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World J Diabetes. Dec 15, 2025; 16(12): 112789
Published online Dec 15, 2025. doi: 10.4239/wjd.v16.i12.112789
Methylation status of leptin gene promoter in relatively lean Chinese adults with prediabetes and type 2 diabetes mellitus
Shi-Qi Sun, Sheng-Ze Liang, Qi Huang, Jia-Zhong Sun
Shi-Qi Sun, Sheng-Ze Liang, Clinical Laboratory, The Sixth Hospital of Wuhan (Affiliated Hospital of Jianghan University), Wuhan 430014, Hubei Province, China
Qi Huang, Jia-Zhong Sun, Department of Endocrinology, Zhongnan Hospital of Wuhan University, Wuhan 430071, Hubei Province, China
Author contributions: Sun SQ designed the study and performed methylation experiments and statistical analysis; Liang SZ collected clinical samples and conducted enzyme-linked immunosorbent assay and data curation; Huang Q assisted in molecular assays and manuscript drafting; Sun JZ as corresponding author supervised the project, secured funding, revised the manuscript critically, and approved the final version; all authors reviewed and approved the manuscript.
Institutional review board statement: This study was conducted following the ethical standards outlined in the Declaration of Helsinki. Ethical clearance was obtained from the Institutional Review Board of Zhongnan Hospital of Wuhan University (No. 2025054KJ).
Conflict-of-interest statement: The authors declare that they have no competing interests. All stages of the study, including data analysis and interpretation, were performed independently and were free from any external financial, professional, or institutional influence.
Data sharing statement: The data supporting the findings of this study are available from the corresponding author upon reasonable request.
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: Jia-Zhong Sun, Chief, Professor, Department of Endocrinology, Zhongnan Hospital of Wuhan University, No. 169 Donghu Road, Wuhan 430071, Hubei Province, China. sjz300@163.com
Received: August 6, 2025
Revised: September 29, 2025
Accepted: October 29, 2025
Published online: December 15, 2025
Processing time: 131 Days and 12.2 Hours
Core Tip

Core Tip: This study reveals progressive hypomethylation of the leptin (LEP) gene promoter in peripheral leukocytes of relatively lean Chinese adults (body mass index < 24 kg/m2) across glycemic states: (1) Normoglycemia (59.2%); (2) Prediabetes (43.6%); and (3) Type 2 diabetes mellitus (31.5%). The methylation decline correlated inversely with serum LEP levels (r = -0.95, P < 0.001), suggesting epigenetic dysregulation precedes metabolic dysfunction independent of obesity. These findings position LEP promoter methylation as a potential blood-based biomarker for early diabetes risk stratification in lean populations, highlighting its clinical utility for preventive strategies.