Both Alzheimer’s disease (AD) and type 2 diabetes are products of insulin resistance. Type 2 diabetes has insulin resistance in the peripheral organs, muscle and adipose tissue, while in AD, the insulin signaling pathway in the brain is impaired. This common molecular mechanism between the two diseases is theorized as the reason why 70% of individuals diagnosed with Type 2 diabetes will eventually develop Alzheimer’s. This connection has led to nicknaming AD as Type 3 diabetes. So what is insulin resistance? Is it actually a good theory for the risk of developing Alzheimer’s? Let’s take a look.
Insulin Resistance
Insulin is a hormone that regulates the amount of glucose in the blood. When insulin binds to a tyrosine kinase receptor, the phosphorylation or activation of proteins occurs, sending a signal down the pathway. This signal allows for the uptake of glucose, fatty acids and amino acids into cells where they are stored in the liver, adipose tissue and muscle as nutrients. If these nutrients are not able to be taken up, diabetes occurs. In the case of Type 2 diabetes, the body becomes resistant to insulin, so the signaling pathway never occurs to cause the uptake of these nutrients. The body’s resistance to insulin can be due to the inability of the insulin receptors to bind insulin and unlock the cells to allow glucose and other molecules into the cell.
Type 3 Diabetes
The term “type 3 diabetes” is given to Alzheimer’s because it has the insulin pathway impairment that is a trademark of diabetes, but in AD it occurs in the brain. The brain dysfunction occurring in AD has similar molecular and biochemical mechanisms as type 1 and type 2 diabetes. The reason why AD would be another form of diabetes and not just a symptom of type 2 diabetes is due to the brain specific issues that are disrupted. These issues stem from abnormalities in gene expression that encode insulin, insulin growth factor (IGF), insulin growth factor peptides, receptors and more signaling mechanisms. Problems with gene expression lead to the disruption of signaling pathways that control insulin and insulin growth factor neuronal survival, along with problems with tau expression, energy metabolism, and mitochondrial function. Together, these abnormalities create the symptoms observed in Alzheimer’s.
Is it a viable hypothesis?
There are multiple different studies showing that abnormalities with insulin and IGF signaling mechanisms occur in the early stages of Alzheimer’s, so they likely play a large role in the disease’s pathology. While AD and diabetes have a lot of similarities, it has not yet been entirely determined what the role of having type 2 diabetes plays in the development of AD. However, there are obvious conclusions that can still be drawn. Since issues with insulin pathways stem from poor diet, excess weight and inactivity, having a healthy lifestyle will keep you out of risk for issues with these pathways. Therefore, if these pathways stay healthy and functional, you will be less likely to develop both type 2 diabetes and Alzheimer’s disease. Alzheimer’s does have a genetic component to its development as well, so staying healthy may decrease the chances that these genetic abnormalities causing the development of the disease. While the research into disease pathology continues and more and more connections are found, it is important to remember the role you play in your own health.
