Circulating beta-carotene levels and type 2 diabetes-cause or effect?
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 vitami...
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
2009
|
| _version_ | 1797080430859517952 |
|---|---|
| author | Perry, JR Ferrucci, L Bandinelli, S Guralnik, J Semba, R Rice, N Melzer, D Saxena, R Scott, L McCarthy, M Hattersley, A Zeggini, E Weedon, M Frayling, T |
| author_facet | Perry, JR Ferrucci, L Bandinelli, S Guralnik, J Semba, R Rice, N Melzer, D Saxena, R Scott, L McCarthy, M Hattersley, A Zeggini, E Weedon, M Frayling, T |
| author_sort | Perry, JR |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-07T00:59:56Z |
| format | Journal article |
| id | oxford-uuid:895e89a0-51f2-4719-a7fe-7564bc345deb |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T00:59:56Z |
| publishDate | 2009 |
| record_format | dspace |
| spelling | oxford-uuid:895e89a0-51f2-4719-a7fe-7564bc345deb2022-03-26T22:24:04ZCirculating beta-carotene levels and type 2 diabetes-cause or effect?Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:895e89a0-51f2-4719-a7fe-7564bc345debEnglishSymplectic Elements at Oxford2009Perry, JRFerrucci, LBandinelli, SGuralnik, JSemba, RRice, NMelzer, DSaxena, RScott, LMcCarthy, MHattersley, AZeggini, EWeedon, MFrayling, T 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. |
| spellingShingle | Perry, JR Ferrucci, L Bandinelli, S Guralnik, J Semba, R Rice, N Melzer, D Saxena, R Scott, L McCarthy, M Hattersley, A Zeggini, E Weedon, M Frayling, T Circulating beta-carotene levels and type 2 diabetes-cause or effect? |
| title | Circulating beta-carotene levels and type 2 diabetes-cause or effect? |
| title_full | Circulating beta-carotene levels and type 2 diabetes-cause or effect? |
| title_fullStr | Circulating beta-carotene levels and type 2 diabetes-cause or effect? |
| title_full_unstemmed | Circulating beta-carotene levels and type 2 diabetes-cause or effect? |
| title_short | Circulating beta-carotene levels and type 2 diabetes-cause or effect? |
| title_sort | circulating beta carotene levels and type 2 diabetes cause or effect |
| work_keys_str_mv | AT perryjr circulatingbetacarotenelevelsandtype2diabetescauseoreffect AT ferruccil circulatingbetacarotenelevelsandtype2diabetescauseoreffect AT bandinellis circulatingbetacarotenelevelsandtype2diabetescauseoreffect AT guralnikj circulatingbetacarotenelevelsandtype2diabetescauseoreffect AT sembar circulatingbetacarotenelevelsandtype2diabetescauseoreffect AT ricen circulatingbetacarotenelevelsandtype2diabetescauseoreffect AT melzerd circulatingbetacarotenelevelsandtype2diabetescauseoreffect AT saxenar circulatingbetacarotenelevelsandtype2diabetescauseoreffect AT scottl circulatingbetacarotenelevelsandtype2diabetescauseoreffect AT mccarthym circulatingbetacarotenelevelsandtype2diabetescauseoreffect AT hattersleya circulatingbetacarotenelevelsandtype2diabetescauseoreffect AT zegginie circulatingbetacarotenelevelsandtype2diabetescauseoreffect AT weedonm circulatingbetacarotenelevelsandtype2diabetescauseoreffect AT fraylingt circulatingbetacarotenelevelsandtype2diabetescauseoreffect |