持续皮下胰岛素注射对糖尿病视网膜病变影响的研究进展

胰岛素强化治疗对糖尿病视网膜病变（DR）结局的影响一直存在争议。著名的大型研究如糖尿病控制与并发症试验（DCCT）/糖尿病干预及并发症流行病学（EDIC）研究和英国前瞻性糖尿病研究（UKPDS）已经表明,1型或2型糖尿病（T1DM/T2DM）患者通过胰岛素强化治疗可在短期内使患者的血糖达标,延缓糖尿病视网膜病变的发生和进展,但一些研究发现对血糖控制不佳 T1DM患者进行强化治疗中会发生一过性糖尿病视网膜病变加重。诸多大型研究多采用皮下多点注射（MDI）模式进行胰岛素强化治疗,而短期持续皮下胰岛素注射（CSII）治疗对 T2DM视网膜 病变的长期疗效的研究报道国内外尚不多见。本文就 CSI I治疗对 DR发生发展影响的相关研究进展及发展趋势进行综述。     

关注钠-葡萄糖转运蛋白2抑制剂引起的非高血糖性酮症酸中毒

钠-葡萄糖转运蛋白2抑制剂（SGLT2i）是新型的口服降糖药,通过抑制肾脏近曲小管对葡萄糖的重吸收、增加尿中葡萄糖排泄而降低血糖。SGLT2i治疗糖尿病疗效确切,但也存在一些安全性问题,其中糖尿病酮症酸中毒（DKA）属于该类药物的严重不良反应。SGLT2i可使2型糖尿病患者DKA的发生风险增加至少7倍,其中约70%为非...     

糖尿病性眼底病变的药物治疗进展

糖尿病眼底病变是糖尿病最严重的微血管并发症，可导致不可逆性失明，糖尿病患者比非糖尿病患者发生失明的危险高25倍。糖尿病眼底病的主要表现形式为糖尿病视网膜病变（DR）。DR病变类型分为两种：非增殖性糖尿病视网膜病变（NPDR）和增殖性糖尿病视网膜病变（PDR）。NPDR表现为静脉扩张及串珠样变、微血管瘤、视网膜内出血、硬性渗出、微血管异常、棉絮斑。NPDR继续发展为PDR，以新生血管形成、神经胶质增生为特点。     

半导体激光治疗糖尿病视网膜病变的疗效观察

糖尿病视网膜病变（diabetic retinopathy，DR）是以微血管受损为主要特征的视网膜血管性疾病，为糖尿病的主要并发症之一，也是致盲的主要原因之一。如果不能及时有效治疗，许多病例最终因牵引性视网膜脱离或新生血管性青光眼而失明。激光光凝治疗糖尿病视网膜病变可以改善或稳定病情。现对76例（135眼）DR患者行半导体激光全视网膜光凝治疗的疗效分析报告如下。     

基层社区糖尿病视网膜病变早期发现及结果分析

糖尿病视网膜病变（DR）是糖尿病严重并发症之一,也是目前主要致盲原因之一。近年来,随着我国膳食结构的改变,生活模式的日益现代化,社会的老龄化,DR发病率呈逐年上升趋势,严重影响了患者的生存质量。目前DR尚无有效的治疗方法,且在DR治疗有效阶段患者无明显症状,因此对糖尿病患者及早进行社区干预,早期诊断,避免或延缓DR变的发生具有极其重要的意义。我院自2006年9月至2008年9月对确诊的381名糖尿病患者进行早期社区干预,报告如下。     

糖尿病视网膜病变眼底荧光血管造影分析

日前我国糖尿病患者日趋增多．糖尿病视网膜病变（diabetic retinopathv,DR）是其严重并发症之一,也是主要的致盲眼病之一。早期发现DR微血管异常．控制与减慢DR的发展将有效保存患者中心视力,降低致盲率,提高患者生活质量。眼底荧光血管造影（fundus fluorescence angiography,FFA）对于糖尿病视网膜病变的早期发现．及时治疗有指导意义。我院于2003～2008年对内分泌科确诊为2型糖尿病的72例（141眼）行FFA检查回顾性分析结果分析如下．     

