Association of early post-transplant hyperglycaemia and diabetes mellitus on outcomes following heart transplantation.

AIMS: Early post-transplant hyperglycaemia (EPTH) and post-transplant diabetes mellitus (PTDM) are common following solid organ transplantation and may be associated with adverse outcomes. We studied the prevalence of EPTH and cumulative 5-year prevalence of PTDM in a modern cohort of heart transplant recipients who were free from diabetes at baseline as well as the association of EPTH, PTDM and pre-transplant T2DM with adverse transplant-related outcomes. METHODS: Retrospective cohort study of heart transplant recipients followed for 5 years at a single centre in Sydney, Australia. RESULTS: A total of 141 patients were included, of whom 25 had pre-existing type 2 diabetes mellitus (T2DM) and 116 were free from diabetes at baseline. In patients without pre-existing T2DM, 88 of 116 (76%) experienced EPTH, which was associated with higher rates of acute rejection and hospitalizations, and lower 5-year survival. PTDM developed in 45 of 116 (39%) patients, all of whom had experienced EPTH. Both PTDM and pre-existing T2DM were associated with increased rates of graft rejection and hospitalization, and greater than three-fold increased likelihood of death compared to patients that remained free from diabetes. CONCLUSION: EPTH and PTDM are highly prevalent following cardiac transplantation. EPTH develops within days of transplant and is strongly associated with progression to PTDM. Pre-existing T2DM, PTDM and EPTH are associated with greater hospitalization, increased episodes of rejection and worse 5-year survival compared to patients who remained free from diabetes during follow-up.

International consensus on post-transplantation diabetes mellitus.

Post-transplantation diabetes mellitus (PTDM) remains a leading complication after solid organ transplantation. Previous international PTDM consensus meetings in 2003 and 2013 provided standardized frameworks to reduce heterogeneity in diagnosis, risk stratification and management. However, the last decade has seen significant advancements in our PTDM knowledge complemented by rapidly changing treatment algorithms for management of diabetes in the general population. In view of these developments, and to ensure reduced variation in clinical practice, a 3rd international PTDM Consensus Meeting was planned and held from 6-8 May 2022 in Vienna, Austria involving global delegates with PTDM expertise to update the previous reports. This update includes opinion statements concerning optimal diagnostic tools, recognition of prediabetes (impaired fasting glucose and/or impaired glucose tolerance), new mechanistic insights, immunosuppression modification, evidence-based strategies to prevent PTDM, treatment hierarchy for incorporating novel glucose-lowering agents and suggestions for the future direction of PTDM research to address unmet needs. Due to the paucity of good quality evidence, consensus meeting participants agreed that making GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) recommendations would be flawed. Although kidney-allograft centric, we suggest that these opinion statements can be appraised by the transplantation community for implementation across different solid organ transplant cohorts. Acknowledging the paucity of published literature, this report reflects consensus expert opinion. Attaining evidence is desirable to ensure establishment of optimized care for any solid organ transplant recipient at risk of, or who develops, PTDM as we strive to improve long-term outcomes.

Prognostic Impact of Post-Transplant Diabetes Mellitus in Kidney allograft recipients: A Meta-analysis.

