Yuan Shuai, Li Xue, Liu Qianwen, Wang Zhe, Jiang Xia, Burgess Stephen, Larsson Susanna C
Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, 17165, Sweden.
School of Public Health and the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310000, China.
J Endocr Soc. 2023 Jun 26;7(8):bvad090. doi: 10.1210/jendso/bvad090. eCollection 2023 Jul 3.
The causality and pathways of the associations between physical activity and inactivity and the risk of type 2 diabetes remain inconclusive.
We conducted an updated mendelian randomization (MR) study to explore the associations of moderate-to-vigorous physical activity (MVPA) and leisure screen time (LST) with type 2 diabetes mellitus (T2DM).
Genetic variants strongly associated with MVPA or LST with low linkage disequilibrium were selected as instrumental variables from a genome-wide meta-analysis including more than 600 000 individuals. Summary-level data on T2DM were obtained from the DIAbetes Genetics Replication And Meta-analysis consortium including 898 130 individuals. Data on possible intermediates (adiposity indicators, lean mass, glycemic traits, and inflammatory biomarkers) were extracted from large-scale genome-wide association studies (n = 21 758-681 275). Univariable and multivariable MR analyses were performed to estimate the total and direct effects of MVPA and LST on T2DM. Methylation MR analysis was performed for MVPA in relation to diabetes.
The odds ratio of T2DM was 0.70 (95% CI, 0.55-0.88; = .002) per unit increase in the log-odds ratio of having MVPA and 1.45 (95% CI, 1.30-1.62; = 7.62 × 10) per SD increase in genetically predicted LST. These associations attenuated in multivariable MR analyses adjusted for genetically predicted waist-to-hip ratio, body mass index, lean mass, and circulating C-reactive protein. The association between genetically predicted MVPA and T2DM attenuated after adjusting for genetically predicted fasting insulin levels. Two physical activity-related methylation biomarkers (cg17332422 in and cg09531019) were associated with the risk of T2DM ( < .05).
The study suggests causal associations of MVPA and LST with T2DM that appear to be mediated by obesity, lean mass, and chronic low-grade inflammation.
体力活动与缺乏体力活动和2型糖尿病风险之间关联的因果关系及途径仍不明确。
我们进行了一项更新的孟德尔随机化（MR）研究，以探讨中度至剧烈体力活动（MVPA）和休闲屏幕时间（LST）与2型糖尿病（T2DM）之间的关联。
从一项纳入超过600000人的全基因组荟萃分析中，选择与MVPA或LST强烈相关且连锁不平衡较低的基因变异作为工具变量。T2DM的汇总数据来自糖尿病遗传学复制与荟萃分析联盟，包括898130人。从大规模全基因组关联研究（n = 21758 - 681275）中提取可能的中间变量（肥胖指标、瘦体重、血糖特征和炎症生物标志物）的数据。进行单变量和多变量MR分析，以估计MVPA和LST对T2DM的总体和直接影响。对MVPA与糖尿病进行甲基化MR分析。
每单位MVPA对数优势比增加，T2DM的优势比为0.70（95%CI，0.55 - 0.88；P = 0.002），遗传预测的LST每增加1个标准差，优势比为1.45（95%CI，1.30 - 1.62；P = 7.62×10）。在对遗传预测的腰臀比、体重指数、瘦体重和循环C反应蛋白进行调整的多变量MR分析中，这些关联减弱。在对遗传预测的空腹胰岛素水平进行调整后，遗传预测的MVPA与T2DM之间的关联减弱。两个与体力活动相关的甲基化生物标志物（EN1中的cg17332422和cg09531019）与T2DM风险相关（P < 0.05）。
该研究表明MVPA和LST与T2DM之间存在因果关联，这些关联似乎由肥胖、瘦体重和慢性低度炎症介导。
