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.
OBJECTIVE
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, HbA1, 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, HbA1 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.
Bosnyak
Z
Z
Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, PA 15213, USA.
Forrest
K Y-Z
KY
Maser
R E
RE
Becker
D
D
Orchard
T J
TJ
D000328:Adult; D003922:Diabetes Mellitus, Type 1 / Q000097:blood*; D003929:Diabetic Neuropathies / Q000097:blood*; D005260:Female; D006801:Humans; D008297:Male; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism*; D011237:Predictive Value of Tests; D011446:Prospective Studies; D010959:Tissue Plasminogen Activator / Q000378:metabolism*
D017395:Plasminogen Activator Inhibitor 1; D010959:Tissue Plasminogen Activator