糖尿病肾病发病机制研究进展及防治

糖尿病肾病 (ｄｉａｂｅｔｉｃｎｅｐｈｒｏｐｈｔｈｙ,ＤＮ)是糖尿病 (简称ＤＭ)危害性最大的慢性并发症之一。在 1型糖尿病 (1 ＤＭ)患者 ,ＤＮ是首要的致死、致残原因 ;在 2型糖尿病 (2 ＤＭ)患者 ,ＤＮ仅次于大血管并发症。1　ＤＮ的病理改变及临床分期ＤＮ的病理改变最初为肾脏肥大、肾小球血流量增加 ,接着肾小球系膜细胞增殖、系膜细胞外基质增加、肾小球基底膜增厚 ,最后发展成为肾小球硬化。临床上一般分为 4期(有的资料分 5期 )。Ⅰ期 :肾增大 ,肾小球血流量增加 ,无组织学改变。Ⅱ期 :肾小球基底膜增厚 ,尿白蛋白排泄率(ＡＥＲ)…     

糖尿病肾病发病机制研究进展

糖尿病肾病（diabeticnephropathy,DN）是糖尿病（diabetesmellitus,DM）最常见的慢性并发症,也是终末期肾脏疾病的主要死亡原因之一。DN发病机制复杂,涉及遗传因素、糖代谢紊乱及由此所致的非酶糖基化、多元醇通路激活、血流动力学改变、氧化应激等多个因素的相互作用,本文就DN发病机制最近的研究进展予以综述。     

糖尿病肾病分子遗传学发病机制的研究进展

糖尿病肾病是糖尿病常见的微血管并发症之一,也是糖尿病的主要死亡原因之一,其发病机制复杂,其中遗传因素在糖尿病肾病肾损害中起着重要作用。本文将对近年发现的与糖尿病肾病发生、发展有关的分子遗传学机制做简要阐述,为糖尿病肾病的早期诊断提供新的思路和方向,也为糖尿病肾病的治疗提供新的靶点。     

糖尿病肾病的发病机制

糖尿病肾病(DN)是糖尿病常见的慢性并发症之一。其特征性的病理改变是系膜细胞肥大以及细胞外基质成分堆积，肾小球基底膜增厚，最终导致肾小球硬化。DN发病机制十分复杂，到目前为止尚不能完全阐明。近几年来，国内外学者从整体水平、细胞水平、分子水平乃至基因水平对DN进行了广泛而深入的研究，从不同水平上阐述了DN的发病机制。现综述如下。     

糖尿病肾病的发病机制及治疗新进展

糖尿病肾病在我国继发性肾小球肾炎中占重要地位,已经成为全世界范围内首当其冲亟待解决的问题之一。随着对糖尿病肾病发病机制的不断深入,新的治疗措施不断浮现。本文简述了糖尿病肾病的发病机制,概括了糖尿病肾病药物治疗的新进展。     

糖尿病肾病发病机制及治疗研究新进展

糖尿病肾病(DN)是糖尿病最严重的并发症,近年在世界范围内患病人数不断增长,成为导致终末期肾脏病的主要原因之一[1]。表现为肾小球高滤过、滤出清蛋白、肾小球基底膜增厚、系膜细胞增生及细胞外基质增多,导致肾小管及间质的纤维化,最终引起肾脏功能衰竭[2-3]。DN是一种多因素参与诱发的疾病,发病机制包含多种不同的细胞、分子及其相关因素[4],目前已知的机制有高血糖状态、血流动力学改变、肾素-血管紧张素Ⅱ-醛固酮系统激活、炎症信号通路等,但具体机制仍未详细阐明。本文就DN的发病机制及治疗研究进行如下综述。     

