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fuckmeuntilicecream t1_j0o9umu wrote

Can someone smart dumb this down for me some?


china_catsunflower t1_j0ocmrd wrote

Cells need energy, they get energy from glucose, glucose requires insulin to enter the cell. Insulin requires a receptor to attach to in order to allow glucose to get into a cell. Dysfunctional insulin receptors prevent glucose from getting into the cell in order to provide it energy. I am guessing that if the cells can’t get the energy they need it contributes to the aforementioned Alzheimer’s disease


Sputnik_Butts t1_j0oes3w wrote

To add with a conclusion quote from the paper

>"Results of these experiments show that Alzheimer’s disease-like neuropathology impairs the activation of vascular INSRs in the 3xTg-AD mouse model. This collection of data indicates that circulating insulin primarily interacts with INSRs exposed on the luminal side of the BBB in both human and mice and that the INSR-mediated response is blunted in Alzheimer’s disease."

According to this research, it has been suggested that Alzheimer's disease may decrease the response of cells to insulin in both mice and humans, due to physiological similarities. The paper implies that the symptoms of Alzheimer's may not necessarily be caused by a deficiency in insulin, but rather by damage to the cells' ability to respond to it.

At least that's what I understood, I'm not a scientist for reference.


moondoggy25 t1_j0ompah wrote

So does that mean people who are prediabetic or diabetic might also be at risk for Alzheimer’s?


Sputnik_Butts t1_j0on0j6 wrote

I'm a type 1 diabetic and I always assumed depending on how long I live I probably will end up with Alzheimer's. Some people refer to Alzheimer's as type 3 diabetes.

I'm speculating, but yes


dv_ t1_j0pflkz wrote

I'd rather expect type 2 diabetics to be more at risk, since type 2 diabetes is characterized by insulin resistance, while type 1 isn't.


EchoCyanide t1_j0pk1ze wrote

This is the logical answer.


Sputnik_Butts t1_j0r1hz0 wrote

They're speculating


EchoCyanide t1_j0r1n1r wrote

Yes, and that speculation makes total sense based on what I know about diabetes.


Sputnik_Butts t1_j0r1rlx wrote

Look at my source that I replied to them with


EchoCyanide t1_j0r245q wrote

I didn't realize that people assumed you couldn't develop insulin resistance as a type 1. It's just not the cause of type 1 diabetes. But if you eat a poor diet and don't stay active, you will develop insulin resistance no matter what. So then a type 1 will be insulin dependent and insulin resistant, needing to take more insulin than would be typical of someone with a good diet.


Sputnik_Butts t1_j0r0ugx wrote

"Type 1"s develop insulin resistance as well...

>"The existence of reduced tissue insulin sensitivity in children, adolescents, and adults diagnosed in T1DM is no longer being questioned. Our present analysis, which focused on IR in T1DM, presented that many factors influence the development of this disorder."

IR is insulin resistance.



dv_ t1_j0r84gz wrote

This paper states that T1s can develop IR. The possibility of T1s developing IR is not news. Having T1 does not make you immune to developing IR. The same factors that drive IR in T2s can affect T1s - these diseases are entirely separate, and in fact you can have "double diabetes". What the paper does not state is that T1s inevitably develop IR. Thus, your statement is wrong. The correct sentence is:

> "Type 1"s can develop insulin resistance as well


Sputnik_Butts t1_j0r8rld wrote

Read the whole paper word to word, before you write another silly message to me. I don't think you understand diabetes at all


dv_ t1_j0r93mm wrote

I did read it. And I myself have T1D. See for example:

> IR is not a direct cause of T1DM, but rather an accompanying phenomenon. Nevertheless, it is a burden, since people with this type of DM and concomitant IR will need higher insulin doses in order to keep their blood glucose level stable (as compared to the people with DM, but without IR).


Sputnik_Butts t1_j0ra5cf wrote

Then you should know that it's almost impossible to make it to 70y/o without a highblood sugar. The paper states that a large dose of insulin increases the risk of insulin resistance.

You should also know that low blood sugar damage and kills brain cells, which would imply cells with damaged functioning. If cells aren't functioning correctly how do you think they are going to respond to insulin efficiently?

I'm not saying near perfect control doesn't exist, but type 1 diabetics are at a significant risk to develop Alzheimer's. At least this paper is giving us more insight into the issue, and who knows maybe in the next 30 years we'll develop a way to repair cell receptors for insulin.


dv_ t1_j0rc6qr wrote

> Then you should know that it's almost impossible to make it to 70y/o without a highblood sugar.

