Persistent elevations in circulating INS DNA among subjects with longstanding type 1 diabetes

Anna Neyman, Jennifer Nelson, Sarah A. Tersey, Raghavendra G. Mirmira, Carmella Evans-Molina, Emily K. Sims

Research output: Contribution to journalArticle

2 Scopus citations


Aim: To evaluate whether β cells continue to undergo death in the later stages of type 1 diabetes (T1D). Materials and Methods: Fasting banked sera from a cross-section of 90 participants in the T1D Exchange Registry with longstanding T1D (median duration of 9 years) were analysed. Subjects were determined to be C-peptide (−) or (+) based on mixed-meal tolerance testing. Results were compared with 54 adult non-diabetic controls. Stimulated samples were assayed in a subset of subjects. Levels of unmethylated and methylated preproinsulin (INS) DNA were analysed using digital droplet PCR. Results: Fasting and stimulated circulating unmethylated INS DNA levels were increased among both C-peptide (−) and C-peptide (+) subjects with longstanding T1D compared with non-diabetic controls (P < 0.01). Consistent with prior reports, unmethylated INS DNA values correlated with methylated INS DNA values, which were also elevated among T1D subjects (P < 0.001). There was wide variation in the effects of mixed-meal stimulation on DNA levels, with fasting values in the highest quartiles decreasing with stimulation (P < 0.05). Conclusions: These results could reflect ongoing β cell death in individuals with longstanding T1D, even in the absence of detectable C-peptide production, suggesting that therapies targeting β cell survival could be beneficial among individuals with longstanding T1D.

Original languageEnglish (US)
Pages (from-to)95-102
Number of pages8
JournalDiabetes, Obesity and Metabolism
Issue number1
StatePublished - Jan 2019


  • beta cell function
  • type 1 diabetes

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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