The progress in understanding and treatment of diabetic retinopathy

Diabetic retinopathy is the most frequently occurring complication of diabetes mellitus and remains a leading cause of vision loss globally. Its aetiology and pathology have been extensively studied for half a century, yet there are disappointingly few therapeutic options. Although some new treatments have been introduced for diabetic macular oedema (DMO) (e.g. intravitreal vascular endothelial growth factor inhibitors (‘anti-VEGFs’) and new steroids), up to 50% of patients fail to respond. Furthermore, for people with proliferative diabetic retinopathy (PDR), laser photocoagulation remains a mainstay therapy, even though it is an inherently destructive procedure.This review summarises the clinical features of diabetic retinopathy and its risk factors. It describes details of retinal pathology and how advances in our understanding of pathogenesis have led to identification of new therapeutic targets. We emphasise that although there have been significant advances, there is still a pressing need for a better understanding basic mechanisms enable development of reliable and robust means to identify patients at highest risk, and to intervene effectively before vision loss occurs.     

玉液汤对糖尿病性黄斑水肿的疗效观察及机制探讨

目的:观察玉液汤对糖尿病性黄斑水肿的临床疗效及其与IL-6、VEGF的影响。方法:将60例糖尿病性黄斑水肿患者随机分成2组,治疗组给予玉液汤+激光光凝治疗,对照组予激光光凝治疗,观察治疗4周后2组视力、视网膜厚度、视网膜血管情况等;应用ELISA检测2组患者血清中IL-6、VEGF含量表达情况。结果:2组经不同方法治疗4周后视力、视网膜厚度、视网膜血管情况比较差异有统计学意义(P0.05),治疗组经玉液汤口服治疗与对照组比较,IL-6、VEGF的血清含量情况明显低于对照组,差异有统计学意义(P0.05)。结论:玉液汤治疗糖尿病性黄斑水肿可以有效提高视力、改善视网膜厚度、视网膜血管情况,是一种安全有效的治疗方式,值得临床推广应用,而调节IL-6和VEGF可能是玉液汤发挥治疗作用的重要靶点。     

益肾活血颗粒对气虚血瘀型早期糖尿病肾病患者尿CTGF影响的临床研究

目的:探讨益肾活血颗粒对气虚血瘀型早期糖尿病肾病患者患者纤维化的影响及其对结缔组织生长因子(Connective Tissue Growth Factor,CTGF)的作用。方法:将90例气虚血瘀型2型糖尿病肾病(Diabetic Nephropathy,DN)患者采用采用随机信封方式分为常规组和治疗组,每组各45例,另将同期45例健康体检者设为对照组,其中2组DN患者均接受积极控制血糖,治疗高血压,调节脂质代谢异常等治疗,治疗组则在该基础上加用益肾活血颗粒。2组均以12周为1个疗程,于治疗前及治疗12周后检测3组蛋白尿排泄率(u AER)、糖化血红蛋白(Hb Alc)、空腹血糖(FGC)、餐后2 h血糖(2 h BG)、I、Ⅲ型胶原(PI NP、PⅢNP)以及尿结缔组织生长因子(CTGF)的变化。结果:1)2组患者治疗前24 h蛋白尿排泄率、Hb Alc、FGC、2 h BG比较差异无统计学意义(P0.05),2组治疗后24 h蛋白尿排泄率、FPG、OGTT均较治疗前降低,与常规组比较,治疗组降低的程度较为明显(P0.05);治疗组的临床有效率明显高于对照组(P0.05)。2)治疗前相比,治疗12周后治疗组和常规治疗组患者u AER、I、Ⅲ型胶原以及CTGF水平均有明显下降(P0.01),其中治疗组上述指标均显著低于常规治疗组(P0.05)。3)利用Spearman法进行相关参数相关性分析后可知CTGF与PI NP、PⅢNP均具有正相关性(P0.05)。结论:益肾活血颗粒可以显著降低尿CTGF水平,该效应可能是益肾活血颗粒防治气虚血瘀型早期糖尿病肾病纤维化的作用机制之一。     

