Is Alzheimer’s Just Type 3 Diabetes?

How brain insulin resistance may underlie Alzheimer’s, linking metabolic dysfunction to cognitive decline

Many experts now consider Alzheimer’s to be a metabolic disease of the brain, pointing to insulin resistance as a key factor in the buildup of toxic proteins like amyloid‑β and tau. The evidence suggests that impaired insulin signaling leads to energy deficits and neuronal stress. Animal models and early clinical trials show promising results. Below, I explain the concept and share recent research findings.

What Is Type 3 Diabetes?

Insulin is vital for brain function. In healthy brains, insulin ensures that neurons use glucose effectively. It also helps clear harmful proteins like amyloid‑β. When brain cells become resistant to insulin, they do not get enough energy. This state is similar to type 2 diabetes in the body, but it occurs in the brain. Researchers call this condition type 3 diabetes. Impaired insulin signaling may lead to the buildup of amyloid‑β plaques and tau protein tangles. These protein deposits harm neurons and disrupt connections.

In type 3 diabetes, the insulin-degrading enzyme (IDE) plays a key role. IDE normally breaks down insulin and amyloid‑β. However, chronic high insulin levels can overwhelm IDE. This reduces the enzyme’s ability to clear amyloid‑β. A vicious cycle may then form. Amyloid‑β buildup further impairs insulin signaling. This feedback loop worsens the condition. The result is energy deficits and cellular stress that drive Alzheimer’s pathology.

Studies show that people with type 2 diabetes are more likely to develop Alzheimer’s. Even those without diabetes may exhibit brain insulin resistance before symptoms appear (Nguyen et al., 2020). This evidence supports the idea that Alzheimer’s has a metabolic component. It also opens the door to novel treatment approaches.

Insulin in the Brain: Molecular and Cellular Mechanisms

Insulin binds to receptors on brain cells. This binding activates the IRS-1/PI3K/Akt signaling pathway. This pathway is essential for cell survival and synaptic plasticity. Synaptic plasticity is the brain’s ability to form new connections. It underpins learning and memory. In Alzheimer’s, this pathway is disrupted. Neurons do not take up enough glucose, and energy deficits result.

When insulin signaling fails, abnormal protein processing occurs. Amyloid‑β is overproduced, and tau becomes hyperphosphorylated. Hyperphosphorylated tau forms tangles inside neurons. These molecular changes damage cells and impair cognitive function (Nguyen et al., 2020). The brain enters a hypometabolic state. In this state, neurons struggle to function and eventually degenerate. Researchers have noted these changes in both animal models and human studies.

The disruption of insulin signaling affects glucose homeostasis. The brain depends on a steady supply of glucose for energy. Insulin resistance limits the ability of neurons to absorb glucose. This further weakens brain function and may accelerate Alzheimer’s progression.

GLP-1 and Lifestyle Changes for Type 3 Diabetes

Emerging research highlights GLP-1’s potential in supporting brain health. In Alzheimer’s disease, GLP-1 RAs have been shown to improve glucose transport across the blood-brain barrier and reduce inflammation in neural pathways. These findings suggest that microdosing GLP-1 could play a role in preventing or slowing cognitive decline. I explore the research on GLP-1s and Alzheimer’s here.

These antidiabetic drugs have gained attention based on how helpful they are for “regular” insulin resistance (in the body). Further, nutraceuticals and lifestyle changes also offer benefits. Compounds like curcumin, omega‑3 fatty acids, and polyphenols show anti-inflammatory effects. Regular exercise improves overall insulin sensitivity. Such changes may help lower Alzheimer’s risk. Each of these therapeutic strategies offers a way to target the metabolic dysfunction in the brain. More clinical trials will determine their long-term effectiveness.

What Does Current Research Say About Type 3 Diabetes?

Epidemiological studies reveal that type 2 diabetes raises Alzheimer’s risk. Animal models have demonstrated that impaired insulin signaling in the brain leads to Alzheimer’s-like changes. Early clinical trials show modest cognitive improvements with intranasal insulin and GLP‑1 receptor agonists. These treatments have a good safety profile in early studies.

Researchers continue to debate whether brain insulin resistance is a cause or a consequence of Alzheimer’s pathology. Nonetheless, the evidence supports further exploration of metabolic therapies. Ongoing studies and clinical trials will refine these treatment options.

A Holistic Approach to Cognitive Health with GLP-1

Are you curious about exploring GLP-1 for Alzheimer’s prevention? Whether for weight loss, cognitive support, inflammation reduction, or a blend of any/all of these, we are here to help. I personally prefer the “microdose” method, as the the “low and slow” approach aligns with sustainable, long-term well-being.

At NeuroPain Health, we specialize in customized care plans that integrate cutting-edge treatments with holistic health strategies. If you’re curious about whether microdosing GLP-1 is right for you, contact us to learn more.