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

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 1985-86 and followed until 2015-16 in the Coronary Artery Risk Development in Young Adults study. Dietary assessment was conducted by a validated dietary-history questionnaire at baseline, in 1992-93 and 2005-06. 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 anti-diabetic medications. RESULTS During 30 years (mean = 20.5±8.9 years) 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 to the lowest quintile of total folate intake, the multivariable-adjusted hazard ratios (95% confidence interval) in quintile 2 to 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 <0.01) and insulin (Ptrend <0.01). Among supplement users, folate intake was inversely associated with serum C-reactive protein levels (Ptrend <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.