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中华眼科医学杂志(电子版) ›› 2020, Vol. 10 ›› Issue (04) : 212 -218. doi: 10.3877/cma.j.issn.2095-2007.2020.04.004

论著

脂类代谢异常与糖尿病视网膜微血管病变及神经元退行性改变的相关性研究
王凯悦1, 张新媛1,†(), 聂瑶1, 邱冰洁1, 赵琳1, 康文婷2   
  1. 1. 100730　首都医科大学附属北京同仁医院　北京同仁眼科中心　北京市眼科研究所　北京市眼视光与视觉科学重点实验室
    2. 100730　首都医科大学附属北京同仁医院中心实验室
  • 收稿日期:2020-07-26 出版日期:2020-08-28
  • 通信作者: 张新媛
  • 基金资助:
    国家自然科学基金面上项目(81570850；81170859); 国家科技部国家重点研发计划重大慢性非传染性疾病防控研究项目(2016YFC1305604)

Effects of dyslipidemia on retinal micro-vasculopathy and retinal neuron degeneration in patients with diabetic

Kaiyue Wang1, Xinyuan Zhang1,†(), Yao Nie1, Bingjie Qiu1, Lin Zhao1, Wenting Kang2   

  1. 1. Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Institute of Ophthalmology, Beijing Key Laboratory of Ophthalmology and Visual Sciences, Beijing 100730, China
    2. Medical Research Center, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China
  • Received:2020-07-26 Published:2020-08-28
  • Corresponding author: Xinyuan Zhang
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引用本文：

王凯悦, 张新媛, 聂瑶, 邱冰洁, 赵琳, 康文婷. 脂类代谢异常与糖尿病视网膜微血管病变及神经元退行性改变的相关性研究[J]. 中华眼科医学杂志(电子版), 2020, 10(04): 212-218.

Kaiyue Wang, Xinyuan Zhang, Yao Nie, Bingjie Qiu, Lin Zhao, Wenting Kang. Effects of dyslipidemia on retinal micro-vasculopathy and retinal neuron degeneration in patients with diabetic[J]. Chinese Journal of Ophthalmologic Medicine(Electronic Edition), 2020, 10(04): 212-218.

目的

探究脂类代谢异常在糖尿病(DM)视网膜微血管病变及神经元退行性病变中的作用。

方法

前瞻性病例对照研究。随机入组2016年4月至2017年6月于北京同仁医院门诊就诊的2型DM患者111例(176只眼)。其中，男性62例(104只眼)，女性49例(72只眼)，年龄27~76岁，平均年龄(55.05±10.65)岁。根据美国DM协会关于DM及糖尿病视网膜病变(DR)指南将患者进一步分为DM组、非增生性DR(NPDR)组及增生性DR(PDR)组。全部患者均行视力、眼压、裂隙灯检查、散瞳眼底检查、彩色眼底照相及扫频光学相干断层扫描成像(OCT)-光学相干断层扫描血管成像(OCTA)检查。空腹生化检查检测患者血清空腹血糖、糖化血红蛋白、胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)及甘油三酯(TG)等。定量分析OCT-OCTA图像黄斑无血管区(FAZ)面积、视网膜神经纤维层(RNFL)、神经节细胞层(GCL+)及神经节细胞复合体层(GCC)平均厚度。患者年龄、DM病程、糖化血红蛋白、TG、TC及LDL-C水平采用均数±标准差描述，组间比较采用单因素方差分析。年龄、性别、DM病程、糖化血红蛋白、TG、TC、LDL-C水平及其他因素对DM及DR患者的影响采用多元Logistic回归分析。患者FAZ面积、RNFL、GCL+、及GCC平均厚度用均数±标准差描述，组间比较采用独立样本t检验。

