Why Is Alzheimer’s Being Called Type 3 Diabetes?

Alzheimer’s disease (AD) and diabetes mellitus are two of the most common and rapidly growing chronic issues in the world. In the United States, 5.8 million Americans over the age of 65 suffer from Alzheimer’s, ​[1]​ while according to the American Diabetes Association, 38.4 million Americans have diabetes. It is estimated that 700 million people or 10.9% of the world population will have diabetes by 2045. ​[2]​  

As both conditions continue to impact millions of people, researchers have started to identify a growing list of links between the two; so much so that some researchers are now referring to Alzheimer’s as Type 3 diabetes [T3DM]. ​[1,3,4]​ Others aren’t willing to go that far, but describe Type 3 diabetes as a lesser-known form of diabetes in the brain that plays a key role in neurodegeneration, including the accumulation of neurotoxins—such as amyloid-beta (Aβ)—and the development of neuronal stress. ​[3]​  

RELATED: Can The Paleo Diet Diminish Alzheimer’s Disease Risk? 

In the end, it may just be semantics. Whether Alzheimer’s is another type of diabetes, or Type 3 diabetes is a key contributor to AD progression, what’s clear in the research is that the two conditions share a growing list of common pathological mechanisms.    

The Pathological Links Between Alzheimer’s and Type 2 Diabetes 

The most studied form of diabetes is Type 2 diabetes (T2DM) which is characterized by insulin resistance, glucose dysregulation, metabolic syndrome, and overproduction of insulin in the pancreas.  

T2DM is distinct from Alzheimer’s in that it is a peripheral disease, whereas AD occurs in the central nervous system which is protected from the rest of the body. But, despite this difference, there are several striking links between the two conditions. ​[3]​ In fact, they share 17 biomarkers that aren’t seen in healthy controls. ​[5]​ Oxidative stress, mitochondrial dysfunction, and inflammation are key components of both.  

Considering these links, it shouldn’t be surprising that T2DM is a major risk factor for Alzheimer’s. In fact, diabetes patients have a 73% increased risk of developing dementia and a 56% increased risk of AD specifically. ​[6]​  Having diabetes also increases the risk that mild cognitive impairment will develop into Alzheimer’s.  

While they have many pathological links, what seems to be at the core of both conditions is insulin resistance and disordered insulin signaling. ​[1,3,7]​  

Insulin Resistance as a Key Component of Alzheimer’s Disease 

It has been known for a while that insulin can cross the blood-brain barrier and get into the brain. ​[8]​ This has led research to explore the potential roles of insulin in the brain, and they have discovered that insulin signaling is crucial to the health of our brains. Insulin has many roles including regulating glucose homeostasis, protecting neuronal integrity, regulating neurotransmitters, and maintaining the health of long-term memory. ​[1,4]​  Some studies even suggest that the brain produces insulin itself, further demonstrating the importance of insulin for the brain.  

With insulin serving so many key functions, it shouldn’t be surprising that insulin resistance—a hallmark of Type 2 diabetes—has been linked to many of the cognitive impairments that are hallmarks of AD, including memory deficits, protein accumulation, and general cognitive decline. Hyperglycemia, another hallmark of diabetes, has also been closely linked to cognitive impairment. ​[9,10]​  

Researchers are continuing to uncover more evidence that insulin resistance is central to both diabetes and neurodegeneration. And it’s this common central role of insulin resistance that has given traction to the idea that Alzheimer’s disease may be a brain-specific form of diabetes or Type 3 diabetes.  

Insulin Resistance Plays a Key Role in Amyloid-Beta and Tau Protein Buildup 

In 2006, a groundbreaking study demonstrated conclusively that the buildup of Aβ deposits in the brain was the cause of Alzheimer’s disease. ​[11]​ Unfortunately, the integrity of this study was seriously challenged in recent years after it was discovered the images central to the study were modified. However, even if the buildup of amyloid plaques and tau protein deposits in the brain aren’t the cause of AD, they are still key symptoms of the disease.  

More importantly, insulin resistance has been linked to the formation of both. A key enzyme called insulin degrading factor enzyme (IDE) regulates insulin levels in the brain, but it is also responsible for breaking down Aβ and preventing its accumulation. ​[4,12]​ When the brain becomes insulin resistant, insulin starts to accumulate, causing the available IDE to divert to regulating insulin. As a result, Aβ is allowed to accumulate. ​[1]​ This creates a vicious cycle because Aβ toxicity can further contribute to insulin resistance. ​[1,13]​  

While amyloid buildup is generally only discussed in the context of the brain and neurodegeneration, it’s important to point out that scientists have detected amyloid buildup in the pancreas of diabetics. So, while Aβ isn’t the cause of either condition, the fact that it’s a symptom of both provides further evidence of the importance of insulin resistance to both conditions. ​[4,14,15]​  

Likewise, the impaired function of tau proteins is another hallmark of AD. Insulin resistance leads to the hyperphosphorylation of tau. In other words, insulin resistance impairs its function. So, it should come as no surprise that hyperphosphorylation of tau has also been found in the pancreas of people with T2DM. ​[15]​  

