhibitors (CNI) emerged after the FDA approval of cyclosporine-A. Several studies followed, and the proof of concept was well established by the late 1990s. This also continued for the next blockbuster immunosuppressant, tacrolimus. The driver for such research was an endeavor to save costs, as both drugs were expensive due to patent protection. Two CYP inhibitors, ketoconazole and diltiazem, have been extensively studied in this context and continue to be prescribed off-label along with the CNI. It has been observed that using ketoconazole reduces the dose requirement of tacrolimus by about 50% and 30% with diltiazem, which is in conformity with their pharmacological actions. Off-label co-prescription of these drugs with CNI is often encountered in low and middle-income countries. The foremost reason cited is economic. This article collates the evidence from the clinical studies that evaluate the PK-boosting effects of CNI and also reviews the gaps in the current evidence base. The current knowledge prevents the transplant community from making meaningful inferences about the risks and benefits of such strategies. Although the PK-boosting strategy can lead to serious adverse events, emerging evidence suggests that it may be advantageous for individuals with high CNI dose requirements. Hence, PK boosting may be an unmet need in the therapeutics of CNI. Nevertheless, there are several unanswered questions surrounding such use, and therefore, this merits testing in well-designed clinical studies. Moreover, drugs with better safer profiles and a history of successful PK boosting may be considered for evaluation with CNI.

Diabetes is the commonest cause of end stage kidney disease globally, accounting for almost 40% of new cases requiring renal replacement therapy. Management of diabetes in people with advanced kidney disease on renal replacement therapy is challenging due to some unique aspects of assessment and treatment in this group of patients. Standard glycaemic assessment using glycated haemoglobin may not be valid in such patients due to altered red blood cell turnover or iron/erythropoietin deficiency, leading to changed red blood cell longevity. Therefore, use of continuous glucose monitoring may be beneficial to enable more focussed glycaemic assessment and improved adjustment of therapy. People with advanced kidney disease may be at higher risk of hypoglycaemia due to a number of physiological mechanisms, and in addition, therapeutic options are limited in such patients due to lack of experience or license. Insulin therapy is the basis of treatment of people with diabetes with advanced kidney disease due to many other drugs classes being contraindicated. Targets for glycaemic control should be adjusted according to co-morbidity and frailty, and continuous glucose monitoring should be used in people on dialysis to ensure low risk of hypoglycaemia. Post-transplant diabetes is common amongst people undergoing solid organ transplantation and confers a greater risk of mortality and morbidity in kidney transplant recipients. It should be actively screened for and managed in the post-transplant setting.

Although post-transplant diabetes mellitus (PTDM) is a common complication after kidney transplantation, there are few data on prevention, optimal screening, and treatment strategies.

The European Renal Association's DESCARTES working group distributed a web-based survey to European transplant centres to gather information on risk assessment, screening procedures, and management practices for preventing and treating PTDM in kidney transplant recipients.

Answers were obtained from 121/241 transplant centres (50%) across 15 European countries. Screening practices for diabetes mellitus during the transplant work-up varied, with only 13% of centres using the recommended oral glucose tolerance test (OGTT) and 14% not screening at all. At transplantation, 19% of centres tailored the immunosuppressive regimen based on perceived PTDM risk, using strategies such as cyclosporin use or early steroid withdrawal. Fifty-two percent adopted strict glycaemic control with basal insulin in the first days post-transplant. Sixty-eight percent had defined screening protocols for early PTDM (45 days-6 months), primarily based on fasting glycaemia and/or HbA1c, while only a minority (7%) incorporated an OGTT. Changes in immunosuppression were considered by 41% in cases of early hyperglycaemia (<45 days) and by 58% in established PTDM (>45 days). Besides insulin therapy, dipeptidyl peptidase-4 (DPP4) inhibitors and metformin were most frequently used to manage early hyperglycaemia (<45 days) and PTDM (>45 days). The use of SGLT2 inhibitors and GLP-analogues increased >45 days post-transplantation.

This European survey underscores the significant variation in PTDM prevention, screening, and treatment practices, emphasizing the imperative for more explicit guidance in approaching this complication.

