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, Kevan C. Herold, Raghavendra G. Mirmira, Yuval Dor, Carmella Evans-Molina

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Context: There 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. Objective: To assess the performance of three unmethylated insulin DNA assays. Design and Participants: Plasma 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. Results: All 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. Conclusions: The 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.

Original languageAmerican English
Article numberdgaa008
JournalJournal of Clinical Endocrinology and Metabolism
Volume105
Issue number3
DOIs
StatePublished - 8 Jan 2020

Bibliographical note

Publisher Copyright:
© 2020 Endocrine Society 2020.

Keywords

  • Beta cell
  • cell-free DNA
  • islet transplantation
  • type 1 diabetes

Fingerprint

Dive into the research topics of 'Circulating Unmethylated Insulin DNA As a Biomarker of Human Beta Cell Death: A Multi-laboratory Assay Comparison'. Together they form a unique fingerprint.

Cite this