[A study on the effects of animal-based foods and TXNIP gene DNA methylation on the incidence of type 2 diabetes mellitus].

Objective: To investigate the associations of animal-sourced food consumption, TXNIP gene DNA methylation, and their interaction with the risk of incident type 2 diabetes mellitus (T2DM) in a population from Fangshan District, Beijing. Methods: This study was based on baseline and follow-up data from the Fangshan Family-based Cohort in Beijing. A total of 1 942 participants with complete dietary data and free of T2DM at baseline survey were included. The baseline survey was conducted between 2005 and 2017, with follow-up until January 2025. Dietary intake was assessed using a semi-quantitative food frequency questionnaire. Animal-sourced foods included meat, fish, eggs, and milk. For each food, intake levels were standardized and then scored into tertiles from high to low: 3 points (high), 2 points (medium), and 1 point (low). The scores for all four foods were summed to obtain the animal-sourced food group score, ranging from 4 (lowest) to 12 (highest). DNA methylation was measured using EPIC arrays in 387 participants from the cohort. Mixed-effects linear models were used to assess associations between DNA methylation levels and T2DM, and family-based Cox proportional hazards regression models were used to examine the association between dietary factors and incident T2DM. Furthermore, the interaction between diet and DNA methylation on T2DM risk was explored. Results: During a median follow-up of 9.7 years, 432 T2DM cases were documented among the 1 942 participants. Each one-point increase in the animal-based food group score was associated with a 12% higher risk of T2DM (HR=1.12, 95%CI: 1.05-1.19, P=0.001). Among the individual components, each unit increase in fish intake was associated with a 19% (HR=1.19, 95%CI: 1.08-1.32, P<0.001) higher risk of T2DM, and each unit increase in egg intake was associated with a 21% (HR=1.21, 95%CI: 1.08-1.35, P=0.001) higher risk. In the DNA methylation analysis, two CpG sites of the TXNIP gene, cg19693031 and cg26974062, remained significantly associated with T2DM after Bonferroni correction (P_Bonferroni=0.006 and 0.032, respectively). Interaction analysis showed that cg19693031 may modify the effects of animal-based food and egg intake on T2DM risk (P for interaction=0.042 and 0.014, respectively). However, after stratifying by the median methylation level of cg19693031, no significant associations between animal-sourced food or egg intake and T2DM risk were observed in either methylation subgroup. Conclusions: Animal-sourced food consumption is associated with an increased risk of incident T2DM, and DNA methylation may modify this association. These findings suggest that future dietary guidance for individuals at high risk of T2DM may need to also consider the epigenetic risk of T2DM-related genes.