Association between alterations in global DNA methylation and predisposing factors in diabetes: a high pressure liquid chromatography based study

Minerva Med. 2015 Aug;106(4):221-31. Epub 2014 Jul 31.

Abstract

Aim: The aim of this study was to investigate the relationship between inter-individual global DNA methylation and diabetes predisposing factors.

Methods: The 5-methyl cytosine content was assessed by reverse phase high pressure liquid chromatography (RP-HPLC) of peripheral blood leukocytes obtained from 178 type 2 diabetes patients to determine individual global DNA methylation status.

Results: There was a positive significant correlation between diabetes duration and DNA methylation levels (P=0.002) with increasing levels of DNA methylation associated with age (P=0.047). There was no significant correlation between DNA methylation levels and HbA1c (P=0.15). No significant differences were observed between patients with and without diabetes predisposing factors including: hypertension (P=0.772), dyslipidemia (P=0.617), insulin resistance (homeostatic model assessment index) (P=0.156) and obesity (P=0.609). As such, the duration of diabetes (>10 years) was the most important predictor of global DNA methylation levels in diabetic patients after adjusting for age and sex (P=0.023).

Conclusion: Our findings indicate that chronic hyperglycemic exposure plays an independent role in global DNA methylation levels in type 2 diabetes patients.

MeSH terms

  • Albuminuria / urine
  • Biomarkers / blood
  • Body Mass Index
  • Chromatography, High Pressure Liquid*
  • Cross-Sectional Studies
  • DNA Methylation*
  • Diabetes Mellitus, Type 2 / blood*
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / diagnosis*
  • Diabetes Mellitus, Type 2 / urine
  • Disease Progression
  • Dyslipidemias / complications
  • Female
  • Glycated Hemoglobin / metabolism
  • Humans
  • Hypertension / complications
  • Leukocytes / metabolism
  • Male
  • Middle Aged
  • Obesity / complications
  • Predictive Value of Tests
  • Reproducibility of Results
  • Risk Factors
  • Sensitivity and Specificity
  • Severity of Illness Index

Substances

  • Biomarkers
  • Glycated Hemoglobin A