More than just memory loss: Why Alzheimer's is now called Type 3 diabetes
Studies going back to the 1970s link Alzheimer's to insulin resistance in the brain
A hidden connection between insulin resistance (IR) and Alzheimer's Disease (AD) is now starting to unravel.
For decades, researchers have been untangling the complex relationship between the two.
For one, studies dating back to the 1970s have revealed the presence of insulin receptors in the brain, particularly the hippocampus.
The brain has a sweet tooth
It turns out that the brain does have a sweet tooth. Insulin, the hormone responsible for regulating blood sugar, also plays a vital role in brain function.
Let’s dive into it:
What is Alzheimer’s disease (AD), and why is it being called Type 3 diabetes mellitus (T3DM)?
AD is characterised by decline in cognition. It is often age-dependent. In its earliest stages, AD is the result of amyloid-β (Aβ)-mediated dysregulation.
This dysfunction affects the key pathway involved in learning and memory in the hippocampus.
Calling Alzheimer's disease “Type 3 diabetes mellitus” (T3DM) has gained significant traction recently. This suggests that insulin resistance and dysfunction in the brain – similar to what occurs in Type 2 diabetes mellitus (T2DM) – play a crucial role in the development of Alzheimer’s.
Damage to the hippocampus can lead to memory loss, disorientation, and other cognitive impairments.
Fact: Both Alzheimer’s disease (AD) and Type 2 diabetes mellitus (T2DM) are associated with chronic inflammation in the brain and body.
This suggests that shared inflammatory pathways may contribute to the development of both conditions.
Why are AD and IR called a ‘vicious cycle’?
Alzheimer's disease is a cascade of cognitive decline, while insulin resistance is also known as the “silent killer”. The two often coexist, creating a vicious cycle.
Research has shown that individuals with Alzheimer’s disease often exhibit insulin resistance in their brains, similar to the insulin resistance seen in Type 2 diabetes. This suggests a potential link between the two conditions.
Studies have demonstrated that these conditions mutually exacerbate each other.
For example, insulin resistance can contribute to the formation of amyloid-beta plaques and tau tangles, hallmarks of Alzheimer's disease. Conversely, Alzheimer's disease can impair insulin signalling in the brain, further worsening cognitive function.
How many people are affected by Alzheimer’s Disease?
AD is a global issue.
In 2023, more than 55 million people had dementia worldwide, over 60% of whom live in low-and middle-income countries, according to the WHO.
The statistics are alarming: In the US, the number of Alzheimer’s patients jumped from 4.5 million in 2010 to over 6 million today, marking a nearly 50% increase in just over a decade.
Understanding and treatment strategies need to improve in order to address the root of the problem and improve outcomes.
• It happens when cells in the muscles, fat and liver don't respond as they should to insulin, a hormone made by the pancreas that's essential for life and regulating blood glucose (sugar) levels.
• With insulin resistance, the cells don’t react, and don’t open up, resulting in excessive sugar in the blood.
• Over time, the pancreas keeps trying to regulate the blood sugar, producing more and more insulin until it wears out and can't produce large amounts of insulin anymore.
What are the earliest signs of AD?
Most neuroscientists recognise that one of the earliest detectable traits of Alzheimer's disease is when the hippocampus function and structure are compromised.
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The hippocampus is the part of the brain known to be the vital integrator for new memory formation.
The hippocampus is known to have a high glucose demand and insulin sensitivity. Studies show that a person diagnosed with insulin resistance also has a high risk of age-related disease states such as AD.
Is Type 3 diabetes an official term?
No.
The Mayo Clinic, however, already refers to Alzheimer’s as “Type 3 Diabetes.”
What triggers insulin resistance?
Insulin resistance is a metabolic problem, primarily caused and worsened by modern diets – high in refined sugars and processed foods.
Sharp spikes in blood sugar cause an overproduction of insulin, leading to insulin resistance. Think of insulin as a key that unlocks the cell to let glucose in.
The more resistant cells are to insulin, the harder it becomes to deliver energy to them, particularly in the brain.
Over time, this leads to significant cognitive decline, and the eventual onset of Alzheimer’s. An increasing number of experts argue that Alzheimer’s, like T2DM, stems from insulin resistance.
Dr Mike Hansen highlights how the brain’s ability to process insulin is compromised with constant fructose attack.
Dr Hansen, who specialises in internal medicine, critical care medicine and pulmonary disease, has dedicated over 15 years of his life to understanding how to prevent, diagnose, and treat diseases that affect adults. A leading campaigner for maintaining health and fitness, Dr Hansen explains: “Whether you consume sucrose or high fructose corn syrup, it goes into your intestines, gets absorbed, and is delivered to the liver. Fructose directly impacts the brain.
“If you thought uric acid was bad, fructose alters brain metabolism even more. It affects astrocytes, the cells that nourish neurons, through glycation and oxidative stress. Glycation occurs when sugar molecules combine with amino acids in proteins, forming advanced glycation end products (AGEs).
“This process is also known as the Maillard reaction or ‘caramelisation’. Both glucose and fructose cause glycation, but fructose does it seven times faster. Essentially, your brain becomes ‘caramelised’ if you consume too much fructose.
“Fructose generates 100 times more oxygen radicals compared to glucose, increasing oxidative stress. This stress makes the mitochondria sick and eventually dysfunctional. As mitochondria fail, cells start to die.”
