ArticleEndocrinology2013
Detection of islet β-cell death in vivo by multiplex PCR analysis of differentially methylated DNA.
Article in Endocrinology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04139369 (Study of DNA Methylation in Children and Adolescents With Type 1 Diabetes Mellitus), which is not on this map. Cited by 40 papers.
What it found
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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.
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.
Study of DNA Methylation in Children and Adolescents With Type 1 Diabetes Mellitus
Who cites it
40 citing papers in PubMed, 46 citations in OpenAlex.
- Plasma GAD65, a Marker for Early β-Cell Loss After Intraportal Islet Cell Transplantation in Diabetic Patients.The Journal of clinical endocrinology and metabolism · 2015Trial
- Messenger RNA delivery to islet β cells using conjugated lipid nanoparticles.Cell reports. Medicine · 2026Article
- Preclinical Diagnosis of Type 1 Diabetes: Reality or Utopia.Biomedicines · 2025Review
- RISING STARS: Evidence for established and emerging forms of β-cell death.The Journal of endocrinology · 2024Review
- Metabolic memory: mechanisms and diseases.Signal transduction and targeted therapy · 2024Review
- Beta cell dedifferentiation in type 1 diabetes: sacrificing function for survival?Frontiers in endocrinology · 2024Article
- Liquid Biopsy in Type 2 Diabetes Mellitus Management: Building Specific Biosignatures via Machine Learning.Journal of clinical medicine · 2022Article
- β-Cell Death in Diabetes: Past Discoveries, Present Understanding, and Potential Future Advances.Metabolites · 2021Review
- Cell-Free DNA Fragments as Biomarkers of Islet β-Cell Death in Obesity and Type 2 Diabetes.International journal of molecular sciences · 2021Review
- Insulin gene promoter methylation status in Greek children and adolescents with Type 1 Diabetes.Biomedical reports · 2020Article
- The role of beta-cell dysfunction in early type 1 diabetes.Current opinion in endocrinology, diabetes, and obesity · 2020Review
- Controversial Roles of Gut Microbiota-Derived Short-Chain Fatty Acids (SCFAs) on Pancreatic β-Cell Growth and Insulin Secretion.International journal of molecular sciences · 2020Review
- The role of proteomics in assessing beta-cell dysfunction and death in type 1 diabetes.Expert review of proteomics · 2019Article
- Levels of circulating insulin cell-free DNA in women with polycystic ovary syndrome - a longitudinal cohort study.Reproductive biology and endocrinology : RB&E · 2019Article
- Persistent elevations in circulating INS DNA among subjects with longstanding type 1 diabetes.Diabetes, obesity & metabolism · 2019Article
- Comparative analysis of diagnostic platforms for measurement of differentially methylated insulin DNA.Journal of biological methods · 2019Article
- Postpartum Circulating Cell-Free Insulin DNA Levels Are Higher in Women with Previous Gestational Diabetes Mellitus Who Develop Type 2 Diabetes in Later Life.Journal of diabetes research · 2019Article
- Biomarkers of islet beta cell stress and death in type 1 diabetes.Diabetologia · 2018Review
- Episodic β-cell death and dedifferentiation during diet-induced obesity and dysglycemia in male mice.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2018Article
- Elevated unmethylated and methylated insulin DNA are unique markers of A+β+ ketosis prone diabetes.Journal of diabetes and its complications · 2018Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Noninvasive detection of early β-cell death in type 1 diabetes might identify individuals in whom therapeutic interventions would preserve β-cell mass and prevent hyperglycemia. Recent studies in mice have shown that β-cell death produces a corresponding increase in unmethylated preproinsulin (PPI) DNA in serum. Here, we report the development of a novel assay using dual fluorescent-probe multiplex PCR (TaqMan) to detect differential methylation of circulating PPI DNA. Key assay features include low background signals, linear assay output across a large range of values, and simultaneous detection of methylated and unmethylated PPI DNA in a single reaction. We defined the "unmethylation index" as a summary parameter that reflects the relative amounts of unmethylated vs methylated PPI DNA. To validate this assay's ability to detect β-cell death in vivo, we measured the unmethylation index in the serum of diabetic mouse models, including high- and multiple low-dose streptozotocin-induced diabetes, and the nonobese diabetic mouse model of type 1 diabetes. Our data show a significantly increased unmethylation index concordant with the known timeline of β-cell death that precedes the onset of hyperglycemia. Subsequently, we observed a decrease in the unmethylation index following diabetes development, likely reflecting the absence of further β-cell death in the pancreas. We conclude that simultaneous measurement of methylated and unmethylated PPI DNA using the multiplex PCR method described here is a readily available and sensitive indicator of dying β-cells that may be useful to track diabetes progression and response to therapeutic intervention.
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Registered trials
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.