血清肿瘤坏死因子-α、血管内皮生长因子与糖尿病视网膜病变

目的:探讨血清肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、血管内皮生长因子(vascular endothelial growth factor,VEGF)水平与糖尿病视网膜病变的关系。方法:将108例糖尿病患者分为糖尿病视网膜病变组(DR,60例)、非糖尿病视网膜病变组(NDR,48例),DR组又分为非增生性糖尿病视网膜病变亚组(NPDR,34例)、增生性糖尿病视网膜病变亚组(PDR,26例)。健康对照组40例。采用ELISA法检测血清TNF-α和VEGF水平,分析对比。结果:糖尿病患者血清TNF-α和VEGF水平与健康对照组比较,有显著性差异(P<0.01)。DR组血清TNF-α和VEGF水平显著高于NDR组(P<0.01);PDR组血清TNF-α和VEGF水平显著高于NPDR组(P<0.05)。结论:血清TNF-α和VEGF可能参与了DR的发生、发展,血清TNF-α、VEGF水平可反映DR病情严重程度。     

趋化素、肿瘤坏死因子-α与2型糖尿病视网膜病变的相关性

目的　探讨２型糖尿病视网膜病变（ｔｙｐｅ２ｄｉａｂｅｔｉｃｒｅｔｉｎｏｐａｔｈｙ,Ｔ２ＤＲ）患者血清中趋化素（ｃｈｅｍｅｒｉｎ）、肿瘤坏死因子-α（ｔｕｍｏｒｎｅｃｒｏｓｉｓｆａｃｔｏｒ-α,ＴＮＦ-α）水平及其临床意义。方法　将１６０例研究对象分为增殖性糖尿病视网膜病变（ｐｒｏｌｉｆｅｒａｔｉｖｅｄｉａ-ｂｅｔｉｃｒｅｔｉｎｏｐａｔｈｙ,ＰＤＲ）组４０例,非增殖性糖尿病视网膜病变（ｎｏｎ-ｐｒｏｌｉｆｅｒａｔｉｖｅｄｉａｂｅｔｉｃｒｅｔｉｎｏｐａｔｈｙ,ＮＰＤＲ）组４０例,单纯糖尿病（ｄｉａｂｅｔｅｓｍｅｌｌｉｔｕｓ,ＤＭ）组患者４０例以及健康对照（ｎｏｒｍａｌｃｏｎｔｒｏｌｓ,ＮＣ）组４０例。观察４组研究对象的体检指标,并检测空腹胰岛素、血糖、血脂、糖化血红蛋白及血清中ｃｈｅｍｅｒｉｎ、ＴＮＦ-α等含量。计算稳态模型评估的胰岛素抵抗指数（ｉｎｓｕｌｉｎｒｅｓｉｓｔａｎｃｅｉｎ-ｄｅｘ,ＨＯＭＡ-ＩＲ）。结果　ＤＭ组［ｃｈｅｍｅｒｉｎ为（３．８３±０．４６）ｍｇ?Ｌ－１、ＴＮＦ-α为（３７．６９±５．０７）ｎｇ?Ｌ－１］、ＮＰＤＲ组［ｃｈｅｍｅｒｉｎ为（４．６８±０．７４）ｍｇ?Ｌ－１、ＴＮＦ-α为（４０．６９±５．９０）ｎｇ?Ｌ－１］、ＰＤＲ组［ｃｈｅｍｅｒｉｎ为（５．８６±１．２９）ｍｇ?Ｌ－１、ＴＮＦ-α为（４４．１７±６．６３）ｎｇ?Ｌ－１］血清中ｃｈｅｍｅｒｉｎ、ＴＮＦ-α水平均较ＮＣ组［ｃｈｅｍｅｒｉｎ为（２．０１±０．５４）ｍｇ?Ｌ－１、ＴＮＦ-α为（２２．６０±９．７８）ｎｇ?Ｌ－１］升高,且随着ＤＲ病情的进展逐渐升高,差异均有统计学意义（均为Ｐ＜０．０５）。相关分析显示血清中ｃｈｅｍｅｒｉｎ水平与收缩压、空腹血糖、甘油三酯、总胆固醇、低密度脂蛋白胆固醇、糖化血红蛋白、胰岛素抵抗指数均呈正相关（ｒ＝０．３３１、０．３６１、０．２５１、０．３４８、０．３０６、０．５２３、０．６４４,均为Ｐ＜０．０５）;血清中ＴＮＦ-α水平与收缩压、舒张压、空腹血糖、甘油三酯、总胆固醇、低密度脂蛋白胆固醇、糖化血红蛋白、胰岛素抵抗指数均呈正相关（ｒ＝０．２９９、０．１５９、０．６０５、０．２６２、０．４０７、０．２８２、０．６１９、０．８０９,均为Ｐ＜０．０５）;血清中ｃｈｅｍｅｒｉｎ与ＴＮＦ-α水平呈正相关（ｒ＝０．７３８,Ｐ＜０．０５）。结论　血清中ｃｈｅｍｅｒｉｎ和ＴＮＦ-α水平的升高是Ｔ２ＤＲ的危险因子,可能共同参与了Ｔ２ＤＲ的发生发展。     

