2型糖尿病肾病和糖尿病性视网膜病变的相关性研究

目的探讨2型糖尿病肾病和糖尿病性视网膜病变的发病机制及其两者之间的相关性。方法选择2004年1月至2014年12月北京中日友好医院肾内科经肾穿刺活检确诊的2型糖尿病肾病(diabetic nephropathy,DN)患者95例,按照肾脏病理改变程度分为5组,即DNⅠ组10例,DNⅡa组12例,DNⅡb组16例,DNⅢ组54例,DNⅣ组3例;将不同组间视网膜病变进行比较,分析视网膜病变与肾脏损伤之间的关系,以及视网膜病变与常用临床指标[24 h尿蛋白定量、空腹血糖(fasting blood glucose,FBG)、糖化血红蛋白(glycosylated hemoglobin,HbA1c)、血肌酐(SCr)及肌酐清除率(creatinine clearance rate,Ccr)]之间的关系。结果 DN患者肾脏损伤病理分型与视网膜病变呈正相关(r=0.458,P=0.016),但仍有23.2%患者无视网膜病变,分别发生在80.00%的DNⅠ组、33.33%的DNⅡa组、12.50%的DNⅡb组、14.81%的DNⅢ组患者中。临床指标中仅24 h尿蛋白定量与糖尿病视网膜病变的发生和发展相关。结论尽管糖尿病性视网膜病变常被提示DN,但少部分DN不存在视网膜病变的情况也应被重视。     

糖尿病肾病及其视网膜病变

糖尿病的并发症一般分三类：①微血管病变，主要是视网膜病变和糖尿病肾脏病变；②大血管病变，主要为冠脉疾病，脑血管疾病；③外周血管神经病变。这些血管神经病变涉及全身各器官脏器，导致各种并发症。本文主要讨论糖尿病视网膜病变和肾脏病变的发病机理、监测和预防措施。     

糖尿病肾病及其视网膜病变

糖尿病的并发症一般分三类:①微血管病变,主要是视网膜病变和糖尿病肾脏病变;②大血管病变,主要为冠脉疾病,脑血管疾病;③外周血管神经病变。这些血管神经病变涉及全身各器官脏器,导致各种并发症。本文主要讨论糖尿病视网膜病变和肾脏病变的发病机理、监测和预防措施。     

糖尿病肾病和糖尿病视网膜病变应激相关关键基因的生物信息学分析

目的:通过生物信息学方法分析共同影响糖尿病肾病(diabetic nephropathy, DN)和糖尿病视网膜病变(diabetic retinopathy, DR)发生发展的应激相关关键基因。方法:从DisGeNET、CTD、Genecards数据库收集DN和DR的共致病基因数据,通过STRING数据库和Cytoscape软件构建蛋白互作网络图,进行共致病基因的GO和KEGG富集分析。同时,利用“limma”包筛选出GEO数据库中DN和DR数据集的共同差异基因,通过MCC插件筛选出Top20基因,并对两个芯片数据集进行GSEA富集分析。筛选出上述两组基因数据共同的应激相关关键基因,对其进行相关性和富集分析。最后,借助GeneMANIA、NetworkAnalyst 3.0、DGIdb数据库,构建蛋白互作网络以及TF-miRNA-gene网络,并预测应激相关关键基因的靶向治疗药物。结果:我们发现了5个高度正相关的应激相关关键基因(CCL2、THBS1、PECAM1、SPARC、POSTN),在高糖环境下,它们可通过介导应激反应影响肾脏以及视网膜的细胞外基质重构和炎症。同时,我们预测了...     

2型糖尿病患者视网膜病变与肾功能关系的临床研究

目的 :观察 2型糖尿病视网膜病变 (DR)与肾功能之间的关系。方法 :通过对 92例不同程度视网膜病变的 2型糖尿病患者进行空腹血糖、餐后 2h血糖、糖化血红蛋白、2 4h尿微量白蛋白、尿素氮、肌酐及双侧眼底镜检查 ,并与 30例不伴视网膜病变的 2型糖尿病患者进行对比分析。结果 :糖尿病伴DRⅢ期及增殖期的空腹血糖、餐后2h血糖、糖化血红蛋白与对照组相比有统计学差异 (P <0 .0 5 ,P <0 .0 1) ,糖尿病出现DR各期的 2 4h尿微量白蛋白与对照组相比有统计学差异 (P <0 .0 1)。结论 :2型糖尿病视网膜病变程度是随着 2 4h尿微量白蛋白增加而加重的 ,提示二者之间密切相关。     

