Case Control Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Dec 26, 2021; 9(36): 11156-11164
Published online Dec 26, 2021. doi: 10.12998/wjcc.v9.i36.11156
Association between serum Sestrin2 level and diabetic peripheral neuropathy in type 2 diabetic patients
En-Wen Mao, Xue-Bing Cheng, Wen-Chao Li, Cheng-Xia Kan, Na Huang, Hong-Sheng Wang, Ning-Ning Hou, Xiao-Dong Sun
En-Wen Mao, Cheng-Xia Kan, Xiao-Dong Sun, Department of Endocrinology and Metabolism, Clinical Research Center, The Affiliated Hospital of Weifang Medical University, Weifang 261031, Shandong Province, China
Xue-Bing Cheng, Wen-Chao Li, Na Huang, Hong-Sheng Wang, Ning-Ning Hou, Department of Endocrinology and Metabolism, The Affiliated Hospital of Weifang Medical University, Weifang 261031, Shandong Province, China
Author contributions: Mao EW and Cheng XB performed the majority of experiments and wrote the manuscript, contributing equally to this article; Hou NN and Sun XD designed the study and corrected the manuscript; Li WC, Kan CX, Huang N, and Wang HS were involved in the sample collected and analytical tools.
Supported by National Natural Science Foundation of China, No. 81870593; Natural Science Foundation of Shandong Province of China, No. ZR2020MH106; Medical Health Science and Technology Project of Shandong Province, No. 202003060396 and No. 202003060400; and Quality Improvement of Postgraduate Education in Shandong Province, No. SDYAL19156.
Institutional review board statement: The study was approved by the Medical Ethics Committee of Affiliated Hospital of Weifang Medical University.
Informed consent statement: Informed consent was obtained prior to enrollment.
Conflict-of-interest statement: The authors have nothing to disclose.
Data sharing statement: The original contributions presented in the study are included in the article/supplementary material. Further inquiries can be directed to the corresponding authors.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
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: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Xiao-Dong Sun, MD, PhD, Associate Chief Physician, Department of Endocrinology and Metabolism, Clinical Research Center, The Affiliated Hospital of Weifang Medical University, No. 2428 Yuhe Road, Weifang 261031, Shandong Province, China.xiaodong.sun@wfmc.edu.cn
Received: July 12, 2021
Peer-review started: July 12, 2021
First decision: September 5, 2021
Revised: September 6, 2021
Accepted: November 14, 2021
Article in press: November 14, 2021
Published online: December 26, 2021
Processing time: 164 Days and 13.1 Hours
Abstract
BACKGROUND

Diabetic peripheral neuropathy (DPN) is a chronic and serious microvascular complication of diabetes linked to redox imbalance. Sestrin2, a novel inducible stress protein, participates in glucose metabolic regulation and redox homeostasis. However, the association between serum Sestrin2 and DPN is unknown.

AIM

To explore the association between serum Sestrin2 and DPN in patients with type 2 diabetes mellitus (T2DM).

METHODS

A total of 96 T2DM patients and 39 healthy volunteers, matched by age and sex, participated in this cross-sectional study. Clinical features and metabolic indices were identified. Serum Sestrin2 was measured by ELISA. The association between Sestrin2 and DPN was studied. Correlation and logistic regression analyses were used to evaluate the associations of different metabolic indices with Sestrin2 and DPN.

RESULTS

The 96 patients with T2DM were divided into DPN (n = 47) and patients without DPN (n = 49). Serum Sestrin2 was significantly lower in healthy volunteers than in all T2DM patients combined [9.10 (5.41-13.53) ng/mL vs 12.75 (7.44-23.80) ng/mL, P < 0.01]. T2DM patients without DPN also had significantly higher levels of Sestrin2 than healthy volunteers [14.58 (7.93-26.62) ng/mL vs 9.10 (5.41-13.53) ng/mL, P < 0.01]. However, T2DM patients with DPN had lower circulating Sestrin2 levels compared to T2DM patients without DPN [9.86 (6.72-21.71) ng/mL vs 14.58 (7.93-26.62) ng/mL, respectively, P < 0.01]. Bivariate correlation analysis revealed that serum Sestrin2 was positively correlated with body mass index (r = 0.672, P = 0.000), hemoglobin A1c (HbA1c) (r = 0.292, P = 0.000), serum creatinine (r = 0.206, P = 0.016), triglycerides (r = 0.731, P = 0.000), and fasting glucose (r = 0.202, P = 0.040), and negatively associated with estimated glomerular filtration rate (r = -0.230, P = 0.007). After adjustment for sex, age, HbA1c, and diabetes duration, multiple regression analysis revealed that Sestrin2 was independently correlated with body mass index and triglyceride levels (P = 0.000). Logistic regression analyses indicated that Sestrin2, diabetes duration, and high-density lipoprotein were strongly associated with DPN (odds ratio = 0.855, 1.411, and 0.041, respectively).

CONCLUSION

Our results show Sestrin2 is decreased in T2DM patients with DNP. As lower Sestrin2 is independently associated with DPN, Sestrin2 may contribute to progression of DPN in T2DM patients.

Keywords: Sestrin2, Diabetic peripheral neuropathy, Type 2 diabetes mellitus, Diabetic

Core Tip: This study demonstrated that serum Sestrin2 is increased in patients with type 2 diabetes but reduced in type 2 diabetic patients with diabetic peripheral neuropathy. Sestrin2 may be a novel modulatory factor for metabolic disturbances in diabetes complications.