Skip to main content
NCBI home page
Journal of Southern Medical University logoLink to Journal of Southern Medical University
. 2021 Mar 20;41(3):459–463. [Article in Chinese] doi: 10.12122/j.issn.1673-4254.2021.03.21

2型糖尿病患者血清CTRP9水平与糖尿病视网膜病变的相关性

Association between serum CTRP9 levels and diabetic retinopathy in patients with type 2 diabetes mellitus

Pengpeng ZHOU 1,2, Liyan LIU 1, Weiping GAO 2,*
PMCID: PMC8075780  PMID: 33849840

Abstract

Objective

To investigate the relationship between serum C1q tumor necrosis factor-related protein 9 (CTRP9) level and the risk of diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM).

Methods

A total of 291 patients with T2DM underwent fundus examination, and their serum levels of CTRP9, insulin and adiponectin were measured using enzyme- linked immunosorbent assay. According to results of fundus examination, the patients were divided into DR group and non-DR (NDR) group, and logistic regression was used to analyze the relationship between serum CTRP9 levels and DR in T2DM patients.

Results

Compared with those in NDR group, the patients with DR showed significantly increased serum CTRP9 level (P < 0.001) and decreased serum adiponectin level (P < 0.001). Pearson correlation analysis showed that in patients with T2DM complicated by DR, serum CTRP9 levels had a significant positive correlation with DR stage (P < 0.05) and a negative correlation with serum adiponectin level (P < 0.001). Multivariate logistic regression analysis showed that with the increase of serum CTRP9 level, the risk of DR is significantly increased in patients with T2DM.

Conclusion

In patients with T2DM complicated by DR, an increased serum CTRP9 level suggests a compensatory response to DR.

Keywords: diabetes mellitus, type 2; diabetic retinopathy; C1q tumor necrosis factor-related protein 9

糖尿病视网膜病变(DR)是糖尿病常见的微血管并发症之一，是成人视力低下和失明的主要原因[1-3]。补体C1q肿瘤坏死因子相关蛋白9(CTRP9)是一种与脂联素高度同源的脂肪因子[4]，具有抗炎，抗氧化，舒张血管的作用[5-9]。此外，它可以增加胰岛素敏感性，降低血糖水平并抑制血管内皮细胞凋亡[10-13]。动物实验研究显示CTRP9对DR具有治疗作用，CTRP9抑制2型糖尿病(T2DM)模型小鼠视网膜炎症因子白介素-1β(IL-1β)，肿瘤坏死因子-α(TNF-α)，单核细胞趋化蛋白1(MCP-1) 和粘附分子的表达，平衡色素上皮衍生因子(PEDF)和血管内皮生长因子(VEGF)的表达，防止T2DM模型小鼠血视网膜屏障(BRB)的破坏和紧密连接蛋白的下调[14]。尽管上述动物实验显示CTRP9在DR的发病过程中发挥着重要作用，但尚缺乏有关CTRP9与DR关联的临床证据。本研究调查了T2DM患者血清CTRP9水平是否与DR有关，结果显示随着血清CTRP9水平的升高，T2DM并发DR的风险显著升高，提示T2DM并发DR患者血清CTRP9水平升高可能是糖尿病视网膜微血管病变的代偿反应。

1. 资料和方法

1.1. 研究对象

收集2017年6月~2020年9月于我院眼科或内分泌科门诊就诊且临床生化资料完整的291例T2DM患者。排除标准：(1)1型糖尿病; (2)严重心血管疾病; (3) 严重肝损害; (4)结缔组织疾病; (5)恶性肿瘤; (6)急性感染期; (7)妊娠或经期妇女; (8)可能影响眼循环的任何其他眼疾; (9)之前进行玻璃体内注射; (10)影响体重的任何因素，甲状腺功能亢进症，皮质类固醇或避孕药具。本研究是经昆山市中医院伦理委员会审核批准的横断面研究(批准号：KZY2017-06)。

1.2. 方法

1.2.1.

一般资料收集患者临床基本资料包括: 性别、年龄、T2DM病程、高血压病史、收缩压(SBP)、舒张压(DBP)、体质量指数(BMI，BMI=体质量/身高2)。

1.2.2.

生化检测所有患者的血液样本均在禁食过夜后获得。罗氏ROCHE8000全自动生化分析仪检测血脂，包括高密度脂蛋白(HDL-C)，低密度脂蛋白(LDL-C)，甘油三酸酯(TG)，总胆固醇(TC)，载脂蛋白A(APOA)和载脂蛋白B(APOB); 肾功能，包括血尿素、血肌酐; 血糖，血尿酸和C反应蛋白(CRP)。美国伯乐糖化血红蛋白分析仪检测糖化血红蛋白(HbA1c); 放免法检测胰岛素; 计算胰岛素抵抗指数(HOMA-IR)空腹血糖×空腹胰岛素/22.5

1.2.3.

