Article Text

Association of physical activity and sedentary behavior with type 2 diabetes and glycemic traits: a two-sample Mendelian randomization study
  1. Christa Meisinger1,2,
  2. Jakob Linseisen1,2,
  3. Michael Leitzmann3,
  4. Hansjoerg Baurecht3,
  5. Sebastian Edgar Baumeister1,2
  1. 1Chair of Epidemiology at UNIKA-T Augsburg, Ludwig-Maximilians-Universitat Munchen, Munchen, Germany
  2. 2Independent Research Group Clinical Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
  3. 3Department of Epidemiology and Preventive Medicine, University of Regensburg, Regensburg, Germany
  1. Correspondence to Dr Christa Meisinger; christa.meisinger{at}helmholtz-muenchen.de

Abstract

Introduction Observational studies suggest that physical activity lowers and sedentary behavior increases the risk of type 2 diabetes. Despite of some supportive trial data for physical activity, it is largely unresolved whether these relations are causal or due to bias.

Objective We investigated the associations between accelerometer-based physical activity and sedentary behavior with type 2 diabetes and several glycemic traits using two-sample Mendelian randomization analysis.

Research design and methods Single nucleotide polymorphisms (SNPs) associated at p<5×10−8 with accelerometer-based physical activity average accelerations, vigorous physical activity (fraction of accelerations >425 milligravities), and sedentary behavior (metabolic equivalent task ≤1.5) in a genome-wide analysis of the UK Biobank served as instrumental variables.

Outcomes Type 2 diabetes, hemoglobin A1c (HbA1c), fasting glucose, homeostasis model assessment of beta-cell function (HOMA-B), and homeostasis model assessment of insulin resistance (HOMA-IR).

Results Physical activity and sedentary behavior were unrelated to type 2 diabetes, HbA1c, fasting glucose, HOMA-B, and HOMA-IR. The inverse variance weighted ORs per SD increment for the association between average accelerations and vigorous physical activity with type 2 diabetes were 1.00 (95% CI 0.94 to 1.07, p=0.948) and 0.83 (95% CI 0.56 to 1.23, p=0.357), respectively. These results were confirmed by sensitivity analyses using alternative MR-methods to test the robustness of our findings.

Conclusions Based on these results, genetically predicted objectively measured average or vigorous physical activity and sedentary behavior is not associated with type 2 diabetes risk or with glycemic traits in the general population. Further research is required to deepen the understanding of the biological pathways of physical activity.

  • diabetes mellitus
  • type 2
  • physical fitness
  • blood glucose
  • glycated hemoglobin A
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Footnotes

  • HB and SEB contributed equally.

  • Contributors CM, SEB, and HB designed the work and interpreted the data; HB conducted the analysis; CM drafted the work; all authors critically revised the work and approved the submitted version. All authors have agreed both to be personally accountable for the author’s own contributions and to ensure that questions related to the accuracy or integrity of any part of the work, even ones in which the author was not personally involved, are appropriately investigated, resolved, and the resolution documented in the literature.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Ethics approval The UK Biobank study was ethically approved by the North West Multicentre Research Ethics Committee, the National Information Governance Board for Health & Social Care, and the Community Health Index Advisory Group.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available in a public, open access repository. The present study is based on summary-level data that have been made publically available. In all original studies, ethical approval had been obtained. The summary statistics for the PA and SB GWAS is available at https://klimentidis.lab.arizona.edu/content/data and at https://doi.org/10.5287/bodleian:yJp6zZmdj. The summary data for the type 2 diabetes GWAS is available at http://diagram-consortium.org/downloads.html, for the HbA1c, fasting glucose, HOMA-B and HOMA-IR GWASs at www.magicinvestigators.org/downloads.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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