Glucose Metabolism After Kidney Transplantation: Insulin Release and Sensitivity With Tacrolimus- Versus Belatacept-Based Immunosuppression

Müller, Martin; Schwaiger, Elisabeth; Kurnikowski, Amelie; Haidinger, Michael; Ristl, Robin; Tura, Andrea; Pacini, Giovanni; Werzowa, Johannes; Hecking, Manfred

doi:10.1053/j.ajkd.2020.07.016

Cited by 7 publications

(7 citation statements)

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“…The tacrolimus‐treated kidney transplant recipients had lower insulin release in the presence of higher insulin sensitivity, when compared to belatacept‐treated kidney transplant recipients. The study also confirmed a lower PTDM rate with belatacept, compared to tacrolimus [62], which has recently been observed in another retrospective study [63]. The tacrolimus‐belatacept comparison represents new information, as the available literature had previously only suggested superiority of belatacept, in terms of a reduced PTDM incidence [64,65], when this immunosuppressive agent was compared to cyclosporine.…”

Section: Management Of Ptdm: Immunosuppressionsupporting

confidence: 77%

“…In this trial [60], concomitant changes in insulin secretion and/or sensitivity were unfortunately not reported, but a study from Vienna suggested that the balance between these two entities might be deranged in kidney transplant recipients, compared with general population subjects as controls [61]. Recently, Müller et al analyzed belatacept‐treated kidney transplant recipients as yet another control group, in comparison to tacrolimus‐treated kidney transplant recipients [62]. The tacrolimus‐treated kidney transplant recipients had lower insulin release in the presence of higher insulin sensitivity, when compared to belatacept‐treated kidney transplant recipients.…”

Section: Management Of Ptdm: Immunosuppressionmentioning

confidence: 99%

“…Furthermore, from a mechanistic point of view, tacrolimus seems to interact with free fatty acids to impair beta cell function [67]. The recent re‐classification of individuals from the general population with type 1 diabetes, type 2 diabetes, and late autoimmune diabetes in adults into 5 novel categories (clusters), by their degree of insulin deficiency, respective to insulin resistance [68] may help the PTDM community in solving the conflict whether it is impaired insulin secretion [61,62,69] or higher insulin resistance that dominates the pathophysiology of PTDM patients [70]. As in the general population, there may be individual differences in PTDM patients, which are further modified by the type of immunosuppression that these individuals are receiving after solid organ transplantation.…”

Section: Management Of Ptdm: Immunosuppressionmentioning

confidence: 99%

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Management of post‐transplant diabetes: immunosuppression, early prevention, and novel antidiabetics

et al. 2020

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Summary Post‐transplant diabetes mellitus (PTDM) shows a relationship with risk factors including obesity and tacrolimus‐based immunosuppression, which decreases pancreatic insulin secretion. Several of the sodium–glucose‐linked transporter 2 inhibitors (SGLT2is) and glucagon‐like peptide 1 receptor agonists (GLP1‐RAs) dramatically improve outcomes of individuals with type 2 diabetes with and without chronic kidney disease, which is, as heart failure and atherosclerotic cardiovascular disease, differentially affected by both drug classes (presumably). Here, we discuss SGLT2is and GLP1‐RAs in context with other PTDM management strategies, including modification of immunosuppression, active lifestyle intervention, and early postoperative insulin administration. We also review recent studies with SGLT2is in PTDM, reporting their safety and antihyperglycemic efficacy, which is moderate to low, depending on kidney function. Finally, we reference retrospective case reports with GLP1‐RAs that have not brought forth major concerns, likely indicating that GLP1‐RAs are ideal for PTDM patients suffering from obesity. Although our article encompasses PTDM after solid organ transplantation in general, data from kidney transplant recipients constitute the largest proportion. The PTDM research community still requires data that treating and preventing PTDM will improve clinical conditions beyond hyperglycemia. We therefore suggest that it is time to collaborate, in testing novel antidiabetics among patients of all transplant disciplines.

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Section: Management Of Ptdm: Immunosuppressionsupporting

confidence: 77%

Section: Management Of Ptdm: Immunosuppressionmentioning

confidence: 99%

Section: Management Of Ptdm: Immunosuppressionmentioning

confidence: 99%

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Management of post‐transplant diabetes: immunosuppression, early prevention, and novel antidiabetics

et al. 2020

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“…Data from kidney, 1–8 liver, 9–12 lung, 13,14 and heart 15 transplant recipients indicate diabetes mellitus (DM) diagnosed after transplantation is associated with mortality and cardiovascular events. Post-transplantation DM (PTDM) is a unique form of diabetes, 16–18 which has been best studied in kidney transplant recipients (KTRs). 19,20 KTRs develop early post-transplant hyperglycemia because the abrupt reversal of kidney failure generates higher insulin demand, partly through increased insulin clearance, but also as a result of individual risk factors and transplant-specific mechanisms such as perioperative stress, adding to the diabetogenicity of immunosuppressive therapy (glucocorticosteroids and tacrolimus).…”

mentioning

confidence: 99%

Early Postoperative Basal Insulin Therapy versus Standard of Care for the Prevention of Diabetes Mellitus after Kidney Transplantation: A Multicenter Randomized Trial

