Kind 2 Diabetes Linked to Elevated Threat for Parkinson’s

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New analyzes of both observational and genetic data have provided “compelling evidence” that type 2 diabetes is associated with an increased risk of Parkinson’s disease.

Dr. Alastair Noyce

“The fact that we are seeing the same effects in both types of analyzes separately makes these results more likely to be real – this type 2 diabetes is really a driver of Parkinson’s risk,” said Alastair Noyce, PhD, senior author of the new studies, said Medscape Medical News.

The two analyzes are reported in an article published online March 8 in Movement Disorders magazine.

Noyce, a clinical lecturer in the Department of Preventive Neurology at the Wolfson Institute of Preventive Medicine at Queen Mary University in London, UK, stated that his group is interested in risk factors for Parkinson’s disease, especially those that are population-relevant and which one could be modifiable.

“Several studies have looked at diabetes as a risk factor for Parkinson’s, but very few have focused on type 2 diabetes and since this is such a growing health problem we wanted to take a closer look,” he said.

The researchers performed two different analyzes: a meta-analysis of observational studies examining an association between type 2 diabetes and Parkinson’s disease; and a separate Mendelian randomization analysis of genetic data on the two conditions.

They found similar results in both studies, with observational data indicating that type 2 diabetes was associated with a 21% increased risk of Parkinson’s disease and genetic data indicating that the risk increased by 8%. There was also evidence that type 2 diabetes could also be linked to faster progression of Parkinson’s symptoms.

“I don’t think type 2 diabetes is a major cause of Parkinson’s, but it probably contributes and can increase the risk of a more aggressive form of the disease,” said Noyce sadly.

“I would say that the increased risk of Parkinson’s disease due to type 2 diabetes may be similar to that from head injuries or pesticide exposure, but it’s important because type 2 diabetes is very common and on the increase,” added he added. “As we see the growth of type 2 diabetes, it could lead to a later rise in Parkinson’s, which is already one of the fastest growing diseases in the world.”

For the meta-analysis of observational data, the researchers included nine studies examining previous type 2 diabetes and its effects on the risk of Parkinson’s disease and the progression of Parkinson’s disease.

The estimates of the pooled effects showed that type 2 diabetes was associated with an increased risk of Parkinson’s disease (odds ratio 1.21; 95% confidence intervals 1.07-1.36), and there was evidence that that type 2 diabetes was associated with faster progression of motor symptoms (standardized mean difference [SMD] 0.55) and cognitive decline (SMD –0.92).

The observational meta-analysis included seven cohort studies and two case-control studies, and these different types of studies showed different results regarding the association between diabetes and Parkinson’s disease. While the cohort studies showed an adverse effect of diabetes on the risk of Parkinson’s disease (OR, 1.29), the case-control studies indicated a protective effect (OR, 0.51).

In this context, Noyce noted that the case-control studies may be less reliable because they suffered more from survivor bias. “Diabetes can cause mid-life deaths before people develop Parkinson’s. This would create a protective effect. However, we believe this is a false result. Cohort studies are generally more reliable and less prone to bias to survival,” he said .

For genetic analysis, the researchers combined results from two large publicly available genome-wide association studies – one for type 2 diabetes and one for Parkinson’s disease, to determine whether people with a genetic tendency towards type 2 diabetes were at higher risk. to have Parkinson’s disease.

The results showed an increased risk of Parkinson’s disease in people with genetic variants associated with type 2 diabetes with an odds ratio of 1.08 (P = 0.010). There was also evidence of an effect on motor progression (OR 1.10; P = 0.032), but not on cognitive progression.

Regarding the possible mechanism behind this observation, Noyce noted that type 2 diabetes and Parkinson’s have some similarities in biology, including abnormal protein aggregation.

In the study, the authors also suggest that circulating insulin may play a neuroprotective role, while systemic and local insulin resistance may affect pathways known to be important in Parkinson’s pathogenesis, including those related to mitochondrial dysfunction , Neuroinflammation, synaptic plasticity, and mitochondrial dysfunction.

Noyce also noted that several drugs used to treat type 2 diabetes have been repurposed as possible treatments for Parkinson’s disease and are now being tested for this new indication. “Our results support this approach and suggest that some of these drugs might prevent Parkinson’s disease in people at risk,” he commented.

Most people with type 2 diabetes will not get Parkinson’s, he added. Other outcomes such as heart disease, kidney disease, and microvascular complications are far more likely, and the main goal of preventing and treating type 2 diabetes is to prevent these far more common outcomes. “However, our data suggest that this could also have a potential benefit in reducing future Parkinson’s risk,” he said.

Currently, the possibility of screening patients with type 2 diabetes for signs of early Parkinson’s disease is not in sight, Noyce said.

“There is still no test to identify presymptomatic neurodegenerative diseases like Parkinson’s, but there may be in the future and type 2 diabetes could be a risk factor to consider when considering such a screening,” he added.

This work was supported financially by grants from the Michael J. Fox Foundation; the Canadian Consortium for Neurodegeneration in Old Age (CCNA); the Canada First Research Excellence Fund (CFREF), awarded to McGill University for the Healthy Brain For A Healthy Living (HBHL) initiative; and Parkinson Canada and the NIH Intramural Research Program, National Institute on Aging.

Noyce reports on grants from the Barts Charity, Parkinson’s in the UK, Aligning Science Across Parkinson and the Michael J. Fox Foundation, and the Virginia Keiley Benefaction; and personal fees / fees from Britannia, BIAL, AbbVie, Global Kinetics Corporation, Profile, Biogen, Roche, and UCB outside of work submitted.

Movement disorders. Published online March 8, 2021. Full text

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