Chohan Harneek, Senkevich Konstantin, Patel Radhika K, Bestwick Jonathan P, Jacobs Benjamin M, Bandres Ciga Sara, Gan-Or Ziv, Noyce Alastair J
Preventive Neurology Unit, Wolfson Institute of Preventive Medicine, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
Department of Neurology and Neurosurgery, McGill University, Montréal, Quebec, Canada.
Mov Disord. 2021 Jun;36(6):1420-1429. doi: 10.1002/mds.28551. Epub 2021 Mar 8.
Type 2 diabetes (T2DM) and Parkinson's disease (PD) are prevalent diseases that affect an aging population. Previous systematic reviews and meta-analyses have explored the relationship between diabetes and the risk of PD, but the results have been conflicting.
The objective was to investigate T2DM as a determinant of PD through a meta-analysis of observational and genetic summary data.
A systematic review and meta-analysis of observational studies was undertaken by searching 6 databases. We selected the highest-quality studies investigating the association of T2DM with PD risk and progression. We then used Mendelian randomization (MR) to investigate the causal effects of genetic liability toward T2DM on PD risk and progression, using summary data derived from genome-wide association studies.
In the observational part of the study, pooled effect estimates showed that T2DM was associated with an increased risk of PD (odds ratio [OR] 1.21, 95% confidence interval [CI] 1.07-1.36), and there was some evidence that T2DM was associated with faster progression of motor symptoms (standardized mean difference [SMD] 0.55, 95% CI 0.39-0.72) and cognitive decline (SMD -0.92, 95% CI -1.50 to -0.34). Using MR, we found supportive evidence for a causal effect of diabetes on PD risk (inverse-variance weighted method [IVW] OR 1.08, 95% CI 1.02-1.14; P = 0.010) and some evidence of an effect on motor progression (IVW OR 1.10, 95% CI 1.01-1.20; P = 0.032) but not on cognitive progression.
Using meta-analyses of traditional observational studies and genetic data, we observed convincing evidence for an effect of T2DM on PD risk and new evidence to support a role in PD progression. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
2型糖尿病（T2DM）和帕金森病（PD）是影响老年人群的常见疾病。以往的系统评价和荟萃分析探讨了糖尿病与PD风险之间的关系，但结果相互矛盾。
通过对观察性和基因汇总数据进行荟萃分析，研究T2DM作为PD的一个决定因素。
通过检索6个数据库，对观察性研究进行系统评价和荟萃分析。我们选择了研究T2DM与PD风险及进展相关性的质量最高的研究。然后，我们使用孟德尔随机化（MR）方法，利用全基因组关联研究得出的汇总数据，研究T2DM遗传易感性对PD风险及进展的因果效应。
在研究的观察性部分，汇总效应估计显示T2DM与PD风险增加相关（优势比[OR]1.21，95%置信区间[CI]1.07-1.36），并且有一些证据表明T2DM与运动症状进展更快相关（标准化均数差[SMD]0.55，95%CI 0.39-0.72）以及认知功能下降相关（SMD -0.92，95%CI -1.50至-0.34）。使用MR方法，我们发现糖尿病对PD风险有因果效应的支持性证据（逆方差加权法[IVW]OR 1.08，95%CI 1.02-1.14；P = 0.010）以及对运动进展有影响的一些证据（IVW OR 1.10，95%CI 1.01-1.20；P = 0.032），但对认知进展没有影响。
通过对传统观察性研究和基因数据进行荟萃分析，我们观察到T2DM对PD风险有影响的令人信服的证据，以及支持其在PD进展中起作用的新证据。© 2021作者。《运动障碍》由Wiley Periodicals LLC代表国际帕金森和运动障碍协会出版。
