Evidence map›Paper›PMID 27111653›Full record

ArticlePloS one2016

Circulating Differentially Methylated Amylin DNA as a Biomarker of β-Cell Loss in Type 1 Diabetes.

John A Olsen, Lauren A Kenna, Michael G Spelios, Martin J Hessner, Eitan M Akirav

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
8.2field-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

28 citing papers in PubMed, 52 citations in OpenAlex.

  1. Review
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  11. The role of beta-cell dysfunction in early type 1 diabetes.Current opinion in endocrinology, diabetes, and obesity · 2020
    Review
  12. Article
  13. Article
  14. Article
  15. Epigenetic Regulation in Etiology of Type 1 Diabetes Mellitus.International journal of molecular sciences · 2019
    Review
  16. Article
  17. Review
  18. Serum biomarkers for diagnosis and prediction of type 1 diabetes.Translational research : the journal of laboratory and clinical medicine · 2018
    Review
  19. Review
  20. Review
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

5 authors at 2 institutions in 1 country.

John A OlsenResearch Institute, Islet Biology, Winthrop-University Hospital, Mineola, NY, United States of America.
Lauren A KennaResearch Institute, Islet Biology, Winthrop-University Hospital, Mineola, NY, United States of America.
Michael G SpeliosResearch Institute, Islet Biology, Winthrop-University Hospital, Mineola, NY, United States of America.
Martin J HessnerMax McGee National Research Center for Juvenile Diabetes, Children's Research Institute of Children's Hospital of Wisconsin, Milwaukee, WI, United States of America.
Eitan M AkiravResearch Institute, Islet Biology, Winthrop-University Hospital, Mineola, NY, United States of America.
Winthrop-University Hospital · USMedical College of Wisconsin · US

Funding

Translational Research CoreP30DK020541 · NIDDK · ALBERT EINSTEIN COLLEGE OF MEDICINE, INC · PI STREAMSON C CHUA · 2015 to 2026
$27.7M
Clincal and Translational Science AwardUL1TR000055 · NCATS · MEDICAL COLLEGE OF WISCONSIN · PI SHAKER, REZA NONE · 2012 to 2015
$11.3M
NCATS NIH HHS UL1 TR000055NIDDK NIH HHS P30 DK020541
6 · The paper itself

Abstract

In type 1 diabetes (T1D), β-cell loss is silent during disease progression. Methylation-sensitive quantitative real-time PCR (qPCR) of β-cell-derived DNA in the blood can serve as a biomarker of β-cell death in T1D. Amylin is highly expressed by β-cells in the islet. Here we examined whether demethylated circulating free amylin DNA (cfDNA) may serve as a biomarker of β-cell death in T1D. β cells showed unique methylation patterns within the amylin coding region that were not observed with other tissues. The design and use of methylation-specific primers yielded a strong signal for demethylated amylin in purified DNA from murine islets when compared with other tissues. Similarly, methylation-specific primers detected high levels of demethylated amylin DNA in human islets and enriched human β-cells. In vivo testing of the primers revealed an increase in demethylated amylin cfDNA in sera of non-obese diabetic (NOD) mice during T1D progression and following the development of hyperglycemia. This increase in amylin cfDNA did not mirror the increase in insulin cfDNA, suggesting that amylin cfDNA may detect β-cell loss in serum samples where insulin cfDNA is undetected. Finally, purified cfDNA from recent onset T1D patients yielded a high signal for demethylated amylin cfDNA when compared with matched healthy controls. These findings support the use of demethylated amylin cfDNA for detection of β-cell-derived DNA. When utilized in conjunction with insulin, this latest assay provides a comprehensive multi-gene approach for the detection of β-cell loss.

Indexed as

DNA MethylationAdolescentAnimalsBiomarkersB-LymphocytesChildDiabetes Mellitus, Type 1FemaleHumansIslet Amyloid PolypeptideMaleMiceBiomarkersIslet Amyloid Polypeptide

Identifiers

PMID27111653
PMCPMC4844136
OpenAlexW2342741654

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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.