Neuroinflammation and Oxidative Stress: Drivers of Neurodegeneration 

What the research is beginning to show is that amyloid plaques and tau hyperphosphorylation are symptoms of insulin resistance and it’s the insulin resistance that drives both conditions. So, what may be more crucial to the progression of each condition is the inflammation, oxidative stress, and mitochondrial dysfunction that results from insulin resistance. ​[1]​  

In the brain, insulin resistance and the buildup of Aβ can lead to neuroinflammation (inflammation in the brain) and oxidative stress. This is particularly concerning because despite being only 2% of our total body mass, the brain is responsible for 20% of the oxygen we consume. This makes the brain particularly vulnerable to oxidative damage which in turn can damage the mitochondria in our neurons. This has led researchers to theorize that neuroinflammation and oxidative stress may be two key factors that contribute directly to neurodegeneration in Alzheimer’s disease. ​[1]​  

One other contributor to oxidative stress and inflammation in both AD and diabetes is the buildup of advanced glycation end-products (AGEs). These are molecules that are formed when a protein or fat is exposed to sugar and becomes glycated. Ultra-processed foods are high in AGEs, but we also produce them in our bodies when we are insulin resistant because of our inability to properly regulate glucose. AGE formation is a key part of diabetes development but also plays a role in many other conditions, including Alzheimer’s. ​[3,16–19]​  

How Understanding Alzheimer’s as a Form of Diabetes May Help Treatment of the Condition 

Despite billions of dollars being spent on medication development for Alzheimer’s, at best, the top drugs only slow the progression. However, much of this medication targets the amyloid plaques which we now know may only be a symptom and not the cause of AD.  

For anyone suffering from Alzheimer’s, the traditional treatments have so far been discouraging. But, if AD is indeed a new type of diabetes, or even if Type 3 diabetes is a separate condition but a cause of Alzheimer’s, this opens up the possibility for new and exciting treatments for the condition. To make this point, traditional diabetes medications such as Metformin and GLP-1 have been shown to reduce the risk of AD. ​[3]​  

More importantly, lifestyle factors that have already been shown to reduce insulin sensitivity may also help prevent or even treat Alzheimer’s. Dr. Dale Bredesen, an MD who has worked with Alzheimer’s his entire career, has demonstrated resounding success treating AD patients with many of the lifestyle factors recommended for diabetes. ​[20–22]​  

Some recommendations found in the literature include: ​[4]​   

• Curcumin, which can enter the brain and is able to both reduce oxidative stress and target Aβ and tau proteins. There’s also evidence that curcumin can help inhibit the formation of AGEs. ​[23]​   
• Eating lots of fruits and vegetables with high antioxidant and anti-inflammatory polyphenols and flavonoids.  
• Eating a healthy omega-6-to-omega-3 ratio as close to 1:1 as possible is important for brain health. That means reducing omega-6s in the diet and increasing omega-3s.  
• Reducing simple sugars and ultra-processed foods. Overconsumption of high-glycemic foods has been linked to diabetes for a long time now. But a growing body of research is also linking simple sugars (especially sugary beverages) to AD. Further, reducing ultra-processed foods can bring down the AGE burden in our bodies.  
• Ketones and short-term ketosis. Periodic ketosis has been shown to reduce inflammation and help rebuild insulin sensitivity. Preliminary research on ketosis and Alzheimer’s is promising, but a lot more research needs to be done. ​[24]​  
• Consuming coconut oil, which is high in medium-chain fatty acids that can be converted to ketones.  
• Exercise is one of our most powerful ways of reducing oxidative stress, improving insulin sensitivity, regulating glucose, and improving vascular health in general.  

Of course, a Paleo diet has been shown through multiple peer-reviewed studies to improve insulin resistance and glycemic control, while being one of the best diets to reduce inflammation. ​[25–28]​  

We always recommend listening to the advice of your doctor, but if ongoing research continues to show the strong links between Alzheimer’s and diabetes, adopting The Paleo Diet may be a great addition to any treatment regimen your doctor gives you. More importantly, it may prevent you from needing to see the neurologist in the first place.  

Rethinking Alzheimer’s Disease 

Ultimately, you may not care whether Alzheimer’s disease is a new form of diabetes or if it just shares common pathologies with diabetes. What’s important is that research is showing more and more that insulin resistance and poor glucose control is at the heart of both conditions. And this opens new and exciting ways to bring relief to people facing cognitive decline.  

Diabetes remains the most adjustable risk factor for developing AD. ​[4]​ With the important word there being “adjustable.” Type 2 diabetes can be controlled and even reversed with lifestyle and exercise. We’ve heard from many followers of The Paleo Diet® that the diet brought their A1C levels back down to a healthy range and put their diabetes into remission. If similar lifestyle changes can play a significant role in preventing neurodegeneration and even help treat the condition, then there’s reason for hope for the millions of people suffering from Alzheimer’s.  

References

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2. ​Saeedi P, Petersohn I, Salpea P, Malanda B, Karuranga S, Unwin N, et al. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas, 9th edition. Diabetes Res Clin Pr 2019;157:107843. https://doi.org/10.1016/j.diabres.2019.107843. 
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