Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing, China.
Beijing Retinal and Choroidal Vascular Disorders Study Group, Beijing, China.
Front Endocrinol (Lausanne). 2022 Jul 22;13:915575. doi: 10.3389/fendo.2022.915575. eCollection 2022.
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.
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.
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.
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.
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。
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。
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。
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。