Evidence mapPaperPMID 40533821Full record

ArticleDiabetology & metabolic syndrome2025

Association of DNA methylation epigenetic markers with all-cause mortality and cardiovascular disease-related mortality in diabetic population: a machine learning-based retrospective cohort study.

Yuxin Nong, Huazhen Huang, Lulu Xu, Xin Tan, Shuai Xu, Xinyu Zhou, Yiyao Zeng, Yufeng Jiang, Hezi Jiang, Xiangyu Wang and 9 more

Abstract read
In one paragraph

Article in Diabetology & metabolic syndrome, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

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2citing papers in PubMed
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1 · What the graph read from it

What it found

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2 · The registry

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3 · Its place in the literature

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2 citing papers in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

19 authors.

Yuxin Nong *Department of Cardiology, The Fourth Affiliated Hospital of Soochow University (Suzhou Dushu Lake Hospital), Medical Center of Soochow University, Suzhou, 215000, China.ORCID http://orcid.org/0000-0001-8217-2460
Huazhen Huang *Institute of Advanced Computing and Digital Engineering, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China.ORCID https://orcid.org/0009-0007-6841-505X
Lulu Xu *Department of Cardiac Surgery, Guangdong Provincial People's Hospital, Guangdong Cardiovascular Institute, Guangdong Academy of Medical Sciences, Guangzhou, 510080, China.
Xin TanDepartment of Cardiology, The Fourth Affiliated Hospital of Soochow University (Suzhou Dushu Lake Hospital), Medical Center of Soochow University, Suzhou, 215000, China.
Shuai XuDepartment of Cardiology, The Fourth Affiliated Hospital of Soochow University (Suzhou Dushu Lake Hospital), Medical Center of Soochow University, Suzhou, 215000, China.
Xinyu ZhouDepartment of Cardiology, The Fourth Affiliated Hospital of Soochow University (Suzhou Dushu Lake Hospital), Medical Center of Soochow University, Suzhou, 215000, China.
Yiyao ZengDepartment of Cardiology, The Fourth Affiliated Hospital of Soochow University (Suzhou Dushu Lake Hospital), Medical Center of Soochow University, Suzhou, 215000, China.
Yufeng JiangDepartment of Cardiology, The Fourth Affiliated Hospital of Soochow University (Suzhou Dushu Lake Hospital), Medical Center of Soochow University, Suzhou, 215000, China.
Hezi JiangDepartment of Cardiology, The Fourth Affiliated Hospital of Soochow University (Suzhou Dushu Lake Hospital), Medical Center of Soochow University, Suzhou, 215000, China.
Xiangyu WangDepartment of Cardiology, The Fourth Affiliated Hospital of Soochow University (Suzhou Dushu Lake Hospital), Medical Center of Soochow University, Suzhou, 215000, China.
Xian LiDepartment of Cardiology, The Fourth Affiliated Hospital of Soochow University (Suzhou Dushu Lake Hospital), Medical Center of Soochow University, Suzhou, 215000, China.
Anchen XuDepartment of Cardiology, The Fourth Affiliated Hospital of Soochow University (Suzhou Dushu Lake Hospital), Medical Center of Soochow University, Suzhou, 215000, China.
Qiaoyi SunDepartment of Cardiology, The Fourth Affiliated Hospital of Soochow University (Suzhou Dushu Lake Hospital), Medical Center of Soochow University, Suzhou, 215000, China.
Hongju WangDepartment of Cardiovascular Disease, The First Affiliated Hospital of Bengbu Medical University, Bengbu, 233000, China.
Pinfang KangDepartment of Cardiovascular Disease, The First Affiliated Hospital of Bengbu Medical University, Bengbu, 233000, China.
Jili FanDepartment of Cardiovascular Disease, Taihe County People's Hospital, Fuyang, 236600, China.
Xiaohong BoDepartment of Cardiovascular Disease, Taihe County People's Hospital, Fuyang, 236600, China.
Huimin FanDepartment of Cardiology, The Fourth Affiliated Hospital of Soochow University (Suzhou Dushu Lake Hospital), Medical Center of Soochow University, Suzhou, 215000, China. fhm_sunshine@163.com.ORCID https://orcid.org/0009-0004-5530-974X
Yafeng ZhouDepartment of Cardiology, The Fourth Affiliated Hospital of Soochow University (Suzhou Dushu Lake Hospital), Medical Center of Soochow University, Suzhou, 215000, China. Dryafengzhou@163.com.ORCID https://orcid.org/0009-0005-2606-3776

Funding

Clinical Medicine Expert Team (Class A) of Jinji Lake Health Talents Program of Suzhou Industrial Park SZYQTD202102Demonstration of Scientific and Technological Innovation Project SKY2021002National Natural Science Foundation of China 81873486Natural Science Research of Jiangsu Higher Education Institutions of China BK20240637Research on Collaborative Innovation of medical engineering combination SZM2021014Science and Technology Development Program of Jiangsu Province-Clinical Frontier Technology BE2022754Suzhou Dedicated Project on Diagnosis and Treatment Technology of Major Diseases LCZX202132Suzhou Key Discipline for Medicine SZXK202129Suzhou Science and Education Youth Science and Technology Project KJXW2023086
6 · The paper itself

Abstract

backgroundDiabetes has a large and diverse population, with individuals exhibiting significant heterogeneity in the disease. The factors influencing survival and prognosis are complex, making early intervention in diabetic populations particularly challenging. Research has demonstrated a close relationship between DNA methylation (DNAm) clocks and aging as well as various diseases, showing superior predictive capabilities. However, the relationship between DNAm clocks and long-term survival in diabetic patients, particularly concerning cardiovascular-related mortality, remains unclear.

methodsWe analyzed the data of the diabetes population cohort in the National Health and Nutrition Examination Survey, which was followed for 20 years. We employed eight machine learning (ML) models to analyze 29 potential DNAm derived epigenetic markers and utilized Cox regression models to assess the risks of all-cause mortality and cardiovascular disease-related mortality in the diabetic population. Additionally, we applied restricted cubic spline (RCS) to analyze potential influence trends.

resultsA total of 454 people with diabetes were followed up, with a median follow-up time of 177.6 months. Through machine learning methods, we identified several high-performing DNAm markers, finding that four epigenetic biomarkers, ZhangAge (HR = 2.86, 95% CI: 2.19-3.73, P < 0.001), GrimAge2Mort (HR = 3.06, 95% CI: 2.26-4.14, P < 0.001), TIMP1Mort (HR = 2.95, 95% CI: 2.18-4.01, P < 0.001), and PhenoAge (HR = 2.94, 95% CI: 1.23-3.88, P < 0.001), were significantly associated with all-cause mortality in the diabetic population. Further research indicated that GrimAge2 Mort (HR = 2.86, 95% CI: 1.30-6.29, P = 0.009) and TIMP1Mort (HR = 4.08, 95% CI: 2.17-7.68, P < 0.001) were associated with cardiovascular disease-related mortality. RCS curves demonstrated that the mortality risk for all diabetic patients increased with rising levels of these DNAm epigenetic markers.

conclusionWe found four DNAm-derived epigenetic markers (ZhangAge, GrimAge2 Mort, TIMP1Mort, PhenoAge) that are associated with all-cause mortality risk in the diabetic population. Further research suggested that GrimAge and PhenoAge influence the risk of cardiovascular-related mortality.

Indexed as

All-cause mortalityCardiovascular disease-related mortalityDiabetesDNA methylation biomarkers

Identifiers

PMID40533821
PMCPMC12175400

What Socratic holds

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.