尿毒清颗粒联合缬沙坦胶囊治疗糖尿病肾病大量蛋白尿临床观察

目的观察尿毒清颗粒联合缬沙坦胶囊治疗糖尿病肾病大量蛋白尿的临床疗效。方法将78例糖尿病肾病大量蛋白尿患者随机分为2组。对照组38例予缬沙坦胶囊治疗,治疗组40例在对照组治疗基础上加用尿毒清颗粒治疗。2组均治疗1个月后统计临床疗效,并观察2组治疗前后24h尿微量蛋白、24h尿蛋白定量、血肌酐(Cr)及尿素氮(BUN)。结果治疗组总有效率95.00%,对照组总有效率78.95%,2组比较差异有统计学意义(P0.05),治疗组疗效优于对照组。2组治疗后24h尿微量蛋白、24h尿蛋白定量、Cr及BUN均降低(P0.05),且治疗组降低优于对照组(P0.05)。结论尿毒清颗粒联用缬沙坦胶囊治疗糖尿病肾病大量蛋白尿疗效确切。     

消渴浴足方治疗糖尿病周围神经病变临床研究

目的：评价消渴浴足方治疗糖尿病周围神经病变(diabetic peripheral neuropathy, DPN)的临床疗效。方法将符合入选标准的100例DPN住院患者按随机数字表法分为2组各50例,对照组采用西医常规治疗,治疗组在此基础上配合消渴浴足方足浴。对2组治疗前后中医症状积分、DPN临床评分(多伦多积分)进行比较,评价临床疗效。结果治疗后,治疗组多伦多评分中,症状分[(1.50±0.94)分比(2.23±1.01)分,t＝-2.920]、反射分[(3.60±1.77)分比(4.27±1.72)分,t＝-1.980]、感觉分[(1.53±0.63)分比(2.10±0.84)分,t＝-2.950]均显著低于对照组(P＜0.05);治疗组中医证候主症积分[(1.77±1.17)分比(3.17±1.82)分,t＝-3.550]、次症积分[(2.23±1.59)分比(4.27±1.57)分,t＝-4.980]、舌苔脉象积分[(1.83±0.65)分比(2.47±0.51)分,t＝-4.220]均显著低于对照组(P＜0.01)。结论消渴浴足方可改善DPN患者的临床症状。     

复荣通脉胶囊对糖尿病模型大鼠坐骨神经白细胞介素-1及肿瘤坏死因子-α表达的影响

目的 观察复荣通脉胶囊对糖尿病模型大鼠坐骨神经IL-1、TNF-α表达的影响.方法 50只大鼠按随机数字表法随机分为正常组、模型组及复荣通脉低、中、高剂量组,每组10只.采用腹腔注射STZ (60 mg/kg)诱导糖尿病.诱导糖尿病后1周,复荣通脉低、中、高剂量组分别灌胃复荣通脉胶囊混悬液0.7、1.4、2.8 g/kg,正常组和模型组灌胃等体积生理盐水,1d/次,共8周.采用免疫组化染色法检测坐骨神经IL-1和TNF-α表达水平.结果 模型组IL-1[(1.43±0.17)％比(0.21±0.09)％;P＜0.05]和TNF-α[(1.98±0.12)％比(0.35±0.03)％;P＜0.05]表达均较正常对照组显著增高.复荣通脉胶囊中、高剂量组IL-1[(0.54±0.14)％、(0.51±0.13)％比(1.43±0.17)％;P＜0.05]、TNF-α[(0.57±0.17)％、(0.49±0.15)％比(1.98±0.12)％;P＜0.05]均较模型组显著降低,且显著低于复荣通脉低剂量组(IL-1:1.08％±0.18％,TNF-α:1.11％±0.09％;P＜0.05).结论 复荣通脉胶囊可降低糖尿病大鼠坐骨神经IL-1和TNF-α表达.     

Clinical outcomes of toe amputation in patients with type 2 diabetes in Tianjin,China

The aim of this study is to determine the predictors for reulceration, reamputation and mortality in patients with diabetes following toe amputation, and the impact of activities of daily living on clinical outcomes. This prospective cohort study included 245 patients who had undergone toe amputation (202 healing and 43 non‐healing) and was followed for a 5‐year period. Data regarding new foot ulceration, reamputation and mortality were recorded, and the patients' activities of daily living were evaluated. The rate of wound healing was 82·4%. The rate of follow‐up in the healed group was 91·6%. In years 1, 3 and 5, the cumulative incidence of patients who developed a new foot ulcer was 27·3%, 57·2% and 76·4%, respectively, leading to reamputation in 12·5%, 22·3% and 47·1%, respectively. The cumulative mortality was 5·8%, 15·1% and 32·7% at 1, 3 and 5 years, respectively. Multivariate analysis showed that GHbA1c > 9% (75 mmol/mol) was identified as an independent predictor of impaired wound healing, reulceration and reamputation. An age of >70 years was identified as an independent predictor of reamputation, mortality and impairment of activities of daily living. Despite a satisfactory initial healing rate after the first toe amputation, with the extension course after the toe amputation, the long‐term outcomes are not optimistic. In developing countries like China, taking measures to prevent reulceration and reamputation is very important for patients with diabetic foot minor amputations, especially following toe amputation.     

