Evidence map›Paper›PMID 29164275›Full record

SynthesisDiabetologia2018

DNA methylation markers associated with type 2 diabetes, fasting glucose and HbA

Eliza Walaszczyk, Mirjam Luijten, Annemieke M W Spijkerman, Marc J Bonder, Helen L Lutgers, Harold Snieder, Bruce H R Wolffenbuttel, Jana V van Vliet-Ostaptchouk

Open access · hybridAbstract readSystematic Review
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in Diabetologia, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers, 10 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
88citing papers in PubMed, 10 pooled it
3.8field-weighted citation impact, top 6% 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

88 citing papers in PubMed, 10 syntheses or guidelines pooled it, 184 citations in OpenAlex.

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  15. Metformin Alone and in Combinations Alter the Methylation Patterns ofEndocrine, metabolic & immune disorders drug targets · 2026
    Article
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28 more citing papers are in PubMed but not listed here.

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

8 authors at 3 institutions in 1 country.

Eliza WalaszczykDepartment of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Mirjam LuijtenCentre for Health Protection, National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands.
Annemieke M W SpijkermanCentre for Nutrition, Prevention and Health Services, RIVM, Bilthoven, the Netherlands.
Marc J BonderDepartment of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Helen L LutgersDepartment of Endocrinology, University of Groningen, University Medical Center Groningen, HPC AA31, P.O. Box 30001, 9700 RB, Groningen, the Netherlands.
Harold SniederDepartment of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Bruce H R WolffenbuttelDepartment of Endocrinology, University of Groningen, University Medical Center Groningen, HPC AA31, P.O. Box 30001, 9700 RB, Groningen, the Netherlands.
Jana V van Vliet-OstaptchoukDepartment of Endocrinology, University of Groningen, University Medical Center Groningen, HPC AA31, P.O. Box 30001, 9700 RB, Groningen, the Netherlands. j.v.van.vliet@umcg.nl.
University of Groningen · NLNational Institute for Public Health and the Environment · NLUniversity Medical Center Groningen · NL

Funding

Diabetes Funds 2013.81.1673National Consortium for Healthy Ageing 050-060-810National Institute for Public Health and the Environment and the Ministry of Health,Welfare and Sport of The Netherlands S/132005
6 · The paper itself

Abstract

aims/hypothesisEpigenetic mechanisms may play an important role in the aetiology of type 2 diabetes. Recent epigenome-wide association studies (EWASs) identified several DNA methylation markers associated with type 2 diabetes, fasting glucose and HbA

methodsWe performed a systematic literature search in PubMed and EMBASE for EWASs to test the association between DNA methylation and type 2 diabetes and/or glycaemic traits and reviewed the search results. For replication purposes we selected 100 unique CpGs identified in peripheral blood, pancreas, adipose tissue and liver from 15 EWASs, using study-specific Bonferroni-corrected significance thresholds. Methylation data (Illumina 450K array) in whole blood from 100 type 2 diabetic individuals and 100 control individuals from the Lifelines study were available. Multivariate linear models were used to examine the associations of the specific CpGs with type 2 diabetes and glycaemic traits.

resultsFrom the 52 CpGs identified in blood and selected for replication, 15 CpGs showed nominally significant associations with type 2 diabetes in the Lifelines sample (p < 0.05). The results for five CpGs (in ABCG1, LOXL2, TXNIP, SLC1A5 and SREBF1) remained significant after a stringent multiple-testing correction (changes in methylation from -3% up to 3.6%, p < 0.0009). All associations were directionally consistent with the original EWAS results. None of the selected CpGs from the tissue-specific EWASs were replicated in our methylation data from whole blood. We were also unable to replicate any of the CpGs associated with HbA CONCLUSIONS/

interpretationA number of differentially methylated CpGs reported to be associated with type 2 diabetes in the EWAS literature were replicated in blood and show promise for clinical use as disease biomarkers. However, more prospective studies are needed to support the robustness of these findings.

Indexed as

Blood GlucoseCpG IslandsDiabetes Mellitus, Type 2DNA MethylationEpigenesis, GeneticFastingGenome-Wide Association StudyGlycated HemoglobinHumansBlood GlucoseGlycated HemoglobinDNA methylationEpigenome-wide association studiesGlucoseGlycated haemoglobinSystematic reviewType 2 diabetes

Identifiers

PMID29164275
PMCPMC6448925
OpenAlexW2768591422

What OpenQuestion holds

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LicenceCC BY
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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.