Circulating β-carotene levels and type 2 diabetes-cause or effect?

Aims/hypothesis: Circulating β-carotene levels are inversely associated with risk of type 2 diabetes, but the causal direction of this association is not certain. In this study we used a Mendelian randomisation approach to provide evidence for or against the causal role of the antioxidant vitamin β-carotene in type 2 diabetes. Methods: We used a common polymorphism (rs6564851) near the BCMO1 gene, which is strongly associated with circulating β-carotene levels (p=2×10^-24), with each G allele associated with a 0.27 standard deviation increase in levels. We used data from the InCHIANTI and Uppsala Longitudinal Study of Adult Men (ULSAM) studies to estimate the association between β-carotene levels and type 2 diabetes. We next used a triangulation approach to estimate the expected effect of rs6564851 on type 2 diabetes risk and compared this with the observed effect using data from 4549 type 2 diabetes patients and 5579 controls from the Diabetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium. Results: A 0.27 standard deviation increase in β-carotene levels was associated with an OR of 0.90 (95% CI 0.86-0.95) for type 2 diabetes in the InCHIANTI study. This association was similar to that of the ULSAM study (OR 0.90 [0.84-0.97]). In contrast, there was no association between rs6564851 and type 2 diabetes (OR 0.98 [0.93-1.04], p=0.58); this effect size was also smaller than that expected, given the known associations between rs6564851 and β-carotene levels, and the associations between β-carotene levels and type 2 diabetes. Conclusions/interpretation: Our findings in this Mendelian randomisation study are in keeping with randomised controlled trials suggesting that β-carotene is not causally protective against type 2 diabetes.