Hypofibrinolytic State in Subjects with Type 2 Diabetes Mellitus Aggravated by the Metabolic Syndrome before Clinical Manifestations of Atherothrombotic Disease

Background. Metabolic and genetic factors induce plasminogen activator inhibitor type-1 (PAI-1) overexpression; higher PAI-1 levels decrease fibrinolysis and promote atherothrombosis.Aim. To assess PAI-1 antigen levels among subjects with type 2 diabetes mellitus (T2DM) plus Metabolic Syndrome (MetS) before clinical manifestations of atherothrombosis and the contribution of metabolic factors and 4G/5G polymorphism of PAI-1 gene on the variability of PAI-1.Methods. We conducted an observational, cross-sectional assay in a hospital in Mexico City from May 2010 to September 2011. MetS was defined by the International Diabetes Federation criteria. PAI-1 levels and 4G/5G polymorphism were determined by ELISA and PCR-RFLP analysis.Results. We enrolled 215 subjects with T2DM plus MetS and 307 controls. Subjects with T2DM plus MetS had higher PAI-1 levels than the reference group (58.4 ± 21 versus 49.9 ± 16 ng/mL, p=0.026 ). A model with components of MetS explained only 12% of variability on PAI-1 levels ( R2 = 0.12; p=0.001 ), with β=0.18 ( p=0.03 ) for hypertension, β=-0.16 ( p=0.05 ) for NL HDL-c, and β=0.15 ( p=0.05 ) for NL triglycerides.Conclusion. Subjects with T2DM plus MetS have elevated PAI-1 levels before clinical manifestations of atherothrombotic disease. Metabolic factors have a more important contribution than 4G/5G polymorphism on PAI-1 plasma variability.