葛根素治疗糖尿病视网膜病变的疗效观察

目的观察葛根素对糖尿病视网膜病变的治疗效果,探讨护理方法。方法对86例糖尿病视网膜病变的患者,应用葛根素0.4 g加入0.9%氯化纳注射液250 ml中静脉滴注,1次/d,15 d为1个疗程,并对患者进行用药护理。2个疗程后观察患者用葛根素治疗前后各指标的改变。结果治疗前后比较,各血液流变学指标和血液动力学指标均显著改善,眼底病变好转(均P<0.05)。结论使用葛根素治疗早期糖尿病视网膜病变疗效可靠。     

2型糖尿病患者骨密度及骨代谢指标与糖尿病视网膜病变相关性的研究

目的探究2型糖尿病(type 2 diabetes mellitus,T2DM)患者骨密度(bone mineral density,BMD)、骨代谢指标及骨量异常情况与糖尿病视网膜病变(diabetic retinopathy,DR)的关系,为T2DM患者骨健康提供科学依据。方法入选2018年12月至2019年12月北京大学深圳医院内分泌科收治的T2DM患者,根据是否合并DR分为无DR组和DR组,比较2组间的性别、年龄、糖尿病病程、BMI、吸烟/饮酒史、BMD、骨代谢指标及骨量异常患病情况。结果总纳入T2DM患者616例,无DR组452例,DR组164例。与无DR组相比,DR组糖尿病病程较长,腰椎L1～L4、股骨及股骨颈BMD、T值、Z值均偏低,血Ca、24 h尿Ca、25(OH) D3偏低及血P、β-CTX偏高。T2DM合并视网膜病变骨量异常患病率偏高(59.8%vs 50.2%,OR=1.48; 95%CI:0.99～2.22)。结论 T2DM患者合并视网膜病变时骨形成及骨吸收指标表达均升高,骨转换率加速,PTH升高,破骨细胞活性增强,BMD下降,骨量异常患病率偏高。     

不同性别老年2型糖尿病患者视网膜病变与骨质疏松的相关性研究

目的探讨不同性别的老年2型糖尿病(type 2 diabetes mellitus,T2DM)患者视网膜病变与骨质疏松的相关性。方法选取我院老年病科住院的老年T2DM患者250例,其中老年男性T2DM组132例,老年女性T2DM组118例,通过眼底检查,每组各再分为两组:视网膜病变组DR(+)、非视网膜病变组DR(-),分别记录患者的一般情况、年龄、糖尿病病程、饮酒史、吸烟史、体质量指数(body mass index,BMI),采用化学仪检测空腹血糖(fasting blood glucose,FBG)、糖化血红蛋白(HbA1c)、微量蛋白尿、血脂,双能X线吸收仪测定腰椎、股骨颈和全髋骨密度值。结果老年男性T2DM组中校正年龄、BMI、吸烟史、饮酒史等混杂因素后,与DR(-)组相比,DR(+)组腰椎、髋骨、股骨颈骨密度相比差异无统计学意义(P0.05);老年女性T2DM组中校正年龄、BMI、吸烟史、饮酒史等混杂因素后,与DR(-)组相比,DR(+)组腰椎、髋骨骨密度值偏低,差异有统计学意义(P0.05)。结论本研究显示不同性别的糖尿病视网膜病变与骨质疏松相关性有差异,老年男性T2DM患者视网膜病变与骨质疏松无明显相关性,而老年女性T2DM患者视网膜病变与骨质疏松存在一定相关性,积极预防老年女性糖尿病视网膜病变可能在延缓骨质疏松发生发展中起到一定作用。     

微小RNA在糖尿病肾病中的作用机制研究进展

糖尿病肾病(DN)是糖尿病重要的微血管并发症之一,目前临床上缺乏可用于DN无创诊断的具有高度敏感性和特异性的诊断生物标志物。微小RNA(microRNA, miRNA)广泛存在于生物体中,在多种生理和病理过程均起关键作用,参与DN的发病机制。DN患者血液及尿液特异性miRNA的发现为寻找DN的诊断标志物提供了新的方向,将在DN的诊断及疾病严重程度评估中发挥重要的作用。     

Diabetic retinopathy may predict the renal outcomes of patients with diabetic nephropathy

Background: The patients with Type 2 diabetes mellitus (T2DM) and diabetic retinopathy (DR) are prone to develop diabetic nephropathy (DN). In this study, we aimed to clarify the relationship between DR and the progression of DN in patients with T2DM.