糖尿病视网膜病变患者玻璃体样本中白细胞介素-8和肿瘤坏死因子-α水平

目的:测量糖尿病性视网膜病变(DR)行玻璃体切除术(PPV)患者玻璃体样品中白细胞介素-8(IL-8),肿瘤坏死因子-α(TNF-α)的水平,与对照组比较结果并探讨其对DR的影响。方法:将伊斯坦布尔Bilim大学眼科系的57例(57眼)DR患者和22例黄斑裂孔未伴有增生性玻璃体视网膜病变患者分为研究组和对照组。对所有79例患者行3切口,20G PPV。PPV手术眼内灌注前,用Vitrector抽吸0.5mL玻璃体样品并稀释。样品转至冷藏室,存放在-70℃。IL-8和TNF-α的测量结果用酶联免疫吸附法以pg/mL为单位计算。结果:DR患者玻璃体样本中IL-8水平[82.7891±74.08700(0.08-307.09)pg/mL]明显高于对照组患者[2.9805±3.77546(0.08-18.53)pg/mL](P<0.001)。同样,DR患者TNF-α水平[18.0007±13.90015(2.32-51.11)pg/mL]也显着高于对照组[1.7005±1.26949(0.1-5.17)pg/mL](P<0.001)。结论:在视网膜新生血管形成中起重要作用的TNF-α和作为炎症和血管生成介体的IL-8水平在DR患者玻璃体样本中明显高。     

血清中血管内皮生长因子、白细胞介素-2及肿瘤坏死因子α在糖尿病视网膜病变中的作用

背景糖尿病视网膜病变（DR）是一种严重的糖尿病并发症,其确切的发病机制尚不清楚,有研究认为细胞因子增加单核细胞和内皮细胞黏附的过程,进而引起视网膜毛细血管炎症反应是DR发生发展的关键因素。目的检测2型DR患者血清中血管内皮生长因子（VEGF）、白细胞介素-2（IL-2）、肿瘤坏死因子α（TNF—α）的质量浓度,并探讨其临床意义。方法采用前瞻性病例对照研究设计。对90例2型糖尿病患者血清中VEGF、IL-2和TNF-α的质量浓度采用双抗体夹心ELISA法进行检测。根据散瞳后眼底检查和荧光素眼底血管造影（FFA）检查,将实验组分为无DR组30例、单纯性DR组30例、增生型糖尿病视网膜病变（PDR）组30例,对照组为健康体检者30名。结果无DR组、单纯性DR组、PDR组血清中VEGF的质量浓度为（217．35±27．87）、（298．31±49．26）、（341．23±40．18）ng／L,IL-2的质量浓度为（12．12±1．57）、（16．43±2．26）、（21．36±0．86）ng／L,TNF-α的质量浓度为（11．63±0．94）、（17．52±0．65）、（22．01±0．87）ng／L,与对照组VEGF、IL-2和TNF—α的质量浓度（193．46±37．39）、（8．99±0．57）、（7．31±0．52）ng／L比较,4个组间差异均有统计学意义（F=126．380,P〈0．01;F=120．370,P〈0．01;F=99．840,P〈0．01）。对照组、无DR组、单纯性DR组与PDR组血清VEGF、IL-2、TNF—α的质量浓度有依次增加的趋势。各组患者血清中的VEGF、IL-2、TNF—α质量浓度间存在正相关关系（r=0．749,P〈0．01;r=0．631,P〈0．01）。无DR组、单纯性DR组、PDR组间病程比较差异有统计学意义,且有明显增加的趋势（F=137．230,P〈0．01）;各DR组血清中VEGF、IL-2、TNF-α质量浓度组与病程均呈正相关（r=0．791,P〈0．01;r=0．665,P〈0．01;r=0．632,P〈0．01）。结论VEGF、IL-2及TNF-α存DR的发病和进展过程中起重要作用。     

