Vitreous levels of vascular cell adhesion molecule and vascular endothelial growth factor in patients with proliferative diabetic retinopathy: a case-control study

OBJECTIVE: To evaluate the intravitreous concentration of vascular cell adhesion molecule (VCAM)-1 in diabetic patients with proliferative diabetic retinopathy (PDR) and the relationship of VCAM-1 with vascular endothelial growth factor (VEGF). RESEARCH DESIGN AND METHODS: Serum and vitreous fluid samples were obtained simultaneously at the onset of vitrectomy from 20 diabetic patients with PDR and 20 nondiabetic control subjects with nonproliferative ocular disease. Both groups were matched by serum levels of VCGM-1 and VEGF. VCAM-1 and VEGF were determined by enzyme-linked immunosorbent assay. Statistics were determined using the Mann-Whitney U test and Spearman's rank correlation test. RESULTS: The intravitreous concentration of VCAM-1 was signifcantly elevated in diabetic patients with PDR compared with control subjects (26 ng/ml [19-118] vs. 22 ng/ml [20-47], P < 0.05). A direct correlation between VCAM-1 and total vitreous proteins was detected in diabetic patients (r = 0.64, P = 0.003), but not in control subjects. After adjusting for total intravitreous proteins, VCAM-1 was significantly lower in diabetic patients with PDR than in control subjects (8.2 ng/ml [4-31.4] vs. 43.1 ng/ml [9.7-100], P < 0.001). Intravitreous VEGF concentrations were higher in patients with PDR than in control subjects in absolute terms (1.34 ng/ml [0.16-6.22] vs. 0.009 ng/ml [0.009-0.044], P < 0.0001) and after correcting for total vitreal proteins (0.33 ng/ml [0.01-2.3] vs. 0.013 ng/ml [0.003-0.035], P = 0.0001). Finally, the vitreous ratio of VCAM-1 to proteins correlated with the vitreous ratio of VEGF to proteins in both diabetic patients (r = 0.74, P = 0.001) and control subjects (r = 0.84, P = 0.005). CONCLUSIONS: The low proportion of VCAM-1 in relation to total vitreal proteins observed in diabetic patients with PDR suggests that VCAM-1 is quenched by diabetic retina. In addition, the direct correlation detected between VCAM-1 and VEGF suggests that cellular adhesion and neovascularization may be linked processes.     

Association between subclinical hypothyroidism and proliferative diabetic retinopathy in type 2 diabetic patients: a case-control study

Subclinical hypothyroidism (SCH) is defined as an asymptomatic state characterized by normal serum levels of free thyroxine and elevated serum concentrations of thyrotropin (> 4.0 μU/ml). The association between SCH and type 2 diabetes has been well established. Proliferative diabetic retinopathy (PDR) that is characterized by neovascularization is a leading cause of visual loss in adults worldwide. However, whether SCH is related to PDR has not been studied. This study thus aimed to evaluate the relationship between SCH and PDR in type 2 diabetes. A total of 371 type 2 diabetic subjects were enrolled: 187 subjects with PDR and 184 subjects without diabetic retinopathy (with HbA1c above 6.5% and at least 10 years of diabetes duration). Subjects with PDR had higher blood pressure, higher serum levels of total cholesterol, low-density lipoprotein cholesterol and thyrotropin, and higher urinary albumin excretion rate. Of the 371 diabetics, 83 subjects (22.4%) were diagnosed as SCH (male 12.1% and female 29.9%). The prevalence of SCH in the PDR group (51/187, 27.3%) was higher than that in the subjects without diabetic retinopathy (32/184, 17.4%). Logistic regression analysis showed that after adjusting for compounding variables, SCH was independently related with PDR (p = 0.032, adjusted OR = 2.485). These results indicate that type 2 diabetic patients with PDR are at an increased risk of SCH. A routine screening for thyroid function may thus be considered advisable in PDR subjects. This may be helpful in investigating new strategies preventing or treating PDR in clinical practice.     

