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- Type of diabetes
- I reversed my Type 2
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Slightly different tack ....
As I was watching and taking notes of a reaction to a breakdown on YouTube (honestly, in order to make sense of some of this high level biochemistry, I need to consume so much interlinking information, that sometimes it feels like an scene from Inception) of the Randle Cycle, the host just stopped and said something to the effect of "it's so frustrating; this is so unbelievably complex, but there is no simple version, it's all complex, and that's part of the problem, because you can't just tell the simple story, so people grab one part of it and tell that, and then suddenly you have a nice story, but it's wrong".
This guy was hard to keep up with, and for me; this is my third time at trying to wrap my head around it, and I feel like my fingertips are still scrabbling at the top of the hole... but let's see where we get to.
File this under - "it's all chemistry really"
I've had a long-term issue with phrases like "the liver dumps glucose", or "the brain's preferred fuel", because, as humans; we tend to think of the way that things happen, like there is a collection of tiny humans somewhere making decisions the way that humans do. Sometimes it can be a highly useful analogy (think Pixar's "Inside Out") but often it's unhelpful, because we ascribe an emotional element that just isn't there; you don't need to stress that your liver is somehow conspiring against you, if you can just understand enough of the biochemistry to see what is going on.
So, one of the single most important questions that underpins T2DM, dietary approaches, metabolism - the whole shaboodle - is - "under what conditions will the body burn fat, or glucose?"
This was what Dr Randle was trying to answer in 1963, and the experiment was basically to remove a bunch of rodent hearts, keep them alive and pumping, then suffuse them in different fuel sources (or substrates) to see what happens.
The short version of the answer is the Glucose-Fatty acid cycle of cross-inhibition; but in detail it's really - and I mean really - complicated, and I've been trying for some time now to figure out how best to describe it; because there are very few things that are more important, but it's so ferociously complicated that you just won't find anything about this except for the kind of nerd science back alleys that I've been wandering around.
At a basic level, the Randle cycle can be expressed as: the very action of burning glucose for energy blocks the pathways for the cell to burn fat, and at the same time; the very action of burning fat for energy blocks the pathways for the cell to burn glucose. That's it. Factually. Nothing more, but it'll require a little more to get to why that's important.
The best way I can come up with to visualise that, is a toggle-switch. You may not know the term, but you will almost certainly have used one - a switch with a long stalk; you push it over the tipping point, then a spring will toggle it to the other position. To switch back, you push it in the other direction, and again you need to push it past the middle point. If you push the switch a little bit, it will just spring back to where it was, and you just cannot find a middle ground, where the switch is neither in one position or the other.
This is what is going on in virtually all of your cells, all the time. There is a chemical "pressure" caused by the concentration of fat or glucose (in the cell, available to the mitochondria, which is different to - in the body, or in the blood stream). More glucose puts pressure on shutting down fat burning, and more fat puts pressure on shutting down glucose burning. If there is more of one than the other - the system "toggles" and it requires a bigger pressure from the other substrate to reverse the toggle.
The relative concentration of insulin and glucagon plays a part in this as well (think in terms of insulin having a thumb on the scale, as it were) but for now, lets just think about the substrates, the fuel.
This, you may understand, is why we talk about "becoming fat adapted" or "metabolic flexibility" or any of the other terms that acknowledge you cannot be both burning glucose and fat at the same time; it has to be one or the other.
But - so far so good, you have a switch, and it toggles or not; what's the deal?
The deal is, that while the fuel burning can only be one or the other - the pressure can be both, and can be high, and is happening at the same time.
This has taken me a year to figure out: right down at the cellular level - if the food you eat is a mix of fat and sugar; sugar will win (because of insulin, natch) but the fight between fat and glucose will go on, and that means inflammation.
Now - I when I say that this took a year to understand, I mean it, and both the reason why and the effect it has is quite subtle. It's all to do with that idea of pressure. Go back to that toggle switch, but this time, instead of imagining yourself, calmly flicking it with your finger, imagine an arm wrestle over it; an arm wrestle that keeps going even after someone loses... and keeps going ... and keeps going. That is essentially what is happening... your cells are in a state of conflict because both fuels want to be used, and the result of that conflict is a massive production of inflammatory particles - Cytokines, and this is also a direct part of what insulin resistance is... that inflammation directly drives insulin resistance - as a survival mechanism for the cell - it's a toxic situation for the cell, and as a response, it closes down the transporters to stop more glucose getting in.
I've just realised I've done the same thing. It isn't that both fuels want to be used, it's simply that chemically, if a thing can happen, it will, and so fat and glucose will be oxidised, but the part products of both pathways interfere with each other. The arm wrestlers have no option but to keep going, even though they are both in pain.
How do we see that ? as resistance to the action of insulin -and how can you change it ? one way is with a relatively massive dose of insulin (to force those transports back open to get the glucose out of the blood and into the cells).
To some extent this then starts to make sense of why there are really two (apparrently opposite) ways to affect T2DM with dietary changes - one that focuses on reducing fat, and one that focuses on reducing sugar. If you remove the conflict, you remove the inflammation.
Seen through this lens - it's a totally different way of looking at food. It's much more about avoiding food which results in glucose and fatty acids hitting your cells at the same time.