糖尿病视网膜病变程度依据2002年国际分级标准[15]分为：无明显视网膜病变(NDR); 轻度非增殖期糖尿病性视网膜病变(NPDR)——仅见微动脉瘤; 中度NPDR——有微动脉瘤，但程度轻于重度NPDR; 重度NPDR——无PDR表现，但有下列任一表现：(1)任一象限有多于20处的视网膜内出血; (2)超过2个象限内静脉串珠样改变; (3)1个或以上象限有显著的视网膜内微血管异常; 增殖期糖尿病性视网膜病变(PDR)——有明显的新生血管形成、视网膜前出血或玻璃体出血。本研究中NDR为NDR组，轻、中、重度NPDR及PDR为DR组。

1.2.4.

血清CTRP9、脂联素的测定酶联免疫吸附(ELISA)法测定血清CTRP9、脂联素的水平(BioVendor)。具体操作，按照试剂盒说明进行。CTRP9可检测水平为25~800 pg/mL，脂联素可检测水平为0.1~10 μg/mL，批内及批间变异系数均 < 10%。

1.3. 统计学分析

使用易侕统计软件包(Empower Stats)和R软件进行数据分析。均进行正态性检验，计量资料若服从正态分布用均数±标准差表示，若非正态分布用中位数(上下四分位数)表示。正态分布计量资料进行t检验，非正态分布计量资料进行秩和检验(u检验)，计数资料采用率来描述并进行卡方检验(χ2检验)。两变量之间的相关性采用Pearson相关性分析。采用Logistic回归分析，计算OR值，并计算95%可信区间(95%CI)。P < 0.05为差异有统计学意义。

2. 结果

2.1. 研究人群的基线特征

291例T2DM患者中，男性162例(55.64%)，女性129例(44.38%)，平均年龄58±15岁，平均糖尿病病程9.8±8.0年。其中109例T2DM并发DR，轻、中、重NPDR及PDR所占比例分别为9.17%、42.20%、25.68%、22.94%。NDR组与DR组分别为182例(62.54%)和109例(37.46%)。DR组血清CTRP9水平显著高于NDR组; DR组血清脂联素水平显著低于NDR组; 与NDR组相比，DR组糖尿病病程较长; 空腹胰岛素水平显著升高; HOMA-IR显著升高; DR组合并高血压的比例较NDR组明显升高; DR组收缩压显著高于NDR组; DR组血肌酐显著高于NDR组; DR组血清尿素显著高于NDR组; DR组CRP显著高于NDR组(表 1)。

1.

2型糖尿病患者的基线资料

Clinical and biochemical data of type 2 diabetic patients with and without DR

Variable NDR (n=182) DR (n=109) T value (vswvalue, χ2 value) P
Note: T2DM: Type 2 diabetes; DR: Diabetic retinopathy; HbA1c: Glycosylated hemoglobin; FBG: Fasting blood glucose; HOMA-IR: Homeostasis model assessment for insulin resistance; SBP: Systolic blood pressure; DBP: Diastolic blood Pressure; TC: Total cholesterol; LDL-C: Low density lipoprotein cholesterol; HDL-C: High density lipoprotein cholesterol; TG: Triglyceride; UA: uric acid; BMI: Body mass index; Scr: Serum creatinine; UA: uric acid; APOA: Apolipoprotein A; APOB: Apolipoprotein B; CRP: C-reactive protein; CTRP9: C1q tumour necrosis factor-related protein 9.
Gender (male/female) 112/70 50/59 6.78 0.009
Age (year) 56±16 60±13 -2.27 0.024
History of hypertension 85(46.70%) 75 (68.81%) 13.45 < 0.001
SBP (mmHg) 135.2±18.6 147.6±23.5 -4.98 < 0.001
DBP (mmHg) 81.1±11.8 80.6±14.1 0.36 0.719
Duration of T2DM 6.00 (1.00-10.00) 13.00(10.00-20.00) -6.94 < 0.001
BMI (kg/m2) 26.0±3.6 25.1±3.0 2.03 0.030
HbA1C (%) 9.45 (7.80-11.12) 8.80(7.60-11.30) -1.99 0.926
FBG (mmol/L) 8.35(7.23-9.47) 8.50(7.30-10.40) -1.53 0.250
Insulin (μU/mL) 8.30 (7.10-9.40) 11.40 (9.80-13.80) -10.87 < 0.001
HOMA-IR 3.10 (2.40-3.90) 4.30 (3.50-5.60) -7.95 < 0.001
Serum urea (mmol/L) 5.28 (4.29-6.75) 6.55 (5.03-11.60) -1.79 < 0.001
Scr (μmol/L) 73.08 (65.02-87.21) 86.80 (73.00-129.50) -5.79 < 0.001
UA (μmol/L) 348.5 (304.0-431.00) 401.0 (327.0-481.0) -2.11 0.024
TG (mmol/L) 1.55 (1.05-2.59) 1.85 (0.96-2.55) 1.43 0.857
TC (mmol/L) 4.75 (3.90-5.60) 4.90 (3.90-6.27) -1.90 0.075
HDL-C (mmol/L) 0.94 (0.81-1.12) 1.01 (0.83-1.17) -1.38 0.110
LDL-C (mmol/L) 3.14±0.92 3.32±1.12 -1.48 0.139
APOA(g/L) 1.13 (0.98-1.26) 1.12 (1.01-1.28) -0.58 0.416
APOB(g/L) 0.94 (0.74-1.10) 0.94 (0.73-1.24) -0.81 0.648
CRP (mg/dL) 0.58 (0.22-1.54) 1.13 (0.58-1.99) -0.40 0.003
Adiponectin (μg/mL) 7.25 (5.95-8.68) 5.95 (5.04-6.79) 8.15 < 0.001
CTRP9 (pg/mL) 122.3 (110.8-134.0) 153.5 (140.0-161.0) -12.27 < 0.001
Open in a new tab

