Bin Cao,1,2,* Kun Li,1,2,* Jing Ke,1,2 Dong Zhao1,2 

1Center for Endocrine Metabolism and Immune Diseases, Beijing Luhe Hospital, Capital Medical University, Beijing, 101149, People’s Republic of China; 2Beijing Key Laboratory of Diabetes Research and Care, Beijing, 101149, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Jing Ke; Dong Zhao, Email kejing@ccmu.edu.cn; zhaodong@ccmu.edu.cn

Objective: This study aimed to investigate the potential association between long-term variations in remnant cholesterol (RC) levels and the development of diabetic foot ulcers (DFU) in participants with type 2 diabetes (T2D).
Methods: This was a retrospective cohort study. Variation in RC was assessed by the following metrics: mean, standard deviation (SD), coefficient of variation (CV) and trajectories pattern of RC. To identify RC trajectories, we employed the latent class mixture model. The primary endpoint was the development of DFU, and the time-to-event data were analyzed using Cox regression.
Results: A total of 1874 patients with T2D were included, with a median follow-up duration of 4.7 years. Among them, 129 individuals (6.9%) developed DFU. The proportion of DFU was significantly higher in the U-shaped group compared to the median group (P for trend < 0.001). Upon adjustment for confounding variables, the U-shaped trajectory correlated with a higher risk of DFU, demonstrating a hazard ratio (HR) of 2.57 (95% CI, 1.54– 4.27). Subgroup analysis showed the U-shaped trajectory had a higher DFU risk regardless of gender (HR=2.40 and 2.81, respectively), glycemic control (HR=1.89 and 7.41, respectively), smoking (HR=2.36 and 2.93, respectively), or hypertension (HR=2.30 and 2.97, respectively). No association was found between mean, SD and CV of RC and DFU.
Conclusion: A U-shape trajectory of RC was independently associated with an elevated risk of DFU among patients with T2D.

Keywords: diabetic foot ulcer, remnant cholesterol, trajectories, type 2 diabetes