BACKGROUND AND AIM: Post-transplant diabetes mellitus (PTDM) is a complex condition arising from various factors including immunosuppressive medications, insulin resistance, impaired insulin secretion, and inflammatory processes. Its impact on patient and graft survival is a significant concern in kidney transplant recipients. PTDM's impact on kidney transplant recipients, including patient and graft survival and cardiovascular mortality, is a significant concern, given conflicting findings in previous studies. This meta-analysis was imperative to not only incorporate emerging evidence but also to delve into cause-specific mortality considerations. We aimed to comprehensively evaluate the association between PTDM and clinical outcomes, including all-cause and cardiovascular mortality, sepsis-related mortality, malignancy-related mortality, and graft loss, in kidney transplant recipients. MATERIALS AND METHODS: PubMed, Ovid/Medline, Web of Science, Scopus, and Cochrane Library databases were screened and studies evaluating the effect of PTDM on all-cause mortality, cardiovascular mortality, sepsis-related mortality, malignancy-related mortality, and overall graft loss in adult kidney transplant recipients were included. RESULTS: 53 studies, encompassing a total of 138,917 patients, to evaluate the association between PTDM and clinical outcomes were included. Our analysis revealed a significant increase in all-cause mortality (RR 1.70, 95% CI 1.53 to 1.89, P<0.001) and cardiovascular mortality (RR 1.86, 95% CI 1.36 to 2.54, P<0.001) among individuals with PTDM. Moreover, PTDM was associated with a higher risk of sepsis-related mortality (RR 1.96, 95% CI 1.51 to 2.54, P<0.001) but showed no significant association with malignancy-related mortality (RR 1.20, 95% CI 0.76 to 1.88). Additionally, PTDM was linked to an increased risk of overall graft failure (RR 1.33, 95% CI 1.16 to 1.54, P<0.001). CONCLUSION: These findings underscore the importance of comprehensive management strategies and the need for research targeting PTDM to improve outcomes in kidney transplant recipients.

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

BACKGROUND AND AIM: 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. METHOD: 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. RESULTS: 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. CONCLUSION: Our study illustrates that recipients' pancreatic steatosis is an independent predictive factor for post-transplant diabetes mellitus including in kidney transplant patients.

Role of leptin and adiponectin in the pathogenesis of post-transplant diabetes mellitus.

Solid organ transplantation is a life-saving treatment for patients with end-stage organ failure, but it poses unique challenges due to metabolic and immunological changes in recipients. One significant complication is post-transplant diabetes mellitus (PTDM), which affects a variety of solid organ recipients. Leptin, a hormone produced by adipose tissue, regulates appetite and affects glucose metabolism. High leptin levels are associated with the development of PTDM, especially in kidney transplant recipients. Adiponectin, another adipokine, increases insulin sensitivity and has anti-diabetic properties. Low adiponectin levels are associated with insulin resistance and increase the risk of PTDM. As the incidence of PTDM increases due to the increased life expectancy among transplant patients, understanding the role of adipokines such as leptin and adiponectin becomes crucial for early detection and treatment. Additional studies on other adipokines may also provide valuable information on the pathogenesis of PTDM.

Myosteatosis as a novel predictor of new-onset diabetes mellitus after kidney transplantation.

OBJECTIVES: We evaluate the effect of myosteatosis on new-onset diabetes mellitus after kidney transplantation. METHODS: Consecutive patients who had renal transplant between 2006 and 2021 were reviewed, and 219 patients were finally included. Psoas muscle index was used to evaluate sarcopenia and average total psoas density (calculated by computed tomography before surgery) for myosteatosis. We used Cox proportional regression analyses in investigation of whether skeletal muscle depletion before surgery inclusive of sarcopenia and myosteatosis is a new additional predictor of new-onset diabetes mellitus. RESULTS: Median recipient age and body mass index were 45 years and 21.1 kg/m2 , respectively, and 123 patients (56%) were male. Preoperative impaired glucose tolerance was present in 58 patients (27%) and new-onset diabetes mellitus in 30 patients (14%), with median psoas muscle index of 6 cm2 /m2 and average total psoas density of 41 Hounsfield Unit. In multivariate analysis, significant risk factors were body mass index ≥25 kg/m2 (p < 0.01), impaired glucose tolerance (p < 0.01), and average total psoas density < 41.9 Hounsfield Unit (p = 0.03). New-onset diabetes mellitus had incidence rates of 3.7% without risk factors, 10% with a single risk factor, 33% with two, and 60% with three. Patients with new-onset diabetes mellitus were effectively stratified by the number of risk factors (p < 0.01). CONCLUSIONS: Myosteatosis could be a new risk factor used to predict new-onset diabetes mellitus.

Regular Physical Activity in the Prevention of Post-Transplant Diabetes Mellitus in Patients after Kidney Transplantation.

