Risk Factors For Post-transplant Diabetes Mellitus Research Articles

Pancreatic steatosis is an independent risk factor for post-transplant diabetes mellitus in kidney transplant patients.

Post-transplant diabetes mellitus (PTDM) is associated with an increased risk of post-transplant cardiovascular diseases, and several risk factors of PTDM have been shown in the literature. Yet, the relationship between hepatic and pancreatic steatosis with post-transplant diabetes mellitus remains vague. We aimed to evaluate pancreatic steatosis, a novel component of metabolic syndrome, and hepatic steatosis association with post-transplant diabetes mellitus in a single-center retrospective cohort study conducted on kidney transplant recipients. We have performed a single-center retrospective cohort study involving all kidney transplant recipients. We have utilized pretransplant Fibrosis-4, nonalcoholic fatty liver disease fibrosis score, and abdominal computed tomography for the assessment of visceral steatosis status. We have included 373 kidney transplant recipients with a mean follow-up period of 32 months in our final analysis. Post-transplant diabetes mellitus risk is associated with older age (p<.001), higher body-mass index (p<.001), nonalcoholic fatty liver disease-fibrosis score (p=.002), hepatic (p<.001) or pancreatic (p<.001) steatosis on imaging and higher pre-transplant serum triglyceride (p=.003) and glucose levels (p=.001) after multivariate analysis. Our study illustrates that recipients' pancreatic steatosis is an independent predictive factor for post-transplant diabetes mellitus including in kidney transplant patients.

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.

Progress of new-onset diabetes after liver and kidney transplantation.

Organ transplantation is currently the most effective treatment for end-stage organ failure. Post transplantation diabetes mellitus (PTDM) is a severe complication after organ transplantation that seriously affects the short-term and long-term survival of recipients. However, PTDM is often overlooked or poorly managed in its early stage. This article provides an overview of the incidence, and pathogenesis of and risk factors for PTDM, aiming to gain a deeper understanding of PTDM and improve the quality of life of recipients.

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.

Incidence, Risk Factors and Clinical Implications of Glucose Metabolic Changes after Heart Transplant.

Diabetes mellitus (DM) arising de novo after transplant is a common complication, sharing many features with type 2 DM but also specific causes, such as administration of steroids and immunosuppressive drugs. Although post-transplant DM (PTDM) is generally assumed to worsen recipients' outcomes, its impact on renal function, cardiac allograft vasculopathy and mortality remains understudied in heart transplant (HT). We evaluated incidence and risk factors of PTDM and studied glucose metabolic alterations in relation to major HT outcomes. 119 subjects were included in this retrospective, single centre, observational study. A comprehensive assessment of glucose metabolic state was done pre-transplant and a median of 60 months [IQR 30-72] after transplant. Most patients were males (75.6%), with prior non-ischemic cardiomyopathy (64.7%) and median age of 58 years [IQR 48-63]. 14 patients developed PTDM, an incidence of 3.2 cases/100 patient-years. Patients with worsening glucose metabolic pattern were the only who showed a significant increase of BMI and metabolic syndrome prevalence after transplant. 23 (19.3%) patients died during follow up. Early mortality was lower in those with stably normal glucose metabolism, whereas improvement of glucose metabolic state favorably affected mid-term mortality (log-rank p = 0.028). No differences were observed regarding risk of infections and cancer. PTDM is common, but glucose metabolism may also improve after HT. PTDM is strictly related with BMI increase and metabolic syndrome development and may impact recipient survival.

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.

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

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

Risk factors associated with diabetes after liver transplant.

