Development Of Post-transplant Diabetes Mellitus Research Articles

Microbial and metabolic features in renal transplant recipients with post-transplantation diabetes mellitus.

Post-transplantation diabetes mellitus (PTDM) is a common complication in renal transplant recipients (RTRs). Gut microbiome plays important roles in a variety of chronic metabolic diseases, but its association with the occurrence and development of PTDM is still unknown. The present study integrates the analysis of gut microbiome and metabolites to further identify the characteristics of PTDM. A total of 100 RTRs fecal samples were collected in our study. Among them, 55 samples were submitted to Hiseq sequencing, and 100 samples were used for non-targeted metabolomics analysis. The gut microbiome and metabolomics of RTRs were comprehensively characterized. The species Dialister invisus was significantly associated with fasting plasma glucose (FPG). The functions of tryptophan and phenylalanine biosynthesis were enhanced in RTRs with PTDM, while the functions of fructose and butyric acid metabolism were reduced. Fecal metabolome analysis indicated that RTRs with PTDM had unique metabolite distribution characteristics, and two differentially expressed specific metabolites were significantly correlated with FPG. The correlation analysis of gut microbiome and metabolites showed that gut microbiome had an obvious effect on the metabolic characteristics of RTRs with PTDM. Moreover, the relative abundance of microbial function is associated with the expression of several specific gut microbiome and metabolites. Our study identified the characteristics of gut microbiome and fecal metabolites in RTRs with PTDM, and we also found two important metabolites and a bacterium were significantly associated with PTDM, which might be used as novel targets in the research field of PTDM.

Risk Factors for Development of Early Onset Post-Transplant Diabetes Mellitus (PTDM) – A Prospective Study from a Tertiary Care Centre in India

ABSTRACT Introduction: Kidney transplantation is the best form of kidney replacement therapy. Posttransplant diabetes mellitus (PTDM) is an important complication seen in transplant recipients. The present study was done to identify the incidence and risk factors for the development of early-onset PTDM at a tertiary care center in India. Materials and Methods: This was a prospective study carried out from May 1, 2016, to April 30, 2017, at a tertiary care center and included all the adult first transplant recipients. The patients were followed up for six months after transplantation and the incidence of early PTDM was noted. The patients were divided into two groups, namely, PTDM and non-PTDM groups to identify risk factors for PTDM and to compare the outcome between the two groups. Results: This study included 66 patients. Patients developing PTDM had higher age (44.07 ± 9.69 years vs. 35.98 ± 11.17 years; P = 0.013), significantly higher prevalence of family history of diabetes (57.14% vs. 15.38%; P = 0.001), higher pretransplant fasting plasma blood glucose (93.86 ± 8.59 mg/dL vs. 86.21 ± 7.53 mg/dL; P = 0.007), and higher pretransplant glycated hemoglobin (HbA1c) level (5.2% ± 0.39% vs. 4.9% ± 0.52%; P = 0.006). We did not find any association of PTDM with obesity, gender, type of induction therapy, hepatitis C infection, cytomegalovirus infection, and mean trough tacrolimus levels. Conclusions: In our study, patients who developed PTDM were of higher age, with increased levels of fasting blood sugar and HbA1c pretransplant, had a family history of diabetes, and were likely to have received antirejection therapy.

Post-Transplant Diabetes Mellitus in Renal Transplant Recipients, Single-Centre Data: Incidence, Risk Factors, and Effect on Graft Function and Mortality

Background: De novo post-transplant diabetes mellitus (PTDM) is a frequent complication among renal transplant recipients; it confers a high risk for graft failure and patient mortality. This single-centre study aimed to determine the incidence and risk factors of PTDM and its effects on graft outcome and mortality. Methods: In a single-centre longitudinal cohort analysis of 383 non-diabetic renal transplant follow-up recipients, outcomes were analysed through a detailed chart review. We hypothesized that different donor and recipient characters such as age, gender, and HLA mismatch would affect PTDM development in renal transplant recipients. PTDM is defined on basis of fasting plasma sugar (≥7 mmol/L or ≥126 mg/dL), random plasma sugar (≥11.1 mmol/L or ≥200 mg/dL), and glycated haemoglobin (HBA1C: >6.5% or 48 mmol/mol). We assessed PTDM incidence, risk factors, and its effect on patient mortality and graft outcome using Cox regression. Results: The mean age at the time of transplantation was 35.70 (±14.27) years, and 50.91% were male. PTDM incidence in the study period was 23.30%. Independent risk factors include older age at the time of transplantation, cyclosporine immunosuppression, cytomegalovirus, and hepatitis C virus infection. PTDM is not associated with graft dysfunction, whereas it significantly carries high mortality. Conclusion: PTDM is common among renal transplant recipients. Older age at the time of transplantation, cyclosporine immunosuppression, cytomegalovirus, and hepatitis C virus are risk factors. PTDM carries high mortality but is not associated with graft failure.

