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

Abstract EN

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.