BMI change during childhood, DNA methylation change at TXNIP, and glucose change during midlife

Obesity (Silver Spring). 2023 Aug;31(8):2150-2158. doi: 10.1002/oby.23806. Epub 2023 Jul 6.


Objective: This study investigated whether changes in DNA methylation (DNAm) at TXNIP are associated with glycemic changes and whether such an association differs with early-life adiposity changes.

Methods: A total of 594 Bogalusa Heart Study participants who had blood DNAm measurements at two time points in midlife were included. Of them, 353 participants had at least four BMI measurements during childhood and adolescence. The incremental area under the curve was calculated as a measure of long-term trends of BMI during childhood and adolescence.

Results: Increase in DNAm at TXNIP was significantly associated with decrease in fasting plasma glucose (FPG) independent of covariates (p < 0.001). The study found that the strength of this relationship was significantly modified by a trend of increasing BMI during childhood and adolescence (p-interaction = 0.003). Each 1% increase in DNAm at TXNIP was associated with a 2.90- (0.77) mg/dL decrease in FPG among participants with the highest tertile of BMI incremental area under the curve and a 0.96- (0.38) mg/dL decrease among those with the middle tertile, whereas no association was observed among participants with the lowest tertile.

Conclusions: These results indicate that changes in blood DNAm at TXNIP are significantly associated with changes in FPG in midlife, and this association was modified by BMI trends during childhood and adolescence.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adiposity* / genetics
  • Birth Weight* / genetics
  • Blood Glucose / genetics
  • Body Mass Index*
  • Carrier Proteins* / genetics
  • Child
  • DNA Methylation
  • Epigenesis, Genetic*
  • Glucose* / metabolism
  • Humans


  • TXNIP protein, human
  • Carrier Proteins
  • Blood Glucose
  • Glucose