糖尿病视网膜病变患者检测糖化血红蛋白的临床意义

目的探讨糖尿病视网膜病变 (DR)患者检测糖化血红蛋白 (HbA1c)的临床意义。方法对154例2型糖尿病患者DR情况和HbA1c水平进行检测。并对71例、病程5～10年的糖尿病患者正常眼底 (NDR)或单纯型糖尿病视网膜病变 (BDR)患者进行1年的随访 ,检测DR进展情况和HbA1c水平。结果DR组HbA1c高于NDR组。增殖型糖尿病视网膜病变 (PDR)组HbA1c高于BDR组。随访1年 ,视网膜病变进展组(A组)平均HbA1c高于视网膜病变稳定组(B组),差异具有统计学意义 (P<0.01)。结论DR的程度和进展与HbA1c增高有关     

Nitric oxide-cGMP and prostacyclin-cAMP pathways in patients with type II diabetes and different types of retinopathy

The aim of this study was to investigate two factors of endothelial dysfunction and their platelet second messengers in patients with type II diabetes and different types of retinopathy. We compared 20 healthy volunteers and 117 patients with type II diabetes (34 with no signs of diabetic retinopathy, 26 with background diabetic retinopathy, 29 with ischemic-proliferative diabetic retinopathy and 28 with edematous diabetic retinopathy). The following parameters were recorded: platelet aggregometry, nitrites, 6-keto-prostaglandin-F(1alpha) and intraplatelet cAMP and cGMP. Platelet aggregation was greater in patients with diabetic retinopathy. The concentration of ADP that produced 50% maximum intensity of aggregation was 1.81 microM in patients without diabetic retinopathy, 0.92 microM in patients with background diabetic retinopathy, 0.85 microM in patients with ischemic-proliferative diabetic retinopathy and 0.44 microM in patients with edematous diabetic retinopathy. The platelets in these patients were more resistant to inhibition by SIN-1 (concentrations of SIN-1 that produced 50% inhibition of maximum intensity of collagen-induced aggregation in the four patient groups: 18.1, 13.6, 16.2 and 33.2 microM, respectively). Nitrite concentration in patients with ischemic-proliferative diabetic retinopathy was one sixth of the value in healthy controls, but there was no significant difference between the control group and patients with edematous diabetic retinopathy. In the latter group, neutrophils increased nitrite production by 68.7 +/- 3%, whereas in patients with ischemic-proliferative diabetic retinopathy, this increase was 18.7 +/- 2.0%. We conclude that nitric oxide production is higher in patients with type II diabetes and edematous retinopathy than in those with ischemic-proliferative retinopathy. This finding, together with the possibly greater production of free radicals, may explain the greater impairment of platelet function in the former patients.     

Prevalence and associated factors of diabetic retinopathy in rural Korea: the Chungju metabolic disease cohort study

This study was aimed to investigate the prevalence of diabetic retinopathy and its associated factors in rural Korean patients with type 2 diabetes. A population-based, cross-sectional diabetic retinopathy survey was conducted from 2005 to 2006 in 1,298 eligible participants aged over 40 yr with type 2 diabetes identified in a rural area of Chungju, Korea. Diabetic retinopathy was diagnosed by a practicing ophthalmologist using funduscopy. The overall prevalence of diabetic retinopathy in the population was 18% and proliferative or severe non-proliferative form was found in 5.0% of the study subjects. The prevalence of retinopathy was 6.2% among those with newly diagnosed type 2 diabetes and 2.4% of them had a proliferative or severe non-proliferative diabetic retinopathy. The odds ratio of diabetic retinopathy increased with the duration of diabetes mellitus (5-10 yr: 5.2- fold; > 10 yr: 10-fold), postprandial glucose levels (> 180 mg/dL: 2.5-fold), and HbA1c levels (every 1% elevation: 1.34-fold). The overall prevalence of diabetic retinopathy in rural Korean patients was similar to or less than that of other Asian group studies. However, the number of patients with proliferative or severe non-proliferative diabetic retinopathy was still high and identified more frequently at the time of diagnosis. This emphasizes that regular screening for diabetic retinopathy and more aggressive management of glycemia can reduce the number of people who develop diabetic retinopathy.     

