Association of PAI-1 and Fibrinogen With Diabetic Retinopathy in the Veterans Affairs Diabetes Trial (VADT)

• Published in: Diabetes care Vol. 37; no. 2; pp. 501 - 506
• Main Authors: AZAD, Nasrin, AGRAWAL, Lily, EMANUELE, Nicholas V, KLEIN, Ronald, BAHN, Gideon D, McCARREN, Madeline, REAVEN, Peter, HAYWARD, Rodney, DUCKWORTH, William
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.02.2014
• Subjects: Aged; Biological and medical sciences; Blood Glucose - analysis; Clinical trials; Diabetes; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - complications; Diabetes. Impaired glucose tolerance; Diabetic retinopathy; Diabetic Retinopathy - metabolism; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Female; Fibrinogen - metabolism; Glycemic index; Humans; Male; Medical sciences; Metabolic diseases; Middle Aged; Ophthalmology; Pathophysiology/Complications; Plasminogen Activator Inhibitor 1 - metabolism; Prescription drugs; Prospective Studies; Retinopathies; Veterans; United States; North America; America; Endocrinopathy; Human; Health system; Health insurance; Retinopathy; Nutrition; Diabetes mellitus; Metabolic diseases; Plasminogen activator inhibitor 1; Eye disease; Association; Fibrinogen; Clinical trial; Veteran; Endocrinology
• ISSN: 0149-5992; 1935-5548
• DOI: 10.2337/dc13-1193

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). 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. 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). 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.