Background and Objectives: Post-transplant diabetes mellitus (PTDM) is a 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. Weight gain, obesity, and dyslipidemia are strong predictors of PTDM, and by modifying them with an active lifestyle it is possible to reduce the incidence of PTDM and affect the long-term survival of patients and grafts. The aim of our study was to determine the effect of regular physical activity on the development of PTDM and its risk factors in patients after KT. Materials and Methods: Participants in the study had to achieve at least 150 min of moderate-intensity physical exertion per week. The study group (n = 22) performed aerobic or combined (aerobic + strength) types of sports activities. Monitoring was provided by the sports tracker (Xiaomi Mi Band 4 compatible with the Mi Fit mobile application). The control group consisted of 22 stable patients after KT. Each patient underwent an oral glucose tolerance test (oGTT) at the end of the follow-up. The patients in both groups have the same immunosuppressive protocol. The total duration of the study was 6 months. Results: The patients in the study group had significantly more normal oGTT results at 6 months compared to the control group (p < 0.0001). In the control group, there were significantly more patients diagnosed with PTDM (p = 0.0212) and with pre-diabetic conditions (impaired plasma glucose and impaired glucose tolerance) at 6 months (p = 0.0078). Conclusions: Regular physical activity after KT provides significant prevention against the development of pre-diabetic conditions and PTDM.

Pretransplant evaluation and the risk of glucose metabolic alterations after renal transplantation: a prospective study.

BACKGROUND: Post-transplant prediabetes (PreDM) and diabetes (PTDM) are common and have an impact on cardiovascular events. We sought to investigate the pathogenesis and best approach for prediction. METHODS: We prospectively studied 115 waitlisted patients from a single center without manifest diabetes. An oral glucose tolerance test (OGTT) was performed yearly until transplantation and 12 months later. Insulin secretion, insulin sensitivity (IS) and disposition index (DI) were derived from the OGTT. RESULTS: PreDM and PTDM were observed in 27% and 28.6% of patients, respectively. Pretransplant age, body mass index (BMI), 120 min glucose, IS, DI, and prediabetes or undiagnosed diabetes were significantly associated with these alterations. In multivariate analysis, pretransplant age [odds ratio (OR) 1.5; 95% confidence interval (CI) 1.04-2.1], BMI (OR 1.16; 95% CI 1.04-1.3) and cumulative steroids (OR 1.5; 95% CI 1.02-2.2) were predictors of PreDM or PTDM. Receiver operating characteristic curve analysis showed that pretransplant BMI and 120 min glucose had the highest area under the curve (0.72; 95% CI 0.62-0.8; and 0.69; 95% CI 0.59-0.79, respectively). The highest discrimination cut-off for BMI (≥28.5 kg/m2) and 120 min glucose (≥123.5 mg/dL) yielded a similar number needed to diagnose (2.5). CONCLUSIONS: PreDM or PTDM develops in waitlisted patients with an ineffective insulin secretion and BMI shows a similar diagnostic capacity to OGTT. Pretransplant interventions may reduce post-transplant glucose alterations.

Patient and nursing experience of flash glucose monitoring following kidney transplantation.

Flash glucose monitoring (FGM) is increasingly used for blood glucose assessment due to ease of use and is now subsidized in Australia for blood glucose measurement for patients with Type 1 Diabetes Mellitus. Dysglycaemia is common following kidney transplantation and is associated with worse outcomes and there are data to support the use of FGM post-transplant to better detect and manage changes in blood glucose levels. There is, however, no data on patient or staff perceptions of FGM, or resource implications in this setting. We prospectively evaluated patients and nursing staff experiences of FGM compared to traditional capillary glucose measurement in the immediate post-transplant setting, along with resource utilization, cost of testing, staff time taken to test and accuracy. Twenty-one kidney transplant recipients had a FGM sensor applied in the post-operative period and results compared to capillary blood glucose monitoring (CBGM) measured at least four times a day. Six-hundred-fifty-six glucose measurements were obtained, median per patient of 30 readings (IQR 10). Pearson's correlation between FGM and CBGM readings is 0.95 (p < .001). FGM readings were lower than CBGM by an average of 1.2 mmol/L (SD 0.7). Using a 5-point preference questionnaire (with ratings varying from strongly disagree-strongly agree), both patients and nurses were highly satisfied with the usability and convenience of FGM, with all preferring FGM over CBGM. Average time to perform FGM was 3.6 s versus 64 s for CBGM. In average, cost of FGM was $58 less than traditional testing per patient. FGM is an accurate, convenient and cost-effective tool that may support optimal management of glycaemic control in the post-transplant period.