Blood antioxidant parameters in patients with diabetic retinopathy

It has been postulated that enhanced generation of reactive oxygen species (ROS) may take part in a pathogenesis of diabetic microvascular complication - retinopathy. There are two types of diabetic retinopathy, non-proliferative (simplex) and proliferative. ROS are anihilated by an intracelluar enzymatic system composed mainly of glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT). Beta-carotene, tocopherols and ascorbic acid are major components of serum antioxidants. All serum antioxidants are usually measured together as total antioxidant status (TAS). Erythrocyte activities of GPx, SOD, CAT and TAS were measured in diabetic patients without retinopathy, with non-proliferative and proliferative retinopathy. Obtained results were correlated with a period of diabetic history and a period of insulin treatment. SOD was significantly elevated in diabetics with non-proliferative retinopathy compared to patients without retinopathy. TAS was significantly lower in patients with proliferative retinopathy than in diabetics not developing retinopathy. Only CAT was significantly negatively correlated with the period of insulin treatment. This significant negative correlation was also observed in a subgroup of patients with proliferative retinopathy.     

Ophthalmological morbidity in very-low-birthweight infants with bronchopulmonary dysplasia.

This study was undertaken to determine the relationship between retinopathy of prematurity, ocular sequelae of retinopathy, and bronchopulmonary dysplasia in infants weighing < 1250 g at birth prior to the introduction of steroid therapy for chronic lung disease. Ophthalmological data from 67 infants (22 with severe bronchopulmonary dysplasia and 45 controls) who were enrolled prospectively in an early intervention program were analyzed. The infants had two or more eye examinations prior to discharge and a follow-up examination at 12 to 18 months postconceptual age. The incidence of any retinopathy of prematurity was 33%, and severe retinopathy was 25%. Infants with severe bronchopulmonary dysplasia were 1.7 times more likely to develop any retinopathy and 1.8 times more likely to develop severe retinopathy than controls. The incidence of ocular sequelae, was 45%. Infants with any retinopathy had a 2.3 odds of developing sequelae, and infants with severe retinopathy had a 2.64 odds ratio. When adjusted for bronchopulmonary dysplasia, the odds ratio for developing sequelae was 1.36 in infants with any retinopathy and 1.27 in those with severe retinopathy. The predictors of retinopathy were lower birthweight and gestational age, acidosis, and hypoxemia. Bronchopulmonary dysplasia per se has an adverse effect on ophthalmologic morbidity. Evaluation of the adverse effect of any therapy for chronic lung disease on retinopathy of prematurity should make adjustments for the underlying lung disease.     

Progression of diabetic retinopathy after pancreas transplantation for insulin-dependent diabetes mellitus

We studied the effect of successful pancreas transplantation and consequent normoglycemia (mean total hemoglobin A1, 7.0 percent; range, 5.8 to 8.3) on visual function and diabetic retinopathy in 22 patients with Type I diabetes mellitus (study group). Sixteen similar patients in whom pancreas transplantation had been unsuccessful (mean total hemoglobin A1, 12.0 percent; range, 8.0 to 18.0) served as a control group. The majority of patients in both groups had advanced proliferative retinopathy. At a mean follow-up of 24 months we found no significant difference between the groups in the rate of progression of retinopathy, expressed as a score. Success of the transplantation did not prevent progression of retinopathy across the range of retinopathy studied. Progressive retinopathy was observed more commonly in patients with low retinopathy scores (nonproliferative or mild proliferative retinopathy) at base line in both the study group (13 of 17 eyes, or 76 percent) and the control group (7 of 12 eyes, or 58 percent). Further analysis suggested the possibility that after three years of euglycemia, the study group had less deterioration than the control group, particularly in eyes with advanced retinopathy. We observed no difference in the rate of loss of vision between the two groups. This study provides evidence that pancreas transplantation and subsequent normoglycemia neither reverse nor prevent the progression of diabetic retinopathy.     

Manganese superoxide dismutase gene polymorphism (V16A) is associated with diabetic retinopathy in Slovene (Caucasians) type 2 diabetes patients

Substantial data indicate that oxidative stress is involved in the development of diabetic retinopathy. Two candidate genes that affect the oxidative stress are manganese mitochondrial superoxide dismutase (Mn-SOD) and endothelial nitric oxide synthase (eNOS). The aim of the present study was to examine the role of the V16A polymorphism of the Mn-SOD gene and the 4a/b polymorphism of the eNOS gene in the development of diabetic retinopathy in Caucasians with type 2 diabetes. In this cross sectional case-control study 426 unrelated Slovene subjects (Caucasians) with type 2 diabetes mellitus were enrolled: 283 patients with diabetic retinopathy and the control group of 143 subjects with type 2 diabetes of duration of more than 10 years who had no clinical signs of diabetic retinopathy. A significantly higher frequency of the VV genotype of the V16A polymorphism of the Mn-SOD was found in patients with diabetic retinopathy compared to those without diabetic retinopathy (OR=2.1, 95% whereas the 4a/b polymorphism of the eNOS gene failed to yield an association with diabetic retinopathy. We may conclude that the VV genotype of the V16A polymorphism of the Mn-SOD gene was associated with diabetic retinopathy in Caucasians with type 2 diabetes, therefore it might be used as a genetic marker of diabetic retinopathy in Caucasians.     