Methods: In the cross-section study, 250 patients with T2DM and biopsy-proven DN were divided into two groups: 130 in the DN without DR group (DN group) and 120 in the DN?+?DR group. Logistic regression analysis was performed to identify risk factors for DR. Of the above 250 patients, 141 were recruited in the cohort study who received follow-up for at least 1 year and the influence of DR on renal outcome was assessed using Cox regression. Renal outcome was defined as the progression to end-stage renal disease (ESRD).

Results: In the cross-section study, the severity of glomerular lesions (class IIb?+?III) and DM history?>10 years were significantly associated with the odds of DR when adjusting for baseline proteinuria, hematuria, e-GFR, and interstitial inflammation. In the cohort study, a multivariate COX analysis demonstrated that the DR remained an independent risk factor for progression to ESRD when adjusting for important clinical variables and pathological findings (p?Conclusions: These findings indicated that the severity of glomerular lesions was significantly associated with DR and DR was an independent risk factor for the renal outcomes in patients with DN, which suggested that DR may predict the renal prognosis of patients with T2DM and DN.     

糖尿病肾病研究进展

糖尿病肾病是糖尿病最严重的微血管并发症。近10年来,糖尿病肾病患者快速增长,已成为危害人类健康的公共卫生疾病。目前在欧美等发达国家,DN约占终末期肾病(ESRD)的50%,已成为尿毒症的首位原发病;在我国约占25%～40%,是患者血液透析的重要原因。因此,及时发现与防治DN,对于延缓病情进展、提高患者生活质量意义重大。     

The predictive value of diabetic retinopathy on subsequent diabetic nephropathy in patients with type 2 diabetes: a systematic review and meta-analysis of prospective studies

This systematic review and meta-analysis aimed to assess the predictive value of diabetic retinopathy (DR) on further diabetic nephropathy (DN) risk in patients with type 2 diabetes (T2D) based on the prospective cohort studies. PubMed, Embase, and the Cochrane Library were systematically searched for eligible prospective cohort studies through March 2020. The predictive value of DR was assessed using sensitivity, specificity, positive likelihood ratio (PLR) and negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the receiver operating characteristic curve (AUC) through the bivariate generalized linear mixed model and the random-effects model. Ten prospective cohort studies recruited 635 patients with T2D. The pooled sensitivity and specificity of DR for predicted DN were noted to be 0.64 (95% CI, 0.54–0.73) and 0.77 (95% CI, 0.60–0.88), respectively. The pooled PLR and NLR of DR for predicted DN were 2.72 (95% CI, 1.42–5.19) and 0.47 (95% CI, 0.33–0.67), respectively. The summary DOR for the relationship between DR and subsequent DN for T2D patients was 5.53 (95% CI, 2.00–15.30), and the AUC of DR for predicted DN was 0.73 (95% CI, 0.69–0.77). This study found significant associations between DR and subsequent DN risk for patients with T2D. Moreover, the predictive value of DR on subsequent DN risk was relatively lower.     

血管紧张素-Ⅰ转换酶基因多态性与糖尿病及糖尿病肾病的关系

目的　探讨血管紧张素Ⅰ转换酶基因（ＡＣＥ基因） 多态性与糖尿病及糖尿病肾病（ＤＮ） 的易感性之间的关系。方法　应用聚合酶链式反应（ＰＣＲ）方法扩增４８ 例正常人、７４ 例胰岛素依赖型糖尿病（ＩＤＤＭ） 患者（ 其中４０ 例不伴ＤＮ,３４ 例合并ＤＮ） 、１０２ 例非胰岛素依赖型糖尿病（ＮＩＤＤＭ） 患者（５７ 例不伴ＤＮ,４５ 例伴ＤＮ） 的ＡＣＥ基因上２８７ｂｐ 片断,根据插入（Ｉ） 或缺失（Ｄ） 来判断其多态性。结果　健康对照组与ＩＤＤＭ 及ＮＩＤＤＭ 组ＡＣＥ 等位基因、基因型均无显著性差异（ Ｐ＞０－０５）;在ＩＤＤＭ 组中,Ｄ等位基因及ＤＤ基因型在伴ＤＮ亚组中显著升高;在ＮＩＤＤＭ 组中,与不伴ＤＮ者比较,伴ＤＮ者其Ｉ等位基因、ＩＩ基因型频率明显为低。结论ＡＣＥ 基因多态性与糖尿病易感性无关,与ＤＮ密切相关。     

