Inflammatory, Hemostatic, and Other Novel Biomarkers for Diabetic Retinopathy

Inflammatory, Hemostatic, and Other Novel Biomarkers for Diabetic Retinopathy The Multi-Ethnic Study of Atherosclerosis Thanh T. Nguyen , MBBS 1 , Ekaterina Alibrahim , MBBS 1 , F.M. Amirul Islam , PHD 1 , Ronald Klein , MD, MPH 2 , Barbara E.K. Klein , MD, MPH 2 , Mary Frances Cotch , PHD 3 , Steven Shea , MD 4 and Tien Y. Wong , MD, PHD 1 , 5 1 Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, University of Melbourne, Melbourne, Australia; 2 Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin; 3 Division of Epidemiology and Clinical Applications, National Eye Institute, National Institutes of Health, Bethesda, Maryland; 4 Departments of Medicine and Epidemiology, Schools of Medicine and Public Health, Columbia University, New York, New York; 5 Singapore Eye Research Institute, National University of Singapore, Singapore. Corresponding author: Tien Y. Wong, twong{at}unimelb.edu.au . Abstract OBJECTIVE There are conflicting data regarding relationships of systemic biomarkers of inflammation, hemostasis, and homocysteine with diabetic retinopathy. We examined these relationships in the Multi-Ethnic Study of Atherosclerosis. RESEARCH DESIGN AND METHODS A total of 921 participants with diabetes were included. Diabetic retinopathy was graded from retinal photographs. We defined two outcomes: any diabetic retinopathy and vision-threatening diabetic retinopathy (severe nonproliferative diabetic retinopathy or worse). Systemic markers analyzed were C-reactive protein, homocysteine, fibrinogen, plasmin-α 2 -antiplasmin complex (PAP), interleukin-6, d -dimer, factor VIII, serum creatinine, and urinary albumin-to-creatinine (UAC) ratio. RESULTS Prevalence of diabetic retinopathy was 33.2% and vision-threatening diabetic retinopathy 7.1%. After adjusting for established risk factors (diabetes duration, A1C, systolic blood pressure, waist-to-hip ratio, and use of diabetes medications), fibrinogen (odds ratio 1.14 [95% CI 1.01–1.32], P = 0.05) and PAP (1.25 [1.05–1.50], P = 0.01) were associated with any diabetic retinopathy, while PAP (1.54 [1.13–2.11], P = 0.007) and homocysteine (1.57 [1.16–2.11], P = 0.003) were associated with vision-threatening diabetic retinopathy. Only PAP remained significant after additional adjustment for serum creatinine and UAC ratio. Area under receiver-operator characteristic curve (AUROC) for diabetic retinopathy was constructed for esta