Evidence map›Paper›PMID 31913467›Full record

ArticleThe Journal of clinical endocrinology and metabolism2020

Circulating Unmethylated Insulin DNA As a Biomarker of Human Beta Cell Death: A Multi-laboratory Assay Comparison.

Cate Speake, Alyssa Ylescupidez, Daniel Neiman, Ruth Shemer, Benjamin Glaser, Sarah A Tersey, Sahar Usmani-Brown, Pamela Clark, Joshua J Wilhelm, Melena D Bellin and 4 more

Open access · bronzeAbstract readComparative StudyEvaluation Study
In one paragraph

Article in The Journal of clinical endocrinology and metabolism, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
3.7field-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

18 citing papers in PubMed, 25 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  4. Review
  5. Circulating Cell-Free DNA in Metabolic Diseases.Journal of the Endocrine Society · 2025
    Review
  6. Review
  7. Review
  8. Article
  9. Article
  10. Review
  11. Quantification of Unmethylated Insulin DNA Using Methylation Sensitive Restriction Enzyme Digital Polymerase Chain Reaction.Transplant international : official journal of the European Society for Organ Transplantation · 2022
    Article
  12. Review
  13. Article
  14. Article
  15. Review
  16. Review
  17. The role of beta-cell dysfunction in early type 1 diabetes.Current opinion in endocrinology, diabetes, and obesity · 2020
    Review
  18. 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

14 authors at 6 institutions in 2 countries.

Cate SpeakeDiabetes Clinical Research Program, Benaroya Research Institute at Virginia Mason, Seattle, WA, US.
Alyssa YlescupidezDiabetes Clinical Research Program, Benaroya Research Institute at Virginia Mason, Seattle, WA, US.
Daniel NeimanDepartment of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Ruth ShemerDepartment of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Benjamin GlaserEndocrinology and Metabolism Service, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
Sarah A TerseyHerman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, US.
Sahar Usmani-BrownL2 Diagnostics, New Haven, CT, US.
Pamela ClarkDepartments of Immunobiology and Internal Medicine, Yale University School of Medicine, New Haven, CT, US.
Joshua J WilhelmDepartment of Surgery, Schulze Diabetes Institute, University of Minnesota, Minneapolis, MN, US.
Melena D BellinDepartments of Pediatrics and Surgery, University of Minnesota, Minneapolis, MN, US.
Kevan C HeroldDepartments of Immunobiology and Internal Medicine, Yale University School of Medicine, New Haven, CT, US.
Raghavendra G MirmiraHerman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, US.
Yuval DorDepartment of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Carmella Evans-MolinaHerman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, US.
Benaroya Research InstituteIndiana University School of MedicineUniversity of Minnesota · USYale University · USHadassah Medical Center · ILRichard L. Roudebush VA Medical Center · US