糖尿病肾病的蛋白质组学研究进展

糖尿病肾病(DN)是糖尿病最常见的微血管并发症,也是导致终末期肾病(ESRD)的重要原因。微量白蛋白尿作为预测DN进展的指标并不可靠,寻找DN早期生物学标志物以及对DN早期肾脏病变的机制研究为目前研究的重点。蛋白质组学技术近年来飞速发展,对DN患者的尿液、血液以及肾组织的蛋白质组学研究可能会为我们早期诊治DN提供新的希望。本文对蛋白质组学主要技术及DN蛋白质组学研究的近期研究进展进行综述。     

Classification of diabetic retinopathy and diabetic macular edema

The global incidence and prevalence of diabetes mellitus (DM) have reached epidemic proportions. Estimates indicate that more than 360 million people will be affected by DM by 2030. All of these individuals will be at risk of developing diabetic retinopathy (DR). It is extremely important to categorize, classify and stage the severity of DR in order to establish adequate therapy. With proper management more than 90% of cases of visual loss can be prevented. The purpose of the current paper is to review the classification of DR with a special emphasis on the International Clinical Disease Severity Scale for DR. This new classification is simple to use, easy to remember and based on scientific evidence. It does not require specialized examinations such as optical coherence tomography or fluorescein angiography. It is based on clinical examination and applying the Early Treatment of Diabetic Retinopathy Study 4:2:1 rule.     

糖尿病肾病不同程度蛋白尿的相关因素分析及随访

目的分析糖尿病肾病不同程度蛋白尿的临床病理特征及随访资料,探索糖尿病肾病蛋白尿的相关因素及临床意义。方法1993—2003年本科经肾活检诊断为糖尿病肾病的患者,剔除糖尿病肾病合并其它类型肾脏疾病以及诊断不明确者,共60例。按蛋白尿程度分为4组:A组10例.蛋白尿<1.0g/24h;B组16例,蛋白尿≥1.0g/24h且<3.5g/24h;C组20例,蛋白尿≥3.5g/24h且<6g/24h;D组14例,蛋白尿≥6g/24h。对相关因素进行统计分析并记录随访情况。结果多因素回归分析结果显示,糖尿病史(OR=1.015,P=0.038)、收缩压(OR=1.018.P=0.047)、系膜区占肾小球面积比(OR=1.220,P=0.009)、基底膜增厚(OR=3.594,P=0.011)、肾小管萎缩(OR=6.190,P=0.045)、间质病变(OR=1.339,P=0.043)是糖尿病肾病蛋白尿程度的独立相关因素。随访结果显示肾活检时蛋白尿≥3.5g/24h的患者的中位肾存活时间小于蛋白尿<3.5g/24h的患者。C、D组中位肾存活时间为22个月,A、B组为36个月。肾活检时蛋白尿≥3.5g/24h的患者随访1年、2年、3年的肾存活率分别为79.3%、35.7%、17.9%,低于蛋白尿<3.5g/24h的患者的94.4%,83.9%、41.9%。结论糖尿病肾病的蛋白尿与诸多临床指标及病理改变相关,能较好的反映肾小球和肾小管间质病变的程度,并提示肾脏的预后。     

Relationship between E - cadherin and diabetic nephropathy

Objective To identify novel biomarker for diabetic nephropathy (DN) by urinary proteomic methods, and to detect the expression of E-cadherin in urine and renal tissue of patients with DN. Methods Urine samples were collected from 12 cases of type 1 diabetic nephropathy patients (T1DN), 12 cases of type 2 diabetic nephropathy patients (T2DN), 12 cases of nephritic syndrome patients (NS), and 12 cases of healthy Controls. Comparative proteomic approach of two-dimensional gel electrophoresis (2-DE) and mass spectrometry (MS) were employed to identify DN-related biomarker in urine samples. The differential expression of the identified biomarker in urine samples and renal biopsy specimens were detected by Western blotting and immunohistochemistry method. Results E-cadherin was identified by 2DE/MS, which was significantly up-regulated in T1DN and T2DN groups (all P＜ 0.01). Western blotting confirmed the expression of E-cadherin was significantly higher in T1DN and T2DN groups than in NS and Control groups (all P＜0.01). Immunohistochemical stain showed E-cadherin was mainly expressed in the membrane and cytoplasm of renal tubular epithelial cell, and its expression was markedly decreased in DN kidneys compared with healthy Controls (P＜0.05). Conclusions E-cadherin is identified as a novel DN-related biomarker, which is specifically increased in urine of DN patients.