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Diabetologia

, Volume 62, Issue 5, pp 789–799 | Cite as

Lean mass, grip strength and risk of type 2 diabetes: a bi-directional Mendelian randomisation study

  • Chris Ho Ching Yeung
  • Shiu Lun Au Yeung
  • Shirley Siu Ming Fong
  • C. Mary SchoolingEmail author
Article

Abstract

Aims/hypothesis

Muscle mass and strength may protect against type 2 diabetes as a sink for glucose disposal. In randomised controlled trials, resistance training improves glucose metabolism in people with the metabolic syndrome. Whether increasing muscle mass and strength protects against diabetes in the general population is unknown. We assessed the effect of markers of muscle mass and strength on diabetes and glycaemic traits using bi-directional Mendelian randomisation.

Methods

Inverse variance weighting estimates were obtained by applying genetic variants that predict male lean mass, female lean mass and grip strength, obtained from the UK Biobank GWAS, to the largest available case–control study of diabetes (DIAbetes Genetics Replication And Meta-analysis [DIAGRAM]; n = 74,124 cases and 824,006 controls) and to a study of glycaemic traits (Meta-Analyses of Glucose and Insulin-related traits Consortium [MAGIC]). Conversely, we also applied genetic variants that predict diabetes, HbA1c, fasting glucose, fasting insulin and HOMA-B to UK Biobank summary statistics for genetic association with lean mass and grip strength. As sensitivity analyses we used weighted median, Mendelian randomisation (MR)-Egger and Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO) and removed pleiotropic SNPs.

Results

Grip strength was not significantly associated with diabetes using inverse variance weighting (OR 0.72 per SD increase in grip strength, 95% CI 0.51, 1.01, p = 0.06) and including pleiotropic SNPs but was significantly associated with diabetes using MR-PRESSO (OR 0.77, 95% CI 0.62, 0.95, p = 0.02) after removing pleiotropic SNPs. Female lean mass was significantly associated with diabetes (OR 0.91, 95% CI 0.84, 0.99, p = 0.02) while male lean mass was not significant but directionally similar (OR 0.94, 95% CI 0.88, 1.01, p = 0.09). Conversely, diabetes was inversely and significantly associated with male lean mass (β −0.02 SD change in lean mass, 95% CI −0.04, −0.00, p = 0.04) and grip strength (β −0.01, 95% CI −0.02, −0.00, p = 0.01).

Conclusions/interpretation

Increased muscle mass and strength may be related to lower diabetes risk. Diabetes may also be associated with grip strength and lean mass. Muscle strength could warrant further investigation as a possible target of intervention for diabetes prevention.

Keywords

Body composition Diabetes mellitus Grip strength Hand strength Lean mass Mendelian randomisation Muscle Type 2 diabetes 

Abbreviations

DIAGRAM

DIAbetes Genetics Replication And Meta-analysis

GWAS

Genome-wide association study

InSIDE

Instrument Strength Independent of Direct Effect

MAGIC

Meta-Analyses of Glucose and Insulin-related traits Consortium

MR-Egger

Mendelian randomisation-Egger

MR-PRESSO

Mendelian Randomization Pleiotropy RESidual Sum and Outlier

Notes

Acknowledgements

Data on diabetes have been contributed by DIAGRAM investigators and have been downloaded from http://www.diagram-consortium.org. Data on glycaemic traits have been contributed by MAGIC investigators and have been downloaded from www.magicinvestigators.org.

Contribution statement

CHCY conducted the literature review and the analysis and drafted the manuscript. SLAY, CMS and SSMF conceptualised ideas and designed the study. SLAY and CMS directed the analytical strategy and supervised the study from conception to completion. SLAY, CMS and SSMF revised drafts of the manuscript. All the authors contributed to the interpretation of the data, critically revising the paper and approval of the final version. CHCY is the guarantor of this work.

Funding

This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.

Duality of interest

The authors declare that there is no duality of interest associated with this manuscript.

Supplementary material

125_2019_4826_MOESM1_ESM.pdf (2.9 mb)
ESM (PDF 2932 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Chris Ho Ching Yeung
    • 1
  • Shiu Lun Au Yeung
    • 1
  • Shirley Siu Ming Fong
    • 1
  • C. Mary Schooling
    • 1
    • 2
    Email author
  1. 1.School of Public Health, Li Ka Shing Faculty of MedicineThe University of Hong KongHong Kong SARChina
  2. 2.Graduate School of Public Health and Health PolicyCity University of New YorkNew YorkUSA

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