糖尿病视网膜病变光凝后渗出性视网膜脱离3例

糖尿病视网膜病变（diabetic retinopathy,DR）是糖代谢异常造成的眼部严重并发症,造成视力损害和失明的主要原因是增殖性糖尿病视网膜病变和糖尿病黄斑水肿。对眼底荧光血管造影（fluorescein fundus angiography,FFA）诊断为增殖性糖尿病视网膜病变的患者,目前,激光治疗是唯一被证实有效的方法。在激光治疗可能出现的并发症中渗出性视网膜脱离较为少见,本科在临床治疗中遇到3例该种并发症患者，现报道如下。     

糖尿病性黄斑水肿的中西医治疗进展

糖尿病作为一种常见病、多发病,随着慢性病程的影响,它可以引起多系统的损害,如眼、肾、心脏等组织病变。糖尿病性视网膜病变（diabetic retinopathy,DR）是糖尿病（DM）患者最常见和严重的微血管并发症。糖尿病性黄斑水肿（diabetic macularedema,DME）是导致DR患者视力下降的主要原因之一,若不及时治疗,可造成不可逆的视功能损害。随着人均寿命的延长和饮食结构的变化,     

姜黄素治疗糖尿病视网膜病变作用机制的研究进展

糖尿病视网膜病变（DR）是糖尿病微血管病变的重要表现,是糖尿病的诸多并发症之一,可导致视力下降,是全球中老年人群的几大致盲原因之一,使发病人群生活质量严重下降。其发病机制与多种因素相关,如高血糖、高血脂、炎症反应和氧化应激等,但具体发病机制尚未完全清楚。目前DR的治疗效果有限,因此,寻找针对DR研制的药品成为当务之急。姜黄素具有包括抗凋亡自噬、抗炎、抗氧化、抗血管生成和抗肿瘤生成等多种生物活性。近年来,很多研究也证实姜黄素可以预防多种糖尿病并发症,包括糖尿病导致的视网膜病变。然而,目前没有确切姜黄素治疗DR的作用机制。本文结合国内外研究的最新进展,探讨姜黄素对DR保护作用的机制。     

糖化血红蛋白等七项指标检测对2型糖尿病视网膜病的早期诊断意义

糖尿病视网膜病变（diabetic retinopathy，DR）是糖尿病（diabetes mellitus，DM）常见的严重并发症，2型糖尿病致盲患者中DR最常见。由于DR具有不可逆性且进行性加重的特点，早发现、早治疗DR，并有效地监测其发展，对预防DR致盲非常重要。微循环障碍是DR发生发展的重要环节，其中血小板功能和凝血指标的异常对DR的发生起着重要作用，初步明确了血小板参数变化在糖尿病的病程中对血液高凝倾向的预测性。     

糖尿病视网膜病变危险因素的研究进展

糖尿病视网膜病变(DR)是高血糖导致的视网膜微血管或神经的病变,是糖尿病常见的慢性并发症之一,目前已经成为工作人群中首要的致盲眼病。现对DR相关危险因素进行综述,使糖尿病病人远离视力损害的风险,降低DR的患病率与致盲率,维持糖尿病病人的视力健康及生活质量。     

Neurodegeneration in Diabetic Retina and Its Potential Drug Targets

Diabetic retinopathy (DR) is one of the major complications of diabetes causing vision loss and blindness worldwide. DR is widely recognized as a neurodegenerative disease as evidenced from early changes at cellular and molecular levels in the neuronal component of the diabetic retina, which is further supported by various retinal functional tests indicating functional deficits in the retina soon after diabetes progression. Diabetes alters the level of a number of neurodegenerative metabolites, which increases influx through several metabolic pathways which in turn induce an increase in oxidative stress and a decrease in neurotrophic factors, thereby damage retinal neurons. Loss of neurons may implicate in vascular pathology, a clinical signs of DR observed at later stages of the disease. Here, we discuss diabetes-induced potential metabolites known to be detrimental to neuronal damage and their mechanism of action. In addition, we highlight important neurotrophic factors, whose level have been found to be dysregulated in diabetic retina and may damage neurons. Furthermore, we discuss potential drugs and strategies based on targeting diabetes-induced metabolites, metabolic pathways, oxidative stress, and neurotrophins to protect retinal neurons, which may ameliorate vision loss and vascular damage in DR.     