Occasional high BG does nothing. Persistently/frequently high BG is the huge problem. If the BG is chronically high, glycation damage builds up, the body has a hard time keeping up with repairs, and over time, this culminates in complications. The higher glycation rate is precisely what the HbA1c measurement is based on. But if the BG is only sometimes high, then the body can repair that, no problem.

> The paper states that a large dose of insulin increases the risk of insulin resistance.

From the paper:

> In line with that notion, a chronically elevated insulin level (e.g., due to improper insulin injections) produces an adaptive reduction in the number of plasma membrane receptors for the hormone (due to their adaptive internalization and degradation) [6]. Consequently, greater insulin dosage is required to elicit the same physiological effect, hence IR begins. Moreover, secondary alterations in target tissues are also possible. Marban et al. demonstrated that transgenic mice over-expressing insulin showed diminished insulin responsiveness despite fasting normoglycaemia and proper body weight [7]. This could be explained by an impaired binding of insulin to its receptors and/or stem from hypertriglyceridemia, which may impair insulin signal transduction [8].

It is well known that elevated insulin levels downregulate insulin receptors. This is a normal adaptation. (Persistent hyperinsulinemia is not normal though, and one classic sign of metabolic syndrome; but elevated insulin levels do not necessarily equal that type of hyperinsulinemia.) T1s experience this as well. One common situation is when during holidays, a lot more carbs (in form of sweets for example) are consumed. Typically, this can be reverted by reducing carb intake for a few days. The endocrinologist Bernhard Teupe wrote about this. And yes, if you inject tons of insulin due to a rollercoaster, you end up with the same downregulation. That's why I like to do a no-carb day after I've had had a rollercoaster day.

As for impaired insulin binding due to hypertriglyceridemia, if your triglyceride levels are normal in your quarterly checkup, then this is not an issue.

> You should also know that low blood sugar damage and kills brain cells

Only prolonged very severe hypoglycemia does this. That was the big scare before CGMs were available - prolonged serious hypoglycemia during sleep, especially after people developed hypoglycemia unawareness (which is a maladaptation of the CNS to frequently low BG levels). And this has nothing to do with IR. Cells can't survive without fuel for long. They need a constant energy supply. That's why they die - too low BG means they aren't getting sufficient energy.


Sputnik_Butts t1_j0rceyq wrote

Ok but how can you say all this and not acknowledge the risk T1s have...


dv_ t1_j0rcpox wrote

I am not negating the risk, I am negating the claim that T1D inevitably leads to IR. That's what your statements seemingly imply. I instead state that IR is entirely separate to T1D. T1D itself does not cause IR, but it also does not make you immune to it. Again, there is the informal term "double diabetes" - when one has T1D and IR.


Sputnik_Butts t1_j0rdlzm wrote

I think if you think about this with less bias you'll see the conclusions I see. You can be T1DM and have perfect control I suppose and never gain IR. But even perfect control won't prevent you from a tiny bit of wear and tear. You might not notice till you're 70 or 80, but by then everything will be significantly harder and the damage will add up faster.

I'm just saying as a T1, unless you're cured it's inevitable that we will get Alzheimer's even from micro adjustments. The only difference is what age we get it at.

Alzheimer's develops in healthy people without diabetes, you can't assume there's no risk for a T1. It's only logical that we have an increased risk, due to even a tiny IR gain.


dv_ t1_j0reo1x wrote

> it's inevitable that we will get Alzheimer's even from micro adjustments

Again with the inevitability... The paper does not state anything about inevitability! And I see no other sources proving that T1D inevitably causes Alzheimer's.

> Alzheimer's develops in healthy people without diabetes, you can't assume there's no risk for a T1.

It can develop. It does not inevitably develop. The amount of old T1s with Alzheimer's is not 100%.

> It's only logical that we have an increased risk, due to even a tiny IR gain.

Some degree of IR is normal. There is no such thing as zero IR. The cause for concern is the pathological IR that is one key aspect of metabolic syndrome. And T1D does not cause that IR, nor does it inevitably (!) increase the risk for it. Occasional excess dosages do not equal persistent hyperinsulinemia.


Sputnik_Butts t1_j0rgo07 wrote

We just disagree, I still believe that T1 causes Alzheimer's because that's what the pathology of Alzheimer's suggests to me. Have a nice life.


dv_ t1_j0rjrlk wrote

Then say that you believe this instead of stating it as if it were a proven fact next time.


Sputnik_Butts t1_j0rjwsd wrote

You as well kid

Actually I said "I assumed" and "I'm speculating" but only you have been writing like the words of god flow through you.