肿瘤坏死因子基因多态性与糖尿病视网膜病变关系的研究进展

糖尿病视网膜病变（ｄｉａｂｅｔｉｃｒｅｔｉｎｏｐａｔｈｙ,ＤＲ）是糖尿病最常见的的微血管并发症之一,是糖尿病患者视功能损害的根本原因。然而,其机制尚未完全明了。目前,ＤＲ被认为是一种受基因多态性影响的炎性疾病,肿瘤坏死因子是主要的炎症细胞因子之一,本文就肿瘤坏死因子的功能及其基因多态性与ＤＲ之间可能的关系作一综述。     

肿瘤坏死因子-α、脂联素与糖尿病视网膜病变的关系

近年来，细胞因子与糖尿病视网膜病变（DR）的关系日益受到关注。研究发现肿瘤坏死因子-α（TNF-α）和脂联素与DR的发生发展有关。我们通过测定糖尿病大鼠不同时期血清TNF-α和脂联素水平并观察其在视网膜组织局部的表达，探讨二者在DR发病中的作用及其存在的相互关系。     

血清Leptin和TNF-α与2型糖尿病视网膜病变的相关关系研究

目的 探讨血清中瘦素(Leptin)、肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)的水平与2型糖尿病视网膜病变发生发展之间的关系.方法 对88例2型糖尿病患者(按照糖尿病视网膜病变分级标准,再将其分为3个亚组)及30例健康对照者,采用放射免疫法测定血清中Leptin和TNF-α,免疫抑制比浊法测定糖化血红蛋白,记录相关的临床和生化指标.结果 2型糖尿病视网膜病变组患者血清Leptin水平(10.57±1.84)μg·L-1显著高于无视网膜病变组的(7.90±1.58)μg·L-1(P<0.01);增生性糖尿病视网膜病变组血清Leptin水平(11.66±1.21)μg·L-1显著高于非增生性糖尿病视网膜病变组的(9.56±1.75)μg·L-1(P<0.01)及无视网膜病变组的(7.90±1.58)μg·L-1(P<0.01).2型糖尿病视网膜病变组患者血清TNF-α水平(60.45±13.33)pmol·L-1显著高于无视网膜病变组的(39.97±8.38)pmol·L-1(P<0.01);增生性糖尿病视网膜病变组血清TNF-α水平(69.93±10.86)pmol·L-1显著高于非增生性糖尿病视网膜病变组的(51.60±8.47)pmol·L-1(P<0.01)及无视网膜病变组(39.97±8.38)pmol·L-1(P<0.01).血清Leptin水平与病程、糖化血红蛋白、体质量指数成正相关(r=0.639,P<0.01;r=0.260,P<0.05;r=0.468,P<0.01);血清TNF-α与病程、空腹血糖、体质量指数成正相关(r=0.680、0.355、0.299,P<0.01),与收缩压、舒张压成正相关(r=0.281、0.234,P<0.05),与高密度脂蛋白胆固醇成负相关(r=-0.423,P<0.01).血清Leptin、TNF-α水平成正相关(r=0.660,P<0.05).结论 2型糖尿病合并糖尿病视网膜病变患者血清Leptin、TNF-α水平增高;随着糖尿病视网膜病变程度的加重,血清中的Leptin、TNF-α水平也逐渐升高,提示其与糖尿病视网膜病变,特别是糖尿病视网膜痛变的严重程度相关.     

