von Willebrand factor and retinal circulation in early-stage retinopathy of type 1 diabetes.

Feng, Deng; Bursell, Sven–Erik; Clermont, Allen C.; Lipinska, Izabella; Aiello, Lloyd Paul; Laffel, Lori; King, George L.; Tofler, Geoffrey H.

doi:10.2337/diacare.23.11.1694

Cited by 25 publications

(18 citation statements)

References 27 publications

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“…However, plasma levels of vWF were not correlated with progression of diabetic retinopathy perhaps due to the small size of the retina. 23,24 Here we demonstrate that a careful analysis of vWF in diabetic retina blood vessels shows a marked increase in expression as a function of our non-dimensional expansion parameter (Fig. 3D) but not as a function of microaneurysm size (Fig.…”

Section: Discussionmentioning

confidence: 56%

Non-dimensional analysis of retinal microaneurysms: critical threshold for treatment

et al. 2013

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Fluid dynamics play a fundamental role in the development of diabetic retinopathy, one of the leading causes of blindness in the Western world, affecting over 4 million people in the US alone. The disease is defined by microaneurysms, local expansions of capillaries that disturb the hemodynamic forces experienced by the endothelium leading to dysfunction, leakage and edema. Here we present a method to identify microaneurysms with a high risk of leakage based on a critical ratio of microaneurysm to vessel diameter. We derive this non-dimensional parameter from an analytical solution and generalize it using experimentally validated numerical methods. We show that this non-dimensional parameter defines the shear force experienced by endothelial cells, below which endothelial dysfunction is evident in vivo. Our results demonstrate the involvement of vWF in diabetic retinopathy, and explain a perceived disconnect between microaneurysm size and leakage. This method will allow experts to treat microaneurysms poising a high-risk of leakage, prior to edema, minimizing damage and saving vision.

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Section: Discussionmentioning

confidence: 56%

Non-dimensional analysis of retinal microaneurysms: critical threshold for treatment

et al. 2013

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“…Results on the relationship between vWf and retinopathy have been conflicting. On the one hand, in early-stage retinopathy in type 1 diabetes, vWf has been associated with a prolonged retinal circulation time and reduced retinal blood flow, which may promote stasis in the retinal circulation, leading to hypoxaemia [33]. On the other hand, vWf was not found to be related to the presence and development of very early retinopathy in type 1 diabetes [34].…”

Section: Discussionmentioning

confidence: 69%

Inflammation and endothelial dysfunction are associated with retinopathy: the Hoorn Study

et al. 2005

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Aims/hypothesis: The exact pathogenesis of retinopathy in diabetic and non-diabetic individuals is incompletely understood, but may involve chronic low-grade inflammation and dysfunction of the vascular endothelium. The aim of this study was to investigate the association of inflammation and endothelial dysfunction with prevalent retinopathy in individuals with and without type 2 diabetes. Methods: As part of a population-based cohort study, 625 individuals aged 50-74 years, stratified according to age, sex and glucose tolerance status, underwent an extensive physical examination. Retinopathy was assessed by an ophthalmological examination, including funduscopy and two-field 45°fundus photography with mydriasis in both eyes. Levels of C-reactive protein (CRP), soluble intercellular adhesion molecule-1 (sICAM-1), von Willebrand factor, and soluble vascular adhesion molecule-1 (sVCAM-1) were assessed, together with the urinary albumin : creatinine ratio, and the results were combined to obtain summarising z scores for inflammation and endothelial dysfunction. Results: The prevalence of retinopathy was positively associated with tertiles of CRP and sICAM-1. When compared with the lowest tertile, the highest tertile of the inflammatory z score was associated with retinopathy in all subjects (odds ratio [OR]=2.2, 95% CI 1.2-4.1, adjusted for age, sex and glucose tolerance status). The highest tertile of the endothelial dysfunction z score was associated with retinopathy among diabetic individuals (OR=4.4, 95% CI 1.2-15.9, adjusted for age and sex) but not in non-diabetic individuals. Additional adjustment for other risk factors, such as systolic and diastolic blood pressure, BMI, total cholesterol and triglycerides, or mutual adjustment of the inflammatory and endothelial dysfunction z scores did not change the results. Conclusions/interpretation: In this study, inflammatory activity and endothelial dysfunction were associated with retinopathy, which suggests their involvement in the pathogenesis of retinopathy.

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“…Accordingly, we speculate that higher levels of gray matter in the occipital gyrus may serve to compensate for early retinal changes that occur in type 1 diabetic patients (even in patients without clinically evident diabetic retinopathy) (48). We know that retinal blood flow is reduced in type 1 diabetic patients with early stages of diabetic retinopathy (49) and elevated gray matter density in the occipital gyrus may be another early sign of retinopathy.…”

Section: Discussionmentioning

confidence: 99%

Effects of Type 1 Diabetes on Gray Matter Density as Measured by Voxel-Based Morphometry

et al. 2006

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The effects of type 1 diabetes and key metabolic variables on brain structure are not well understood. Sensitive methods of assessing brain structure, such as voxel-based morphometry (VBM), have not previously been used to investigate central nervous system changes in a diabetic population. Using VBM, we compared type 1 diabetic patients aged 25-40 years with disease duration of 15-25 years and minimal diabetes complications with an agematched, nondiabetic control group. We investigated whether lower than expected gray matter densities were present, and if so, whether they were associated with glycemic control and history of severe hypoglycemic events. In comparison with control subjects, diabetic patients showed lower density of gray matter in several brain regions. Moreover, in the patient group, higher HbA 1c levels and severe hypoglycemic events were associated with lower density of gray matter in brain regions responsible for language processing and memory. Our study represents the first comprehensive study of gray matter density changes in type 1 diabetes and suggests that persistent hyperglycemia and acute severe hypoglycemia have an impact on brain structure. Diabetes 55:326 -333, 2006

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von Willebrand factor and retinal circulation in early-stage retinopathy of type 1 diabetes.

Cited by 25 publications

References 27 publications

Non-dimensional analysis of retinal microaneurysms: critical threshold for treatment

Non-dimensional analysis of retinal microaneurysms: critical threshold for treatment

Inflammation and endothelial dysfunction are associated with retinopathy: the Hoorn Study

Effects of Type 1 Diabetes on Gray Matter Density as Measured by Voxel-Based Morphometry

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