Transplant-Associated Hyperglycemia

Reese, Peter P.; Bloom, Roy D.

doi:10.2215/cjn.01430210

Cited by 3 publications

(2 citation statements)

References 19 publications

(23 reference statements)

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“…In 2007, Crutchlow and Bloom proposed the term transplant-associated hyperglycaemia (TAH) [60], specifying also in a subsequent editorial, that this term encompasses the full range of new-onset, post-transplant glycaemic abnormalities, including the prediabetic states of impaired fasting glucose and IGT, as well as NODAT [61]. Although the authors did not focus on immediate postoperative TAH, their definition was a major step forward, not only by naming hyperglycaemia as the root of subsequent disease in context with the disease itself, but also by expanding the risk population to KTRs who have 'only' IGT.…”

Section: Novel Terminology and Collective Mechanismsmentioning

confidence: 99%

Novel views on new-onset diabetes after transplantation: development, prevention and treatment

Hecking

Werzowa

Haidinger

et al. 2013

Nephrology Dialysis Transplantation

107

101

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New-onset diabetes after transplantation (NODAT) is associated with increased risk of allograft failure, cardiovascular disease and mortality, and therefore, jeopardizes the success of renal transplantation. Increased awareness of NODAT and the prediabetic states (impaired fasting glucose and impaired glucose tolerance, IGT) has fostered previous and present recommendations, based on the management of type 2 diabetes mellitus (T2DM). Unfortunately, the idea that NODAT merely resembles T2DM is potentially misleading, because the opportunity to initiate adequate anti-hyperglycaemic treatment early after transplantation might be given away for 'tailored' immunosuppression in patients who have developed NODAT or carry personal risk factors. Risk factor-independent mechanisms, however, seem to render postoperative hyperglycaemia with subsequent development of overt or 'full-blown' NODAT, the unavoidable consequence of the transplant and immunosuppressive process itself, at least in many cases. A proof of the concept that timely preventive intervention with exogenous insulin against post-transplant hyperglycaemia may decrease NODAT was recently provided by a small clinical trial, which is awaiting confirmation from a multicentre study. However, because early insulin therapy aimed at beta-cell protection seems to contrast the currently recommended, stepwise approach of 'watchful waiting' prior to pancreatic decompensation, we here aim at reviewing recent concepts regarding the development, prevention and treatment of NODAT, some of which seem to challenge the traditional view on T2DM and NODAT. In summary, we suggest a novel, risk factor-independent management approach to NODAT, which includes glycaemic monitoring and anti-hyperglycaemic treatment in virtually everybody after transplantation. This approach has widespread implications for future research and is intended to tackle NODAT and also ultimately cardiovascular disease.

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Section: Novel Terminology and Collective Mechanismsmentioning

confidence: 99%

Novel views on new-onset diabetes after transplantation: development, prevention and treatment

Hecking

Werzowa

Haidinger

et al. 2013

Nephrology Dialysis Transplantation

107

101

View full text Add to dashboard Cite

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“…Increased insulin clearance also reduces insulin levels and leads to hyperglycemia. The issue of the contribution of IR as compared to impaired insulin secretion as the seminal event that leads to PTDM remains unresolved [8]. …”

Section: Introductionmentioning

confidence: 99%

Association of Inflammation prior to Kidney Transplantation with Post-Transplant Diabetes Mellitus

et al. 2016

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Background/Objective: Post-transplant diabetes mellitus (PTDM) is both common and associated with poor outcomes after kidney transplantation. Our objective was to examine relationships of uremia-associated inflammation and adiponectin with PTDM. Methods: Nondiabetic kidney transplant patients were enrolled with donor controls. Inflammatory cytokines and adiponectin were measured before and after transplantation. Adipose tissue was obtained for gene expression analysis. Glucose transport was quantified in vitro in C2C12 cells following cytokine exposure. The patients were monitored up to 12 months for PTDM. Results: We studied 36 controls and 32 transplant patients, of whom 11 (35%) developed PTDM. Compared to controls, plasma TNFα, IL-6, MCP-1, and CRP levels were higher in transplant patients (p < 0.01). In multivariable analysis, TNFα plasma levels before transplantation were associated with development of PTDM (OR = 2.03, p = 0.04). Visceral adipose tissue TNFα mRNA expression was higher in transplant patients than controls (fold change 1.33; p < 0.05). TNFα mRNA expression was also higher in patients who developed PTDM than in those who did not (fold change 1.42; p = 0.05), and adiponectin mRNA expression was lower (fold change 0.48; p < 0.05). The studies on the C2C12 cells demonstrated an increase in glucose uptake following exposure to adiponectin and no significant change after exposure to TNFα alone. Concomitant TNFα and adiponectin exposure blunted adiponectin-induced glucose uptake (11% reduction; p < 0.001). Conclusion: Our in vitro and clinical observations suggest that TNFα could contribute to PTDM through an effect on adiponectin. Our study proposes that inflammation is involved in glucose regulation after kidney transplantation.

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CircFOXN2 alleviates glucocorticoid- and tacrolimus-induced dyslipidemia by reducing FASN mRNA stability by binding to PTBP1 during liver transplantation

Chen

Yang

Yuan

et al. 2023

American Journal of Physiology-Cell Physiology

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Objective: We aimed to examine impacts and functional mechanism of circular RNA forkhead box N2 (FOXN2) in tacrolimus (TAC)- and dexamethasone (Dex)-induced lipid metabolism disorders. Methods: RNA level and protein contents in TAC, Dex or combined TAC plus Dex treated patients and Huh-7 cells were were measured utilizing quantitative real-time (qRT)-PCR and western blotting assays. Total cholesterol (TC) and triglyceride (TG) levels were determined using corresponding commercial kits and Oil red O staining. RNA immunoprecipitation and RNA pull-down verified the binding relationship among circFOXN2, polypyrimidine tract binding protein 1 (PTBP1) and fatty acid synthase (FASN). Male C57BL/6 mice were used to establish a dyslipidemia mouse model to validate the discoveries at the cellular level. Results: Dex treatment significantly promoted TAC-mediated the increase of TC and TG in serum samples and Huh-7 cells. Moreover, circFOXN2 was reduced but FASN was elevated in TAC-treated Huh-7 cells, and these expression trends were markedly enhanced by Dex co-treatment. Overexpression of circFOXN2 could reverse the accumulation of TC and TG and the upregulation of FASN and sterol regulatory element binding transcription factor 2 (SREBP2) mediated by Dex and TAC cotreatment. Mechanistically, circFOXN2 reduced FASN mRNA stability by recruiting PTBP1. The protective roles of circFOXN2 overexpression on lipid metabolism disorders were weakened by FASN overexpression. In vivo finding also disclosed that circFOXN2 greatly alleviated the dysregulation of lipid metabolism triggered by TAC plus Dex. Conclusion: CircFOXN2 alleviated the dysregulation of lipid metabolism induced by the combination of TAC and Dex by modulating the PTBP1/FASN axis.

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Transplant-Associated Hyperglycemia

Cited by 3 publications

References 19 publications

Novel views on new-onset diabetes after transplantation: development, prevention and treatment

Novel views on new-onset diabetes after transplantation: development, prevention and treatment

Association of Inflammation prior to Kidney Transplantation with Post-Transplant Diabetes Mellitus

CircFOXN2 alleviates glucocorticoid- and tacrolimus-induced dyslipidemia by reducing FASN mRNA stability by binding to PTBP1 during liver transplantation

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