Sodium-glucose cotransporter 2 inhibitors for treatment of diabetes mellitus after kidney transplantation.

INTRODUCTION: Diabetes mellitus in kidney transplant recipients is a risk factor for cardiovascular events and premature death. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are increasingly used in nontransplant populations to improve diabetes control and cardiovascular and renal benefits. Limited literature exists regarding the safety and efficacy of these agents in renal transplant recipients. METHODS: We retrospectively reviewed all kidney transplant recipients within our health system who were prescribed a SGLT2i after transplantation for diabetes. The safety, tolerability, and effectiveness of SGLT2i were analyzed. RESULTS: Thirty-nine kidney transplant recipients were initiated on SGLT2i therapy, twenty-seven of which remained on therapy for at least 1 year. Ten (25%) patients experienced an adverse event while on a SGLT2i, with urinary tract infections (UTI) being the most common. Seventeen patients (43%) discontinued the SGLT2i at the time of chart review, most commonly due to cost and kidney function decline. The median [IQR] hemoglobin A1c (HbA1c) at SGLT2i initiation of 8.4% [7.8-9.2] decreased to 7.5% [6.8-8.0%] after 3 months and 7.5% [6.5-7.9] after 12 months. No meaningful change in kidney function or tacrolimus exposure was observed. CONCLUSION: SGLT2i may be a safe and effective treatment for diabetes in kidney transplant recipients. Cost is a barrier to SGLT2i therapy, and UTIs were the most frequently encountered adverse events in this cohort. More studies are needed to understand the safety profile and determine the effect of SGLT2i on diabetes-related comorbidities among kidney transplant recipients.

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

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

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

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

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

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

Glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter 2 inhibitors for diabetes after solid organ transplantation.

Post-transplant diabetes mellitus (PTDM) is a common complication of solid organ transplantation and a major cause of increased morbidity and mortality. Additionally, solid organ transplant patients may have pre-existent type 2 diabetes mellitus (T2DM). While insulin is the treatment of choice for hyperglycemia in the first weeks after transplantation, there is no preferred first line agent for long-term management of PTDM or pre-existent T2DM. Glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium-glucose cotransporter 2 (SGLT2) inhibitors improve glycemic control, lower body weight, and blood pressure, are recommended after lifestyle and metformin as initial therapy for diabetic patients with cardiovascular or kidney comorbidities regarding their cardiorenal benefits. Furthermore, the mechanisms of action of GLP-1RA may counteract some of the driving forces for PTDM, as calcineurin-induced ß cell toxicity as per preclinical data, and improve obesity. However, their use in the treatment of PTDM is currently limited by a paucity of data. Retrospective observational and small exploratory studies suggest that GLP-1RA effectively improve glycemic control and induce weight loss in patients with PTDM without interacting with commonly used immunosuppressive agents, although randomized-controlled clinical trials are required to confirm their safety and efficacy. In this narrative review, we evaluate the risk factors and pathogenesis of PTDM and compare the potential roles of GLP-1RA and SGLT2 inhibitors in PTDM prevention and management as well as in pre-existent T2DM, and providing a roadmap for evidence generation on newer antidiabetic drugs for solid organ transplantation.

Sodium-glucose cotransporter 2 inhibitors for diabetes mellitus control after kidney transplantation: Review of the current evidence.

