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OBJECTIVE To prospectively examine intakes of folate, vitamin B6, and vitamin B12 in relation to diabetes incidence in a large U.S. cohort. RESEARCH DESIGN AND METHODS A total of 4,704 American adults aged 18–30 years and without diabetes were enrolled in 1985–1986 and monitored until 2015–2016 in the Coronary Artery Risk Development in Young Adults (CARDIA) study. Dietary assessment was conducted by a validated dietary history questionnaire at baseline, in 1992–1993, and in 2005–2006. The cumulative average intakes of folate, vitamin B6, and vitamin B12 were used in the analyses. Incident diabetes was ascertained by plasma glucose levels, oral glucose tolerance tests, hemoglobin A1c concentrations, and/or antidiabetic medications. RESULTS During 30 years (mean 20.5 ± 8.9) of follow-up, 655 incident cases of diabetes occurred. Intake of folate, but not vitamin B6 or vitamin B12, was inversely associated with diabetes incidence after adjustment for potential confounders. Compared with the lowest quintile of total folate intake, the multivariable-adjusted hazard ratios (95% CI) in quintiles 2–5 were 0.85 (0.67–1.08), 0.78 (0.60–1.02), 0.82 (0.62–1.09), and 0.70 (0.51–0.97; Ptrend = 0.02). Higher folate intake was also associated with lower plasma homocysteine (Ptrend &amp;lt; 0.01) and insulin (Ptrend &amp;lt; 0.01). Among supplement users, folate intake was inversely associated with serum C-reactive protein levels (Ptrend &amp;lt; 0.01). CONCLUSIONS Intake of folate in young adulthood was inversely associated with diabetes incidence in midlife among Americans. The observed association may be partially explained by mechanisms related to homocysteine level, insulin sensitivity, and systemic inflammation.

Intakes of Folate, Vitamin B6, and Vitamin B12 in Relation to Diabetes Incidence Among American Young Adults: A 30-Year Follow-up Study