Platelet and coagulation factors in proliferative diabetic retinopathy.

Plasma beta-thromboglobulin, platelet factor 4, fibrinogen, fibrinopeptide A, antithrombin III, factor VIII related antigen, alpha 2-macroglobulin, platelet count, and total glycosylated haemoglobin were measured in three well matched groups of subjects: non-diabetic controls, diabetics without retinopathy, and diabetics with proliferative retinopathy. beta-thromboglobulin and platelet factor 4 concentrations were significantly higher in the diabetics with retinopathy than in the controls and platelet factor 4 was also increased in the diabetics without retinopathy compared with controls. Fibrinogen concentration was raised in diabetics without retinopathy compared with controls, diabetics with retinopathy compared with controls, and diabetics with retinopathy compared with those without. Fibrinopeptide A concentration did not differ significantly between groups. Antithrombin III levels were increased in diabetics with retinopathy compared with controls, and in diabetics with retinopathy compared with those without. Factor VIII related antigen values were higher in both the diabetic groups when compared with the controls. Fibrinopeptide A concentration correlated with both beta-thromboglobulin and platelet factor 4 in each of the three groups. Haemostatic abnormalities in diabetes have been shown, although a hypercoagulable state has not been confirmed. These changes in platelet and coagulation function may be secondary to the development of microvascular disease and their role in the pathogenesis of retinopathy remains uncertain.     

The effect of diabetic control on the incidence of, and changes in, retinopathy in type 2 non-insulin dependent diabetic patients.

The purpose of this study was to investigate the association between retinopathy and the levels of diabetic control found in type 2 non-insulin dependent diabetic patients. The study covered a four-year period and used retrospective, routinely recorded general practice and optometry records from 260 patients; those with retinopathy (n = 38) and those without retinopathy (n = 222). The study demonstrated a strong relationship between the presence of retinopathy and long-term diabetic control as measured by glycosylated HbA1c, disease duration and, to a lesser extent, the level of urine microalbumin. Blood pressure, cholesterol, body-mass index, and smoking status showed little association with the presence of retinopathy. We conclude that retinopathy, assessed by community optometrists, is a significant correlate of poor diabetic control.     

The relationship of soluble immune complexes, insulin antibodies and insulin-anti-insulin complexes to platelet and coagulation factors in type 1 diabetic patients with and without proliferative retinopathy.

The possible correlation between soluble immune factors and platelet and coagulation factors has been evaluated in Type 1 diabetic patients with and without proliferative retinopathy, and in non-diabetic controls. Soluble immune complexes, platelet factor IV (PF4), beta-thromboglobulin, fibrinogen, factor VIII related antigen and anti-thrombin III were significantly increased in Type 1 diabetic patients with retinopathy as compared to non-diabetic controls. Fibrinogen and anti-thrombin III were also higher in those patients with retinopathy compared to those without retinopathy. A significant correlation was found between positive values of soluble immune complexes and increased levels of PF4 and beta-thromboglobulin in diabetic patients with retinopathy. The presence of soluble immune complexes and insulin-anti-insulin complexes was associated with a significantly greater number of elevated haemostatic factors in retinopathic patients. Our findings suggest that the interaction of platelets and soluble immune complexes or insulin-anti-insulin complexes may be pathologically relevant to the development of diabetic retinopathy.     

糖尿病视网膜病变相关基因多态性的研究进展

糖尿病视网膜病变是目前国际上最主要的致盲性眼病之一,患病率日渐升高.其发生和发展与血糖水平、糖尿病病程、环境及遗传等多种因素有关.近些年来,随着基因多态性与糖尿病视网膜病变关系的研究不断深入和进展,已经筛选出了可能与之相关的数十 种基因,其中几种基因多态性已经被证实为糖尿病视网膜病变发生的独立危险因素.现将与糖尿病视网膜病变密切相关的基因多态性研究进展作一综述.     

