Retinol-Binding Protein-4—A Predictor of Insulin Resistance and the Severity of Coronary Artery Disease in Type 2 Diabetes Patients with Coronary Artery Disease

SIMPLE SUMMARY: Cytokines are cell-signaling molecules that cause cells to migrate to inflammation, infection, or trauma sites. An imbalance of cytokines in the body can result in severe illness. Increased cytokine retinol-binding protein-4 levels cause muscle, fat, and liver cells to become unresponsive to insulin and not absorb sugar from the blood. Type 2 diabetes, the most common type of diabetes, is caused by the unresponsiveness of insulin (insulin resistance). Moreover, elevated retinol-binding protein-4 causes fat and cholesterol buildup in the arteries of the heart. This results in coronary artery disease, a type of heart disease. These two diseases are hypothesized to share a common underlying cause, but the details have not been fully elucidated. Therefore, this study was conducted to find the association between retinol-binding protein-4 with insulin resistance and the severity of coronary artery disease. We postulated that retinol-binding protein-4 is linked to insulin resistance and the severity of coronary artery disease. This study proves a definitive relationship between retinol-binding protein-4 and insulin resistance and coronary artery disease severity. Hence, retinol-binding protein-4 may serve as a valuable biological indicator to depict insulin resistance and the severity of coronary artery disease. ABSTRACT: (1) Background: Insulin resistance (IR) is the fundamental cause of type 2 diabetes (T2D), which leads to endothelial dysfunction and alters systemic lipid metabolism. The changes in the endothelium and lipid metabolism result in atherosclerotic coronary artery disease (CAD). In insulin-resistant and atherosclerotic CAD states, serum cytokine retinol-binding protein-4 (RBP-4) levels are elevated. The adipocyte-specific deletion of glucose transporter 4 (GLUT4) results in higher RBP-4 expression and IR and atherosclerotic CAD progression. (2) Aim: This study aimed to investigate the association of RBP-4 and clinical factors with IR and the severity of CAD. (3) Methods: Patients were recruited from diabetes and cardiology clinics and divided into three subgroups, namely (i) T2D patients with CAD, (ii) T2D-only patients, and (iii) CAD-only patients. The severity of CAD was classified as either single-vessel disease (SVD), double-vessel disease (DVD), or triple-vessel disease (TVD). An enzyme-linked immunosorbent assay was conducted to assess the concentration of serum RBP-4. Univariate (preliminary analysis) and multivariate (secondary analysis) logistic regressions were applied to assess the associations of RBP-4 and clinical factors with IR and the severity of CAD. (4) Results: Serum RBP-4 levels were associated with IR and the severity of CAD in all the three groups (all p-values are less than 0.05). Specifically, serum RBP-4 levels were associated with IR (p = 0.030) and the severity of CAD (SVD vs. DVD, p = 0.044; SVD vs. TVD, p = 0.036) in T2D patients with CAD. The clinical factors fasting plasma glucose (FPG) and angiotensin-converting-enzyme inhibitor (ACEI) were also associated with both IR and the severity of CAD in T2D patients with CAD. (5) Conclusion: RBP-4, FPG, and ACEI are predictors of IR and severity of CAD in T2D patients with CAD.