CHICAGO—A prospective analysis of more than 20,000 participants revealed an association between type 2 diabetes and Parkinson’s disease, reported investigators at Brigham and Women’s Hospital in Boston. Diabetes has long been suspected of being a risk factor for Parkinson’s disease, but few prospective studies have investigated the association, and two of the most recent resulted in contradictory findings.
Greater Risk of Parkinson’s Disease in Patients With Diabetes
In the current study, patients with diabetes were found to have an increased risk for Parkinson’s disease, with a relative risk of 1.34 after adjusting for age and smoking. The association remained statistically significant after adjustment for multiple potential confounders and exclusion of patients with known vascular disease.
The risk for Parkinson’s disease was higher among diabetic patients with a normal BMI at baseline than it was for those with a greater BMI, and Parkinson’s disease risk did not increase with longer duration or greater severity of diabetes. In addition, the investigators found that the diagnosis of diabetes was clustered around the diagnosis of Parkinson’s disease, raising the possibility of detection bias owing to increased medical surveillance of those with Parkinson’s disease. But when the investigators assessed patients for the diagnosis of hypercholesterolemia, the same pattern of increased detection around the Parkinson’s disease diagnosis failed to materialize.
Although ascertainment bias cannot be ruled out, the findings may suggest that an alternative explanation for the association may be at work, according to lead author Jane Driver, MD, Instructor in Medicine at Harvard Medical School in Boston, who presented the study at the 60th Annual Meeting of the American Academy of Neurology.
“Our results don’t suggest that diabetes is a cause of Parkinson’s disease—that’s pretty clear,” she said in an interview with Neurology Reviews. “But the association exists, and whether that association is merely because of a detection bias, or whether it is caused by an underlying biologic relationship between Parkinson’s and diabetes—between the dopaminergic neurons and the glucose control system—is something that remains to be determined.”
Could Parkinson’s Predispose Patients to Diabetes?
The association between Parkinson’s disease and diabetes extends back to the 1960s, when clinicians who cared for patients with Parkinson’s disease reported higher-than-expected incidence rates of diabetes—increases that have been observed in numerous small case series. Experimental studies have examined the relationship between the cells of the substantia nigra, which are damaged in Parkinson’s disease, and peripheral glucose control.
In 2007, two large prospective studies were published that sought to determine whether diabetes is a risk factor for Parkinson’s disease. A Finnish study of more than 50,000 adults found an increased relative risk of Parkinson’s disease of 1.85 among patients with type 2 diabetes at baseline. However, this study did not evaluate the effect of diabetes duration or severity. The second study, which assessed men in the Health Professionals Follow-Up Study, found no association between Parkinson’s disease and diabetes.
The current study was designed to assess diabetes as a potential cause of Parkinson’s disease while also evaluating length and severity of diabetes. Dr. Driver and her colleagues drew on participants in the Physicians’ Health Study, a cohort of more than 22,000 male physicians in the United States.
Their initial finding of a significantly increased risk of Parkinson’s disease among patients with a history of diabetes led the investigators to dig deeper and yielded observations that Dr. Driver termed “counterintuitive.” First, the researchers wanted to confirm that they were encountering Parkinson’s disease and not vascular parkinsonism, which resembles Parkinson’s disease but has a different pathophysiology. After patients with known vascular disease were excluded, the association between Parkinson’s disease and diabetes became even stronger.
When the investigators assessed duration and severity of diabetes, however, the results were surprising. “What we expected was that the longer you have the diabetes, the higher your risk would be for Parkinson’s [disease], and if you had complications, you’d also have a higher risk,” Dr. Driver said. “But we found the exact opposite: that people with the shortest duration of diabetes—less than a year or two—had, by far, the highest risk of Parkinson’s disease. And the people who had no complications of diabetes had the highest risk of Parkinson’s disease. So that’s clearly counterintuitive if you think that diabetes might be causing Parkinson’s disease.”
The clustering of the diagnosis of diabetes around the time of Parkinson’s disease diagnosis was found when the investigators matched patients with Parkinson’s disease with controls. And while Dr. Driver does not rule out the possibility that, because they see physicians more frequently, patients with Parkinson’s disease are more likely to have diagnoses for other conditions than people without the disease, she is clearly intrigued by the alternative explanation.