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

Cullinane, Patrick W.; Pablo-Fernández, Eduardo De; König, Anika; Outeiro, Tiago F.; Jaunmuktane, Zane; Warner, Thomas T.

doi:10.1002/mds.29298

Cited by 21 publications

(19 citation statements)

References 263 publications

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“…Diabetes and prediabetes increased the risk of PD by 27 and 4%, respectively, as compared to those without diabetes ( 17 ). Type 2 diabetes can enhance neurodegeneration through reduced brain insulin signaling, which can be more facilitated in patients with a lower BMI ( 18 ). Furthermore, an observational study showed that PD patients with diabetes were more severe in motor and non-motor symptoms and had a faster progression ( 19 ).…”

Section: Discussionmentioning

confidence: 99%

Mortality and causes of death in patients with Parkinson's disease: a nationwide population-based cohort study

Ryu,

Han,

Cho

2023

Front. Neurol.

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ObjectiveParkinson's disease (PD) is a neurodegenerative disease involving multiple systems that can affect mortality. This study aimed to compare all-cause and cause-specific mortality between people with PD and without PD.MethodsThis population-based prospective cohort study is based on Korean National Health Insurance Service data. The primary outcome was the hazard ratio (HR) of all-cause and cause-specific mortality for PD from 2010 to 2019. Cox proportional hazards regression was applied to calculate HRs under crude and three adjusted models with epidemiologic variables.ResultsA total of 8,220 PD patients and 41,100 age- and sex-matched controls without PD were registered. Ten-year mortality was 47.9% in PD patients and 20.3% in non-PD controls. The mortality rate was higher among older and male participants. The leading cause of death in PD was nervous system diseases (38.73%), and 97.1% of those were extrapyramidal and movement disorders, followed by circulatory diseases (15.33%), respiratory diseases (12.56%), and neoplasms (9.7%). PD contributed to an increased risk of all-cause death with an HR of 2.96 (95% CI = 2.84–3.08). HRs of death for PD were 3.07 (95% CI = 2.74–3.45) from respiratory diseases, 1.93 (95% CI = 1.75–2.13) from circulatory diseases, 2.35 (95% CI = 2.00–2.77) from external causes, and 2.69 (95% CI = 2.10–3.43) from infectious diseases.ConclusionThese results showed that PD was related to a higher risk of mortality in all ages and sexes. The leading causes of death in PD were nervous, circulatory, respiratory, infectious diseases, and external causes.

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Section: Discussionmentioning

confidence: 99%

Mortality and causes of death in patients with Parkinson's disease: a nationwide population-based cohort study

Ryu,

Han,

Cho

2023

Front. Neurol.

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“…DM constitutes a great global health challenge for around 460 million people worldwide [ 153 ]. According to preclinical assays, possible neuropathological mechanisms involved in these pathologies have been postulated [ 154 , 155 ]: (i) cerebrovascular disease; (ii) misfolding of proteins; (iii) chronic insulin resistance, which is associated with PGC-1α downregulation, mitochondrial complex I dysfunction, neuroinflammation, and impaired autophagy; (iv) amylin neuropathology. Amylin, a highly amyloidogenic pancreatic peptide, is increased in DM patients, can cross the BBB and accelerate α-syn [ 156 ] aggregation, Tau [ 157 ] phosphorylation, and Aβ [ 158 ] aggregates.…”

Section: Effects Of Ppars Agonists On Other Neurodegenerative Disordersmentioning

confidence: 99%

PPARs and Their Neuroprotective Effects in Parkinson’s Disease: A Novel Therapeutic Approach in α-Synucleinopathy?

Pérez-Segura

Santiago-Balmaseda

Rodríguez-Hernández

et al. 2023

IJMS

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Parkinson’s disease (PD) is the most common α-synucleinopathy worldwide. The pathognomonic hallmark of PD is the misfolding and propagation of the α-synuclein (α-syn) protein, observed in post-mortem histopathology. It has been hypothesized that α-synucleinopathy triggers oxidative stress, mitochondrial dysfunction, neuroinflammation, and synaptic dysfunction, leading to neurodegeneration. To this date, there are no disease-modifying drugs that generate neuroprotection against these neuropathological events and especially against α-synucleinopathy. Growing evidence suggests that peroxisome proliferator-activated receptor (PPAR) agonists confer neuroprotective effects in PD, however, whether they also confer an anti-α-synucleinopathy effect is unknown. Here we analyze the reported therapeutic effects of PPARs, specifically the gamma isoform (PPARγ), in preclinical PD animal models and clinical trials for PD, and we suggest possible anti-α-synucleinopathy mechanisms acting downstream from these receptors. Elucidating the neuroprotective mechanisms of PPARs through preclinical models that mimic PD as closely as possible will facilitate the execution of better clinical trials for disease-modifying drugs in PD.

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“…Because of FoxO1’s role in regulating brain metabolism, it may link metabolic dysfunction and neurodegenerative disease ( 185 ). For example, neurodegenerative diseases like Alzheimer’s disease (AD), Huntington’s disease (HD), and Parkinson’s disease (PD) are worsened by T2D ( 186 – 188 ), and FoxO1 expression is elevated in each of these conditions ( 189 – 193 ). Furthermore, increased FoxO1 has been shown to reduce pathological AD features such as tau hyperphosphorylation and amyloid beta (Aβ) plaques ( 190 , 194 – 196 ).…”

Section: Foxo1 and T2d – Brainmentioning

confidence: 99%

FoxO1 as a tissue-specific therapeutic target for type 2 diabetes

Teaney,

Cyr

2023

Front. Endocrinol.

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Forkhead box O (FoxO) proteins are transcription factors that mediate many aspects of physiology and thus have been targeted as therapeutics for several diseases including metabolic disorders such as type 2 diabetes mellitus (T2D). The role of FoxO1 in metabolism has been well studied, but recently FoxO1’s potential for diabetes prevention and therapy has been debated. For example, studies have shown that increased FoxO1 activity in certain tissue types contributes to T2D pathology, symptoms, and comorbidities, yet in other tissue types elevated FoxO1 has been reported to alleviate symptoms associated with diabetes. Furthermore, studies have reported opposite effects of active FoxO1 in the same tissue type. For example, in the liver, FoxO1 contributes to T2D by increasing hepatic glucose production. However, FoxO1 has been shown to either increase or decrease hepatic lipogenesis as well as adipogenesis in white adipose tissue. In skeletal muscle, FoxO1 reduces glucose uptake and oxidation, promotes lipid uptake and oxidation, and increases muscle atrophy. While many studies show that FoxO1 lowers pancreatic insulin production and secretion, others show the opposite, especially in response to oxidative stress and inflammation. Elevated FoxO1 in the hypothalamus increases the risk of developing T2D. However, increased FoxO1 may mitigate Alzheimer’s disease, a neurodegenerative disease strongly associated with T2D. Conversely, accumulating evidence implicates increased FoxO1 with Parkinson’s disease pathogenesis. Here we review FoxO1’s actions in T2D conditions in metabolic tissues that abundantly express FoxO1 and highlight some of the current studies targeting FoxO1 for T2D treatment.

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

Cited by 21 publications

References 263 publications

Mortality and causes of death in patients with Parkinson's disease: a nationwide population-based cohort study

Mortality and causes of death in patients with Parkinson's disease: a nationwide population-based cohort study

PPARs and Their Neuroprotective Effects in Parkinson’s Disease: A Novel Therapeutic Approach in α-Synucleinopathy?

FoxO1 as a tissue-specific therapeutic target for type 2 diabetes

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