1152-OR: ABC Transporters as Surrogate Biomarkers of HDL Functionality for Early Atherosclerosis Risk Assessment in Type 2 Diabetes Mellitus

Introduction and Objective: In type 2 diabetes mellitus (T2DM) with atherosclerosis, high-density lipoprotein cholesterol (HDL-C) levels may appear normal, but may exhibit reduced functionality. ATP-binding cassette transporters play a crucial role in HDL functionality, but there are only a few clinical studies. We evaluated the levels of ABC transporters (ABCA1 and ABCG1) in T2DM compared to those with normal glucose tolerance (NGT). Methods: Study groups included NGT (n=47), T2DM without atherosclerosis (T2DM; n=47), and T2DM with atherosclerosis (T2DM+A; n=61). Circulatory levels of ABCA1 and ABCG1 were measured using ELISA, and HDL functionality was assessed by macrophage cholesterol efflux (CE) assay. Associations between ABC transporters and HDL functionality were analysed using correlation analysis and multinomial logistic regression studies. ROC curve analyses were performed to evaluate the discriminatory performance. Results: Circulatory ABCA1 and ABCG1 levels were significantly lower in T2DM+A and T2DM than in NGT group, but were positively associated with CE. No significant differences were observed in HDL-C levels among groups. However, HDL functionality was significantly reduced in T2DM+A (25.08±1.90) and T2DM (29.72±1.75) compared to NGT (32.86±2.07). ROC curve analysis for ABCA1 yielded an AUC of 0.782 (95% CI: 0.684-0.861; Cutoff 0.5086 ng/mL) while ABCG1 yielded an AUC of 0.752 (95% CI: 0.669-0.824; Cutoff 0.3576 ng/mL). Conclusion: HDL functionality as measured by CE was significantly reduced in patients with T2DM+A and T2DM, and positively associated with ABC transporters. ABCA1 and ABCG1 may serve as surrogate markers for HDL functionality and early risk indicators of atherosclerosis.