早产儿视网膜病变发病率的临床研究

目的 研究以人群为基础的早产儿视网膜病变发病率。方法 对我院2003年9月至2005年12月产科接生的1365例新生儿进行广泛普查，特别是早产儿，均对其进行眼底检查及早产儿视网膜病变风险评估。结果 在205例早产儿中，确诊为早产儿视网膜病变患儿为31人。结论 在普查的1365例新生儿中，早产儿视网膜病变发病率为2．27％，1-3期病变患儿占早产儿百分比为12％，4—5期患儿占早产儿百分比为3％。     

2型糖尿病视网膜病变患者血清sVCAM-1水平的变化和意义

研究糖尿病视网膜病变不同时期血清可溶性血管内皮细胞粘附分子-1(sVCAM-1)与视网膜病变严重程度、诊断病程、血清胰岛素和血糖的相关性.采用ELISA法检测85例2型糖尿病视网膜病变患者血清sVCAM-1含量, 由同一眼科医师通过眼底镜或荧光造影检查, 将患者分为无视网膜病变组(NDR)、背景期视网膜病变组(BDR)和增殖期视网膜病变组(PDR).结果显示, 三组糖尿病患者血清sVCAM-1水平均高于对照组, 其中PDR组、BDR组血清sVCAM-1水平与对照组和NDR组比较, 均有显著性差异(P＜0.01), NDR组与对照组比较也存在显著性差异(P＜0.01).糖尿病患者血清sVCAM-1水平与血糖、血清胰岛素、诊断病程均无相关性(P＞0.05).研究表明, 糖尿病视网膜病变不同时期血清sVCAM-1水平的变化可作为判断视网膜病变发展和严重程度的指标, 为临床早期发现和治疗糖尿病视网膜病变提供较好的依据.     

Leukocyte lipid peroxidation, superoxide dismutase and catalase activities of type 2 diabetic patients with retinopathy

Increased oxidative stress might play an important role in the initiation and progression of diabetic complications. The present study has been undertaken to investigate whether there is any relationship between retinopathy degree and leukocyte superoxide dismutase (SOD) and catalase (CAT) activities and lipid peroxidation (LPO) in diabetic individuals with type 2 diabetic retinopathy. Patients were groupped with respect to the degree of retinopathy. Leukocyte malondialdehyde (MDA) levels, and SOD and CAT activities were measured in patients with type 2 diabetes mellitus (n=41) and nondiabetic healthy controls (n=23). Leukocyte LPO of the type 2 diabetic patients with retinopathy was significantly increased (p < 0.001), whereas SOD and CAT activities were decreased (p<0.001 and p<0.001, respectively) compared to those of controls. MDA concentrations rose while SOD and CAT activities fell with increasing severity of diabetic retinopathy, altough there was no significant difference in comprasion of the parameters mentioned above between the diabetic patients with and without retinopathy. Our results show that leukocytes in patients with type 2 diabetic retinopathy are affected by oxidative stress which might be contribute to pathogenesis of diabetic retinopathy. Prospective studies are needed to evaulate the relationship between the leukocyte antioxidants status and DR.     

Prognostic factors and retinopathy in type 1 diabetics in Iceland

Prognostic factors, particularly those related to metabolic control, were analysed individually over a period of 12 months prior to fundus photography in 149 type 1 (insulin-dependent, ketosis-prone) diabetics in Iceland. Patients without retinopathy in their first 20 years of diabetes visited the Diabetic Clinic significantly more frequently than those with retinopathy (p less than 0.05). Mean blood sugar values and mean per cent body weight did not differ between patients with or without retinopathy. Few between patients with or without retinopathy. Few patients were obese. In patients with 5-9 years' duration of diabetes, retinopathy was first seen after 7.7 +/- 0.3 years (mean +/- SEM). Those with retinopathy were significantly older at the time of the diagnosis of diabetes than those without eye lesions (p less than 0.025), a tendency also noted in those with 10-19 years' duration (p less than 0.10). Conversely, patients without retinopathy after diabetes for 20 years or more were significantly older at the time of diagnosis (p less than 0.02). They used significantly less insulin daily than those with retinal lesions (p less than 0.005) and 70% were females. Subsequently, a significant (p less than 0.047) male excess was found to characterize a group of patients with proliferative retinopathy.     

UCP 3基因多态性与DR关系的研究

目的:探讨解偶联蛋白(UCP)3基因G304A多态性与糖尿病视网膜病变(diabetic retinopathy, DR)的关系.方法:201例糖尿病患者(分为伴有DR组45例,不伴有DR的糖尿病患者作为对照组156例),检测所有患者的基因组,用聚合酶链反应(PCR)对UCP 3基因进行扩增,记录各组UCP 3等位基因及基因型频率并进行比较.结果:UCP 3基因G304A多态性和基因频率在各组间无显著性差异(P＞0.05).结论:解偶联蛋白(UCP)3基因G304A多态性与中国人糖尿病视网膜病变无关系.     

