Do Tissue Plasminogen Activator-Plasminogen Activator Inhibitor-1 Complexes Relate to the Complications of Insulin-Dependent Diabetes Mellitus? Pittsburgh Epidemiology of Diabetes Complications Study

The purpose of this study was to examine the potential relationship of tissue plasminogen activator-plasminogen activator inhibitor-1 (tPA-PAI-1) complexes and diabetic complications in individuals with insulin-dependent diabetes mellitus (IDDM). To address this issue, data from the third follow-up visit of participants in the Epidemiology of Diabetes Complications (EDC) study were examined. There were 454 participants, aged 32 ± 8 years, with duration of IDDM of 23 ± 8 years. Higher levels of tPA-PAI-1 complexes were seen for both men and women with IDDM complications. Specifically, statistically significant differences were seen in men with neuropathy (1.81 ± 0.9 versus 1.42 ± 0.8 ng/mL, p < 0.01), microalbuminuria (1.77 ± 1.1 versus 1.35 ± 0.6 ng/mL, p < 0.01), retinopathy (1.67 ± 0.9 versus 1.43 ± 0.8 ng/mL, p < 0.05), and lower extremity arterial disease (1.93 ± 0.7 versus 1.50 ± 0.9 ng/mL, p < 0.05) versus men without the particular complication. In women, higher complex levels were shown for those with retinopathy (1.51 ± 0.8 versus 1.29 ± 1.1 ng/mL, p < 0.01). Potential mechanisms for the relationship of higher complex levels and diabetic complications include an altered fibrinolytic response and/or insulin resistance. Because the results are cross sectional, it cannot be established whether the higher concentration of complexes is a result of the presence of complications or are antecedent. Prospective follow-up will be required to determine if tPA-PAI-1 complexes are predictive of the development of IDDM complications.