Lipoprotein(a) and Small Dense LDL Profiles and Statin Response in Type 2 Diabetes Mellitus: A Case-Control Study

Abstract Lipoprotein subfraction research has emerged as a promising approach for risk stratification, warranting investigation in type 2 diabetes mellitus (T2DM), cardiovascular disease (CVD), and lipid-lowering therapy. This cross-sectional, case-control study aimed to characterize lipoprotein particle profiles, including small dense LDL (sdLDL) and lipoprotein(a) [Lp(a)], in individuals with T2DM and CVD compared with healthy controls, and to evaluate their associations with clinical risk factors. Fasting plasma samples from 118 participants were analyzed: T2DM (n = 52), CVD (n = 14), and healthy controls (n = 52). Lipoprotein levels and subclasses were quantified using proton nuclear magnetic resonance (¹H NMR) spectroscopy with Bruker’s In-Vitro Diagnostic research (IVDr) Lipoprotein Subclass Analysis (B.I.LISA). Participants had a mean age of 46.9 ± 9.0 years, and 79% were female. Compared with controls, individuals with T2DM had significantly higher Lp(a) (p = 0.012), triglycerides, total cholesterol, LDL, and apolipoprotein B100 (apoB100) (p < 0.05), while HDL remained unchanged; sdLDL levels were higher but not statistically significant. Statin therapy reduced large buoyant and intermediate-density LDL particles but had limited effects on sdLDL and Lp(a). Physical activity was associated with higher HDL and lower LDL (p < 0.001). In conclusions, Lp(a) and sdLDL contribute to CVD risk in T2DM, with partial response to statin therapy.