临床研究
ENGLISH ABSTRACT
血清CysC和CTRP9水平对2型糖尿病视网膜病变的诊断价值
张书
景海霞
刘勤
马建军
白惠玲
作者及单位信息
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DOI: 10.3760/cma.j.cn115989-20220818-00382
Diagnostic value of serum cystatin C and C1q tumor necrosis factor-related protein 9 for diabetic retinopathy in type 2 diabetes
Zhang Shu
Jing Haixia
Liu Qin
Ma Jianjun
Bai Huiling
Authors Info & Affiliations
Zhang Shu
Department of Ophthalmology, Gansu Provincial Hospital, Lanzhou 730000, China
Jing Haixia
The First Clinical Medical College of Gansu University of Traditional Chinese Medicine, Lanzhou 730000, China
Liu Qin
Department of Ophthalmology, Gansu Provincial Hospital, Lanzhou 730000, China
Ma Jianjun
Department of Ophthalmology, Gansu Provincial Hospital, Lanzhou 730000, China
Bai Huiling
Department of Ophthalmology, Gansu Provincial Hospital, Lanzhou 730000, China
·
DOI: 10.3760/cma.j.cn115989-20220818-00382
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摘要

目的探讨血清胱抑素C(CysC)和C1q肿瘤坏死因子相关蛋白9(CTRP9)水平对2型糖尿病患者糖尿病视网膜病变(DR)及糖尿病黄斑水肿(DME)的诊断价值。

方法采用横断面研究方法,纳入2021年4月至2022年4月在甘肃省人民医院就诊的135例2型糖尿病患者,年龄45~75岁,按照DR分级标准将患者分为无DR(NDR)组、非增生型DR(NPDR)组和增生型DR(PDR)组,每组45例。根据有无DME将NPDR组和PDR组患者分为DME组51例和非DME组39例。另选取45名健康体检者作为正常对照组。采集受检者空腹外周静脉血,检测血清中糖化血红蛋白、空腹血糖、三酰甘油、总胆固醇、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇、CysC和CTRP9水平。比较各组CysC和CTRP9表达差异。采用多因素Logistic回归分析模型评估DR及DME的独立影响因素,采用受试者工作特征(ROC)曲线评价血清CysC和CTRP9对DR及DME的诊断价值。

结果正常对照组、NDR组、NPDR组和PDR组血清CysC水平分别为0.74(0.67,0.83)、1.03(0.85,1.22)、1.40(0.98,1.63)和1.66(1.31,1.85)mg/L,呈逐渐升高趋势;CTRP9水平分别为(136.90±14.95)、(120.23±16.31)、(109.50±14.71)和(90.99±13.88)pg/ml,呈逐渐降低趋势;组间总体比较差异均有统计学意义( Z=89.430, P<0.001; F=74.242, P<0.001),组间两两比较差异均有统计学意义(均 P<0.05)。与非DME组相比,DME组血清CysC水平显著升高、CTRP9水平显著降低,差异均有统计学意义(均 P<0.05)。多因素Logistic回归分析结果显示,血清CysC( OR=19.742,95% CI:4.515~86.316, P<0.001)是DR发生的独立危险因素,CTRP9水平( OR=0.937,95% CI:0.908~0.966, P<0.001)是DR发生的保护因素;血清CTRP9水平( OR=0.838,95% CI:0.778~0.903, P<0.001)为DME发生的保护因素。ROC曲线结果显示,血清CysC和CTRP9水平单独及联合诊断2型糖尿病患者并发DR的ROC曲线下面积(AUC)分别为0.798、0.802和0.870,血清CysC和CTRP9水平截断值分别取1.34 mg/L和110.12 pg/ml时可获得最佳诊断效能;其单独及联合诊断DR患者并发DME的AUC分别为0.682、0.923和0.923,血清CTRP9水平的截断值取104.68 pg/ml时可获得最佳诊断效能。

结论血清CysC水平升高及CTRP9水平降低是2型糖尿病患者发生DR的危险因素,血清CTRP9水平降低为DR患者发生DME的危险因素之一。

糖尿病;糖尿病视网膜病变;黄斑水肿;胱抑素C;C1q肿瘤坏死因子相关蛋白9;诊断
ABSTRACT

ObjectiveTo explore the diagnostic value of serum cystatin C (CysC) and C1q tumor necrosis factor-related protein 9 (CTRP9) levels for diabetic retinopathy (DR) and diabetic macular edema (DME) in patients with type 2 diabetes.

MethodsA cross-sectional study was conducted.A total of 135 patients with type 2 diabetes, aged 45-75 years, who were treated in Gansu Provincial Hospital from April 2021 to April 2022 were included.According to DR grading standard, patients were divided into non-DR (NDR) group, non-proliferative DR (NPDR) group and proliferative DR (PDR) group, with 45 patients in each group.The DR patients were subdivided into DME group (51 cases) and non-DME group (39 cases).A total of 45 healthy subjects were selected as the normal control group.Fasting peripheral venous blood was collected to detect serum glycosylated hemoglobin, fasting blood glucose, triacylglycerol, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, CysC and CTRP9 levels.The expression of CysC and CTRP9 levels among different groups were compared.The independent influencing factors of DR and DME were evaluated by multivariate logistic regression analysis model.The diagnostic value of serum CysC and CTRP9 in DR and DME were evaluated by receiver operating characteristic (ROC) curve.This study adhered to the Declaration of Helsinki and the study protocol was approved by the Ethics Committee of Gansu Provincial Hospital (No.2021-301).All patients were informed about the purpose and methods of the study and signed an informed consent form.

