Association of PAI-1 and fibrinogen with diabetic retinopathy in the veterans affairs diabetes trial (VADT) Journal Article

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Authors: Azad, N; Agrawal, L; Emanuele, N. V.; Klein, R.; Bahn, G. D.; McCarren, M.; Reaven, P.; Hayward, R.; Duckworth, W.; VADT Study Group
Article Title: Association of PAI-1 and fibrinogen with diabetic retinopathy in the veterans affairs diabetes trial (VADT)
Abstract: OBJECTIVE: To test the hypothesis that high levels of plasminogen-activating inhibitor (PAI)-1 and fibrinogen at baseline were associated with the onset or progression of diabetic retinopathy (DR) during the Veterans Affairs Diabetes Trial (VADT). RESEARCH DESIGN AND METHODS: The VADT was an open-label, prospective, randomized controlled trial to test the effect of standard glycemic control (STD) compared with intensive control (INT) on cardiovascular events in patients with advanced type 2 diabetes mellitus (T2DM). Diabetic retinopathy (DR) outcomes were also collected. Incidence and progression of DR were assessed by grading seven-field stereoscopic fundus photographs at baseline and 5 years later taken in 858 of a total of 1,791 participants who completed both eye examinations. RESULTS: Assignment to INT was not independently associated with decreased risk of onset of DR. However, after adjustment for multiple covariates, baseline level of PAI-1 was an independent risk factor for the onset of DR. The risk for incidence of DR increased by 12% for each 10 ng/dL increase in baseline PAI-1 concentration (odds ratio [OR] 1.012 [95% CI 1.00-1.024], P = 0.042). Assignment to INT was not independently associated with decreased risk of progression of DR. However, there was an interaction between glycemic treatment assignment and fibrinogen level at baseline. INT was associated with decreased progression of retinopathy in those with fibrinogen 296 mg/dL (OR 0.55 [95% CI 0.31-1.00], P = 0.03). CONCLUSIONS: The results require confirmation but are consistent with greater hypercoagulabilty and inflammation, as measured by higher levels of PAI-1 and fibrinogen, being related to DR and responsiveness to INT.
Journal Title: Diabetes care
Volume: 37
Issue: 2
ISSN: 1935-5548; 0149-5992
Publisher: Unknown  
Journal Place: United States
Date Published: 2014
Start Page: 501
End Page: 506
Language: eng
DOI/URL:

10.2337/dc13-1193
Notes: GR: 84698/Medical Research Council/United Kingdom; GR: G0700704/Medical Research Council/United Kingdom; JID: 7805975; OID: NLM: PMC3898766 [Available on 02/01/15]; PMCR: 2015/02/01 00:00; 2013/10/07 [aheadofprint]; ppublish