结果

DM组、NPDR组及PDR组的DM病程分别为(7.92±6.06)年、(12.72±5.87)年及(12.25±7.12)年，PDR组和NPDR组大于DM组，差异有统计学意义(F＝5.46，P<0.05)；三组患者血清TC含量分别为(4.42±1.02)mmol/L、(4.66±1.18)mmol/L及(5.15±1.33)mmol/L，PDR组高于DM组，差异有统计学意义(F＝3.08，P<0.05)；血清LDL-C含量分别为(2.48±0.97)mmol/L、(2.85±1.01)mmol/L及(3.24±0.99)mmol/L，PDR组高于DM组，差异有统计学意义(F＝4.38，P<0.05)；血清TG含量分别为(1.91±1.33)mmol/L、(1.50±1.11)mmol/L及(1.62±1.05)mmol/L，三组间差异无统计学意义(F＝1.07，P>0.05)。多元Logistic回归分析结果显示，DM病程、LDL-C是DR发生与发展的危险因素且其相关性具有统计学意义(OR＝1.10，1.69；P<0.05)。高TC组患者FAZ面积、RNFL、GCL+及GCC厚度分别为(413.27±180.85)mm2、(41.25±20.05)μm、(81.18±18.65)μm及(125.84±34.51)μm；TC正常组分别为(327.03±103.36)mm2、(35.26±12.92)μm、(77.50±11.28)μm及(114.96±17.12)μm。高TC组患者FAZ面积、RNFL厚度及GCC厚度均大于TC正常组，差异有统计学意义(t＝2.59，2.26，2.06；P<0.05)。高LDL-C组患者FAZ面积、RNFL、GCL+及GCC厚度分别为(393.74±169.71)mm2、(39.80±19.76)μm、(79.13±18.37)μm及(128.43±32.53)μm；LDL-C正常组分别为(324.20±100.91)mm2、(35.77±13.08)μm、(78.50±11.36)μm及(115.32±15.056)μm，高LDL-C组患者FAZ面积、RNFL及GCC厚度均大于LDL-C正常组，差异有统计学意义(t＝2.31，1.53，2.55；P<0.05)。高TG组患者FAZ面积、RNFL、GCL+及GCC厚度分别为(371.95±169.92)mm2、(36.05±14.29)μm、(79.52±14.32)μm及(118.11±21.34)μm；TG正常组分别为(348.73±116.99)mm2、(38.15±15.54)μm、(78.42±14.09)μm及(118.60±25.73)μm，差异均无统计学意义(t＝0.80，0.77，0.42，0.11；P>0.05)。

结论

LDL-C是DR发生与发展的危险因素，血脂异常是DM患者视网膜微血管病变和神经元退行性病变重要的始动因素。

关键词: 血脂代谢异常, 糖尿病视网膜微血管病变, 神经元退行性改变, 扫频源相干光断层扫描技术
Objective

To investigate the correlation between dyslipidemia with retinal microangio-pathy and neuronal degeneration in diabetic patients.

Methods

Prospective cohort study. 111 patients 62 males and 49 females, average age (55.05±10.65) years with diabetic mellitus (DM) and diabetic retinopathy(DR) were enrolled during April 2016 to June 2017 in Beijing Tongren Hospital. According to the Diabetes Association guidelines on DM and DR, patients were divided into DM, non-proliferative DR and proliferative DR (PDR) groups. All patients underwent routine ophthalmologic examinations and swept source optical coherent tomography(OCT)-optical coherent tomography angiography (OCTA). Serum fasting blood glucose, glycated hemoglobin, total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), and triglyceride(TG) were determined by biochemical examination. The area of foveal avascular zone (FAZ) and the average thickness of the retinal nerve fiber layer(RNFL), ganglion cell layer (GCL+ ) and ganglion cell complex (GCC) were obtained by quantitative analysis of OCT and OCTA. The age, DM duration, serum levels of glycated hemoglobin, TG, TC and LDL-C of patients were described by mean±standard deviation. One-way ANOVA was used for comparison among three groups. The risk factors such as age, sex, DM duration, glycated hemoglobin, TG, TC, LDL-C levels and other factors on DM and DR patients were analyzed by Logistic regression. The area of FAZ and the average thickness of RNFL, GCL+ , GCC were described by mean±standard deviation. Independent sample t testing was used for comparison between groups.

Results

DM duration of DM group, NPDR group and PDR group was (7.92±6.06) years, (12.72±5.87) years and (12.25±7.12) years, respectively, and the DM duration of PDR and NPDR groups were longer than the DM group. The difference was statistically significant (F=5.46, P<0.05). The content of TC in three groups was (4.42±1.02) mmol/L, (4.66±1.18) mmol/L, and (5.15±1.33) mmol/L. The content of LDL-C in three groups was (2.48±0.97) mmol/L, (2.85±1.01) mmol/L and (3.24±0.99) mmol/L. Compared to the DM group, the serum of TC and LDL-C in PDR group was significantly higher (F=3.08, 4.38, P<0.05 ). The content of TG in three groups was (1.91±1.33) mmol/L, (1.50±1.11) mmol/L and (1.62±1.05) mmol/L; the difference among three groups is not statistically significant (F=1.07, P>0.05). The results of Logistic regression analysis showed that DM duration and the content of LDL-C were risk factors for DR progression (OR=1.10, 1.69; P<0.05). The area of FAZ and the average thickness of RNFL, GCL+ , GCC in high TC group were (413.27±180.85)mm2, (41.25±20.05)μm, (81.18±18.65)μm and (125.84±34.51)μm , respectively. Those of normal TC group were (327.03±103.36) mm2, (35.26±12.92)μm, (77.50±11.28)μm and (114.96±17.12)μm, respectively. Compared to the normal TC group, the area of FAZ and the average thickness of RNFL and GCC of high TC group were significantly higher (t=2.59, 2.26, 2.06; P<0.05). The area of FAZ and the average thickness of RNFL, GCL+ , GCC of high LDL-C group were (393.74±169.71) mm2, (39.80±19.76)μm, (79.13±18.37)μm and (128.43±32.53)μm. Those of normal LDL-C group were (324.20±100.91) mm2, (35.77±13.08)μm, (78.50±11.36)μm and (115.32±15.056)μm. Compared to the normal LDL-C group, the area of FAZ and the average thickness of RNFL and GCC of high LDL-C group were significantly higher (t=2.31, 1.53, 2.55; P<0.05). The area of FAZ and the average thickness of RNFL, GCL+ , GCC of high TG group were (371.95±169.92) mm2, (36.05±14.29)μm, (79.52±14.32)μm and (118.11±21.34)μm. Those of normal TG group were (348.73±116.99) mm2, (38.15±15.54)μm, (78.42±14.09)μm and (118.60±25.73)μm. There was no significant difference between two groups (t=0.80, 0.77, 0.42, 0.11; P>0.05).

