Department of Endocrinology, Sun Yat-Sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
Guangdong Clinical Research Center for Metabolic Diseases, Guangzhou key laboratory for Metabolic Diseases, Guangzhou, China.
Eur J Clin Invest. 2023 Mar;53(3):e13893. doi: 10.1111/eci.13893. Epub 2022 Nov 8.
Extensive observational evidence put forward the association between psychiatric disorders and type 2 diabetes mellitus (T2DM). However, causal relationships between these two diseases required further research. Thus, we evaluated the bidirection casual effect between five psychiatric disorders and T2DM using two-sample mendelian randomization (MR).
By selecting single nucleotide polymorphisms associated with T2DM and five psychiatric disorders (attention-deficit hyperactivity disorder (ADHD), major depressive disorder (MDD), schizophrenia, anxiety disorder and panic disorder), a bidirectional two-sample MR was applied to evaluate causality between these diseases. The inverse-variance weighted (IVW) method was used as the primary analysing approach for estimating possible causal effects. MR-Egger and weighted median were also conducted to verify the results. The funnel plot, Cochran's Q test and MR-Egger intercept test were used for sensitivity analyses. In addition, potential mediators were investigated by risk factor analyses.
Genetic susceptibilities of ADHD and MDD would increase the risk of T2DM (ADHD: OR = 1.14, 95%CI 1.08-1.20; ; MDD: OR = 1.22, 95%CI 1.09-1.36; ). In addition, genetic predisposition to T2DM was also associated with ADHD (OR = 1.09, 95%CI 1.04-1.14; p = 0.0004). Several risk factors of T2DM were implicated in the above causal associations, including smoking, high body mass index, waist-to-hip ratio and elevated serum triglycerides.
Our studies indicated a causal effect of ADHD and MDD on increasing the risk of T2DM, which was potentially mediated by smoking and obesity-related phenotypes. Meanwhile, we found a causal effect of T2DM on ADHD. Thus, prevention strategies for T2DM should also include mental health and vice versa.
大量观察性证据表明，精神障碍与 2 型糖尿病（T2DM）之间存在关联。然而，这两种疾病之间的因果关系需要进一步研究。因此，我们使用两样本孟德尔随机化（MR）评估了五种精神障碍与 T2DM 之间的双向因果关系。
通过选择与 T2DM 和五种精神障碍（注意力缺陷多动障碍（ADHD）、重度抑郁症（MDD）、精神分裂症、焦虑症和恐慌症）相关的单核苷酸多态性，我们进行了双向两样本 MR，以评估这些疾病之间的因果关系。逆方差加权（IVW）法被用作估计可能的因果效应的主要分析方法。MR-Egger 和加权中位数也被用来验证结果。漏斗图、Cochran's Q 检验和 MR-Egger 截距检验用于敏感性分析。此外，通过风险因素分析研究了潜在的中介因素。
ADHD 和 MDD 的遗传易感性会增加 T2DM 的风险（ADHD：OR=1.14，95%CI 1.08-1.20； ；MDD：OR=1.22，95%CI 1.09-1.36； ）。此外，T2DM 的遗传易感性也与 ADHD 相关（OR=1.09，95%CI 1.04-1.14；p=0.0004）。T2DM 的几种风险因素包括吸烟、高体重指数、腰臀比和血清甘油三酯升高，与上述因果关系有关。
我们的研究表明，ADHD 和 MDD 对增加 T2DM 的风险有因果影响，这可能是通过吸烟和肥胖相关表型介导的。同时，我们发现 T2DM 对 ADHD 有因果影响。因此，T2DM 的预防策略也应该包括心理健康，反之亦然。
