Diagnosis Of Posttransplant Diabetes Mellitus Research Articles

#1888 Association between intrapatient variability of serum tacrolimus levels with the development of diabetes in post-kidney transplantation patients

Abstract Background and Aims Kidney transplantation is the most cost-effective renal replacement therapy compared to dialysis. Diabetes is main cause of increased cardiovascular risk and death. Post-transplant Diabetes Mellitus (PTDM) it refers to presence of diabetes in an environment after kidney transplantation; According to the ADA (American Diabetes Association) criteria, the diagnosis must be made with a tolerance test with 75 grams of oral glucose (Oral glucose tolerance test-OGTT) or the determination of glycosylated hemoglobin 1Ac (Hb1Ac) in a post-transplant period of stability of the immunosuppression dose and without infections. There are various risk factors for the development of PTDM: hypomagnesemia, glucocorticoids, calcineurin inhibitors (tacrolimus and cyclosporine); hepatitis C virus and cytomegalovirus infections. In a Mexican kidney transplant recipients in Guadalajara, Andrade SG demonstrated that the incidence of PTDM was 10.1% at 1 year post-transplant. In the Spanish population, Porrini E demonstrated that tacrolimus represents a risk factor for the development of PTDM, increasing the incidence of prediabetes by 33% at 12 months post-transplant. Several mechanisms have been implicated in the association of calcineurin inhibitor and PTDM: decreased insulin secretion, glucose intolerance, reduced pancreatic beta cell mass, increased islet apoptosis and decreased insulin gene expression. Studies mention that tacrolimus (FK) is more diabetogenic than cyclosporine (CsA) especially at levels above 20 ng/mL. The DIRECT study (Diabetes Incidence after Renal Transplantation) showed the incidence in 73 kidney transplant patients with CsA (26%) and 96 FK patients (33.6%, p = 0.046). By the other side, Malik RF mentions that FK levels aren´t a risk factor for the development of PTDM. To demonstrate that the high intrapatient variability of tacrolimus/cyclosporine serum levels correlates with the development of diabetes (PTDM) in kidney transplant recipients at the central military hospital in Mexico City. Method Observational, analytical, longitudinal and retrospective study. All kidney transplant recipients from living donors and cadaveric donors from January 2002 to December 2020 were included. FK and CsA were used as maintenance immunosuppression. Serum levels of FK/CsA, Hb1Ac and glucose were measured at months 0, 3, 6, 9 and 12 and intra-patient variability (IPV) of FK/CsA levels was calculated for each patient. The patients were separated into 2 groups, IPV low and IPV high according to the mean the coefficient of variability (CV). The IPV of the calcineurin inhibitor was estimated by calculating the CV in each patient according to the following equation: CV(%)= (SD/mean trough concentration of FK/ CsA)×100. The diagnosis of PTDM followed the criteria of the American Diabetes Association. The Mann Whitney U test was used. Results 638 kidney transplant recipients were included. The mean age of the recipients was 36.78 (±12.81) years. At the time of kidney transplant, the BMI was 22.67 (±3.90) and 25.76 (±3.99) kg/m² BS at 1 year post-transplant for whole cohort. At 1 year post-transplant, 72.3% patients were on FK and 27.7% on CsA. Hb1Ac for whole cohort was 4.81 (±0.71)% and 4.84 (±0.77)% at month 0 and 12 post-kidney transplant, respectively. FK and CsA levels were 12.41 (±5.31) and 234.34 (±87.80) ng/mL and 9.13 (±5.3) and 194.38 (±92.44) ng/mL in the PTDM and non-PTDM groups, respectively (p = 0.029). 17.96% of patients developed PTDM. Mean CV of the entire cohort was 33.84 (±20.41)%. When performing the analysis of the IPV coefficient by subgroups of maintenance immunosuppression used at 1 year post-transplant: the IPV of FK was 43.39 (±18.49)% and 29.99 (±17.56)% in the PTDM and non-PTDM groups respectively, p = 0.000, which shows that patients with a high IPV coefficient of tacrolimus developed more PTDM than those with low variability, student's t-test to compare IPV was 0.03. The IPV of CsA was 38.61 (±18.76)% and 37.51 (±25.67)% in the PTDM and non-PTDM groups respectively, p = 0.819. Conclusion High intrapatient variability of tacrolimus was correlated with the development of PTDM in Mexican kidney transplant recipients.