Is your bloodsugar good right now?


faen_du_sa t1_j0seqwv wrote

Yes, you assumed and speculated, then someone chimed in with their seemingly more science based assumptions and also facts! Then you just said no, I have my assumptions.


Sputnik_Butts t1_j0sf8wo wrote

Yeah they provided more facts, but they didnt extrapolate anything to convince me otherwise from their facts.


tretower424 t1_j0sftp5 wrote

Both my uncle snd his sister (my mother) had Type Ii Diabetes and both developed Dementia/Alzheimers. Also their father had the same, so it's intriguing to read this news.


weaselmaster t1_j0saxrr wrote

Came to say the same (re: Alzheimer’s being called Type 3 Diabetes) - my father, who has developed Alzheimer’s, has always been a sugar junkie of sorts - 2am ice cream raids, gas station apple pies, opens a root beer when he hasn’t finished his previous root beer, etc.

Are we any closer to understanding some sort of causality of decades of sugar abuse?


jvLin t1_j0osthy wrote

This has been known for a long time, but has been downplayed due to 1) not knowing the exact mechanism behind the relationship between diabetes and Alzheimer’s, and 2) the sugar industry shifting blame to fat in the 1980’s.

Sugar/big sugar are evil.


Hedgehogz_Mom t1_j0qusr0 wrote

Yes but the combining of refined sugars into refined simple carbohydrates is the evil of the delivery system imo


Knichols2176 t1_j0qt15w wrote

Not necessarily. It’s about the receptors taking in glucose, not the glucose level.


Wazootyman13 t1_j0p1omp wrote

Ermmm... dumb it down for me more... as in, I'm a Type 1 diabetic... this probably won't affect me as much as if I were a Type 2, right?

(Though, I do have a family history of Type 2)


Pr0gr3s t1_j0pf7iu wrote

If you manage your insulin levels well, exercise, and keep a good diet then your risk levels will be about the same as the general population.

(This is pretty much my scientific wheelhouse)


Organic-Proof8059 t1_j0ofgan wrote

“Cerebrovascular insulin receptors are defective in Alzheimer’s disease”

  1. Cerebrovascular: brain and blood vessels

  2. “Insulin” is needed to bring sugar into a cell. Sugar is needed for energy for the cell. Without insulin the sugar stays outside of the cell in the blood. A glucose/sugar test for diabetics measures how much sugar is in the blood. Regular sugar levels are between 90-120.

  3. Receptor: a docking port on the outside of a cell. A molecule docks on the receptor, and a variety of things can happen afterwards. In this case sugar is simply brought into the cell.

  4. Blood Brain Barrier: The brain has a “border wall” so to say. It is highly selective of what it allows into the brain. In the article it explains that insulin is created in the pancreas which isn’t in the brain. Insulin transport across the blood brain barrier is low in Alzheimer’s patients, meaning that the brain isn’t getting the energy it needs for various functions namely, I suppose, to contribute to a reaction that stops the buildup of amyloid plaques on the brain, which are highly associated with Alzheimer’s.

  5. Amyloid plaques (not mentioned in the article but I’ll write what I’ve studied about Alzheimer’s and the brain in general). Cells have a internal highway called microtubules which serve a variety of functions outside of the one relevant to this discussion. In nerve cells, neurotransmitters like dopamine, serotonin, noradrenaline, etc travel across microtubules (roughly) from one nerve to the other.

Amyloid are protein fragments that are naturally made in the body. Beta amyloids are the unfinished versions of the protein fragments. An accumulation of beta amyloid are called Amyloid plaques which play a role in destroying the microtubule highway up. This in turn prevents neurotransmitters from traveling across a cell.

  1. (This is a very rough explanation of something that is way more complex, just trying to keep it as simple as possible) I’m assuming that since the brain isn’t receiving enough insulin from the pancreas, that the docking mechanism on the blood brain barrier isn’t taking sugar into the brain. This in turn is limiting the brain’s ability to catalyze the amyloid protein to completion and leaving behind the unfinished beta amyloid version, which forms a complex with (tau based) microtubules, triggering a disassembly of the highway. This makes it almost impossible for nutrients to travel across the cell and leads to “impaired long term potentiation,” leading to massive NEURON DEATH which is typical of AD brain.

seedpod02 t1_j0px7j7 wrote

>If I may ask, is sugar the only source of energy for a brain cell?


Organic-Proof8059 t1_j0pynx7 wrote

To my knowledge glucose metabolism is the only energy source for neurons.


elizabethjane50 t1_j0rsqky wrote

Ketones- so, if you get insulin resistance, you could go on a keto diet, give your brain energy, and eventually regain insulin sensitivity.


thatsthefactsjack t1_j0r4ow1 wrote

Thank you for this breakdown. Based on the confirmation of this finding, the impact reaches beyond type 1 and type 2 diabetics and would also affect individuals that develop insulin resistance due to hormone changes.