New-Onset Diabetes Mellitus in Post-renal Transplant Patients on Tacrolimus and Mycophenolate: A Systematic Review.

A frequent complication in kidney transplantation is post-transplant diabetes mellitus (PTDM). The primary goal of this study is to review the risk factors and preventive methods and compare the different available anti-diabetic medications for the management of PTDM. We searched databases like Pubmed and Google Scholar for related articles using specific terms and phrases. Following a thorough investigation, we applied the inclusion and exclusion criteria and completed a quality assessment. Modifiable risk factors have a significant role in the development of PTDM.The combinations of immunosuppressive treatment tacrolimus (TAC), cyclosporine A (CYC), and everolimus (EVL), steroids increase the incidence of PTDM significantly. Insulin is the most effective treatment for PTDM in the early transplant period; however, oral anti-diabetic medications look promising. Further clinical trials are required to determine the optimum treatment method for reducing the occurrence of PTDM and treating the existing condition with novel anti-hyperglycemic medications.

426.5: Regular Physical Activity in the Prevention of Post-transplant Diabetes Mellitus and Associated Metabolic Conditions in Kidney Transplant Recipients

Introduction: Post-transplant diabetes mellitus (PTDM) is significant risk factor for the survival of graft recipients and occurs in 10-30% of patients after kidney transplant (KT). PTDM is associated with premature cardiovascular morbidity and mortality. Insulin resistance (IR) at the time of KT is the most significant risk factor for the development of PTDM in patients after KT, as demonstrated by several analyzes. It is possible to reduce the high incidence of PTDM and affect the long-term survival of patients and grafts by influencing just modifiable risk factors, including obesity and the associated IR. The aim of this work is to determine the effect of regular physical activity on the development of PTDM and its risk factors in patients after KT. Methods: This was a prospective controlled analysis, which included 44 patients after primary KT in the Martin Transplant Center. Half consisted of a study group (n = 22) whose patients were assigned to perform regular physical activity. The primary goal was to complete at least 150 minutes of moderate intensity physical exertion per week. They performed an aerobic or combined (aerobic + strength) type of sports activity. Monitoring was provided by a sports tracker (Xiaomi Mi Band 4 compatible with Mi Fit mobile application). The other half was made up of a control group. The exclusion criterion at that time was already diagnosed with diabetes mellitus or a pre-diabetic condition. IR was assessed using the HOMA-IR (Homeostatic Model Assessment for Insulin Resistance) index from fasting blood glucose and insulinemia values. Each patient underwent an oral glucose tolerance test (oGTT) at the end of follow-up. Patients in both groups have the same immunosuppressive protocol. The duration of follow-up was 6 months. Results: We confirmed a statistically significantly higher IR at 6 months (P = 0.0202) and fasting blood glucose at 3 and 6 months (P = 0.0279) by multivariate analysis in the control group (figure 1, 2). After the end of the follow-up, there were significantly fewer patients with normal oGTT in the control group compared to the study group at 6 months (P < 0.0001), significantly more patients with pre-diabetic condition (impaired plasma glucose, impaired glucose tolerance) (P = 0.0078) and diagnosed with PTDM (P = 0.0212) (figure 3). Significantly lower waist circumference at 3 and 6 months (P = 0.0437, P = 0.0372) and low-density lipoprotein at 6 months (P = 0.0444) were found in the study group compared to the control group. In the study group, the subgroup performing intensive training achieved a significant additional effect on the reduction of waist circumference (P = 0.0173). Patients practicing only aerobic activity achieved significant decrease in triglycerides compared to those practicing combined activity (P = 0.046). Conclusion: In our study, we confirmed a significant effect of regular physical activity in preventing the development of PTDM and associated pre-diabetic conditions.