#1680 Cardiovascular disease in kidney transplant recipients with post-transplant diabetes mellitus—retrospective analysis from a randomized trial

Abstract Background and Aims Kidney transplant recipients are at risk for glucometabolic deterioration. While many individuals recover their glycemic profiles, some develop posttransplant diabetes mellitus (PTDM). Previous reports have shown that PTDM is associated with increased risk for cardiovascular disease (CVD) and mortality. Here we aimed at assessing the association of PTDM with the development of CVD in kidney transplant recipients from a randomized trial. Method CVD with functioning graft (WFG), all-cause death WFG and death-censored graft loss were retrospectively investigated in N = 263 participants from the Insulin Therapy for the Prevention of New Onset Diabetes after Transplantation multicenter randomized-controlled trial (ITP-NODAT, ClinicalTrials.gov NCT03507829). The clinical trial was conducted from November 2012 through May 2018; kidney transplant recipients without previous diabetes diagnosis had received basal insulin therapy or control for afternoon hyperglycemia. For the current analysis, CVD was defined as a composite of cerebrovascular disease (stroke, transient ischemic attack), coronary artery disease (myocardial infarction, revascularization, stenting), hospitalization for heart failure and vascular/peripheral arterial disease interventions. Participants were to perform three OGTTs at 6, 12 and 24 months posttransplant, which we handled as landmarks in our present analysis. Besides PTDM versus NON-PTDM, we stratified according to basal insulin intervention and control. Cox proportional hazard models were presented unadjusted and adjusted for age, sex and pre-transplant CVD. All patients gave informed consent to participate in the trial and we obtained institutional review board approval for the present analysis. Results Cumulative incidence curves for CVD WFG are presented in Fig. 1. The associated risk of PTDM at 6, 12 and 24 months for CVD WFG tended to be higher in PTDM versus NON-PTDM. At the respective timepoints, the control versus basal insulin groups were similar (Fig. 1). Cause-specific hazard ratios for CVD WFG, all-cause death WFG and death-censored graft loss are presented in Table 1. PTDM was associated with CVD WFG in the univariable models. Corresponding Hazard Ratios (with 95% Confidence Intervals) at 6, 12 and 24 months were 2.53 (1.23, 5.18), 3.19 (1.51, 6.78) and 4.28 (1.94, 9.48), respectively. After adjustment for age, sex and pre-transplant history of CVD, corresponding HRs (95% CIs) were 1.37 (0.64, 2.91), 1.37 (0.61, 3.06) and 3.01 (1.26, 7.22), respectively. PTDM was not associated with all-cause death WFG in the univariable models. Corresponding HRs (95% CIs) at 6, 12 and 24 months were 1.97 (0.82, 4.75), 2.44 (0.95, 6.25) and 2.32 (0.89, 6.05), respectively. PTDM was also not associated with death-censored graft loss in the univariable models. Corresponding HRs (95% CIs) at 6, 12 and 24 months were 1.44 (0.62, 3.36), 2.10 (0.89, 4.94) and 1.15 (0.39, 3.37), respectively. PTDM was neither associated with all-cause death WFG or death-censored graft loss in the adjusted models. Conclusion PTDM diagnosed by OGTT at month 24 was significantly associated with cardiovascular disease independent of age, sex or pre-transplant CVD. The association, however, was not significant when PTDM was diagnosed before month 24. It is possible that transient PTDM diagnosis, early CVD events and study discontinuations before month 24 may have contributed to the differing results over time. Timely PTDM diagnosis may open a window of opportunity for interventions, such as in the form of novel glucose-lowering agents, that may reduce cardiovascular risk in kidney transplant recipients.

Oral Glucose Tolerance Test as a Risk Marker for Developing Post-Transplant Diabetes Mellitus

