Department of Pediatrics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
Diabetes. 2019 Oct;68(10):1915-1923. doi: 10.2337/db18-1267. Epub 2019 Aug 2.
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%]; = 0.001). Kaplan-Meier analysis showed a lower risk for incident NODAT with increasing sex-stratified tertiles of HDL efflux capacity ( = 0.004). Linear regression analysis indicated that CEC is independently associated with incident NODAT ( = 0.04). In Cox regression analyses, CEC was significantly associated with NODAT (hazard ratio 0.53 [95% CI 0.38-0.76]; < 0.001), independent of HDL cholesterol levels ( = 0.015), adiposity ( = 0.018), immunosuppressive medication ( = 0.001), and kidney function ( = 0.01). Addition of CEC significantly improved the predictive power of the Framingham Diabetes Risk Score ( = 0.004). This study establishes HDL CEC as a strong predictor of NODAT in RTRs, independent of several other recognized risk factors.
在肾移植受者（RTR）中，移植后新发糖尿病（NODAT）是一种常见且严重的并发症，限制了移植物和患者的生存。然而，其潜在的病理生理学仍不完全清楚。在体外和临床前模型中，HDL 可以通过介导胆固醇流出来维持β细胞功能，但这一概念尚未在人类中进行评估。本研究旨在探讨 RTR 中基线胆固醇流出能力（CEC）是否与随访期间 NODAT 的发生有关。这项前瞻性纵向研究纳入了 405 例移植后>1 年且有功能移植物的无糖尿病 RTR。在中位（四分位间距）9.6（6.6-10.2）年的随访期间，57 例患者（14.1%）发生 NODAT。使用载脂蛋白 B 耗尽的血浆孵育人巨噬细胞泡沫细胞来定量测定 HDL CEC。与无 NODAT 组相比，随访期间发生 NODAT 的患者的基线 CEC 显著降低（中位数 6.84%[四分位间距 5.84-7.50%]）（ = 0.001）。Kaplan-Meier 分析显示，随着 HDL 流出能力的性别分层三分位升高，发生 NODAT 的风险降低（ = 0.004）。线性回归分析表明，CEC 与 NODAT 的发生独立相关（ = 0.04）。在 Cox 回归分析中，CEC 与 NODAT 显著相关（风险比 0.53[95%CI 0.38-0.76]； < 0.001），与 HDL 胆固醇水平（ = 0.015）、肥胖（ = 0.018）、免疫抑制药物（ = 0.001）和肾功能（ = 0.01）无关。加入 CEC 可显著提高 Framingham 糖尿病风险评分的预测能力（ = 0.004）。本研究确立了 HDL CEC 作为 RTR 中 NODAT 的一个强有力预测因子，独立于其他几个公认的危险因素。
