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Do plasminogen activator inhibitor (PAI‐1) or tissue plasminogen activator PAI‐1 complexes predict complications in Type 1 diabetes: The Pittsburgh Epidemiology of Diabetes Complications Study
Author(s) -
Bosnyak Z.,
Forrest K. Y.Z.,
Maser R. E.,
Becker D.,
Orchard T. J.
Publication year - 2003
Publication title -
diabetic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.474
H-Index - 145
eISSN - 1464-5491
pISSN - 0742-3071
DOI - 10.1046/j.1464-5491.2003.00898.x
Subject(s) - medicine , endocrinology , diabetes mellitus , plasminogen activator inhibitor 1 , plasminogen activator , body mass index , diabetic nephropathy , nephropathy , gastroenterology
Aims To examine the predictive power of plasminogen activator inhibitor‐1 (PAI‐1) and the complexes it forms with tissue plasminogen activator (tPA–PAI‐1) for the two major Type 1 diabetes (T1D) complications (coronary artery disease (CAD) and overt nephropathy) in the context of standard risk factors. Methods Observational prospective study of 454 participants with childhood onset (< 17 years) T1D, aged 18+ years at baseline. PAI‐1 and tPA–PAI‐1 were determined using ELISA methodology. Follow‐up (6 years) was limited to 382 individuals for CAD and 294 individuals for overt nephropathy, after excluding baseline cases. Total, HDL and LDL‐cholesterol, triglycerides, HbA 1 , blood pressure, body mass index (BMI), waist–hip ratio (WHR), leucocyte count, Beck depression score and fibrinogen were also examined. Results The 56 incident cases of CAD had marginally lower PAI‐1 and higher tPA–PAI‐1 levels compared with those free of CAD. However, marginally higher PAI‐1 and significantly higher tPA–PAI‐1 ( P = 0.04) levels were seen in those who developed nephropathy. After controlling for age, both PAI‐1 and tPA–PAI‐1 showed significant negative correlations with HDL‐cholesterol, and positive correlations with triglycerides, WHR, HbA 1 and fibrinogen. tPA–PAI‐1 was also positively correlated with total and LDL‐cholesterol. In multivariate analyses, neither PAI‐1 nor tPA–PAI‐1 was an independent predictor of CAD or overt nephropathy. Conclusions These results suggest little association between PAI‐1 and later CAD in patients with T1D. However, tPA–PAI‐1 complexes may be involved in the pathogenesis of overt nephropathy.