S2E5. Glucose And Ketones And Insulin…Oh My!

I began the week with the goal of understanding why some researchers refer to dementia as ‘Type 3 Diabetes.’ I had seen the phrase often enough, but I hadn’t really wrapped my head around what it actually meant. But, like Dorothy in The Wizard of Oz, I wound up going on a wild detour en route to my destination. Let’s start at the beginning:

Type 1 diabetes occurs when your pancreas stops making enough insulin. 

Type 2 diabetes occurs when your cells become insensitive or resistant to using the insulin you do produce.

The Type 3 variant was proposed because it posits that insulin insensitivity in the brain is the cause of cellular malfunctions resulting in dementia. 

All of this raises the obvious question: what does insulin do that causes so many problems when it doesn’t do its job?

The answer introduces us to glucose. Glucose is a sugar that is the most plentiful source of energy for all of the cells in your body. It is floating around in your bloodstream all the time. You can increase your blood glucose very quickly by eating sweets or refined flours, or by drinking sugary liquids. Foods with complex carbohydrates will also be converted into glucose, but it takes a little longer.

The connection between insulin and glucose is that insulin binds to your cells and opens the door for the glucose to enter, thus providing the energy the cells need to conduct all of their functions. Needless to say, when that energy supply is disrupted, there are major problems throughout multiple systems in your body, including your brain.

If your production of insulin isn’t high enough to accommodate all of the energy demands from all of your cells, you have Type 1 diabetes. If your cells have developed a resistance to using insulin so they can’t get enough glucose to power them, then you have Type 2 diabetes.

As I understand it, then, it seems like Type 3 diabetes isn’t really a separate disorder, but more appropriately the way that Type 2 diabetes affects the brain, and this is why diabetes and dementia are strongly correlated. 

Enter ketones!

Ketones are compounds that are created when your body burns stored fat. There is a relatively low concentration of them floating in your bloodstream at all times and cells can use them instead of glucose to provide energy. In one sense, they seem to be a back-up energy source in case you don’t get or can’t process enough glucose. On the other hand, converting ketones to energy is more efficient and, if you raise your relative level of ketones enough, your body prefers to use them instead of glucose.

And now for that detour along the yellow brick road:

A theory has recently been offered suggesting that it is chronic energy deficiency in the brain that is the cause of the breakdowns in cellular functions that we see in dementia.* This is based, in part, on the observation that there are brain regions that are intensive energy consumers and that each type of dementia is associated with at least one of these areas whose breakdown results in the signature symptoms of that dementia. In Alzheimer’s, for example, it’s the hippocampus and pre-frontal cortex.

So if there is something impeding the flow of energy to the brain, then those areas which demand the most energy will be the first to experience problems. Insufficient energy availability, in turn, unleashes a cascade of events that lead to the accumulation of plaques and tangles, the loss of myelin in white matter, and synaptic degradation, to name just a few. And this is on top of the impairments that emerge because that region can’t do it’s job because it doesn’t have sufficient energy available to it.

All of which brings us back to insulin. Age is the biggest risk factor for dementia and we know that insulin production decreases with normal aging. This means that glucose metabolism drops off as we grow older, putting enormous stress on our high-energy brain centers. 

It’s a prescription for dementia.

To close the circle—and to offer a ray of hope—a number of studies have shown that burning more ketones can actually improve cognitive functions like memory, language and global functioning.** Although it’s way too early to draw any conclusions, it’s possible that increasing ketone utilization to offset deficits in available glucose just might be a protective strategy as we age.

I can’t wait for the research! 

P.S.: The above post is largely based on my reading of two recent journal articles (see footnotes). To be honest, I only understood a small percentage of what I read, as cell metabolism is a highly technical topic written in a language I barely understand! But I think I got the gist of them. Please feel free to correct anything that isn’t right, or expand on any of these topics. I’d appreciate it!

* Neurodegenerative Diseases: Is Metabolic Deficiency the Root Cause?Muddapu, Vignayanandam Ravindernath, Dharshini, S. Akila Parvathy, Chakravarthy, V. Srinivasa, Gromiha, M. Michael, Frontiers in Neuroscience, March 2020, Vol. 14

** Effects of Ketone Bodies on Brain Metabolism and Function in Neurodegenerative Diseases. Jensen, Nicole Jacqueline, Wodschow, Helena Zander, Nilsson, Malin, Rungby, JÃrgen. International Journal of Molecular Sciences, November 2020, Vol. 21

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