Free insulin-like growth factor 1 in the vitreous fluid of diabetic patients with proliferative diabetic retinopathy: a case-control study

The aim of the study was to evaluate the vitreous levels of free insulin-like growth factor 1 (IGF-1) in patients with proliferative diabetic retinopathy (PDR). For this, a total of 36 diabetic patients with PDR (group A) and 28 non-diabetic patients (group B) in whom a vitrectomy was performed were compared. Both groups were matched by age, sex and serum-free IGF-1. In a subgroup of diabetic patients (n =21) and non-diabetic patients (n =13), vitreous and serum total IGF-1, IGF-binding protein 1 (IGFBP-1) and IGFBP-3 were also determined. Serum and vitreous levels of free IGF-1, total IGF-1, IGFBP-1 and IGFBP-3 were measured by immunological methods. Vitreal proteins were assessed by a turbidimetric method and adjusted for vitreous haemoglobin. Vitreous levels of free IGF-1 were elevated in group A (median, 0.16 ng/ml; range 0.06-0.57 ng/ml) in comparison with group B (median, 0.12 ng/ml; range 0.06-0.22 ng/ml; P <0.001); however, after adjusting for vitreal proteins, free IGF-1 levels were significantly lower in group A in comparison with group B [0.05 ng/mg (0.01-0.45 ng/mg) versus 0.15 ng/mg (0.07-0.66 ng/mg); P <0.001]. The relatively lower free IGF-1 level observed in group A could not be attributed to differences in the distribution of intravitreous IGFBP-1 and IGFBP-3 in relation to total IGF-1. Notably, the contribution of free IGF-1 to total IGF-1 in vitreous fluid was 10% in group A and 42% in group B; these percentages largely exceed that obtained in serum (<1%). Our results suggest that although there is an enhancement of intravitreous free IGF-1 in diabetic patients due to serum diffusion, a deficit in its intraocular production also exists. In addition, these findings support the concept that intraocular-produced free IGF-1 plays a relevant role in retinal homoeostasis.     

ACE gene polymorphism and proliferative retinopathy in type 1 diabetes: results of a case-control study.

OBJECTIVE: To evaluate the relationship between the ACE insertion/deletion polymorphism and proliferative diabetic retinopathy in patients with type 1 diabetes of long duration. Based on epidemiological and pathophysiological findings, risk factors apart from glycemic control and duration of disease are likely to be involved in the development of proliferative retinopathy. RESEARCH DESIGN AND METHODS: In this case-control study, we compared 81 patients with longstanding (> or =20 years) type 1 diabetes who had nonproliferative (mild or moderate background) retinopathy with 95 patients with diabetes of similar duration and HbA1c who had proliferative retinopathy. To avoid the confounding effect of nephropathy, patients with overt nephropathy were excluded, and microalbuminuria was introduced into the multiple logistical regression model. The polymorphic region in intron 16 of the ACE gene (17q23) was analyzed using the polymerase chain reaction. RESULTS: The ACE genotype distribution in patients with proliferative retinopathy (DD 39.4%, ID 48.9%, II 11.7%) was significantly different (P < 0.001) from that of patients with nonproliferative retinopathy (DD 17.3%, ID 54.3%, II 28.4%). In a multiple logistical regression analysis, the adjusted relative risk for proliferative retinopathy in a patient with a DD genotype compared with a patient with an II genotype was 6.6 (95% CI 2.2-19.5), P = 0.0026. In addition to genotype, systolic blood pressure (odds ratio 1.027 [95% CI 1.0-1.1], P = 0.0093) but not microalbuminuria (< or =20 vs. > or =20 microg/min) reached statistical significance in the multiple regression model. Because subjects were matched regarding diabetes duration and HbA1c, we did not interpret the respective parameter estimates. CONCLUSIONS: These data provide evidence that deletion in the ACE gene is associated with the prevalence of proliferative retinopathy in type 1 diabetes and suggest that the DD genotype confers susceptibility to proliferative retinopathy independent of diabetic nephropathy     

糖尿病增殖性视网膜病变术后护理

目的探讨糖尿病增殖性视网膜病变手术后护理方法,以提高手术成功率.方法观察并总结对120例糖尿病增殖性视网膜病变手术后患者护理经验.结果体位、四肢及眼部特殊护理可有效提高手术成功率.结论规范而得当的护理是保证糖尿病增殖性视网膜病变手术成功的关键之一.     

HLA-DRB1等位基因对增殖性糖尿病视网膜病变的保护作用

目的 研究增殖性糖尿病视网膜病变(PDR)与HLA-DRB1等位基因的相关性,探讨PDR形成的保护因素.方法 随机收集于门诊就诊和住院治疗的156例2型糖尿病(T2DM)患者作为研究对象.将病程>10年但未发展为PDR的T2DM患者纳入DR组,病程<5年但发展为PDR的T2DM患者纳入PDR组.通过基因芯片检测所有患者...     