P15.05: Safety of Once-Weekly Dulaglutide on Post-transplant Diabetes Mellitus: A Preliminary Single-Centre Experience

Introduction: Almost all immunosuppressive drugs (IS), including glucocorticoids, calcineurin and mTOR inhibitors, play a central role in the development of Post-Transplant Diabetes Mellitus (PTDM). IS potentially cause the development of a dysglycemic state, both for the direct cytotoxic action on pancreatic beta cells and for the induction of insulin resistance. PTDM is also associated with increased risk for cardiovascular disease and with worse graft and patients’ survival. Currently there are no clear recommendations on the choice of the most safe and effective anti-diabetic drug for PTDM. IS are linked with several pharmacokinetic interactions and burdened with vary degree of nephrotoxicity. Glucagon like peptide- 1 receptor agonists (GLP1RA) are largely used for the treatment of type 2 diabetes. They act stimulating endogenous insulin secretion in a glucose-dependent manner. GLP1RAs reduce blood sugar by stimulating insulin release, suppressing high glucagon levels, delaying gastric emptying, and reducing food intake. Furthermore, GLP1 has been shown to promote proliferation of beta cells in animal models. GLP1RA has proven to be safe and effective in reducing HbA1c without directly causing hypoglycemia and has shown a clear association with cardiovascular risk reduction and renal protection. Despite GLP1RA seems to act with a mechanism that perfectly contrasts the pathogenetic aspects of PTDM, in the literature clinical experience is entirely limited to case series and retrospective studies. Method: In order to assess primarily safety of GLP1RA therapy in patients with PTDM we have prospectively enrolled a sample of N = 20 patients referred to liver (N = 10), renal (N = 5), as well as heart (N = 4) and lung (N = 1) transplant at ISMETT. All patients were placed on once-weekly dulaglutide therapy. Weight, HbA1c Level, as well as complete lipid profile and liver function tests were performed at 3 months and again at 6 months. One-way Repeated measurements ANOVA was used to test significant change in collected variables over time. Results: The study was closed at 6 months follow-up visit. Mild gastrointestinal symptoms were experienced by patients at the treatment start and resolved in 2 weeks. There were no persistent side effects due to dulaglutide in our study population and all recruited patients were on dulaglutide at 6 months evaluation. Body weight, Total cholesterol, Fibrosis-4 Index, alanine aminotransferase and aspartate aminotransferase levels were all reduced at the end of the follow-up, while blood glucose as well as HbA1c were stable over time (Table 1, Figure 1). Conclusion: Dulaglutide has proven to be safe in a population of transplanted patients with PTDM. In addition, a significative reduction of metabolic parameters was found. GLP1RA could be a preferred treatment for patients with PTDM considering also the extraglycemic effects of cardiovascular and renal protection.

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.

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.

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.

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.

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.

Hyperleptinemia as a risk factor for post-transplant diabetes mellitus development after kidney transplantation.

Adipose tissue is involved in the synthesis of hormones that have an impact on food intake regulation, control of insulin sensitivity or regulation of inflammatory processes. The aim of this study was to determine the importance of adipocytokines and interleukins levels for the development of post-transplant diabetes mellitus (PTDM) after kidney transplantation (KT). In the prospective analysis, the studied sample (n = 104) was divided into the control group, prediabetes group and PTDM group. Prior to 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 and anthropometric parameters. At the same time, we monitored the levels of adiponectin, leptin and interleukins during the monitored period. Using multivariate logistic regression, 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)]. At the same time, we confirmed that age at the time of KT is also an independent risk factor for PTDM [OR 1.0903; 95% Cl 1.0149-1.1714 (p=0.0180)]. We confirmed that elevated leptin level 12 months after KT is associated with the development of PTDM (Tab. 3, Fig. 4, Ref. 22). Text in PDF www.elis.sk Keywords: adipocytokines, interleukins, post-transplant diabetes mellitus, kidney transplantation, leptin.

Androgens and Development of Posttransplantation Diabetes Mellitus in Male Kidney Transplant Recipients: A Post Hoc Analysis of a Prospective Study.

Posttransplantation diabetes mellitus (PTDM) effects up to 30% of all kidney transplant recipients (KTR). Recent studies in mice found that sufficient androgen levels are necessary for β-cell health and adequate insulin secretion. This raises the question whether a similar relationship might be present in KTR. Hence, we hypothesized that dihydrotestosterone and testosterone are associated with the development of PTDM in male KTR. We conducted a post hoc analyses of a prospective single-center cohort study including adult male KTR with a functioning graft ≥1 year posttransplantation. Androgen levels were assessed by liquid chromatography-tandem mass spectrometry. Development of PTDM was defined according to the American Diabetes Association's criteria. We included 243 male KTR (aged 51 ± 14 years), with a median dihydrotestosterone 0.9 (0.7-1.3) nmol/L and testosterone of 12.1 (9.4-15.8) nmol/L. During 5.3 (3.7-5.8) years of follow-up, 28 KTR (11.5%) developed PTDM. A clear association was observed, as 15 (19%), 10 (12%), and 3 (4%) male KTR developed PTDM in the respective tertiles of dihydrotestosterone (P = 0.008). In Cox regression analyses, both dihydrotestosterone and testosterone as continuous variables were inversely associated with the risk to development PTDM, independent of glucose and HbA1c (hazard ratio [HR] 0.31 [95% CI 0.16-0.59], P < 0.001; and HR 0.32 [95% CI 0.15-0.68], P = 0.003, respectively). Our results suggest that low androgen levels are a novel potential modifiable risk factor for the development of PTDM in male KTR.