血清可溶性肿瘤坏死因子受体与2型糖尿病视网膜病变相关性研究

目的　研究血清可溶性肿瘤坏死因子受体（ｓｏｌｕｂｌｅｔｕｍｏｒｎｅｃｒｏｓｉｓｆａｃｔｏｒｒｅｃｅｐｔｏｒ,ｓＴＮＦＲ）与２型糖尿病视网膜病变的相关性。方法　６６例２型糖尿病患者通过眼底检查和眼底荧光血管造影按照ＥＤＴＲＳ分期分为３组:无糖尿病视网膜病变（ｎｏｄｉａｂｅｔｉｃｒｅｔｉｎｏｐａｔｈｙ,ＮＤＲ;ｎ＝２２）组、非增殖型糖尿病视网膜病变（ｎｏｎｐｒｏｌｉｆｅｒａｔｉｖｅｄｉａｂｅｔｉｃｒｅｔｉｎｏｐａｔｈｙ,ＮＰＤＲ;ｎ＝２４）组和增殖型糖尿病视网膜病变（ｐｒｏｌｉｆｅｒａｔｉｖｅｄｉａｂｅｔｉｃｒｅｔｉｎｏｐａｔｈｙ,ＰＤＲ;ｎ＝２０）组。２１名健康人作为对照组。检测４组研究对象血清中肿瘤坏死因子（ｔｕｍｏｒｎｅｃｒｏｓｉｓｆａｃｔｏｒ,ＴＮＦ）-α、ｓＴＮＦＲ-１、ｓＴＮＦＲ-２水平。组间统计分析采用非参数Ｍａｎｎ-ＷｈｉｔｎｅｙＵ检验。结果　血清中ＴＮＦ-α中位数分别为:对照组０ｐｇ·ｍＬ－１、ＮＤＲ组３．４５ｐｇ·ｍＬ－１、ＮＰＤＲ组３．９２ｐｇ·ｍＬ－１、ＰＤＲ组８．１２ｐｇ·ｍＬ－１。对照组与ＰＤＲ组（Ｐ＜０．００１）、ＮＤＲ组与ＰＤＲ组（Ｐ＝０．００８）比较差异均有统计学意义。血清中ｓＴＮＦＲ-１水平中位数:对照组１．５０ｎｇ·ｍＬ－１、ＮＤＲ组１．８８ｎｇ·ｍＬ－１、ＮＰＤＲ组２．５８ｎｇ·ｍＬ－１、ＰＤＲ组３．００ｎｇ·ｍＬ－１。对照组与ＮＰＤＲ组（Ｐ＜０．００１）、对照组与ＰＤＲ组（Ｐ＜０．００１）、ＮＤＲ组与ＮＰＤＲ组（Ｐ＝０．００７）、ＮＤＲ组与ＰＤＲ组（Ｐ＜０．００１）比较,差异均有统计学意义。血清中ｓＴ-ＮＦＲ-２中位数分别为:对照组３．８８ｎｇ·ｍＬ－１、ＮＤＲ组５．０１ｎｇ·ｍＬ－１、ＮＰＤＲ组５．２１ｎｇ·ｍＬ－１、ＰＤＲ组６．３３ｎｇ·ｍＬ－１。除了ＮＤＲ组与ＮＰＤＲ组（Ｐ＝０．０７０）间差异无统计学意义外,其他组间差异均有统计学意义（均为Ｐ＜０．０５）。结论　血清中ｓＴＮＦＲ与２型糖尿病视网膜病变密切相关,表明ｓＴＮＦＲ在糖尿病视网膜病变的发生发展中起到了一定的作用。对ｓＴＮＦＲ进行进一步研究可以寻找治疗糖尿病视网膜病变新的靶点。     

β-榄香烯对糖尿病大鼠视网膜中肿瘤坏死因子-α表达的影响

目的　探讨β-榄香烯对糖尿病大鼠视网膜肿瘤坏死因子-α（ｔｕｍｏｒｎｅｃｒｏｓｉｓｆａｃｔｏｒ-α,ＴＮＦ-α）表达的影响。方法　１０周龄ＳＤ大鼠３６只,随机分为６组,除Ａ组（每只大鼠腹腔注射等量的柠檬酸钠缓冲液）外其余组腹腔注射链脲佐菌素（ｓｔｒｅｐｔｏｚｏｔｏｃｉｎ,ＳＴＺ）制成糖尿病大鼠模型,成模６周后,Ｃ组每只大鼠双眼球周给予空白乳剂５μＬ,Ｄ组双眼球周给予β-榄香烯５μＬ,Ｅ组每只大鼠同时双眼球内给予空白乳剂５μＬ,Ｆ组双眼球内给予β-榄香烯５μＬ,Ｂ组未采取局部注射作为对照。末次给药４８ｈ后处死大鼠,取眼球固定视网膜行免疫组织化学法检测视网膜中ＴＮＦ-α的表达情况;提取视网膜蛋白,采用ＷｅｓｔｅｒｎＢｌｏｔ检测ＴＮＦ-α蛋白的表达情况。结果　免疫组织化学法检测结果显示:Ａ组视网膜未见阳性染色,Ｂ组视网膜全层可见阳性表达,Ｃ组及Ｅ组阳性表达分布与Ｂ组相同,而Ｄ组及Ｆ组棕色阳性表达下降,其中Ｆ组更显著。ＷｅｓｔｅｒｎＢｌｏｔ检测结果显示:Ｃ组及Ｅ组ＴＮＦ-α蛋白的表达与Ａ组相比差异均无统计学意义（均为Ｐ＞０．０５）,Ｂ组较Ａ组增高（Ｐ＜０．０１）,而Ｄ组及Ｆ组表达与Ｂ组差异均有统计学意义（均为Ｐ＜０．０５）。结论　β-榄香烯球周及球内注射均可降低糖尿病大鼠视网膜内ＴＮＦ-α的表达,且眼内注射效果更好。     