2.2. 血清CTRP9水平与T2DM患者、T2DM并发DR患者临床资料的相关性

血清CTRP9水平与T2DM患者BMI、糖尿病病程、收缩压、空腹血糖、空腹胰岛素、HOMA-IR、血肌酐水平、HDL-C、APOA、CRP呈显著正相关。血清CTRP9水平与T2DM患者血清脂联素呈显著负相关。血清CTRP9水平与T2DM并发DR患者BMI、空腹胰岛素、胰岛素抵抗指数、CRP、DR严重程度呈显著正相关。血清CTRP9水平与T2DM并发DR患者血清脂联素呈显著负相关(表 2)。

2.

血清CTRP9浓度与临床特征的相关性

Correlation between serum CTRP9 concentration and clinical parameters

CTRP9 Variable T2DM (n=291) DR (n=109)
r P r P
T2DM: Type 2 diabetes; DR: Diabetic retinopathy; HbA1c: Glycosylated hemoglobin; FBG: Fasting blood glucose; HOMA-IR: Homeostasis model assessment for insulin resistance; SBP: Systolic blood pressure; DBP: Diastolic blood Pressure; TC: Total cholesterol; LDL-C: Low density lipoprotein cholesterol; HDL-C: High density lipoprotein cholesterol; TG: Triglyceride; UA: uric acid; BMI: Body mass index; Scr: Serum creatinine; UA: Uric acid; APOA: Apolipoprotein A; APOB: Apolipoprotein B; CRP: C-reactive protein; CTRP9: C1q tumour necrosis factor-related protein.
Age (years) 0.06 0.303 0.14 0.136
BMI (kg/m2) 0.25 < 0.001 0.39 < 0.001
Duration of T2DM 0.25 < 0.001 0.07 0.422
SBP (mmHg) 0.17 0.004 0.10 0.304
DBP (mmHg) -0.02 0.792 -0.03 0.765
HbA1C (%) 0.04 0.591 -0.12 0.223
FBG (mmol/L) 0.13 0.031 0.02 0.804
Insulin (μU/mL) 0.34 < 0.001 0.33 < 0.001
HOMA-IR 0.32 < 0.001 0.22 0.019
Serum urea (mmol/L) 0.11 0.061 0.13 0.166
Scr (μmol/L) 0.13 0.027 0.16 0.095
UA (μmol/L) -0.02 0.666 -0.15 0.121
TG (mmol/L) 0.06 0.289 0.07 0.479
TC (mmol/L) 0.09 0.143 -0.11 0.233
HDL-C (mmol/L) 0.16 0.007 -0.05 0.638
LDL-C (mmol/L) 0.05 0.358 -0.08 0.390
APOA (g/L) 0.13 0.027 0.01 0.970
APOB (g/L) 0.10 0.118 0.01 0.979
CP (mg/dL) 0.21 < 0.001 0.39 < 0.001
Adiponectin (μg/mL) -0.27 < 0.001 -0.23 0.017
Stage of DR - - 0.48 < 0.001
Open in a new tab

2.3. T2DM患者血清CTRP9水平与T2DM并发DR的回归分析

以是否有DR为因变量，T2DM患者血清CTRP9水平为自变量，进行单因素Logistic回归分析。T2DM患者血清CTRP9每增加1 pg/mL，发生DR风险增加8%，差异具有统计学意义(OR：1.08，95%CI：1.06~1.10，P < 0.001)。同时校正年龄、BMI、性别、糖尿病病程、高血压、HbA1c、空腹血糖、空腹胰岛素、胰岛素抵抗指数、血清脂联素、HDL-C、LDL-C、TG、TC、APOA、APOB、血肌酐、血尿素、CRP后，T2DM患者血清CTRP9每增加1 pg/mL，发生DR风险增加13%，差异具有统计学意义(OR：1.13，95%CI：1.09~1.18，P < 0.001)。

