Inflammatory, Hemostatic, and Other Novel Biomarkers for Diabetic Retinopathy

The Multi-Ethnic Study of Atherosclerosis

  1. Thanh T. Nguyen, MBBS1,
  2. Ekaterina Alibrahim, MBBS1,
  3. F.M. Amirul Islam, PHD1,
  4. Ronald Klein, MD, MPH2,
  5. Barbara E.K. Klein, MD, MPH2,
  6. Mary Frances Cotch, PHD3,
  7. Steven Shea, MD4 and
  8. Tien Y. Wong, MD, PHD1,5
  1. 1Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, University of Melbourne, Melbourne, Australia;
  2. 2Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin;
  3. 3Division of Epidemiology and Clinical Applications, National Eye Institute, National Institutes of Health, Bethesda, Maryland;
  4. 4Departments of Medicine and Epidemiology, Schools of Medicine and Public Health, Columbia University, New York, New York;
  5. 5Singapore Eye Research Institute, National University of Singapore, Singapore.
  1. 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-α2-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 established and novel risk factors. Established risk factors accounted for a 39.2% increase of the AUROC, whereas novel markers (fibrinogen, PAP, homocysteine, serum creatinine, and UAC ratio) only accounted for an additional 2.2%.

CONCLUSIONS There were few associations of novel markers of inflammation, hemostasis, and homocysteine with diabetic retinopathy after controlling for established risk factors. These data suggest that there is limited clinical use of these biomarkers for prediction of diabetic retinopathy.

Footnotes

  • The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

    • Received January 19, 2009.
    • Accepted June 13, 2009.
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  1. Published online before print June 23, 2009, doi: 10.2337/dc09-0102 Diabetes Care September 2009 vol. 32 no. 9 1704-1709
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