米诺环素对糖尿病大鼠视网膜内肿瘤坏死因子-α表达的干预作用

糖尿病视网膜病变（DR）发病机制复杂，现有观点认为，炎症与免疫反应贯穿DR的全过程。有人提出DR是一种炎症性疾病。肿瘤坏死因子-α（TNF-α）就是炎症反应中最具代表性的细胞因子之一。国外研究表明米诺环素（minocycline）的作用可减少炎症介质的表达及糖尿病时视网膜内细胞凋亡的发生率。我们观察了米诺环素对糖尿病大鼠视网膜内TNF-α表达的干预作用，现将结果报告如下。     

Diabetic Retinopathy Risk Factors: Plasma Erythropoietin as a Risk Factor for Proliferative Diabetic Retinopathy

Purpose

The purpose of this study was to evaluate whether any stage of diabetic retinopathy (DR) is associated with levels of plasma erythropoietin and other plasma parameters.

Methods

It was examined a representative sample of 180 type 2 diabetes patients aged 40 to 79 years. Ophthalmic examination including a funduscopic examination, performed by an experienced ophthalmologist and the retinal finding were classified according to the grading system for diabetic retinopathy of ETDRS (Early Treatment Diabetic Retinopathy Study). It was measured the levels of plasma erythropoietin, cholesterol, triglyceride, apolipoproteins A and B, C-reactive protein, fasting blood glucose and hemoglobin A1C (HbA1C) in 88 DR patients and 92 controls without DR. Risk factors correlated with DR were compared between groups.

Results

The study group of 180 patients included 72 males and 108 females. The mean age of the patients with and without DR was 57.36 ± 8.87 years and 55.33 ± 8.28 years, respectively. Of the 88 patients with DR, only 9 (10%) had proliferative DR and the rest suffered from non-proliferative DR. The mean plasma levels of erythropoietin in proliferative DR group showed a significant difference in comparison to other groups. The mean plasma levels of cholesterol, triglyceride, apolipoproteins A and B, C-reactive protein, and fasting blood glucose were not significantly different in the three groups except for HbA1C. The absolute relative risk (ARR) also showed that erythropoietin was an increasing risk for proliferative DR (ARR, 1.17; 95% confidence interval, 1.060 to 1.420; odds ratio,1.060).

Conclusions

Of the factors studied, erythropoietin level showed significant increase in proliferative DR group. The stepwise raised in mean plasma erythropoietin level which demonstrates significant correlation with proliferative DR versus remaining two groups, will be an indication of its role in proliferative DR.     

Higher Serum Uric Acid Levels Are Associated With an Increased Risk of Vision-Threatening Diabetic Retinopathy in Type 2 Diabetes Patients

PurposeTo investigate the association between serum uric acid (SUA) levels and vision-threatening diabetic retinopathy (VTDR) in patients with type 2 diabetes.MethodsThis cross-sectional study evaluated 3481 patients with type 2 diabetes from four communities in China between 2016 and 2019. VTDR was defined as severe nonproliferative, proliferative diabetic retinopathy, or clinically significant macular edema evaluated by fundus photography and optical coherence tomography. Potential association between SUA and VTDR was examined using multivariable logistic regression. Sub-group analyses based on sex were constructed.ResultsA total of 305 participants had VTDR. Both higher SUA (odds ratio [OR], 1.22 per 100 µmol/L; 95% confidence interval [CI], 1.04–1.44; P = 0.013) and hyperuricemia (OR, 1.47; 95% CI, 1.07–2.04; P = 0.019) were positively associated with VTDR after adjustment for relevant covariates. Compared with those in the lowest SUA quartile, participants in the third (OR, 1.60; 95% CI, 1.07–2.39; P = 0.022) and fourth (OR, 2.05; 95% CI, 1.37–3.08; P = 0.001) sex-specific SUA quartiles showed a significantly increased risk of VTDR after adjustment. No sex-related difference was observed.ConclusionsHigher SUA levels were associated with an increased risk of VTDR in patients with type 2 diabetes in both sexes, although females seemed to be more sensitive to high SUA than males. Prospective cohort studies are needed to verify SUA as a biomarker for predicting the risk of VTDR. Whether decreased SUA levels could decrease the risk of VTDR also requires further investigation.     

