🧠 The Link Between Diabetes and Alzheimer’s Disease: An Explanation

Researchers increasingly agree that diabetes—particularly type 2—may play a significant role in the onset of Alzheimer’s disease. This connection is so widespread that some specialists now label Alzheimer’s as “type 3 diabetes.” But what specifically connects this pancreatic metabolic disorder to a neurodegenerative brain disease?

Let’s delve into the science behind this complex relationship—and its implications for millions across the globe.

🔬 It’s the Sugar

In diabetes, elevated blood sugar (hyperglycemia) becomes a persistent issue. Over time, this surplus glucose harms blood vessels, including the fragile vasculature of the brain. This vascular damage diminishes the delivery of oxygen and nutrients to neurons, rendering them susceptible to degeneration.

Such cerebrovascular harm is a recognized contributor to cognitive decline. Originating from diabetes, it can expedite the onset or aggravate the pathology of Alzheimer’s disease by depriving the brain of the essential fuel it needs for optimal functioning.

🧬 It’s the Insulin

Type 2 diabetes is marked by insulin resistance—where the body’s cells fail to respond properly to insulin. Insulin is not only crucial for managing blood sugar; it also plays an essential role in brain health.

Within the brain, insulin aids in regulating glucose utilization, supports neuronal functioning, and boosts memory formation. When insulin signaling deteriorates—as occurs in diabetes—neurons struggle to efficiently take in glucose. This can impede communication between brain cells and initiate cognitive decline.

Importantly, insulin typically assists in clearing amyloid-beta from the brain—a protein fragment that aggregates into plaques in Alzheimer’s. When insulin regulation is disrupted, amyloid-beta accumulates. Similarly, dysfunctional insulin signaling may lead to abnormal tau protein phosphorylation, resulting in neurofibrillary tangles that constrict neurons from within—two key characteristics of Alzheimer’s pathology.

🔥 It’s the Inflammation

A consequence of poorly managed diabetes is chronic inflammation. Increased blood sugar and oxidative stress stimulate the immune system, leading to systemic inflammation that can penetrate the brain.

Inflamed brain tissues are more susceptible to amyloid-beta buildup and tau tangle formation. Additionally, inflammation might compromise the blood-brain barrier, an essential protective filter. Once breached, detrimental substances and immune cells can invade, exacerbating neural damage and speeding up Alzheimer’s progression.

⚡ It’s the Mitochondria

Mitochondria are the energy factories of cells, and neurons rely heavily on them. In diabetes, excess glucose can damage these organelles, lowering the brain’s energy reserves.

In neurons, this results in fatigue and increased vulnerability. Impaired mitochondria cannot effectively counter oxidative stress, leading to neuronal death and the structural changes associated with Alzheimer’s disease.

🧠 It’s the ACC (Anterior Cingulate Cortex)

Recent research unveiled in 2025 focuses on the anterior cingulate cortex (ACC), a brain region crucial for decision-making and emotional regulation. This area seems particularly susceptible to high blood sugar effects.

Studies in animals showed that even after blood glucose levels were normalized, previous diabetic damage to the ACC led to persistent disruptions in brain activity and cognitive performance. These impairments resemble early signs of Alzheimer’s, suggesting lasting impacts of diabetes on cognitive functions.

💊 Diabetes Medications: Remedy or Risk?

Paradoxically, even diabetes treatments might bear cognitive implications.

1. Insulin

Vital for survival in type 1 diabetes and beneficial in severe type 2 cases, insulin therapy can still carry risks. Hypoglycemia (low blood sugar caused by insulin therapy) can injure brain cells, resulting in acute confusion, memory issues, or worse.

Moreover, external (injected) insulin may result in abnormally elevated brain insulin levels, potentially disrupting the delicate insulin signaling network in the brain.

Nonetheless, the connection isn’t straightforward—some studies indicate possible neuroprotective benefits of insulin, depending on administration methods (e.g., intranasal insulin is under investigation for potential Alzheimer’s treatments).

2. Sulfonylureas

Sulfonylureas, such as glipizide or glyburide, stimulate insulin secretion from the pancreas. However, their tendency to induce hypoglycemia—and their lack of impact on insulin resistance or inflammation—renders them suboptimal for brain health.

Various studies suggest a potential association between sulfonylurea use and accelerated cognitive decline. Yet, this data remains inconclusive, necessitating further comparative research.

3. Metformin

Often the initial recommendation for type 2 diabetes, metformin enhances insulin sensitivity and curbs glucose production in the liver, without raising hypoglycemia risk.

Numerous studies propose that metformin could enhance cognitive performance or at least slow down its decline. Its anti-inflammatory and vasoprotective properties may contribute to this advantage. However, there is a caveat—prolonged use may result in vitamin B12 deficiency, which is itself linked to cognitive decline.