IntroductionThe incidence of post-transplant diabetes mellitus (PTDM) can reach 30% during the first 6 months after kidney transplantation (KT), increasing the risk of graft failure and mortality. There is no well-established biomarker for predicting PTDM occurrence. This study evaluated the association between the abnormal 2-hour oral glucose tolerance test (OGTT) and the PTDM incidence. MethodsA retrospective single-center study, including adult kidney transplant recipients from deceased donors, was performed between March 2021 and June 2022. Exclusion criteria: age <18 years; pretransplant diabetes mellitus (DM); death with a functioning graft; loss of follow-up and/or graft failure before 6 months post-transplant. The results of pretransplant OGTT, fasting (FPG), and afternoon plasma glucose levels at hospitalization and FPG in the first, second, and third months post-transplant were evaluated. For analysis, patients were grouped according to the PTDM diagnosis: PTDM and non-PTDM. ResultsFrom 164 KT performed in the period, 50 (30%) were included, most male (n = 34, 68%), with a mean age of 48.3 ± 12.5 years. Nine patients (18%) developed PTDM, 44% between 3 and 6 months. General characteristics and immunosuppressive therapy were similar between the groups. The mean FPG in the pretransplant OGTT was significantly higher in the PTDM group compared with the non-PTDM group (85.7 ± 7.9 vs 79.1 ± 8.2, P = .03). The number of patients classified as impaired glucose tolerance (IGT) on the pre-transplant OGTT was significantly higher in the PTDM group. ConclusionIGT in the pretransplant OGTT was associated with PTDM cases in kidney transplant recipients without a previous diagnosis of DM.

Genetic and Epigenetic Associations with Post-Transplant Diabetes Mellitus.

Post-transplant diabetes mellitus (PTDM) is a common complication of solid organ transplantation. PTDM prevalence varies due to different diabetes definitions. Consensus guidelines for the diagnosis of PTDM have been published based on random blood glucose levels, glycated hemoglobin (HbA1c), and oral glucose tolerance test (OGTT). The task of diagnosing PTDM continues to pose challenges, given the potential for diabetes to manifest at different time points after transplantation, thus demanding constant clinical vigilance and repeated testing. Interpreting HbA1c levels can be challenging after renal transplantation. Pre-transplant risk factors for PTDM include obesity, sedentary lifestyle, family history of diabetes, ethnicity (e.g., African-Caribbean or South Asian ancestry), and genetic risk factors. Risk factors for PTDM include immunosuppressive drugs, weight gain, hepatitis C, and cytomegalovirus infection. There is also emerging evidence that genetic and epigenetic variation in the organ transplant recipient may influence the risk of developing PTDM. This review outlines many known risk factors for PTDM and details some of the pathways, genetic variants, and epigenetic features associated with PTDM. Improved understanding of established and emerging risk factors may help identify people at risk of developing PTDM and may reduce the risk of developing PTDM or improve the management of this complication of organ transplantation.

An update review of post-transplant diabetes mellitus: Concept, risk factors, clinical implications and management.

Kidney transplantation is the gold standard therapeutic alternative for patients with end-stage renal disease; nevertheless, it is not without potential complications leading to considerable morbidity and mortality such as post-transplant diabetes mellitus (PTDM). This narrative review aims to comprehensively evaluate PTDM in terms of its diagnostic approach, underlying pathophysiological pathways, epidemiological data, and management strategies. Articles were retrieved from electronic databases using predefined search terms. Inclusion criteria encompassed studies investigating PTDM diagnosis, pathophysiology, epidemiology, and management strategies. PTDM emerges as a significant complication following kidney transplantation, influenced by various pathophysiological factors including peripheral insulin resistance, immunosuppressive medications, infections, and proinflammatory pathways. Despite discrepancies in prevalence estimates, PTDM poses substantial challenges to transplant. Diagnostic approaches, including traditional criteria such as fasting plasma glucose (FPG) and HbA1c, are limited in their ability to capture early PTDM manifestations. Oral glucose tolerance test (OGTT) emerges as a valuable tool, particularly in the early post-transplant period. Management strategies for PTDM remain unclear, within sufficient evidence from large-scale randomized clinical trials to guide optimal interventions. Nevertheless, glucose-lowering agents and life style modifications constitute primary modalities for managing hyperglycemia in transplant recipients. The complex interplay between PTDM and the transplant process necessitates individualized diagnostic and management approaches. While early recognition and intervention are paramount, modifications to maintenance immunosuppressive regimens based solely on PTDM risk are not warranted, given the potential adverse consequences such as increased rejection risk. Further research is essential to refine management strategies and enhance outcomes for transplant recipients.

