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

Nandula, Savitri Aninditha; Boddepalli, Chinmayi Sree; Gutlapalli, Sai Dheeraj; Lavu, Vamsi Krishna; Abdelwahab, Rana Abdelwahab Mohamed; Huang, Ruimin; Potla, Shanthi; Bhalla, Sushen; AlQabandi, Yousif; Balani, Prachi

doi:10.7759/cureus.31482

Cited by 3 publications

(3 citation statements)

References 30 publications

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“…Another option could be the use of drugs with protective effects on pancreatic beta cells, such as gliptins or glucagon-like peptide-1 antagonists (GLP-1). In any case, no relevant data are available in this field, which is worth investigating [39, 40]. However, no real information is available on this regard.…”

Section: Discussionmentioning

confidence: 99%

Inflammation on the Waiting List Is a Risk Factor for New-Onset Prediabetes and Post-Transplant Diabetes Mellitus: A Prospective Study

González Delgado,

Hernández,

Marrero

et al. 2023

Nephron

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Introduction: Inflammation is a risk factor for diabetes in the general population. The role of inflammation in prediabetes or post-transplant diabetes mellitus (PTDM) is not clear. We evaluated the association between inflammatory markers in patients on the waiting list for renal transplantation and the onset of prediabetes and PTDM 12 months after transplantation. Methods: This is a post hoc analysis of a prospective study that included nondiabetic patients on the waiting list for kidney transplantation who underwent an oral glucose tolerance test (OGTT) and were followed up to 12 months after transplantation. At this time, those patients without PTDM underwent another OGTT. At pre-transplantation, five cytokines: TNFα, IL6, IL1β, CRP, MCP1 were determined. The association between inflammation and prediabetes/PTDM was evaluated using multiple regression models. Results: 110 patients on the waiting list were enrolled: 74 had normal glucose metabolism and 36 had prediabetes or occult diabetes. At 12 months, 53 patients had normal glucose metabolism, 25 prediabetes, and 32 PTDM. In multiple regression analysis, pre-transplant inflammation was not a risk factor for prediabetes or PTDM. This was attributed to the high interrelation between obesity, prediabetes, and inflammation: about 75% of the cases had these conditions. In a sub-analysis, we analyzed only patients without prediabetes and occult diabetes on the waiting list and found that TNFα levels and BMI at pre-transplantation were independently associated with the onset of prediabetes or PTDM 1 year after transplantation. Conclusions: Pre-transplant inflammation and BMI are risk factors for prediabetes and PTDM in patients without glucose metabolism alterations.

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Section: Discussionmentioning

confidence: 99%

Inflammation on the Waiting List Is a Risk Factor for New-Onset Prediabetes and Post-Transplant Diabetes Mellitus: A Prospective Study

González Delgado,

Hernández,

Marrero

et al. 2023

Nephron

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“…Among calcineurin inhibitors, tacrolimus has been associated with a higher incidence of PTDM [23]. Calcineurin inhibitor-induced hypomagnesemia, which is more common with tacrolimus, has also been shown to be an independent risk factor for developing PTDM [24,25]. Several suggested mechanisms for calcineurin inhibitor-induced PTDM include interference with the nuclear factor of activated T cells signaling in pancreatic β-cells and T-cells and decreasing insulin secretion [26].…”

Section: Risk Factors For the Development Of Ptdmmentioning

confidence: 99%

Genetic and Epigenetic Associations with Post-Transplant Diabetes Mellitus

Abdelrahman,

Maxwell,

McKnight

2024

Genes

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

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“…However, it is prevalent in the first weeks/months after kidney transplantation and may improve in some patients when steroids are tapered. The risk factors for PTDM are classified as modifiable and non-modifiable [22,23]. Non-modifiable factors include age, i.e., age > 40 years, with an increased likelihood that PTDM beta-cell function diminishes, leading to insulin resistance.…”

Section: Post-transplant Diabetes Mellitus (Ptdm)mentioning

confidence: 99%

Adverse Drug Events after Kidney Transplantation

Rostaing,

Jouve,

Terrec

et al. 2023

JPM

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Introduction: Kidney transplantation stands out as the optimal treatment for patients with end-stage kidney disease, provided they meet specific criteria for a secure outcome. With the exception of identical twin donor–recipient pairs, lifelong immunosuppression becomes imperative. Unfortunately, immunosuppressant drugs, particularly calcineurin inhibitors like tacrolimus, bring about adverse effects, including nephrotoxicity, diabetes mellitus, hypertension, infections, malignancy, leukopenia, anemia, thrombocytopenia, mouth ulcers, dyslipidemia, and wound complications. Since achieving tolerance is not feasible, patients are compelled to adhere to lifelong immunosuppressive therapies, often involving calcineurin inhibitors, alongside mycophenolic acid or mTOR inhibitors, with or without steroids. Area covered: Notably, these drugs, especially calcineurin inhibitors, possess narrow therapeutic windows, resulting in numerous drug-related side effects. This review focuses on the prevalent immunosuppressive drug-related side effects encountered in kidney transplant recipients, namely nephrotoxicity, post-transplant diabetes mellitus, leukopenia, anemia, dyslipidemia, mouth ulcers, hypertension, and viral reactivations (cytomegalovirus and BK virus). Additionally, other post-kidney-transplantation drugs such as valganciclovir may also contribute to adverse events such as leukopenia. For each side effect, we propose preventive measures and outline appropriate treatment strategies.

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

Cited by 3 publications

References 30 publications

Inflammation on the Waiting List Is a Risk Factor for New-Onset Prediabetes and Post-Transplant Diabetes Mellitus: A Prospective Study

Inflammation on the Waiting List Is a Risk Factor for New-Onset Prediabetes and Post-Transplant Diabetes Mellitus: A Prospective Study

Genetic and Epigenetic Associations with Post-Transplant Diabetes Mellitus

Adverse Drug Events after Kidney Transplantation

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