Early post-transplant hyperglycaemia (EPTH) and post-transplant diabetes mellitus (PTDM) are common following solid organ transplantation and may be associated with adverse outcomes. We studied the prevalence of EPTH and cumulative 5-year prevalence of PTDM in a modern cohort of heart transplant recipients who were free from diabetes at baseline as well as the association of EPTH, PTDM and pre-transplant T2DM with adverse transplant-related outcomes.

Retrospective cohort study of heart transplant recipients followed for 5 years at a single centre in Sydney, Australia.

A total of 141 patients were included, of whom 25 had pre-existing type 2 diabetes mellitus (T2DM) and 116 were free from diabetes at baseline. In patients without pre-existing T2DM, 88 of 116 (76%) experienced EPTH, which was associated with higher rates of acute rejection and hospitalizations, and lower 5-year survival. PTDM developed in 45 of 116 (39%) patients, all of whom had experienced EPTH. Both PTDM and pre-existing T2DM were associated with increased rates of graft rejection and hospitalization, and greater than three-fold increased likelihood of death compared to patients that remained free from diabetes.

EPTH and PTDM are highly prevalent following cardiac transplantation. EPTH develops within days of transplant and is strongly associated with progression to PTDM. Pre-existing T2DM, PTDM and EPTH are associated with greater hospitalization, increased episodes of rejection and worse 5-year survival compared to patients who remained free from diabetes during follow-up.

The American Diabetes Association (ADA) "Standards of Care in Diabetes" includes the ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, an interprofessional expert committee, are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations and a full list of Professional Practice Committee members, please refer to Introduction and Methodology. Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC.

Posttransplant diabetes mellitus (PTDM) and prediabetes represent serious complications after kidney transplantation and are associated with increased cardiovascular morbidity and mortality. We assessed the predictive performance of continuous glucose monitoring (CGM) compared with plasma glucose and hemoglobin A1c in 46 kidney transplant recipients (KTRs) without known preexisting diabetes mellitus. CGM (14-day recording duration) was performed on days 8, 30, 45, 60, 90, and 180 posttransplant. Eight patients (17%) developed PTDM and nine (20%) impaired glucose tolerance (IGT), as diagnosed by oral glucose tolerance test (oGTT)-derived 2-hour plasma glucose (2hPG) or glucose-lowering therapy on day 90. CGM-readouts percent of time >140 mg/dL (%TAR (140 mg/dL)) and percent of time >180 mg/dL (%TAR (180 mg/dL)) showed excellent in-sample test characteristics regarding PTDM from day 8 onward (days 8-90 receiver operating characteristic area under the curve: 0.88-0.99) and regarding PTDM/IGT with the commencement of maintenance immunosuppression from day 30 onward (days 30-90 receiver operating characteristic area under the curve: 0.88-0.91). Exploratory CGM-%TAR (140 mg/dL)-screening thresholds of 31.8% on day 8 and 13.2% on day 30 yielded sensitivities/specificities of 88%/83% for PTDM and 94%/78% for PTDM/IGT on day 90, respectively. Although our findings need to be replicated in studies with larger sample sizes, CGM bears promising potential to facilitate clinical practice and research regarding PTDM.

Diabetic cardiomyopathy (DCM) represents a critical complication of Diabetes mellitus (DM), characterized by structural and functional changes in the myocardium independent of coronary artery disease or hypertension. Emerging evidence highlights the significant roles of phytochemicals, particularly astilbin and apigenin, in modulating key molecular pathways implicated in DCM. This review synthesizes current mechanistic insights and therapeutic potential of these compounds, focusing on their interactions with AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptors (PPARs), O-linked N-acetylglucosamine (O-GlcNAc), sodium-glucose co-transporter 2 (SGLT2), protein kinase C (PKC), nuclear factor kappa B (NF-κB), mitogen-activated protein kinase (MAPK), and c-Jun N-terminal kinase (JNK) pathways. Astilbin and apigenin have demonstrated the ability to improve cardiac function, mitigate oxidative stress, and reduce inflammatory responses in diabetic conditions. By activating AMPK and PPARs, these flavonoids enhance glucose uptake and fatty acid oxidation, contributing to improved metabolic homeostasis. Their inhibition of O-GlcNAcylation, SGLT2 activity, and PKC signaling further attenuates hyperglycemia-induced cellular damage. Additionally, suppression of NF-κB, MAPK, and JNK pathways by astilbin and apigenin results in reduced pro-inflammatory cytokine production and apoptotic cell death. Collectively, these interactions position astilbin and apigenin as promising therapeutic agents for ameliorating DCM, offering novel avenues for treatment strategies aimed at modulating multiple pathogenic pathways.

