Clinical significance of serum thrombospondin-4 for interventional restenosis in diabetes patients complicated by lower extremity arteriosclerosis obliterans

doi:10.4239/wjd.124271

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World Journal of Diabetes

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1948-9358

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

Prospective Study

Copyright: ©Author(s) 2026. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution-NonCommercial (CC BY-NC 4.0) license. No commercial re-use. See permissions. Published by Baishideng Publishing Group Inc.

World J Diabetes. Oct 15, 2026; 17(10): 124271
Published online Oct 15, 2026. doi: 10.4239/wjd.124271

Clinical significance of serum thrombospondin-4 for interventional restenosis in diabetes patients complicated by lower extremity arteriosclerosis obliterans

Die Hu, Xiao-Yue Lin, Tian-Qi Zhao, Hua Ji, Ming-Wei Chen, Xiao-Tong Zhao

Die Hu, Hua Ji, Ming-Wei Chen, Xiao-Tong Zhao, Department of Endocrinology, The First Affiliated Hospital of Anhui Medical University, Hefei 230032, Anhui Province, China

Xiao-Yue Lin, Department of General Practice, The First Affiliated Hospital of Anhui Medical University, Hefei 230032, Anhui Province, China

Tian-Qi Zhao, Department of Endocrinology, The Affiliated Chuzhou Hospital of Anhui Medical University, Chuzhou 239001, Anhui Province, China

Co-first authors: Die Hu and Xiao-Yue Lin.

Co-corresponding authors: Ming-Wei Chen and Xiao-Tong Zhao.

Author contributions: Hu D and Lin XY contributed to the conception and design of the study, they contributed equally to this article, they are the co-first authors of this manuscript; Hu D, Lin XY, Zhao TQ, and Ji H contributed to participant recruitment and clinical sample collection; Hu D, Lin XY, and Zhao XT performed data collection and analysis; Chen MW supervised the study and acquired funding; Chen MW and Zhao XT contributed equally to this article, they are the co-corresponding authors of this manuscript; and all authors reviewed and approved the final manuscript and agreed to its publication.

AI contribution statement: AI tools, specifically DeepSeek, were used solely for language polishing and formatting assistance. No AI tool was used to generate research data, interpret results, or formulate conclusions. All AI-assisted content was critically reviewed and revised by the authors, who take full responsibility for the accuracy, originality, and integrity of the manuscript.

Supported by the Clinical Medical Research Translation Special Project of Anhui Province in China, No. 202427b10020133; and the Anhui Provincial Health Research Project, No. AHWJ2023BAc10012.

Institutional review board statement: This study was approved by the Medical Ethics Committee of the First Affiliated Hospital of Anhui Medical University, approval No. PJ 2024-09-88.

Clinical trial registration statement: This study is registered at the Chinese Clinical Trial Registry (Registration ID: ChiCTR2500096943). Details are available at https://www.chictr.org.cn/bin/project/edit?pid=258670.

Informed consent statement: All study participants provided written consent prior to study enrollment.

Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.

CONSORT 2010 statement: The authors have read the CONSORT 2010 Statement, and the manuscript was prepared and revised according to the CONSORT 2010 Statement.

Data sharing statement: There are no additional data available.

Corresponding author: Xiao-Tong Zhao, MD, Department of Endocrinology, The First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Hefei 230032, Anhui Province, China. zxt522154846@163.com

Received: June 11, 2026
Revised: July 20, 2026
Accepted: September 4, 2026
Published online: October 15, 2026
Processing time: 124 Days and 0.6 Hours

Abstract

BACKGROUND

Restenosis after interventional procedures is a big challenge for type 2 diabetes mellitus (T2DM) patients who also have lower extremity arteriosclerosis obliterans (LEASO). Identifying biomarkers that predict restenosis risk and developing precise predictive models are essential for improving patient treatment outcomes. Thrombospondin-4 (TSP-4) is an extracellular matrix protein, which is associated with vascular inflammation. However, its relationship with postoperative restenosis still unclear.

AIM

To investigate whether TSP-4 levels predict restenosis in T2DM patients with LEASO and to develop a nomogram for risk estimation.

METHODS

This prospective cohort study included 143 T2DM patients with LEASO who underwent endovascular intervention. Clinical data and preoperative TSP-4 levels were collected. After 6 months of follow-up, they were divided into restenosis and non-restenosis groups. The cohort was randomly divided into a training and a validation set. Logistic regression was used to select independent factors and construct a nomogram model. The performance of the model was evaluated by receiver operating characteristic analysis, calibration curve, and decision curve analysis.

RESULTS

Among the 100 patients in the training cohort, 45 patients developed restenosis (45.0%). Patients in the restenosis group had significantly higher preoperative serum TSP-4 levels compared to those without restenosis (P < 0.001). Multivariate logistic regression analysis showed that TSP-4, low-density lipoprotein cholesterol, and age were independent predictors of restenosis (all P < 0.05). The nomogram demonstrated good discrimination. The area under the curve was 0.839 in the training cohort and 0.826 in the validation cohort. Calibration curves indicated a high degree of agreement between predicted probabilities and actual observations. Additionally, decision curve analysis confirmed a notable net clinical benefit across a wide range of threshold probabilities.

CONCLUSION

In T2DM patients with LEASO, serum TSP-4 is a useful predictor of restenosis after interventional treatment. The nomogram incorporating this marker provides risk stratification and guides individualized management.

Keywords: Thrombospondin-4; Type 2 diabetes mellitus; Lower extremity arteriosclerosis obliterans; Interventional therapy; Restenosis; Nomogram model

Core Tip: In this prospective study on type 2 diabetes mellitus patients with lower extremity arteriosclerosis obliterans, after multivariable adjustment, serum thrombospondin-4 was found to be a new independent factor for restenosis, along with age and low-density lipoprotein cholesterol. The nomogram with these three variables, had strong discriminative power and good calibration, so it allows for earlier recognition of high risk patients and personalized interventions.