Post-transplant diabetes mellitus (PTDM) is a common metabolic complication after liver transplant that negatively affects a recipient's survival and graft function. This study aims to identify risk factors associated with diabetes after liver transplant. This is a cross-sectional study conducted from September to November 2019. Data collection was performed by chart review, and patients were divided into 3 groups: patients without diabetes mellitus (DM), patients with pre-transplant diabetes mellitus, and patients with PTDM. Two hundred and forty-seven patients' medical charts were screened, and 207 patients were included: 107 without DM, 42 with pre-transplant DM, and 58 with PTDM. The leading cause for liver transplant was hepatitis C, followed by hepatocellular carcinoma secondary to alcohol. There was a higher exposure to tacrolimus in patients without DM (P = 0.02) and to ciclosporin in patients with pre-transplant DM, compared to others (P = 0.005). Microscopic interface inflammatory activity was more severe in patients without DM as well as those with PTDM (P = 0.032). There was a higher prevalence of steatosis in recipients with pre-transplant DM than there was in others (P < 0.001). Multivariate logistic regression identified the following independent risk factors for DM: cirrhosis due to alcohol, hepatitis C, and triglycerides. For PTDM, these independent risk factors were cirrhosis due to alcohol, hepatitis C, and prednisone exposure. Alcoholic cirrhosis is a risk factor for PTDM in liver recipients. Liver transplant recipients with a pre-transplant history of cirrhosis due to alcohol, hepatitis C, and prednisone exposure deserve more caution during PTDM screening.

Effect of Hepatitis C Viremia on Posttransplant Diabetes Mellitus in Liver Transplant Recipients.

Posttransplant diabetes mellitus (PTDM) can increase morbidity and mortality in liver transplant recipients. Although hepatitis C seropositivity is a known risk factor for PTDM, the impact of viremia versus no viremia at time of transplant is unknown. This program evaluation sought to compare PTDM in hepatitis C seropositive patients with and without viremia at the time of liver transplant. This single-center retrospective review included adult hepatitis C seropositive liver transplant recipients transplanted between January 1, 2010 to September 5, 2017 without pretransplant diabetes. Primary outcome was PTDM within 1 year. Secondary outcomes included evaluating 1-year posttransplant death-censored graft loss, mortality, and metabolic outcomes. Fifty-seven liver transplant recipients with hepatitis C were included, of which 53% (n = 30) were viremic at transplant. Baseline characteristics were similar between groups. Significantly more patients with pretransplant viremia developed PTDM by 1-year posttransplant compared to the patients without viremia (43% vs 11%, P = 0.01). There were no differences between groups outside of more patients with viremia requiring antihypertensives by 1-year posttransplant compared to patients without viremia (57% vs 22%, P = 0.01). Liver transplant patients with hepatitis C viremia at transplant were more likely to develop PTDM at 1 year compared to those without pretransplant viremia. This is an added consideration when deciding the timing of direct-acting antiviral (DAA) utilization in the context of liver transplant for hepatitis C seropositive patients.

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.