Abstract 12489: Sex Differences in Incidence and Outcomes of Patients With New-Onset Post-Transplant Diabetes Mellitus After Heart Transplantation

Introduction: Post-transplant diabetes mellitus (PTDM) is a common complication following heart transplantation (HT), mostly commonly occurring in the first year after transplant. A few risk factors for the development of PTDM have been identified, including immunosuppressive medications such as calcineurin inhibitors and glucocorticoids. Some studies have suggested that among HT recipients, women have higher rates of acute rejection which may necessitate higher doses of steroids and further hyperglycemia. However, differences between sexes in the incidence of PTDM after HT have not been established. Methods: A retrospective review of patients who underwent HT at a large-volume center between January 1, 2010 and December 31, 2019 was performed. Patients undergoing re-transplantation or dual-organ transplantation were excluded. PTDM was defined as hemoglobin A1C≥6.5% or a random glucose &gt;200 after HT among patients with no prior history of DM. Predictors of PTDM by sex were analyzed with logistic regression, and post-transplant outcomes were analyzed with Chi-Square analysis. Results: Among 317 transplant patients without pre-transplant DM, 71 (22.4%) patients were identified who had PTDM: 24 females (33.7%), 47 males (66.2%). There were no statistically significant differences in baseline characteristics between males and females who developed PTDM including age, race, pre-transplant HTN, calcineurin or steroid dosing at 1 month and 1 year post-transplant. Baseline HTN (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 females but not in males, and mean tacrolimus dose was a predictor in males (OR 1.1, [1.0, 1.2], p=0.001) but not in females. Time to PTDM diagnosis did not differ by sex (log-rank p=0.56). Additionally, post-transplant outcomes in patients with PTDM including acute cellular rejection, antibody-mediated rejection, coronary allograft vasculopathy and death did not differ by sex. Conclusion: PTDM is a common complication of HT. Our study suggests that risk factors for PTDM among HT recipients differ by sex. Future studies should investigate the mechanisms underlying these differences to further guide sex-specific post-HT care.

#2502 THE FREQUENCY AND RISK FACTORS OF NODAT AND ELECTROLYTE DISORDERS IN KIDNEY TRANSPLANT PATIENTS

Abstract Background and Aims The purpose of the study is to investigate at the incidence and risk factors for post-transplant diabetes mellitus (PTDM) in non-diabetic kidney transplant patients (KTrs). Method The study included 120 KTRs who did not have diabetes in the pretransplant period. The diagnosis of PTDM was made according to the 2003 ADA DM diagnostic criteria. The relationship between PTDM and clinical and laboratory data on the 0th, 1st, 3rd, 6th, 12th and 24th months was investigated. Results The mean age of the patients was 33.3±11.5 years, 65% (78) of them were male. PTDM was developed in 29.1% (35) and 80% of PTDM at first 3 months. The risk factors for PTDM were found to be older (4.4%), family history of diabetes mellitus (5.24 times), beta-blocker use (2.55 times). KTRs with and without PTDM; Pretransplant dialysis type (Hemodialysis (P=0.822) and Peritoneal dialysis (P = .583)), living donor (101/84.2%)/cadaveric donor (19/ 15.8%), donor age and gender were similar. Serum magnesium and potassium were different only in the first month between the groups with and without PTDM (P = .019 and 0.008 respectively). The negative effect of PTDM on GFR was not observed in the 2-year follow-up. Conclusion It can be predicted that diabetes mellitus may develop with a family history of diabetes, advanced age and the use of beta-blockers. The risk of developing PTDM is higher in the first 3 months and hypomagnesemia in the first month may contribute to diabetes development.

Glycated albumin and post-transplant diabetes mellitus in kidney transplant recipients.

Post-transplant diabetes mellitus is one of the most important cardiovascular risk factors after solid organ transplantation. Factors other than hyperglycaemia found in patients post-transplant, affect the level of haemoglobin A1c (HbA1c), and new markers of hyperglycaemia are needed. Our aim was to establish a 95% reference interval for glycated albumin in kidney transplant recipients, and to compare glycated albumin concentrations to the diagnostic criteria for diabetes mellitus post-transplant using oral glucose tolerance test and HbA1c. A total of 341 non-diabetic kidney transplant recipients aged ≥18years who underwent an oral glucose tolerance test at 8weeks and 1year after transplantation were included. Glycated albumin was determined by liquid chromatography coupled with tandem mass spectrometry. The 95% reference interval for glycated albumin was 8.2 (90% CI: 7.2-8.5) to 12.8% (90% CI: 12.2-13.5) which is not significantly different from our laboratory's 95% reference interval for persons without diabetes. At both 8weeks and 1year after transplantation, 35 patients (10.3%) fulfilled one, two or all three diagnostic criteria for diabetes mellitus. One year after transplantation, eight additional patients had glycated albumin concentration >12.8%. Our findings are in accordance with the notion that kidney transplant recipients form glycation end products like normal controls as estimated by glycated albumin and HbA1c. Further studies should address glycated albumin as a supplemental tool for the diagnosis of post-transplant diabetes mellitus in kidney transplant recipients.

