Inflammatory, Hemostatic and Other Novel Biomarkers for Diabetic Retinopathy: The Multi-Ethnic Study of Atherosclerosis (MESA)

  1. Thanh T Nguyen, MBBS1,
  2. Ekaterina Alibrahim, MBBS1,
  3. FM Amirul Islam, PhD1,
  4. Ronald Klein, MD, MPH2,
  5. Barbara EK Klein, MD, MPH2,
  6. Mary Frances Cotch, PhD3,
  7. Steven Shea, MD4 and
  8. Tien Y Wong, MD, PhD (twong{at}unimelb.edu.au)1,5
  1. 1. Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, University of Melbourne, Australia
  2. 2. Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, WI
  3. 3. Division of Epidemiology and Clinical Applications, National Eye Institute, NIH, Bethesda, MD
  4. 4. Departments of Medicine and Epidemiology, Schools of Medicine and Public Health, Columbia University, New York, NY
  5. 5. Singapore Eye Research Institute, National University of Singapore, Singapore

    Abstract

    Objective: There are conflicting data regarding relationships of systemic biomarkers of inflammation, hemostasis and homocysteine with diabetic retinopathy (DR). We examined these relationships in the Multi-Ethnic Study of Atherosclerosis (MESA).

    Research design and methods: 921 participants with diabetes were included. DR was graded from retinal photographs. We defined two outcomes: any DR and vision-threatening DR (severe non-proliferative DR or worse). Systemic markers analyzed were C-reactive protein (CRP), homocysteine, fibrinogen, plasmin-α2-antiplasmin complex (PAP), interleukin-6, D-Dimer, factor VIII, serum creatinine, and urinary albumin-creatinine (UAC) ratio.

    Results: Prevalence of DR was 33.2% and vision-threatening DR 7.1%. After adjusting for established risk factors (diabetes duration, hemoglobinA1C, systolic blood pressure, waist-hip ratio, and use of diabetic medications), fibrinogen (odds ratio [OR] 1.14, 95% Confidence Interval [CI] 1.01-1.32, p=0.05) and PAP (OR 1.25, 95% CI 1.05-1.50, p=0.01) were associated with any DR, while PAP (OR 1.54, 95% CI 1.13-2.11, p=0.007) and homocysteine (OR 1.57, 95% CI 1.16-2.11, p=0.003) were associated with vision-threatening DR. Only PAP remained significant after additional adjustment for serum creatinine and UAC ratio. Area under receiver operator characteristic curve (AUC) for DR was constructed for established and novel risk factors. Established risk factors accounted for 39.2% increase of the AUC whereas novel markers (fibrinogen, PAP, homocysteine, serum creatinine and UAC ratio) only accounted for an additional 2.2%.

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

    Footnotes

      • Received January 19, 2009.
      • Accepted June 13, 2009.

    This Article

    1. Published online before print June 23, 2009, doi: 10.2337/dc09-0102
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