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Multiple variables can increase the risk for Parkinson's disease, and a previous meta-analysis examined the effects of environmental exposures on the risk for Parkinson's disease. This study by Breckinridge and colleagues was published in the April 7, 2016, issue of PLoS One.[1]
The exposure with the clearest association with the risk for Parkinson's disease was cigarette smoking, although the relationship was not intuitive. It appears that smoking cigarettes is associated with a lower risk for incident Parkinson's disease. Similar favorable results were found in comparing long-term smokers with current smokers.
There has been interest in whether other chemical exposures might increase the risk for Parkinson's disease, but this study could not find conclusive evidence for causation linking exposure to pesticides, herbicides, fungicides, and insecticides and an altered risk for Parkinson's disease. Moreover, the same could be said for living in a rural area or drinking well water.
Diabetes has been implicated as a risk factor for Parkinson's disease, with heterogeneity in previous research and difficulty in proving causation. The current study addresses this issue.
New analyses of both observational and genetic data have provided "convincing evidence" that type 2 diabetes is associated with an increased risk for Parkinson's disease.
"The fact that we see the same effects in both types of analysis separately makes it more likely that these results are real, that type 2 diabetes really is a driver of Parkinson's disease risk," Alastair Noyce, PhD, senior author of the new studies, told Medscape Medical News.
The 2 analyses are reported in an article published online March 8 in Movement Disorders.[2]
Dr Noyce, who is clinical senior lecturer in the preventive neurology unit at the Wolfson Institute of Preventive Medicine, Queen Mary University of London, United Kingdom, explained that his group is interested in risk factors for Parkinson's disease, particularly those that are relevant at the population level and that might 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 as this is such a growing health issue, we wanted to look at that in more detail," he said.
The researchers performed 2 different analyses: a meta-analysis of observational studies investigating an association between type 2 diabetes and Parkinson's and a separate Mendelian randomization analysis of genetic data on the 2 conditions.
They found similar results in both studies, with the observational data suggesting type 2 diabetes was associated with a 21% increased risk for Parkinson's disease and the genetic data suggesting an 8% increase in risk. There were also hints that type 2 diabetes might be associated with faster progression of Parkinson's symptoms.
"I don't think type 2 diabetes is a major cause of Parkinson's, but it probably makes some contribution and may increase the risk of a more aggressive form of the condition," Dr Noyce said.
"I would say the increased risk of Parkinson's disease attributable to type 2 diabetes may be similar to that of head injury or pesticide exposure, but it is important, as type 2 diabetes is very prevalent and is increasing," he added. "As we see the growth in type 2 diabetes, this could lead to a later increase in Parkinson's, which is already one of the fastest-growing diseases worldwide."
For the meta-analysis of observational data, the researchers included 9 studies that investigated preceding type 2 diabetes specifically, as well as its effect on the risk for Parkinson's disease and progression.
The pooled effect estimates showed that type 2 diabetes was associated with an increased risk for Parkinson's disease (odds ratio [OR], 1.21; 95% confidence interval [CI], 1.07-1.36), and there was some evidence 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 7 cohort studies and 2 case-control studies, and these different types of studies showed different results with regard to the association between diabetes and Parkinson's. Although the cohort studies showed a detrimental effect of diabetes on Parkinson's risk (OR, 1.29), the case-control studies suggested a protective effect (OR, 0.51).
Addressing this, Dr Noyce noted that the case-control studies may be less reliable as they suffered more from survivor bias. "Diabetes may cause deaths in midlife before people go on to develop Parkinson's, and this would cause a protective effect to be seen, but we believe this to be a spurious result. Cohort studies are generally more reliable and are less susceptible to survivor bias," he said.
For the genetic analysis, the researchers combined results from 2 large publicly available genomewide association studies -- 1 for type 2 diabetes and 1 for Parkinson's disease -- to assess whether individuals with a genetic tendency to type 2 diabetes had a higher risk of developing Parkinson's.
Results showed an increased risk for Parkinson's in those individuals with genetic variants associated with type 2 diabetes, with an OR of 1.08 (P = .010). There was also some evidence of an effect on motor progression (OR, 1.10; P = .032), but not on cognitive progression.
On the possible mechanism behind this observation, Dr 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 have a neuroprotective role, whereas systemic and local insulin resistance can influence pathways known to be important in Parkinson's pathogenesis, including those that relate to mitochondrial dysfunction, neuroinflammation, synaptic plasticity, and mitochondrial dysfunction.
Dr Noyce further pointed out that several drugs used for the treatment of 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 that approach and raise the idea that some of these drugs may event prevent Parkinson's in people at risk," he commented.
Most people who have type 2 diabetes will not get Parkinson's disease, he added. Other outcomes such as heart disease, kidney disease, and microvascular complications are far more likely, and the main aim of preventing and treating type 2 diabetes is to prevent these far more common outcomes. "But our data suggests that this could also have a possible benefit in reducing future Parkinson's risk," he said.
Not on the horizon at present is the possibility of screening patients with type 2 diabetes for signs of early Parkinson's, Dr Noyce said.
"There isn't a test for identifying presymptomatic neurodegenerative diseases such as Parkinson's yet, but perhaps in the future there will be, and type 2 diabetes may be one risk factor to take into account when considering such screening," he added.
This work was financially supported by grants from The Michael J. Fox Foundation; the Canadian Consortium on Neurodegeneration in Aging; the Canada First Research Excellence Fund, awarded to McGill University for the Healthy Brains for Healthy Lives initiative; Parkinson Canada; and the Intramural Research Program of the National Institutes of Health, National Institute on Aging. Dr Noyce reports receiving grants from the Barts Charity, Parkinson's UK, Aligning Science Across Parkinson's, Michael J. Fox Foundation, and the Virginia Keiley Benefaction and personal fees/honoraria from Britannia, BIAL, AbbVie, Global Kinetics Corporation, Profile, Biogen, Roche, and UCB outside of the submitted work.
Mov Disord. Published online March 8, 2021.