MO994POST-TRANSPLANT DIABETES MELLITUS PREDICTORS AFTER PANCREAS-KIDNEY TRANSPLANT

Abstract Background and Aims Pancreas-kidney transplantation (PKT) is an established treatment for selected patients with type 1 diabetes mellitus (T1DM) with either advanced or end-stage chronic kidney disease. We aimed to evaluate predictors for post-transplant diabetes mellitus (PTDM) at 24 months of follow-up after PKT. Method We analysed a longitudinal cohort of patients with chronic kidney disease and T1DM who underwent PKT at a tertiary referral centre from January 2011 to December 31, 2017. PTDM (post-transplant diabetes mellitus) was defined as the persistent need for pharmacologic treatment of diabetes mellitus after transplant. Continuous variables were recorded as means (±SD) or as medians (25-75% interquartile range), accordingly to data distribution. Categorical variables were recorded as proportions. Comparisons were made using t-tests, Wilcoxon rank-sum tests, or X2 test as appropriate. Unadjusted and adjusted multivariate logistic regression models were fitted to identify risk factors for PTDM at 24 months of follow-up. STATA 14.2 statistical package was used and p &amp;lt;0.05 was considered statistically significant. Results From a total of 72 patients who underwent PKT during the study period, 47 patients completed at least 24 months of follow-up. The mean age at transplantation was 37±8 years, 30 (64%) were male, 43 (91%) were white and 4 (9%) were black. At 24-months of follow-up, the prevalence of diabetes mellitus was 28% (13/47). Number of mismatches, accumulated prednisolone dose, tacrolimus levels, previous rejection episodes, body mass index, cytomegalovirus status, serum creatinine, lipase, amilase at discharge were not associated with PTDM. Patients with persistent diabetes at 24-months of follow-up had a significantly longer pretransplant diabetes duration (29±10 versus 23±6 years; p-value = 0.026), had higher pretransplant LDL-cholesterol (137±46 versus 100±27 years; p-value = 0.003), and lower C-peptide at post-transplant hospital discharge (3.0 [2.0-3.3] versus 5.8 [4.5-6.5]; p-value = 0.004). Likewise, in univariate logistic regression models, longer diabetes duration and higher pretransplant LDL-cholesterol were found to be risk factors for PTDM at 24-months (OR 1.11, CI95% 1.00-1.22, p-value = 0.041; OR 1.03, CI95% 1.01-1.06, p-value = 0.014; respectively), while higher C-peptide at post-transplant hospital discharge was found to be protector (OR 1.03, CI95% 1.01-1.06, p-value = 0.014). In a multivariate model including age, pretransplant diabetes duration, pretransplant LDL-cholesterol, and C-peptide at post-transplant hospital discharge, only C-peptide at post-transplant hospital discharge remained significant (OR: 0.41, CI95% 0.18-0.95, p-value = 0.04). Conclusion Despite previous results in other studies, and new data researched, in our multivariate model, only lower C-peptide at post-transplant hospital discharge revealed being a predictor of PTDM after PKT.

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.

Abstract 15777: Induction Immunosuppression is Associated With a Lower Incidence of Post-transplant Diabetes Mellitus in Heart Transplant Recipients: A Propensity-adjusted Analysis

Introduction: Post-transplant diabetes mellitus (PTDM) is a common complication among heart transplant recipients resulting in heightened risk of diabetes-related complications and death. While there is evidence that certain maintenance immunosuppression drugs like tacrolimus increase the risk of PTDM, it is not known whether induction immunosuppression does the same. We therefore evaluated whether induction immunosuppression in the early post-transplant period with IL-2 inhibitors, alemtuzumab or anti-thymocyte globulin is associated with PTDM after accounting for potential confounding by indication. Methods: Using data from the Scientific Registry of Transplant Recipients, we conducted a cohort study of 23,946 US adults who received a heart transplant in January 2008-December 2018. PTDM was defined as new diagnosis of diabetes at any time 6 months after transplant. We excluded patients with prior organ transplants and diabetes. We used logistic regression to construct propensity scores for predictors of induction immunosuppression and risk factors for PTDM including demographic, clinical and immunologic factors, pre-transplant therapies, steroids, functional status, and transplant year. We estimated the effect of induction immunosuppression in propensity-adjusted Cox proportional hazards models and produced fully adjusted Kaplan-Meier curves using inverse probability of treatment weights. Results: The average age was 54 (SD=12.5) years, 26% were female and 12,303 (51%) received induction immunosuppression. Over 84,969 person-years, 2,678 (11%) developed PTDM (32 cases/1,000 person-years). In the propensity-adjusted analysis, induction immunosuppression was associated with a 20% lower rate of PTDM (Figure 1; hazard ratio=0.80, 95% confidence interval 0.74-0.87). Conclusions: Adult heart transplant recipients who received induction immunosuppression had a 20% lower rate of PTDM compared to those who did not receive it.

