The combined effect of pre-transplant triglyceride levels and the type of calcineurin inhibitor in predicting the risk of new onset diabetes after renal transplantation

Porrini, Esteban; Delgado, Patricia; Alvarez, Alejandra; Cobo, Marian; Pérez, L. Figuero; González-Posada, José Manuel; Hortal, L; Gallego, Roberto; Garcia, J.; Checa, María Dolores; Morales, Adelaida; Salido, Eduardo; Hernández, Domingo; Torres, Armando

doi:10.1093/ndt/gfm762

Cited by 69 publications

(70 citation statements)

References 19 publications

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“…Interestingly, suppression of calcineurin activity improves insulin sensitivity in normoglycemic human subjects but exacerbates insulin resistance in diabetics (Ozbay et al, 2012; Porrini et al, 2008), supporting our observation that the therapeutic window for calcineurin intervention is in normoglycemic 5MO, but not older, insulin resistant Tg2576 (Figure 2). These observations may reveal the AD equivalent of the prediabetes state (De Felice and Ferreira, 2014) where elevated glucose, in the absence of overt insulin dyshomeostasis, can increase the risk of cognitive decline (Kerti et al, 2013).…”

Section: Therapeutic Opportunitiessupporting

confidence: 78%

Insulin resistance in Alzheimer's disease

Dineley

Jahrling

Denner

2014

Neurobiology of Disease

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Insulin is a key hormone regulating metabolism. Insulin binding to cell surface insulin receptors engages many signaling intermediates operating in parallel and in series to control glucose, energy, and lipids while also regulating mitogenesis and development. Perturbations in the function of any of these intermediates, which occur in a variety of diseases, cause reduced sensitivity to insulin and insulin resistance with consequent metabolic dysfunction. Chronic inflammation ensues which exacerbates compromised metabolic homeostasis. Since insulin has a key role in learning and memory as well as directly regulating ERK, a kinase required for the type of learning and memory compromised in early Alzheimer's disease (AD), insulin resistance has been identified as a major risk factor for the onset of AD. Animal models of AD or insulin resistance or both demonstrate that AD pathology and impaired insulin signaling form a reciprocal relationship. Of note are human and animal model studies geared toward improving insulin resistance that have led to the identification of the nuclear receptor and transcription factor, peroxisome proliferator-activated receptor gamma (PPARγ) as an intervention tool for early AD. Strategic targeting of alternate nodes within the insulin signaling network has revealed disease-stage therapeutic windows in animal models that coalesce with previous and ongoing clinical trial approaches. Thus, exploiting the connection between insulin resistance and AD provides powerful opportunities to delineate therapeutic interventions that slow or block the pathogenesis of AD.

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Section: Therapeutic Opportunitiessupporting

confidence: 78%

Insulin resistance in Alzheimer's disease

Dineley

Jahrling

Denner

2014

Neurobiology of Disease

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“…Israni et al (26) found posttransplant metabolic syndrome independently associated with subsequent risk of PTDM. When occurring pretransplantation, the metabolic syndrome (27) and its components such as pretransplant hypertriglyceridemia and BMI (28), as well as prediabetes (17) have predicted increased risk for PTDM. Specifically pretransplantation insulin resistance, putatively the underlying pathophysiology of metabolic syndrome, was found to be a risk factor for PTDM (7).…”

Section: Recommendation 4: Identify Patients At Risk For Ptdmmentioning

confidence: 99%

Proceedings From an International Consensus Meeting on Posttransplantation Diabetes Mellitus: Recommendations and Future Directions

Sharif

Hecking

Vries

et al. 2014

American Journal of Transplantation

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421

471

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A consensus meeting was held in Vienna on September 8–9, 2013, to discuss diagnostic and therapeutic challenges surrounding development of diabetes mellitus after transplantation. The International Expert Panel comprised 24 transplant nephrologists, surgeons, diabetologists and clinical scientists, which met with the aim to review previous guidelines in light of emerging clinical data and research. Recommendations from the consensus discussions are provided in this article. Although the meeting was kidney-centric, reflecting the expertise present, these recommendations are likely to be relevant to other solid organ transplant recipients. Our recommendations include: terminology revision from new-onset diabetes after transplantation to posttransplantation diabetes mellitus (PTDM), exclusion of transient posttransplant hyperglycemia from PTDM diagnosis, expansion of screening strategies (incorporating postprandial glucose and HbA1c) and opinion-based guidance regarding pharmacological therapy in light of recent clinical evidence. Future research in the field was discussed with the aim of establishing collaborative working groups to address unresolved questions. These recommendations are opinion-based and intended to serve as a template for planned guidelines update, based on systematic and graded literature review, on the diagnosis and management of PTDM.