Risk of proliferative diabetic retinopathy in juvenile-onset type I diabetes: a 40-yr follow-up study

The development of proliferative diabetic retinopathy was studied in three cohorts consisting of 292 patients with recent juvenile-onset, type I (insulin-dependent) diabetes who were followed 20-40 yr beginning in 1939, 1949, and 1959. The risk of this severe eye complication was almost nonexistent during the first 10 yr of diabetes, rose abruptly to its maximum level (approximately 30/100 person-years), and remained at that level for the next 25 yr. This pattern did not vary with sex, age at onset of diabetes, or level of glycemic control during the first 5 yr of diabetes. However, the risk of proliferative retinopathy was strongly related to the level of glycemic control during the several years preceding onset of this complication. This was a dose-dependent relationship, with patients in the highest quartile of the distribution of the index of frequency of hyperglycemia having a 10-fold higher risk than individuals in the lowest quartile. A virtually identical pattern was observed in patients who developed diabetes in 1959 as was observed in those who developed diabetes in 1949 or 1939. In contrast, diabetic nephropathy as evidenced by persistent proteinuria showed a lower incidence in the 1959 than in the 1939 cohort. In conclusion, these incidence data do not support the notion that the risk of proliferative retinopathy is mainly a function of duration of diabetes. Instead, the pattern of occurrence of this severe eye complication in type I diabetes suggests that the process leading to the development of proliferative retinopathy consists of two or more stages and that progression through each stage may be governed by different factors.     

Influence of acute exercise on urinary protein, creatinine, insulin-like growth factor-I (IGF-I) and IGF binding protein-3 concentrations in children

Insulin-like growth factor-I (IGF-I) is a polypeptide hormone and present in human urine. Insulin-like growth factor binding protein-3 (IGFBP-3) is the major form of binding protein in human circulation and functions as a carrier for IGF-I. Our goal was to determine the effects of volleyball exercise on the concentrations of urine protein, creatinine, IGF-I, and IGFBP-3 in children and to find out whether these effects differ between boys and girls. Volunteer children (13 females and 14 males), aged 10-13 years old were included in this work. Weight and height of the subjects were measured, and urine samples of their were collected before and after 2 hours of exercise. Urinary protein, creatinine, IGF-I and IGFBP-3 levels were analysed. Urinary protein, creatinine and IGF-I concentrations were increased after two hours of exercise wheres urinary IGFBP-3 concentrations did not change. In addition, no statistically significant difference in all parameters analysed was observed between boys and girls of similar age and body mass index.     

Functional vascular endothelial growth factor -634G>C SNP is associated with proliferative diabetic retinopathy: a case-control study in a Brazilian population of European ancestry

OBJECTIVE: The purpose of this study was to evaluate the effect of the single nucleotide polymorphism (SNP) -634G>C at the 5' regulatory region of the vascular endothelial growth factor (VEGF) in the risk of proliferative diabetic retinopathy (PDR) in the Brazilian population of European ancestry with type 2 diabetes. RESEARCH DESIGN AND METHODS: A case-control study was conducted in 501 type 2 diabetic patients of European ancestry. Patients underwent a standardized clinical, ophthalmological, and laboratory evaluation. Of these, 167 patients had PDR (case patients), and 334 were considered as control subjects (patients without PDR) for PDR. A reference population (110 individuals of European ancestry) was also evaluated. RESULTS: No evidence of association between -634G>C/VEGF and the presence of diabetic retinopathy or type 2 diabetes was observed (P > 0.05). However, CC homozygous for the SNP -634G>C was significantly more frequent in patients with PDR (37 of 167; 22.2%) than in the corresponding control group (40 of 334; 12%) in accordance with a recessive model (P = 0.003). This effect was further observed when creatinine, BMI, sex, duration of type 2 diabetes, HDL cholesterol, and systolic blood pressure were taken into account (odds ratio 1.9 [95% CI 1.01-3.79], P = 0.04). CONCLUSIONS: The presence of the allele -634C/VEGF in homozygosity is an independent risk factor for the development of PDR in type 2 diabetic patients of European ancestry.     

