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. 2025 Jul 1;24(1):226.
doi: 10.1186/s12944-025-02636-0.

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

Bin Feng #  1   2 , Yi Wang #  3 , Jingjie Xu  1   2 , Liang Sang  4 , Yanhua Zhao  1   2 , Wei Gan  5   6
Affiliations

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

Bin Feng et al. Lipids Health Dis. .

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) and further increased in those with T2DM, correlating strongly with triglycerides (TG; r = 0.59), non-high-density lipoprotein cholesterol (nonHDL-C; r = 0.69), and apolipoprotein B (ApoB; r = 0.62). Existing formulas overestimated sdLDL-C in controls and treated T2DM (P < 0.05), though both Han’s and Sampson’s formula performed better in newly diagnosed T2DM (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.

Supplementary Information: The online version contains supplementary material available at 10.1186/s12944-025-02636-0.

Keywords: Estimation formula; Small dense LDL cholesterol; Type 2 diabetes mellitus.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: This study adhered to the Declaration of Helsinki and was approved by the Ethics Committee of West China Hospital of Sichuan University [Approval No. 2019 (392)]. Consent for publication: Not applicable. Use of AI and AI-assisted technologies statement: In preparing this manuscript, ChatGPT (OpenAI, GPT-4) was employed to assist with grammar corrections and language polishing. Following the application of this tool, the content was meticulously reviewed, revised, and verified. The authors assume complete responsibility for the accuracy and integrity of the study and its published content. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Study design flowchart
Fig. 2
Fig. 2
Integrated Analysis of sdLDL-C: Correlation with Blood Lipid Indices and Validation of Sampson’s and Srisawasdi’s Estimation Models. a: correlation analysis between sdLDL-C and blood lipid indices. b: regression analysis of measured and calculated sdLDL-C
Fig. 3
Fig. 3
Comprehensive Assessment of sdLDL-C Estimation: Residual Correlation with Lipid Profiles, Validation of a Novel Formula, and External Verification of Model Accuracy. a: Correlation analysis between residual and TG, LDL-C and nonHDL-C b: Regression analysis of measured sdLDL-C and calculated sdLDL-C by the new formula. c: Comparison of sdLDL-C residuals between estimated and measured in the external verification group
See this image and copyright information in PMC

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