EGFR inhibitor,AG1478, inhibits inflammatory infiltration and angiogenesis in mice with diabetic retinopathy

Diabetic retinopathy (DR) is one of the most frequently occurring microvascular complications of diabetes. Recent evidence indicates that epidermal growth factor receptors (EGFRs) are critical pathogenic players in non‐neoplastic diseases, including diabetic cardiomyopathy and DR. However, the precise pathogenic mechanism of EGFR in DR has yet to be fully understood. In this study, we developed a type 1 diabetic early‐stage retinopathy mouse model using injections of streptozotocin and an oxygen‐induced end‐stage diabetic retinopathy (OIR) model characterized by hypoxia‐induced revascularization. We tested the hypothesis that the pathogenesis of DR can be reduced by the classic EGFR inhibitor, AG1478, in the mouse models. Our data indicated that treatment of AG1478 prevented retinal dysfunction, and reduced impairment of retinal structures as well as mitochondrial structures in retinal blood vessels in diabetic mice. Furthermore, AG1478 reduced neovascular tufts formation but had no effects on revascularization at the avascular sites when compared to untreated littermates in the OIR model. Our findings provide strong evidence that EGFR critically promoted retinal dysfunction, retinal structural impairment, and retinal vascular abnormalities in models of DR. We conclude that EGFR can be a potential important therapeutic target for treatment of DR.     

Old and new drug targets in diabetic retinopathy: from biochemical changes to inflammation and neurodegeneration

Diabetic Retinopathy (DR) is a major complication of diabetes and is a leading cause of blindness in western countries. DR has been considered a microvascular disease, and the blood-retinal barrier breakdown is a hallmark of this disease. The available treatments are scarce and not very effective. Despite the attempts to control blood glucose levels and blood pressure, many diabetic patients are affected by DR, which progresses to more severe forms of disease, where laser photocoagulation therapy is needed. DR has a huge psychological impact in patients and tremendous economic and social costs. Taking this into account, the scientific community is committed to find a treatment to DR. Understanding the cellular and molecular mechanisms underlying the pathogenesis of DR will facilitate the development of strategies to prevent, or at least to delay the progression of the disease. The involvement of the polyol pathway, advanced glycation end products, protein kinase C and oxidative stress in the pathogenesis of DR is well-documented, and several clinical trials have been conducted to test the efficacy of various drugs. More recent findings also demonstrate that DR has characteristics of chronic inflammatory disease and neurodegenerative disease, which increases the opportunity of intervention at the pharmacological level. This review presents past and recent evidences demonstrating the involvement of different molecules and processes in DR, and how different approaches and pharmacological tools have been used to prevent retinal cell dysfunction.     

波动性高糖对糖尿病视网膜病变的作用研究进展

糖尿病视网膜病变(diabetic retinopathy,DR)是糖尿病微血管严重并发症之一,其发生发展不仅与长期的高血糖水平有关,而且与血糖波动幅度呈现明显正相关。波动性高糖通过启动细胞自噬和细胞凋亡,激活氧化应激,损伤视网膜组织DNA,促进血管内皮生长因子(vascular endothelial growth factor,VEGF)的释放等多种途径参与DR的发生进展。     

Treating diabetic retinopathy by tackling growth factor pathways

Diabetic retinopathy (DR) remains a major cause of new cases of blindness onset in adults. The prevalence of diabetic eye disease is strongly related to the duration of diabetes, blood pressure and glycemic control, although a multifactorial pathogenesis is likely to be probable. Despite the effectiveness of current prevention (by tight metabolic and blood pressure control) and treatment (with laser photocoagulation) methods, and with the help of screening programs, diabetic eye disease is still a problem. Recent advances in our understanding of the pathogenesis of microvascular complications and particularly of the role of growth factors (GFs) in retinal changes have allowed significant advances in the medical management of DR. Studies of the biochemical process underlying DR have clearly demonstrated an important role for a number of aberrantly expressed GFs or their second messengers (eg, vascular endothelial growth factor, growth hormone, insulin-like growth factor-1, protein kinase C and pigment epithelium derived factor) possibly acting together in the development of structural changes characterizing early stages of vascular DR. The critical role of GF expression has led to new experimental therapeutic intervention in DR. In fact, timely pharmacological intervention in GF synthesis and activities may arrest the development of early vascular changes. As the effects of GFs become better understood, pharmacological manipulation of GF synthesis and action will be useful in the early stages of vascular change with the potential to prevent diabetes-related visual loss.     