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.

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.

Impact of diabetes mellitus on clinical outcomes after heart transplantation.

Diabetes mellitus (DM) is common among recipients of heart transplantation (HTx) but its impact on clinical outcomes is unclear. We evaluated the associations between pretransplant DM and posttransplant DM (PTDM) and outcomes among adults receiving HTx at a single center. We performed a retrospective study (range 01/2008 - 07/2018), n=244. The primary outcome was survival; secondary outcomes included acute rejection, cardiac allograft vasculopathy, infection requiring hospitalization, macrovascular events, and dialysis initiation post-transplant. Comparisons were performed using Kaplan-Meier and multivariable Cox regression analyses. Pretransplant DM was present in 75 (30.7%) patients and was associated with a higher risk for infection requiring hospitalization (p<0.05), but not with survival or other outcomes. Among the 144 patients without pretransplant DM surviving to 1 year, 29 (20.1%) were diagnosed with PTDM at the 1-year follow-up. After multivariable adjustment, PTDM diagnosis at 1-year remained associated with worse subsequent survival (hazard ratio 2.72, 95% confidence interval 1.03-7.16). Predictors of PTDM at 1-year included cytomegalovirus seropositivity and higher prednisone dose (>5mg/day) at 1-year follow-up. Compared to HTx recipients without baseline DM, those with baseline DM have a higher risk for infections requiring hospitalization, and those who develop DM after HTx have worse survival.

Interdisciplinary problem of post-transplant diabetes mellitus: literature review

The number of transplantation and transplant survival rates increase steadily. Patients after solid organ transplantation re-ceive lifelong immunosuppressive therapy which may have adverse effects on carbohydrate and lipid metabolism. The most diabetogenic drugs are calcineurin inhibitors and corticosteroids. Posttransplant diabetes mellitus (PTDM) is hyperglycemia that meets American Diabetes Association and World Health Organization diabetes criteria for nontransplant patients and that was newly diagnosed after transplantation. PTDM may worsen both short-term and long-term transplantation outcomes so that the problem of timely diagnosis, proper treatment and prevention is critical. In early post-transplant period, transient hyperglycemia is found in the vast majority of patients; therefore, PTDM screening is carried out at least one month after transplantation. The gold standard test for PTDM diagnosis is oral glucose tolerance test. In the same time diagnostic value of hemoglobin A1C is limited. Lifestyle therapy and antidiabetic drugs are considered as possible preventive measures. Stress induced hyperglycemia management in solid organ recipients is the same with other surgical patients. Which organ was transplanted, patient characteristics and possible drug interactions with immunosuppressive therapy should be taken into account while managing PTDM. Blood pressure and lipid profile should be under control for comprehensive cardiovascu-lar risk reduction. It remains unclear which PTDM treatment and prevention strategy is the best and for better understanding interdisciplinary approach is needed.

Novel management of diabetes in kidney transplantation.

Posttransplant diabetes mellitus (PTDM) is a prevalent complication in kidney transplant recipients, and has been associated with worse short-term and long-term outcomes. While hyperglycemia is frequently seen in the early posttransplant period because of surgical stress, infection, and use of high-dose steroids, the diagnosis of PTDM should be established after patients are clinically stable and on stable maintenance immunosuppression. In the early posttransplant period, hyperglycemia is typically treated with insulin, and pilot data have suggested potential benefit of lower vs. higher glycemic targets in this setting. Growing data indicate lifestyle modifications, including dietary interventions, physical activity, and mitigation of obesity, are associated with improved posttransplant outcomes. While there are limited data to support a first-line antidiabetic medication for PTDM, more established pharmacotherapies such as sulfonylureas, meglitinides, and dipetidyl peptidase IV inhibitors are commonly used. Given recent trials showing the benefits of sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide 1 receptor agonists upon kidney outcomes in nontransplant patients, further study of these agents specifically in kidney transplant recipients are urgently needed. Increasing evidence supports a multidisciplinary approach, including lifestyle modification, obesity treatment, judicious immunosuppression selection, and careful utilization of novel antidiabetic therapies in PTDM patients.

