Prediabetes, type 2 diabetes mellitus and risk of Parkinson’s disease: A population-based cohort study

Sánchez-Gómez, Almudena; Díaz, Yesika; Duarte‐Salles, Talita; Compta, Yaroslau; Martı́, Marı́a José

doi:10.1016/j.parkreldis.2021.06.002

Cited by 34 publications

(43 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Other similar studies have also reported that diabetes is an independent risk factor for PD. For example, a recently published observational study with the same database as ours reported an increased risk of PD among T2DM subjects (adj-HR of 1.19, 95% CI: 1.13; 1.25) and subjects with prediabetes (adj-HR of 1.07, 95% CI: 1.00; 1.14) compared to those subjects without these conditions ( 28 ). Despite the different periods of observation and definition of the study outcome, as well as the variable of exposure (prediabetes state and T2DM), a similar number of events for PD were observed in this study (PD among T2DM, 1,789 events) compared with our study (PD with and without DR, 1,748 events) ( 28 ).…”

Section: Discussionsupporting

confidence: 52%

“…For example, a recently published observational study with the same database as ours reported an increased risk of PD among T2DM subjects (adj-HR of 1.19, 95% CI: 1.13; 1.25) and subjects with prediabetes (adj-HR of 1.07, 95% CI: 1.00; 1.14) compared to those subjects without these conditions ( 28 ). Despite the different periods of observation and definition of the study outcome, as well as the variable of exposure (prediabetes state and T2DM), a similar number of events for PD were observed in this study (PD among T2DM, 1,789 events) compared with our study (PD with and without DR, 1,748 events) ( 28 ). Knowing the fact that subjects with prediabetes are at an increased risk of developing T2DM ( 29 ), that the diagnosis of T2DM is usually delayed by between 4 and 7 years ( 30 ), and that both prediabetes and T2DM increase with age ( 31 ), could explain findings in our model that subjects with longer T2DM duration had a higher risk for PD.…”

Section: Discussionsupporting

confidence: 52%

“…For most of the longitudinal studies, according to a recent review on the epidemiology of PD, no associations between BMI and PD were observed ( 4 ). However, in a Spanish retrospective study, overweight and obese individuals were associated with higher PD risk (adj-HR: 1.21; 95% CI 1.15–1.27), compared with normal weight ( 28 ). This could be explained due to the different population characteristics or different variables considered in the HR analysis.…”

Section: Discussionmentioning

confidence: 94%

See 2 more Smart Citations

Associations Between Diabetic Retinopathy and Parkinson's Disease: Results From the Catalonian Primary Care Cohort Study

et al. 2022

View full text Add to dashboard Cite

The purpose of this study was to assess the risk of occurrence of Parkinson's disease (PD) among subjects with type 2 diabetes and diabetic retinopathy (DR) in our large primary health care database from Catalonia (Spain). A retrospective cohort study with pseudo-anonymized routinely collected health data from SIDIAP was conducted from 2008 to 2016. We calculated the number of events, time to event, cumulative incidence, and incidence rates of PD for subjects with and without DR and for different stages of DR. The proportional hazards regression analysis was done to assess the probability of occurrence between DR and PD. In total, 26,453 type 2 diabetic subjects with DR were identified in the database, and 216,250 subjects without DR at inclusion. During the follow-up period, 1,748 PD events occurred. PD incidence rate and cumulative incidence were higher among subjects with DR (16.95 per 10,000 person-years and 0.83%, respectively). In the unadjusted analysis, subjects with DR were at 1.25 times higher risk (hazard ratio: 1.22, 95% confidence interval: 1.06; 1.41) of developing PD during the study period. However, we did not find any statistically significant HR for DR in any models after adjusting for different risk factors (age, sex, duration of diabetes, smoking, body mass index, glycosylated hemoglobin, comorbidities). In conclusion, in our primary health care population database, DR was not associated with an increased risk of PD after adjusting for different risk factors. In our retrospective cohort study, age, male sex, and diabetes duration were independent risk factors for developing PD.

show abstract

Section: Discussionsupporting

confidence: 52%

Section: Discussionsupporting

confidence: 52%

Section: Discussionmentioning

confidence: 94%

See 1 more Smart Citation

Associations Between Diabetic Retinopathy and Parkinson's Disease: Results From the Catalonian Primary Care Cohort Study

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Along this notion, several epidemiological studies have insinuated crosstalk between brain and islet amyloid proteins, as well as a common ethological link between T2DM and neurodegenerative diseases, such as AD and PD [ 144 , 145 , 146 , 147 ]. Additionally, it is becoming increasingly clear that both hIAPP and Aβ share similar aggregation and toxic features, thus indicating common pathogenic mechanisms (reviewed in Reference [ 148 ]).…”