A prospective observational study on the traditional and novel risk factors associated with post-transplant diabetes mellitus in renal transplant recipients

Introduction and Aim: Post Transplant Diabetes Mellitus (PTDM) constitutes a major co-morbidity that has significant impact on the patient and renal allograft outcome. Various traditional risk factors like dialysis vintage, immunosuppressive medication, viral infections have known to be associated with PTDM. Novel risk factors and its causative role in PTDM remains unexplored. The study looked at the incidence of PTDM at 6 months post renal transplantation and correlation of PTDM with known traditional and novel risk factors like pre-transplant C-reactive protein (CRP) level and Trace element deficiency.&#x0D; &#x0D; Material and Methods: 30 consecutive renal transplant recipients more than 18 years of age were inducted into the study. Demographic data, known pre-transplant and post-transplant risk factors associated with development of PTDM were collected. Pre-transplant CRP and serum Trace element (Aluminum, Copper, Selenium and Zinc) levels were estimated. PTDM was diagnosed by home based glucometer monitoring and confirmed by Oral glucose tolerance test (OGTT).&#x0D; &#x0D; Results: The incidence of PTDM was 36.6% at six months post renal transplant. Among the pre-transplant risk factors, higher age and positive family history of diabetes mellitus had a strong association with the occurrence of PTDM. Pre-transplant Zinc deficiency emerged as a significant novel risk factor for the development of PTDM.&#x0D; &#x0D; Conclusion: Apart from known traditional risk factors, novel risk factors are associated with development of PTDM.

Post-transplant Diabetes Mellitus in Kidney Transplant Recipients: A Multicenter Study.

De novo post-transplant diabetes mellitus (PTDM) is a common complication after kidney transplant (KT). Most recent studies are single center with various approaches to outcome ascertainment. In a multicenter longitudinal cohort of 632 nondiabetic adult kidney recipients transplanted in 2010-2013, we ascertained outcomes through detailed chart review at 13 centers. We hypothesized that donor characteristics, such as sex, HCV infection, and kidney donor profile index (KDPI), and recipient characteristics, such as age, race, BMI, and increased HLA mismatches, would affect the development of PTDM among KT recipients. We defined PTDM as hemoglobin A1c ≥6.5%, pharmacological treatment for diabetes, or documentation of diabetes in electronic medical records. We assessed PTDM risk factors and evaluated for an independent time-updated association between PTDM and graft failure using regression. Mean recipient age was 52±14 years, 59% were male, 49% were Black. Cumulative PTDM incidence 5 years post-KT was 29% (186). Independent baseline PTDM risk factors included older recipient age (P<0.001) and higher BMI (P=0.006). PTDM was not associated with all-cause graft failure (adjusted hazard ratio (aHR), 1.10; 95% CI, 0.78 to 1.55), death-censored graft failure (aHR, 0.85; 95% CI, 0.53 to 1.37), or death (aHR, 1.31; 95% CI, 0.84 to 2.05) at median follow-up of 6 (interquartile range, 4.0-6.9) years post-KT. Induction and maintenance immunosuppression were not different between patients who did and did not develop PTDM. PTDM occurred commonly, and higher baseline BMI was associated with PTDM. PTDM was not associated with graft failure or mortality during the 6-year follow-up, perhaps due to the short follow-up time.

