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

J. R.B. Perry, L. Ferrucci, S. Bandinelli, J. Guralnik, R. D. Semba, N. Rice, D. Melzer, R. Saxena, L. J. Scott, M. I. McCarthy, A. T. Hattersley, E. Zeggini, M. N. Weedon, T. M. Frayling

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2117-2121
Number of pages5
JournalDiabetologia
Volume52
Issue number10
DOIs
StatePublished - Oct 1 2009

Keywords

  • Mendelian randomisation
  • Type 2 diabetes
  • β-Carotene

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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    Perry, J. R. B., Ferrucci, L., Bandinelli, S., Guralnik, J., Semba, R. D., Rice, N., Melzer, D., Saxena, R., Scott, L. J., McCarthy, M. I., Hattersley, A. T., Zeggini, E., Weedon, M. N., & Frayling, T. M. (2009). Circulating β-carotene levels and type 2 diabetes-cause or effect? Diabetologia, 52(10), 2117-2121. https://doi.org/10.1007/s00125-009-1475-8