For years, scientists have observed a curious and troubling link between diabetes and Alzheimer’s disease (AD), the most common form of dementia. Recent studies suggest that some cases of Alzheimer’s might actually represent a form of diabetes specific to the brain, often referred to as “Type 3 diabetes.” This groundbreaking hypothesis has profound implications for how we understand, prevent, and treat one of the most devastating neurodegenerative diseases.
This idea isn’t just theoretical. As Dr. Guojun Bu, a neuroscientist at the Mayo Clinic, explained, “What it refers [to] is that their brain’s insulin utilization or signaling is not functioning. Their risk of developing Alzheimer’s disease is about 10 to 15 times higher.” The emerging connection between insulin resistance and brain health is reshaping research and offering new hope for millions of patients worldwide.
The Diabetes-Alzheimer’s Connection
The term “Type 3 diabetes” was first introduced by neuropathologist Dr. Suzanne de la Monte to describe a condition in which the brain’s ability to use insulin becomes impaired. Insulin, commonly associated with regulating blood sugar levels, is also critical for brain health, especially for memory and cognition. When the brain’s insulin signaling is disrupted, it can lead to the buildup of amyloid plaques and tau protein tangles, the pathological hallmarks of Alzheimer’s disease.
Statistically, the connection is striking. People with Type 2 diabetes are up to twice as likely to develop Alzheimer’s. Dr. Bu elaborated on one possible explanation: “One reason may be reduced blood flow to the brain because of damaged blood vessels. And, therefore, the supply of essential nutrients to the brain is also impaired.” Chronic insulin resistance, systemic inflammation, and oxidative stress—all of which are common in diabetes—create an environment where the brain struggles to function properly, accelerating neurodegeneration.
Adding to this, genetic factors also play a significant role. Dr. Bu’s research highlights the impact of the APOE4 gene, a major genetic risk factor for Alzheimer’s. “About 20 percent of the human population carries this riskier form of [the gene] APOE, called the E4,” he said, adding that it is linked to more than 50 percent of Alzheimer’s cases. This gene appears to interfere with brain cells’ ability to use insulin effectively, potentially causing cells to starve and die.
Research Advances and Clinical Trials
Leading research institutions, such as the Mayo Clinic and Emory University, are at the forefront of studying the relationship between diabetes and Alzheimer’s. One particularly promising avenue of research involves insulin-based therapies. The Mayo Clinic recently conducted a phase 2 clinical trial to test whether intranasal insulin delivery could treat Alzheimer’s symptoms. The results were encouraging. “The outcome is very positive. The patient’s cognitive decline is slowed, if not improved,” reported Dr. Bu. These results have led to a larger phase 3 trial supported by the National Institutes of Health, offering hope to patients and their families.
Meanwhile, the Emory Global Diabetes Research Center (EGDRC) received a $22 million grant to investigate the connection between diabetes and Alzheimer’s. Dr. K.M. Venkat Narayan, executive director of the EGDRC, stated, “This funding will bring a new dimension to the massive CARRS program and dive deeply into the natural history of dementia, and the connections between cardiometabolic disease and dementia.” This research aims to uncover the specific biological mechanisms linking these two conditions, paving the way for earlier detection and innovative treatments.
How Does This Impact Treatment?
The hypothesis that Alzheimer’s might be a form of diabetes is not merely academic. It has far-reaching implications for how the disease is treated. Traditional Alzheimer’s therapies primarily aim to manage symptoms or slow progression, but a focus on diabetes-related treatments could address the underlying causes of neurodegeneration.
- Insulin-Based Therapies: Intranasal insulin delivery bypasses the blood-brain barrier, allowing insulin to directly target areas of the brain affected by insulin resistance. Early trials have shown that this approach can stabilize or even improve cognitive function in some patients.
- Antidiabetic Medications: Drugs like metformin, commonly prescribed for Type 2 diabetes, are being studied for their potential to enhance insulin sensitivity and reduce inflammation in the brain. Preliminary findings suggest that metformin could improve cognitive performance and delay the progression of Alzheimer’s.
- Lifestyle Interventions: Since many risk factors for Type 2 diabetes—such as obesity, high blood sugar, and lack of physical activity—are also linked to Alzheimer’s, lifestyle modifications play a critical role. Eating a balanced diet, exercising regularly, and maintaining a healthy weight can significantly reduce the risk of both conditions.
Prevention and Awareness
Although genetics, such as carrying the APOE4 gene, increase the risk of Alzheimer’s, lifestyle changes offer a powerful opportunity for prevention. Dr. Daniel Murman, a neurologist at Nebraska Medicine, emphasized the importance of proactive health measures. “Treating abnormalities in these areas and changing an unhealthy lifestyle early on is one of the best ways to prevent Alzheimer’s disease,” he said.
Regular physical exams can help detect risk factors like high blood sugar, high cholesterol, and hypertension, which contribute to both diabetes and Alzheimer’s. Early intervention can mitigate these risks and potentially delay the onset of cognitive decline.
The Path Forward
While “Type 3 diabetes” is not an officially recognized diagnosis, the concept has provided researchers with a new framework to study the complex relationship between metabolic health and neurodegeneration. As Dr. Allan Levey, director of the Goizueta Alzheimer’s Disease Research Center, stated, “Understanding the link between diabetes and Alzheimer’s could revolutionize how we approach both conditions.”
This growing body of research underscores the importance of managing diabetes not only to prevent cardiovascular and kidney complications but also to protect the brain. By viewing Alzheimer’s through the lens of insulin resistance, researchers and clinicians are uncovering new ways to slow or prevent the progression of this devastating disease. The hope is that these efforts will lead to treatments that not only address symptoms but also target the root causes, preserving cognitive function and improving quality of life for millions of individuals worldwide.