Somatostatin molecular variants in the vitreous fluid: a comparative study between diabetic patients with proliferative diabetic retinopathy and nondiabetic control subjects

OBJECTIVE: There is growing evidence to indicate that somatostatin could be added to the list of natural antiangiogenic factors that exist in the vitreous fluid. In addition, a deficit of intravitreous somatostatin-like immunoreactivity (SLI) has been found in diabetic patients with proliferative diabetic retinopathy (PDR). In the present study, we have determined the main molecular variants of somatostatin (somatostatin-14 and somatostatin-28) in the vitreous fluid and plasma of nondiabetic control subjects and diabetic patients with PDR. In addition, the contribution of cortistatin, a neuropeptide with strong structural similarities to somatostatin, to SLI and its levels in vitreous and plasma in both nondiabetic and diabetic patients has also been measured. RESERCH DESIGN AND METHODS: Plasma and vitreous fluid from 22 diabetic patients with PDR and 22 nondiabetic control subjects were analyzed. Somatostatin-14, somatostatin-28 and cortistatin were measured by radioimmunoassay but separation by high-performance liquid chromatography was required to measure somatostatin-14. RESULTS: The predominant molecular form of somatostatin within the vitreous fluid was somatostatin-28 (fivefold higher than somatostatin-14 in control subjects and threefold higher in patients with PDR). Cortistatin significantly contributed to SLI and its intravitreous levels were higher than those detected in plasma (nondiabetic control subjects: 147 [102-837] vs. 78 [24-32] pg/ml; patients with PDR: 187 [87-998] vs. 62 [24-472] pg/ml; P = 0.01 for both). Intravitreous somatostatin-14 was similar in both subjects with PDR and the control group (P = 0.87). By contrast, somatostatin-28 concentration was lower in patients with PDR than in nondiabetic control subjects (350 +/- 32 vs. 595 +/- 66 pg/ml; P = 0.004). CONCLUSIONS: Somatostatin-28 is the main molecular variant in the vitreous fluid. The intravitreous SLI deficit detected in patients with PDR is mainly due to somatostatin-28. Cortistatin is abundant in the vitreous fluid and significantly contributes to SLI. These findings could open up new strategies for PDR treatment.     

The efficacy of octreotide in the therapy of severe nonproliferative and early proliferative diabetic retinopathy: a randomized controlled study

OBJECTIVE: The pilot study examined the ability of octreotide to retard progression of diabetic retinopathy (DR) and delay the need for panretinal photocoagulation (PRP) in patients with advanced stages of retinal disease. RESEARCH DESIGN AND METHODS: Patients with severe nonproliferative DR (NPDR) or early non-high-risk proliferative DR (PDR) were randomly assigned to conventional diabetes management (control group, 12 patients) or to treatment with maximally tolerated doses of octreotide (200-5,000 microg/day subcutaneously; 11 patients). Ocular changes in each eye were assessed at a minimum of every 3 months for 15 months or until disease progressed to high-risk PDR requiring laser surgery. Endocrine assessments occurred at 3-month intervals during the study RESULTS: Only 1 of 22 eyes from patients treated with octreotide reached high-risk PDR requiring PRP, compared with control patients, in whom 9 of 24 eyes required PRP. The decreased incidence of progression requiring laser surgery was statistically significant if events were considered independently (P < 0.006). The incidence of ocular disease progression was only 27% in patients treated with octreotide compared with 42% in patients with conventional diabetes management. This treatment effect on whether the retina worsened approached statistical significance using repeated measures analysis (P = 0.0605). Endocrine management was similar between treatment groups. Thyroxine replacement therapy was administered to maintain a euthyroid state for all octreotide-treated patients and 7 of 12 control patients. CONCLUSIONS: Our results suggest that octreotide treatment in euthyroid patients may retard progression of advanced DR and may delay the time to laser surgery.     

Associations of blood levels of insulin-like growth factor (IGF)-I, IGF-II and IGF binding protein (IGFBP)-3 in schizophrenic Arab subjects.

BACKGROUND: Insulin-like growth factors (IGFs) are believed to be important in brain development and repair following neuronal damage. It is also speculated that IGFs are involved in the association of foetal and pre-adult growth with schizophrenia (SZ). METHODS: The aim of this study was to assess levels of IGF-I, IGF-II and IGF binding protein (IGFBP)-3 and their associations in male Arab patients with SZ (n=53) and healthy control subjects (HC; n=52). Anthropometric and demographic data were collected for each subject for whom blood specimens were analysed for serum lipoproteins, apolipoprotein B (apoB), IGF-I, IGF-II and IGFBP-3. RESULTS: The SZ group had lower serum total cholesterol, apoB and uric acid levels than the HC group (p<0.05). IGF-II levels were significantly higher in the SZ group (p=0.02) and correlated positively with levels of atherogenic lipoproteins--total cholesterol, low-density lipoprotein, apoB--and IGFBP-3. The pattern of correlations between the IGFs and the various parameters differed somewhat between the HC and SZ groups. CONCLUSIONS: These results demonstrate that IGF-II levels are increased in patients with SZ and show significant associations with atherogenic lipoproteins. We suggest a possible link between IGF-II metabolism and atherogenesis in SZ.     