KAPOSI SARCOMA COEXISTING WITH NEW ONSET DIABETES MELLITUS IN A 42-YEAR-OLD KIDNEY TRANSPLANT RECIPIENT: A CASE REPORT

Background: Renal allograft recipients develop several complications such as infections and neoplasms. New onset diabetes mellitus is a common transplant complication but rarely coexist with Kaposi sarcoma. Case report: We report the case of a 42-year-old banker who presented with polyuria, polydipsia, polyphagia, weight loss and dark spots in the lower limbs 8 months after he had received a live-related kidney transplant in India. He is not a known diabetic and had no family history of diabetes mellitus. His post-transplant immunosuppressive drugs included Myfortic® (mycophenolate), tacrolimus and prednisolone. At presentation he was wasted, dehydrated and afebrile, with multiple hyperpigmented nodules and plaques in both his lower limbs. Random blood glucose was 38mmol/l, had 2+ glucosuria and no ketones. Biopsy of skin lesions showed features of Kaposi sarcoma. A diagnosis of post-transplant diabetes mellitus and Kaposi sarcoma was made. His treatment included soluble insulin and antibiotics. Tacrolimus was changed to sirolimus and mycophenolate was reduced to 360mg twice daily. Conclusion: Coexistence of diabetes mellitus and karposi sarcoma occurs rarely among kidney transplant recipients. Evaluation of transplant recipient who developed diabetes for malignancies such as karposi sarcoma will improve patient and graft survival.

New-onset post-transplant diabetes mellitus after haploidentical hematopoietic cell transplant with post-transplant cyclophosphamide.

Haploidentical hematopoietic cell transplantation (haplo‐HCT) with posttransplant cyclophosphamide (PTCY) is utilized for patients with hematological disorders but without conventional donors. The effects of new‐onset posttransplant diabetes mellitus (PTDM) following haplo‐HCT are unknown. We examined PTDM incidence and outcomes after haplo‐HCT with PTCY. Patients without diabetes receiving haplo‐HCT (n = 64) were analyzed for PTDM diagnosis (defined as blood glucose ≥ 200 mg/dL). By day 100, 14 (22%) patients developed PTDM (median, 18 days). Hyperglycemia (blood glucose ≥ 200 mg/dL) preceded corticosteroids in 11 (79%) individuals. PTDM patients had increased death/relapse (P = .029). PTDM occurs frequently, precedes corticosteroids, and leads to inferior outcomes following haplo‐HCT. PTDM prophylaxis/treatment may improve HCT survival.

Post-Heart Transplant Diabetes Mellitus: Incidence, Prevalence and Outcomes

De novo diabetes mellitus (DM) is a common complication of solid organ transplantation. However, studies about post-transplant DM (PTDM) following heart transplantation (HT) are scarce. This study aims to compare baseline characteristics and clinical outcomes between patients who developed PTDM and those who did not as well as investigate the incidence and prevalence of PTDM following HT. 148 consecutive patients undergoing HT between 4/2014 and 12/2018 were enrolled to this retrospective study. PTDM diagnosis was made based on a HbA1c ≥6.5%, fasting blood glucose ≥ 126mg/dL or use of insulin or oral hypoglycemic agents. Of the 148 patients, 57 (39%) had no DM, 37 (25%) had DM prior to HT, and 54 (36%) developed PTDM. Among the patients without DM at the time of HT, cumulative incidence of PTDM was 37% at discharge, 46% at 6 months, and 48% at 1 year post-HT. The prevalence of PTDM at 6 months post-HT was 44% and decreased to 36%, 26%, and 17% at 1, 2, and 3 years, respectively (Figure 1A). PTDM patients had a significantly higher pre-HT HbA1c compared to those without DM (5.8 (5.6, 6.0) vs 5.5 (5.3, 5.9)%; p=0.017). There was no difference in the dose of immunosuppressive medications between the groups. PTDM patients had a higher rate of infection requiring hospitalization compared to patients with no DM post-HT (80% vs 61%; p=0.036). Infection free survival was significantly lower in the PTDM group at 2 years (16% vs 35%; p=0.046) (Figure 1B). Overall survival (96% vs 96% at 2 years; p=0.986), rejection-free survival (46% vs 51% at 2 years; p=0.410), rate of cardiac allograft vasculopathy (33% vs 22%; p=0.267), kidney function and number of hospitalizations were similar between the PTDM and no DM groups. The incidence of PTDM after HT was high but prevalence decreased after 6 months. Patients with PTDM had increased pre-HT HbA1c and higher post-HT rates of infection compared to patients without DM. Further studies are needed to determine the clinical impact of PTDM.

