Plasma Protein Oxidation as a Determinant of Impaired Fibrinolysis in Type 2 Diabetes.

OBJECTIVE:  We investigated clinical and laboratory determinants of plasma protein oxidation and its associations with clot fibrinolysis in type 2 diabetes patients.

MATERIALS AND METHODS:  Our cross-sectional study consisted of 246 type 2 diabetic patients, 143 (58%) with concomitant cardiovascular disease (CVD), including 41 (17%) with previous myocardial infarction (MI). We measured total protein carbonylation (PC), thiobarbituric acid reactive substances (TBARS) and total antioxidant capacity (TAC) along with clot lysis time (CLT) and clot permeation ( Ks ), fibrinogen, plasminogen, α-2-antiplasmin, plasminogen activator inhibitor-1 (PAI-1), thrombin activatable fibrinolysis inhibitor (TAFI) and thrombomodulin.

RESULTS:  Total PC correlated positively, while TAC correlated inversely with glycated haemoglobin and diabetes duration (all p  < 0.05). Diabetic patients with CVD had higher total PC, TBARS and lower TAC compared with the remainder (all p  < 0.001). Among correlations of total PC with Ks , PAI-1, thrombomodulin and TAFI, the strongest was with CLT ( r  = 0.687, all p  < 0.01). High total PC, defined as ≥ 3.45 nmol/mg, was predicted by time since diabetes diagnosis ≥ 5 years (odds ratio [OR]: 3.0, 95% confidence interval [CI]: 1.36-6.63) and previous MI (OR: 11.31, 95% CI: 4.37-29.32). After adjustment for potential confounders, total PC accounted for 34.9% of the total variance in CLT. Total PC at a cut-off of 3.44 nmol/mg showed high discriminatory power for identifying patients with prolonged CLT (area under the curve: 0.845, 95% CI: 0.792-0.898, p  < 0.001).

CONCLUSION:  Elevated plasma PC, largely driven by a long history of diabetes and concomitant CVD, is an important determinant of hypofibrinolysis in type 2 diabetes.