Long-term b-Carotene Supplementation and Risk of Type 2 Diabetes Mellitus

INCREASED FREE RADICAL ACTIVITY and high lipid oxidation impair glucose disposal in the peripheral tissues and exacerbate diabetic complications. These observations suggest a role for oxidative stress in the pathogenesis of type 2 diabetes mellitus (DM). Because of its extended system of conjugated double bonds, b-carotene can scavenge peroxyl radicals and exert strong antioxidant activity, suggesting a protective effect against the development of type 2 DM. Indirect evidence supporting such a protective role for b-carotene comes from several observational studies relating increased intake of vegetables that are rich in carotenoids with a lower risk of type 2 DM. In addition, a recent dietary trial indicates that among people with impaired glucose tolerance, those assigned to a diet with more vegetables have a lower incidence of type 2 DM. It is possible, however, that the observed reduction in risk associated with vegetables rich in carotenoids may be due not to their b-carotene content but rather to other nutrients in these foods or to other dietary or lifestyle factors. Moreover, biases due to selection of subjects, misclassification of exposure, and residual confounding cannot be fully addressed in observational studies, and no previous randomized trial has directly assessed the efficacy of b-carotene to prevent type 2 DM. To address this question, we examined the effect of long-term supplementation with b-carotene on the incidence of type 2 DM in the Physicians’ Health Study, a randomized 12-year trial of 22 071 US male physicians.