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Influence of type 2 diabetes on Parkinson's disease: emerging insights into pathogenesis and progression

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Ageing Neur Dis 2025;5:[Accepted].
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Abstract

Parkinson’s disease (PD) is the second most common neurodegenerative disorder worldwide and is characterized by progressive motor and non-motor manifestations. Its rising prevalence poses significant challenges for clinical management and public health. Type 2 diabetes mellitus (T2DM), the most frequent metabolic disorder, shares several pathogenic mechanisms with PD, including mitochondrial dysfunction, insulin resistance, and oxidative stress. Epidemiological studies suggest a higher incidence of PD among individuals with T2DM, with growing evidence that diabetes may accelerate the onset and progression of motor and cognitive symptoms. This narrative review summarizes current knowledge on the relationship between T2DM and PD, with emphasis on epidemiological associations, shared biological pathways, and the therapeutic implications of antidiabetic agents. Available data indicate that patients with both PD and T2DM tend to experience a faster progression of motor and cognitive decline. Clinical trials assessing hypoglycemic agents have reported heterogeneous findings: pioglitazone failed to demonstrate neuroprotective effects, while exenatide showed temporary improvements in motor function that were not sustained after treatment discontinuation. Experimental studies also suggest possible neuroprotective actions of metformin and DPP4 inhibitors, although well-designed clinical trials are still lacking. The interaction between T2DM and PD highlights the importance of metabolic factors in neurodegeneration. Further studies are required to determine the impact of diabetes and its treatments on PD course and to explore antidiabetic drugs as potential disease-modifying therapies.

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Neuroprotection, movement disorders, cognitive dysfunction, thiazolidinediones, glucagon-like peptide 1

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Rodriguez-Gonzalez IC, Botello-Villagrana F, Gomez-Villalobos SR, Gonzalez-Cantu A, Torres-Mancilla XM, Luna-Rangel FA, Gonzalez-Bedolla B, Robles E, González-González M, Martinez-Ramirez D. Influence of type 2 diabetes on Parkinson's disease: emerging insights into pathogenesis and progression. Ageing Neur Dis 2025;5:[Accept]. http://dx.doi.org/10.20517/and.2025.22

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© The Author(s) 2025. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
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