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Background <p>Dietary choices influence both risk and development of type 2 diabetes (T2D), but the precise mechanisms remain incompletely described. Dietary intake and lifestyle behaviors can alter epigenetic states with subsequent modulations on gene expression which then can change the risk of T2D.</p> Methods <p>An epigenome-wide association study was conducted to identify any epigenetic links to diabetes risk by investigating epigenetic changes during a 6-year follow-up in 374 participants who were free of T2D at baseline. The identified epigenetic changes were examined for their association with any dietary and lifestyle factors. Additionally, mediation analysis determined whether the associated dietary factors contribute to diabetes risk through epigenetic changes.</p> Results <p>The epigenome-wide association study identified significant epigenetic changes during the 6-year follow-up at seven loci within genes <i>REPIN1</i>, <i>BMP2</i>, <i>LINC01723</i>, and <i>SEL1L2</i>, all of which were associated with insulin resistance. Further analysis revealed strong associations between three specific differentially methylated sites (DMSs) cg16400647 in <i>REPIN1</i>, cg12344389, and cg00625573, and dietary vitamin B12 intake. Additionally, cg26719314 on the X chromosome showed separate robust correlations with total sugar intake. Mediation analysis showed that higher vitamin B12 intake might reduce insulin resistance through epigenetic modification in <i>REPIN1</i> and <i>DNAAF9.</i> Conversely, higher total sugar intake correlated significantly with elevated diabetes risk, with cg26719314 acting as a mediator. Furthermore, increased vitamin B12 supplementation was associated with decreased insulin resistance at 6-year follow-up in the entire cohort.</p> Conclusions <p>These findings suggest that vitamin B12 intake may influence insulin resistance through specific epigenetic changes, thus describing the epigenetic links between diet and development of T2D.</p>

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Epigenetic changes reveal that vitamin B12 intake is associated with lower insulin resistance in older adults

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年8月4日

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  • Chao-Qiang Lai,
  • Laurence D. Parnell,
  • Yu-Chi Lee,
  • Bruce S. Kristal,
  • Oladimeji J. Akinlawon,
  • Margaret P. Winderman,
  • Tamara K. Reed,
  • Liam Fouhy,
  • Kelsey M. Mangano,
  • Josiemer Mattei,
  • Katherine L. Tucker,
  • José M. Ordovás

摘要

Background

Dietary choices influence both risk and development of type 2 diabetes (T2D), but the precise mechanisms remain incompletely described. Dietary intake and lifestyle behaviors can alter epigenetic states with subsequent modulations on gene expression which then can change the risk of T2D.

Methods

An epigenome-wide association study was conducted to identify any epigenetic links to diabetes risk by investigating epigenetic changes during a 6-year follow-up in 374 participants who were free of T2D at baseline. The identified epigenetic changes were examined for their association with any dietary and lifestyle factors. Additionally, mediation analysis determined whether the associated dietary factors contribute to diabetes risk through epigenetic changes.

Results

The epigenome-wide association study identified significant epigenetic changes during the 6-year follow-up at seven loci within genes REPIN1, BMP2, LINC01723, and SEL1L2, all of which were associated with insulin resistance. Further analysis revealed strong associations between three specific differentially methylated sites (DMSs) cg16400647 in REPIN1, cg12344389, and cg00625573, and dietary vitamin B12 intake. Additionally, cg26719314 on the X chromosome showed separate robust correlations with total sugar intake. Mediation analysis showed that higher vitamin B12 intake might reduce insulin resistance through epigenetic modification in REPIN1 and DNAAF9. Conversely, higher total sugar intake correlated significantly with elevated diabetes risk, with cg26719314 acting as a mediator. Furthermore, increased vitamin B12 supplementation was associated with decreased insulin resistance at 6-year follow-up in the entire cohort.

Conclusions

These findings suggest that vitamin B12 intake may influence insulin resistance through specific epigenetic changes, thus describing the epigenetic links between diet and development of T2D.