3. 讨论

DR是糖尿病性微血管病变中最重要的表现，是糖尿病的严重并发症之一[16-17]。血管内皮功能障碍、BRB破坏和新生血管形成是DR的基本病理变化[18-20]。高血糖、高血脂以及在此基础上引发的炎症反应是导致DR基本病理变化的关键因素[21-23]。CTRP9是2009年新发现的一种脂肪因子，与脂联素具有高度同源性[4, 24]。CTRP9可以激活AMPK，MAPK或其他信号通路促进脂质代谢，改善胰岛素敏感性，降低血糖，减轻炎症反应，保护血管。Wong等[4]研究显示CTRP9通过AMPK，Akt及MAPK信号通路降低ob/ob肥胖小鼠血清胰岛素及葡萄糖水平。Jung等[25]研究显示CTRP9通过AMPK信号通路阻碍炎症因子TNF-α诱导的NF-κB活化，并抑制血管内皮细胞中黏附分子和趋化因子的表达，减轻血管炎症。

本研究显示，与NDR组比较，DR组T2DM患者血清CTRP9、CRP、HOMA-IR显著升高，血清脂联素显著降低。随着血清CTRP9水平的升高，T2DM并发DR的风险显著升高，且血清CTRP9水平与DR严重程度、CRP、HOMA-IR及BMI呈正相关，与血清脂联素水平呈负相关。既往有多项研究显示，T2DM并发DR患者较未并发DR患者血清CRP、HOMA-IR显著升高，血清脂联素显著降低[26-28]，与本研究结果一致。

血液中的CTRP9主要由脂肪组织分泌，CTRP9蛋白在ob/ob肥胖小鼠脂肪组织、外周血中表达水平上调[4]。研究发现，T2DM患者血清CTRP9水平与BMI呈正相关[29]，肥胖患者肥胖外科手术治疗后CTRP9水平降低[30]。本研究也显示T2DM患者(NDR组和DR组)血清CTRP9水平与BMI呈正相关。这些研究结果提示血清CTRP9水平与机体肥胖状态有关。CTRP9对糖代谢和胰岛素敏感性的有利作用已被证实，流行病学调查研究显示血清CTRP9水平与糖代谢参数呈正相关。Jung、Moradi等[29]研究显示T2DM患者血清CTRP9水平与HOMA-IR呈正相关。Jia等[31]研究显示新诊断的T2DM患者及糖耐量异常患者血清CTRP9水平较糖耐量正常受试者显著升高，且血清CTRP9水平与HOMA-IR呈正相关。脂联素具有增加胰岛素敏感性，抗炎，抗新生血管化等作用，并与CTRP9[32]形成异源二聚体，T2DM患者血清CTRP9水平与血清脂联素呈负相关，提示CTRP9水平的升高可能是脂联素水平降低的代偿反应[33]。体内、外实验研究证实CTRP9对血管内皮细胞具有保护，T2DM患者血清CTRP9水平与脉搏波速度呈负相关，脉搏波速度是反应动脉粥样硬化的指标[29]。Moradi等[33]研究显示T2DM患者血清CTRP9水平与血清粘附分子、IL-6及TNF-α水平呈正相关。鉴于CTRP9具有改善胰岛素敏感性、抗炎和保护血管内皮的作用，本研究T2DM并发DR患者血清CTRP9水平升高可能是机体对胰岛素抵抗、微血管炎症损伤的代偿反应[26-28]。

此外，通过查阅文献，至目前为止，我们只发现一项关于血清CTRP9水平与DR关系的研究，王欣荣等研究显示随着血清CTRP9水平降低，DR患病风险显著增加，与本研究的结果相反。导致这些差异结果的原因尚不清楚，可能是由于研究对象的纳排标准不同所致。且王欣荣等的研究，其研究对象样本例数较少，其中无DR的T2DM患者(n=50)及DR患者(n=60)[34]。

本研究为单中心、小样本、横断面研究，尚需多中心、大样本和前瞻性队列研究加以证实。此外，本研究纳入的T2DM患者，未排除降血糖、降血压及降血脂药物对CTRP9的影响，这些药物是否对CTRP9产生影响目前尚不清楚。

综上所述，本研究发现血清CTRP9浓度与T2DM并发DR呈显著正相关，提示CTRP9可能是糖尿病视网膜微血管病变的代偿反应，有必要进一步研究CTRP9在DR中的分子作用机制。

Biography

周鹏鹏，博士研究生，副主任中医师，E-mail: 13584939429@139.com

Funding Statement

国家自然科学基金(81774419)；昆山社会发展科技专项(KS1932)

Supported by National Natural Science Foundation of China (81774419)

Contributor Information

周 鹏鹏 (Pengpeng ZHOU), Email: 13584939429@139.com.

