T2 or NAFLD? ...or, a funny thing happened on the way to the surgery

[Chris24Main]

Actually that leads nicely to the next point - I've now finished the "Life without Diabetes" book - and really only disagree on two things - Roy Taylor talks about Fructose being turned into Glucose by the liver, (whereas he talks about alcohol being better thought of as liquid fat - I think that's closer to the position with Fructose) and while he dismisses the narrative about saturated fat leading to heart disease via raised LDL, he does continue the narrative about saturated fat itself being undesirable (albeit in quite a nuanced way) in the diet. I think things have simply moved on since this book was written.

Also, it may well be that he's a better politicker than I am - you don't get to be a professor of medicine and raise several million pounds, and single handedly overturn the concept that T2DM is inevitably progressive without being able to choose your battles.

Overall, I was amazed at how much I agree with - and everything else is really a question of emphasis. You emphasise the problem with too much fat deposits, and de-emphasise the role that the hormones have to play, and you change a condition of hormone dysregulation to one of fat dysregulation - but to some extent it's as useful as arguing about which came first, the chicken or the egg? - does the existence of chickens depend on one of the theories being the correct one? - not really.

You can also take his entire book, and say that I, personally have done everything precisely according to his plan, and had the desired outcome. I just haven't used meal-replacement shakes, I've focused on a way of eating that priorities lowering insulin - however, I did it in a stepped way, with a very sudden and extreme first step, a transition step, and a long term phase, I've lost about the amount of weight he recommends (I just know that my way has avoided any loss of muscle) and my long term eating is probably about 3/4 the amount of calories (I just get there by eating more fat, and therefore naturally feeling more full more quickly) - but all of the things I've done are discussed in his book, and he talks about the pros and cons, and that different things work for different people.

I could turn it around, and say that the meal-replacement shakes are really one form of extreme intermittent fast. You can't take them forever, and you can't fast forever.

But - for a lot of people - buying into the idea of meal-replacement shakes is easier than accepting, or even trying intermittent fasting. So - you meet people where they are, and everyone benefits.

I'm certainly more happy recommending the Newcastle approach having read the book.

Personally - I still think that in the long term, you will be healthier and more mentally resilient by becoming metabolically fat-adapted, and that the Newcastle approach is easier to achieve by working with your hormones to avoid hunger, but I no longer feel that this is an obstacle - it's just that I think there are subtleties on top.

 

[zand]

The ND approach is 'lose weight and you can lose weight from your organs and improve your BGs'. Yet some folk on here have done it the other way round - improve BGs by going low carb and then the weight loss happens.

So, with NAFLD the ND approach is 'lose weight overall and your liver will slim down'.
What if it also works the other way round? Slim your liver first and then the weight loss occurs?

I'll explain, but first I need to say I am not recommending that anyone else tries what I did without consulting their doctor, some say what I did is dangerous. This is simply my own experience.

A few years ago I had a horrendous pain in my side and my poo was pale and always floated. I had an appointment with my GP but had to get through the long Easter weekend first. Wanting to just do 'something' to stop the pain I did a gall bladder and liver flush, thinking this was a blocked bile duct, but I didn't have time to do the week's preparation to soften the stones first. I just went straight into it. It worked. I felt a worse pain when the stone was flushed from the duct then a steady painless gush as several small stones followed. There were also 4 white, perfectly round marble sized objects. I told my GP after the event and he said that in this instance that was the right thing to do. Liver flushes are controversial though with some consultants dismissing that they ever work.

Fast forward to November 2024. 13 years from diagnosis I had slowly lost around 4 and a half stones, making me the same weight I was 20 years before. I followed LCHF for most of that time. But I had been stuck at that weight, gaining a bit, losing it again, but never going below it. I was getting frustrated. For all of those 20 years my tests showed I had fatty liver of varying degrees, even 7 years before T2 diagnosis.

Then I thought of something another poster on here said to someone else. The lady also had those small white marble like objects, but these came up in her vomit one day. Someone said that he felt these objects were metformin tablets doing what they were supposed to do...mop up the fat.

