Zhang JW. Letter to the Editor: Leptin gene hypomethylation - a missing epigenetic link in lean type 2 diabetes? World J Diabetes 2026; 17(8): 116265 [DOI: 10.4239/wjd.116265]
Corresponding Author of This Article
Jin-Wei Zhang, PhD, Professor, State Key Laboratory of Chemical Biology, Research Center of Chemical Kinomics, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, No. 345 Lingling Road, Shanghai 200032, China. jinweizhang@sioc.ac.cn
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Biology
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letter
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Zhang JW. Letter to the Editor: Leptin gene hypomethylation - a missing epigenetic link in lean type 2 diabetes? World J Diabetes 2026; 17(8): 116265 [DOI: 10.4239/wjd.116265]
World J Diabetes. Aug 15, 2026; 17(8): 116265 Published online Aug 15, 2026. doi: 10.4239/wjd.116265
Letter to the Editor: Leptin gene hypomethylation - a missing epigenetic link in lean type 2 diabetes?
Jin-Wei Zhang
Jin-Wei Zhang, State Key Laboratory of Chemical Biology, Research Center of Chemical Kinomics, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, China
Author contributions: Zhang JW designed the overall concept and outline of the manuscript, contributed to the discussion and design of the manuscript, write and edit of the manuscript, illustrations, and review of the literature.
AI contribution statement: Limited auxiliary AI tools including Grammarly and DeepL were only adopted for basic grammatical check, wording refinement and minor expression optimization during manuscript preparation. No large language model such as ChatGPT was used in any stage of this study and manuscript writing.
Supported by National Natural Science Foundation of China, No. 82170406 and No. 81970238.
Conflict-of-interest statement: The author reports no relevant conflicts of interest for this article.
Corresponding author: Jin-Wei Zhang, PhD, Professor, State Key Laboratory of Chemical Biology, Research Center of Chemical Kinomics, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, No. 345 Lingling Road, Shanghai 200032, China. jinweizhang@sioc.ac.cn
Received: November 6, 2025 Revised: December 19, 2025 Accepted: January 26, 2026 Published online: August 15, 2026 Processing time: 272 Days and 5.1 Hours
Abstract
Emerging research links diabetes pathogenesis to epigenetic modifications beyond genetics and metabolism. We read with great interest the study published in World Journal of Diabetes by Sun et al. They investigate leptin (LEP) gene promoter methylation via methylation-specific polymerase chain reaction and serum LEP quantification (enzyme-linked immunosorbent assay) in non-obese Chinese adults with prediabetes/type 2 diabetes (T2DM). It shows progressive promoter methylation decline from normoglycemia to T2DM, strongly inversely correlated with circulating LEP. This letter critically evaluates their findings, contextualizes them in diabetes epigenetics research, and highlights translational value for early risk stratification and precision prevention in non-obese individuals. Briefly, LEP hypomethylation may drive “LEP-insulin axis” dysfunction (a T2DM hallmark) by disrupting β-cell function and insulin sensitivity. Key terms: DNA methylation (methylation of cytosine-guanine cytosines, repressing transcription); epigenetics (heritable gene expression changes without DNA sequence alteration).
Core Tip: This letter critically analyzes the study by Sun et al, which demonstrates that progressive hypomethylation of the leptin (LEP) gene promoter parallels glycemic deterioration in non-obese Chinese adults. The strong inverse correlation between methylation and serum LEP levels (r = -0.95, P < 0.001) highlights an adiposity-independent epigenetic mechanism that may represent a risk factor for diabetes pathogenesis. These findings position LEP promoter methylation as a promising blood-based biomarker for early detection and intervention in non-obese individuals at risk of diabetes.