1691-P: Alcohol-Related Liver Disease as Independent Risk Factor for Posttransplant Diabetes Mellitus in Liver Recipients

Background and Aims: There are few data related to identification of risk factors for post transplant diabetes mellitus (PTDM) in liver transplantation (Tx). The aim of this study was to investigate the risk factors for PTDM. Patients and methods: A retrospective study of adult patients submitted to liver Tx. Data for sex, age, BMI, pre and PTDM, Tx cause, presence of hepatocellular carcinoma (HCC), use of immunosuppressants, hepatitis B, hepatitis C (HepC) and liver biopsy were analyzed. Mann-Whitney and Chi Square tests as well as a multivariate logistic regression were performed. Results: Among 207 consecutive patients, 60.4% had no diabetes (group 1), 18.8% had pre Tx DM (group 2) and 20.8% were classified as PTDM (group 3). The major cause of transplantation was HepC (48.8%). Triglycerides (164 vs. 106mg/dL, p= 0.002) and creatinine (1.24 vs. 1.1mg/dL, p = 0.029) were higher in group 2 than in group 1, probably due to long-standing DM and metabolic syndrome in group 2. Comparisons using the Chi-Square test showed higher frequencies in group 3 than group 1 and 2, respectively, for HepC (65.1% vs. 35.1% and 37.9%, p=0.004), tacrolimus use (95.3% vs. 81.6% and 71.1%, p&amp;lt;0.001) and prednisone use (48.8% vs. 24% and 36.8%, p=0.009). HCC before Tx was more common in group 2 than in groups 1 and 3 (64.1% vs. 40.8% and 41.9%, respectively; p=0.034). Regarding biopsy data, interface activity was more severe in groups 1 and 3 compared to group 2 (62.2% and 64%% vs. 11%; p=0.040, respectively). The independent risk factors for PTDM according to the multivariate logistic model were HepC (OR 4.4; CI 95% 1.73-11.22; p=0.002), alcoholism (OR = 3.7, 95% CI, 1.2-11.5, p = 0.025), the use of tacrolimus (OR = 6.3, 95% CI 1.2-32.5, p = 0.029) and prednisone (OR = 7.2, 95% CI 2.4-21.8, p&amp;lt;0.001). Conclusion: Alcohol-related liver disease is an independent risk factor for PTDM in liver recipients. Patients with HepC and those exposed to tacrolimus and prednisone are other groups of high risk for PTDM. Disclosure M.B. Campos: None. I.D. Boin: None. A.M. Neto: None.

Risk Factors in and Long-Term Survival of Patients with Post-Transplantation Diabetes Mellitus: A Retrospective Cohort Study.

Post-transplant diabetes mellitus (PTDM) is associated with infection, cardiovascular morbidity, and mortality. A retrospective cohort study involving patients who underwent renal transplantation in a transplantation center in Taiwan from January 2000 to December 2018 was conducted to investigate the incidence and risk factors of PTDM and long-term patient and graft survival rates. High age (45–65 vs. <45 years, adjusted odds ratio (aOR) = 2.90, 95% confidence interval (CI) = 1.64–5.13, p < 0.001), high body mass index (>27 vs. <24 kg/m2, aOR = 5.35, 95% CI = 2.75–10.42, p < 0.001), and deceased organ donor (cadaveric vs. living, aOR = 2.01, 95% CI = 1.03–3.93, p = 0.04) were the three most important risk factors for the development of PTDM. The cumulative survival rate of patients and allografts was higher in patients without PTDM than in those with PTDM (p = 0.007 and 0.041, respectively). Concurrent use of calcineurin inhibitors and mammalian target of rapamycin inhibitors (mTORis) decreased the risk of PTDM (tacrolimus vs. tacrolimus with mTORi, aOR = 0.28, 95% CI = 0.14–0.55, p < 0.001). Investigating PTDM risk factors before and modifying immunosuppressant regimens after transplantation may effectively prevent PTDM development.

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.

Exploring the Mechanism of Skeletal Muscle in a Tacrolimus-Induced Posttransplantation Diabetes Mellitus Model on Gene Expression Profiles.

