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

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posted on 31.07.2020 by Jie Zhu, Cheng Chen, Liping Lu, Kefeng Yang, Jared Reis, Ka He

To prospectively examine intakes of folate, vitamin B6, and vitamin B12 in relation to diabetes incidence in a large U.S. cohort.


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.


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).


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.


This study is partially supported by NIH grants (R01DK116603 and R01HL081572). The Coronary Artery Risk Development in Young Adults Study (CARDIA) is conducted and supported by the National Heart, Lung, and Blood Institute (NHLBI) in collaboration with the University of Alabama at Birmingham (HHSN268201800005I & HHSN268201800007I), Northwestern University (HHSN268201800003I), University of Minnesota (HHSN268201800006I), and Kaiser Foundation Research Institute (HHSN268201800004I). This manuscript has been reviewed by CARDIA for scientific content. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.