Management Of Post-transplant Diabetes Mellitus Research Articles

Diabetic Kidney Disease in Post-Kidney Transplant Patients

Post-transplant diabetes mellitus (PTDM) is a common occurrence in post-kidney transplantation and is associated with greater mortality, allograft failure, and increased risk of infections. The primary goal in the management of PTDM is to achieve glycemic control to minimize the risk of complications while balancing the need for immunosuppression to maintain the health of the transplanted kidney. This review summarizes the effects of maintenance immunosuppression and therapeutic options among kidney transplant recipients. Patients with PTDM are at increased risk of diabetic kidney disease development; therefore, in this review, we focus on evidence supporting the use of novel antidiabetic agents and discuss their benefits and potential side effects in detail.

Diabetic Kidney Disease in Post-Transplant Diabetes Mellitus: Causes, Treatment and Outcomes

Kidney transplant recipients are a unique subgroup of chronic kidney disease patients due to their single functioning kidney, immunosuppressive agent usage, and long-term complications related to transplantation. Post-transplant diabetes mellitus (PTDM) has a significant adverse effect on renal outcomes in particular. As transplantations enable people to live longer, cardiovascular morbidity and mortality become more prevalent, and PTDM is a key risk factor for these complications. Although PTDM results from similar risk factors to those of type 2 diabetes, the conditions differ in their pathophysiology and clinical features. Transplantation itself is a risk factor for diabetes due to chronic exposure to immunosuppressive agents. Considering current evidence, this article describes the risk factors, pathogenesis, diagnostic criteria, prevention strategies, and management of PTDM. The therapeutic options are discussed regarding their safety and potential drug-drug interactions with immunosuppressive agents.

Diabetes medication following heart transplantation: a focus on novel cardioprotective therapies-a joint review from endocrinologists and cardiologists.

There is accumulating evidence that novel glucose-lowering agents infer potent cardiovascular and renal benefits. Therefore, it is imperative to reassess the management of post-transplant diabetes mellitus and consider the role of newer agents. With improved transplant-related survival and high prevalence of post-transplant diabetes, management of long-term complications such as diabetes are increasingly important. There are limited guidelines to assist in choice of appropriate agents after solid organ transplantation. Traditional therapies including insulin and sulfonylureas may still have a role; however, other agents should be considered prior. The evidence of novel glucose-lowering agents in post-transplant care is limited, and most studies have focused on kidney transplant recipients. While there are some parallels between renal and cardiac transplant recipients, the potential cardiovascular benefits, particularly on cardiac fibrosis are unique to cardiac transplantation. The treatment of diabetes, with a focus on additional cardiac and renal benefits, needs to be brought to the forefront of post-transplant care with incorporation of recent evidence outside of transplantation. The role for novel glucose-lowering agents in cardiac transplant recipients will be explored, with a summary of available evidence.

Dietary interventions on the prevention and management of diabetes in post-kidney transplantation - A systematic review.

Post-transplant diabetes mellitus is associated with long-term immunosuppression and weight gain, and is related to an increased risk of cardiovascular disease, accelerated loss of graft and increased mortality. There is an absence of strong evidence-based dietary guidelines for the prevention and management of post-transplant diabetes mellitus in kidney transplant recipients. The aim of this study was to systematically review all dietary evidence for kidney transplant recipients on clinical outcomes relating to diabetes, patient-reported outcomes and economic outcomes. A comprehensive literature search was conducted in August 2020 using the databases Medline, Embase, CENTRAL and CINAHL. Studies were critically appraised using Cochrane risk of bias tools and GRADE. A total of 12 studies and 1928 participants were included. Four papers focused on diet and exercise, one paper on diet only, two papers on magnesium supplementation, one paper on magnesium and fibre intake, two papers on Mediterranean diet, one paper on marine n-3 fatty acid supplementation and one paper on fruit and vegetable intake. There were no significant effects on outcomes relating to dietary counselling, magnesium supplementation, magnesium and fibre intake or marine n-3 fatty acid supplementation. Low-quality evidence supports the Mediterranean diet in reducing the risk of post-transplant diabetes mellitus and fasting plasma glucose levels. Low-quality evidence suggests vegetable intake being associated with a lower risk of post-transplant diabetes mellitus. This review demonstrates limited evidence for dietary interventions in the prevention and management of diabetes in post-kidney transplantation. The findings suggest that further high-quality research with robust study designs is required.