1145-P: Association of Muscle Mass Loss and Diabetes Development in Liver Allograft Recipients

There has been increased recognition of the importance of post transplantation diabetes mellitus (PTDM), which is one of the most frequent complications after liver transplantation. Patients with end-stage liver diseases requiring transplantation are prone to be sarcopenic but the association between sarcopenia and PTDM remains inconclusive. We investigated the effect of postoperative muscle mass loss on the risk of PTDM development by measuring muscle area using computed tomography (CT) in Liver Allograft Recipients before and after transplantation. A total of five hundred patients who received liver transplantation between 2005 and 2020 were included from tertiary care hospital. Skeletal muscle area (cm2) at the level of vertebra L3-L5 was measured using CT scans performed before and 1 year after the transplantation, and the area was normalized to height squared (m2). Cox proportional hazard model was used to investigate the associations between the change in the muscle area after the transplantation (Δmuscle area) and the incidence of PTDM. Patients were divided into two groups (with muscle loss and without muscle loss). During the study follow-up period (median 4.9 years), PTDM occurred in 165 patients (33%). Muscle depletion was significantly associated with the increased risk of incident PTDM after adjustment for age, BMI, model for end-stage liver disease score and fasting blood glucose after liver transplantation (hazard ratio, 1.47; 95% confidence interval, 1.23-1.76; p&amp;lt;0.001). Δmuscle area predicted PTDM development with a receiver operating characteristic area under the curve of 0.633 (95% confidence interval, 0.573-0.694). The cumulative incidence of PTDM was significantly higher in the patients with muscle loss than in the patients without muscle loss (P=0.026). The muscle depletion after liver transplantation is associated with the increased risk of PTDM development. Disclosure S. Lee: None. H. Kim: None. Y. Kim: None. M. Lee: None. D. Joo: None. M. Kim: None. E. Kang: None.

FC 086GLOMERULI PROTEOME ANALYSIS REVEALS EARLY DIFFERENCES BETWEEN PRE-EXISTING AND DE-NOVO TYPE 2 DIABETES IN HUMAN RENAL ALLOGRAFTS

Abstract Background and Aims Diabetes mellitus, either preexisting or developing after kidney transplantation remains a crucial clinical problem. The aim of this study is to compare the proteome of histologically normal glomeruli from normoglycemic (NG), T2DM, and PTDM patients one year after kidney transplantation to identify novel early biomarkers detectable prior to the development of histologically visible diabetic nephropathy. Method We comparatively analyzed the proteome of histologically normal glomeruli from normoglycemic (NG) recipients, and recipients with pre-existing type 2 diabetes mellitus (T2DM), or post-transplant diabetes mellitus (PTDM), in protocol biopsies obtained one year after kidney transplantation. Glomerular cross-sections were microdissected in core biopsies from 8 NG, 8 PTDM and 8 T2DM kidney transplant recipients. Proteome was determined by liquid chromatography-tandem mass spectrometry. Relative differences in protein abundance and significantly dysregulated pathways were analyzed. Results Proteins related to immune response and inflammation, transport regulation and cell organization and communication, including the nephrin family, were more abundant in NG, as compared to the combined groups of diabetic patients. Proteins involved in cell morphogenesis and adhesion were less abundant in PTDM, as compared to T2DM. In contrast, CCT3, CCT4 and CNDP2 diabetic nephropathy markers, LDHB and tacrolimus binding protein FKBP1A were significantly overrepresented in glomeruli from PTDM, as compared to T2DM patients. Conclusion These data suggest that glomerular proteome profile differentiates PTDM from NG and T2DM, and disruption of cell-cell interactions at molecular level represents an early event in PTDM development.

