Type 2 Diabetes as a Determinant of Parkinson's Disease Risk and Progression

Abstract

A BS TRACT: 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.

The Parkinson’s Real-World Impact Assessment (PRISM) Study: A European Survey of the Burden of Parkinson’s Disease in Patients and their Carers

“…The relatively low rate in PRISM might have been due to under-reporting among participants with well-controlled blood pressure. Previous evidence of a potential association between Type 2 diabetes and PD [24] was not supported by the current study.…”

L-dopa-Dependent Effects of GLP-1R Agonists on the Survival of Dopaminergic Cells Transplanted into a Rat Model of Parkinson Disease

“…This indicates that insulin resistance causes changes in the micro-environment of the host striatum that could lead to effects on graft survival. Another study showed that the nigral dopaminergic neurons are more vulnerable to degeneration when exposed to the toxin MPTP in a mouse model of type 2 diabetes mellitus [53,54] consistent with many clinical studies suggesting aggravation of PD with existing comorbidity of diabetes [55][56][57]. The elevation of microglial density around the graft of the exendin-4 group/ + LD compared to exendin-4/-LD lends credence to this hypothesis, and accumulation of activated microglia around the graft has been shown to limit graft survival and function [7,58,59].…”

Diabetic retinopathy as a potential marker of Parkinson’s disease: a register-based cohort study

“… 13 , 33 Some studies agree that diabetes is a risk factor for Parkinson’s disease while other studies find no evidence of this association. 34–38 A meta-analysis from 2021 by Chohan et al 38 observed evidence for type 2 diabetes being positively associated with an increased risk of Parkinson’s disease. Nevertheless, we did not find this association in our analysis when investigating the effect of diabetes of all kinds or type 2 diabetes specifically.…”