Elevations in circulating methylated and unmethylated preproinsulin DNA in new-onset type 1 diabetes

Marisa M. Fisher, Renecia A. Watkins, Janice Blum, Carmella Evans-Molina, Naga Chalasani, Linda A. Dimeglio, Kieren J. Mather, Sarah A. Tersey, Raghavendra G. Mirmira

Research output: Contribution to journalArticle

48 Scopus citations

Abstract

Elevated ratios of circulating unmethylated to methylated preproinsulin (INS) DNA have been suggested to reflect b-cell death in type 1 diabetes (T1D). We tested the hypothesis that absolute levels (rather than ratios) of unmethylated and methylated INS DNA differ between subjects with new-onset T1D and control subjects and assessed longitudinal changes in these parameters. We used droplet digital PCR to measure levels of unmethylated and methylated INS DNA in serum from subjects at T1D onset and at 8 weeks and 1 year post-onset. Compared with control subjects, levels of both unmethylated and methylated INS DNA were elevated at T1D onset. At 8 weeks post-onset, methylated INS DNA remained elevated, but unmethylated INS DNA fell. At 1 year postonset, both unmethylated and methylated INS DNA returned to control levels. Subjects with obesity, type 2 diabetes, and autoimmune hepatitis exhibited lower levels of unmethylated and methylated INS compared with subjects with T1D at onset and no differences compared with control subjects. Our study shows that elevations in both unmethylated and methylated INS DNA occurs in new-onset T1D and that levels of these DNA species change during T1D evolution. Our work emphasizes the need to consider absolute levels of differentially methylated DNA species as potential biomarkers of disease.

Original languageEnglish (US)
Pages (from-to)3867-3872
Number of pages6
JournalDiabetes
Volume64
Issue number11
DOIs
StatePublished - Nov 2015

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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