Lipoprotein trajectories from prediabetes to type 2 diabetes with complications: a Chinese population-specific formula for sdLDL-C estimation

Abstract

Abstract Objective This study aimed to (1) evaluate small dense low-density lipoprotein cholesterol (sdLDL-C) dynamics from prediabetes to type 2 diabetes mellitus (T2DM) with complications, (2) validate existing sdLDL-C estimation formulas (Sampson’s, Srisawasdi’s, Han’s) in Chinese populations, and (3) develop a population-specific formula for enhanced accuracy. Methods A multicenter study recruited 1,944 participants (216 controls, 70 with prediabetes, 212 with newly diagnosed T2DM, 164 with treated T2DM, and 1,286 in validation cohorts). Lipid profiles, including sdLDL-C (measured via enzymatic assays), were analyzed. Formula performance was assessed using spearman correlation, intraclass correlation coefficients (ICC), and multivariable linear regression. A novel formula was derived via multivariable regression. Results Atherogenic lipid triad manifestations emerged early: sdLDL-C was significantly elevated in participants with prediabetes (1.07 [0.73, 1.40] vs. 0.57 [0.44, 0.72] mmol/L in controls, P 0.05). A novel sdLDL-C estimation formula, incorporating low-density lipoprotein cholesterol (LDL-C), TG, nonHDL-C, age, and sex, achieved superior accuracy (R²=0.743; ICC = 0.681) and minimized residuals (Δ = 0.16 vs. 0.28–0.29, P < 0.05). Conclusion sdLDL-C elevation begins in prediabetes, highlighting its value for early atherosclerotic cardiovascular disease (ASCVD) risk assessment. Current formulas show population-specific limitations, whereas the new model provides improved accuracy for Chinese T2DM patients, enabling cost-effective sdLDL-C estimation and personalized lipid management.

Keywords

• Small dense LDL cholesterol
• Type 2 diabetes mellitus
• Estimation formula