Chances and risks of sodium-glucose cotransporter 2 inhibitors in solid organ transplantation: A review of literatures.

Solid organ transplantation offers life-saving treatment for patients with end-organ dysfunction. Patient survival and quality of life have improved over the past few decades as a result of pharmacological development, expansion of the donor pool, technological advances and standardization of practices related to transplantation. Still, transplantation is associated with cardiovascular complications, of which post-transplant diabetes mellitus (PTDM) is one of the most important. PTDM increases mortality, which is best documented in patients who have received kidney and heart transplants. PTDM results from traditional risk factors seen in patients with type 2 diabetes mellitus, but also from specific post-transplant risk factors such as metabolic side effects of immunosuppressive drugs, post-transplant viral infections and hypomagnesemia. Oral hypoglycaemic agents are the first choice for the treatment of type 2 diabetes mellitus in non-transplanted patients. However, the evidence on the safety and efficacy of oral hypoglycaemic agents in transplant recipients is limited. The favourable risk/benefit ratio, which is suggested by large-scale and long-term studies on new glucose-lowering drug classes such as glucagon-like peptide 1 receptor agonists and sodium-glucose cotransporter 2 inhibitors, makes studies warranted to assess the potential role of these agents in the management of PTDM.

Management of post-transplant diabetes mellitus: an opportunity for novel therapeutics

ABSTRACTPost-transplant diabetes mellitus (PTDM) is a common problem after kidney transplantation (KT), occurring in 50% of high-risk recipients. The clinical importance of PTDM lies in its impact as a significant risk factor for cardiovascular and chronic kidney disease (CKD) after solid organ transplantation. Kidney Disease: Improving Global Outcomes (KDIGO) has recently updated the treatment guidelines for diabetes management in CKD with emphasis on the newer antidiabetic agents such as dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 receptor agonists and sodium–glucose co-transporter 2 inhibitors as add-on therapy to metformin. Given all these new diabetes treatments and the updated KDIGO guidelines, it is necessary to evaluate and give guidance on their use for DM management in KT recipients. This review summarizes the scarce published literature about the use of these new agents in the KT field. In summary, it is absolutely necessary to generate evidence in order to be able to safely use these new treatments in the KT population to improve blood glucose control, but specially to evaluate their potential cardiovascular and renal benefits that would seem to be independent of blood glucose control in PTDM patients.

Efficacy and Safety of Dipeptidyl Peptidase-4 Inhibitors in Kidney Transplant Recipients with Post-transplant Diabetes Mellitus (PTDM)- a Systematic Review and Meta-Analysis.

Kidney transplant recipients may develop post-transplant diabetes mellitus (PTDM). Dipeptidyl peptidase 4(DPP-4) inhibitors are evolving agents in the management of patients with diabetes mellitus. To evaluate the efficacy and safety of DPP-4 inhibitors in the management of post-transplant diabetes mellitus (PTDM) in renal transplant recipients. We performed a systematic search of the electronic databases using keys words and Mesh terms. Data were extracted and reviewed using structured proforma. A comprehensive review of the eligible studies was performed independently by each of two reviewers; conflicts were resolved by the third reviewer. The primary efficacy endpoint was the difference in glycosylated hemoglobin (HbA1c) comparing any of the DPP-4 inhibitors to either placebo or other hypoglycaemic agent. The primary safety endpoints were the worsening of graft functions and change in Tacrolimus trough level. We performed the Random effect model using standardised mean difference. We identified seven studies that were eligible for the systematic review; only one study compared Sitagliptin to insulin Glargine. One study involved head to head comparison of three DPP-4 inhibitors. The other five studies were pooled in the meta-analysis. DPP-4 inhibitors had a favourable glycemic effect as measured by HbA1c when compared to either placebo or oral anti-hyperglycemic medications (standardised mean difference in HbA1c = -0.993, 95% CI= -1.303 to -0.683, P=0.001). DPP-4 inhibitors use did not result in significant change in eGFR ((standardised mean difference = 0.147, 95% CI= -0.139 - 0.433, p=0.312).) nor Tacrolimus level (standardised Mean Difference= 0.152, 95% CI= -0.172 to 0.477, P=0.354). Current evidence supports the short term efficacy and safety of DDP-4 inhibitor agents in the management of post transplantation diabetes mellitus (PTDM) in kidney transplant recipients. However, more RCTs are required to investigate the long-term safety and efficacy of these agents in kidney transplant recipients.