Prevalence and Associated Factors of Diabetic Retinopathy among Type 2 Diabetes Mellitus Patients in Brunei Darussalam: A Cross-sectional Study

PurposeTo determine the prevalence of diabetic retinopathy (DR) and the factors associated with retinopathy among type 2 diabetes mellitus (DM) patients in Brunei Darussalam.MethodsCross-sectional study of all type 2 DM patients who attended diabetic eye screening over a 3-month period at one of four government hospitals. We assessed association between DR with the following variables: age, sex, glycated hemoglobin (HbA1c), duration of DM, hypertension, hyperlipidemia, and microalbuminuria.ResultsThere were 341 patients (female, 58.9%; mean age, 55.3 ± 11.9 years) with a mean duration of DM of 9.4 ± 7.4 years and mean serum HbA1c of 8.4% ± 1.9%. The overall prevalence of any DR was 22.6% (95% confidence interval, 18.8–27.1) with prevalence rates of 4.1% (95% confidence interval, 2.1–6.4) for proliferative DR and 9.7% (95% confidence interval, 6.8–13.2) for vision-threatening DR. Multivariate analysis showed that DR was significantly associated with certain age groups (reduced in older age groups), longer duration of DM (11 years or more), poor control (HbA1c >9.0%) and presence of any microalbuminuria.ConclusionsDR affects one in five patients with DM in Brunei Darussalam, comparable to rates reported for other Asian populations. It is especially worrying that one in ten patients with DM had vision-threatening DR. DR was significantly associated with longer duration of DM, poor control and presence of microalbuminuria but reduced in older age groups. It is important to advocate good control right from the time of diagnosis of DM and institute timely and effective management of retinopathy. DR was significantly associated with longer duration of DM, poor control of diabetes, and presence of microalbuminuria but reduced in older age groups.     

Risk Factors for Proliferative Diabetic Retinopathy in African Americans with Type 2 Diabetes

Purpose: To assess personal and demographic risk factors for proliferative diabetic retinopathy in African Americans with type 2 diabetes.

Methods: In this prospective, non-interventional, cross-sectional case-control study, 380 African Americans with type 2 diabetes were enrolled. Participants were recruited prospectively and had to have either: (1) absence of diabetic retinopathy after ≥10 years of type 2 diabetes, or (2) presence of proliferative diabetic retinopathy when enrolled. Dilated, 7-field fundus photographs were graded using the Early Treatment Diabetic Retinopathy Study scale. Covariates including hemoglobin A_1C (HbA_1C), blood pressure, height, weight and waist circumference were collected prospectively. Multivariate regression models adjusted for age, sex and site were constructed to assess associations between risk factors and proliferative diabetic retinopathy.

Results: Proliferative diabetic retinopathy was associated with longer duration of diabetes (odds ratio, OR, 1.62, p < 0.001), higher systolic blood pressure (OR 1.65, p < 0.001) and insulin use (OR 6.65, p < 0.001) in the multivariate regression analysis. HbA_1C was associated with proliferative diabetic retinopathy in the univariate analysis (OR 1.31, p = 0.002) but was no longer significant in the multivariate analysis.

Conclusions: In this case-control study of African Americans with type 2 diabetes, duration of diabetes, systolic hypertension and insulin use were strong risk factors for the development of proliferative diabetic retinopathy. Interestingly, HbA_1C did not confer additional risk in this cohort.     

Association Analysis of Polymorphisms in Genes Related to Oxidative Stress in South Indian Type 2 Diabetic Patients with Retinopathy

Background: Diabetic Retinopathy (DR) is one of the most common microvascular complications of type 2 diabetes mellitus (T2DM) and is polygenic with a multitude of genes contributing to disease susceptibility. The present study aimed at exploring the association between DR and seven polymorphisms in oxidative stress-related genes, i.e. ACE, eNOS, p22phox subunit of NAD(P)H oxidase, PARP-1 and XRCC1 in South Indian T2DM subjects.

Materials and methods: The study included 149 T2DM subjects with DR (diagnosed through funduscopic examination) and 162 T2DM patients with no evidence of DR. The selected polymorphisms were genotyped by polymerase chain reaction (PCR) and Taqman allele discrimination assay.

