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

Diabetologia. 2009 Oct;52(10):2117-21. doi: 10.1007/s00125-009-1475-8. Epub 2009 Aug 7.


Aims/hypothesis: Circulating beta-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 beta-carotene in type 2 diabetes.

Methods: We used a common polymorphism (rs6564851) near the BCMO1 gene, which is strongly associated with circulating beta-carotene levels (p = 2 x 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 beta-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 beta-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 beta-carotene levels, and the associations between beta-carotene levels and type 2 diabetes.

Conclusions/interpretation: Our findings in this Mendelian randomisation study are in keeping with randomised controlled trials suggesting that beta-carotene is not causally protective against type 2 diabetes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Diabetes Mellitus, Type 2 / epidemiology*
  • Diabetes Mellitus, Type 2 / genetics*
  • Diabetes Mellitus, Type 2 / metabolism
  • Humans
  • Polymorphism, Single Nucleotide / genetics
  • beta Carotene / metabolism*
  • beta-Carotene 15,15'-Monooxygenase / genetics


  • beta Carotene
  • BCO1 protein, human
  • beta-Carotene 15,15'-Monooxygenase