Evidence map›Paper›PMID 31575611›Full record

ArticleClinical chemistry2019

5-Hydroxymethylcytosines in Circulating Cell-Free DNA Reveal Vascular Complications of Type 2 Diabetes.

Ying Yang, Chang Zeng, Xingyu Lu, Yanqun Song, Ji Nie, Ruoxi Ran, Zhou Zhang, Chuan He, Wei Zhang, Song-Mei Liu

Open access · bronzeAbstract read
In one paragraph

Article in Clinical chemistry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
1.9field-weighted citation impact, top 14% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

22 citing papers in PubMed, 69 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Circulating Cell-Free DNA in Metabolic Diseases.Journal of the Endocrine Society · 2025
    Review
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  17. Microvascular Inflammation and Cardiovascular Prevention: The Role of Microcirculation as Earlier Determinant of Cardiovascular Risk.High blood pressure & cardiovascular prevention : the official journal of the Italian Society of Hypertension · 2022
    Review
  18. Article
  19. Properties and Application of Cell-Free DNA as a Clinical Biomarker.International journal of molecular sciences · 2021
    Review
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 6 institutions in 2 countries.

Ying YangDepartment of Clinical Laboratory, Center for Gene Diagnosis, and Program of Clinical Laboratory, Zhongnan Hospital of Wuhan University, Wuhan, China.
Chang ZengDriskill Graduate Program in Life Sciences, Northwestern University Feinberg School of Medicine, Chicago, IL.
Xingyu LuShanghai Epican Genetech Co. Ltd., Shanghai, China.
Yanqun SongShanghai Epican Genetech Co. Ltd., Shanghai, China.
Ji NieDepartment of Chemistry, The University of Chicago, Chicago, IL.
Ruoxi RanDepartment of Clinical Laboratory, Center for Gene Diagnosis, and Program of Clinical Laboratory, Zhongnan Hospital of Wuhan University, Wuhan, China.
Zhou ZhangDepartment of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL.
Chuan HeDepartment of Chemistry, The University of Chicago, Chicago, IL; chuanhe@uchicago.edu wei.zhang1@northwestern.edu smliu@whu.edu.cn.
Wei ZhangDepartment of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL; chuanhe@uchicago.edu wei.zhang1@northwestern.edu smliu@whu.edu.cn.
Song-Mei LiuDepartment of Clinical Laboratory, Center for Gene Diagnosis, and Program of Clinical Laboratory, Zhongnan Hospital of Wuhan University, Wuhan, China; chuanhe@uchicago.edu wei.zhang1@northwestern.edu smliu@whu.edu.cn.
Northwestern University · USEvive Biotech (China) · CNZhongnan Hospital of Wuhan University · CNHoward Hughes Medical Institute · USUniversity of Chicago · USWuhan University · CN

Funding

Tumor Environment and Metastasis (TEAM) Research ProgramP30CA060553 · NCI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI LEONIDAS C. PLATANIAS · 1993 to 2026
$153.9M
NCI NIH HHS P30 CA060553
6 · The paper itself

Abstract

backgroundLong-term complications of type 2 diabetes (T2D), such as macrovascular and microvascular events, are the major causes for T2D-related disability and mortality. A clinically convenient, noninvasive approach for monitoring the development of these complications would improve the overall life quality of patients with T2D and help reduce healthcare burden through preventive interventions.

methodsA selective chemical labeling strategy for 5-hydroxymethylcytosines (5hmC-Seal) was used to profile genome-wide 5hmCs, an emerging class of epigenetic markers implicated in complex diseases including diabetes, in circulating cell-free DNA (cfDNA) from a collection of Chinese patients (n = 62). Differentially modified 5hmC markers between patients with T2D with and without macrovascular/microvascular complications were analyzed under a case-control design.

resultsStatistically significant changes in 5hmC markers were associated with T2D-related macrovascular/microvascular complications, involving genes and pathways relevant to vascular biology and diabetes, including insulin resistance and inflammation. A 16-gene 5hmC marker panel accurately distinguished patients with vascular complications from those without [testing set: area under the curve (AUC) = 0.85; 95% CI, 0.73-0.96], outperforming conventional clinical variables such as urinary albumin. In addition, a separate 13-gene 5hmC marker panel could distinguish patients with single complications from those with multiple complications (testing set: AUC = 0.84; 95% CI, 0.68-0.99), showing superiority over conventional clinical variables.

conclusionsThe 5hmC markers in cfDNA reflected the epigenetic changes in patients with T2D who developed macrovascular/microvascular complications. The 5hmC-Seal assay has the potential to be a clinically convenient, noninvasive approach that can be applied in the clinic to monitor the presence and severity of diabetic vascular complications.

Indexed as

5-MethylcytosineAdultAgedAged, 80 and overBiomarkersCell-Free Nucleic AcidsDiabetes Mellitus, Type 2Diabetic AngiopathiesHumansMaleMiddle AgedRisk Factors5-hydroxymethylcytosine5-MethylcytosineBiomarkersCell-Free Nucleic Acids

Identifiers

PMID31575611
PMCPMC7055673
OpenAlexW2977603165

What OpenQuestion holds

Textmetadata
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Registered trials

None linked

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 OpenQuestion graph.