Diabetes Linked to Increased Risk for Parkinson's

June 15, 2018

People with type 2 diabetes appear to have an increased risk of developing Parkinson's disease later in life, a large cohort study suggests.

"Our study considerably strengthens the link between diabetes and Parkinson's. It may also help us understand better the mechanisms underlying Parkinson's disease — with the possibility that insulin sensitivity may somehow be involved," senior author Thomas T. Warner, FRCP, PhD, UCL Institute of Neurology, London, United Kingdom, told Medscape Medical News.

"The research also gives more weight to the idea that antidiabetic drugs may be useful in slowing the progression of Parkinson's disease — something that has been suggested previously," he added.

The study was published online in Neurology on June 13. 

Warner explained that there have been some suggestions in the literature about a link between diabetes and Parkinson's but this has been somewhat equivocal.

"We wanted to look at this in more detail and our study is the largest by far to investigate such an association," he said.  

The study analyzed data from all hospitalizations in England to identify patients with a diagnosis of type 2 diabetes and those with a later diagnosis of Parkinson's disease.

"The power of this study is its sheer size, with 2 million people with type 2 diabetes. They were compared with a control group of 6 million people without diabetes, with results controlled for sex, age, and place of residence," Warner commented.  

The researchers analyzed mortality data and data from English national Hospital Episode Statistics — which records every episode of day-case or inpatient care in all National Health Service hospitals in England —  from January 1999 to December 2011.

A cohort of 2,017,115 individuals admitted for hospital care with a coded diagnosis of type 2 diabetes was constructed and compared to a reference cohort of 6,173,208 people without diabetes. Exposed and reference cohorts were then searched for any subsequent hospital admission with a diagnosis of Parkinson's disease. Individuals with a coded diagnosis of any condition mimicking Parkinson's were excluded.  

Results showed significantly elevated rates of Parkinson's disease in the type 2 diabetes cohort (hazard ratio [HR], 1.32, 95% confidence interval [CI], 1.29 - 1.35; P < .001).

The relative increase was greater in patients with diabetic complications (HR, 1.49; 95% CI, 1.42 - 1.56) and in younger individuals with type 2 diabetes aged 25 to 44 years (HR, 3.81; 95% CI, 2.84 - 5.11). 

"Overall, we found that people with type 2 diabetes had a 32% increased risk of developing later Parkinson's disease than those without diabetes," he said. "This risk was considerably higher in younger patients with type 2 diabetes who had a fourfold increased risk of developing Parkinson's compared with nondiabetics, and in patients who had diabetic complications, who had a 49% increased risk."

"I would say this is pretty good evidence that there is a link between type 2 diabetes and Parkinson's disease," he added.

However, Warner cautioned that people with type 2 diabetes should not be alarmed by the findings.

"Although the relative risk of developing Parkinson's appears to be increased quite substantially, the absolute risk is still very low and the vast majority of people with type 2 diabetes will not develop Parkinson's," he said. Parkinson's disease has quite a low prevalence. In the United Kingdom there are about 140,000 people with Parkinson's, whereas there are 3 million people with type 2 diabetes.

On possible clinical implications, Warner emphasized that their results only show a connection. "We don't understand how this risk manifests itself —  that will be the subject of future research. So it is far too early to be able to advise on preventative strategies," he said. "However, our findings could have implications for new treatment targets for patients with Parkinson's disease." 

Speculating on the potential mechanism, he noted that previous anecdotal reports have suggested that some antidiabetic drugs have been associated with a slowing of Parkinson's disease, leading to the hypothesis that Parkinson's may be linked in some way to problems with insulin sensitivity in the brain.

"Type 2 diabetes is caused by a lack of insulin and tissues becoming resistant to the effects of insulin. Neurons in the brain are more reliant on glucose to produce energy than other cells in the body as they can't use fat in the same way as other cells can," he said. "Therefore, it follows that if there is a problem with insulin sensitivity, this could have a particularly detrimental effect on neurons in the brain."

In the Neurology paper, the researchers suggest that "disrupted brain insulin signaling could lead to shared dysregulated cellular pathways including neuroinflammation (microglia activation, production of proinflammatory cytokines), mitochondrial dysfunction, and increased oxidative stress ultimately promoting synuclein aggregation and contributing to the development of PD [Parkinson's disease]."

Anecdotal reports have suggested that patients with Parkinson's disease who are receiving antidiabetic drugs may do better, and a small randomized trial published last year suggested that the diabetes drug exenatide might slow the progression of Parkinson's, Warner noted.

The study was supported by the NIHR Biomedical Research Centre, Oxford,  and NIHR Biomedical Research Centre, University College London. Warner receives research support from the Brain Research Trust, Cure Huntington's Disease Initiative, Medical Research Council, and Corticobasal Degeneration Solutions. Disclosures for coauthors appear in the paper.

Neurology. Published online June 13, 2018. Abstract

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