Results: There was no significant difference in the genotype and allele distribution of ACE ins/del, eNOS-786T>C, 894G>T, 4a4b and p22phox 242C>T polymorphisms between T2DM groups with and without DR. Contrastingly, there appeared to be a significant association of PARP-1 Val762Ala and XRCC1 Arg399Gln polymorphisms with DR, wherein 762Ala allele seemed to confer significant protection against DR (p?=?0.01; OR?=?0.51 [0.3–0.86]), while the presence of 399Gln allele was associated with an enhanced risk for DR (p?=?0.02; OR?=?1.52 [1.07–2.15]). Multiple logistic regression analysis revealed a significant and independent association of Val762Ala and Arg399Gln polymorphisms and other putative risk factors with DR in T2DM individuals.

Conclusions: The polymorphisms in the DNA repair genes PARP-1 and XRCC1 tended to associate significantly with DR. While Val762Ala polymorphism was associated with reduced susceptibility to DR, the Arg399Gln polymorphism contributed an elevated to risk for DR in South-Indian T2DM individuals.     

糖尿病视网膜病变与血清25-羟基维生素D浓度相关性的Meta分析

目的：探讨糖尿病视网膜病变（DR）与血清25-羟基维生素D[25（OH）D]浓度的关系,为DR的病因探索和防治提供证据。方法：循证医学研究。运用Cochrane系统评价方法,检索美国国立图书馆医学文献检索系统、荷兰医学文摘数据库、考克兰图书馆、维普中文科技期刊全文数据库、万方期刊论文数据库等从建库到2016 年5 月发表的中英文文献。采用Newcastle-Ottawa Scale（NOS）量表进行文献质量评价,并应用Review Manager 5.2 对提取的数据进行Meta分析。对于连续变量,采用相应模型计算标准化均数差(SMD )及其95%置信区间(CI )。采用I 2 检验进行研究间异质性分析,根据不同年龄层次、洲界、维生素D测量方法等进行亚组分析,并采用倒漏斗图评价发表偏倚。结果：共纳入6 项研究,总计1 317 例患者。其中,DR组634 例,非糖尿病性视网膜病变（NDR）组683 例。Meta分析显示DR组血清25（OH）D浓度低于NDR组,差异有统计学意义[SMD =-0.41,95%CI（-0.63,-0.18）,P =0.0004]。亚组分析均未发现明显的异质性来源。去除引起高异质性的文献,并采用固定效应模型进行敏感性分析后,2组血清中25（OH）D浓度差异仍有统计学意义[SMD=-0.33,95%CI (-0.45,-0.21),P <0.01]。结论：DR的发生可能与血清25（OH）D浓度下降有一定相关性,血清25（OH）D浓度的监测对DR的预防、临床诊断及治疗具有一定意义。     

Population-Based Study of Nonproliferative Diabetic Retinopathy Among Type 2 Diabetic Patients in Kinmen, Taiwan

Purpose

This study was conducted to assess the prevalence and associated factors of nonproliferative diabetic retinopathy among type 2 diabetic patients in Kinmen, Taiwan.

Methods

From 1991 to 1993, 971 type 2 diabetic patients in Kinmen underwent diabetic retinopathy screening performed by a panel of ophthalmologists using indirect ophthalmoscopy and 45° color fundus retinal photographs.

Results

Of the 971 patients screened in 1991–1993, 578 (59.5%) were examined for this study. Diabetic retinopathy was diagnosed in 127 patients (22.0%), including nonproliferative diabetic retinopathy in 13.3%, proliferative diabetic retinopathy in 1.4%, legal blindness in 1.4%, and ungradable diabetic retinopathy in 5.9%. Significant associated factors of nonproliferative diabetic retinopathy based on multiple logistic regression analysis were fasting plasma glucose (FPG) at baseline [≥126?mg/dl vs. <126?mg/dl; odds ratio (OR) = 2.89; 95% confidence interval (CI), 1.01–9.09], 2-h postload at baseline (≥200 vs. <200?mg/dl; OR = 1.48; 95% CI, 1.09–2.07); HbA_1c at follow-up (≥7% vs. <7%; OR = 6.54; 95% CI, 3.01–14.20), duration of diabetes (≥15 years vs. <10 years; OR = 6.72; 95% CI, 2.13–21.18), and incremental systolic blood pressure between baseline and follow-up (OR = 1.02; 95% CI, 1.00–1.04).