糖尿病肾病的发病机制和干预治疗进展

糖尿病肾病（DN）是糖尿病（DM）的严重并发症之一。在欧美等发达国家，糖尿病已是导致终末期肾病（ESRD）最常见的病因。在我国，随着人民生活水平的提高，糖尿病发病率的逐年增多，糖尿病肾病在ESRD病因中所占比例也逐年上升，成为影响人民健康水平的重要威胁之一。因此，研究DN的发病机制，并在DM的发生发展中阻止或延缓DN的发生具有重要意义。DN的发病机制主要与遗传、血糖和血脂代谢紊乱、肾血流动力学改变以及一些细胞因子的产生密切相关，积极干预这些因素有利于阻止或延缓DN的发生发展。     

2型糖尿病肾病易感基因的研究进展

随着 2型糖尿病 (ｔｙｐｅ 2ｄｉａｂｅｔｅｓｍｅｌｌｉｔｕｓ,Ｔ2ＤＭ )的患病率在全球范围内迅速增长 ,糖尿病肾病 (ｄｉａｂｅｔｉｃｎｅｐｈｒｏｐａｔｈｙ ,ＤＮ)作为糖尿病最严重、最常见的并发症之一 ,在美国已成为引起终末期肾病 (ｅｎｄ ｓｔａｇｅｒｅｎａｌｄｉｓｅａｓｅ ,ＥＳＲＤ)的首要原因 ,并有上升趋势。大量证据显示 ,Ｔ2ＤＭ患者中仅有 2 0 %～30 %发生肾脏损害 ,且与病程长短及血糖控制情况无关 ,在不同种族间 ,ＤＮ的发病率也存在着很大差异 ,另外ＤＮ的家族聚集性已得到广泛证实。这些均表明遗传因素在ＤＮ的发生、…     

糖尿病肾病肾纤维化病变的发病机制研究进展

综述了国外在糖尿病重要并发症糖尿病肾病的肾纤维化病变发病机制方面的最新进展,指出多元醇糖代谢支路与醛糖还原酶的异常激活、转化生长因子-β(TGF-β)/Smad信号转导途径的异常激活可能是糖尿病肾病肾脏炎症和肾纤维化病变的主要机制,此外,miR-NAs也可能通过影响TGF-β信号转导途径达到影响糖尿病肾病肾纤维化病变进程的作用。     

辛伐他汀对2型糖尿病合并肾病葡萄糖代谢的影响

【目的】探讨辛伐他汀治疗对2型糖尿病（T2DM）合并肾病患者的糖代谢影响。【方法】选取本医院60名T2DM合并肾病患者进行辛伐他汀治疗3个月。比较治疗前后空腹血糖（FBG）、C肽、糖化血红蛋白（HbA1c）,C反应蛋白（CRP）、空腹胰岛素（FINs）水平、胰岛素敏感指数（ISI）、胰岛素／葡萄糖比率（IGR）、HOMA—IR、脂联素（ANP）以及游离脂肪酸水平等变化,以评价辛伐他汀对T2DM病合并肾病患者的治疗效果。【结果】在辛伐他汀治疗3个月后的葡萄糖耐量试验（0GTT）中,各时点血糖水平较治疗前均显著下降（P〈0．05）,而胰岛素与C肽在0min和30rain时较治疗前显著下降（P〈0．05）。在辛伐他汀治疗后,对比治疗前,FBG、HbA1c、CRP、血糖曲线下面积（AUC）、胰岛素AUC、FINS、ISI、游离脂肪酸（FFA）以及HO-MA—IR均显著下降（P〈0．05）,尿白蛋白排泄率（UAER）也明显下降（P〈0．01）,但是C肽AUC（P〈0．05）以及APN（P〈0．01）均显著上升,而IGR及校正胰岛素反应（CIR）无显著变化（P〉0．05）。【结论】辛伐他汀治疗可以显著降低血糖,提高患者对胰岛素的敏感性,改善胰岛素抵抗,从而改善T2DM合并肾病患者的糖代谢。     