MO933EFFECT OF PHYSICAL ACTIVITY AND LIFESTYLE CHANGES ON INSULIN RESISTANCE IN PATIENTS AFTER KIDNEY TRANSPLANTATION

Abstract Background and Aims The incidence of post-transplant diabetes mellitus (PTDM) after kidney transplantation (KT) is high and ranges from 15-30%. Insulin resistance (IR) at the time of KT is the most significant risk factor for the development of PTDM in patients after KT, as demonstrated by several analyzes. It is possible to reduce the high incidence of PTDM by influencing just modifiable risk factors, including obesity and the associated IR. The aim of this work is to determine the effect of precisely determined physical activity and lifestyle changes on IR and other risk factors for PTDM in patients after KT. Method This is a prospective controlled analysis, which included 44 patients after primary KT in the Martin Transplant Center. Half consisted of a study group (n = 22) whose patients were assigned to perform regular physical activity. The primary goal was to complete at least 150 minutes of moderate intensity physical exertion per week. They performed an aerobic or combined (aerobic + anaerobic) type of sports activity. Monitoring was provided by a sports tracker (Xiaomi Mi Band 3 compatible with Mi Fit mobile application). The other half was made up of a control group. The exclusion criterion at that time was already diagnosed with diabetes mellitus or a pre-diabetic condition. IR was assessed using the HOMA-IR (Homeostatic Model Assessment for Insulin Resistance) index from fasting blood glucose and insulinemia values. Each patient underwent an oral glucose tolerance test (oGTT) at the end of follow-up. Patients in both groups have the same immunosuppressive protocol. The duration of follow-up was 6 months. Results In the observed group we univariately found in the 3rd and 6th month of monitoring significantly lower waist circumference (P = 0.0437, P = 0.0372), better graft function (P = 0.0036, P = 0.0137), lower value glycemia (P = 0.0016, P = 0.0003), C-peptide (P = 0.0447, P = 0014) and lower low-density lipoprotein (LDL) at 6 months (P = 0.0444) compared to the control group. We confirmed a statistically significantly lower IR at 6 months (P = 0.0202) and fasting blood glucose at 3 and 6 months (P = 0.0227) by multivariate analysis in the observed group. After the end of the follow-up, we identified statistically significantly fewer patients with a negative oGTT result in the control group (P &amp;lt; 0.0001), significantly more patients with impaired glucose tolerance, fasting hyperglycemia (P = 0.0078) and diagnosed with PTDM (P = 0.0212). In the control group, we found a statistically significant increase in glycemia at 30 (P = 0.0034) as well as at 120 minutes (P = 0.0011) during oGTT compared to the observed group. Conclusion In our study, we confirmed a significant effect of regular physical activity in preventing the development of IR and associated pre-diabetic conditions and PTDM.

Effect of Everolimus with Low-Dose Tacrolimus on Development of New-Onset Diabetes After Transplantation and Allograft Function in Kidney Transplantation: A Multicenter, Open-Label, Randomized Trial.

BackgroundThis randomized controlled trial aimed to investigate the effect of everolimus (EVL) with low-dose tacrolimus (Tac) on the development of post-transplantation diabetes mellitus (PTDM) in kidney transplantation (KT).Material/MethodsSeventy-seven kidney transplant patients from 4 transplant centers were included. Patients were randomized to the “EVL group” (n=38) and the “TAC group” (n=39). The target Tac trough level was 2 to 5 ng/mL in the EVL group and 5 to 10 ng/mL in the TAC group.ResultsThe 1-year cumulative incidence of PTDM in all patients was 7.8%, and no difference was found between the 2 groups (P=0.0819). Insulin resistance measured with the homeostatic model assessment for insulin resistance showed a significant increase only in the TAC group (1.11 to 1.30, P=0.0492). Allograft rejection rate and estimated glomerular filtration rate (eGFR) follow-ups every 3 months were not significantly different between the 2 groups. However, the EVL group showed a significant increase in the mean eGFR at 9 months and 12 months after KT compared to the baseline value (P=0.0242 and 0.0491, respectively).The EVL group showed lower insulin resistance and higher allograft function in comparison to the TAC group.ConclusionsEVL-based immunosuppressive therapy with lower Tac exposure could be a safer alternative for maintenance treatment.

Incidence and relative risk factors in posttransplant diabetes mellitus patients: a retrospective cohort study.

BackgroundPosttransplant diabetes mellitus (PTDM) has a long-term impact on kidney transplantation outcomes, such as graft and patient survival. The incidence and risk factors of PTDM are well studied, but long-term follow-up results remain unavailable. We examined the long-term incidence and relative risk factors of PTDM.MethodsA hospital information system database for kidney transplant recipients (KTRs) for a transplantation center between 1983 and 2018 was used to perform this retrospective cohort study. KTRs with DM diagnosis and continuous use of hypoglycemic agents for more than 3 months were defined as having PTDM. Demographics and comorbidities before transplantation were also collected. Kaplan-Meier analyses were used to determine the cumulative incidence and relative risk factors.ResultsA total of 296 PTDM cases were confirmed (28.46%) in this study. An increased cumulative incidence associated with age was noted, which was significantly increased in those aged ≥40 years. Male sex, hypertension, hyperlipidemia before transplantation, cytomegalovirus (CMV) infection, and tacrolimus-based regimens were also risk factors. No significant correlation was found between the development of PTDM and the increase of human leukocyte antigen mismatches, the primary causes of end-stage renal disease, and acute rejection.ConclusionsPTDM incidence was high in this cohort study. Characteristics such as age ≥40 years, tacrolimus use, comorbidity of hypertension and hyperlipidemia before transplantation, and CMV infection were associated with a high risk of PTDM. Monitoring and adjusting preventable risk factors such as CMV infection might be useful to prevent PTDM.