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HDL Cholesterol Efflux Predicts Incident New-Onset Diabetes After Transplantation (NODAT) in Renal Transplant Recipients Independent of HDL Cholesterol Levels.

Abstract：

:In renal transplant recipients (RTRs), new-onset diabetes after transplantation (NODAT) is a frequent and serious complication limiting survival of graft and patient. However, the underlying pathophysiology remains incompletely understood. In vitro and in preclinical models, HDL can preserve β-cell function, largely by mediating cholesterol efflux, but this concept has not been evaluated in humans. This study investigated whether baseline cholesterol efflux capacity (CEC) in RTRs is associated with incident NODAT during follow-up. This prospective longitudinal study included 405 diabetes-free RTRs with a functioning graft for >1 year. During a median (interquartile range) follow-up of 9.6 (6.6-10.2) years, 57 patients (14.1%) developed NODAT. HDL CEC was quantified using incubation of human macrophage foam cells with apolipoprotein B-depleted plasma. Baseline CEC was significantly lower in patients developing NODAT during follow-up (median 6.84% [interquartile range 5.84-7.50%]) compared with the NODAT-free group (7.44% [6.46-8.60%]; P = 0.001). Kaplan-Meier analysis showed a lower risk for incident NODAT with increasing sex-stratified tertiles of HDL efflux capacity (P = 0.004). Linear regression analysis indicated that CEC is independently associated with incident NODAT (P = 0.04). In Cox regression analyses, CEC was significantly associated with NODAT (hazard ratio 0.53 [95% CI 0.38-0.76]; P < 0.001), independent of HDL cholesterol levels (P = 0.015), adiposity (P = 0.018), immunosuppressive medication (P = 0.001), and kidney function (P = 0.01). Addition of CEC significantly improved the predictive power of the Framingham Diabetes Risk Score (P = 0.004). This study establishes HDL CEC as a strong predictor of NODAT in RTRs, independent of several other recognized risk factors.

journal_name

Diabetes

journal_title

Diabetes

authors

Szili-Torok T,Annema W,Anderson JLC,Bakker SJL,Tietge UJF

doi

10.2337/db18-1267

subject

Has Abstract

pub_date

2019-10-01 00:00:00

pages

1915-1923

issue

eissn

0012-1797

issn

1939-327X

pii

db18-1267

journal_volume

pub_type

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HDL Cholesterol Efflux Predicts Incident New-Onset Diabetes After Transplantation (NODAT) in Renal Transplant Recipients Independent of HDL Cholesterol Levels.