Emerging Type 3 Diabetes

By: Zarnab Jillani PharmD Candidate c/o 2022

             The link between diabetes and Alzheimer’s disease (AD) is a new and ongoing debate given the etiology of AD is still not fully understood. Diabetes continues to be a major public health crisis as diagnoses around the world continue to rise. Diabetes is a chronic disease that is split into two categories- type I and type II diabetes. Type I diabetes, an autoimmune disorder, is characterized by the pancreas’s inability to produce insulin which is needed to store glucose. Type II diabetes is acquired and results from cells becoming resistant to insulin. According to the American Diabetes Association, in 2018, 34.2 million people had diabetes, which is linked to the leading cause of death in America, heart disease. ¹ Diabetes affects both the younger and older population, since it can be either a disease one is born with or one that is acquired through lifestyle and hereditary factors. ¹ On the other hand, AD is categorized as a form of dementia, in which the majority of people that are affected are 65 and older. ² Recent studies suggest that the link between diabetes and Alzheimer’s is closer than it may seem, despite the differences between the two disease states.

One of the most well understood theories surrounding the cause of AD is the accumulation of β-amyloid in the brain. A recent study suggests that excess insulin levels may cause accumulation of β-amyloid in the brain. Normally, an insulin degrading enzyme (IDE), known as insulysin, helps to degrade excess insulin in the body. However, research in animals and humans suggests that in patients with Alzheimer’s, both insulin and the Alzheimer’s protein (β amyloid) compete to be degraded by insulysin. Therefore, the insulin that is being accumulated is being degraded by insulysin whereas β amyloid does not have adequate enzyme to “clean it up”. The connection between IDE and β amyloid protein was first made in 1996 by a Harvard Medical School neurobiologist, Dennis Selkoe, MD. ³

A study conducted by the Mayo Clinic in Rochester, Minnesota in 1997 suggests that patients with type II diabetes were more likely to develop Alzheimer’s. The study followed 1,500 patients with type II diabetes for seven years and found that they had twice the risk of developing AD as patients without diabetes of the same age and sex. ¹³ However, this study like many others, does not conclude a direct correlation between insulin and the onset of Alzheimer’s disease. Similarly, the Rotterdam study found that of 6,730 subjects, 126 developed dementia, of which 89 patients were diagnosed with AD. This study concluded that type II diabetes doubled the risk of a patient having dementia and patients on insulin had four times the risk. ³ These studies were conducted in the late ‘90s but seem to be receiving more attention now due to the growing number of people with concomitant diabetes and AD.

In order to test the correlation between the two disease states, a study was conducted in which researchers tested the effects of plasma insulin on humans when it is raised experimentally. Patients with type II diabetes were injected with either insulin or saline and after 90 minutes, their cerebrospinal fluid was collected. Each patient went through this process twice, once with saline and once with insulin so they served as their own controls. This resulted in increased β-amyloid levels after the insulin infusions, therefore providing insight into how insulin affects β-amyloid levels, which in turn can result in Alzheimer’s disease. ⁴ The term ‘type 3 diabetes’ was first coined by Suzanne De La Monte, MD, MPH, Associate Professor of Pathology and Medicine and neuropathologist at Brown Medical School when her team found that elements of type I and type II diabetes were found in patients with AD, such as a decrease in insulin production and resistance to insulin receptors. ⁴

In conclusion, while not all studies confirm the connection, some evidence suggests that patients with type II diabetes are at a higher risk for developing AD. Many people with diabetes acquire changes in their brain that can be attributed to AD due to the increase of β amyloid which leads many researchers to believe that the two diseases are linked. ⁵ Ongoing research is aimed at better understanding the link between the two disease states.

Sources:

1. Statistics About Diabetes. American Diabetes Association. https://www.diabetes.org/resources/statistics/statistics-about-diabetes. Accessed November 6, 2020.
2. Alzheimer’s Disease and Dementia. Alzheimer’s Association. https://www.alz.org/alzheimers-dementia/what-is-alzheimers. Accessed November 6, 2020.
3. Taubes G. Neuroscience. Insulin insults may spur Alzheimer’s disease. Science. 2003;301(5629):40-1.
4. Kroner Z. The relationship between Alzheimer’s disease and diabetes: Type 3 diabetes? Altern Med Rev. 2009;14(4):373-9.
5. The Link Between Diabetes And Alzheimer’s. Mayo Clinic. https://www.mayoclinic.org/diseases-conditions/type-2-diabetes/in-depth/diabetes-and-alzheimers/art-20046987. Accessed November 6, 2020.