A Retrospective Study of Glucagon-Like Peptide1 Receptor Agonists for the Management of Diabetes After Transplantation.

IntroductionManagement of post-transplant diabetes mellitus is challenging; there is a lack of prospective randomized controlled trials for safety and efficacy of antidiabetic medications in solid organ recipients. Glucagon-like peptide 1 receptor agonists (GLP-1RA) are a relatively new class of medications used to manage type 2 diabetes in the general population. They have several benefits besides glycemic control, including weight loss and improved cardiovascular risk. However, they have not been studied extensively in the post-transplant population for safety and efficacy.MethodsWe conducted a retrospective study of patients who had received kidney, liver, or heart transplant, had diabetes either pre- or post-transplant, and were treated with GLP-1RA. We identified seven kidney, seven liver, and five heart transplant recipients who had received GLP-1RA. We assessed changes in immunosuppressant levels, rejection episodes, changes in hemoglobin A1c (HbA1c), weight, and body mass index (BMI) while on the GLP-1RA. We also looked at changes in insulin dose, other diabetes medications, heart rate, blood pressure, and renal function.ResultsAfter a mean follow-up period of 12 months, there were no significant changes in tacrolimus (FK506) levels and renal function for the period of GLP-1RA use. At the end of 12 months, the mean drop in weight was 4.86 kg [95% CI − 7.79, − 1.93]. The BMI decreased by a mean of 1.63 kg/m2 at the end of 12 months [95% CI − 2.53, − 0.73]. HbA1c decreased from baseline by 1.08% [95% CI − 1.65, − 0.51], 0.96% [95% CI − 1.68, − 0.25], and 0.75% [95% CI − 1.55, 0.05] at 3, 6, and 12 months, respectively.ConclusionsOur data suggest that GLP-1RA do not affect tacrolimus levels or transplant outcomes in solid organ transplant (SOT) recipients in the short term. GLP-1RA also seem to be as effective in SOT recipients for glycemic control and weight loss as in the non-transplant population with diabetes.

Diabetogenic Effects of Immunosuppression: An Integrative Analysis.

Posttransplant diabetes mellitus (PTDM) affects up to 50% of solid organ transplant recipients and compromises long-term outcomes. The goal of this study was to investigate how immunosuppressants affect gene expression in a manner that increases diabetes risk, by performing integrative analysis on publicly available, high-throughput gene expression data. All high-throughput gene expression datasets of solid organ transplant recipients were retrieved from the Gene Expression Omnibus. Significantly dysregulated genes and pathways were determined, and those in common with type 2 diabetes were identified. THP-1 and HepG2 cells were exposed in vitro to tacrolimus, and validation of genes involved in insulin signaling and glucose metabolism was performed using specific arrays. These cells were then treated with the hypoglycemic agents, metformin, and insulin to assess for appropriate reversion of specific diabetogenic genes. Insulin signaling and secretion were the most commonly dysregulated pathways that overlapped with diabetes in transplant recipients. KRAS, GRB2, PCK2, BCL2L1, INSL3, DOK3, and PTPN1 were among the most significantly upregulated genes in both immunosuppression and diabetes subsets and were appropriately reverted by metformin as confirmed in vitro. We discovered that the significantly dysregulated genes in the context of immunosuppression are implicated in insulin signaling and insulin secretion, as a manifestation of pancreatic β-cell function. In vitro validation confirmed key diabetes-related genes in the context of immunosuppression. Further analysis and in vitro validation revealed that metformin optimally reverts diabetogenic genes dysregulated in the context of immunosuppression. The optimal therapeutic management of posttransplant diabetes mellitus needs to be further investigated, taking into account the mechanistic impact of immunosuppressants.

Diabetic Nephropathy Following Posttransplant Diabetes Mellitus.

