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- Publisher Website: 10.1007/s00125-020-05243-z
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- PMID: 32748028
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Article: Evaluating the impact of AMPK activation, a target of metformin, on risk of cardiovascular diseases and cancer in the UK Biobank: a Mendelian randomisation study
Title | Evaluating the impact of AMPK activation, a target of metformin, on risk of cardiovascular diseases and cancer in the UK Biobank: a Mendelian randomisation study |
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Authors | |
Keywords | AMPK Cancer Coronary artery disease Mendelian randomisation Metformin |
Issue Date | 2020 |
Publisher | Springer Verlag. The Journal's web site is located at http://link.springer.de/link/service/journals/00125/index.htm |
Citation | Diabetologia, 2020, v. 63 n. 11, p. 2349-2358 How to Cite? |
Abstract | Aims/hypothesis: Whether metformin reduces cardiovascular or cancer risk is unclear owing to concerns over immortal time bias and confounding in observational studies. This study evaluated the effect of AMP-activated protein kinase (AMPK), the target of metformin, on risk of cardiovascular disease and cancer.
Methods: This is a Mendelian randomisation design, using AMPK, the pharmacological target of metformin, to infer the AMPK pathway-dependent effects of metformin on risk of cardiovascular disease and cancer in participants of white British ancestry in the UK Biobank.
Results: A total of 391,199 participants were included (mean age 56.9 years; 54.1% women), including 26,690 cases of type 2 diabetes, 38,098 cases of coronary artery disease and 80,941 cases of overall cancer. Genetically predicted reduction in HbA1c (%) instrumented by AMPK variants was associated with a 61% reduction in risk of type 2 diabetes (OR 0.39; 95% CI 0.20, 0.78; p = 7.69 × 10−3), a 53% decrease in the risk of coronary artery disease (OR 0.47; 95% CI 0.26, 0.84; p = 0.01) and a 44% decrease in the risk of overall cancer (OR 0.56; 95% CI 0.36, 0.85; p = 7.23 × 10−3). Results were similar using median or quartiles of AMPK score, with dose–response effects (p for trend = 4.18 × 10−3 for type 2 diabetes, 4.37 × 10−3 for coronary artery disease and 4.04 × 10−3 for overall cancer).
Conclusions/interpretation: This study provides some genetic evidence that AMPK activation by metformin may protect against cardiovascular disease and cancer, which needs to be confirmed by randomised controlled trials. |
Persistent Identifier | http://hdl.handle.net/10722/289531 |
ISSN | 2023 Impact Factor: 8.4 2023 SCImago Journal Rankings: 3.355 |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Luo, S | - |
dc.contributor.author | Schooling, CM | - |
dc.contributor.author | Wong, ICK | - |
dc.contributor.author | Au Yeung, SLR | - |
dc.date.accessioned | 2020-10-22T08:13:57Z | - |
dc.date.available | 2020-10-22T08:13:57Z | - |
dc.date.issued | 2020 | - |
dc.identifier.citation | Diabetologia, 2020, v. 63 n. 11, p. 2349-2358 | - |
dc.identifier.issn | 0012-186X | - |
dc.identifier.uri | http://hdl.handle.net/10722/289531 | - |
dc.description.abstract | Aims/hypothesis: Whether metformin reduces cardiovascular or cancer risk is unclear owing to concerns over immortal time bias and confounding in observational studies. This study evaluated the effect of AMP-activated protein kinase (AMPK), the target of metformin, on risk of cardiovascular disease and cancer. Methods: This is a Mendelian randomisation design, using AMPK, the pharmacological target of metformin, to infer the AMPK pathway-dependent effects of metformin on risk of cardiovascular disease and cancer in participants of white British ancestry in the UK Biobank. Results: A total of 391,199 participants were included (mean age 56.9 years; 54.1% women), including 26,690 cases of type 2 diabetes, 38,098 cases of coronary artery disease and 80,941 cases of overall cancer. Genetically predicted reduction in HbA1c (%) instrumented by AMPK variants was associated with a 61% reduction in risk of type 2 diabetes (OR 0.39; 95% CI 0.20, 0.78; p = 7.69 × 10−3), a 53% decrease in the risk of coronary artery disease (OR 0.47; 95% CI 0.26, 0.84; p = 0.01) and a 44% decrease in the risk of overall cancer (OR 0.56; 95% CI 0.36, 0.85; p = 7.23 × 10−3). Results were similar using median or quartiles of AMPK score, with dose–response effects (p for trend = 4.18 × 10−3 for type 2 diabetes, 4.37 × 10−3 for coronary artery disease and 4.04 × 10−3 for overall cancer). Conclusions/interpretation: This study provides some genetic evidence that AMPK activation by metformin may protect against cardiovascular disease and cancer, which needs to be confirmed by randomised controlled trials. | - |
dc.language | eng | - |
dc.publisher | Springer Verlag. The Journal's web site is located at http://link.springer.de/link/service/journals/00125/index.htm | - |
dc.relation.ispartof | Diabetologia | - |
dc.rights | This is a post-peer-review, pre-copyedit version of an article published in Diabetologia. The final authenticated version is available online at: https://doi.org/10.1007/s00125-020-05243-z | - |
dc.subject | AMPK | - |
dc.subject | Cancer | - |
dc.subject | Coronary artery disease | - |
dc.subject | Mendelian randomisation | - |
dc.subject | Metformin | - |
dc.title | Evaluating the impact of AMPK activation, a target of metformin, on risk of cardiovascular diseases and cancer in the UK Biobank: a Mendelian randomisation study | - |
dc.type | Article | - |
dc.identifier.email | Schooling, CM: cms1@hkucc.hku.hk | - |
dc.identifier.email | Wong, ICK: wongick@hku.hk | - |
dc.identifier.email | Au Yeung, SLR: ayslryan@hku.hk | - |
dc.identifier.authority | Schooling, CM=rp00504 | - |
dc.identifier.authority | Wong, ICK=rp01480 | - |
dc.identifier.authority | Au Yeung, SLR=rp02224 | - |
dc.description.nature | postprint | - |
dc.identifier.doi | 10.1007/s00125-020-05243-z | - |
dc.identifier.pmid | 32748028 | - |
dc.identifier.scopus | eid_2-s2.0-85088873956 | - |
dc.identifier.hkuros | 316616 | - |
dc.identifier.volume | 63 | - |
dc.identifier.issue | 11 | - |
dc.identifier.spage | 2349 | - |
dc.identifier.epage | 2358 | - |
dc.identifier.isi | WOS:000555362500001 | - |
dc.publisher.place | Germany | - |
dc.identifier.issnl | 0012-186X | - |