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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Increased vascular permeability and excessive neovascularization are the hallmarks of endothelial dysfunction, which can lead to diabetic macular edema and proliferative diabetic retinopathy in the eye. Vascular endothelial growth factor (VEGF) is an important mediator of ocular neovascularization and a known vasopermeability factor in nonocular tissues. In these studies, we demonstrate that intravitreal injection of VEGF rapidly activates protein kinase C (PKC) in the retina at concentrations observed clinically, inducing membrane translocation of PKC isoforms alpha, betaII, and delta and >threefold increases in retinal vasopermeability in vivo. The effect of VEGF on retinal vascular permeability appears to be mediated predominantly by the beta-isoform of PKC with >95% inhibition of VEGF-induced permeability by intravitreal or oral administration of a PKC beta-isoform-selective inhibitor that did not inhibit histamine-mediated effects. These studies represent the first direct demonstration that VEGF can increase intraocular vascular permeability through activation of PKC in vivo and suggest that oral pharmacological therapies involving PKC beta-isoform-selective inhibitors may prove efficacious for the treatment of VEGF-associated ocular disorders such as diabetic retinopathy.
Diabetes 1997 Sep
PMID:Vascular endothelial growth factor-induced retinal permeability is mediated by protein kinase C in vivo and suppressed by an orally effective beta-isoform-selective inhibitor. 928 49

We investigated familial clustering of diabetic retinopathy and nephropathy in the families of 372 subjects from the Diabetes Control and Complications Trial (DCCT). These subjects had 467 first-degree relatives with IDDM or NIDDM. Family sizes ranged from two to six. A complete data set was obtained from 241 relatives of 217 DCCT subjects. Among the DCCT subjects, 53% were in the intensive treatment group and 47% were in the conventional group; 44% were from the primary prevention cohort (no retinopathy or microalbuminuria at the DCCT baseline) and 56% were from the secondary intervention cohort (mild-to-moderate nonproliferative retinopathy and <200 mg/24 h albumin excretion rate [AER] at baseline). Retinopathy and nephropathy were assessed with seven-field stereo fundus photography and timed urinary AER measurements. Retinopathy was assessed using the Early Treatment Diabetic Retinopathy Study (ETDRS) scale. ETDRS scores and AERs were adjusted for the DCCT treatment group and for significant covariates from among sex, age, diabetes duration, HbA1c value, and body weight. Familial associations were assessed by comparing the prevalence of retinopathy and nephropathy in diabetic relatives of the respective positive versus negative DCCT subjects. To determine family clustering of the severity of retinopathy or nephropathy, the intraclass (familial) correlation was computed from the log-adjusted retinopathy and nephropathy scores of DCCT subjects and their relatives for all family members and sib-sib relationships. For parent-offspring, mother-child, and father-child relationships, the pairwise estimate of the correlations was computed. A correlation of 0.2 was considered to be biologically meaningful a priori. Among families of patients in the intensive and conventional groups combined, there was an increased risk of severe retinopathy (an ETDRS score > or =47, clinically significant macular edema, or laser treatment in either eye) among relatives of retinopathy-positive vs. retinopathy-negative DCCT subjects in the secondary intervention cohort (odds ratio [OR], 3.1; 95% CI 1.2-7.8; P < 0.05). There was no increase in the risk of retinopathy of any severity (microaneurysms or worse) in the relatives of retinopathy-positive vs. retinopathy-negative DCCT subjects of the primary prevention cohort. There was an increased risk of nephropathy (AER >40 mg/24 h) in relatives of nephropathy-positive versus nephropathy-negative DCCT subjects of the secondary intervention cohort (OR, 5.4; 95% CI 2.2-13.7; P < 0.001). The risk of severe retinopathy in the relatives of positive versus negative subjects from the conventional treatment group alone (OR, 4.3; 95% CI 1.01-18.6; P < 0.05) was statistically significant and somewhat greater than that among relatives of the subjects in intensive treatment group (OR, 2.4; 95% CI 0.7-8.1), which was not significant. Correlations for the severity of retinopathy were 0.187 (all family members), 0.327 (parent-offspring), 0.249 (father-child), 0.391 (mother-child), and 0.060 (sib-sib), using the combined treatment group families. All these correlations were statistically significant (P < 0.05), except for sib-sib. The results showed similar trends when the families from the conventional and intensive treatment groups were analyzed separately. Correlations for nephropathy in the combined treatment group families were 0.063 (all family members), 0.138 (parent-offspring), 0.170 (father-child), 0.103 (mother-child), and 0.107 (sib-sib). None of these correlations is statistically significant. The lack of significant correlation for the severity of nephropathy may reflect the relatively short duration of diabetes in the offspring of these families and the known high intrasubject variability of AERs. These data provide the first available evidence that the severity of diabetic retinopathy is influenced by familial (possibly genetic) factors and confirmatory evidence that such factors influence the development
Diabetes 1997 Nov
PMID:Clustering of long-term complications in families with diabetes in the diabetes control and complications trial. The Diabetes Control and Complications Trial Research Group. 935 33