Sodium-glucose cotransporter type 2 inhibitors (SGLT2i) are promising drugs to treat chronic kidney disease patients with or without diabetes mellitus (DM). Besides improving glycemic control, SGLT2i are cardioprotective and kidney protective and decrease bodyweight, serum uric acid, blood pressure, albuminuria and glomerular hyperfiltration. These effects may benefit graft function and survival in kidney transplant (KT) patients. In this review, we evaluate data on the efficacy and safety of SGLT2i for KT patients with DM. Eleven studies with 214 diabetic KT patients treated with SGLT2i have been reported. SGLT2i lowered haemoglobin A1c and bodyweight. While glomerular filtration rate may be reduced in the short-term, it remained similar to baseline after 3-12 months. In two studies, blood pressure decreased and remained unchanged in the others. There were no significant changes in urine protein to creatinine ratio. Regarding safety, 23 patients had urinary tract infections, 2 patients had a genital yeast infection, one had acute kidney injury, and one had mild hypoglycaemia. No cases of ketoacidosis or acute rejection were reported. In conclusion, the limited experience so far suggests that SGLT2i are safe in KT patients with DM, decrease bodyweight and improve glycemic control. However, some of the benefits observed in larger studies in the non-KT population have yet to be demonstrated in KT recipients, including preservation of kidney function, reduction in blood pressure and decreased proteinuria.

Diabetes and Cardiovascular Risk in Renal Transplant Patients.

End-stage kidney disease (ESKD) is a main public health problem, the prevalence of which is continuously increasing worldwide. Due to adverse effects of renal replacement therapies, kidney transplantation seems to be the optimal form of therapy with significantly improved survival, quality of life and diminished overall costs compared with dialysis. However, post-transplant patients frequently suffer from post-transplant diabetes mellitus (PTDM) which an important risk factor for cardiovascular and cardiovascular-related deaths after transplantation. The management of post-transplant diabetes resembles that of diabetes in the general population as it is based on strict glycemic control as well as screening and treatment of common complications. Lifestyle interventions accompanied by the tailoring of immunosuppressive regimen may be of key importance to mitigate PTDM-associated complications in kidney transplant patients. More transplant-specific approach can include the exchange of tacrolimus with an alternative immunosuppressant (cyclosporine or mammalian target of rapamycin (mTOR) inhibitor), the decrease or cessation of corticosteroid therapy and caution in the prescribing of diuretics since they are independently connected with post-transplant diabetes. Early identification of high-risk patients for cardiovascular diseases enables timely introduction of appropriate therapeutic strategy and results in higher survival rates for patients with a transplanted kidney.

Beta-Cell Dysfunction Induced by Tacrolimus: A Way to Explain Type 2 Diabetes?

The combination of insulin resistance and ß-cells dysfunction leads to the onset of type-2 diabetes mellitus (T2DM). This process can last for decades, as ß-cells are able to compensate the demand for insulin and maintain normoglycemia. Understanding the adaptive capacity of ß-cells during this process and the causes of its failure is essential to the limit onset of diabetes. Post-transplant diabetes mellitus (PTDM) is a common and serious disease that affects 30% of renal transplant recipients. With the exception of immunosuppressive therapy, the risk factors for T2D are the same as for PTDM: obesity, dyslipidaemia, insulin resistance and metabolic syndrome. Tacrolimus (TAC) is the immunosuppressant of choice after renal transplantation but it has the highest rates of PTDM. Our group has shown that insulin resistance and glucolipotoxicity, without favouring the appearance of apoptosis, modify key nuclear factors for the maintenance of identity and functionality of ß-cells. In this context, TAC accelerates or enhances these changes. Our hypothesis is that the pathways that are affected in the progression from pre-diabetes to diabetes in the general population are the same pathways that are affected by TAC. So, TAC can be considered a tool to study the pathogenesis of T2DM. Here, we review the common pathways of ß-cells dysfunction on T2DM and TAC-induced diabetes.