Schwaiger¹,

Krenn²,

Kurnikowski³

et al. 2021

JASN

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BackgroundPost-transplantation diabetes mellitus (PTDM) might be preventable.MethodsThis open-label, multicenter randomized trial compared 133 kidney transplant recipients given intermediate-acting insulin isophane for postoperative afternoon glucose ≥140 mg/dl with 130 patients given short-acting insulin for fasting glucose ≥200 mg/dl (control). The primary end point was PTDM (antidiabetic treatment or oral glucose tolerance test–derived 2 hour glucose ≥200 mg/dl) at month 12 post-transplant.ResultsIn the intention-to-treat population, PTDM rates at 12 months were 12.2% and 14.7% in treatment versus control groups, respectively (odds ratio [OR], 0.82; 95% confidence interval [95% CI], 0.39 to 1.76) and 13.4% versus 17.4%, respectively, at 24 months (OR, 0.71; 95% CI, 0.34 to 1.49). In the per-protocol population, treatment resulted in reduced odds for PTDM at 12 months (OR, 0.40; 95% CI, 0.16 to 1.01) and 24 months (OR, 0.54; 95% CI, 0.24 to 1.20). After adjustment for polycystic kidney disease, per-protocol ORs for PTDM (treatment versus controls) were 0.21 (95% CI, 0.07 to 0.62) at 12 months and 0.35 (95% CI, 0.14 to 0.87) at 24 months. Significantly more hypoglycemic events (mostly asymptomatic or mildly symptomatic) occurred in the treatment group versus the control group. Within the treatment group, nonadherence to the insulin initiation protocol was associated with significantly higher odds for PTDM at months 12 and 24.ConclusionsAt low overt PTDM incidence, the primary end point in the intention-to-treat population did not differ significantly between treatment and control groups. In the per-protocol analysis, early basal insulin therapy resulted in significantly higher hypoglycemia rates but reduced odds for overt PTDM—a significant reduction after adjustment for baseline differences—suggesting the intervention merits further study.Clinical Trial registration number:NCT03507829

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“…Muller et al compared abnormalities of glucose metabolism in kidney transplant patients on tacrolimus to those on belatacept and found that belatacept treated patients had 93% lower odds of developing diabetes and prediabetes than those on tacrolimus (odds ratio [OR], 0.08; 95% CI 0.02–0.35; P < 0.001 ). Patients on tacrolimus also had higher hemoglobin A1c levels, lower insulin release, and higher insulin sensitivity compared to those on belatacept [29 ▪ ].…”

Section: Belatacept and Metabolic Considerationsmentioning

confidence: 98%

Use of belatacept in kidney transplantation: what's new?

Yakubu¹,

Moinuddin

Gupta

2022

Current Opinion in Organ Transplantation

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Purpose of reviewThe advent of calcineurin inhibitors have led to a significant improvement in short term outcomes after kidney transplantation. However, long term outcomes are hindered by the cardiovascular, metabolic and chronic renal toxicity associated with these agents. Belatacept is a selective T cell costimulation blocker that is approved for prevention of rejection in kidney transplantation, and has been associated with favorable cardiovascular, metabolic and renal outcomes in kidney transplant recipients. This review provides an overview of recent updates in the use of belatacept in kidney transplant recipients.Recent findingsBelatacept may be a safe alternative to calcineurin inhibitors for select kidney transplant populations. Patients converted to belatacept from a calcineurin inhibitor-based immunosuppression generally experience improvement in renal function, and may be less likely to develop de novo donor specific antibodies or new onset diabetes after transplantation. Although, belatacept based immunosuppression may increase the risk of early acute cellular rejection, it may however be beneficial in stabilization of long-term renal function and improvement in inflammation in patients with chronic active antibody mediated rejection. These benefits need to be counterweighed with risks of lack of response to severe acute respiratory syndrome coronavirus 2 vaccination and other adverse infectious outcomes.SummaryBelatacept may be an alternative to calcineurin inhibitors and may contribute to improved long term metabolic and allograft outcomes in kidney transplant recipients. Careful selection of patients for belatacept-based immunosuppression is needed, to obviate the risk of acute rejection shown in clinical studies.

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Glucose Metabolism After Kidney Transplantation: Insulin Release and Sensitivity With Tacrolimus- Versus Belatacept-Based Immunosuppression

Cited by 7 publications

References 10 publications

Management of post‐transplant diabetes: immunosuppression, early prevention, and novel antidiabetics

Management of post‐transplant diabetes: immunosuppression, early prevention, and novel antidiabetics

Early Postoperative Basal Insulin Therapy versus Standard of Care for the Prevention of Diabetes Mellitus after Kidney Transplantation: A Multicenter Randomized Trial

Use of belatacept in kidney transplantation: what's new?

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