Conclusions

LDL-C is an independent risk factor for progression of DR. Dyslipidemia may aggravate retinal microangiopathy and retinal neuron degeneration in micro-vasculopathy in diabetic patients.

Key words: Dyslipidemia, Retinal microangiopathy, Retinal neuron degeneration, Optical coherence tomography
图1 正常人光学相干断层扫描及光学相干断层扫描血管成像的分层图　图A~图E示正常人光学相干断层扫描B扫描图像上，视网膜黄斑区神经纤维层与视网膜内丛状层及神经节细胞层厚度之和、视网膜内丛状层与神经节细胞层及神经纤维层厚度之和定量分析的示意图；图F示正常人在光学相干断层扫描血管成像扫描模式下获得的图像，使用拓普康IMAGEnet? 6软件测量画线区黄斑无血管区的面积
图2 三组患者血清总胆固醇、低密度脂蛋白胆固醇、甘油三酯、糖化血红蛋白水平及糖尿病病程的比较　图A示三组患者血清总胆固醇的含量；图B示三组患者血清低密度脂蛋白胆固醇的含量；图C示三组患者血清总甘油三酯的含量；图D示三组患者血清糖化血红蛋白的含量；图E示三组患者糖尿病的病程。注：*表示P<0.05
表1 三组患者一般情况的比较
组别 例数 平均年龄(岁) 性别(男性/女性) 糖尿病病程(年)
糖尿病组 25 58.36±9.81 13/12 7.92±6.06
非增生性糖尿病视网膜病变组 50 55.22±10.55 31/19 12.72±5.87
增生性糖尿病视网膜病变组 36 52.53±10.95 18/18 12.25±7.12
F/χ2值   2.23* 1.42** 5.46*
P值   >0.05 >0.05 <0.05
表2 不同因素对糖尿病视网膜病变进程影响Logistic回归分析的结果
变量 OR值 P值
年龄(Ref＝年龄<60岁) 0.502(0.222, 1.134) >0.05
性别(Ref＝女) 0.817(0.380, 1.756) >0.05
糖尿病病程 1.075(1.041, 1.140) <0.05
高血压(Ref＝病程<15年) 0.717(0.173, 2.967) >0.05
高胆固醇(Ref＝无) 5.682(1.201，26.880) <0.05
高甘油三酯(Ref＝无) 0.530(0.224, 1.252) >0.05
高密度脂蛋白(Ref＝无) 0.452(0.107, 1.910) >0.05
低密度脂蛋白胆固醇 2.324(1.014, 5.326) <0.05
糖化血红蛋白 1.230(0.975, 1.551) >0.05
表3 高胆固醇组与胆固醇正常组患者影像学指标的比较(±s)
组别 例数 FAZ面积(mm2) RNFL平均厚度(μm) GCL+平均厚度(μm) GCC平均厚度(μm)
高胆固醇组 35 413.27±180.85 41.25±20.05 81.18±18.65 125.84±34.51
胆固醇正常组 76 327.03±103.36 35.26±12.92 77.50±11.28 114.96±17.12
t值   2.59 2.26 1.26 2.06
P值   <0.05 <0.05 >0.05 <0.05
表4 高低密度脂蛋白胆固醇组与低密度脂蛋白胆固醇正常组患者影像学指标的比较(±s)
组别 例数 FAZ面积(mm2) RNFL平均厚度(μm) GCL+平均厚度(μm) GCC平均厚度(μm)
高低密度脂蛋白胆固醇组 36 393.74±169.71 39.80±19.76 79.13±18.37 128.43±32.53
低密度脂蛋白胆固醇正常组 75 324.20±100.91 35.77±13.08 78.50±11.36 115.32±15.06
t值   2.31 1.53 0.22 2.55
P值   <0.05 <0.05 >0.05 <0.05
表5 高甘油三酯组与甘油三酯正常组患者影像学指标的比较(±s)
组别 例数 FAZ面积(mm2) RNFL平均厚度(μm) GCL+平均厚度(μm) GCC平均厚度(μm)
高甘油三酯组 35 371.95±169.92 36.05±14.29 79.52±14.32 118.11±21.34
甘油三酯正常组 76 348.73±116.99 38.15±15.54 78.42±14.09 118.60±25.73
t值   0.80 0.77 0.42 0.11
P值   >0.05 >0.05 >0.05 >0.05
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