Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland.
Am J Clin Nutr. 2019 Nov 1;110(5):1079-1087. doi: 10.1093/ajcn/nqz187.
Mendelian randomization studies in adults suggest that abdominal adiposity is causally associated with increased risk of type 2 diabetes and coronary artery disease in adults, but its causal effect on cardiometabolic risk in children remains unclear.
We aimed to study the causal relation of abdominal adiposity with cardiometabolic risk factors in children by applying Mendelian randomization.
We constructed a genetic risk score (GRS) using variants previously associated with waist-to-hip ratio adjusted for BMI (WHRadjBMI) and examined its associations with cardiometabolic factors by linear regression and Mendelian randomization in a meta-analysis of 6 cohorts, including 9895 European children and adolescents aged 3-17 y.
WHRadjBMI GRS was associated with higher WHRadjBMI (β = 0.021 SD/allele; 95% CI: 0.016, 0.026 SD/allele; P = 3 × 10-15) and with unfavorable concentrations of blood lipids (higher LDL cholesterol: β = 0.006 SD/allele; 95% CI: 0.001, 0.011 SD/allele; P = 0.025; lower HDL cholesterol: β = -0.007 SD/allele; 95% CI: -0.012, -0.002 SD/allele; P = 0.009; higher triglycerides: β = 0.007 SD/allele; 95% CI: 0.002, 0.012 SD/allele; P = 0.006). No differences were detected between prepubertal and pubertal/postpubertal children. The WHRadjBMI GRS had a stronger association with fasting insulin in children and adolescents with overweight/obesity (β = 0.016 SD/allele; 95% CI: 0.001, 0.032 SD/allele; P = 0.037) than in those with normal weight (β = -0.002 SD/allele; 95% CI: -0.010, 0.006 SD/allele; P = 0.605) (P for difference = 0.034). In a 2-stage least-squares regression analysis, each genetically instrumented 1-SD increase in WHRadjBMI increased circulating triglycerides by 0.17 mmol/L (0.35 SD, P = 0.040), suggesting that the relation between abdominal adiposity and circulating triglycerides may be causal.
Abdominal adiposity may have a causal, unfavorable effect on plasma triglycerides and potentially other cardiometabolic risk factors starting in childhood. The results highlight the importance of early weight management through healthy dietary habits and physically active lifestyle among children with a tendency for abdominal adiposity.
成人孟德尔随机化研究表明，腹部肥胖与成人 2 型糖尿病和冠心病风险增加有关，但它对儿童心脏代谢风险的因果影响仍不清楚。
我们旨在通过孟德尔随机化研究腹部肥胖与儿童心脏代谢风险因素的因果关系。
我们使用先前与 BMI 调整后的腰臀比（WHRadjBMI）相关的变异构建了遗传风险评分（GRS），并在包括 9895 名 3-17 岁欧洲儿童和青少年的 6 个队列的荟萃分析中，通过线性回归和孟德尔随机化来检验其与心脏代谢因素的关联。
WHRadjBMI GRS 与较高的 WHRadjBMI（β=0.021 SD/等位基因；95%CI：0.016，0.026 SD/等位基因；P=3×10-15）和不利的血脂浓度相关（较高的 LDL 胆固醇：β=0.006 SD/等位基因；95%CI：0.001，0.011 SD/等位基因；P=0.025；较低的 HDL 胆固醇：β=-0.007 SD/等位基因；95%CI：-0.012，-0.002 SD/等位基因；P=0.009；较高的甘油三酯：β=0.007 SD/等位基因；95%CI：0.002，0.012 SD/等位基因；P=0.006）。在青春期前和青春期/青春期后儿童中未检测到差异。在超重/肥胖的儿童和青少年中，WHRadjBMI GRS 与空腹胰岛素的相关性更强（β=0.016 SD/等位基因；95%CI：0.001，0.032 SD/等位基因；P=0.037），而不是正常体重的儿童和青少年（β=-0.002 SD/等位基因；95%CI：-0.010，0.006 SD/等位基因；P=0.605）（P 差异=0.034）。在 2 阶段最小二乘法回归分析中，WHRadjBMI 每增加 1 个 SD，循环中的甘油三酯增加 0.17 mmol/L（0.35 SD，P=0.040），这表明腹部肥胖与循环中的甘油三酯之间的关系可能是因果关系。
腹部肥胖可能对儿童时期的血浆甘油三酯和潜在的其他心脏代谢风险因素产生不利的因果影响。结果强调了在有腹部肥胖倾向的儿童中通过健康饮食和积极的生活方式进行早期体重管理的重要性。