Diabetic foot disease is associated with reduced erythrocyte deformability

The pathogenesis of diabetic foot disease is multifactorial and encompasses microvascular and macrovascular pathologies. Abnormal blood rheology may also play a part in its development. Using a cell flow analyser (CFA), we examined the association between erythrocyte deformability and diabetic foot disease. Erythrocytes from diabetic patients with no known microvascular complications (n = 11) and patients suffering from a diabetic foot ulcer (n = 11) were isolated and their average elongation ratio (ER) as well as the ER distribution curve were measured. Average ER was decreased in the diabetic foot patients compared with the patients with diabetes and no complications (1·64 ± 0·07 versus 1·71 ± 0·1; P = 0·036). A significant rise in the percentage of minimally deformable red blood cells RBCs in diabetic foot patients compared with the patients with no complications was observed (37·89% ± 8·12% versus 30·61% ± 10·17%; P = 0·039) accompanied by a significant decrease in the percentage of highly deformable RBCs (12·47% ± 4·43% versus 17·49% ± 8·17% P = 0·046). Reduced erythrocyte deformability may slow capillary flow in the microvasculature and prolong wound healing in diabetic foot patients. Conversely, it may be the low‐grade inflammatory state imposed by diabetic foot disease that reduces erythrocyte deformability. Further study of the rheological changes associated with diabetic foot disease may enhance our understanding of its pathogenesis and aid in the study of novel therapeutic approaches.     

氯沙坦钾联合环磷酰胺治疗2型糖尿病肾病大鼠肾组织中TGF-β1、CD68和MCP-1表达的影响

目的 探讨氯沙坦钾联合环磷酰胺在治疗2型糖尿病肾病大鼠时对转化生长因子β1 (TGF-β1)、CD68和单核细胞趋化因子蛋白-1(MCP-1)表达的影响.方法 选择45只雄性健康SD大鼠,按随机数字表法分为正常对照组、2型糖尿病肾病模型组和氯沙坦钾联合环磷酰胺治疗组大鼠各15只.造模成功后,观察三组大鼠的血生化指标和肾脏病理学改变等,并采用免疫组化染色比较其TGF-β1、CD68和MCP-1的表达情况.结果 与正常对照组相比,模型组和治疗组的体质量较低,在尿蛋白、血糖、甘油三酯、胆固醇和肌酐等血生化指标以及TGF-β1、CD68和MCP-1表达方面均显著高于对照组,且差异均有统计学意义(P＜0.05);治疗组与模型组相比,甘油三酯、肌酐以及TGF-β1、CD68和MCP-1表达均较低(P＜0.05).结论 氯沙坦钾联合环磷酰胺在治疗2型糖尿病肾病大鼠时,可以通过降低肾组织中TGF-β1、CD68和MCP-1的表达水平来降低炎细胞浸润和免疫反应程度,从而延缓糖尿病肾病病情的进展,但是否能用于临床有待于进一步研究.     

Receptor for advanced glycation end products (RAGE) knockout reduces fetal dysmorphogenesis in murine diabetic pregnancy

The receptor for Advanced Glycation End products (RAGE) is implicated in the pathogenesis of diabetic complications, but its importance in diabetic embryopathy is unclear. We therefore investigated the role of RAGE in diabetic embryopathy using streptozotocin induced diabetes in female wild type (WT) C57Bl/6N and RAGE knockout C57Bl/6N (RAGE^−/−) mice, mated with control males of the same genotype. Maternal diabetes induced more fetal resorption and malformation (facial skeleton, neural tube) in the WT than in the RAGE^−/− fetuses. Maternal plasma glucose and methylgyoxal concentrations, as well as embryonic N(ε)-carboxymethyl-lysine (CML) levels were increased to the same extent in diabetic WT and RAGE^−/− pregnancy. However, maternal diabetes induced increased fetal hepatic isoprostane 8-iso-PGF_2α levels (oxidative stress marker) and embryonic activation of NFκB in WT only (not in RAGE^−/− embryos). The association between RAGE knockout and diminished embryonic dysmorphogenesis in diabetic pregnancy suggests that embryonic RAGE activation is involved in diabetic embryopathy.