I_Shuuya t1_j0rohch wrote

So why people with diabetes are more prone to developing Alzheimer's disease? Shouldn't it have the opposite effect since they're synthesizing less beta amyloid?


Organic-Proof8059 t1_j0s8azs wrote

Enlighten me on “shouldn’t it have the opposite effect.” I’m not saying you’re wrong I just don’t understand it to work that way. I could be completely wrong, it’s been a long while since I’ve looked over the mechanisms if any are known.


I_Mix_Stuff t1_j0ocknn wrote

remember Alzheimers being referred as 3rd stage insulin resistance, with diabetes being the second


Pr0gr3s t1_j0pic39 wrote

It's more "type 3", since the diabetic types aren't stages. Also, patients can show brain insulin resistance without showing peripheral insulin resistance (diabetes). That's the crazy part.


skekzok t1_j0og37d wrote

I have heard of that back when my father was alive and I researched the heck out of Alzheimers to better help him.


Smooth_Imagination t1_j0pibfj wrote

It was referred to as 'type 3' diabetes as I recall, as analogus to diabetes in the brain, I'm sure that could have covered an additional progression from type 2 but that it could manifest separately as well.


jawshoeaw t1_j0oojb6 wrote

What’s confusing is that the brain doesn’t need insulin to use sugar. And yet insulin is an important hormone in the brain


Pr0gr3s t1_j0ph8te wrote

This is an old and thoroughly disproven concept that wont seem to die. The brain is absolutely responsive to insulin. GLUT4 is highly expressed in some parts of the brain and requires insulin binding to translocate from storage vehicles to the plasma membrane. Hippocampal memory gets a lot of focus in this regard, which dovetails into Alzheimer's.


Ferris440 t1_j0p5a92 wrote

Yes that was my understanding as well - it uses a different GLUT channel or something like that.

I’d love to know if anyone who understands this area can comment re: the paper.


Pr0gr3s t1_j0piyww wrote

See my comment above, but you're thinking of GLUT4.


r0cafe1a t1_j0olytm wrote

So would Metformin or a Ketogenic diet be protective in this case like for regular IR? Or when dealing with the brain and bbb treatments may be a whole different type?


Pr0gr3s t1_j0pivn4 wrote

There have been several trials with metformin. Mixed results I believe, but there's certainly something there.

Ketogenic diet confuses me as well. I've always assumed that effect is mostly mediated by immune regulation, but I'm not sure.


Agora2020 t1_j0owewt wrote

You read all over the ketogenic diet helps Alzheimer’s. But I don’t understand because keytone is supposed to be harder to break down vs glucose.


BafangFan t1_j0stxq3 wrote

Cells don't need Insulin to uptake ketones. The brain can readily burn ketones when they are available.


StuartGotz t1_j0rwzw1 wrote

In principle, a ketogenic diet keeps insulin levels steady and low, minimizing insulin resistance. People do ingest some carbohydrate (low glycemic load) and the body does produce some glucose via gluconeogenesis.


amp1212 t1_j0pqe1r wrote

Credit to the researchers and the [posthumous] study participants here. It is really hard to do this kind of work, involving enrollment of participants in their lifetimes, cognitive testing, and then having access to their brains after their death for study - much of this kind of neurology can't be done except post mortem.

The investigators and participants get a big vote of thanks here. The effort here is extraordinary; the researchers are all in Quebec, I think the study participants, members of Religious Orders, were too . . . but not clear on that.


Johnnygunnz t1_j0p7q08 wrote

Makes sense. There was some research a few years ago calling Alzheimer's "type 3 diabetes" for similar reasons.


reason2listen t1_j0pqnbz wrote

Hasnt there been some conjecture that Alzheimer’s should be considered type 3 diabetes?


StuartGotz t1_j0rx3p4 wrote

Yes, so this seems like at least one plausible mechanism.


vinbullet t1_j0qhb41 wrote

Hasn't alzheimers been referred to as diabetes of the brain informally for a while now (at least by some doctors)?


Smooth_Imagination t1_j0pl0bi wrote

In type 1 and type 2 diabetes thiamine levels are deficient and kidney excretion greatly increased.

>Renal clearance of thiamine is increased by 8-fold in experimental model of diabetes. Interestingly, increased clearance was prevented by high-dose thiamine supplementation[26]. Thiamine renal clearance is also increased in subjects with T1DM (by 24-fold) and T2DM (by 16-fold)[24].

