Causal relationship between diabetes mellitus, glycemic traits and Parkinson's disease: a multivariable mendelian randomization analysis.
Diabetes mellitus
Genetic epidemiology
Mendelian randomization
Parkinson's disease
Journal
Diabetology & metabolic syndrome
ISSN: 1758-5996
Titre abrégé: Diabetol Metab Syndr
Pays: England
ID NLM: 101488958
Informations de publication
Date de publication:
05 Mar 2024
05 Mar 2024
Historique:
received:
18
11
2023
accepted:
23
02
2024
medline:
5
3
2024
pubmed:
5
3
2024
entrez:
4
3
2024
Statut:
epublish
Résumé
Observational studies have indicated an association between diabetes mellitus (DM), glycemic traits, and the occurrence of Parkinson's disease (PD). However, the complex interactions between these factors and the presence of a causal relationship remain unclear. Therefore, we aim to systematically assess the causal relationship between diabetes, glycemic traits, and PD onset, risk, and progression. We used two-sample Mendelian randomization (MR) to investigate potential associations between diabetes, glycemic traits, and PD. We used summary statistics from genome-wide association studies (GWAS). In addition, we employed multivariable Mendelian randomization to evaluate the mediating effects of anti-diabetic medications on the relationship between diabetes, glycemic traits, and PD. To ensure the robustness of our findings, we performed a series of sensitivity analyses. In our univariable Mendelian randomization (MR) analysis, we found evidence of a causal relationship between genetic susceptibility to type 1 diabetes (T1DM) and a reduced risk of PD (OR = 0.9708; 95% CI: 0.9466, 0.9956; P = 0.0214). In our multivariable MR analysis, after considering the conditions of anti-diabetic drug use, this correlation disappeared with adjustment for potential mediators, including anti-diabetic medications, insulin use, and metformin use. Our MR study confirms a potential protective causal relationship between genetically predicted type 1 diabetes and reduced risk of PD, which may be mediated by factors related to anti-diabetic medications.
Sections du résumé
BACKGROUND
BACKGROUND
Observational studies have indicated an association between diabetes mellitus (DM), glycemic traits, and the occurrence of Parkinson's disease (PD). However, the complex interactions between these factors and the presence of a causal relationship remain unclear. Therefore, we aim to systematically assess the causal relationship between diabetes, glycemic traits, and PD onset, risk, and progression.
METHOD
METHODS
We used two-sample Mendelian randomization (MR) to investigate potential associations between diabetes, glycemic traits, and PD. We used summary statistics from genome-wide association studies (GWAS). In addition, we employed multivariable Mendelian randomization to evaluate the mediating effects of anti-diabetic medications on the relationship between diabetes, glycemic traits, and PD. To ensure the robustness of our findings, we performed a series of sensitivity analyses.
RESULTS
RESULTS
In our univariable Mendelian randomization (MR) analysis, we found evidence of a causal relationship between genetic susceptibility to type 1 diabetes (T1DM) and a reduced risk of PD (OR = 0.9708; 95% CI: 0.9466, 0.9956; P = 0.0214). In our multivariable MR analysis, after considering the conditions of anti-diabetic drug use, this correlation disappeared with adjustment for potential mediators, including anti-diabetic medications, insulin use, and metformin use.
CONCLUSION
CONCLUSIONS
Our MR study confirms a potential protective causal relationship between genetically predicted type 1 diabetes and reduced risk of PD, which may be mediated by factors related to anti-diabetic medications.
Identifiants
pubmed: 38438892
doi: 10.1186/s13098-024-01299-8
pii: 10.1186/s13098-024-01299-8
doi:
Types de publication
Journal Article
Langues
eng
Pagination
59Subventions
Organisme : National Natural Science Foundation of China
ID : 81060096
Informations de copyright
© 2024. The Author(s).
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