尿Ⅳ型胶原测定对糖尿病肾病早期诊断的意义

目的探讨尿Ⅳ型胶原(Ⅳ-C)的检测在糖尿病肾病(DN)中的早期诊断价值。方法65例2型糖尿病(DM)患者根据尿白蛋白排泄率(UAER)分为正常白蛋白尿组(DM1)、微量白蛋白尿组(DM2)和大量白蛋白尿组(DM3),检测各组尿Ⅳ-C及尿微量白蛋白(MA)含量,并与42例正常对照组(NC)进行比较。结果DM患者尿Ⅳ-C含量显著高于NC组(P<0.05),且尿Ⅳ-C在DM 1、2、3组间呈逐组增高趋势,均有显著差异(P<0.01),尿Ⅳ-C与UAER呈显著正相关(P<0.01)。结论尿Ⅳ-C测定可作为DN早期诊断更有用的指标。     

银杏黄酮甙对糖尿病大鼠肾组织病理变化的影响

目的:观察银杏黄酮甙对糖尿病大鼠肾组织MMPs-3、PAI-1表达及肾组织病理变化的影响,探讨其对糖尿病大鼠肾脏保护作用。方法:选择雄性SD大鼠48只,随机分为3组,即正常组(N组),糖尿病组(DM组),银杏黄酮甙治疗组(C组)。DM组、C组腹腔注射链脲佐菌素(STZ)制模成功后,C组给予银杏黄酮甙灌胃,分别于6、10周各组随机抽取8只宰杀,留肾组织标本用于做病理及免疫组化检查,所有数据以均数±标准差表示,用SPSS10.0统计软件处理,组间比较用方差分析。结果:免疫组化:第6周时,DM组、C组PAI-1表达均高于N组(统计学处理分别为P<0.01,P<0.05),至第10周时,C组PAI-1表达低于DM组(P<0.01)。第6周时,MMPs-3在DM组的表达低于N组(统计学处理P<0.05),持续至第10周,C组则高于N组、DM组(与两组比较P<0.01)。病理组织观察:6周时DM组、C组肾小球体积增大,电镜显示肾小球基底膜增厚,10周时DM组肾小球局部毛细血管袢玻璃样物质沉积,C组肾小球系膜区少量玻璃样物质的沉积,病变较DM组轻。结论:STZ诱导的糖尿病大鼠存在纤溶系统功能紊乱,细胞外基质积聚,PAI-1在肾组织表达增强,MMPs-3表达减弱,应用银杏黄酮甙干预治疗,可以使PAI-1的表达下调,MMPs-3的表达明显上调,使肾脏的病变减轻,其对糖尿病大鼠肾脏具有保护作用。     

Predicting Development of Proliferative Diabetic Retinopathy

OBJECTIVE

Identifying individuals most at risk for diabetic retinopathy progression and intervening early can limit vision loss and reduce the costs associated with managing more advanced disease. The purpose of this study was to identify factors associated with progression from nonproliferative diabetic retinopathy (NPDR) to proliferative diabetic retinopathy (PDR).

RESEARCH DESIGN AND METHODS

This was a retrospective cohort analysis using a claims database of all eye care recipients age ≥30 years enrolled in a large managed-care network from 2001 to 2009. Individuals with newly diagnosed NPDR were followed longitudinally. Multivariable Cox regression analyses identified factors associated with progression to PDR. Three- and five-year probabilities of retinopathy progression were determined.

RESULTS

Among the 4,617 enrollees with incident NPDR, 307 (6.6%) developed PDR. After adjustment for confounders, every 1-point increase in HbA_1c was associated with a 14% (adjusted hazard ratio 1.14 [95% CI 1.07–1.21]) increased hazard of developing PDR. Those with nonhealing ulcers had a 54% (1.54 [1.15–2.07]) increased hazard of progressing to PDR, and enrollees with nephropathy had a marginally significant increased hazard of progressing to PDR (1.29 [0.99–1.67]) relative to those without these conditions. The 5-year probability of progression for low-risk individuals with NPDR was 5% (range 2–8) and for high-risk patients was 38% (14–55).