Orthotopic liver transplantation (OLT) has greatly improved short-term survival for end-stage liver disease. However, cardiovascular events (CVE) still pose a significant threat to long-term post-transplant health. Aim of this study is to assess the occurrence of long-term cardiovascular events and whether it relates to new-onset diabetes after liver transplantation (NODALT).

We conducted a multicentric retrospective analysis of adult OLT recipients with regular follow-up visits spanning from January 1995 to December 2020. Data collection included anamnestic, clinical, anthropometric, and laboratory data from two centers. NODALT was diagnosed following ADA guidelines. The primary outcome was incident CVE (a composite of fatal and non-fatal stroke and myocardial infarction). CVE occurrence was analyzed in relation to NODALT diagnosis, along with clinical characteristics associated with its development.

Ninety-three eligible Caucasian patients, with a median age of 57.0 years (IQR: 49.0-62.0, 69.9% male), were enrolled. Over the median follow-up period of 100.5 months, 29 patients (31.2%) developed NODALT, and 14 patients (15.1%) developed any CVE, with 9 being in the NODALT group. A significant association between NODALT and cardiovascular complications was confirmed by both generalized estimating equation (OR 5.31; 95% CI 1.59-17.72, p = 0.006) and Kaplan-Meier analysis (log-rank = 0.046). Metabolic syndrome and impaired fasting glucose were identified as baseline risk factors for the incident NODALT (OR 5.75; 95% CI 1.44-22.92, p = 0.013 and OR 7.29; 95% CI 1.46-36.41, p = 0.015, respectively).

Post-OLT cardiovascular events are less frequent than previously reported but are notably linked to NODALT, highlighting the interplay between metabolic syndrome and impaired fasting glucose.

Background/Objectives: Glucocorticoids are commonly used for maintenance immunosuppressive therapy in kidney transplant recipients (KTRs). We aimed to investigate the prevalence of hypothalamic-pituitary-adrenal (HPA) axis suppression and its association with metabolic disorders in stable KTRs on low-dose glucocorticoids. Methods: This cross-sectional study included adult KTRs on low-dose glucocorticoids. HPA axis suppression was defined as baseline morning cortisol < 5 μg/dL. Adrenocorticotropic hormone (ACTH), dehydroepiandrosterone-sulphate (DHEAS) and 24 h urinary free cortisol (UFC) levels were also assessed. Examined metabolic disorders included hypertension, dyslipidemia, central obesity and post-transplant diabetes mellitus (PTDM). Results: Eighty adult KTRs with a median 57 months (IQR 24-102) since transplantation were included in the study. The mean prednisolone dose was 5.0 ± 1.3 mg/day. Baseline cortisol < 5.0 μg/dL was observed in 27.5% of the KTRs. Participants with baseline cortisol < 5.0 μg/dL were older (55.1 vs. 47.4 years, p = 0.023) and had had a transplant for a longer time (101.4 vs. 67.0 months, p = 0.043), compared with the rest of the cohort. Baseline cortisol correlated positively with ACTH (rho = 0.544, p < 0.001), DHEAS (rho:0.459, p < 0.001) and UFC (rho: 0.377, p = 0.002). The area under the receiver-operating characteristic curve for ACTH as a predictor of baseline cortisol > 5.0 μg/dL was 0.79 [95% confidence interval (CI): 0.68-0.89]. After adjustment for covariates, HPA axis suppression was not associated with the examined metabolic disorders. Conclusions: Our study showed that stable KTRs on chronic low-dose glucocorticoids exhibited an increased prevalence of HPA axis suppression. ACTH may serve as a surrogate biomarker for HPA axis activity in this population. Further research could evaluate the association of glucocorticoid-induced HPA axis inhibition with metabolic disorders.