As I was watching and taking notes of a reaction to a breakdown on YouTube (honestly, in order to make sense of some of this high level biochemistry, I need to consume so much interlinking information, that sometimes it feels like an scene from Inception) of the Randle Cycle, the host just stopped and said something to the effect of "it's so frustrating; this is so unbelievably complex, but there is no simple version, it's all complex, and that's part of the problem, because you can't just tell the simple story, so people grab one part of it and tell that, and then suddenly you have a nice story, but it's wrong".
This guy was hard to keep up with, and for me; this is my third time at trying to wrap my head around it, and I feel like my fingertips are still scrabbling at the top of the hole... but let's see where we get to.
File this under - "it's all chemistry really"
I've had a long-term issue with phrases like "the liver dumps glucose", or "the brain's preferred fuel", because, as humans; we tend to think of the way that things happen, like there is a collection of tiny humans somewhere making decisions the way that humans do. Sometimes it can be a highly useful analogy (think Pixar's "Inside Out") but often it's unhelpful, because we ascribe an emotional element that just isn't there; you don't need to stress that your liver is somehow conspiring against you, if you can just understand enough of the biochemistry to see what is going on.
So, one of the single most important questions that underpins T2DM, dietary approaches, metabolism - the whole shaboodle - is - "under what conditions will the body burn fat, or glucose?"
This was what Dr Randle was trying to answer in 1963, and the experiment was basically to remove a bunch of rodent hearts, keep them alive and pumping, then suffuse them in different fuel sources (or substrates) to see what happens.
The short version of the answer is the Glucose-Fatty acid cycle of cross-inhibition; but in detail it's really - and I mean really - complicated, and I've been trying for some time now to figure out how best to describe it; because there are very few things that are more important, but it's so ferociously complicated that you just won't find anything about this except for the kind of nerd science back alleys that I've been wandering around.
At a basic level, the Randle cycle can be expressed as: the very action of burning glucose for energy blocks the pathways for the cell to burn fat, and at the same time; the very action of burning fat for energy blocks the pathways for the cell to burn glucose. That's it. Factually. Nothing more, but it'll require a little more to get to why that's important.
The best way I can come up with to visualise that, is a toggle-switch. You may not know the term, but you will almost certainly have used one - a switch with a long stalk; you push it over the tipping point, then a spring will toggle it to the other position. To switch back, you push it in the other direction, and again you need to push it past the middle point. If you push the switch a little bit, it will just spring back to where it was, and you just cannot find a middle ground, where the switch is neither in one position or the other.
This is what is going on in virtually all of your cells, all the time. There is a chemical "pressure" caused by the concentration of fat or glucose (in the cell, available to the mitochondria, which is different to - in the body, or in the blood stream). More glucose puts pressure on shutting down fat burning, and more fat puts pressure on shutting down glucose burning. If there is more of one than the other - the system "toggles" and it requires a bigger pressure from the other substrate to reverse the toggle.
The relative concentration of insulin and glucagon plays a part in this as well (think in terms of insulin having a thumb on the scale, as it were) but for now, lets just think about the substrates, the fuel.
This, you may understand, is why we talk about "becoming fat adapted" or "metabolic flexibility" or any of the other terms that acknowledge you cannot be both burning glucose and fat at the same time; it has to be one or the other.
But - so far so good, you have a switch, and it toggles or not; what's the deal?
The deal is, that while the fuel burning can only be one or the other - the pressure can be both, and can be high, and is happening at the same time.
This has taken me a year to figure out: right down at the cellular level - if the food you eat is a mix of fat and sugar; sugar will win (because of insulin, natch) but the fight between fat and glucose will go on, and that means inflammation.
Now - I when I say that this took a year to understand, I mean it, and both the reason why and the effect it has is quite subtle. It's all to do with that idea of pressure. Go back to that toggle switch, but this time, instead of imagining yourself, calmly flicking it with your finger, imagine an arm wrestle over it; an arm wrestle that keeps going even after someone loses... and keeps going ... and keeps going. That is essentially what is happening... your cells are in a state of conflict because both fuels want to be used, and the result of that conflict is a massive production of inflammatory particles - Cytokines, and this is also a direct part of what insulin resistance is... that inflammation directly drives insulin resistance - as a survival mechanism for the cell - it's a toxic situation for the cell, and as a response, it closes down the transporters to stop more glucose getting in.
I've just realised I've done the same thing. It isn't that both fuels want to be used, it's simply that chemically, if a thing can happen, it will, and so fat and glucose will be oxidised, but the part products of both pathways interfere with each other. The arm wrestlers have no option but to keep going, even though they are both in pain.
How do we see that ? as resistance to the action of insulin -and how can you change it ? one way is with a relatively massive dose of insulin (to force those transports back open to get the glucose out of the blood and into the cells).
To some extent this then starts to make sense of why there are really two (apparrently opposite) ways to affect T2DM with dietary changes - one that focuses on reducing fat, and one that focuses on reducing sugar. If you remove the conflict, you remove the inflammation.
Seen through this lens - it's a totally different way of looking at food. It's much more about avoiding food which results in glucose and fatty acids hitting your cells at the same time.
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