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

Nasrin Azad, Lily Agrawal, Nicholas V. Emanuele, Ronald Klein, Gideon D. Bahn, Madeline McCarren, Peter Reaven, Rodney Hayward, William Duckworth

Research output: Contribution to journalArticle

16 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)501-506
Number of pages6
JournalDiabetes Care
Volume37
Issue number2
DOIs
StatePublished - Feb 1 2014
Externally publishedYes

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Plasminogen
Veterans
Diabetic Retinopathy
Fibrinogen
Odds Ratio
Incidence
Sexually Transmitted Diseases
Type 2 Diabetes Mellitus
Research Design
Randomized Controlled Trials
Inflammation

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Advanced and Specialized Nursing

Cite this

Azad, N., Agrawal, L., Emanuele, N. V., Klein, R., Bahn, G. D., McCarren, M., ... Duckworth, W. (2014). Association of PAI-1 and fibrinogen with diabetic retinopathy in the veterans affairs diabetes trial (VADT). Diabetes Care, 37(2), 501-506. https://doi.org/10.2337/dc13-1193

Association of PAI-1 and fibrinogen with diabetic retinopathy in the veterans affairs diabetes trial (VADT). / Azad, Nasrin; Agrawal, Lily; Emanuele, Nicholas V.; Klein, Ronald; Bahn, Gideon D.; McCarren, Madeline; Reaven, Peter; Hayward, Rodney; Duckworth, William.

In: Diabetes Care, Vol. 37, No. 2, 01.02.2014, p. 501-506.

Research output: Contribution to journalArticle

Azad, N, Agrawal, L, Emanuele, NV, Klein, R, Bahn, GD, McCarren, M, Reaven, P, Hayward, R & Duckworth, W 2014, 'Association of PAI-1 and fibrinogen with diabetic retinopathy in the veterans affairs diabetes trial (VADT)', Diabetes Care, vol. 37, no. 2, pp. 501-506. https://doi.org/10.2337/dc13-1193
Azad, Nasrin ; Agrawal, Lily ; Emanuele, Nicholas V. ; Klein, Ronald ; Bahn, Gideon D. ; McCarren, Madeline ; Reaven, Peter ; Hayward, Rodney ; Duckworth, William. / Association of PAI-1 and fibrinogen with diabetic retinopathy in the veterans affairs diabetes trial (VADT). In: Diabetes Care. 2014 ; Vol. 37, No. 2. pp. 501-506.
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AU - Emanuele, Nicholas V.

AU - Klein, Ronald

AU - Bahn, Gideon D.

AU - McCarren, Madeline

AU - Reaven, Peter

AU - Hayward, Rodney

AU - Duckworth, William

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N2 - 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.

AB - 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.

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