In type I (insulin-dependent) diabetes mellitus, nephropathy may be identified in its early stages by the development of persistent microalbuminuria. This longitudinal study sought to examine the development of vision-threatening retinal disease (VTRD) (proliferative retinopathy and clinically significant macular edema) in such patients with early and evolving diabetic kidney disease. Eighty patients with type I diabetes and at least 8 yr of longitudinal data were identified. Glycated hemoglobin and albumin excretion rate (AER) were measured every 3 mo. Ophthalmologic examination was performed at least yearly. Thirteen patients were identified as having evolving nephropathy by a progressive increase in AER and the presence of microalbuminuria during the study period. Sixty-seven patients remained persistently normoalbuminuric. VTRD developed in eight of 13 (62%) patients with evolving nephropathy compared with five of 69 (7%) patients who were persistently normoalbuminuric (P < 0.001) in the absence of any difference in long-term glycemic control or duration of diabetes between the two groups. Clinically significant macular edema (P < 0.05) and proliferative retinopathy (P < 0.01) were both more common in patients with evolving nephropathy. In such patients, AER was 150 x/divided by 1.7 micrograms/min at the time of laser photocoagulation for VTRD. These data suggest that patients with type I diabetes and evolving nephropathy may be at higher risk of developing VTRD than patients who remain persistently normoalbuminuric despite similar long-term glycemic control and duration of diabetes.
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PMID:Early nephropathy predicts vision-threatening retinal disease in patients with type I diabetes mellitus. 944 91

