Retrospective Study
Copyright ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Mar 15, 2025; 16(3): 98590
Published online Mar 15, 2025. doi: 10.4239/wjd.v16.i3.98590
Association between serum retinol-binding protein and lower limb atherosclerosis risk in type 2 diabetes mellitus
Yu-Ling Zhang, Gui-Liang Peng, Wei-Ling Leng, Yu Lian, Li-Qing Cheng, Xing Li, Yu-Lin Wang, Ling Zhou, Min Long
Yu-Ling Zhang, Gui-Liang Peng, Wei-Ling Leng, Li-Qing Cheng, Yu-Lin Wang, Ling Zhou, Min Long, Department of Endocrinology, Southwest Hospital, Army Medical University (The Third Military Medical University), Chongqing 400038, China
Yu-Ling Zhang, Yu Lian, Li-Qing Cheng, Department of Endocrinology, Southwest Hospital Jiangbei Area (The 958th Hospital of Chinese People’s Liberation Army), Chongqing 400000, China
Xing Li, Department of Endocrinology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210093, Jiangsu Province, China
Xing Li, Department of Endocrinology, Jinling Hospital, Nanjing Medical University, Nanjing 210093, Jiangsu Province, China
Xing Li, Department of Endocrinology, Jinling Hospital, School of Medicine, Southeast University, Nanjing 210093, Jiangsu Province, China
Co-first authors: Yu-Ling Zhang and Gui-Liang Peng.
Author contributions: Zhang YL and Peng GL performed study concept and design and data analysis, and they contributed equally to this work as co-first authors; Zhou L, Lian Y, Cheng LQ, and Wang YL performed data collection; Leng WL performed data verification; Long M and Li X revised the manuscript and make final approval of the version; and all authors read and approved the final version of manuscript.
Supported by Chongqing Young and Middle-aged Medical High-end Talents Project; Chongqing Young and Middle-aged Medical High-end Talents Studio Project; and Southwest Outstanding Youth and Talents Project.
Institutional review board statement: The study was approved by the ethics committee of Southwest Hospital, the First Affiliated Hospital of Army Medical University of Chinese People's Liberation Army (No. KY2024007).
Informed consent statement: Given the retrospective nature of this study and the anonymity of participant data, the institutional reviewer waived the requirement for informed consent.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: The data underlying this article will be shared on reasonable request to the corresponding author.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Min Long, Associate Chief Physician, Associate Professor, Department of Endocrinology, Southwest Hospital, Army Medical University (The Third Military Medical University), No. 30 Gaotanyan Main Street, Shapingba District, Chongqing 400038, China. longmin@tmmu.edu.cn
Received: June 30, 2024
Revised: November 13, 2024
Accepted: December 30, 2024
Published online: March 15, 2025
Processing time: 205 Days and 1.9 Hours
Abstract
BACKGROUND

Serum retinol-binding protein (RBP) is the primary transport protein of circulating vitamin A. RBP has a crucial role in maintaining nutrient metabolism and physiologic homeostasis. Several studies have indicated that serum RBP participates in the progression of diabetes and diabetes-related complications. However, the impact of serum RBP on lower limb atherosclerosis has not been determined in individuals with type 2 diabetes mellitus (T2DM).

AIM

To determine the association between serum RBP and lower limb atherosclerosis in individuals with T2DM.

METHODS

This retrospective study enrolled 4428 eligible T2DM patients and divided the patients into non-lower limb atherosclerosis (n = 1913) and lower limb atherosclerosis groups (n = 2515) based on lower limb arterial ultrasonography results. At hospital admission, baseline serum RBP levels were assessed, and all subjects were categorized into three groups (Q1-Q3) based on RBP tertiles. Logistic regression, restricted cubic spline regression, subgroup analysis, and machine learning were used to assess the association between RBP levels and lower limb atherosclerosis risk.

RESULTS

Among 4428 individuals with T2DM, 2515 (56.80%) had lower limb atherosclerosis. Logistic analysis showed that lower limb atherosclerosis risk increased by 1% for every 1 unit rise in serum RBP level (odds ratio = 1.01, 95% confidence interval: 1.00-1.02, P = 0.004). Patients in the highest tertile group (Q3) had a higher lower limb atherosclerosis risk compared to the lowest tertile group (Q1) (odds ratio = 1.36, 95% confidence interval: 1.12-1.67, P = 0.002). The lower limb atherosclerosis risk gradually increased with an increase in RBP tertile (P for trend = 0.005). Restricted cubic spline analysis indicated a linear correlation between serum RBP levels and lower limb atherosclerosis risk (non-linear P < 0.05). Machine learning demonstrated the significance and diagnostic value of serum RBP in predicting lower limb atherosclerosis risk.

CONCLUSION

Elevated serum RBP levels correlate with an increased lower limb atherosclerosis risk in individuals with T2DM.

Keywords: Retinol-binding protein; Type 2 diabetes mellitus; Lower limb atherosclerosis; Peripheral arterial disease; Biomarker

Core Tip: This cross-sectional study determined the association between the serum retinol-binding protein (RBP) level and lower limb atherosclerosis risk in individuals with type 2 diabetes mellitus (T2DM). The lower limb atherosclerosis risk increased with each unit increase in serum RBP level. Individuals with T2DM in the highest tertile group (Q3) had a higher lower limb atherosclerosis risk compared to the lowest tertile group (Q1) and there was a linear association between the serum RBP level and the lower limb atherosclerosis risk in T2DM. Therefore, clinical attention should be focused on the serum RBP level in T2DM patients.