Abstract
Background: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.Objective:The objective was to investigate T2DM as a determinant of PD through a meta-analysis of observational and genetic summary data.Methods: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.Results: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.Conclusions: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.
Highlights
Type 2 diabetes (T2DM) and Parkinson’s disease (PD) are prevalent diseases that affect an aging population
Pooled effect estimates from case–control studies suggest that diabetes has a negative association with PD risk,[4,5,6] whereas meta-analyses that focus on prospective cohort studies suggest an increased risk of PD in patients with diabetes.[5,7]
Cohort studies provided strong evidence for T2DM being associated with higher PD risk, but there was an inverse association between T2DM and PD in case–control studies
Summary
Type 2 diabetes (T2DM) and Parkinson’s disease (PD) are prevalent diseases that affect an aging population. Emerging evidence suggests biological relationships between the two. Both are characterized by aberrant protein accumulation, lysosomal and mitochondrial dysfunction, and chronic systemic inflammation.[1,2] Insulin resistance is a hallmark of T2DM and may be an important contributing factor to PD too.[3]. The association between T2DM and risk of PD has not been explored thoroughly using modern causal methods. Mendelian randomization (MR) is a method in genetic epidemiology that can be used to follow up observational associations for evidence of true causal effects.[8] Genetic variants are distributed randomly at birth; the genetic determinants of an exposure (here T2DM) are not affected by the presence of the outcome (here PD). The current study combines the meta-analysis of observational data with that of genetic data (MR) to evaluate the effect T2DM has on the risk of developing PD and on motor and cognitive progression in patients with PD
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