Inflammatory, hemostatic, and other novel biomarkers for diabetic retinopathy: the multi-ethnic study of atherosclerosis.
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.


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-alpha(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 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.
Nguyen
Thanh T
TT
Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, University of Melbourne, Melbourne, Australia.
Alibrahim
Ekaterina
E
Islam
F M Amirul
FM
Klein
Ronald
R
Klein
Barbara E K
BE
Cotch
Mary Frances
MF
Shea
Steven
S
Wong
Tien Y
TY
D000368:Aged; D000419:Albuminuria / Q000652:urine; D050197:Atherosclerosis / Q000097:blood* / Q000453:epidemiology / Q000208:ethnology*; D002097:C-Reactive Protein / Q000032:analysis; D003404:Creatinine / Q000097:blood / Q000652:urine; D003930:Diabetic Retinopathy / Q000097:blood* / Q000453:epidemiology / Q000503:physiopathology*; D005169:Factor VIII / Q000032:analysis; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis; D005341:Fibrinolysin / Q000032:analysis; D006710:Homocysteine / Q000097:blood; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D000073718:Pancreatitis-Associated Proteins; D000979:alpha-2-Antiplasmin / Q000032:analysis
D005338:Fibrin Fibrinogen Degradation Products; D015850:Interleukin-6; D000073718:Pancreatitis-Associated Proteins; C000612141:REG3A protein, human; D000979:alpha-2-Antiplasmin; C036309:fibrin fragment D; C037742:plasmin-plasmin inhibitor complex; D006710:Homocysteine; D005169:Factor VIII; D002097:C-Reactive Protein; D003404:Creatinine; D005341:Fibrinolysin