Objective Posttransplantation diabetes mellitus (PTDM) is a known complication of transplantation that affects the prognosis. Tacrolimus (Tac or FK506) is a widely used immunosuppressant that has been reported to be a risk factor for PTDM and to further induce complications in heart and skeletal muscles, but the mechanism is still largely unknown. In our preliminary experiments, we found that after Tac treatment, blood glucose increased, and the weight of skeletal muscle declined. Here, we hypothesize that tacrolimus can induce PTDM and influence the atrophy of skeletal muscle. Methods We designed preliminary experiments to establish a tacrolimus-induced PTDM model. Gene expression profiles in quadriceps muscle from this rat model were characterized by oligonucleotide microarrays. Then, differences in gene expression profiles in muscle from PTDM rats that received tacrolimus and control subjects were analyzed by using GeneSpring GX 11.0 software (Agilent). Functional annotation and enrichment analysis of differentially expressed genes (DEGs) helped us identify clues for the side effects of tacrolimus. Results Our experiments found that the quadriceps in tacrolimus-induced PTDM group were smaller than those in the control group. The study identified 275 DEGs that may be responsible for insulin resistance and the progression of PTDM, including 86 upregulated genes and 199 downregulated genes. GO and KEGG functional analysis of the DEGs showed a significant correlation between PTDM and muscle development. PPI network analysis screened eight hub genes and found that they were related to troponin and tropomyosin. Conclusions This study explored the molecular mechanism of muscle atrophy in a tacrolimus-induced PTDM model by bioinformatics analyses. We identified 275 DEGs and identified significant biomarkers for predicting the development and progression of tacrolimus-induced PTDM.

Administration of metformin in renal transplant patients with post-transplant diabetes mellitus

Diabetes is the most common cause of renal failure which is frequently seen in candidates of solid organ transplant both before and after of the transplantation. For successful long-term tissue graft, it is important to control blood glucose level particularly after transplantation. Post-transplant diabetes mellitus (PTDM) is the main issue contributing to cardiovascularrelated mortality in kidney transplant recipients. Important risk factors of PTDM include using immunosuppressive drugs, post-transplant weight gain and obesity, and the presence of pre-transplant diabetes. Because of safety concerns, there has been a consensus from 2003 onward to cease metformin as the first-line anti-diabetic drug in patients with PTDM. The relationship between PTDM and metformin administration in high-risk renal transplant patients needs to be validated by more trial studies to establish the risk-benefit balance using this drug. Here, we reviewed the pros and cons of using metformin by presenting conclusions from several retrospective and clinical trial studies.

Post-transplantation diabetes in kidney transplant recipients: an update on management and prevention

Post-transplantation diabetes mellitus (PTDM) may severely impact both short- and long-term outcomes of kidney transplant recipients in terms of graft and patient survival. However, PTDM often goes undiagnosed is underestimated or poorly managed. A diagnosis of PTDM should be delayed until the patient is on stable maintenance doses of immunosuppressive drugs, with stable kidney graft function and in the absence of acute infections. Risk factors for PTDM should be assessed during the pre-transplant evaluation period, in order to reduce the likelihood of developing diabetes. The oral glucose tolerance test is considered as the gold standard for diagnosing PTDM, whereas HbA1c is not reliable during the first months after transplantation. Glycaemic targets should be individualised, and comorbidities such as dyslipidaemia and hypertension should be treated with drugs that have the least possible impact on glucose metabolism, at doses that do not interact with immunosuppressants. While insulin is the preferred agent for treating inpatient hyperglycaemia in the immediate post-transplantation period, little evidence is available to guide therapeutic choices in the management of PTDM. Metformin and incretins may offer some advantage over other glucose-lowering agents, particularly with respect to risk of hypoglycaemia and weight gain. Tailoring immunosuppressive regimens may be of help, although maintenance of good kidney function should be prioritised over prevention/treatment of PTDM. The aim of this narrative review is to provide an overview of the available evidence on management and prevention of PTDM, with a focus on the available therapeutic options.