(P41-34-26) One-carbon Metabolism Nutrients intake, Genetic Polymorphisms, and Risk of Diabetes in Hispanic Community Health Study/Study of Latinos: A Prospective Cohort Study

Objectives: To examine intake of one-carbon metabolism (OCM) nutrients, genetic polymorphisms, and diabetes risk in Hispanic/Latino adults.

Methods: This prospective cohort study included 12,410 adults aged 18-74 years and free of diabetes at baseline (2008-2010) from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), followed through 2023-2025. Dietary intake was assessed at baseline using two validated 24-hour recalls and a food propensity questionnaire. Average intakes of OCM nutrients (folate, choline, betaine, vitamins B₂, B₆, B₁₂, and zinc) were estimated. Genotyping data were obtained from a custom Illumina Omni2.5M array, and six a priori-selected OCM-related polymorphisms were analyzed. Incident diabetes was defined by clinical testing, physician diagnosis, or glucose-lowering medication usage. Logistic regression assessed genetic associations. Incidence density ratios (IDRs) were estimated using complex survey Poisson regression, adjusting for demographic, socioeconomic, biomedical, lifestyle, and dietary factors.

Results: Over 121,862 person-years of follow-up, 2,585 incident diabetes cases were identified. Total intake of each OCM nutrients was not associated with diabetes risk. The phosphatidylethanolamine N-methyltransferase (PEMT) C523T (rs7946) polymorphism was associated with diabetes risk: Individuals with the TT genotype had lower risk, compared with CC (OR 0.82; 95% CI 0.70, 0.96) and CC+CT genotypes (OR 0.86; 95% CI 0.77, 0.97). Higher choline intake was associated with increased diabetes risk among CC genotype carriers (IDR 1.44; 95% CI 1.12, 1.84; P_trend < 0.01), but not among T-allele carriers. These findings were robust across stratified analyses by age, sex, and education attainment.

Conclusions: PEMT C523T polymorphism may modify the association between choline intake and diabetes risk in Hispanic/Latino adults, highlighting the relevance of integrating OCM nutrients intake and genetic susceptibility, when evaluating diabetes risk.

Funding Sources: NIH National Heart, Lung, and Blood Institute