Endothelial Dysfunction and Advanced Glycation End Products in Patients with Newly Diagnosed Versus Established Diabetes: From the CORDIOPREV Study.

Silvia De La Cruz-Ares,María M Malagón,José D Torres-Peña,Niki Katsiki,Francisco M Gutiérrez-Mariscal,Elena M Yubero-Serrano,Pablo Pérez-Martínez,Magdalena P Cardelo,Antonio García-Rios,José López-Miranda

doi:10.3390/nu12010238

Abstract

Endothelial dysfunction and intima-media thickness of common carotid arteries (IMT-CC) are considered subclinical markers of atherosclerotic cardiovascular disease (ASCVD). Advanced glycation end products (AGEs) are increased in type 2 diabetes mellitus (T2DM) patients, compared with non-diabetics, being implicated in micro- and macrovascular complications. Our aim was to compare serum AGEs levels and subclinical atherosclerotic markers between patients with established and newly diagnosed T2DM. Among 540 patients with T2DM and coronary heart disease from the CORDIOPREV study, 350 patients had established T2DM and 190 patients had newly diagnosed T2DM. Serum levels of AGEs (methylglyoxal (MG) and N-carboxymethyl lysine (CML)) and subclinical atherosclerotic markers (brachial flow-mediated vasodilation (FMD) and IMT-CC) were measured. AGEs levels (all p < 0.001) and IMT-CC (p = 0.025) were higher in patients with established vs. newly diagnosed T2DM, whereas FMD did not differ between the two groups. Patients with established T2DM and severe endothelial dysfunction (i.e., FMD < 2%) had higher serum MG levels, IMT-CC, HOMA-IR and fasting insulin levels than those with newly diagnosed T2DM and non-severe endothelial dysfunction (i.e., FMD ≥ 2%) (all p < 0.05). Serum CML levels were greater in patients with established vs. newly diagnosed T2DM, regardless of endothelial dysfunction severity. Serum AGEs levels and IMT-CC were significantly higher in patients with established vs. newly diagnosed T2DM, highlighting the progressively increased risk of ASCVD in the course of T2DM. Establishing therapeutic strategies to reduce AGEs production and delay the onset of cardiovascular complications in newly diagnosed T2DM patients or minimize ASCVD risk in established T2DM patients is needed.

Highlights

Type 2 diabetes mellitus (T2DM) is associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD) which is fostered by chronic exposure to hyperglycemia, as well as other factors such as hypertension, dyslipidemia or genetic predisposition [1]
intima-media thickness of common carotid arteries (IMT-CC) was higher in patients with established vs. newly diagnosed T2DM (p = 0.025), with all average values higher than 0.7 mm, which is the suggested cutoff value to determine the presence or absence of carotid atherosclerotic disease [28]
Flow-mediated vasodilation (FMD) did not differ between these two study groups, IMT-CC was increased in patients with established vs. newly diagnosed T2DM

Summary

Introduction

Type 2 diabetes mellitus (T2DM) is associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD) which is fostered by chronic exposure to hyperglycemia, as well as other factors such as hypertension, dyslipidemia or genetic predisposition [1]. In a more advanced stage of the disease, changes in the intima-media thickness of common carotid arteries (IMT-CC) can be seen as structural modifications within the vessel wall occur. In this context, increased IMT-CC is used as a surrogate marker of elevated CV risk [6]. As endothelial dysfunction represents a key early step in the development of atherosclerosis, establishing strategies to prevent or improve endothelial dysfunction may minimize the risk of developing atherosclerotic diseases

Objectives

Methods

Results

Discussion

Conclusion