Evidence map›Paper›PMID 26418287›Full record

ArticleThe Journal of clinical endocrinology and metabolism2015

Epigenetic Alterations in Human Liver From Subjects With Type 2 Diabetes in Parallel With Reduced Folate Levels.

Emma Nilsson, Ashok Matte, Alexander Perfilyev, Vanessa D de Mello, Pirjo Käkelä, Jussi Pihlajamäki, Charlotte Ling

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of clinical endocrinology and metabolism, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 112 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
112citing papers in PubMed, 2 pooled it
8.0field-weighted citation impact, top 2% 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

112 citing papers in PubMed, 2 syntheses or guidelines pooled it, 196 citations in OpenAlex.

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52 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

7 authors at 2 institutions in 2 countries.

Emma NilssonEpigenetics and Diabetes Unit (E.N., A.P., C.L.), Department of Clinical Sciences, Lund University Diabetes Centre, 205 02 Malmö, Sweden; Department of Clinical Nutrition (A.M., V.D.d.M., J.P.), Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Department of Surgery (P.K.), University of Eastern Finland and Kuopio University Hospital, and Clinical Nutrition and Obesity Center (J.P.), Kuopio University Hospital, 70211 Kuopio, Finland.
Ashok MatteEpigenetics and Diabetes Unit (E.N., A.P., C.L.), Department of Clinical Sciences, Lund University Diabetes Centre, 205 02 Malmö, Sweden; Department of Clinical Nutrition (A.M., V.D.d.M., J.P.), Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Department of Surgery (P.K.), University of Eastern Finland and Kuopio University Hospital, and Clinical Nutrition and Obesity Center (J.P.), Kuopio University Hospital, 70211 Kuopio, Finland.
Alexander PerfilyevEpigenetics and Diabetes Unit (E.N., A.P., C.L.), Department of Clinical Sciences, Lund University Diabetes Centre, 205 02 Malmö, Sweden; Department of Clinical Nutrition (A.M., V.D.d.M., J.P.), Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Department of Surgery (P.K.), University of Eastern Finland and Kuopio University Hospital, and Clinical Nutrition and Obesity Center (J.P.), Kuopio University Hospital, 70211 Kuopio, Finland.
Vanessa D de MelloEpigenetics and Diabetes Unit (E.N., A.P., C.L.), Department of Clinical Sciences, Lund University Diabetes Centre, 205 02 Malmö, Sweden; Department of Clinical Nutrition (A.M., V.D.d.M., J.P.), Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Department of Surgery (P.K.), University of Eastern Finland and Kuopio University Hospital, and Clinical Nutrition and Obesity Center (J.P.), Kuopio University Hospital, 70211 Kuopio, Finland.
Pirjo KäkeläEpigenetics and Diabetes Unit (E.N., A.P., C.L.), Department of Clinical Sciences, Lund University Diabetes Centre, 205 02 Malmö, Sweden; Department of Clinical Nutrition (A.M., V.D.d.M., J.P.), Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Department of Surgery (P.K.), University of Eastern Finland and Kuopio University Hospital, and Clinical Nutrition and Obesity Center (J.P.), Kuopio University Hospital, 70211 Kuopio, Finland.
Jussi PihlajamäkiEpigenetics and Diabetes Unit (E.N., A.P., C.L.), Department of Clinical Sciences, Lund University Diabetes Centre, 205 02 Malmö, Sweden; Department of Clinical Nutrition (A.M., V.D.d.M., J.P.), Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Department of Surgery (P.K.), University of Eastern Finland and Kuopio University Hospital, and Clinical Nutrition and Obesity Center (J.P.), Kuopio University Hospital, 70211 Kuopio, Finland.
Charlotte LingEpigenetics and Diabetes Unit (E.N., A.P., C.L.), Department of Clinical Sciences, Lund University Diabetes Centre, 205 02 Malmö, Sweden; Department of Clinical Nutrition (A.M., V.D.d.M., J.P.), Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Department of Surgery (P.K.), University of Eastern Finland and Kuopio University Hospital, and Clinical Nutrition and Obesity Center (J.P.), Kuopio University Hospital, 70211 Kuopio, Finland.
Lund University · SEUniversity of Eastern Finland · FI

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveEpigenetic variation may contribute to the development of complex metabolic diseases such as type 2 diabetes (T2D). Hepatic insulin resistance is a hallmark of T2D. However, it remains unknown whether epigenetic alterations take place in the liver from diabetic subjects. Therefore, we investigated the genome-wide DNA methylation pattern in the liver from subjects with T2D and nondiabetic controls and related epigenetic alterations to gene expression and circulating folate levels. RESEARCH DESIGN AND

methodsLiver biopsies were obtained from 35 diabetic and 60 nondiabetic subjects, which are part of the Kuopio Obesity Surgery Study. The genome-wide DNA methylation pattern was analyzed in the liver using the HumanMethylation450 BeadChip. RNA expression was analyzed from a subset of subjects using the HumanHT-12 Expression BeadChip.

resultsAfter correction for multiple testing, we identified 251 individual CpG sites that exhibit differential DNA methylation in liver obtained from T2D compared with nondiabetic subjects (Q < .05). These include CpG sites annotated to genes that are biologically relevant to the development of T2D such as GRB10, ABCC3, MOGAT1, and PRDM16. The vast majority of the significant CpG sites (94%) displayed decreased DNA methylation in liver from subjects with T2D. The hypomethylation found in liver from diabetic subjects may be explained by reduced folate levels. Indeed, subjects with T2D had significantly reduced erythrocyte folate levels compared with nondiabetic subjects. We further identified 29 genes that displayed both differential DNA methylation and gene expression in human T2D liver including the imprinted gene H19.

conclusionsOur study highlights the importance of epigenetic and transcriptional changes in the liver from subjects with T2D. Reduced circulating folate levels may provide an explanation for hypomethylation in the human diabetic liver.

Indexed as

DNA MethylationEpigenesis, GeneticGene Expression RegulationNutritional StatusAdultBiopsyBody Mass IndexCohort StudiesCpG IslandsDiabetes Mellitus, Type 2FemaleFinlandFolic AcidFolic Acid DeficiencyGastric BypassGene Expression ProfilingFolic Acid

Identifiers

PMID26418287
PMCPMC4702449
OpenAlexW2166199493

What OpenQuestion holds

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Registered trials

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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 OpenQuestion graph.