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Individuals with metabolic syndrome have a 39% higher risk of developing Parkinson’s disease (PD) than those without the syndrome, a new study showed.

Investigators followed over 400,000 people for 15 years for the cohort study, which also revealed that the risk for PD was even higher among those with both metabolic syndrome and a genetic predisposition to PD.

“Our findings suggest that clinicians should consider metabolic health as part of a broader brain health strategy. For patients with metabolic syndrome, especially those who have genes that increase their risk for Parkinson’s, doctors may be encouraged to monitor neurological health more closely,” study co-author Jiao Wang, PhD, researcher at the Karolinska Institute, Solna, Sweden, told Medscape Medical News.

“Most importantly, it reinforces the message that lifestyle interventions — such as diet, exercise, and weight management — aimed at improving metabolic health could potentially also reduce the risk of developing Parkinson’s disease,” she added.

The study was published online on August 20 in Neurology.

A Modifiable Risk Factor

Metabolic syndrome affects an estimated 1 in 3 adults in the US and is a known risk factor in chronic diseases like diabetes and dementia.

Previous research on PD and metabolic syndrome has shown mixed results, often due to limited follow-up periods or small sample sizes, the investigators noted.

Their primary analysis included 467,200 people aged 37-73 years without PD at baseline (mean age, 56.5 years; 54% women) from the UK Biobank. 

Metabolic syndrome was defined as having three or more of the typical risk factors, including excess belly fat, high blood pressure, dyslipidemia, hypertriglyceridemia, and hyperglycemia. In their cohort, 177,407 participants (37.97%) had metabolic syndrome.

The researchers used a polygenic risk score based on PD-related genetic variants to evaluate the role of genetics in the association between PD and metabolic syndrome and Cox proportional hazard models to analyze how long it took people to develop PD after entering the study.

To understand the interaction of genetics and metabolism and compare risk based on conditions, six-category variable models were used.

Genetics Plays a Role

Over the follow-up period, 3222 individuals developed PD.

After adjusting for covariates including age, alcohol use, physical activity, sleep, and genetics, metabolic syndrome was associated with a 39% higher risk for PD (hazard ratio [HR], 1.39; 95% CI, 1.11-1.74).

Of note, the association with PD risk was dose-dependent: The higher the number of metabolic syndrome risk factors, the greater the likelihood of developing PD (HR, 1.14; P for trend = .001). People with all five metabolic risk factors had the highest PD risk.

“It’s like turning up a dial: Each additional condition — such as adding high blood pressure to existing obesity and high blood sugar — pushes the risk higher than having just one or two. It’s not just about having metabolic syndrome or not; it’s about how severe the condition is.” Wang said.

Certain factors were associated with varying levels of PD risk. For example, risk was increased 33% in those with excess belly fat, 43% in people with low levels of high-density lipoprotein cholesterol, and 28% in those with hyperglycemia.

“Having a high genetic predisposition to PD seemed to exacerbate the metabolic syndrome-PD association,” the investigators wrote. 

Those with a high polygenic risk score and metabolic syndrome had nearly double the risk for PD vs those with the syndrome who had a low score (HR, 1.69; P < .001).

The researchers found similar results when they repeated their analysis for sensitivity, further adjusting for BMI and excluding certain groups like those with likely undiagnosed PD.

An additional meta-analysis of nine studies, which included nearly 25 million participants and 98,582 cases of PD, further confirmed their findings.

A Potential Route of Lowering PD Risk

Based on the findings, those with a high genetic predisposition should take extra care to manage metabolic syndrome, Wang said.

“While they cannot change their genetics, improving metabolic factors through a healthy lifestyle could help offset part of their inherited risk,” he noted.

Study limitations included that the study cohort mainly had individuals who were White and likely in better health than the rest of the UK population. Early-stage PD cases also might not have been included.

Commenting on the findings for Medscape Medical News, Jori Fleisher, MD, MSCE, associate professor of neurological sciences at Rush University in Chicago, said the study adds to a growing body of research on modifiable risk factors for PD.

As a clinician who treats patients with PD, Fleisher said patients often ask how they can change the course of their disease. 

This study gives “more concrete evidence to suggest that if someone has metabolic syndrome, they can act on those symptoms and take control of those symptoms…and that may lower the risk of ultimately developing Parkinson’s. I think that’s really important,” she said.

The study was supported by the Swedish Research Council, the National Institute of Neurological Disorders and Stroke Intramural Research Program, and others. Full funding sources are included in the original article. Fleisher and Wang reported having no disclosures.