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高密度脂蛋白胆固醇流出率与载脂蛋白 A-I 标准化与 2 型糖尿病的未来发展相关:来自 CORDIOPREV 试验。

HDL cholesterol efflux normalised to apoA-I is associated with future development of type 2 diabetes: from the CORDIOPREV trial.

机构信息

Lipids and Atherosclerosis Unit, UGC Internal Medicine, Reina Sofia University Hospital, Cordoba, Spain.

Nutrigenomics and Metabolic Syndrome Group, Maimonides Institute for Biomedical Research at Cordoba (IMIBIC), Cordoba, Spain.

出版信息

Sci Rep. 2017 Oct 2;7(1):12499. doi: 10.1038/s41598-017-12678-9.

Abstract

This prospective study evaluated whether baseline cholesterol efflux is associated with future development of type 2 diabetes (T2DM) in cardiovascular patients. We measured cholesterol efflux in all CORDIOPREV study (NCT00924937) participants free of T2DM at baseline (n = 462) and assessed its relationship with T2DM incidence during a 4.5 years of follow-up. Cholesterol efflux was quantified by incubation of cholesterol-loaded THP-1 cells with the participants' apoB-depleted plasma. Disposition index was estimated as beta-cell function indicator. During follow-up 106 individuals progressed to T2DM. The cholesterol efflux/apoA-1 ratio was inversely associated with T2DM development independently of traditional risk factors (model-1, OR: 0.647, 95%CI: 0.495-0.846), and after additional adjustment for glycaemic parameters (model-2, OR: 0.670, 95%CI: 0.511-0.878). When cumulative incidence of diabetes was analysed by quartiles of cholesterol efflux/apoA-I, incidence of T2DM was reduced by 54% in subjects who were in the higher cholesterol efflux/apoA-I quartile compared to subjects in the lowest quartile (p = 0.018 and p = 0.042 for model-1 and 2). Moreover, participants who were in the higher cholesterol efflux/apoA-I presented significantly higher disposition index (β = 0.056, SE = 0.026; p = 0.035). In conclusion, HDL-cholesterol efflux normalised to apoA-I was inversely associated with T2DM development in cardiovascular patients. This association was independent of several T2DM risk factors, and may be related to a preserved beta-cell function.

摘要

这项前瞻性研究评估了胆固醇外排功能基线值是否与心血管病患者未来发生 2 型糖尿病(T2DM)有关。我们在所有 CORDIOPREV 研究(NCT00924937)参与者中测量了基线时无 T2DM(n=462)的胆固醇外排功能,并在 4.5 年的随访期间评估其与 T2DM 发病率的关系。胆固醇外排功能通过载有胆固醇的 THP-1 细胞与参与者的载脂蛋白 B 耗尽的血浆孵育来定量。处置指数被估计为胰岛β细胞功能的指标。在随访期间,有 106 人进展为 T2DM。胆固醇外排/载脂蛋白 A-1 比值与 T2DM 的发生呈负相关,与传统危险因素无关(模型 1,OR:0.647,95%CI:0.495-0.846),并且在进一步调整血糖参数后(模型 2,OR:0.670,95%CI:0.511-0.878)。当按胆固醇外排/载脂蛋白 A-I 的四分位数分析糖尿病的累积发生率时,与处于最低四分位数的受试者相比,处于胆固醇外排/载脂蛋白 A-I 较高四分位数的受试者 T2DM 发病率降低了 54%(模型 1 和 2 分别为 p=0.018 和 p=0.042)。此外,处于较高胆固醇外排/载脂蛋白 A-I 四分位数的受试者具有显著更高的处置指数(β=0.056,SE=0.026;p=0.035)。总之,高密度脂蛋白胆固醇外排与载脂蛋白 A-I 标准化呈负相关,与心血管病患者的 T2DM 发生有关。这种关联独立于几种 T2DM 危险因素,可能与胰岛β细胞功能的保留有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/844b/5624929/584a40eace1d/41598_2017_12678_Fig1_HTML.jpg

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