Diabetic eye disease is a major cause of blindness in the Western World and remains one of the most serious complications of diabetes mellitus. Retinopathy is the ocular complication of diabetes that most often leads to impaired vision. In recent years laser treatment has been introduced that can significantly decrease the likelihood of blindness in diabetic patients, if the eyes are treated at the appropriate stage of the disease. It remains a public health problem to make sure that each patient is treated at the optimal time in the development of the eye disease. Several types of screening programs have been designed throughout the world to meet this problem. We now report on our active screening program for diabetic eye disease and describe the sight and eye condition of the diabetic patients who have been involved in this program. In 1980, regular eye screening for diabetic retinopathy was initiated at Department of Ophthalmology, Landakot Hospital. The number of diabetic patients seen regularly has increased considerably since then, with 70-80% of type 1 diabetic patients in the country participating in the program in 1990, increasing to over 90% in 1994. About a fifth of type 2 diabetics in the country participated in the program in 1990. The patients have undergone annual eye examinations and fundus photography. Laser treatment is administered for proliferative retinopathy and diabetic macular edema according to the Diabetic Retinopathy Study and Early Treatment Diabetic Retinopathy Study criteria. In 1990, we embarked on a cross-sectional study to evaluate the prevalence of retinopathy and visual impairment of the type 1 and type 2 patients participating in our program. At the time of study, 205 insulin-taking patients, with age at diagnosis of less than 30 years, participated in our screening program. Out of those, retinopathy was present in 106 (52%), patients proliferative retinopathy in 26 (13%) and macular edema in 19 (9%). Visual acuity of 196 patients (96%) was equal or better than 6/12 in their better eye, 6 patients (3%) had 6/18-6/36 in their better eye, and 2 patients (1%) had equal or worse than 6/60 in their better eye, or legally blind. We concluded that the prevalence of retinopathy and visual impairment in type 1 diabetic patients in the country was low compared with other countries. In 1990, out of 245 diabetic patients with Type 2 diabetes, retinopathy was present in 100 patients (41%), proliferative retinopathy had been present in 17 (7%) and 24 (10%) had diabetic macular edema. A total of 224 patients (91%) had visual acuity equal or better than 6/12 in their better eye, 17 patients (7%) with 6/18-6/36 in their better eye, and 4 patients (1.6%) equal or worse than 6/60 in their better eye, or legally blind. We concluded that the prevalence of visual impairment of those type 2 diabetic patients participating in our screening program at the time of study was low compared with population-based studies from other countries. In 1992 we examined ways to make the screening program more efficient by identifying subgroups at low risk for developing eye disease that required treatment and therefore needed less frequent screening. We studied whether diabetic eye disease screening programs could be trimmed by excluding children and examining diabetic patients without retinopathy every other year. We examined all children under the age of 15 at the time of study and went through the files of all patients under age 15 examined from 1980 to 1992 at our diabetic eye screening program. We also followed for two years the type 1 and type 2 diabetic patients found to have no retinopathy in 1990, establishing their retinopathy stage two years later. Our results indicated that diabetic children under the age of 12 do not need regular screening for eye disease. Biannual examinations seemed to suffice in type 1 and 2 diabetic patients without retinopathy. (ABSTRACT TRUNCATED)
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PMID:Diabetic retinopathy. Screening and prevention of blindness. A doctoral thesis. 955 48

Nonproliferative diabetic retinopathy may cause visual loss when associated with macular edema or macular ischemia (secondary to retinal capillary nonperfusion). Proliferative diabetic retinopathy may cause severe visual loss if complicated by vitreous hemorrhage or traction detachment of the macula. Patients with diabetes benefit from collaboration between the internist and ophthalmologist. Tighter control of blood glucose levels and lower blood pressure reduce the risk of progression of diabetic retinopathy. Regular dilated eye examinations and appropriate intervention with laser or vitrectomy surgery help to preserve vision in patients with established macular edema or proliferative diabetic retinopathy.
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PMID:Diabetic retinopathy. 970 24

Blood-retinal barrier (BRB) breakdown is a hallmark of diabetic retinopathy, but the molecular changes that cause this pathology are unclear. Occludin is a transmembrane component of interendothelial tight junctions that may regulate permeability at the BRB. In this study, we examined the effects of vascular endothelial growth factor (VEGF) and diabetes on vascular occludin content and barrier function. Sprague-Dawley rats were made diabetic by intravenous streptozotocin injection, and age-matched animals served as controls. After 3 months, BRB permeability was quantified by intravenous injection of fluorescein isothiocyanate-bovine serum albumin (FITC-BSA), Mr 66 kDa, and 10-kDa rhodamine-dextran (R-D), followed by digital image analysis of retinal sections. Retinal fluorescence intensity for FITC-BSA increased 62% (P < or = 0.05), but R-D fluorescence did not change significantly. Occludin localization at interendothelial junctions was confirmed by immunofluorescence, and relative protein content was determined by immunoblotting of retinal homogenates. Retinal occludin content decreased approximately 35% (P < or = 0.03) in the diabetic versus the control animals, whereas the glucose transporter GLUT1 content was unchanged in rat retinas. Additionally, treatment of bovine retinal endothelial cells in culture with 0.12 nmol/l or 12 nmol/l VEGF for 6 h reduced occludin content 46 and 54%, respectively. These data show that diabetes selectively reduces retinal occludin protein expression and increases BRB permeability. Our findings suggest that the elevated VEGF in the vitreous of patients with diabetic retinopathy increases vascular permeability by downregulating occludin content. Decreased tight junction protein expression may be an important means by which diabetes causes increased vascular permeability and contributes to macular edema.
Diabetes 1998 Dec
PMID:Vascular permeability in experimental diabetes is associated with reduced endothelial occludin content: vascular endothelial growth factor decreases occludin in retinal endothelial cells. Penn State Retina Research Group. 983 30

