Glycoprotein Profile Measured by a 1H-Nuclear Magnetic Resonance Based on Approach in Patients with Diabetes: A New Robust Method to Assess Inflammation.

Núria Amigó,Josefa Girona,Daiana Ibarretxe,Ana Irene Malo,Lluís Masana,Núria Plana,Xavier Correig,Rocío Fuertes-Martín

doi:10.3390/life11121407

Abstract

Patients with type 2 diabetes mellitus (T2DM) and atherogenic dyslipidemia (AD) are at higher risk of developing cardiovascular diseases (CVDs), so an interest in discovering inflammation biomarkers as indicators of processes related to CVD progression is increasing. This study aims (a) to characterize the plasma glycoprotein profile of a cohort of 504 participants, including patients with and without T2DM and/or AD and controls, and (b) to study the associations between the glycoprotein profile and other lipid and clinical variables in these populations. We characterized the plasma glycoprotein profiles by using 1H-NMR. We quantified the two peaks associated with the concentration of plasma glycoproteins (GlycA and GlycB) and their height/width ratios (H/W GlycA and H/W GlycB), as higher and narrower signals have been related to inflammation. We also quantified GlycF, the signal of which is proportional to the concentration of the acetyl groups of free N-acetylglucosamine, N-acetylgalactosamine, and N-acetylneuraminic in the samples. The lipoprotein profile was also determined (Liposcale®). Standard clinical and anthropometric measurements were taken. Multivariate classification models were developed to study the differences between the study groups. Reduced HDL-C levels, increased small dense LDL and HDL particles, and elevated TG levels were significantly associated with glycoprotein variables. Glycoprotein values in the diagnostic groups were significantly different from those in the CT groups. AD and DM conditions together contribute to a positive and significant synergetic effect on the GlycA area (<0.05) and the H/W ratios of GlycA (<0.01) and GlycB (<0.05). By adding the new glycoprotein variables to the traditionally used marker of inflammation C-reactive protein (CRP), the AUC increased sharply for classification models between the CT group and the rest (0.68 to 0.84), patients with and without dyslipidemia (0.54 to 0.86), and between patients with and without diabetes (0.55 to 0.75). 1H-NMR-derived glycoproteins can be used as possible markers of the degree of inflammation associated with T2DM and AD.

Highlights

Type 2 diabetes (T2DM) is one of the most common diseases and has been growing exponentially in recent years [1]
We characterized the plasma 1H-NMR glycoprotein profile of type 2 diabetes mellitus (T2DM) patients with and without atherogenic dyslipidemia (AD); we explored its association with their advanced NMR lipoprotein profile; and, we compared the ability of these new NMR based on inflammatory markers to discriminate specific patterns between study groups, other than those commonly used in clinical settings, including traditional risk factors and C-reactive protein (CRP)
We have characterized the 1H-NMR plasma glycoproteins of T2DM patients with and without AD, we have explored their relation with lipoproteins and clinical variables, and we have evaluated them as new emerging inflammatory markers of disease in comparison to CRP

Summary

Introduction

Type 2 diabetes (T2DM) is one of the most common diseases and has been growing exponentially in recent years [1]. Unlike common biomarkers of inflammation, such as CRP or inflammatory cytokines, GlycA is a composite biomarker that integrates the protein levels and glycation states of several of the most abundant acute-phase proteins in serum (α1-acid glycoprotein, haptoglobin, α1-antitrypsin, α1-antichymotrypsin, and transferrin) [14,16]. This provides a more stable measurement of systemic inflammation with less intra-individual variability for GlycA than for high sensitivity CRP [14]. GlycA, and to a lesser extent GlycB, is the variable that has most been studied in terms of glycoproteins determined by 1H-NMR based on the metabolomic approach, other new variables have recently been reported, such as the derived parameters H/W GlycA and H/W GlycB, which are related to the shape of the signal (higher and narrower signals have been related to inflammation) [15]

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