Global DNA Methylation Is Associated With Insulin Resistance

A Monozygotic Twin Study

  1. Viola Vaccarino5
  1. 1Department of Biostatistics and Epidemiology, College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma
  2. 2Seattle Epidemiologic Research & Information Center, Veterans Affairs Office of Research & Development, Seattle, Washington
  3. 3Department of Epidemiology, University of Washington, Seattle, Washington
  4. 4Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia
  5. 5Department of Epidemiology, Emory University School of Public Health, Atlanta, Georgia
  1. Corresponding author: Jinying Zhao, jinying-zhao{at}


Insulin resistance (IR), the hallmark of type 2 diabetes, may be under epigenetic control. This study examines the association between global DNA methylation and IR using 84 monozygotic twin pairs. IR was estimated using homeostasis model assessment (HOMA). Global DNA methylation of Alu repeats in peripheral blood leukocytes was quantified by bisulfite pyrosequencing. The association between global DNA methylation and IR was examined using generalized estimating equation (GEE) and within–twin pair analyses, adjusting for potential confounders. Results show that methylation levels at all four CpG sites were individually associated with IR by GEE (all false discovery rate–adjusted P values ≤0.026). A 10% increase in mean Alu methylation was associated with an increase of 4.55 units (95% CI 2.38–6.73) in HOMA. Intrapair difference in IR was significantly associated with intrapair difference in global methylation level. A 10% increase in the difference in mean Alu methylation was associated with an increase of 4.54 units (0.34–8.71; P = 0.036) in the difference in HOMA. Confirmation of the results by intrapair analyses suggests that genetic factors do not confound the association between global DNA methylation and IR. Exclusion of twins taking diabetes medication (n = 17) did not change our results.

  • Received July 27, 2011.
  • Accepted November 20, 2011.

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  1. Diabetes vol. 61 no. 2 542-546
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