Kidney transplantation (KT) is the best kidney replacement treatment for autosomal dominant polycystic kidney disease (ADPKD). We aimed to investigate the clinical characteristics and outcomes of KT in ADPKD patients compared to those in non-ADPKD patients.

We retrospectively analyzed KT recipients in two Korean transplantation centers from 2005 to 2020. Propensity score-matching and Cox regression analysis were used to assess the clinical outcomes of ADPKD compared to non-ADPKD and identify prognostic factors influencing outcomes in ADPKD.

Among a total of 4452 KT patients, 189 (4.2%) were ADPKD patients. Median age at transplantation was 53.0 and 47.0 in ADPKD and non-ADPKD patients, respectively. In both groups, living-donor KT was more common than deceased-donor KT. The ADPKD group had a 4.09-fold higher risk of post-transplant diabetes mellitus and a 1.65-fold higher risk of post-transplant infection compared to the non-ADPKD group; however, subjects with ADPKD had similar risk of rejection, graft failure, and mortality. In the ADPKD group, kidney volume decreased after KT, irrespective of kidney volume status (Mayo classification), while the size of hepatic cysts increased. Neither kidney volume nor nephrectomy of native kidneys were associated with risk of infection, graft failure, or mortality in the ADPKD group.

ADPKD patients have a higher risk of post-transplant diabetes mellitus and infection than non-ADPKD patients, with no significant impact of kidney volume or nephrectomy on post-transplant outcomes.

Steroids are widely used in maintenance immunosuppression treatment in kidney transplant recipients. Older individuals undergo age-related immunosenescence that consequently decreases their ability to process and evoke a response to foreign antigens. Thus, steroids may not be necessary in preventing allograft rejection and may consequently increase older recipients' risk of long-term steroid-related adverse effects.

The objective of this study was to analyze the adverse outcomes of long-term steroid immunosuppression in older kidney transplant recipients using real-world electronic medical record data.

The TriNetX database "US Collaborative Network" was utilized to perform a propensity score-matched case-control study comparing 1-year, 3-year, and 5-year adverse effects of steroid immunosuppression in older adults (aged ≥ 65 years) kidney transplant recipients who underwent either an early-steroid withdrawal (ESW) maintenance regimen or a steroid continuous immunosuppression (SCI) regimen between 31 December, 2010 and 31 December, 2020. Early-steroid withdrawal was defined as tacrolimus plus mycophenolate mofetil maintenance with no prednisone after the seventh day post-transplant. Steroid continuous immunosuppression was defined as tacrolimus plus mycophenolate mofetil plus prednisone maintenance. Cohorts were matched on age, race/ethnicity, and risk factors for adverse steroid-related outcomes and rejection. Outcomes included post-transplant diabetes mellitus, dyslipidemia osteoporosis/fractures, myocardial infarction, glaucoma/cataract, stroke, pulmonary embolism, and malignancy. Secondary outcomes analyzed incidences of infection-related outcomes, graft-related outcomes, and recipient mortality.

After matching, there were 304 recipients in each group (ESW, SCI). Mean age at the time of transplant was 69.2 ± 3.7 years (ESW) and 69.2 ± 3.4 years (SCI, p = 0.96). The Kaplan-Meier analysis showed recipients who underwent SCI had increased incidences of post-transplant diabetes mellitus at 1 year (22.36% vs 30.37%, p = 0.01) and 3 years (34.89% vs 44.29%, p = 0.01), but this became non-significant at 5 years post-transplant (41.97% vs 42.6%, p = 0.34). Incidences of acute pancreatitis were higher for the SCI cohort at 3 years (p = 0.02) as well as incidences of acute myocardial infarction at 5 years post-kidney transplant (6.75% vs 14.39%, p < 0.01). No difference was found for other adverse outcomes. Early-steroid withdrawal recipients experienced significantly fewer infection-related outcomes, such as cytomegalovirus, BK virus, sepsis/bacteremia, and fungal infections, compared with SCI recipients. Last, recipients who underwent ESW experienced fewer incidences of rejection and death-censored graft failure at 5 years post-transplant.