高 卫萍 (Weiping GAO), Email: Gaoweiping@163.com.

References

  • 1.Semeraro F, Morescalchi F, Cancarini A, et al. Diabetic retinopathy, a vascular and inflammatory disease: Therapeutic implications. Diabetes Metab. 2019;45(6):517–27. doi: 10.1016/j.diabet.2019.04.002. [Semeraro F, Morescalchi F, Cancarini A, et al. Diabetic retinopathy, a vascular and inflammatory disease: Therapeutic implications[J]. Diabetes Metab, 2019, 45(6): 517-27.] [DOI] [PubMed] [Google Scholar]
  • 2.Roy S, Kern TS, Song B, et al. Mechanistic insights into pathological changes in the diabetic retina: implications for targeting diabetic retinopathy. Am J Pathol. 2017;187(1):9–19. doi: 10.1016/j.ajpath.2016.08.022. [Roy S, Kern TS, Song B, et al. Mechanistic insights into pathological changes in the diabetic retina: implications for targeting diabetic retinopathy[J]. Am J Pathol, 2017, 187(1): 9-19.] [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3.Sorrentino FS, Matteini S, Bonifazzi C, et al. Diabetic retinopathy and endothelin system: microangiopathy versus endothelial dysfunction. Eye: Lond. 2018;32(7):1157–63. doi: 10.1038/s41433-018-0032-4. [Sorrentino FS, Matteini S, Bonifazzi C, et al. Diabetic retinopathy and endothelin system: microangiopathy versus endothelial dysfunction[J]. Eye: Lond, 2018, 32(7): 1157-63.] [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 4.Wong GW, Krawczyk SA, Kitidis-Mitrokostas C, et al. Identification and characterization of CTRP9, a novel secreted glycoprotein, from adipose tissue that reduces serum glucose in mice and forms heterotrimers with adiponectin. FASEB J. 2009;23(1):241–58. doi: 10.1096/fj.08-114991. [Wong GW, Krawczyk SA, Kitidis-Mitrokostas C, et al. Identification and characterization of CTRP9, a novel secreted glycoprotein, from adipose tissue that reduces serum glucose in mice and forms heterotrimers with adiponectin[J]. FASEB J, 2009, 23(1): 241-58.] [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5.Li J, Zhang P, Li TT, et al. CTRP9 enhances carotid plaque stability by reducing pro- inflammatory cytokines in macrophages. Biochem Biophys Res Commun. 2015;458(4):890–5. doi: 10.1016/j.bbrc.2015.02.054. [Li J, Zhang P, Li TT, et al. CTRP9 enhances carotid plaque stability by reducing pro- inflammatory cytokines in macrophages[J]. Biochem Biophys Res Commun, 2015, 458(4): 890-5.] [DOI] [PubMed] [Google Scholar]
  • 6.Sun HJ, Zhu XX, Zhou YT, et al. C1q/TNF-related protein-9 ameliorates ox-LDL-induced endothelial dysfunction via PGC-1α/ AMPK-mediated antioxidant enzyme induction. Int J Mol Sci. 2017;18(6):E1097. doi: 10.3390/ijms18061097. [Sun HJ, Zhu XX, Zhou YT, et al. C1q/TNF-related protein-9 ameliorates ox-LDL-induced endothelial dysfunction via PGC-1α/ AMPK-mediated antioxidant enzyme induction[J]. Int J Mol Sci, 2017, 18(6): E1097.] [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7.Zhang P, Huang CM, Li J, et al. Globular CTRP9 inhibits oxLDLinduced inflammatory response in RAW 264.7 macrophages via AMPK activation. http://smartsearch.nstl.gov.cn/paper_detail.html?id=150c8527695d543c4634a85470f5dc00. Mol Cell Biochem. 2016;417(1/2):67–74. doi: 10.1007/s11010-016-2714-1. [Zhang P, Huang CM, Li J, et al. Globular CTRP9 inhibits oxLDLinduced inflammatory response in RAW 264.7 macrophages via AMPK activation[J]. Mol Cell Biochem, 2016, 417(1/2): 67-74.] [DOI] [PubMed] [Google Scholar]
  • 8.Zhang H, Gong XY, Ni SM, et al. C1q/TNF-related protein-9 attenuates atherosclerosis through AMPK-NLRP3 inflammasome singling pathway. Int Immunopharmacol. 2019;77:105934. doi: 10.1016/j.intimp.2019.105934. [Zhang H, Gong XY, Ni SM, et al. C1q/TNF-related protein-9 attenuates atherosclerosis through AMPK-NLRP3 inflammasome singling pathway[J]. Int Immunopharmacol, 2019, 77: 105934.] [DOI] [PubMed] [Google Scholar]