Funding

Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9M
Yale Diabetes Research CenterP30DK045735 · NIDDK · YALE UNIVERSITY · PI WILLIAM V TAMBORLANE · 1993 to 2026
$44.0M
Translation CoreP30DK097512 · NIDDK · INDIANA UNIVERSITY INDIANAPOLIS · PI Carmella Evans-Molina · 2015 to 2026
$17.4M
Phase II Trial of HOKT3gamma 1 (ALA-ALA) in Type 1 DiabetesR01DK057846 · NIDDK · YALE UNIVERSITY · PI Kevan C Herold · 2000 to 2026
$11.1M
Circulating Biomarker Consortium for Pancreatic Cancer Early DetectionU01CA210171 · NCI · DANA-FARBER CANCER INST · PI Michael H. Rosenthal, Brian Matthew Wolpin · 2016 to 2026
$8.7M
Transcriptional Mechanisms Governing Beta Cell DifferentiationR01DK060581 · NIDDK · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI Raghavendra G Mirmira · 2002 to 2026
$8.5M
Human Islet Research Network (HIRN) Coordinating CenterU01DK104162 · NIDDK · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI NILAND, JOYCE CAROL · 2014 to 2018
$6.1M
Mechanisms of Beta Cell Function in Health and DiseaseR01DK093954 · NIDDK · INDIANA UNIVERSITY INDIANAPOLIS · PI EVANS-MOLINA, CARMELLA · 2011 to 2019
$3.5M
Anti-inflammatory therapy to improve outcomes in patients with chronic pancreatitis undergoing total pancreatectomy with islet autotransplant (TPIAT)R01DK109914 · NIDDK · UNIVERSITY OF MINNESOTA · PI BELLIN, MELENA D. · 2016 to 2020
$2.6M
Epigenetic, Protein, and Cellular Biomarkers of Beta Cell Function in T1DUC4DK104205 · NIDDK · YALE UNIVERSITY · PI HEROLD, KEVAN C · 2014 to 2014
$2.5M
Biomarkers Of Beta Cell Stress In Type 1 Diabetes (BetaMarker)UC4DK104166 · NIDDK · INDIANA UNIVERSITY INDIANAPOLIS · PI EIZIRIK, DECIO LAKS, EVANS-MOLINA, CARMELLA · 2014 to 2014
$2.4M
Novel diagnostics for autoimmunity from checkpoint inhibitor immune therapyR43DK116577 · NIDDK · L2 DIAGNOSTICS, LLC · PI HEROLD, KEVAN C, USMANI-BROWN, SAHAR · 2017 to 2017
$300k
BLRD VA I01 BX001733NCATS NIH HHS UL1 TR001863NCI NIH HHS U01 CA210171NIAID NIH HHS R21 AI135562NIDDK NIH HHS P30 DK045735NIDDK NIH HHS P30 DK097512NIDDK NIH HHS R01 DK057846NIDDK NIH HHS R01 DK093954NIDDK NIH HHS R01 DK109914NIDDK NIH HHS R43 DK116577NIDDK NIH HHS U01 DK104162NIDDK NIH HHS UC4 DK104205
6 · The paper itself

Abstract

contextThere is an unmet need for biomarkers of pancreatic beta-cell death to improve early diagnosis of type 1 diabetes, enroll subjects into clinical trials, and assess treatment response. To address this need, several groups developed assays measuring insulin deoxyribonucleic acid (DNA) with unmethylated CpG sites in cell-free DNA. Unmethylated insulin DNA should be derived predominantly from beta-cells and indicate ongoing beta-cell death.

objectiveTo assess the performance of three unmethylated insulin DNA assays. DESIGN AND

participantsPlasma or serum samples from 13 subjects undergoing total pancreatectomy and islet autotransplantation were coded and provided to investigators to measure unmethylated insulin DNA. Samples included a negative control taken post-pancreatectomy but pretransplant, and a positive control taken immediately following islet infusion. We assessed technical reproducibility, linearity, and persistence of detection of unmethylated insulin DNA for each assay.

resultsAll assays discriminated between the negative sample and samples taken directly from the islet transplant bag; 2 of 3 discriminated negative samples from those taken immediately after islet infusion. When high levels of unmethylated insulin DNA were present, technical reproducibility was generally good for all assays.

conclusionsThe measurement of beta cell cell-free DNA, including insulin, is a promising approach, warranting further testing and development in those with or at-risk for type 1 diabetes, as well as in other settings where understanding the frequency or kinetics of beta cell death could be useful.

Indexed as

Cell DeathAdultAgedBiological AssayBiomarkersCell-Free Nucleic AcidsDNA MethylationFemaleHumansInsulinInsulin-Secreting CellsLaboratory Proficiency TestingMaleMiddle AgedReproducibility of ResultsBiomarkersCell-Free Nucleic AcidsInsulinBeta cellcell-free DNAislet transplantationtype 1 diabetes

Identifiers

PMID31913467
PMCPMC7015459
OpenAlexW3000022031

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.