Type 3 Diabetes: What is it?

Most people are familiar with type 1 and 2 diabetes mellitus. Type 3c diabetes is another recognized condition known as T3cDM or pancreatogenic diabetes. Some studies suggest, however, that there may be another type, type 3, that arises specifically when the brain neurons no longer properly respond to insulin, contributing to the onset of Alzheimer’s disease.

Although type 3 diabetes is not yet widely recognized, studies into the condition are underway in the hopes that they may provide insights into the causes of Alzheimer’s and eventually lead to effective therapeutics for the disease.

What is diabetes mellitus?

Diabetes mellitus (DM) refers to disorders associated with abnormal metabolism secondary to either an inability to produce insulin (type 1) or an inability to use insulin properly (type 2). Another form of insulin dysregulation occurs secondary to pregnancy, known as gestational diabetes. Some researchers are asking whether insulin deficiency and resistance factor into the mental decline and other neurological changes in Alzheimer’s disease (AD).

Type 2 diabetes

According to the Centers for Disease Control and Prevention (CDC), almost 1 in 10 Americans have DM. The vast majority (90–95%) of those with the DM have type 2 diabetes. This condition can arise at any age, though it is traditionally associated with adulthood. In this type of DM, insulin resistance develops. The pancreas's beta-islet cells still produce insulin properly. However, the insulin fails to do its job effectively, leading to high blood glucose levels (hyperglycemia).

People with type 2 diabetes have insulin resistance. That means that the body’s cells aren’t responding properly to insulin, whose job is to get sugar (energy) into your cells to perform needed functions. This resistance causes increased blood sugar levels and, ultimately, DM.

Symptoms of type 2 DM include:

Patients with type 2 DM are more prone to problems with the pancreas. They can develop complications such as pancreatitis (pancreatogenic diabetes, aka T3cDM, or type 3c diabetes). Other conditions that cause damage to the pancreas, including cancer or pancreatic trauma, can also lead to T3cDM.

Type 3 diabetes

Alzheimer's disease (AD) arises when the brain’s neurons (nerve cells) die off prematurely and abnormally functioning synapses (nerve impulses between neurons) develop. This problem in the pathway between nerve cells may be associated with a disruption in metabolism, especially that of glucose. This potential link to abnormal glucose metabolism has led some researchers to suggest a link between diabetes and AD and have dubbed this association type 3 diabetes.

The link between diabetes and Alzheimer’s

A consensus has not yet been reached on the role diabetes plays in AD development or if AD is another form of diabetes. As with many health topics commonly discussed today, more research is needed.

Some research has suggested that certain components are involved in the insulin signaling pathway (e.g., GSK-3β, which plays a key role in the body’s glucose regulation) and may link AD and DM. However, how this happens isn’t yet known. Therefore, we cannot definitively say that a form of DM affecting the brain causes AD. However, there may be an association between many patients with AD and how the brain processes or doesn’t process insulin appropriately, leading to a diabetic disease within the brain.

Further, amyloid plaques (abnormally folded proteins) occur in AD and poorly regulated diabetics. In addition to abnormal insulin regulation pathways (resistance), this has further triggered a possible connection between the two diseases.

Causes & risk factors for type 3 diabetes

The development of AD is multifactorial and complex. Therefore, not all risk factors have been identified, nor has a complete understanding of how the disease manifests been established.

Risk factors for AD

An early-onset form of AD is hereditary, and gene mutations have been identified, for example, the APOE-ε4 gene. However, the sporadic or late-onset form has been associated with high blood pressure, poorly regulated type 2 DM, heart disease, high blood lipid (fat) levels, and variable APOE-ε4 gene expression. Age itself poses another risk for late-onset AD.

The brain is a powerhouse and needs a lot of fuel, requiring 20% of the sugar our body obtains/produces as energy. Therefore, it is logical to infer that issues with sugar processing in the brain might result in memory loss, difficulty processing, and difficulty carrying out everyday tasks (cognitive decline).

Symptoms of AD

With AD on the rise and type 2 DM so prevalent in the U.S., it isn’t a stretch to think there could be a connection between DM and AD. Thus, researchers have examined possible links through animal models and observational human studies.

Early investigations reveal type 2 DM patients have cognitive impairment comparable to AD. More research is required to see if this association holds in large clinical trials and whether it stems from particular genes, insulin resistance, inadequate diabetes management, improperly folded proteins (amyloids), or a combination of these variables leading to AD.

Since medical professionals do not currently use type 3 DM as a diagnosis, it is hard to pinpoint risk factors or symptoms. However, if you or someone you know has trouble with activities of daily living (normal day-to-day tasks), memory loss that prevents living alone, confusion, or changes in personality or temperament, then getting a medical professional involved is key.

Can we diagnose type 3 DM?

If we intervene before clear AD changes have occurred in the brain, perhaps, with a better understanding of how insulin, sugar regulation, and other factors play a role in AD’s development, we can prevent progression. While there is no way to diagnose type 3 DM at this time (since there is no official diagnosis), AD can be diagnosed definitively. Talk to a medical professional if you or your loved one has concerns about DM or AD.

Alzheimer’s & DM, a tentative link

While there still isn’t sufficient scientific evidence to truly define AD as a diabetic condition, it is reasonable to assume that those with DM may have a higher risk of developing Alzheimer's. This alone, even without high-level evidence, should encourage those with pre-DM and DM to seek professional care and follow their doctor’s recommendations to minimize the chances of any potential consequences of DM, including diabetic retinopathy, diabetic macular edema, kidney disease, and AD.