There is currently no standard maintenance immunosuppression protocol for older kidney transplant recipients. Death-censored graft survival, rejection, and patient survival were improved with ESW. Steroid minimization may be beneficial in this population given that it lowers the risk of drug-induced adverse effects.

Posttransplant diabetes mellitus (PTDM) is a prevalent complication of liver transplantation and is associated with cardiometabolic complications. We studied the consequences of genetic effects of liver donors and recipients on PTDM outcomes, focusing on the diverse genetic pathways related to insulin that play a role in the development of PTDM. One thousand one hundred fifteen liver transplant recipients without a pretransplant diagnosis of type 2 diabetes mellitus (T2D) and their paired donors recruited from 2 transplant centers had polygenic risk scores (PRS) for T2D, insulin secretion, and insulin sensitivity calculated. Among recipients in the highest T2D-PRS quintile, donor T2D-PRS did not contribute significantly to PTDM. However, in recipients with the lowest T2D genetic risk, donor livers with the highest T2D-PRS contributed to the development of PTDM (OR [95% CI] = 3.79 [1.10-13.1], P = .035). Recipient risk was linked to factors associated with insulin secretion (OR [95% CI] = 0.85 [0.74-0.98], P = .02), while donor livers contributed to PTDM via gene pathways involved in insulin sensitivity (OR [95% CI] = 0.86 [0.75-0.99], P = .03). Recipient and donor PRS independently and collectively serve as predictors of PTDM onset. The genetically influenced biological pathways in recipients primarily pertain to insulin secretion, whereas the genetic makeup of donors exerts an influence on insulin sensitivity.

Early post-transplant hyperglycemia (EPTH) is an independent risk factor for hospital readmissions, acute rejection, infections and developing post-transplant diabetes mellitus (PTDM). Close glycemic control is prudent in the early post-transplant period. The management of EPTH was evaluated among a cohort of kidney transplant recipients, who either received routine care (RC) or dedicated endocrine care (DEC).

A retrospective analysis was conducted on kidney transplant recipients from 2019 to 2023. The impact of DEC on post-transplant glycemic control was investigated. Hospitalized patients receiving post-transplant insulin therapy were included. DEC involved at least twice-daily blood glucose (BG) assessment by an endocrinologist, while the RC received usual care. A mixed-model analysis was employed to assess differences in BG trajectories between DEC and RC over an eight-day period. Additionally, various glycemic control metrics were compared, including glucose variability, time-in-range for target BG, rates of hypoglycemia and response to hyperglycemia.

The cohort comprised 113 patients. In the DEC group, 91% had pre-transplant DM compared to 15% in the RC group (p < 0.001). Patients under DEC had higher baseline BG and glycated hemoglobin compared to those under RC (p < 0.001, for both). The DEC group displayed a lower trajectory of BG over time compared to the RC group (p = 0.002). Patients under DEC were more likely to receive insulin if BG measured above 200 mg/dL (66% vs. 46%) and displayed less below-range BG (<110 mg/dL) compared to those under RC (12.9% vs. 23.6%, p < 0.001).

Management of EPTH by DEC improves glycemic outcomes in renal transplant recipients.

Little is known either about either physical activity patterns, or other lifestyle-related prevention measures in heart transplantation (HTx) recipients. The history of HTx started more than 50 years ago but there are still no guidelines or position papers highlighting the features of prevention and rehabilitation after HTx. The aims of this scientific statement are (i) to explain the importance of prevention and rehabilitation after HTx, and (ii) to promote the factors (modifiable/non-modifiable) that should be addressed after HTx to improve patients' physical capacity, quality of life and survival. All HTx team members have their role to play in the care of these patients and multidisciplinary prevention and rehabilitation programmes designed for transplant recipients. HTx recipients are clearly not healthy disease-free subjects yet they also significantly differ from heart failure patients or those who are supported with mechanical circulatory support. Therefore, prevention and rehabilitation after HTx both need to be specifically tailored to this patient population and be multidisciplinary in nature. Prevention and rehabilitation programmes should be initiated early after HTx and continued during the entire post-transplant journey. This clinical consensus.

