Clinical Trials Study
Copyright ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Jul 15, 2025; 16(7): 105219
Published online Jul 15, 2025. doi: 10.4239/wjd.v16.i7.105219
Efficacy of Xiaokeqing granules and lifestyle intervention in treating prediabetes mellitus considering metabolomic biomarkers: A randomised controlled trial
Jin-Dong Zhao, Meng-Zhu Guo, Yi Zhang, Shao-Hua Zhu, Ya-Ting Wang, Yan-Ping Zhang, Xin Liu, Si Cheng, Fei Wang, Qi Xu, Nuo-Bing Ruan, Zhao-Hui Fang
Jin-Dong Zhao, Zhao-Hui Fang, Department of Endocrinology, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei 230031, Anhui Province, China
Jin-Dong Zhao, Zhao-Hui Fang, Center for Xin’an Medicine and Modernization of Traditional Chinese Medicine of IHM, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei 230031, Anhui Province, China
Meng-Zhu Guo, Yi Zhang, Shao-Hua Zhu, Ya-Ting Wang, Yan-Ping Zhang, Xin Liu, Si Cheng, Fei Wang, Qi Xu, Nuo-Bing Ruan, The First Clinical Medical School, Anhui University of Chinese Medicine, Hefei 230031, Anhui Province, China
Author contributions: Fang ZH designed the research study; Zhao JD wrote the manuscript; Guo MZ, Zhang Y, Zhu SH, Wang YT, Zhang YP, Liu X, Cheng S, Wang F, Xu Q, and Ruan NB performed the research; All the authors have read and approved the final manuscript.
Supported by the Open Bidding for Selecting the Best Candidates for Xin’an Medicine and the Modernization of Traditional Chinese Medicine of IHM, No. 2023CXMMTCM024 and No. 2023CXMMTCM003; the Anhui University Collaborative Innovation Project, No. GXXT-2020-025; the Scientific Research Project of Health and Wellness in Anhui Province, No. AHWJ2023BAc10002; the Anhui Province New Era Education Quality Project, No. 2023gjxslt014; and the Clinical and Translational Research Project of Anhui Province, No. 202427b10020046.
Institutional review board statement: The study was approved by the ethics committee of the First Affiliated Hospital of Anhui University of Chinese Medicine and conducted in accordance with the Declaration of Helsinki.
Clinical trial registration statement: This study is registered at http://itmctr.ccebtcm.org.cn/zh-CN/Home/ProjectView?pid = cba5b9c2-ac64-4081-b349-2b0bfbb0d2b3. The registration identification number is ITMCTR2023000057.
Informed consent statement: Informed consent was obtained from all participants.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
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: No additional data are available.
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: Zhao-Hui Fang, MD, Doctor, Department of Endocrinology, The First Affiliated Hospital of Anhui University of Chinese Medicine, No. 117 Meishan Road, Hefei 230031, Anhui Province, China. fangzhaohui1111@163.com
Received: January 15, 2025
Revised: April 2, 2025
Accepted: May 28, 2025
Published online: July 15, 2025
Processing time: 181 Days and 20 Hours
Abstract
BACKGROUND

Prediabetes mellitus (PDM) is receiving increasing attention as a precursor to type 2 diabetes mellitus. Lifestyle and traditional Chinese medicine (TCM) interventions are effective for PDM prevention and treatment. Therefore, we conducted a preliminary investigation and an exploratory randomised controlled trial to assess the effects of a combined lifestyle and TCM intervention on PDM indicators.

AIM

To study the effectiveness of Xiaokeqing granules (XQG) and lifestyle interventions in PDM participants while using metabolomics to identify potential markers.

METHODS

Forty PDM participants with yin deficiency syndrome with excessive heat were recruited and randomly allocated to the control (Con) group or the XQG group (20 per group). The Con group underwent lifestyle interventions, whereas the XQG group underwent lifestyle and XQG interventions. The follow-up duration was 2 months. Fasting blood glucose, 2-hour postprandial glucose (2hPG), glycated haemoglobin A1c, fasting insulin, homeostasis model assessment-insulin resistance levels, and serum metabolomics characteristics were compared via liquid chromatography-tandem mass spectrometry analysis.

RESULTS

There were significant differences in 2hPG between the two groups (P < 0.05) in the intention-to-treat analysis and per-protocol analysis. The intervention method used in this study was safe (P > 0.05). Groenlandicine, kaempferol, isomangiferin, etc., are the XQG constituents absorbed in the blood. N-Nervonoyl methionine and 5-hydroxy-L-tryptophan are core potential metabolomic biomarkers for the effectiveness of XQG and lifestyle interventions. HTR1A, HTR2C, SLC6A4, etc., are the core targets of XQG and lifestyle interventions, as well as the reason for their clinical efficacy. Possible mechanistic pathways include tryptophan metabolism, pantothenate and certificate of analysis biosynthesis, lysine degradation and biosynthesis of cofactors.

CONCLUSION

This pilot study provides evidence that a combined XQG and lifestyle intervention can improve 2hPG in participants with PDM. The mechanism of action is related to multiple constituents, targets and pathways.

Keywords: Prediabetes mellitus; Xiaokeqing granules; Lifestyle; Two-hour postprandial glucose; Metabolomics; Tryptophan metabolism

Core Tip: In this study, Xiaokeqing granules constitute a new class-three traditional Chinese medicine. They can improve 2-hour postprandial glucose in participants with prediabetes mellitus with yin deficiency syndrome with excessive heat according to a preliminary investigation and an exploratory randomised controlled trial. Groenlandicine and kaempferol are the main Xiaokeqing granule constituents absorbed into the blood. N-Nervonoyl methionine and 5-hydroxy-L-tryptophan are potential biomarkers for the effectiveness of Xiaokeqing granules and lifestyle interventions.