Diabetes mellitus and Parkinson's disease: dangerous liaisons between insulin and dopamine.
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ABSTRACT:
SUBMITTER: De Iuliis A
PROVIDER: S-EPMC8504381 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundPrevious studies showed inconsistent results regarding associations between diabetes mellitus (DM) and risk of Parkinson's disease (PD). The study aimed to make a meta-analysis to clarify whether DM is a risk factor for PD.MethodsWe searched for articles regarding the effect of DM on risk of PD and published before July 2020 with search terms as follows: ("diabetes mellitus" OR "diabetes") AND ("Parkinson's disease" OR "PD") in the following databases: PubMed, Web of Science, MEDLINE, EMBASE, and Google Scholar. We used STATA 12.0 software to compute multivariate odds ratio (OR) or relative risk (RR) and 95% confidence intervals (CI) regarding the association between DM and risk of PD.ResultsThe present study finally included 7 case-control studies (including 26,654 PD patients) and 9 cohort studies (including 3,819,006 DM patients) exploring the association between DM and risk of PD. The meta-analysis indicated that DM was related to elevated risk of PD (OR/RR = 1.15, 95% CI 1.03-1.28, I2 = 92.4%, p < .001). Subgroup study showed that DM was associated with higher risk of PD in cohort studies (RR = 1.29, 95% CI 1.15-1.45, I2 = 93.9%, p < .001), whereas no significant association was indicated between DM and risk of PD in case-control studies (OR = 0.74, 95% CI 0.51-1.09, I2 = 82.3%, p < .001). Sensitivity analysis showed no changes in the direction of effect when any one study was excluded from all meta-analyses. In addition, Begg's test, Egger's test, and funnel plot showed no significant risks of publication bias.ConclusionIn conclusion, we have tried to determine whether prior onset of DM may contribute to the risk of developing PD. More and more large-scale prospective studies should be conducted to evaluate the relationship between DM and PD.
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Project description:Diabetes mellitus (DM) and Parkinson's disease (PD) are both age-related diseases of global concern being among the most common chronic metabolic and neurodegenerative diseases, respectively. While both diseases can be genetically inherited, environmental factors play a vital role in their pathogenesis. Moreover, DM and PD have common underlying molecular mechanisms, such as misfolded protein aggregation, mitochondrial dysfunction, oxidative stress, chronic inflammation, and microbial dysbiosis. Recently, epidemiological and experimental studies have reported that DM affects the incidence and progression of PD. Moreover, certain antidiabetic drugs have been proven to decrease the risk of PD and delay its progression. In this review, we elucidate the epidemiological and pathophysiological association between DM and PD and summarize the antidiabetic drugs used in animal models and clinical trials of PD, which may provide reference for the clinical translation of antidiabetic drugs in PD treatment.
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Project description:BackgroundPrevious compelling evidence suggests an association between Type 2 diabetes (T2D) and neurodegenerative diseases. However, it remains uncertain whether Type 1 diabetes mellitus (T1DM) exerts a causal influence on the risk of Alzheimer's disease (AD) and Parkinson's disease (PD). Consequently, this study employed a bidirectional two-sample Mendelian Randomization (MR) approach to investigate the causal relationship between T1DM and the genetic susceptibility to AD and PD.MethodsWe utilized large-scale cohorts derived from publicly available genome-wide association study datasets involving European populations to perform MR analyses. The primary analytical method employed was the inverse-variance weighted (IVW) approach. Furthermore, sensitivity analyses, including assessments of heterogeneity and horizontal pleiotropy, were carried out using Cochran's Q, MR-Egger intercept, and MR-PRESSO tests to enhance the robustness of our conclusions.ResultsUsing the IVW-based method, the MR analysis indicated no significant association between genetically determined T1DM and AD (OR = 0.984, 95% CI: 0.958-1.011, p = 0.247). Conversely, T1DM appeared to be associated with a reduced risk of genetic susceptibility to PD (IVW: OR = 0.958, 95% CI: 0.928-0.989, p = 0.001). In the reverse direction, no evidence of reverse causality was observed between AD (OR = 1.010, 95% CI: 0.911-1.116, p = 0.881) or PD (OR = 1.164, 95% CI: 0.686-2.025, p = 0.5202) and T1DM. Additionally, our analysis found no indications of the results being influenced by horizontal pleiotropy.ConclusionThis MR study reveals that T1DM is associated with a reduced genetic susceptibility to PD, whereas no significant genetic susceptibility is observed between T1DM and AD. These findings suggest that T1DM may have a distinct role in the development of neurodegenerative diseases compared to T2D. Further investigations are warranted to elucidate the underlying mechanisms and provide a more comprehensive understanding of this relationship.
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