Type 2 Diabetes and Parkinson's Disease: A Focused Review of Current Concepts

• Published in: Movement disorders Vol. 38; no. 2; pp. 162 - 177
• Main Authors: Cullinane, Patrick W., Pablo Fernandez, Eduardo, König, Annekatrin, Outeiro, Tiago Fleming, Jaunmuktane, Zane, Warner, Thomas T.
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01.02.2023; Wiley Subscription Services, Inc
• Subjects: Antidiabetics; Autophagy; Brain - metabolism; Clinical trials; Diabetes; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - drug therapy; Epidemiology; Humans; Hypoglycemic Agents; Insulin; Insulin Resistance; Mitochondria; molecular mechanisms; Movement disorders; Neurodegeneration; Neurodegenerative diseases; Neuroprotection; Parkinson Disease; Parkinson's disease; Pathogenesis; type 2 diabetes; molecular mechanisms; Parkinson's disease; type 2 diabetes; insulin
• ISSN: 0885-3185; 1531-8257
• DOI: 10.1002/mds.29298

Highly reproducible epidemiological evidence shows that type 2 diabetes (T2D) increases the risk and rate of progression of Parkinson's disease (PD), and crucially, the repurposing of certain antidiabetic medications for the treatment of PD has shown early promise in clinical trials, suggesting that the effects of T2D on PD pathogenesis may be modifiable. The high prevalence of T2D means that a significant proportion of patients with PD may benefit from personalized antidiabetic treatment approaches that also confer neuroprotective benefits. Therefore, there is an immediate need to better understand the mechanistic relation between these conditions and the specific molecular pathways affected by T2D in the brain. Although there is considerable evidence that processes such as insulin signaling, mitochondrial function, autophagy, and inflammation are involved in the pathogenesis of both PD and T2D, the primary aim of this review is to highlight the evidence showing that T2D‐associated dysregulation of these pathways occurs not only in the periphery but also in the brain and how this may facilitate neurodegeneration in PD. We also discuss the challenges involved in disentangling the complex relationship between T2D, insulin resistance, and PD, as well as important questions for further research. © 2022 International Parkinson and Movement Disorder Society. Type 2 diabetes (T2D) increases the risk and rate of progression of Parkinson's disease (PD). We provide an up‐to‐date review of the epidemiological evidence for this association and the molecular mechanisms that may be responsible. The potential treatment implications are presented along with important questions for further research. February Infographic: Type 2 Diabetes and Parkinson's Disease: A Focused Review of Current Concepts