The ethanol extract of Zingiber zerumbet rhizomes mitigates vascular lesions in the diabetic retina

Diabetic retinopathy (DR) is a common diabetic eye disease which is well-known as the result of microvascular retinal changes. Although the ethanol extract from Zingiber zerumbet (L.) Smith rhizome (EEZZR) has been indicated to ameliorate hyperglycemia in diabetes, its protective effect on DR remains unclear. The aim of this study was to determine the effects of EEZZR on DR in streptozotocin (STZ) diabetic rats. Diabetic rats were treated orally with EEZZR (200, 300 mg/kg per day) or calcium dobesilate (CD; 500 mg/kg per day) for 12 weeks. EEZZR displayed similar characteristics to CD in reducing blood–retinal barrier permeability in diabetic rats. Retinal histopathological observation showed that retinal vessels were decreased in EEZZR-treated diabetic rats. EEZZR decreased the increased retinal expression of vascular endothelial growth factor (VEGF) and upregulate the expressions of renal pigment epithelium-derived factor (PEDF) in diabetic rats. Retinal mRNA expression of tumor necrosis factor-α, interleukin (IL)-1, IL-6, monocyte chemotactic proteins-1, intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 were all decreased in EEZZR-treated diabetic rats. Moreover, EEZZR could attenuate phosphorylation of nuclear factor Kappa B (NF-κB) p65 and extracellular signal-regulated kinase (ERK)1/2 as well as inhibit the nuclear translocation of pNF-κB p65 induced by diabetes. In conclusion, restoring the balance between stimulators and inhibitors of angiogenesis may be associated with the protective effect of EEZZR on DR. In addition, EEZZR can ameliorate retinal inflammation via transrepression of NF-κB and inhibition of ERK1/2 signaling pathway.     

糖尿病大鼠视网膜血流动力学与视网膜血管形态学关系的研究

经过严格评估,美国《剑桥科学文摘》(Cambridge Scientific Abstracts,CSA)已决定正式将《现代药物与临床》列为其来源期刊。CSA于30多年前创办,是世界著名的二次文献出版公司美国剑桥科学文摘出版公司出版发行的综合性网络数据库,是国际上具有重要影响力的科学技术文献检索系统之一,是近几年发展最快的、大型的、综合性最强的数据库,覆盖的学科范     

SGLT2 inhibitors: a promising new therapeutic option for treatment of type 2 diabetes mellitus

Background Hyperglycemia is an important pathogenic component in the development of microvascular and macrovascular complications in type 2 diabetes mellitus. Inhibition of renal tubular glucose reabsorption that leads to glycosuria has been proposed as a new mechanism to attain normoglycemia and thus prevent and diminish these complications. Sodium glucose cotransporter 2 (SGLT2) has a key role in reabsorption of glucose in kidney. Competitive inhibitors of SGLT2 have been discovered and a few of them have also been advanced in clinical trials for the treatment of diabetes. Objective To discuss the therapeutic potential of SGLT2 inhibitors currently in clinical development. Key findings A number of preclinical and clinical studies of SGLT2 inhibitors have demonstrated a good safety profile and beneficial effects in lowering plasma glucose levels, diminishing glucotoxicity, improving glycemic control and reducing weight in diabetes. Of all the SGLT2 inhibitors, dapagliflozin is a relatively advanced compound with regards to clinical development. Summary SGLT2 inhibitors are emerging as a promising therapeutic option for the treatment of diabetes. Their unique mechanism of action offers them the potential to be used in combination with other oral anti‐diabetic drugs as well as with insulin.     

Dapagliflozin: an emerging treatment option in type 2 diabetes

The global incidence of type 2 diabetes mellitus is increasing. Hyperglycemia contributes to both the complications associated with diabetes mellitus and progression of the underlying disease. New agents that lower blood glucose levels are therefore needed to help slow disease progression and reduce disease complications. The sodium-glucose co-transporter 2 (SGLT2) reabsorbs glucose in the kidney. Inhibition of SGLT2 by new agents, such as dapagliflozin, has the potential to reduce hyperglycemia by inhibiting glucose reabsorption in the kidney. Preclinical trials demonstrated that dapagliflozin is a potent and selective inhibitor of SGLT2. It has shown linear pharmacokinetics over the dose range of 2.5 – 500 mg/day, is not significantly influenced when taken with food and is primarily eliminated via urinary excretion. Clinical trials have shown that dapagliflozin treatment induces glucosuria and improves glycemic parameters in patients with type 2 diabetes. Inhibition of SGLT2 is a new and promising approach to treating type 2 diabetes mellitus. This article reviews the role of dapagliflozin as an emerging treatment option in type 2 diabetes.