To make matters worse, he explained further: “Fructose interferes with two key trophic growth factors: leptin and brain-derived neurotrophic factor (BDNF), which help the brain develop and form new connections.
“Fructose induces insulin resistance and high insulin levels, impairing leptin’s function, leading to cognitive deficits. Beta-hydroxybutyrate, a ketone produced through exercise, intermittent fasting, or a ketogenic diet, increases BDNF activity, helping to form new connections in the hippocampus.
"The hippocampus is the memory center of the brain and the first part to deteriorate in Alzheimer’s disease. Fructose impairs BDNF activity, making it even more harmful.”
Are there new drugs for Alzheimer’s?
Despite the massive expenditure on AD, no new drugs have proven effective at stemming the tide of Alzheimer’s.
Of the 2,000+ drug trials conducted through 2019, none succeeded. Many experts argue that treatments aimed at managing amyloid plaques and neurofibrillary tangles are addressing symptoms rather than addressing the underlying cause – which is poor glucose metabolism in the brain.
An increasing number of experts, however, now think the standard approach is missing the root cause of Alzheimer’s altogether.
How much does it cost to treat Alzheimer’s?
The financial impact of AD is staggering.
The cost to care for Alzheimer’s patients in the US grew from $172 billion in 2010 to $241 billion in 2020. By 2050, it’s expected to surpass $1 trillion.
What studies show the AD-IR connection?
Experts have found that the hippocampus, known to have a high glucose demand and insulin sensitivity, is especially vulnerable to insulin resistance, a key feature of aging and AD.
In 1978, a landmark study by Havrankova J, published in Nature, showed that insulin receptors are widespread in the central nervous system of rats.
Later, in 1982, a study in Neuroscience Letters by Sara VR found that receptors for insulin-like growth factors (IGF-1 and IGF-2) and insulin are present throughout the adult human brain.
In 1997, Frey WH II received a US patent for a method to deliver neurologic agents to the brain non-invasively. This intranasal technique bypasses the blood-brain barrier to deliver therapeutic proteins, growth factors, and hormones, including insulin, to treat neurodegenerative diseases like AD.
In 2012, a study by Suzanne Craft, “The Role of Insulin Resistance in the Pathogenesis of Alzheimer's Disease: Mechanisms and Therapeutic Implications”, published in the journal Experimental Gerontology connected insulin resistance to AD, suggesting that impaired insulin signaling in the brain can lead to cognitive decline and neurodegeneration.
Research published in 2016 in the Journal of Alzheimer's Disease showed that IR exacerbates the development of amyloid plaques, further advancing the understanding of Alzheimer’s.
Takeaways:
• Alzheimer's disease, once a relatively obscure condition, has become a major public health crisis.
• While age and genetic factors play a role, there’s mounting body of clinical data which points to the real issue with AD: it lies with insulin, the hormone critical for transporting glucose—our cells’ energy source—into brain cells.
• Emerging research suggests that lifestyle choices, particularly excessive sugar consumption, may significantly contribute to its development.
• The human brain is a voracious consumer of energy, relying heavily on glucose for fuel. However, excessive sugar intake can lead to insulin resistance, a condition where the body becomes less responsive to the hormone insulin, which regulates blood sugar levels.
• When insulin resistance occurs, especially in those with Type 2 diabetes mellitus (T2DM), glucose can’t enter the cells, leaving neurons starved for energy.
• Over time, these energy-deprived brain cells begin to malfunction and die, which eventually manifests as the symptoms of Alzheimer’s.
• Many scientists believe that the current level of understanding of the molecular processes in the hippocampus could lead to new treatments that may modify the course of early-stage Alzheimer's disease.
• To address Alzheimer’s, it’s crucial to tackle the underlying metabolic dysfunction, at the cellular level, not just the downstream symptoms.
• Tackling the earliest signs of AD often involves problems with hippocampal function and structure.
• Only by addressing this “fire” can the medical community as a whole begin to reduce the alarming rise in Alzheimer’s cases and improve patient outcomes.
• This underscores the complex relationships between lifestyle factors, including diet and physical activity, and health outcomes.
• AD kills more people than breast cancer and prostate cancer combined.
• Deaths from Alzheimer’s have more than doubled between 2000 and 2019, while those from heart disease, the leading cause of death, have decreased.
• Seniors who are 70 years old living with AD are twice as likely to die before age 80 than those who do not have the disease.
• People aged 65 and older survive an average of four to eight years after receiving an AD diagnosis; some live as long as 20 years with AD.
• Finland has the most cases of AD, with 54.65 cases of Alzheimer's for every 100,000 people.
• The UK has 42.70 AD cases for every 100,000 people
• In Europe, some 7 million people already live with AD.
• Among Arab countries, dementia affects between 1.1% and 2.3% among age groups of 50 years and older, as well as between 13.5% and 18.5% among age groups of 80 years and above.
• The highest dementia prevalence among those aged more than 60 years was in Lebanon (4.88%), Tunisia (4.43%) and Algeria (4.19%).
• $8.18 billion: Estimated total direct cost for AD in the Arab region for those over 50 years old.
• 6.7 million Americans age 65 and older are living with AD today, estimated to grow to 13.8 million by 2060.
• Less than 20% of Americans are familiar with mild cognitive impairment (MCI), which can be an early stage of Alzheimer’s.
• In 2021, caregivers provided more than 16 billion hours of care valued at almost $272 billion.
(Sources: WHO | CDC | NIH | Cambridge University Press)