Part of the disease risk manifested in diabetes was also stated to be retained even after glucose regulation back to normal range - indicating that diabetes is not simply a blood sugar dysfunction and the disease mechanisms are not only manifested through it. One scientist I remember stated that two-thirds of the disease risk remains after blood glucose regulation and that this might be largely mitigated with agents such as thiamine and lutein.

Lutein is an interesting compound that negatively correlates to diabetes risk, but it also concentrates above serum levels in the brain, as well as skin and retina.

Lutein hyperaccumulates in brain -

-DHA distribution also correlates with lutein. This suggests a natural tendency to accumulate these compounds together and that this is a functional thing. Lutein upregulates natural production of antioxidants in retinal tissue and might be doing that in the brain. There are associations of both DHA and Lutein to protection against Alzheimers / dementia.

- this is a negative result regarding DHA supplementation (DHA on its own, it may also be oxidised prior to consumption and this is known to reduce tissue distribution of DHA potentially leading to ineffective dosing. So the study may be worthless if there is not means to reduce DHA degradation in vitro or/and prior to consumption.

- this later study addresses this with higher dose but I believe does have connections to a supplier of DHA, full disclosure.

- lutein protects blood lipids, phospholipids and presumably lipoproteins from oxidation - thereby it should protect DHA from oxidation in the main carrier that transports it the brain, although it may act on different lipids rather than DHA, still of relevance to the oxidative stress and inflammatory signalling found in Alzheimers -

Its a complicated picture -

>Lutein/zeaxanthin supplementation significantly increased total concentrations of lutein in serum, PFC and CER, as well as lutein in mitochondrial membranes and total DHA concentrations in PFC only (P<0.05). In PFC and ST, mitochondrial lutein was inversely related to DHA oxidation products, but not those from arachidonic acid (P <0.05).

- It seems reasonably to predict that non-oxidised DHA is superior at lower doses in delivery to the brain and that co-administration of DHA with lutein is potentially superior again, and that this may be beneficial in protecting the brain.

More on Lutein


Consequently thiamine was suggested as a way to reduce some of the residual risks such as peripheral polyneuropathy.

Remember when Alzheimers was referred to as 'Type 3 diabetes' due to insulin, glucose and metabolic dysfunction in the brain?

>Indeed, comparisons of immunocytochemical markers suggest that oxidative stress is more prevalent in AD than are plaques or tangles.8 Indeed, markers of oxidative stress in the urine of mice genetically engineered to make plaques precede plaque formation in the brain.9

- it isn't necessarily the plaques, but more the sub units that form into plaques that act as contributors, and there is a role for Tau as well, but they are just roles in something multi-factorial in origin.

>Glucose metabolism is always diminished in AD
>Extensive research has examined the relationship of cerebrospinal fluid (CSF) biomarkers of amyloid and tau and compared those to glucose metabolism, as measured by [18F]fluorodeoxyglucose ([18F]FDG) positron emission tomography (PET).10 Reduced glucose metabolism occurs in AD long before the patient demonstrates significant clinical signs of AD. The regional changes in glucose metabolism are also highly correlated to changes in cognition. The correlation of changes to amyloid as measured by PET scan is very poor.11 The common explanation for these changes is that glucose metabolism as measured by [18F]FDG PET reflects synaptic activity, and since a loss of synapses accompanies AD, the loss of glucose use merely reflects the decline in synapses. This is likely true but also raises the possibility that reductions in glucose metabolism promote AD.

It seems to have overlapping aspects with the known types of diabetes.

If you have type 2 or 1 diabetes, you may have lower brain thiamine. In Alzheimers additional things could be happening in the brain that emulates low brain thiamine or dysfunction of thiamine pathways that could, like amyloid or tau, have a role in the disease, but maybe not always. Its still likely a multifactorial thing.


Rare-ish_Bird t1_j0rkmux wrote

Fascinating. Both my mom and my mom's friend went through a high-sugar consumption phase 2-3 years before the symptoms of their Alzheimers kicked in. I always wondered if the sugar cravings related to some physiological change in the brain limiting glucose usage. Seems plausible in light of this study.


StuartGotz t1_j0rxjy6 wrote

Makes me wonder whether a low glycemic index/load diet plus supplement with exogenous ketones would be preventative.


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Knichols2176 t1_j0qthw1 wrote

Has there ever been a study of all that are prescribed glucophage? If this has merit, glucophage prescribed should have less incidence of Alzheimer’s.


dobrits t1_j1raul2 wrote

My grandaunt had 500mg glucophage daily and then had rapid Alzheimer’s. There might be some connection but I can’t figure it out.