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

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

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

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)
JournalDiabetes, Obesity and Metabolism
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

Type 1 Diabetes Mellitus
C-Peptide
DNA
Fasting
Meals
Registries
Cell Survival
Cell Death
Polymerase Chain Reaction
Serum

Keywords

  • beta cell function
  • type 1 diabetes

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

Persistent elevations in circulating INS DNA among subjects with longstanding type 1 diabetes. / Neyman, Anna; Nelson, Jennifer; Tersey, Sarah A.; Mirmira, Raghu; Evans-Molina, Carmella; Sims, Emily K.

In: Diabetes, Obesity and Metabolism, 01.01.2018.

Research output: Contribution to journalArticle

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AU - Sims, Emily K.

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