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CW: Scary Diabetes & Brain Science (sly don't read if you are diabetic and prefer blissful ignorance)
So what's the deal with Type 3 Diabetes?
(also so sry I said I would do this two weeks ago but here we are
)
1/
So what's the deal with Type 3 Diabetes?
(also so sry I said I would do this two weeks ago but here we are
)1/
You may have heard the phrase "Alzheimer's Disease (AD) is Type 3 Diabetes" & wondered what that meant. Whelp my diabuddies I'm sorry to say that Diabetes (esp w/ sustained hyperglycemia) is a risk factor for AD. But it's a two-way street, it turns out AD is a risk factor for T2.
Lemme explain how diabetes increases AD risk 1st:
-Hyperglycemia, or high-blood sugars wreak havoc on the tiny blood vessels that snake their way through your feet, eyes, & yes, your brain is full of them (this is why it's important to have your feet & eyes checked diababes!)
-Hyperglycemia, or high-blood sugars wreak havoc on the tiny blood vessels that snake their way through your feet, eyes, & yes, your brain is full of them (this is why it's important to have your feet & eyes checked diababes!)
-Your brain uses these tiny bloody highways as an intricate network for glucose/nutrient/O2 exchange, as well as a route for your brain's "glymphatic system" to run along -basically when you sleep u get a nice brain rinsey-rinse to help clear waste and "clean" up.
-This glymphatic brain bath plays a huge role in clearing amyloid beta plaques (ABeta) & extracellular Tau (Tau is the protein that causes tangles) so compromising this clearance pathway w/ sustained syrup blood is no good. (Also this is another reason to get enough sleep!)
-Hyperglycemia also leads to increased oxidative stress, inflammation, insulin resistance, hyperinsulinemia (too much insulin) etc which can all affect cognition & overall brain health.
-AD is partially thought to be a case of your brain not being able to keep up with all of ...
-AD is partially thought to be a case of your brain not being able to keep up with all of ...
... it's necessary tasks & by damaging part of the system you can trigger a cascade of events that lead to the accumulation of ABeta plaques and neurofibrillary tangles.
-Something I find exceptionally interesting is though T2D increases the risk of developing AD, it decreases..
-Something I find exceptionally interesting is though T2D increases the risk of developing AD, it decreases..
... The actual pathological plaque and tangle load! (but increases stoke risk) (I suspect microglia are involved plz if you are in the market for a postdoc in ~6mo-1 year interested in MG/AD/insulin resistance/diet and want an actual diabetic studying this contact me 
)
)
Okay but why is AD called Type 3 Diabetes, and how does it increase risk for T2?:
-The AD brain becomes very resistant to insulin (which is essentially T2 just in your brain). I should note that most of neuronal glucose uptake is insulin *independent* but one of the places ...
-The AD brain becomes very resistant to insulin (which is essentially T2 just in your brain). I should note that most of neuronal glucose uptake is insulin *independent* but one of the places ...
... where insulin mediated glucose uptake occurs is the hippocampus aka the Haus of Memory aka one reason why AD patients lose their memories. Insulin resistance (among other things) in the hippocampus reduces synaptic plasticity&transmission&neurogenesis&impairs memory formation
-Amyloid beta can actually serve as a competitive inhibitor of the insulin receptor, preventing insulin singling & may be another reason the AD brain is so resistant.
-Insulin Degrading Enzyme is a principle regulator of ABeta degradation as well and reduction of IDE leads..
-Insulin Degrading Enzyme is a principle regulator of ABeta degradation as well and reduction of IDE leads..
to more ABeta plaques and hyperinsulinemia.
-*Neuronal* Amyloid Beta has been linked to more *peripheral* glucose intolerance as well (a hallmark of T2D)
and AD patients accumulate cytotoxic islet amyloid polypeptide (leads to pancreatic islet disfunction aka all T2D)
-*Neuronal* Amyloid Beta has been linked to more *peripheral* glucose intolerance as well (a hallmark of T2D)
and AD patients accumulate cytotoxic islet amyloid polypeptide (leads to pancreatic islet disfunction aka all T2D)
!! Please remember Diabetes â AD and AD â Diabetes !! there are many many other genetic, environmental, and lifestyle factors that influence risk tremendously and science/research has countless caveats & could never encompass a single individual.
Before you go! This is a broad, & by no means complete into to what T3D *might* mean (research is an ongoing process), but if certain aspects pic your interest let me know/ask questions I'd love to make this a
"fun" series on diabetes, glucose metabolism, insulin, & ur brain.
"fun" series on diabetes, glucose metabolism, insulin, & ur brain.
Refs:
Glymphatics: https://pubmed.ncbi.nlm.nih.gov/30813965/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4694579/
Hyperglycemia->AD: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6209735/
AD->T2 & peripheral glucose intolerance: https://www.embopress.org/doi/full/10.15252/emmm.201404183
Hippocampal IR & Neuroinflam: https://www.nature.com/articles/nrn4019
IDE & ABeta degradation: https://www.pnas.org/content/100/7/4162
Glymphatics: https://pubmed.ncbi.nlm.nih.gov/30813965/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4694579/
Hyperglycemia->AD: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6209735/
AD->T2 & peripheral glucose intolerance: https://www.embopress.org/doi/full/10.15252/emmm.201404183
Hippocampal IR & Neuroinflam: https://www.nature.com/articles/nrn4019
IDE & ABeta degradation: https://www.pnas.org/content/100/7/4162
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