title: Prospective study of inflammatory biomarkers and risk of diabetic retinopathy in the diabetes control and complications trial.
abstract: OBJECTIVE
  This study demonstrates that increasing quintiles of baseline high-sensitivity C-reactive protein (hsCRP) level may be associated with higher risk of incident clinically significant macular edema, the leading cause of vision loss in working-aged individuals in North America.
  
  
  OBJECTIVE
  To determine whether baseline levels of hsCRP and intercellular adhesion molecule 1 (ICAM-1) predict development and progression of diabetic retinopathy (DR), clinically significant macular edema (CSME), retinal hard exudates, and proliferative DR in the Diabetes Control and Complications Trial (DCCT) cohort.
  
  
  METHODS
  The DCCT was a large multicenter randomized controlled clinical trial.
  
  
  METHODS
  Twenty-nine medical centers in the United States and Canada.
  
  
  METHODS
  The DCCT population consisted of 1441 subjects with type 1 diabetes mellitus aged 13 to 39 years at study entry.
  
  
  METHODS
  We measured levels of hsCRP, ICAM-1, vascular cell adhesion molecule 1, and tumor necrosis factor α receptor 1 in stored baseline blood samples.
  
  
  METHODS
  We assessed the association of levels of hsCRP, ICAM-1, vascular cell adhesion molecule 1, and tumor necrosis factor α receptor 1 with incident DR end points ascertained from grading of standardized 7-field stereoscopic retinal color photographs taken at baseline and every 6 months during follow-up.
  
  
  RESULTS
  After adjustment for randomized treatment assignment and other factors, we observed a statistically significant association between hsCRP and risk of CSME, with a relative risk (RR) for the top vs bottom quintile of 1.83 (95% CI, 0.94-3.55; P for trend = .01). Similarly, for the development of retinal hard exudates, the RR for the top vs bottom quintile of hsCRP level was 1.78 (95% CI, 0.98-3.25; P for trend = .004), whereas for ICAM-1 level, the RR comparing the top vs bottom quintiles was 1.50 (95% CI, 0.84-2.68; P for trend = .05). There were no statistically significant associations between baseline VCAM-1 or tumor necrosis factor α receptor 1 levels and risk of any of the DR end points.
  
  
  CONCLUSIONS
  After adjusting for known risk factors, increasing quintiles of baseline hsCRP level may be associated with higher risk of incident CSME and macular hard exudate in the DCCT cohort. Circulating levels of ICAM-1 may also be associated with the development of retinal hard exudates.
authors: Department of Ophthalmology and Vision Sciences, University of Toronto, St Michael’s Hospital, Toronto, Canada. rajeev.muni@utoronto.ca
authors: Rajeev H
authors: RH
authors: Muni
authors: Radha P
authors: RP
authors: Kohly
authors: Eudocia Q
authors: EQ
authors: Lee
authors: JoAnn E
authors: JE
authors: Manson
authors: Richard D
authors: RD
authors: Semba
authors: Debra A
authors: DA
authors: Schaumberg
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood*; D002097:C-Reactive Protein / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D003922:Diabetes Mellitus, Type 1 / Q000150:complications; D003930:Diabetic Retinopathy / Q000097:blood / Q000175:diagnosis*; D004797:Enzyme-Linked Immunosorbent Assay; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood*; D008269:Macular Edema / Q000097:blood / Q000175:diagnosis; D009391:Nephelometry and Turbidimetry; D011446:Prospective Studies; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000097:blood*; D018570:Risk Assessment; D012307:Risk Factors; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D002097:C-Reactive Protein; D006442:Glycated Hemoglobin; D018799:Intercellular Adhesion Molecule-1; D047888:Receptors, Tumor Necrosis Factor, Type I; D019010:Vascular Cell Adhesion Molecule-1; C517652:hemoglobin A1c protein, human
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