Why Some Researchers Are Calling Alzheimer’s Disease a ‘Type 3 Diabetes’

How is diabetes related to cognitive decline? It’s complicated and not entirely understood, but more and more evidence connects the two conditions. While the term “type 3 diabetes” has been used in health media and literature to refer to Alzheimer’s disease, the most common cause of dementia, it may not be a direct result of diabetes.

“[Type 3 diabetes] is really more of a research term, rather than a medical term,” says Guojun Bu, PhD, a chair professor in the division of life science at the Hong Kong University of Science and Technology and a leading researcher in the field of genetics and Alzheimer’s.

People with diabetes have at least one vascular risk factor, and this may place them at increased risk of Alzheimer’s. Socioeconomic factors likely contribute to both diabetes and Alzheimer’s disease. For example, a sedentary lifestyle is probably a risk factor for both, but diabetes forms first, so it tricks us into thinking diabetes is causing Alzheimer’s.

While doctors won’t be using type 3 diabetes as a diagnosis anytime soon, it’s a placeholder for a growing body of research into the relationships between insulin resistance and neurodegenerative conditions that can result in cognitive decline, Alzheimer’s disease, or other types of dementia.

Normally, the body uses insulin to admit glucose from the bloodstream into cells. But when a person has insulin resistance, the cells do not respond normally to insulin, and some of the glucose remains in the bloodstream, leading to high blood glucose (high blood sugar).

Initially, the body responds by releasing more insulin from the pancreas to compensate, but if the pancreas cannot keep up with the demand for more insulin, a person will develop prediabetes or type 2 diabetes.

Researchers are still trying to figure out exactly what causes Alzheimer’s disease.

According to Heather M. Snyder, PhD, the vice president of medical and scientific relations at the Alzheimer’s Association in Chicago, the immune system and hormonal pathways may be among the factors involved in the development of the condition.

Yet increasingly, researchers are also looking at a connection between insulin resistance and Alzheimer's disease.

“Individuals who have diabetes have an increased risk of Alzheimer’s disease and related dementias in later life,” says Dr. Snyder. But the exact mechanisms are not fully understood.

“While diabetes increases a person's risk of Alzheimer’s, not everyone with diabetes develops Alzheimer’s and not everyone with Alzheimer’s has diabetes,” says Snyder. “Individuals with diabetes may have an impacted supply of glucose to the brain, and this could influence the metabolism process, but it is likely not that simple. The interactions are complex and engage our processing of energy, immune mechanisms, vascular processes, and clearance and transport systems, for example.”

Our understanding of how insulin resistance may affect the brain is evolving.

“For many years, we thought that the brain was not [made of] insulin-sensitive tissue. But over the past 15 years, this notion has really changed dramatically,” says C. Ronald Kahn, MD, the head of integrative physiology and metabolism at the Joslin Diabetes Center at Harvard University in Boston.

This gene is important because of its link to Alzheimer’s disease. “Twenty percent of the general human population carries at least one allele for the APOE4,” Dr. Bu points out. (An allele is a variant of a gene, and they come in pairs, with one inherited from each parent.) “Somewhere between 50 percent and 70 percent of people with Alzheimer’s disease carry at least one copy of the allele, making it a strong risk factor.”

Genetic testing is available for the APOE4 gene and other variants, but it’s worth noting that the gene is only a risk factor, and not everyone who has it will develop the disease.

Bu points out that ongoing research is exploring potential treatments for preventing Alzheimer’s disease in people with insulin resistance. Knowing how a person’s genetic profile affects the progression of the disease could help healthcare providers customize treatments in the future.

Snyder notes that one of the key translations of the relationship between insulin resistance and the brain has been investigating medications developed for insulin resistance or diabetes as possible therapies in Alzheimer's disease.

Research into the use of metformin, a commonly prescribed type 2 diabetes oral drug that helps improve the body’s response to insulin and control the amount of glucose in the blood, hasn’t shown it to be especially effective with respect to Alzheimer’s.

But Kahn notes that there’s “a lot of interest in the potential of new-generation anti-diabetic drugs, such as GLP-1 analogs, SGLT-2 inhibitors, and DPP-4 inhibitors, as therapeutic approaches for Alzheimer's disease. Studies in animals suggest they may have value, but thus far there are no human studies.” 

Meanwhile, it’s important for people who have type 2 diabetes, prediabetes, or a family history of diabetes to understand that they are not automatically destined to develop Alzheimer’s disease.

Nor will consuming sugar in moderation necessarily lead one down that path, assuming that your blood glucose levels are under control.

But lifestyle changes to reverse or manage type 2 diabetes are important. One of the best preventive measures you can take is to exercise.

“People with diabetes, especially if it is poorly controlled, are at risk of increased vascular problems, including vascular dementia, which can complicate other forms of dementia, including Alzheimer’s disease,” says Kahn. “It is worth emphasizing that in all individuals, including nondiabetics, exercise has been shown to lower the risk of Alzheimer’s disease significantly, so exercise is one of the best ways to reduce your risk of both Alzheimer’s and diabetes.”

Additional reporting by Moira Lawler and Deborah Shapiro.