Circulating unmethylated insulin DNA as a potential non-invasive biomarker of beta cell death in type 1 Diabetes: a review and future prospect

Clin Epigenetics. 2017 Apr 26;9:44. doi: 10.1186/s13148-017-0343-5. eCollection 2017.


Background: The early detection of type 1 diabetes (T1D) largely depends on a reliable approach to monitor β cell loss. An effective way to evaluate the decline of β cell mass would allow early preventative intervention to preserve insulin secretion.

Main body: Recent progress in the development of novel biomarkers, based on tissue-specific methylation patterns, has inspired relevant studies in T1D. In this review, we focus on the application of circulating β cell-derived unmethylated insulin (INS) DNA. Circulating β cell-derived unmethylated INS DNA has a potential clinical value for the early detection of T1D, surveillance of islet transplantation rejection, and evaluation of response to therapy. Utilizing differentiated methylation patterns in different organs and employing a wide variety of molecular technologies also provide insights into the interrogation of biomarkers in other diseases with massive tissue-specific cell loss.

Conclusion: Circulating unmethylated INS DNA is a promising molecular biomarker for the early detection of T1D.

Keywords: Cell-free DNA; Early detection; Molecular biomarkers; Type 1 diabetes; Unmethylated insulin DNA.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers / blood
  • Cell Death
  • DNA Methylation
  • Diabetes Mellitus, Type 1 / blood
  • Diabetes Mellitus, Type 1 / diagnosis*
  • Diabetes Mellitus, Type 1 / genetics
  • Early Diagnosis
  • Humans
  • Insulin / blood
  • Insulin / genetics*
  • Insulin-Secreting Cells / physiology*
  • Organ Specificity


  • Biomarkers
  • Insulin