New-onset diabetes mellitus is a frequent and severe complication arising after liver transplantation (LT). We aimed to identify the risk factors for new-onset diabetes mellitus after liver transplantation (NODALT) and to develop a risk prediction score system for relevant risks.

We collected and analyzed data from all recipients who underwent liver transplantation at the First Affiliated Hospital of Xi'an Jiaotong University. The OR derived from a multiple logistic regression predicting the presence of NODALT was used to calculate the risk prediction score. The performance of the risk prediction score was externally validated in patients who were from the CLTR (China Liver Transplant Registry) database.

A total of 468 patients met the outlined criteria and finished the follow-up. Overall, NODALT was diagnosed in 115 (24.6%) patients. Age, preoperative impaired fasting glucose (IFG), postoperative fasting plasma glucose (FPG), and the length of hospital stay were significantly associated with the presence of NODALT. The risk prediction score includes age, preoperative IFG, postoperative FPG, and the length of hospital stay. The risk prediction score of the area under the receiver operating curve was 0.785 (95% CI: 0.724-0.846) in the experimental population and 0.782 (95% CI: 0.708-0.856) in the validation population.

Age at the time of transplantation, preoperative IFG, postoperative FPG, and length of hospital stay were independent predictive factors of NODALT. The use of a simple risk prediction score can identify the patients who have the highest risk of NODALT and interventions may start early.

Kidney transplantation (KT) improves the cardiovascular outcomes of patients with end-stage kidney disease. However, cardiovascular disease remains the leading cause of premature death and graft loss in KT recipients (KTRs) with diabetes. We evaluated the cardioprotective effects of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in KTRs with diabetes.

A total of 750 KTRs with diabetes were enrolled from 6 tertiary hospitals. Among them, 129 patients (17.2%) were prescribed SGLT2i. The primary outcome was the incidence of major adverse cardiovascular events (MACE), which comprised myocardial infarction (MI), death from cardiovascular causes, hospitalization for heart failure, and stroke. Multivariable Cox regression analysis and propensity score matching were used to investigate the effect of SGLT2i on clinical outcomes.

In the matched cohort, MACE occurred in 5 patients (3.9%) in the SGLT2i group and 15 patients (11.8%) in the non-SGLT2i group, out of 127 patients in each group over 55.3 months. The incidence of MACE and MI was lower in the SGLT2i group than in the non-SGLT2i group (P = 0.036 and 0.008, respectively). In multivariate analysis, the SGLT2i group had a lower risk of MACE and MI than the non-SGLT2i group (adjusted hazard ratio [HR], 0.30 and 0.04; 95% confidence interval [CI], 0.10-0.88 and 0.004-0.40; P = 0.028 and 0.006, respectively). There was no difference in the incidence of urinary tract infection (UTI) between the 2 groups.

SGLT2i significantly decreased the risk of cardiovascular events in KTRs with diabetes, particularly lowering the incidence of MI and death from cardiovascular causes. SGLT2i can be used to reduce the burden of cardiovascular disease in KTRs with diabetes.

Kidney transplantation is the most effective treatment for end-stage renal failure but is associated with complications, including post-transplant diabetes mellitus (PTDM). It affects the quality of life and survival of patients and the transplanted organ. It can cause complications, including infections and episodes of acute rejection, further threatening graft survival. The prevalence of PTDM, depending on the source, can range from 4 to 30% in transplant patients. This article aims to discuss issues related to diabetes in kidney transplant patients and the latest treatments. Knowledge of the mechanisms of action of immunosuppressive drugs used after transplantation and their effect on carbohydrate metabolism is key to the rapid and effective detection of PTDM. Patient therapy should not only include standard management such as lifestyle modification, insulin therapy or pharmacotherapy based on well-known oral and injection drugs. New opportunities are offered by hypoglycemic drugs still in clinical trials, including glucokinase activators, such as dorzagliatin, ADV-1002401, LY2608204, TMG-123, imeglimine, amycretin and pramlintide. Although many therapeutic options are currently available, PTDM often creates uncertainty about the most appropriate treatment strategy. Therefore, more research is needed to individualize therapeutic plans and monitor these patients.