2 型糖尿病患者胆固醇外流与高密度脂蛋白颗粒之间的关系。
Relationships between cholesterol efflux and high-density lipoprotein particles in patients with type 2 diabetes mellitus.
机构信息
Department of Endocrinology, Singapore General Hospital, Outram Road, Singapore 169608.
出版信息
J Clin Lipidol. 2011 Nov-Dec;5(6):467-73. doi: 10.1016/j.jacl.2011.06.016. Epub 2011 Jun 28.
BACKGROUND
High-density lipoprotein (HDL) encompasses a heterogeneous population of lipoproteins with differences in functionality. The impact of HDL heterogeneity on its ability to support HDL-mediated cholesterol efflux has not been previously studied in patients with type 2 diabetes mellitus (T2DM).
OBJECTIVES
To examine the relationships between various HDL subtypes and cholesterol efflux from macrophages in patients with T2DM.
METHODS
Lipoprotein molecular profiles of 44 patients were studied by NMR spectroscopy. Cholesterol efflux was expressed as percentage efflux of radioactivity from lipid-laden THP-1 macrophages preincubated with (3)H-cholesterol and then incubated with serum depleted of apolipoprotein B to provide an HDL-enriched acceptor medium.
RESULTS
There was a predominance of small HDL particles (59%) and small putatively atherogenic low-density lipoprotein particles (56%). Neither HDL-C nor ApoA-I concentrations showed statistically significant correlations with percentage cholesterol efflux, but a significant positive relationship was found with the total HDL particle concentration (r = 0.41, P = .005) contributed to largely by medium HDL particles (r = 0.41, P = .006). The correlation between medium-sized HDL particle concentration remained significantly associated with cholesterol efflux when assessed with the use of a linear regression model that included all the HDL lipoprotein subclass concentrations as well as apolipoprotein A-I. Importantly, no statistically significant association was observed between the number of small HDL particles and cholesterol efflux. Hemoglobin A1c showed a significant inverse correlation with cholesterol efflux (r = -0.31, P = .04).
CONCLUSION
In patients with moderately controlled type 2 diabetes mellitus, cholesterol efflux from macrophages incubated with apolipoprotein B-depleted plasmas correlated significantly and positively with the concentration of total and medium-sized HDL and not with that of the smallest particles.
背景
高密度脂蛋白（HDL）包含具有功能差异的脂蛋白的异质群体。HDL 异质性对其支持 HDL 介导的胆固醇流出能力的影响在 2 型糖尿病（T2DM）患者中尚未得到研究。
目的
研究 2 型糖尿病患者中各种 HDL 亚型与巨噬细胞胆固醇流出之间的关系。
方法
通过 NMR 光谱研究了 44 名患者的脂蛋白分子谱。胆固醇流出率表示用（3）H-胆固醇预孵育载脂 THP-1 巨噬细胞后放射性活性的百分比流出率，然后用缺乏载脂蛋白 B 的血清孵育，提供富含 HDL 的接受介质。
结果
存在小的 HDL 颗粒（59%）和小的推定致动脉粥样硬化的低密度脂蛋白颗粒（56%）占主导地位。HDL-C 和 ApoA-I 浓度与胆固醇流出百分比均无统计学显著相关性，但与总 HDL 颗粒浓度呈显著正相关（r=0.41，P=0.005），主要由中 HDL 颗粒贡献（r=0.41，P=0.006）。当使用包括所有 HDL 脂蛋白亚类浓度以及载脂蛋白 A-I 的线性回归模型评估时，中 HDL 颗粒浓度与胆固醇流出之间的相关性仍然与胆固醇流出显著相关。重要的是，小 HDL 颗粒数量与胆固醇流出之间未观察到统计学显著相关性。糖化血红蛋白 A1c 与胆固醇流出呈显著负相关（r=-0.31，P=0.04）。
结论
在血糖控制适度的 2 型糖尿病患者中，用载脂蛋白 B 耗尽的血浆孵育的巨噬细胞的胆固醇流出与总 HDL 和中 HDL 的浓度显著正相关，而与最小颗粒的浓度无关。
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