Diabetic nephropathy is one of the main long-term diabetic microangiopathies that can complicate type 1 and 2 and other secondary forms of diabetes mellitus, including posttransplant diabetes mellitus. Posttransplant diabetes mellitus was initially reported in the 1960s, with case reports of recurrent and de novo diabetic nephropathy after kidney transplant reported in the early 2000s, mostly as a result of same-risk and precipitating factors of diabetic nephropathy as in native kidneys. The disease may appear early in view of the hyperfiltration risk of being a single grafted kidney. Here, we discuss risk factors, early serologic and genetic biomarkers for early detection, and strategies to avoid and delay the progression of diabetic nephropathy after posttransplant diabetes mellitus. In this overview of published literatures, we searched PubMed and MEDLINE for all articles published in English language between January 1994 and July 2018. Included studies reported on the prevalence, incidence, or determinants of post-transplant diabetes among renal transplant recipients and studies reporting diabetic nephropathy in their cohorts. Our review showed that avoidance or good control of posttransplant diabetes is the cornerstone in management of posttransplant diabetes mellitus and hence diabetic nephropathy. Control and avoidance can be commenced in the preparatory stage before transplant using validated genetic markers that can predict posttransplant diabetes mellitus. The use of well-matched donors with tailored immunosuppression (using less diabetogenic agents and possibly steroid-free regimens) and lifestyle modifications are the best preventative strategies. Tight glycemic control, early introduction of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers, and possibly conversion to less diabetogenic regimens can help to delay progression of diabetic nephropathy.

Management Strategies for Posttransplant Diabetes Mellitus after Heart Transplantation: A Review

Posttransplant diabetes mellitus (PTDM) is a well-recognized complication of heart transplantation and is associated with increased morbidity and mortality. Previous studies have yielded wide ranging estimates in the incidence of PTDM due in part to variable definitions applied. In addition, there is a limited published data on the management of PTDM after heart transplantation and a paucity of studies examining the effects of newer classes of hypoglycaemic drug therapies. In this review, we discuss the role of established glucose-lowering therapies and the rationale and emerging clinical evidence that supports the role of incretin-based therapies (glucagon like peptide- (GLP-) 1 agonists and dipeptidyl peptidase- (DPP-) 4 inhibitors) and sodium-glucose cotransporter 2 (SGLT2) inhibitors in the management of PTDM after heart transplantation. Recently published Consensus Guidelines for the diagnosis of PTDM will hopefully lead to more consistent approaches to the diagnosis of PTDM and provide a platform for the larger-scale multicentre trials that will be needed to determine the role of these newer therapies in the management of PTDM.

Post-transplant diabetes: diagnosis and management.

Post-transplant diabetes mellitus (PTDM) is common after most types of solid organ transplantation, though the actual incidence is as yet unknown because of the use of different diagnostic criteria. PTDM is the result of individual risk factors as well as risk factors associated with the transplant itself, particularly immunosuppressants. Previously called New Onset Diabetes, in many cases inadequate screening for diabetes before transplant cannot assure that the diabetes is new after transplant. The most recent international consensus guidelines suggest diagnosis should be delayed until the patient is taking maintenance doses of immunosuppressants even if they require treatment in the immediate hospitalization. Criteria for diagnosis follow those of the American Diabetes Association and the World Health Organization, although hemoglobin A1C should not be used as the only screening test at least until one year after transplant because of its insensitivity for significant glucose intolerance in the transplant patient and setting. Management of PTDM is best done in a team setting, with an emphasis on glycemic control, dyslipidemia, and hypertension, and taking into consideration immunosuppressant regimens and potential drug side effects and interactions. While PTDM has been associated with changes in outcomes, these have and may continue to improve with improved diabetes care in and out of the hospital, and other changes in post-transplant care.

Posttransplant Diabetes Mellitus: Cause, Impact, and Treatment Options

The incidence of diabetes mellitus (DM) is increased in adult organ transplant recipients. As many as 30% to 45% of solid organ adult transplant patients have DM before transplantation or develop posttransplant diabetes mellitus (PTDM). Risk factors for PTDM include family history, ethnic or genetic background, insulin resistance, and diabetogenic effects of immunosuppressive medications. Posttransplant hyperglycemia may result in increased platelet aggregation, increased wound infections, dehydration, and loss of lean body mass. More significantly, long-term complications of DM such as coronary artery disease and peripheral vascular disease may be exacerbated with the use of immunosuppressive medications whose known side effects include hyperglycemia, hyperlipidemia, and hypertension; these effects may lead to premature transplant graft dysfunction. Treatment goals for PTDM reflect those of the American Diabetes Association guidelines; long-term management is linked with early, patient-centered education and optimizing minimally diabetogenic immunosuppressive medication regimens. A multidisciplinary team including the patient, family/support people, transplant surgeon, transplant physician, transplant nurse coordinator, transplant social worker, pharmacist, dietitian, and diabetes educator is crucial to long-term management of PTDM.

Strategies for risk reduction and management of posttransplant diabetes mellitus

Strategies for risk reduction and management of posttransplant diabetes mellitus