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1.  Circulating β-carotene levels and Type 2 diabetes: Cause or effect? 
Diabetologia  2009;52(10):2117-2121.
Aims and Hypothesis
Circulating β-carotene levels are inversely associated with type 2 diabetes risk, but the causal direction of this association is not certain. In this study we used a Mendelian Randomization approach to provide evidence for or against the causal role of the anti-oxidant vitamin β-carotene in type 2 diabetes.
Methods
We used a common polymorphism (rs6564851) near the β-carotene 15,15'-Monooxygenase 1 (BCMO1) gene that is strongly associated with circulating β-carotene levels (P = 2×10−24) - each G allele is associated with a 0.27 standard deviation increase in levels. We used data from the InCHIANTI study and the ULSAM study 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 to the observed effect using data from 4549 type 2 diabetes cases and 5579 controls from the DIAGRAM consortium.
Results
A 0.27 standard deviation increase in β-carotene levels is associated with an odds ratio of 0.90 (0.86–0.95) for type 2 diabetes in the InCHIANTI study. This association is 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), and this effect size was 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.
Conclusion
Our Mendelian Randomization studies are in keeping with randomized controlled trials that suggest β-carotene is not causally protective against type 2 diabetes.
doi:10.1007/s00125-009-1475-8
PMCID: PMC2746424  PMID: 19662379
type 2 diabetes; β-carotene; mendelian randomization

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