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

Elsa Aburto-Mejía,Alfredo Leaños-Miranda,Eduardo Almeida-Gutiérrez,Mardia López-Alarcón,Antonio Alvarado-Moreno,Abraham Majluf-Cruz,David Santiago-Germán,María Eugenia Galván-Plata María Eugenia Galván-Plata,Jesús Hernández-Juárez,Manuel Martínez-Marino,Irma Isordia-Salas

doi:10.1155/2017/6519704

Abstract

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.

Highlights

Plasminogen activator inhibitor type-1 (PAI-1) is the principal inhibitor of fibrinolysis [1]
A total sample of 215 subjects with type 2 diabetes mellitus (T2DM) plus the Metabolic Syndrome was recruited among an urban population from Mexico City between May 2010 and September 2011
After the inclusion of all the explanatory variables correlated with plasminogen activator inhibitor type-1 (PAI-1) antigen levels in a multivariable linear regression model, we found that metabolic factors with the strongest contribution in the variability of PAI-1 antigen levels in patients with T2DM plus the Metabolic Syndrome were hypertension (β = 0.18; p = 0.03), natural logarithm (NL) high-density lipoprotein cholesterol (HDL-c) (β = −0.16; p = 0.05), and NL triglycerides (β = 0.15; p = 0.05)

Summary

Introduction

Plasminogen activator inhibitor type-1 (PAI-1) is the principal inhibitor of fibrinolysis [1]. Obesity, dyslipidemia, and endothelial dysfunction induce PAI-1 overexpression and are associated with an augmented cardiovascular risk [4]. The cluster of those traits in a same individual is known as the Metabolic Syndrome [5, 6]. 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. 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

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Discussion

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