Incidence of diabetic retinopathy and blindness: a population-based study in Rochester, Minnesota

Among the 1135 Rochester residents discovered to have diabetes in the period 1945-69, the prevalence of retinopathy was 2.6% at the time of initial diagnosis. Among those free of retinopathy at diagnosis of diabetes, the subsequent incidence of any retinopathy was 17.4 per 1000 person-years and for proliferative retinopathy alone was 1.6 per 1000 person-years, based on 12,000 person-years of follow-up. The incidence rate of retinopathy was almost three times greater among residents with insulin-dependent (IDDM) than with non-insulin-dependent diabetes (NIDDM); however, the actual number of retinopathy cases was over four times greater among the more numerous residents with NIDDM. By 20 yr after diagnosis of diabetes, the cumulative incidence of retinopathy approached 70% among IDDM subjects and was 30% and 36%, respectively, among the obese and nonobese NIDDM residents. The epidemiologic patterns for proliferative retinopathy were qualitatively similar to those for nonproliferative retinopathy. The risk of blindness was greater among those with proliferative than with nonproliferative retinopathy but was substantial even for those without retinopathy. Most blindness was caused by factors other than isolated diabetic retinopathy.     

彩色多普勒超声对糖尿病增殖性视网膜病变的诊断价值

目的探讨超声对糖尿病增殖性视网膜病变的诊断价值。方法68例（107只眼）糖尿病患者和60例（60只眼）健康对照组,分析其眼声像图特点。结果107只患眼,检出玻璃体出血32只眼,玻璃体机化膜61只眼,玻璃体下出血14只眼,玻璃体后脱离22只眼,视网膜脱离13只眼;视网膜中央动脉收缩末期和舒张末期血流速度较对照组降低（P〈0．05）,超声诊断符合99只眼,误诊7只眼,漏诊1只眼。结论超声在糖尿病增殖性视网膜病变的诊断中具有重要的价值。     

严重增殖型糖尿病视网膜病变超声声像图特征及诊断准确性

目的：探讨增殖型糖尿病视网膜病声像图特片以及超声诊断与术中所见的符合率，方法：对增殖型糖尿病视网膜病变患者48例（62只眼）在行玻璃体视网膜手术前3d内行超声检查，并将其超声检查结果与术中所见相比较，通过仔细观察记录各种病理改变的位置，形态，程度，范围，活动度等情况作出判断。结果：超声检查不受屈光间质混浊影响，能清楚显示多种玻璃体视网膜病变，对增殖型糖尿病视网膜各种病理改变－玻璃体积血、玻璃体后脱离，视网膜脱离，玻璃体机化物，玻璃体视网膜粘连和视网膜前膜，机化物的诊断符合率分别为100％，91．1％，96．4％，80．0％和87．9％，结论：增殖型糖尿病视网膜变术前超声检查的临床符合率高，能为眼科医生提供可靠的诊断依据。     

Risk factors for diabetic retinopathy: a population-based study in Rochester, Minnesota

Retinopathy is an important sequela of diabetes mellitus, but clinical risk factors for this condition have rarely been assessed in a geographically defined population. In this population-based study, the 1135 Rochester, Minnesota, residents with diabetes mellitus initially diagnosed between 1945 and 1969 (incidence cohort) were followed through their complete medical records in the community to January 1, 1982. Because most of the cases of diabetic retinopathy in Rochester residents developed in patients with non-insulin-dependent diabetes mellitus (NIDDM), risk factors for diabetic retinopathy were examined in this group (N = 1031). A proportional hazards model identified the following risk factors for diabetic retinopathy in NIDDM: elevated initial fasting blood glucose level, marked obesity, and earlier age at onset of diabetes. Stratified analyses indicated that duration of diabetes was also significantly associated with an increased risk of retinopathy. Two secular trends, increasing detection of "mild" NIDDM and decreasing risk of diabetic retinopathy, had a major effect on retinopathy risk assessment. These data also suggest that insulin therapy is not an independent risk factor for diabetic retinopathy.