ObjectiveTo investigate type 2 diabetes mellitus (T2DM) as a determinant of Parkinson’s disease (PD) through a meta-analysis of observational and genetic summary data.MethodsA systematic review and meta-analysis of observational studies was undertaken by searching six 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 causal effects of genetic liability towards T2DM on PD risk and progression, using summary data derived from genome-wide association studies.ResultsIn the observational part of the study, nine studies were included in the risk meta-analysis and four studies were included in the progression meta-analysis. Pooled effect estimates revealed that T2DM was associated with an increased risk of PD (OR 1.21, 95% CI 1.07-1.36), and there was some evidence that T2DM was associated with faster progression of motor symptoms (SMD 0.55, 95% CI 0.39-0.72) and cognitive decline (SMD −0.92, 95% CI −1.50 – −0.34). Using MR we found supportive evidence for a causal effect of diabetes on PD risk (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 for cognitive progression.ConclusionUsing meta-analysis 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. Treatment of diabetes may be an effective strategy to prevent or slow progression of PD.
