School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 7 Sassoon Road, Pokfulam, Hong Kong SAR, China.
Graduate School of Public Health and Health Policy, City University of New York, New York, USA.
Diabetologia. 2019 May;62(5):789-799. doi: 10.1007/s00125-019-4826-0. Epub 2019 Feb 23.
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.
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, HbA, 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.
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.
目的/假设：肌肉质量和力量可能有助于葡萄糖的消耗，从而预防 2 型糖尿病。在随机对照试验中，抗阻训练改善了代谢综合征患者的葡萄糖代谢。但是，增加肌肉质量和力量是否能预防普通人群的糖尿病尚不清楚。我们使用双向孟德尔随机化来评估肌肉质量和力量标志物对糖尿病和血糖特征的影响。
通过应用来自英国生物库 GWAS 的预测男性瘦体重、女性瘦体重和握力的遗传变异，对最大的糖尿病病例对照研究（DIAbetes Genetics Replication And Meta-analysis [DIAGRAM]；n=74124 例病例和 824006 例对照）和血糖特征研究（Meta-Analyses of Glucose and Insulin-related traits Consortium [MAGIC]）进行逆方差加权估计。相反，我们还应用了预测糖尿病、HbA、空腹血糖、空腹胰岛素和 HOMA-B 的遗传变异，以评估它们与瘦体重和握力的遗传关联。作为敏感性分析，我们使用加权中位数、孟德尔随机化（MR）-Egger 和 Mendelian Randomization Pleiotropy RESidual Sum and Outlier （MR-PRESSO），并去除了多效性 SNP。
握力与糖尿病的相关性在逆方差加权（握力每增加 1 SD，OR 0.72，95%CI 0.51, 1.01，p=0.06）和包括多效性 SNP 时不显著，但在去除多效性 SNP 后使用 MR-PRESSO 时显著相关（OR 0.77，95%CI 0.62, 0.95，p=0.02）。女性瘦体重与糖尿病显著相关（OR 0.91，95%CI 0.84, 0.99，p=0.02），而男性瘦体重不显著，但方向相似（OR 0.94，95%CI 0.88, 1.01，p=0.09）。相反，糖尿病与男性瘦体重（β-0.02 SD 瘦体重变化，95%CI -0.04，-0.00，p=0.04）和握力（β-0.01，95%CI -0.02，-0.00，p=0.01）呈负相关且显著。
结论/解释：增加肌肉质量和力量可能与降低糖尿病风险有关。糖尿病也可能与握力和瘦体重有关。肌肉力量可能值得进一步研究，作为预防糖尿病的潜在干预靶点。