CONCLUSIONS

Along with glycemic control, nonophthalmologic manifestations of diabetes mellitus (e.g., nephropathy and nonhealing ulcers) are associated with an increased risk of diabetic retinopathy progression. Our retinopathy progression risk score can help clinicians stratify patients who are most at risk for disease progression.Diabetic retinopathy is the leading cause of new cases of legal blindness in the U.S. (1), affecting 4.2 million Americans, 655,000 of whom have sight-threatening retinopathy (1,2). Identifying patients who are at increased risk of progression from nonproliferative (NPDR) to proliferative diabetic retinopathy (PDR) is important for many reasons. From the patient’s perspective, individuals who progress from NPDR to PDR frequently experience a decline in best-corrected visual acuity, which can have a profound impact on health-related quality of life (3). In addition, those who develop PDR are at substantially increased risk of serious complications that can result in permanent vision loss such as tractional retinal detachment, vitreous hemorrhage, and neovascular glaucoma (4,5). From a societal perspective, the costs of caring for patients with PDR are four times greater than the costs of managing patients with NPDR. One study found the average cost of caring for patients with NPDR to be 292 USD, while it cost 1,207 USD to manage patients who develop PDR (6). Another study conducted by the National Health Services in Taiwan found that individuals who progressed from NPDR to PDR were noted to have an increase in expenditures of 3,482 USD (7). The ability for clinicians to identify and treat patients early in the disease process, before they experience progression to PDR, may result in considerable cost savings, especially in light of the growing number of individuals with diabetes mellitus (DM) in the U.S. population.In patients with DM, metabolic control as measured by HbA_1c and disease duration account for only 11% of the risk of retinopathy, leaving 89% to other factors (8). Several large population-based studies including the Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR), the UK Prospective Diabetes Study (UKPDS), and the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study have identified other risk factors associated with the development or progression of diabetic retinopathy (9–11). From the results of these studies, age, sex, socioeconomic status, and comorbid systemic arterial hypertension are considered important determinants of retinopathy risk. We are unaware of any studies in the literature that have integrated these and other factors into a comprehensive diabetic retinopathy risk score that can help clinicians identify individuals who are at increased risk of progression from NPDR to PDR. Risk calculators such as the Framingham Risk Score for Atrial Fibrillation (12) and the Ocular Hypertension Treatment Study risk calculator (13) have been found to be useful in aiding clinicians with patient decision making.The purpose of this analysis was to assess risk factors associated with progression of diabetic retinopathy among a diverse group of individuals with DM enrolled in a large managed-care network. By following beneficiaries longitudinally, we sought to confirm previously identified risk factors and to define additional risk factors that may be associated with progression from NPDR to PDR. Finally, using the risk factors identified from our regression models, we developed a risk score that clinicians can use to identify groups of individuals who are at low and high risk of retinopathy progression.     

肾病患者血清B因子检测的临床意义

目的探讨肾病患者血清B因子(BF)检测的临床意义。方法对146例不同肾病患者进行了BF水平的检测,对其中28例狼疮肾患者同时作抗核抗体(ANA)、抗ds-DNA及肾功能指标的对比分析。结果各肾病组BF水平由低到高依次为肾病综合征和慢性肾衰<<急性肾炎<慢性肾炎和狼疮肾<<健康对照组("<<"表示P<0.01;"<"表示P<0.05;无比较者表示P>0.05)。狼疮肾患者中ANA阳性组与阴性组,抗ds-DNA阳性组与阴性组之间BF水平均无明显差别(P>0.05),但肾功能受损严重者与肾功受损不明显者有显著差别(P<0.01)。结论动态地监测血清BF对急、慢性肾炎及狼疮肾疗效的观察和预后的判断有一定的指导意义。