  • 9.Han F, Zhang Y, Shao M, et al. C1q/TNF-related protein 9 improves the anti-contractile effects of perivascular adipose tissue via the AMPK-eNOS pathway in diet-induced obese mice. Clin Exp Pharmacol Physiol. 2018;45(1):50–57. doi: 10.1111/1440-1681.12851. [Han F, Zhang Y, Shao M, et al. C1q/TNF-related protein 9 improves the anti-contractile effects of perivascular adipose tissue via the AMPK-eNOS pathway in diet-induced obese mice. Clin Exp Pharmacol Physiol, 2018, 45(1): 50-57.] [DOI] [PubMed] [Google Scholar]
  • 10.Peterson JM, Wei Z, Seldin MM, et al. CTRP9 transgenic mice are protected from diet-induced obesity and metabolic dysfunction. Am J Physiol Regul Integr Comp Physiol. 2013;305(5):R522–33. doi: 10.1152/ajpregu.00110.2013. [Peterson JM, Wei Z, Seldin MM, et al. CTRP9 transgenic mice are protected from diet-induced obesity and metabolic dysfunction[J]. Am J Physiol Regul Integr Comp Physiol, 2013, 305(5): R522-33.] [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11.Wei ZK, Lei X, Petersen PS, et al. Targeted deletion of C1q/TNFrelated protein 9 increases food intake, decreases insulin sensitivity, and promotes hepatic steatosis in mice. Am J Physiol Endocrinol Metab. 2014;306(7):E779–90. doi: 10.1152/ajpendo.00593.2013. [Wei ZK, Lei X, Petersen PS, et al. Targeted deletion of C1q/TNFrelated protein 9 increases food intake, decreases insulin sensitivity, and promotes hepatic steatosis in mice[J]. Am J Physiol Endocrinol Metab, 2014, 306(7): E779-90.] [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 12.Jung TW, Hong HC, Hwang HJ, et al. C1q/TNF-Related Protein 9 (CTRP9) attenuates hepatic steatosis via the autophagy-mediated inhibition of endoplasmic Reticulum stress. Mol Cell Endocrinol. 2015;417:131–40. doi: 10.1016/j.mce.2015.09.027. [Jung TW, Hong HC, Hwang HJ, et al. C1q/TNF-Related Protein 9 (CTRP9) attenuates hepatic steatosis via the autophagy-mediated inhibition of endoplasmic Reticulum stress[J]. Mol Cell Endocrinol, 2015, 417: 131-40.] [DOI] [PubMed] [Google Scholar]
  • 13.Li Y, Geng X, Wang H, et al. CTRP9 Ameliorates Pulmonary Arterial Hypertension Through Attenuating Inflammation and Improving Endothelial Cell Survival and Function. J Cardiovasc Pharmacol. 2016;67(5):394–401. doi: 10.1097/FJC.0000000000000364. [Li Y, Geng X, Wang H, et al. CTRP9 Ameliorates Pulmonary Arterial Hypertension Through Attenuating Inflammation and Improving Endothelial Cell Survival and Function. J Cardiovasc Pharmacol, 2016, 67(5): 394-401.] [DOI] [PubMed] [Google Scholar]
  • 14.Li W, Ma N, Liu MX, et al. C1q/TNF-related protein-9 attenuates retinal inflammation and protects blood-retinal barrier in db/db mice. Eur J Pharmacol. 2019;853:289–98. doi: 10.1016/j.ejphar.2019.04.012. [Li W, Ma N, Liu MX, et al. C1q/TNF-related protein-9 attenuates retinal inflammation and protects blood-retinal barrier in db/db mice [J]. Eur J Pharmacol, 2019, 853: 289-98.] [DOI] [PubMed] [Google Scholar]
  • 15.Wilkinson CP, Ferris FL 3rd, Klein RE, et al. Proposed international clinical diabetic retinopathy and diabetic macular edema disease severity scales. Ophthalmology. 2003;110(9):1677–82. doi: 10.1016/S0161-6420(03)00475-5. [Wilkinson CP, Ferris FL 3rd, Klein RE, et al. Proposed international clinical diabetic retinopathy and diabetic macular edema disease severity scales[J]. Ophthalmology, 2003, 110(9): 1677-82.] [DOI] [PubMed] [Google Scholar]
  • 16.Barrett EJ, Liu ZQ, Khamaisi M, et al. Diabetic microvascular disease: an endocrine society scientific statement. http://www.ncbi.nlm.nih.gov/pubmed/29126250. J Clin Endocrinol Metab. 2017;102(12):4343–410. doi: 10.1210/jc.2017-01922. [Barrett EJ, Liu ZQ, Khamaisi M, et al. Diabetic microvascular disease: an endocrine society scientific statement[J]. J Clin Endocrinol Metab, 2017, 102(12): 4343-410.] [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 17.Wong TY, Cheung CM, Larsen M, et al. Diabetic retinopathy. Nat Rev Dis Primers. 2016;2:16012. doi: 10.1038/nrdp.2016.12. [Wong TY, Cheung CM, Larsen M, et al. Diabetic retinopathy. Nat Rev Dis Primers[J]. 2016, 2: 16012.] [DOI] [PubMed] [Google Scholar]
