Circulating beta-carotene levels and type 2 diabetes-cause or effect?
OBJECTIVE
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
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.
Perry
J R B
JR
Peninsula Medical School, Exeter, UK.
Ferrucci
L
L
Bandinelli
S
S
Guralnik
J
J
Semba
R D
RD
Rice
N
N
Melzer
D
D
Saxena
R
R
Scott
L J
LJ
McCarthy
M I
MI
Hattersley
A T
AT
Zeggini
E
E
Weedon
M N
MN
Frayling
T M
TM
D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology* / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D019207:beta Carotene / Q000378:metabolism*; D050559:beta-Carotene 15,15'-Monooxygenase / Q000235:genetics
D019207:beta Carotene; C493358:BCO1 protein, human; D050559:beta-Carotene 15,15'-Monooxygenase