“The links between diabetes and PD are gradually becoming more compelling, and this review provides interesting ideas about how elevated blood glucose might lead to changes in alpha-synuclein” Dr. Patrik Brundin

Diabetes affects approx. 8% of the global population. It causes problems in blood sugar control, resulting in abnormally high levels throughout the body. The brain has no means of protecting itself from high glucose levels, and insulin doesn’t affect it, so neurons are exposed directly. But what is the link to Parkinson’s? Why might people with diabetes be at greater risk of a PD diagnosis?

The answer lies in the random, haphazard reactions that sugars and proteins undergo inside neurons, a process known as glycation. This can produce up to 300 different medium and advanced end products (known as MGOs and AGEs respectively). Research in animal and human brain tissue has shown that free floating AGEs combine with a-synuclein, the protein which is implicated in Parkinson’s, and causes it to form clumps in a manner that causes damage to neurons. Glycation and its toxic end products, AGEs, can be reduced by controlling blood sugar levels, but also by targeting MGOs, the intermediate end products that go on to form AGEs, and breaking down AGEs directly. Anti-diabetic drugs such as exenatide have disease modifying effects, and metformin has been shown to mop up excess MGOs. High dose thiamine, or vitamin B1, has also been shown to reduce levels of AGEs and improve motor function.

Both preclinical and clinical trials are currently underway.

Summary of the Exenatide trial

Athauda, D., Wyse, R., Brundin, P., & Foltynie, T. (2017). Is Exenatide a Treatment for Parkinson’s Disease? J Parkinsons Dis, 7(3), 451-458. doi:10.3233/JPD-171192

Summary of MSDC-0160