Journal Article

Circulating Factors as Potential Biomarkers of Cardiovascular Damage Progression Associated with Type 2 Diabetes

Lapolla, Annunziata, Banfi, Cristina, Ghilardi, Stefania, Mallia, Alice, Piarulli, Francesco, Carollo, Massimo, Ragazzi, Eugenio, Sartore, Giovanni

2024

Overview

Background: Diabetes, particularly type 2 diabetes (T2D), is linked with an increased risk of developing coronary heart disease (CHD). The present study aimed to evaluate potential circulating biomarkers of CHD by adopting a targeted proteomic approach based on proximity extension assays (PEA). Methods: The study was based on 30 patients with both T2D and CHD (group DC), 30 patients with T2D without CHD (group DN) and 29 patients without diabetes but with a diagnosis of CHD (group NC). Plasma samples were analyzed using PEA, with an Olink Target 96 cardiometabolic panel expressed as normalized protein expression (NPX) units. Results: Lysosomal Pro-X carboxypeptidase (PRCP), Liver carboxylesterase 1 (CES1), Complement C2 (C2), and Intercellular adhesion molecule 3 (ICAM3) were lower in the DC and NC groups compared with the DN groups. Lithostathine-1-alpha (REG1A) and Immunoglobulin lambda constant 2 (IGLC2) were found higher in the DC group compared to DN and NC groups. ROC analysis suggested a significant ability of the six proteins to distinguish among the three groups (whole model test p < 0.0001, AUC 0.83–0.88), with a satisfactory discriminating performance in terms of sensitivity (77–90%) and specificity (70–90%). A possible role of IGLC2, PRCP, and REG1A in indicating kidney impairment was found, with a sensitivity of 92% and specificity of 83%. Conclusions: The identified panel of six plasma proteins, using a targeted proteomic approach, provided evidence that these parameters could be considered in the chronic evolution of T2D and its complications.

• Publisher: MDPI AG,MDPI
• Subject: Biological markers / Biomarkers / Blood diseases / Blood proteins / Carboxylesterase / Carboxypeptidase / Cardiovascular disease / Cell adhesion / Cluster analysis / Complement component C2 / Complications and side effects / Coronary artery disease / Coronary heart disease / Development and progression / Diabetes / Diabetes mellitus (non-insulin dependent) / Heart diseases / Heart failure / Identification and classification / Intercellular adhesion molecule 3 / Lysosomal Pro-X carboxypeptidase / Measurement / Patients / Physiological aspects / Plasma / Plasma proteins / Proteins / Proteomics / Sensitivity analysis / Statistical analysis / targeted proteomics / Type 2 diabetes / Variance analysis