Conclusions

In addition to the longer duration of type 2 diabetes, FPG at baseline, poorly controlled glucose concentration, and altered blood pressure may increase the risk of nonproliferative diabetic retinopathy in type 2 diabetic patients. Jpn J Ophthalmol 2006;50:44–52 © Japanese Ophthalmological Society 2006     

Relation Between Plasma Nitric Oxide Levels and Diabetic Retinopathy

Purpose Nitric oxide (NO) plays an important role in homeostatic vasodilation and the regulation of blood flow. On the other hand, excess release of NO causes various vascular complications. There are only a few reports on the relationship between plasma NO levels and microvascular complications, especially diabetic retinopathy (DR) in patients with type 2 diabetes. The purpose of this study was to determine the relationship between plasma NO levels and DR. Methods In a prospective study, blood samples were obtained from 36 patients with diabetes and no diabetic retinopathy (NDR), 43 patients with nonproliferative diabetic retinopathy (NPDR), 18 patients with proliferative diabetic retinopathy (PDR), and 40 subjects without diabetes mellitus, who served as controls. The levels of plasma NO_x (nitrite and nitrate), the stable metabolites of NO, were measured by high-performance liquid chromatography with the Griess method. Results The plasma NO_x levels were 92.8 ± 16.0, 70.2 ± 6.8, 90.3 ± 9.1, and 53.8 ± 6.1 μmol/l in patients with NDR, NPDR, or PDR, and in the controls, respectively. The plasma NO_x levels in the three diabetic groups were significantly higher than those in the control group (P < 0.05 in each case). Conclusion The increased plasma NO levels in patients with type 2 diabetes indicate that NO may be associated with the pathogenesis of DR. Jpn J Ophthalmol 2006;50:465–468 ? Japanese Ophthalmological Society 2006     

2型糖尿病视网膜病变血清C肽测定及临床意义

目的 探讨血清C肽与2型糖尿病视网膜病变(DR)之间的关系及其临床意义.方法 将2型糖尿病住院病人167例分为3组,其中无糖尿病视网膜病变组(NDR组)60例,非增殖性糖尿病视网膜病变组(NPDR组)76例,增殖性糖尿病视网膜病变组(PDR组)31例.采用化学发光免疫分析法分别测定其空腹血清C肽含量并记录其他可能影响糖尿病视网膜病变发生、发展的因素.根据所测血清C肽值重新将病人分为C肽低值组(LCP组)37例,C肽正常值组(NCP组)78例,C肽高值组(HCP组)52例.结果 NDR组、NPDR组、PDR组空腹血清C肽平均水平呈降低趋势,三组之间空腹血清C肽平均水平比较差异有统计学意义(P＜0.01).LCP组、NCP组、HCP组之间DR发生率比较差异有统计学意义(x2=46.702,P＜0.01).Logistic回归分析显示空腹血清C肽水平与DR有明显相关性(B=-1.415,P=0.000),病程与DR有明显相关性(B=0.404,P=0.000).C肽水平和糖尿病病程呈负相关(r=-0.479,P=0.000),C肽水平与DR的程度呈负相关(r=-0.654,P=0.000).结论 血清C肽在2型DR的发生、发展过程中可能有重要的病理意义,其水平降低可能是2型糖尿病患者DR进展的临床标志.

Abstract：

Objective To explore the relationship of serum C-peptide with diabetic retinopathy (DR)and its clinical significance. Methods A total of 167 inpatients with type 2 diabetes were separated into three groups, NDR group (n=60 examination of ocular fundus showed normal), NPDR group (n=76 examination of ocular fundus showed nonproliferative diabetic retinopathy), PDR group (n=31 examination of ocular fundus showed proliferative diabetic retinopathy). Their fasting serum C-peptide (FCP) was tested with chemiluminescent immunoassay. At the same time, other factors that might affect the onset and progression of DR were recorded. Then all the patients were divided according to their C-peptide fasting levels in quartiles again, low C-peptide group (LCP) [n=37], normal C-peptide group (NCP) [n=78], high C-peptide group (HCP) [n=52].Results In three groups, the mean value of FCP in PDR group was the lowest, the NPDR group had the lower concentration than NDR group, [(0.61±0.33) ng/ml vs (1.34± 0.68) ng/ml vs (2.11 ± 0.80) ng/ml, P ＜0.01]. The incidence of DR among LCP group, NCP group and HCP group showed a significant difference (x2=46.702, P ＜0.01). Logistic regression analysis showed that only C-peptide (B=-1.415, P=0.000), duration of diabetes (B=0.404, P =0.000) were independently associated with DR. A negative correlation was evident between C-peptide levels and duration of diabetes (r=-0.479, P =0.000), a negative correlation was also found between C-peptide levels and DR (r=-0.654, P =0.000). Conclusions Serum C-peptide may have important significance in pathological form of Type 2 DR. The decrease of C-peptide levels may be a maker of the development of DR in type 2 diabetes.