(P41-12-26) Epigenetic Changes Reveal That Vitamin B12 Intake Is Associated With Lower Insulin Resistance in Older Adults

Monday, July 27, 2026

9:30 AM - 10:30 AM ET

Location: Poster Board G-55

Presenting Author(s)

CL

Chao-Qiang Lai, PhD (he/him/his)

Molecular Biologist
USDA Agricultural Research Service, Precision Nutrition, Jean Mayer USDA Human Nutrition Research Center on Aging (HNRCA) at Tufts University
Boston, Massachusetts, United States

Co-Author(s)

LP

Laurence Parnell, Ph. D.

USDA ARS, JM-USDA Human Nutrition Research Ctr on Aging @ Tufts
Boston, Massachusetts, United States
YL

Yu-Chi Lee

USDA ARS, Precision Nutrition Team, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University
Boston, Massachusetts, United States
OA

Oladimeji J. Akinlawon

USDA ARS, Precision Nutrition Team, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University
Boston, Massachusetts, United States
BK

Bruce S. Kristal, PhD (he/him/his)

Senior Scientist
Jean Mayer USDA Human Nutrition Research Center on Aging (HNRCA) at Tufts University
Boston, Massachusetts, United States
LF

Liam Fouhy, MPH

University of Massachusetts, Lowell, United States
Kelsey M. Mangano, PhD

Associate Professor
University of Massachusetts, Lowell
Lowell, Massachusetts, United States
JM

Josiemer Mattei, PhD

Associate Professor
Harvard University
Boston, Massachusetts, United States
Katherine L. Tucker, PhD (she/her/hers)

Professor, Director of the Center for Population Health
University of Massachusetts, Lowell
Zuckerberg College of Health Sciences
Lowell, Massachusetts, United States
Jose M. Ordovas, PhD

Director, Nutrition and Genomics
Jean Mayer USDA Human Nutrition Research Center on Aging (HNRCA) at Tufts University
Boston, Massachusetts, United States

Disclosure(s):

Chao-Qiang Lai, PhD: No relevant financial relationship(s) with ineligible companies to disclose.

Bruce S. Kristal, PhD: No relevant financial relationship(s) with ineligible companies to disclose.

Objectives: To identify 6-year changes in DNA methylation associated with insulin resistance and to evaluate whether dietary intake influences these CpG patterns and mediates type 2 diabetes (T2D) risk.

Methods: In 374 older adults free of T2D at baseline, we performed a longitudinal epigenome-wide association study of 6-year change in DNA methylation. CpG sites associated with insulin resistance were tested for associations with dietary and lifestyle factors. Mediation analyses assessed whether vitamin B12 or total sugar intake contributed to diabetes risk via CpG methylation changes.

Results: Seven CpG loci (including in REPIN1, BMP2, LINC01723, and SEL1L2) were associated with insulin resistance. Three CpGs (cg16400647 - REPIN1, cg12344389, cg00625573) were associated with vitamin B12 intake, whereas cg26719314 (X chromosome) was associated with total sugar intake. Mediation analysis suggested vitamin B12 intake may be linked to lower diabetes risk via methylation changes in REPIN1 and DNAAF9, while higher sugar intake may be linked to higher risk via cg26719314. Furthermore, vitamin B12 supplementation was associated with lower insulin resistance at 6-year follow-up in the entire cohort.

Conclusions: Vitamin B12 intake and supplementation are associated with longitudinal methylation changes at loci related to insulin resistance, supporting a potential epigenetic pathway linking diet to diabetes risk in older adults.

Funding Sources: This study was supported by US Department of Agriculture, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute on Aging (NIA) and the National Heart, Lung and Blood Institute.