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血浆载脂蛋白预测 2 型糖尿病患者糖尿病视网膜病变的发生和严重程度。

Plasma Apolipoproteins Predicting the Occurrence and Severity of Diabetic Retinopathy in Patients With Type 2 Diabetes Mellitus.

机构信息

Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing, China.

Beijing Retinal and Choroidal Vascular Disorders Study Group, Beijing, China.

出版信息

Front Endocrinol (Lausanne). 2022 Jul 22;13:915575. doi: 10.3389/fendo.2022.915575. eCollection 2022.

Abstract

OBJECTIVE

Apolipoproteins are amphipathic molecules and the major components of plasma lipoproteins. This study aims to investigate the effects of dysregulated apolipoprotein (apo) profiles and their ratios on type 2 diabetes mellitus (T2DM) and diabetic retinopathy (DR) further to test the hypothesis that altered serum level of apolipoproteins is strong biomarkers for DR.

RESEARCH DESIGN AND METHODS

This case-control study consists of 157 patients with T2DM including DM without DR, non-proliferative DR (NPDR), and proliferative DR (PDR). Fifty-eight age- and sex-matched healthy subjects were enrolled as normal controls. Blood biochemistry profile including serum levels of glucose, glycated hemoglobin (HbA1c), lipid profile [total cholesterol (TC), Triglycerides (TG), high and low-density lipoprotein (HDL-C and LDL-C)] was estimated. Apolipoproteins (apos, A-I, A-II, B, C-II, C-III, and E) was evaluated by protein chips (Luminex technology). Apolipoprotein ratios and arteriosclerosis-associated plasma indices were calculated. The Kruskal-Wallis test, independent sample t-test or Mann-Whitney U test, and multivariate regression analysis were performed to investigate the association of serum lipid biomarkers and the DR severity.

RESULTS

Serum level of apoA-I was negatively correlated with TC-(HDL-C)/HDL-C ( < 0.001), fasting glucose ( < 0.001), HbA1c ( < 0.001), and (<0.001), while apoE, apoC-II/apoC-III, apoA-II/apoA-I were positively correlated with above traditional biomarkers ( < 0.001). Single variable logistic analysis results showed that body mass index (BMI) ( = 0.023), DM duration ( < 0.001), apoE ( < 0.001), apoC-II/apo C-III ( < 0.001), apoE/apoC-II ( < 0.001), atherogenic index ( = 0.013), fasting glucose ( < 0.001), HbA1c ( < 0.001), LPA ( = 0.001), and LDL-C/HDL-C ( = 0.031) were risk factors for the occurrence and severity of DR. Multivariate logistic regression mode showed that apoC-II/apoC-III and apoB/non-HDL-C ( < 0.001) as well as apoE/apoC-II ( = 0.001) were the independent risk factors for the occurrence and severity of DR-apopA-I and apoA-II are protective factors for DR-after controlling for the duration of DM, HbA1c, fasting glucose, and LPA.

CONCLUSIONS

apoE, apoC-II/apoC-III, apoE/apoC-II, and apoB/non-HDL-C could be used as novel biomarkers for occurrence and severity of DR, whereas apoA-I and apoA-II resulted as protective factors for DR.

摘要

目的

载脂蛋白是两亲分子,也是血浆脂蛋白的主要成分。本研究旨在进一步探讨载脂蛋白(apo)谱及其比值失调对 2 型糖尿病(T2DM)和糖尿病视网膜病变(DR)的影响,并验证血清载脂蛋白水平改变是 DR 的强有力生物标志物这一假说。

研究设计和方法

本病例对照研究包括 157 例 T2DM 患者,包括无 DR 的糖尿病、非增殖性 DR(NPDR)和增殖性 DR(PDR)。58 名年龄和性别匹配的健康受试者作为正常对照组。检测血糖、糖化血红蛋白(HbA1c)、血脂谱[总胆固醇(TC)、甘油三酯(TG)、高低密度脂蛋白(HDL-C 和 LDL-C)]等血液生化指标。采用蛋白芯片(Luminex 技术)检测载脂蛋白(apo)A-I、A-II、B、C-II、C-III 和 E。计算载脂蛋白比值和动脉粥样硬化相关血浆指数。采用 Kruskal-Wallis 检验、独立样本 t 检验或 Mann-Whitney U 检验以及多元回归分析,研究血清脂质生物标志物与 DR 严重程度的关系。

结果

apoA-I 水平与 TC-(HDL-C)/HDL-C(<0.001)、空腹血糖(<0.001)、HbA1c(<0.001)呈负相关,而 apoE、apoC-II/apoC-III、apoA-II/apoA-I 与上述传统生物标志物呈正相关(<0.001)。单变量 logistic 分析结果显示,体重指数(BMI)(=0.023)、糖尿病病程(<0.001)、apoE(<0.001)、apoC-II/apoC-III(<0.001)、apoE/apoC-II(<0.001)、致动脉粥样硬化指数(=0.013)、空腹血糖(<0.001)、HbA1c(<0.001)、脂蛋白相关磷脂酶 A(LPA)(=0.001)和 LDL-C/HDL-C(=0.031)是 DR 发生和严重程度的危险因素。多变量 logistic 回归模型显示,apoC-II/apoC-III 和 apoB/非 HDL-C(<0.001)以及 apoE/apoC-II(=0.001)是 DR 发生和严重程度的独立危险因素,而 apoA-I 和 apoA-II 是 DR 的保护因素(=0.001),控制 DM 病程、HbA1c、空腹血糖和 LPA 后。

结论

apoE、apoC-II/apoC-III、apoE/apoC-II 和 apoB/非 HDL-C 可作为 DR 发生和严重程度的新型生物标志物,而 apoA-I 和 apoA-II 则是 DR 的保护因素。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aafa/9353260/533e9700ebf6/fendo-13-915575-g001.jpg

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