Diabetic macular edema represents an important cause of visual loss in patients with diabetes. Although the pathophysiology of diabetic macular edema is unknown, various demographic, metabolic, and systemic factors have been implicated. More recently, the role of the posterior vitreomacular relationship has been evaluated, and studies suggest that posterior vitreous separation confers a protective effect on the development of diabetic macular edema. Furthermore, vitreomacular separation occurring in eyes with diabetic macular edema may facilitate spontaneous resolution of the edema and improvement in visual acuity. In a subset of patients, diffuse diabetic macular edema can result from a taut and condensed posterior hyaloid and often responds poorly to focal or grid-pattern laser photocoagulation. Previous studies have reported favorable results following vitrectomy and peeling of the posterior hyaloid in such cases.
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PMID:Vitrectomy for diabetic macular edema associated with a taut premacular posterior hyaloid. 1018 5

Diabetic retinopathy is one of the leading causes of preventable blindness in working age population. Diabetes mellitus and this microvascular complication affects frequently Mexican population and presents itself in severe clinical forms. There are no incidence studies of diabetic retinopathy in Mexico. The four year incidence and progression of diabetic retinopathy were investigated in low income diabetic patients of Mexico City. In the follow up phase we studied 164 patients, 76.6% of the patients studied at baseline, 63 were men and 101 women. All participants had a complete ophthalmological exam and seven field stereo photographs. All photographs were graded using internationally accepted criteria in the reading center of our institution. The four year incidence of any level of retinopathy was 22.5%. Worsening of retinopathy occurred in 20.6% and the proliferative diabetic retinopathy stage was reached in 4.5%. Incidence of diabetic retinopathy was associated to age at diagnosis of diabetes mellitus of less than 45 years and progression was associated to duration of disease of more than ten years. The four year incidence of macular edema was 8.8%. These data are important to plan strategies for prevention of blindness and the implementation of optimal care of diabetic patients in our country.
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PMID:[Incidence and progression of diabetic retinopathy in low income population of Mexico City]. 1046 4

Effect of the sympathoadrenal system (SAS) on the results of cataract extraction with IOL implantation was studied by analyzing the stress index in 64 patients with diabetes mellitus and 20 reference patients. SAS reaction to surgical stress was abnormal in 34 (53.1%) diabetics. The level of SAS activity, postoperative complications, and kinetics of regenerative repair processes in the cornea were related. In 15 (23.%) diabetics with a low stress index the postoperative period was characterized by frequent inflammations, longer repair of normal corneal homeostasis, and coarse cicatrization. In 19 (29.7%) diabetics with a high stress index after cataract extraction normalization of the corneal homeostatic parameters was delayed and macular edema developed 4.8 times more often.
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PMID:[The effect of neurohumoral factors of the sympathoadrenal system on the results of cataract extraction with intraocular lens implantation in diabetic patients]. 1058 19

We retrospectively reviewed the medical records of all diabetic patients with benign, transient disc swelling who were evaluated at our institution from 1992 to 1996. The clinical profile of diabetic papillopathy can be expanded to include people who are older or have type II diabetes and that affected eyes commonly have retinal vascular changes and macular edema that can adversely affect the visual outcome. Last, a small physiologic cup may represent an anatomic predisposition to the condition.
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PMID:[Diabetic papillae]. 1075 59


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