Serum magnesium, hepatocyte nuclear factor 1ß genotype and post-transplant diabetes mellitus: a prospective study.

BACKGROUND: Retrospective studies suggest that tacrolimus-induced hypomagnesaemia is a risk factor for post-transplant diabetes mellitus (PTDM), but prospective studies are lacking. METHODS: This was a prospective study with measurements of serum magnesium and tacrolimus at pre-specified time points in the first year after living donor kidney transplantation (KT). The role of single nucleotide polymorphisms (SNPs) in hepatocyte nuclear factor 1ß (HNF1ß) was also explored because HNF1ß regulates insulin secretion and renal magnesium handling. Repeated measurement and regression analyses were used to analyse associations with PTDM. RESULTS: In our cohort, 29 out of 167 kidney transplant recipients developed PTDM after 1 year (17%). Higher tacrolimus concentrations were significantly associated with lower serum magnesium and increased risk of hypomagnesaemia. Patients who developed PTDM had a significantly lower serum magnesium trajectory than patients who did not develop PTDM. In multivariate analysis, lower serum magnesium, age and body mass index were independent risk factors for PTDM. In recipients, the HNF1ß SNP rs752010 G > A significantly increased the risk of PTDM [odds ratio (OR) = 2.56, 95% confidence interval (CI) 1.05-6.23] but not of hypomagnesaemia. This association lost significance after correction for age and sex (OR = 2.24, 95% CI 0.90-5.57). No association between HNF1ß SNPs and PTDM was found in corresponding donors. CONCLUSIONS: A lower serum magnesium in the first year after KT is an independent risk factor for PTDM. The HNF1ß SNP rs752010 G > A may add to this risk through an effect on insulin secretion rather than hypomagnesaemia, but its role requires further confirmation.

Comparison of the glucagon-like-peptide-1 receptor agonists dulaglutide and liraglutide for the management of diabetes in solid organ transplant: A retrospective study.

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are gaining popularity in the management of diabetes in solid organ transplant (SOT) recipients. There are no studies available comparing the two GLP-1RAs dulaglutide and liraglutide in SOT. We performed a retrospective chart review to assess the safety and effectiveness of these agents in adult SOT with diabetes at 6, 12 and 24 months. There were 63 and 25 recipients on dulaglutide and liraglutide, respectively. There was a sustained reduction in primary endpoints of weight, BMI and insulin requirement with dulaglutide when compared to liraglutide. Decrease in weight was 2%, 4% and 5.2% with dulaglutide and 0.09%, 0.87% and 0.89% with liraglutide at 6, 12 and 24 months respectively. BMI reduction followed the same trend in the two groups. The percentage reduction for insulin was 26% with dulaglutide and 3.6% with liraglutide. There was a 10% reduction in creatinine and a 15% increase in estimated glomerular filtration rate (eGFR) at the end of 24 months with dulaglutide. However, there was an increase in creatinine by 7% and an 8% decrease in eGFR at the end of 24 months with liraglutide.

Management of metabolic alterations in adult kidney transplant recipients: A joint position statement of the Italian Society of Nephrology (SIN), the Italian Society for Organ Transplantation (SITO) and the Italian Diabetes Society (SID).

Chronic metabolic alterations such as post-transplant diabetes mellitus (PTDM), dyslipidaemias and overweight/obesity significantly impact on kidney transplant (KT) outcomes. This joint position statement is based on the evidence on the management of metabolic alterations in KT recipients (KTRs) published after the release of the 2009 KDIGO clinical practice guideline for the care of KTRs. Members of the Italian Society of Nephrology (SIN), the Italian Society for Organ Transplantation (SITO) and the Italian Diabetes Society (SID) selected to represent professionals involved in the management of KTRs undertook a systematic review of the published evidence for the management of PTDM, dyslipidaemias and obesity in this setting. The aim of this work is to provide an updated review of the evidence on the prevention, diagnosis and treatment of metabolic alterations in KTRs, in order to support physicians, patients and the Healthcare System in the decision-making process when choosing among the various available options.