ResultsSerum CysC levels in normal control group, NDR group, NPDR group and PDR group were 0.74(0.67, 0.83), 1.03(0.85, 1.22), 1.40(0.98, 1.63) and 1.66(1.31, 1.85)mg/L, respectively, showing a gradually increasing trend, and the serum CTRP9 levels were (136.90±14.95), (120.23±16.31), (109.50±14.71) and (90.99±13.88)pg/ml, respectively, showing a gradually decreasing trend, with statistically significant overall comparison differences among groups ( Z=89.430, P<0.001; F=74.242, P<0.001), the comparison within groups was statistically significant (all at P<0.05).Compared with non-DME group, the serum CysC level was significantly increased and serum CTRP9 level was significantly decreased in DME group (both P<0.05).Multivariate logistic regression analysis showed that serum CysC (odds ratio [ OR]=19.742, 95% confidence interval [ CI]: 4.515-86.316, P<0.001) was the independent risk influencing factors for the occurrence of DR, and CTRP9 ( OR=0.937, 95% CI: 0.908-0.966, P<0.001) was a protective factor for the occurrence of DR.Serum CTRP9 level ( OR=0.838, 95% CI: 0.778-0.903, P<0.001) was a protective factor for DME.The ROC curve showed that the area under ROC curve (AUC) for serum CysC and CTRP9 levels alone and in combination for the diagnosis of DR in patients with type 2 diabetes mellitus complicated by DR were 0.798, 0.802 and 0.870, respectively.The cutoff values of serum CysC and CTRP9 levels to obtain the best diagnostic efficacy were 1.34 mg/L and 110.12 pg/ml, respectively.The AUC for serum CysC and CTRP9 level alone and in combination for the diagnosis of DME in DR patients were 0.682, 0.923 and 0.923, respectively.The cutoff value of serum CTRP9 level to obtain optimal diagnostic efficacy was 104.68 pg/ml.

ConclusionsThe enhanced expression of serum CysC level and reduced expression of serum CTRP9 level are the risk factors for the development of DR in type 2 diabetes patients.The decrease of serum CTRP9 level is one of the risk factors for the development of DME in DR patients.

Diabetes mellitus;Diabetic retinopathy;Macular edema;Cystatin C;C1q tumor necrosis factor-related protein 9;Diagnosis
Liu Qin, Email: mocdef.6ab21uilmmus
引用本文

张书,景海霞,刘勤,等. 血清CysC和CTRP9水平对2型糖尿病视网膜病变的诊断价值[J]. 中华实验眼科杂志,2024,42(03):271-278.

DOI:10.3760/cma.j.cn115989-20220818-00382

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糖尿病视网膜病变(diabetic retinopathy,DR)是2型糖尿病患者常见的眼部微血管并发症。2021年全球糖尿病患病人数为5.366亿人,患病率约为10.5%,预计2045年将增加至7.832亿人,患病率达12.2% [ 1 ],而全球DR患者将增至1.605亿 [ 2 ]。在DR的发展过程中,增生型DR(proliferative diabetic retinopathy,PDR)和糖尿病黄斑水肿(diabetic macular edema,DME)是DR患者视力损伤的主要原因。因此,DR的早期诊断和有效管理至关重要。胱抑素C(cystatin C,CysC)是半胱氨酸蛋白酶抑制剂家族中的一员,在体内广泛表达 [ 3 ]。已有研究证明,CysC是早期糖尿病肾病的敏感标志物,且在DR患者血清中也有显著表达 [ 4 , 5 ]。C1q肿瘤坏死因子相关蛋白9(C1q tumor necrosis factor related protein 9,CTRP9)是一种新发现的脂肪细胞因子,与脂联素的氨基酸高度同源,主要产生于脂肪组织,可降低血清葡萄糖水平,与糖尿病及其并发症的发生和发展有关 [ 6 ]。此外,CysC可通过促进血管内皮生长因子(vascular endothelial growth factor,VEGF)的产生驱动血管生成 [ 4 ],而CTRP9在抑制炎症因子及黏附分子表达的同时还可以平衡VEGF的表达 [ 7 ],推测CysC和CTRP9可能通过共同促进VEGF的生成参与DR及DME的进展。本研究通过分析不同阶段DR及DME患者血清中CysC和CTRP9的表达水平,探讨CysC和CTRP9在DR及DME发病中的作用,以期为DR早期预防、病情监测寻找有效的生物学指标。
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备注信息
A
刘勤,Email: mocdef.6ab21uilmmus
B

张书:酝酿和设计试验、实施研究、采集数据、分析/解释数据、起草及修改文章;景海霞、白惠玲:采集数据、分析/解释数据;刘勤:酝酿和设计试验、实施研究、对文章知识性内容的审阅和智力性内容的修改及定稿;马建军:酝酿和设计试验、对文章知识性内容的审阅和智力性内容的修改及定稿

C
所有作者均声明不存在任何利益冲突
D
兰州市科技计划 (2020-ZD-18)
甘肃省卫生行业科研计划 (GSWSKY-2019-40)
甘肃省人民医院院内科研基金 (20GSSY1-15)
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