  • 18.Lechner J, O'Leary OE, Stitt AW. The pathology associated with diabetic retinopathy. Vision Res. 2017;139:7–14. doi: 10.1016/j.visres.2017.04.003. [Lechner J, O'Leary OE, Stitt AW. The pathology associated with diabetic retinopathy[J]. Vision Res, 2017, 139: 7-14.] [DOI] [PubMed] [Google Scholar]
  • 19.Wang W, Lo ACY. Diabetic retinopathy: pathophysiology and treatments. Int J Mol Sci. 2018;19(6):E1816. doi: 10.3390/ijms19061816. [Wang W, Lo ACY. Diabetic retinopathy: pathophysiology and treatments[J]. Int J Mol Sci, 2018, 19(6): E1816.] [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 20.Capitão M, Soares R. Angiogenesis and inflammation crosstalk in diabetic retinopathy. J Cell Biochem. 2016;117(11):2443–53. doi: 10.1002/jcb.25575. [Capitão M, Soares R. Angiogenesis and inflammation crosstalk in diabetic retinopathy[J]. J Cell Biochem, 2016, 117(11): 2443-53.] [DOI] [PubMed] [Google Scholar]
  • 21.Rübsam A, Parikh S, Fort PE. Role of inflammation in diabetic retinopathy. Int J Mol Sci. 2018;19(4):E942. doi: 10.3390/ijms19040942. [Rübsam A, Parikh S, Fort PE. Role of inflammation in diabetic retinopathy[J]. Int J Mol Sci, 2018, 19(4): E942.] [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 22.Mbata O, Abo El-Magd NF, El-Remessy AB. Obesity, metabolic syndrome and diabetic retinopathy: Beyond hyperglycemia. World J Diabetes. 2017;8(7):317–29. doi: 10.4239/wjd.v8.i7.317. [Mbata O, Abo El-Magd NF, El-Remessy AB. Obesity, metabolic syndrome and diabetic retinopathy: Beyond hyperglycemia[J]. World J Diabetes, 2017, 8(7): 317-29.] [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23.Hammer SS, Busik JV. The role of dyslipidemia in diabetic retinopathy. Vision Res. 2017;139:228–36. doi: 10.1007/s13300-017-0240-0. [Hammer SS, Busik JV. The role of dyslipidemia in diabetic retinopathy[J]. Vision Res, 2017, 139: 228-36.] [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 24.Si Y, Fan W, Sun L. A review of the relationship between CTRP family and coronary artery disease. Curr Atheroscler Rep. 2020;22(6):22. doi: 10.1007/s11883-020-00840-0. [Si Y, Fan W, Sun L. A review of the relationship between CTRP family and coronary artery disease[J]. Curr Atheroscler Rep, 2020, 22(6): 22.] [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 25.Jung CH, Lee MJ, Kang YM, et al. C1q/TNF-related protein-9 inhibits cytokine-induced vascular inflammation and leukocyte adhesiveness via AMP-activated protein kinase activation in endothelial cells. Mol Cell Endocrinol. 2016;419:235–43. doi: 10.1016/j.mce.2015.10.023. [Jung CH, Lee MJ, Kang YM, et al. C1q/TNF-related protein-9 inhibits cytokine-induced vascular inflammation and leukocyte adhesiveness via AMP-activated protein kinase activation in endothelial cells[J]. Mol Cell Endocrinol, 2016, 419: 235-43.] [DOI] [PubMed] [Google Scholar]
  • 26.Yilmaz MI, Sonmez A, Acikel C, et al. Adiponectin may play a part in the pathogenesis of diabetic retinopathy. http://europepmc.org/abstract/MED/15248834. Eur J Endocrinol. 2004;151(1):135–40. doi: 10.1530/eje.0.1510135. [Yilmaz MI, Sonmez A, Acikel C, et al. Adiponectin may play a part in the pathogenesis of diabetic retinopathy[J]. Eur J Endocrinol, 2004, 151(1): 135-40.] [DOI] [PubMed] [Google Scholar]
  • 27.Fan XH, Wu QH, Li Y, et al. Association between adiponectin concentrations and diabetic retinopathy in patients with type 2 diabetes: a meta analysis. http://europepmc.org/abstract/MED/24534238. Chin Med J. 2014;127(4):765–71. [Fan XH, Wu QH, Li Y, et al. Association between adiponectin concentrations and diabetic retinopathy in patients with type 2 diabetes: a meta analysis[J]. Chin Med J, 2014, 127(4). 765-71.] [PubMed] [Google Scholar]
