[The relationship between Parkinson's disease and metabolic disorders: the impact of systemic dysfunctions on...

This review examines the association between Parkinson's disease (PD) and diabetes, two global epidemics closely linked to aging. The analysis is based on recent epidemiological data indicating that diabetes significantly increases the risk of developing PD and exacerbates its progression, affecting both motor and cognitive functions. The paper explores shared pathophysiological mechanisms, including impaired insulin signaling, insulin resistance, oxidative stress, mitochondrial dysfunction, chronic inflammation and neuroinflammation, dysregulated glucose metabolism, and gut microbiota dysbiosis. These interconnected processes create a vicious cycle in which each pathology reinforces the others, driving neurodegeneration, particularly in vulnerable dopaminergic neurons of the substantia nigra. The uniqueness of this review lies in the integration of current research, providing a dual-perspective approach to comorbidity - addressing both neurodegenerative and metabolic dysfunctions. Understanding these shared mechanisms opens avenues for developing multi-targeted therapeutic strategies, including dietary interventions, lifestyle modifications, and gut microbiota modulation. This approach distinguishes the present review from similar works by offering a comprehensive perspective on the issue and emphasizing the need for further studies to identify precise biomarkers and develop effective disease-modifying treatments.