Type 3 Diabetes – Shared Mechanism of Dementia and Diabetes

By Kara McIver

My grandmother was one of those grandmas who would have to cycle through her grandkids’ names before she finally landed on yours. But she could always come up with a reason that it was a “special day”. And to her, special days meant cookies, candy or pie. These luxuries were allowed because it was a “special day”, so they didn’t count towards her diet, and her risk of developing type 2 diabetes wasn’t factored in when company was over. When first diagnosed with the disease, her body couldn’t properly respond to the amount of sugar she was putting into her bloodstream; after years of tracking those levels, she had to start injecting insulin because her body wasn’t responding at all. More than a decade later, her diabetes is gone but so is her memory. It wasn’t until the onset of my grandmother’s dementia that I realized scientists were researching a possible link between type 2 diabetes and dementia.

Diabetes refers to a group of diseases that exhibit elevated blood sugar levels as the key biomarker. Type I diabetes is an autoimmune disease in which the pancreatic cells responsible for the production of insulin are destroyed. Insulin is the primary hormone involved in the clearance of sugar from the blood. This type of diabetes is usually diagnosed in children. Type II diabetes used to be referred to as “adult-onset” diabetes, although kids are developing it these days too. In type II diabetes, tissues that normally take sugar from the blood become increasingly deaf to insulin with long-term elevated blood sugar levels. Eventually, those pancreatic cells die off because they’ve had to work so hard producing increasing levels of insulin to compensate.

Now, what does elevated blood sugar have to do with dementia and Alzheimer’s disease? To understand the theory, we must also understand a little bit about the brain.

According to the Alzheimer’s Association, “An adult brain contains about 100 billion nerve cells. Branches connect the nerve cells at more than 100 trillion points. Scientists call this dense, branching network a ‘neuron forest.’ Signals traveling through the neuron forest form the basis of memories, thoughts, and feelings.” Imagine a game of telephone: our neurons transfer the message–our thoughts and memories–from one cell to the next in a network of finger-like connection points.

Blocked Messages

All brains produce a substance called amyloid protein, which, when edited correctly, will go on to help with the development and continued growth of our brain cells. However, sometimes this protein is produced incorrectly, and these inappropriately produced proteins clump together and inhibit the processes of the brain.

Elevated blood sugar levels that result in type II diabetes play a role in this clumping in two ways:

  1. Experimentally, protein clump production was increased in insulin-resistant rats by increasing the amount of snipping enzymes. These enzymes act like scissors, making the “incorrect” cuts in amyloid protein.
  2. Insulin degrading enzyme (IDE) acts like a vacuum for both insulin and the “incorrect” amyloid clumps. The vacuum clogs because of the high levels of insulin in the brain and therefore can’t remove the ever-increasing dangerous clumps, allowing them to proliferate in the neuronal forest.

Starved Cells

In the brain, type I & type II diabetes, along with the buildup of these amyloid proteins, can all lead to the starvation of our neurons by destroying their necessary delivery system. Like a hose with a kink, nutrients are cut off from the far ends of the cell and eventually lead to cell death. Once neurons die, they cannot be regenerated, and we lose the connections in our memory-making matrix.

Additional disease states, such as oxidative stress and the loss of neurotransmitters, which can also be brought on by diabetic states, have also been implicated in the cascade from healthy brain cells to dementia. As is the case with most chronic diseases, there is also a genetic component to the development of dementia that seems to lie outside the insulin-mediated pathway.

Potential Therapies 

While the aforementioned mechanisms are still being studied, the use of both type I and type II diabetes medications in clinical trials for dementia patients seem to be producing positive results.

A 2018 review of clinical trials that delivered insulin directly to the brain through a nasal spray, found improved story recall performance of patients with Alzheimer’s Disease and mild cognitive impairment who did not carry a genetic predisposition for the disease. If the brain is showing signs that there is a lack of insulin, like type I diabetes, this would deliver more of the hormone to the brain to use before the rest of the body.

Another review from the same year found that patients on Metformin, a first-line type II diabetes drug, showed less frequency of cognitive impairment and in separate trials, dementia incidence was also significantly reduced.

These therapies provide further support for a shared process between the diabetes we know and neurodegeneration, which is why Suzanne de la Monte, MD, of Brown University, began calling Alzheimer’s Disease “type 3 diabetes”.

Over a lifetime of special days and reasons for dessert, high blood sugar levels don’t just increase your waistline, they may also rot your brain.

Peer edited by Dominika Trzilova

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