Why Researchers Are Calling Alzheimer’s Type 3 Diabetes?

Summary: Alzheimer’s disease is increasingly being recognized as “Type 3 Diabetes” due to its strong association with insulin resistance. This connection suggests that the metabolic dysfunction seen in diabetes plays a crucial role in the early stages of Alzheimer’s, contributing to neurodegeneration long before symptoms appear. Addressing insulin resistance may be a key to preventing or managing Alzheimer’s.

 In recent years, an increasing number of researchers have been calling Alzheimer’s type 3 diabetes. Now, a growing number of studies suggest that there is a direct relationship between Alzheimer’s risk and insulin resistance.

To understand how Alzheimer’s is related to insulin resistance, we have to consider a few things. Just consider the fact that when diabetes was uncommon, Alzheimer’s was also a rare neurodegenerative disease. Alzheimer’s pandemic has begun along with obesity and diabetes pandemic, suggesting a link between the two.

Although Alzheimer’s is caused by many factors, but it is quite likely that insulin resistance is among the leading causes. This is evident from the fact that in the last half a century, the human genome has not changed much. Although the environment has changed, such a significant rise in Alzheimer’s cannot be attributed to environmental factors or toxins. 

So, if insulin resistance is among the leading and direct causes of Alzheimer’s, why has science not been able to identify its mechanism, or why do anti-diabetes drugs not help prevent or manage the condition?

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Well, the reason is simple. It is vital to understand that the human brain is a massive organ. It has substantial compensatory abilities. It means that even if some brain cells die, it may not result in a significant disability. Researchers know now for sure that Alzheimer’s begins decades before its diagnosis. The disease is only diagnosed when considerable damage has already occurred. In this late phase, other pathological processes predominate. Hence, it is easy to overlook the role of insulin resistance in the disease development.

Insulin resistance appears to play a significant role in the early stages of the disease. It is known that the human brain is the most energy-hungry organ. It utilizes almost 20-25% of oxygens and calories. Not only that, but the human brain is also unique in a way that, unlike other body organs that can use fatty acids (ketone bodies) as an alternate energy source, the human brain cannot. The human brain is dependent on glucose supply for its energy needs. It means that any changes in glucose metabolism will have a significant impact on brain health. Moreover, the brain would be the first organ to experience such an effect.

Further, insulin resistance also means poor vascular health and consistent inflammation. These factors may also cause changes in the brain, leading to Alzheimer’s.

Alzheimer’s occurs due to proteinopathy, which is due to the accumulation of faulty proteins beta-amyloid and tau. 

It appears that insulin resistance plays a significant role in the development of this proteinopathy. As these faulty proteins keep accumulating in the brain, inflammation worsens. This causes further accumulation of these proteins. This increased accumulation of faulty proteins starts causing the death of brain cells, and this even further worsens the accumulation of faulty proteins.

So, what is happening in the brain is a kind of domino effect provoked by insulin resistance and inflammation. However, once this domino effect ensues, other pathological processes become dominant. Thus, it is pretty easy to ignore or overlook the fact that these pathological processes were initially started by insulin resistance. Hence, it is vital to realize that Alzheimer’s is type 3 diabetes.

Once we accept this fact, we can include it among the complications of insulin resistance. This will help people understand that insulin resistance is not just about type 2 diabetes or increased risk of cardiovascular ailments. 

Finally, some researchers also suggest that insulin resistance causes energy deficiency in the brain. This causes the brain to start breaking myelin sheath. Further, insulin resistance also means disturbed fluid and electrolyte balance. So, insulin resistance causes Alzheimer’s in many ways.

The only reason why the role of insulin resistance remains underappreciated is that these processes occur a decade or two before any person is diagnosed with Alzheimer’s. By the time dementia is diagnosed, the focus shifts towards preventing further death of brain cells and preventing declining cognition. The focus also shifts to reducing the accumulation of beta-amyloid and tau proteins. Hence, if we need to lower Alzheimer’s prevalence, we need to start realizing the role of insulin resistance in the condition. Thus, calling it as a type 3 diabetes is appropriate.

Source:

Yoon, J. H., Hwang, J., Son, S. U., Choi, J., You, S.-W., Park, H., Cha, S.-Y., & Maeng, S. (2023). How Can Insulin Resistance Cause Alzheimer’s Disease? International Journal of Molecular Sciences, 24(4), 3506. https://doi.org/10.3390/ijms24043506