Inhibition of protein kinase C might be harmful to diabetic retinopathy

Selective loss of retinal pericytes is the earliest histopathological hallmark in diabetic retinopathy. Various structural and functional abnormalities in diabetic retinas are the consequent of the loss of pericytes. Therefore, elucidating the molecular mechanisms for pericyte loss and targeting this characteristics change in early diabetic retinopathy may help to slow the development and progression of sight-threatening retinopathy in diabetes. Protein kinase C (PKC) inhibition has been used in therapeutic trials intended to reduce the incidence of proliferative diabetic retinopathy. However, we speculate that it is likely to do more harm than good in diabetic retinopathy because PKC inhibition augments pro-apoptotic effects of high glucose on cultured retinal pericytes. In the DCCT-Epidemiology of Diabetes Interventions and Complications Research, the reduction in the risk of progressive retinopathy resulting from intensive therapy in patients with type 1 diabetes persisted for at least four years, despite increasing hyperglycemia. These clinical studies strongly suggest that so-called "hyperglycemic memory" causes vascular damage in diabetic retinopathy. Glucose react non-enzymatically with the amino groups of proteins to initiate a complex series of rearrangement and dehydration reactions to produce a class of irreversibly cross-linked, fluorescent moieties, termed advanced glycation end products (AGEs). The formation and accumulation of AGEs progress at an extremely accelerated rate in diabetic retinas, and these products have been implicated in the pathogenesis of loss of pericytes in diabetic retinopathy. The nature of AGEs is most compatible with the theory of 'hyperglycemic memory' as well. We hypothesize here that PKC inhibition is likely to do harm in diabetic retinopathy, while inhibition of AGE formation might be a promising therapeutic strategy for treatment of this devastating complication.     

血管内皮生长因子3’非翻译区936C/T 突变与糖尿病视网膜病变的关系

目的: 探讨血管内皮生长因子(VEGF)936C/T突变与糖尿病视网膜病变(DR)的关系。方法: 按WHO的糖尿病(DM)诊断和排除标准及分型标准,选取无亲缘关系的2型糖尿病患者254例,分为非增殖性视网膜病变(NPDR)组、增殖性视网膜病变(PDR)组和单纯2型糖尿病(DM)组,选取健康体检人群120例作为正常对照组(NC)。采用PCR-RFLP方法确定全部人员的基因型,对不同组间的临床与生化指标及VEGF浓度、936C/T多态性进行了统计分析。结果: NPDR 和PDR组的CC基因型频率及C等位基因频率显著高于DM组(²=7.490,²=4.448, P<0.05;²=8.333,²=5.227,P<0.05)和NC组(²=9.934,²=4.899, P<0.05; ²=10.895,²=5.714, P<0.05),而NPDR 和PDR组(CT+TT)基因型频率及T等位基因频率显著低于NC组(²=9.934,²=10.895, P<0.01;²=4.899,²=5.714, P<0.05)和DM组(²=7.490,²=8.333,P<0.01;²=4.448,²=5.227,P<0.05)。DR多重危险因素分析显示血清低密度脂蛋白胆固醇(LDL-C)、总胆固醇(TC)、糖化血红蛋白(HbA1c)水平以及VEGF浓度和DR发病呈正相关,而VEGF 936C/T突变与DR发病危险呈负相关(β=-1.027,OR=0.343,P<0.01,CI:0.157-0.723)。结论: 中国汉族人群中存在VEGF 936C/T突变。VEGF 936C等位基因及CC基因型可能是中国汉族糖尿病患者易于发生DR的危险性遗传标志,而VEGF 936T等位基因和携带T等位基因的基因型(936TT基因型和936CT基因型)可能是DR发病风险降低的遗传标志。血浆VEGF、 LDL-C、TC和HbA1c水平可能是2型糖尿病患者易发DR的危险因素。     

Autoimmune retinopathy: A review and summary

Three main forms of autoimmune retinopathy (AIR) have been identified over the last 15 years: cancer-associated retinopathy (CAR), melanoma-associated retinopathy (MAR), and nonneoplastic autoimmune retinopathy (npAIR). In this chapter, the term AIR will be used to encompass all three disorders where there is commonality to their features. Complicating the issue is that AIR can be a secondary complication of other conditions such as retinitis pigmentosa, ocular trauma, birdshot retinopathy, acute zonal occult outer retinopathy (AZOOR), or multiple evanescent white dot syndrome (MEWDS). The many forms of AIR tend to have common clinical features despite the fact that there has been no uniform set of anti-retinal antibodies circulating in these patients. Patients tend to have a wide variance of anti-retinal antibody activity often with three to six different antibodies found on immunoblots. Patients typically present with a sudden onset of photopsia, rapid visual loss, and abnormal electroretinograms (ERGs). Most patients have a panretinal degeneration without pigment deposits.