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“…9,15–19 The prevalence of and risk factors for diabetes in patients with earlier CKD stages (estimated glomerular filtration rate [eGFR] >60 mL/min/1.73 m 2 ) have not been evaluated previously in large studies. The most commonly used equation to estimate GFR is the Modification of Diet in Renal Disease (MDRD) Study equation.…”

mentioning

confidence: 99%

Comparison of the CKD Epidemiology Collaboration (CKD-EPI) and Modification of Diet in Renal Disease (MDRD) Study Equations: Prevalence of and Risk Factors for Diabetes Mellitus in CKD in the Kidney Early Evaluation Program (KEEP)

McFarlane

McCullough

Sowers

et al. 2011

American Journal of Kidney Diseases

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Background Diabetes is a leading cause of chronic kidney disease (CKD). Whether reclassification of CKD stages based on glomerular filtration rate estimated using the CKD Epidemiology Collaboration (CKD-EPI) equation versus the Modification of Diet in Renal Disease (MDRD) Study equation modifies estimates of prevalent risk factors across stages is unknown. Methods This is a cross-sectional analysis of data from the Kidney Early Evaluation Program (KEEP), a community-based health screening program targeting individuals 18 years and older with diabetes, hypertension, or a family history of diabetes, hypertension, or kidney disease. Of 109,055 participants, 68.2% were women and 31.8% were African American. Mean age was 55.3 ± 0.05 years. Clinical, demographic, and laboratory data were collected from August 2000 through December 2009. Glomerular filtration rate was estimated using the CKD-EPI and MDRD Study equations. Results CKD was present in 25.6% and 23.5% of the study population using the MDRD Study and CKD-EPI equations, respectively. Diabetes was present in 42.4% and 43.8% of participants with CKD, respectively. Prevalent risk factors for diabetes included obesity (body mass index >30 kg/m2), 44.0%; hypertension, 80.5%; cardiovascular disease, 23.2%; family history of diabetes, 55.9%; and dyslipidemia, 43.0%. In a logistic regression model after adjusting for age and other risk factors, odds for diabetes increased significantly compared with no CKD with each CKD stage based on the CKD-EPI equation and similarly with stages based on the MDRD Study equation. Using a CKD-EPI–adjusted model, ORs were: stage 1, 2.08 (95% CI, 1.90–2.27); stage 2, 1.86 (95% CI, 1.72–2.02); stage 3, 1.23 (95% CI, 1.17–1.30); stage 4, 1.69 (95% CI, 1.42–2.03); and stage 5, 2.46 (95% CI, 1.46–4.14). Conclusions Using the CKD-EPI equation led to a lower prevalence of CKD but to similar diabetes prevalence rates associated with CKD across all stages compared with the MDRD Study equation. Diabetes and other CKD risk factor prevalence was increased compared with the non-CKD population.

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The combined effect of pre-transplant triglyceride levels and the type of calcineurin inhibitor in predicting the risk of new onset diabetes after renal transplantation

Abstract: Pre-transplant hypertriglyceridemia was a risk factor for NODAT only in recipients treated with Tacro; it highlights the importance of pre-transplant insulin resistance in the pathogenesis of NODAT.

Cited by 69 publications

References 19 publications

Insulin resistance in Alzheimer's disease

Insulin resistance in Alzheimer's disease

Proceedings From an International Consensus Meeting on Posttransplantation Diabetes Mellitus: Recommendations and Future Directions

Comparison of the CKD Epidemiology Collaboration (CKD-EPI) and Modification of Diet in Renal Disease (MDRD) Study Equations: Prevalence of and Risk Factors for Diabetes Mellitus in CKD in the Kidney Early Evaluation Program (KEEP)

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