Section: Hiapp In Neurodegenerative and Metabolic Diseases: A Possibl...mentioning

confidence: 99%

Molecular Mechanisms of Amylin Turnover, Misfolding and Toxicity in the Pancreas

et al. 2022

View full text Add to dashboard Cite

Amyloidosis is a common pathological event in which proteins self-assemble into misfolded soluble and insoluble molecular forms, oligomers and fibrils that are often toxic to cells. Notably, aggregation-prone human islet amyloid polypeptide (hIAPP), or amylin, is a pancreatic hormone linked to islet β-cells demise in diabetics. The unifying mechanism by which amyloid proteins, including hIAPP, aggregate and kill cells is still matter of debate. The pathology of type-2 diabetes mellitus (T2DM) is characterized by extracellular and intracellular accumulation of toxic hIAPP species, soluble oligomers and insoluble fibrils in pancreatic human islets, eventually leading to loss of β-cell mass. This review focuses on molecular, biochemical and cell-biology studies exploring molecular mechanisms of hIAPP synthesis, trafficking and degradation in the pancreas. In addition to hIAPP turnover, the dynamics and the mechanisms of IAPP–membrane interactions; hIAPP aggregation and toxicity in vitro and in situ; and the regulatory role of diabetic factors, such as lipids and cholesterol, in these processes are also discussed.

show abstract

“…Mercury in the adrenal medulla may contribute to hypertension by raising noradrenaline levels [ 83 ] and therefore raise blood pressure in PD patients [ 77 , 78 ]. Pancreatic samples were not available for our PD cases, but mercury can be taken up by human pancreatic insulin-producing beta cells [ 16 ], so mercury exposure could contribute to the increased incidence of type 2 diabetes in PD [ 22 , 84 ].…”

Section: Discussionmentioning

confidence: 99%

Mercury is present in neurons and oligodendrocytes in regions of the brain affected by Parkinson’s disease and co-localises with Lewy bodies

Pamphlett

Bishop

2022

PLoS ONE

View full text Add to dashboard Cite

Objective Environmental toxicants are suspected to play a part in the pathogenesis of idiopathic Parkinson’s disease (PD) and may underlie its increasing incidence. Mercury exposure in humans is common and is increasing due to accelerating levels of atmospheric mercury, and mercury damages cells via oxidative stress, cell membrane damage, and autoimmunity, mechanisms suspected in the pathogenesis of PD. We therefore compared the cellular distribution of mercury in the tissues of people with and without PD who had evidence of previous mercury exposure by mercury being present in their locus ceruleus neurons. Materials and methods Paraffin sections from the brain and general organs of two people with PD, two people without PD with a history of mercury exposure, and ten people without PD or known mercury exposure, were stained for inorganic mercury using autometallography, combined with immunostaining for a-synuclein and glial cells. All had mercury-containing neurons in locus ceruleus neurons. Laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) was used to confirm the presence of mercury and to look for other potentially toxic elements. Autometallography-stained locus ceruleus paraffin sections were examined to compare the frequency of previous mercury exposure between 20 PD and 40 non-PD individuals. Results In PD brains, autometallography-detected mercury was seen in neurons affected by the disease, such as those in the substantia nigra, motor cortex, striatum, thalamus, and cerebellum. Mercury was seen in oligodendrocytes in white and grey matter. Mercury often co-localised with Lewy bodies and neurites. A more restricted distribution of brain mercury was seen in people without PD (both with or without known mercury exposure), with no mercury present in the substantia nigra, striatum, or thalamus. The presence of autometallography-detected mercury in PD was confirmed with LA-ICP-MS, which demonstrated other potentially toxic metals in the locus ceruleus and high iron levels in white matter. Autometallography-detected mercury was found in locus ceruleus neurons in a similar proportion of PD (65%) and non-PD (63%) individuals. Conclusions In people with PD, mercury was found in neurons and oligodendrocytes in regions of the brain that are affected by the disease, and often co-localised with aggregated a-synuclein. Mercury in the motor cortex, thalamus and striatum could result in bradykinesia and rigidity, and mercury in the cerebellum could cause tremor. People without PD had a restricted uptake of mercury into the brain. The similar frequency of mercury in the locus ceruleus of people with and without PD suggests these two groups have had comparable previous mercury exposures but that PD brains have a greater predisposition to take up circulating mercury. While this post mortem study does not provide a direct link between mercury and idiopathic PD, it adds to the body of evidence that metal toxicants such as mercury play a role in the disease. A precautionary approach would be to reduce rising mercury levels in the atmosphere by limiting the burning of fossil fuels, which may be contributing to the increasing incidence of PD.

show abstract

Prediabetes, type 2 diabetes mellitus and risk of Parkinson’s disease: A population-based cohort study

Cited by 34 publications

References 29 publications

Associations Between Diabetic Retinopathy and Parkinson's Disease: Results From the Catalonian Primary Care Cohort Study

Associations Between Diabetic Retinopathy and Parkinson's Disease: Results From the Catalonian Primary Care Cohort Study

Molecular Mechanisms of Amylin Turnover, Misfolding and Toxicity in the Pancreas

Mercury is present in neurons and oligodendrocytes in regions of the brain affected by Parkinson’s disease and co-localises with Lewy bodies

Contact Info

Product

Resources

About