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Endothelial dysfunction and low-grade inflammation and the progression of retinopathy in Type 2 diabetes

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Author: Spijkerman, A.M.W. · Gall, M.A. · Tarnow, L. · Twisk, J.W.R. · Lauritzen, E. · Lund-Andersen, H. · Emeis, J. · Parving, H.H. · Stehouwer, C.D.A.
Institution: TNO Kwaliteit van Leven
Source:Diabetic Medicine, 9, 24, 969-976
Identifier: 240175
doi: doi:10.1111/j.1464-5491.2007.02217.x
Keywords: Biomedical Research · Endothelium · Inflammation · Retinopathy · Type 2 diabetes · albumin · biological marker · C reactive protein · endothelial leukocyte adhesion molecule 1 · fibrinogen · hemoglobin A1c · tissue plasminogen activator · vascular cell adhesion molecule 1 · von Willebrand factor · adult · article · clinical assessment · confidence interval · controlled study · diabetic patient · diabetic retinopathy · disease association · disease course · disease severity · endothelial dysfunction · eye fundus · female · follow up · hospital · human · inflammation · major clinical study · male · microalbuminuria · mydriasis · non insulin dependent diabetes mellitus · ophthalmoscopy · photography · prevalence · risk factor · statistical analysis · urinary excretion · Blood Glucose · C-Reactive Protein · Cohort Studies · Diabetes Mellitus, Type 2 · Diabetic Retinopathy · Disease Progression · Endothelium, Vascular · Female · Follow-Up Studies · Humans · Male · Middle Aged · Retinal Vasculitis · Retinal Vessels


Aims: To study whether microalbuminuria, endothelial dysfunction and low-grade inflammation are associated with the presence and progression of diabetic retinopathy. Methods: Patients with Type 2 diabetes (n = 328) attending a diabetes clinic were followed for 10 years and examined annually during the last 7 years. Retinopathy was assessed after pupillary dilatation by direct ophthalmoscopy (baseline) and two-field 60°fundus photography (follow-up). Urinary albumin excretion, and markers of endothelial function (von Willebrand factor, tissue-type plasminogen activator, soluble E-selectin (sE-selectin), and soluble vascular cell adhesion molecule 1) and inflammatory activity (C-reactive protein and fibrinogen) were determined. Results: The prevalence of retinopathy was 33.8%. The median diabetes duration at baseline was 7 years (interquartile range 2-12 years). The highest tertiles of baseline urinary albumin excretion and glycated haemoglobin (HbA1c) were associated with prevalent retinopathy: odds ratio (OR) 95% confidence interval (CI) 2.80 (1.44-5.46) and 2.19 (1.11-4.32), respectively. Progression of retinopathy occurred in 188 patients. The second and third tertiles of baseline sE-selectin were associated with progression of retinopathy [1.44 (1.04-2.01) and 1.61 (1.19-2.18)] but not independently of HbA1c. None of the other markers was significantly associated with the presence or progression of retinopathy. High baseline HbA1c was significantly associated with progression of retinopathy: 1.65 (1.21-2.25). Conclusions: In this population of patients with Type 2 diabetes who attended a diabetes clinic, there was some evidence for a role of endothelial dysfunction in the progression of retinopathy. We could not demonstrate a role for low-grade inflammation. Our study emphasizes the importance of glycaemic control in the development and progression of retinopathy. © 2007 The Authors.