Modifiable Variables Are Major Risk Factors for Posttransplant Diabetes Mellitus in a Time-Dependent Manner in Kidney Transplant: An Observational Cohort Study.

Modifiable and nonmodifiable risk factors for developing posttransplant diabetes mellitus (PTDM) have already been established in kidney transplant setting and impact adversely both patient and allograft survival. We analysed 450 recipients of living and deceased donor kidney transplants using current immunosuppressive regimen in the modern era and verified PTDM prevalence and risk factors over three-year posttransplant. Tacrolimus (85%), prednisone (100%), and mycophenolate (53%) were the main immunosuppressive regimen. Sixty-one recipients (13.5%) developed PTDM and remained in this condition throughout the study, whereas 74 (16.5%) recipients developed altered fasting glucose over time. Univariate analyses demonstrated that recipient age (46.2 ± 1.3vs. 40.7 ± 0.6 years old, OR 1.04; P = 0.001) and pretransplant hyperglycaemia and BMI ≥ 25 kg/m2 (32.8% vs. 21.6%, OR 0.54; P = 0.032 and 57.4% vs. 27.7%, OR 3.5; P < 0.0001, respectively) were the pretransplant variables associated with PTDM. Posttransplant transient hyperglycaemia (86.8%. 18.5%, OR 0.03; P = 0.0001), acute rejection (P = 0.021), calcium channel blockers (P = 0.014), TG/HDL (triglyceride/high-density lipoprotein cholesterol) ratio ≥ 3.5 at 1 year (P = 0.01) and at 3 years (P = 0.0001), and tacrolimus trough levels at months 1, 3, and 6 were equally predictors of PTDM. In multivariate analyses, pretransplant hyperglycaemia (P = 0.035), pretransplant BMI ≥ 25 kg/m2 (P = 0.0001), posttransplant transient hyperglycaemia (P = 0.0001), and TG/HDL ratio ≥ 3.5 at 3-year posttransplant (P = 0.003) were associated with PTDM diagnosis and maintenance over time. Early identification of risk factors associated with increased insulin resistance and decreased insulin secretion, such as pretransplant hyperglycaemia and overweight, posttransplant transient hyperglycaemia, tacrolimus trough levels, and TG/HDL ratio may be useful for risk stratification of patients to determine appropriate strategies to reduce PTDM.

Inferior Outcomes for Patients Developing New-Onset Post-Transplant Diabetes Mellitus after Haploidentical Hematopoietic Cell Transplant

The mortality rate triples for the 50% of patients diagnosed with new-onset post-transplant diabetes mellitus (PTDM) after HLA-identical allogeneic hematopoietic cell transplant (HCT) (Griffith, BBMT 2011). Haploidentical HCT (haplo-HCT) with post-transplant cyclophosphamide (PTCY) is increasingly utilized for patients with hematological disorders but without a conventional HLA-matched donor; however, the effects of PTDM after haplo-HCT is unknown. We examined the incidence, outcomes, and risk factors for PTDM in patients undergoing haplo-HCT. Patients receiving haplo-HCT with PTCY at Vanderbilt-Ingram Cancer Center (n= 65) were retrospectively analyzed for PTDM diagnosis (defined as a random blood glucose ≥200 mg/dL). Exclusion criteria included non-haplo-HCTs, second HCT, or pre-existing diabetes mellitus. The primary outcome was the incidence of new-onset PTDM by day 100. Secondary outcomes included: cumulative incidence (CI) of grades 2-4 graft-versus-host disease (GVHD), time to systemic steroids, PTDM risk factors, overall survival (OS), disease free survival (DFS), and non-relapse mortality (NRM). PTDM was diagnosed in 14 (21.5%) patients at a median of 18 days after haplo-HCT (range, 8-72 days). Hyperglycemia preceded grade 2-4 GVHD and steroids in 12 (85.7%) patents. Clinical characteristics including ablative conditioning and GVHD did not predict PTDM development (Table 1). OS was decreased in the PTDM group (Figure 1). Among haplo-HCT recipients with cancer (n= 41) DFS was lower and the CI of relapse was increased in PTDM patients (Figure 1). Similar to HLA-identical transplants, PTDM occurs frequently, precedes alloreactivity, and leads to inferior survival following haplo-HCT. Interestingly, glucose metabolism appears to be associated with relapse risk. Prophylaxis/treatment of PTDM may improve outcomes after conventional and haplo-HCT.

