Peking University Sixth Hospital/Institute of Mental Health, Beijing, China.
NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing, China.
Epidemiol Psychiatr Sci. 2023 May 11;32:e32. doi: 10.1017/S2045796023000173.
Previous observational studies have reported potential associations among attention-deficit/hyperactivity disorder (ADHD), obesity, and diabetes (including type 1 and type 2 diabetes mellitus [T1DM/T2DM]). However, whether the association between ADHD and diabetes is mediated by obesity is unknown.
With two-sample Mendelian randomization, we analysed the causal effect of ADHD on T1DM and T2DM and six obesity-related traits [including body mass index, waist circumference (WC), hip circumference, waist-to-hip ratio (WHR), body fat percentage and basal metabolic rate] and the causal effect of these obesity-related traits on T1DM/T2DM. Finally, with multivariable Mendelian randomization, we explored and quantified the possible mediation effects of obesity-related traits on the causal effect of ADHD on T1DM/T2DM.
Our results showed that ADHD increased the risk of T2DM by 14% [odds ratio (OR) = 1.140, 95% confidence interval (CI) = 1.005-1.293] but with no evidence of an effect on T1DM (OR = 0.916, 95% CI = 0.735-1.141, = 0.433.). In addition, ADHD had a 6.1% increased causal effect on high WC (OR = 1.061, 95% CI = 1.024-1.099, = 0.001) and an 8.2% increased causal effect on high WHR (OR = 1.082, 95% CI = 1.035-1.131, = 0.001). In addition, a causal effect of genetically predicted high WC (OR = 1.870, 95% CI = 1.594-2.192, < 0.001) on a higher risk of T2DM was found. In further analysis, WC mediated approximately 26.75% (95% CI = 24.20%-29.30%) of the causal association between ADHD and T2DM.
WC mediates a substantial proportion of the causal effect of ADHD on the risk of T2DM, which indicated that the risk of T2DM induced by ADHD could be indirectly reduced by controlling WC as a main risk factor.
先前的观察性研究报告了注意力缺陷多动障碍（ADHD）、肥胖症和糖尿病（包括 1 型和 2 型糖尿病）之间存在潜在关联。然而，ADHD 与糖尿病之间的关联是否由肥胖症介导尚不清楚。
我们采用两样本 Mendelian 随机化分析，研究了 ADHD 对 1 型糖尿病和 2 型糖尿病以及六个肥胖相关特征（包括体重指数、腰围[WC]、臀围、腰臀比[WHR]、体脂肪百分比和基础代谢率）的因果效应，以及这些肥胖相关特征对 1 型糖尿病/2 型糖尿病的因果效应。最后，我们采用多变量 Mendelian 随机化，探讨和量化了肥胖相关特征对 ADHD 对 1 型糖尿病/2 型糖尿病的因果效应的可能中介作用。
我们的研究结果表明，ADHD 使 2 型糖尿病的发病风险增加了 14%（比值比[OR] = 1.140，95%置信区间[CI] = 1.005-1.293），但对 1 型糖尿病没有影响（OR = 0.916，95%CI = 0.735-1.141，= 0.433）。此外，ADHD 对高 WC 的因果效应增加了 6.1%（OR = 1.061，95%CI = 1.024-1.099，= 0.001），对高 WHR 的因果效应增加了 8.2%（OR = 1.082，95%CI = 1.035-1.131，= 0.001）。此外，还发现遗传预测的高 WC（OR = 1.870，95%CI = 1.594-2.192，<0.001）与 2 型糖尿病风险增加之间存在因果关系。在进一步的分析中，WC 介导了 ADHD 与 2 型糖尿病之间因果关联的约 26.75%（95%CI = 24.20%-29.30%）。
WC 介导了 ADHD 对 2 型糖尿病风险的因果效应的很大一部分，这表明通过控制 WC 作为主要危险因素，可以间接降低 ADHD 引起的 2 型糖尿病风险。