  • 28.Song J, Chen S, Liu XT, et al. Relationship between C-reactive protein level and diabetic retinopathy: a systematic review and metaanalysis. http://pubmedcentralcanada.ca/pmcc/articles/PMC4670229/ PLoS One. 2015;10(12):e0144406. doi: 10.1371/journal.pone.0144406. [Song J, Chen S, Liu XT, et al. Relationship between C-reactive protein level and diabetic retinopathy: a systematic review and metaanalysis[J]. PLoS One, 2015, 10(12): e0144406.] [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 29.Jung CH, Lee MJ, Kang YM, et al. Association of serum C1q/TNFrelated protein-9 concentration with arterial stiffness in subjects with type 2 diabetes. http://www.ncbi.nlm.nih.gov/pubmed/25105737. J Clin Endocrinol Metab. 2014;99(12):E2477–84. doi: 10.1210/jc.2014-2524. [Jung CH, Lee MJ, Kang YM, et al. Association of serum C1q/TNFrelated protein-9 concentration with arterial stiffness in subjects with type 2 diabetes[J]. J Clin Endocrinol Metab, 2014, 99(12): E2477- 84.] [DOI] [PubMed] [Google Scholar]
  • 30.Wolf RM, Steele KE, Peterson LA, et al. C1q/TNF-related protein-9 (CTRP9) levels are associated with obesity and decrease following weight loss surgery. http://www.ncbi.nlm.nih.gov/pubmed/26982010. J Clin Endocrinol Metab. 2016;101(5):2211–217. doi: 10.1210/jc.2016-1027. [Wolf RM, Steele KE, Peterson LA, et al. C1q/TNF-related protein-9 (CTRP9) levels are associated with obesity and decrease following weight loss surgery[J]. J Clin Endocrinol Metab, 2016, 101(5): 2211- 217.] [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 31.Jia Y, Luo X, Ji Y, et al. Circulating CTRP9 levels are increased in patients with newly diagnosed type 2 diabetes and correlated with insulin resistance. http://www.ncbi.nlm.nih.gov/pubmed/28743061. Diabetes Res Clin Pract. 2017;131:116–23. doi: 10.1016/j.diabres.2017.07.003. [Jia Y, Luo X, Ji Y, et al. Circulating CTRP9 levels are increased in patients with newly diagnosed type 2 diabetes and correlated with insulin resistance[J]. Diabetes Res Clin Pract, 2017, 131: 116-23.] [DOI] [PubMed] [Google Scholar]
  • 32.Wong GW, Krawczyk SA, Kitidis-Mitrokostas C, et al. Identification and characterization of CTRP9, a novel secreted glycoprotein, from adipose tissue that reduces serum glucose in mice and forms heterotrimers with adiponectin. http://europepmc.org/articles/PMC2626616/ FASEB J. 2009;23(1):241–58. doi: 10.1096/fj.08-114991. [Wong GW, Krawczyk SA, Kitidis-Mitrokostas C, et al. Identification and characterization of CTRP9, a novel secreted glycoprotein, from adipose tissue that reduces serum glucose in mice and forms heterotrimers with adiponectin[J]. FASEB J, 2009, 23(1): 241-58.] [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 33.Moradi N, Fadaei R, Emamgholipour S, et al. Association of circulating CTRP9 with soluble adhesion molecules and inflammatory markers in patients with type 2 diabetes mellitus and coronary artery disease. http://europepmc.org/articles/PMC5790264/ PLoS One. 2018;13(1):e0192159. doi: 10.1371/journal.pone.0192159. [Moradi N, Fadaei R, Emamgholipour S, et al. Association of circulating CTRP9 with soluble adhesion molecules and inflammatory markers in patients with type 2 diabetes mellitus and coronary artery disease[J]. PLoS One, 2018, 13(1): e0192159.] [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 34.王 欣荣, 吕 伯昌, 李 海燕. 血清补体C1q肿瘤坏死因子相关蛋白3、补体C1q肿瘤坏死因子相关蛋白9水平对糖尿病视网膜病变患者的影响及相关性研究. https://www.cnki.com.cn/Article/CJFDTOTAL-YYCY201526004.htm. 中国医药导报. 2015;12(26):8–11. [王欣荣, 吕伯昌, 李海燕. 血清补体C1q肿瘤坏死因子相关蛋白3、补体C1q肿瘤坏死因子相关蛋白9水平对糖尿病视网膜病变患者的影响及相关性研究[J]. 中国医药导报, 2015, 12(26): 8-11.] [Google Scholar]

Articles from Journal of Southern Medical University are provided here courtesy of Editorial Department of Journal of Southern Medical University

RESOURCES