New-Onset Post-Transplant Diabetes Mellitus after Allogeneic Hematopoietic Cell Transplant Is Initiated by Insulin Resistance, Not Immunosuppressive Medications.

New-onset post-transplant diabetes mellitus (PTDM) occurs frequently after allogeneic hematopoietic cell transplant (HCT). Although calcineurin inhibitors and corticosteroids are assumed to be the cause for hyperglycemia, patients developing PTDM have elevated fasting C-peptide levels before HCT and before immunosuppressive medications. To determine if PTDM results from established insulin resistance present before transplant, we performed oral glucose tolerance tests (OGTTs) and measured whole body, peripheral, and hepatic insulin sensitivity with euglycemic hyperinsulinemic clamps before and 90 days after HLA-identical sibling donor HCT in 20 patients without pretransplant diabetes. HCT recipients were prospectively followed for the development of new-onset PTDM defined as a weekly fasting blood glucose ≥ 126 mg/dL or random blood glucose ≥ 200 mg/dL. During the first 100 days all patients received calcineurin inhibitors, and 11 individuals (55%) were prospectively diagnosed with new-onset PTDM. PTDM diagnosis preceded corticosteroid treatment. During the pretransplant OGTT, elevated fasting (87 mg/dL versus 101 mg/dL; P = .005) but not 2-hour postprandial glucose levels predicted PTDM diagnosis (P = .648). In response to insulin infusion during the euglycemic hyperinsulinemic clamp, patients developing PTDM had lower whole body glucose utilization (P = .047) and decreased peripheral/skeletal muscle uptake (P = .031) before and after transplant, respectively, when compared with non-PTDM patients. Hepatic insulin sensitivity did not differ. Survival was decreased in PTDM patients (2-year estimate, 55% versus 100%; P = .039). Insulin resistance before HCT is a risk factor for PTDM independent of immunosuppression. Fasting pretransplant glucose levels identified PTDM susceptibility, and peripheral insulin resistance could be targeted for prevention and treatment of PTDM after HCT.

Microvascular Complications of Posttransplant Diabetes Mellitus in Kidney Transplant Recipients: A Longitudinal Study.

To assesses microvascular complications in renal transplant recipients with posttransplant diabetes mellitus (PTDM). In this observational study, patients with ≥5 years of PTDM were included from a cohort of 895 kidney recipients transplanted from 2000 through 2011. Diabetic retinopathy was evaluated by fundus photographs and optical coherence tomography (OCT). Diabetes kidney disease was evaluated by protein to creatinine ratio (PCR) and estimated glomerular filtration rate (eGFR). Distal polyneuropathy was assessed by Michigan Protocol and 10 g-monofilament feet examinations. The Ewing protocol identified cardiovascular autonomic neuropathy. Renal transplant recipients without PTDM diagnosis (NPTDM) were considered controls. After 144.5 months of follow-up, 135 (15%) patients developed PTDM, and 64 had a PTDM duration ≥5 years. None of the patients with PTDM presented diabetic retinopathy at fundus photographs, but thinning of inner retinal layers was observed with OCT. More than 60% of patients with PTDM had distal polyneuropathy (OR, 1.55; 95% CI, 1.26 to 1.91; P < 0.001). Cardiovascular reflex tests abnormalities were similar between patients with PTDM and NPTDM (P = 0.26). During the first year and 8.5 ± 3.0 years after renal transplantation, eGFR and PCR did not differ significantly between patients with PTDM or NPTDM. This longitudinal study assesses microvascular complications in renal transplant patients with PTDM. A lower than expected prevalence as well as a different clinical course of the complications was observed. PTDM seems to be a unique type of diabetes, and its consequences may be milder than expected in type 1 and type 2 diabetes.