I forgot about this until November. So I did a liver flush again (I didn't take the decision lightly, I really hate them!) This time I did the week long preparation first. The lumps released weren't quite spherical this time (I don't take metformin any more as I developed a B12 deficiency) and they were bright green (probably due to the apple juice used in prep beforehand). There were 4 large marble sized ones and 6 ordinary marble sized ones, plus several of the tiny ones that I think were from my gall bladder.

Life got busy. I forgot I had done the flush. Then after Christmas I got on the scales expecting to have put on around 4 pounds...and I was a stone lighter than I thought I would be! So that was around a 10 pounds weight loss since November . Today, it's a stone lost. I panicked, thinking there must be something really wrong with me with such a huge weight loss when I wasn't sticking to low carb much at all and I wasn't exercising. My diabetic review was overdue so I spoke to a doctor who arranged for other tests to be done at the same time to rule out something more sinister. When I printed out the results the penny finally dropped. The ALT liver count which should be lower than 35 was now 29. 29! In the past it has varied from around 50 to 160. I was in shock. A few of the other tests were slightly out of range, but I have recently had a bad virus, so they are in line with my body fighting the virus.

Way back when the ND was first mentioned on TV. they referred to it as a 600 calorie diet. I wasn't yet T2 but knew I was IR. They forgot to mention the 200 cal meal that was also part of the shake diet. Thinking '600 cals' meant 600 cals (silly me). I followed it for 7 weeks, eating mostly veggies, when I had to give up as my bones hurt alot as I hadn't added any fat to my diet. I lost 10 pounds but soon regained it even though I wasn't overeating.

My thyroid was tested several times by my GP. All were 'OK'. Not believing this, I paid for a private test which revealed that although my thyroid produced enough raw hormone , that hormone wasn't being converted to active hormone well enough. A couple of years back I asked a GP about this. He said the liver converts the raw hormone into active. So maybe now my new, slim liver works better at its other many functions, not just glucose regulation etc.

Oh and I am now the same weight I was 23 years ago. I'm still obese but my liver isn't.

 

[Chris24Main]

Yep - totally - that is precisely what I'm saying.

If you focus on reducing insulin, or if you focus on reducing weight - you can get caught up in cause and effect... but in the end, it's the same interconnected causes, and the same end result - so all is good.

 

[Chris24Main]

And - this is really where I'm going next - the danger with the "everything is about insulin" line of thought that I've been ploughing; is that you de-emphasise the effects that fat deposits can have in the organ tissue - even if the cause of those fat deposits is still insulin resistance. So - I'm going into a deep dive on the effect of fat in the liver and pancreas - that insight about thyroid hormone (active or not) is definitely something I want to pursue - thanks for your valuable insight, @zand

 

[Chris24Main]

But one more thought first to put this line of thought to bed.
"Is it the insulin resistance or is it fat?"

Despite saying it doesn't matter, I do want to lay out the mechanism, because I think this is so critical to fully understanding.

To some extent - we are led to think about insulin and Glucose being intrinsically linked - and that one affects the other and that's the end of the story.

However, insulin is the master regulator of energy. Energy is about metabolism, and at the cellular level, we are actually capable of using many many sources of energy. I've talked recently about the mitochondria being evolved from the first bacteria to tame oxygen.. well, they had methods of energy creation before that, and the larger cells that house the mitochondria also have independent ways of creating energy - they had to; they started off as independent organisms. There are even ways that cells can generate energy directly from sunlight (weakly of course, the chloroplast is very similar to the mitochondria in that they suddenly figure out how to really lean in to sunlight, then they get swallowed up by what went on to become all of the plant kingdom).

Anyway - insulin is about energy regulation, and that means storing as well as making fuel available. And in humans, we can store a very small amount of sugar-based energy - about a days' worth, and we can store a lot of fat-based energy (current record is over a year, for comparison).

Now, you can immediately get into an argument about what this tells you about the "body's preferred energy source" - but all of that is irrelevant for now - the simple fact - and this is non-contentious - is that for long-term energy storage, we are adapted to use fat, and insulin manages whether we are storing or releasing that fat.

So - we come back to the key phrase of energy regulation. I won't repeat it again, but if insulin is elevated, the fat storage cells - adipose tissue - are under orders to store (and not release) fat, in the form of triglycerides (fat not being soluble in blood or cell plasma).

In the fat-adapted body - this waxes and wanes - energy comes in after food, energy goes out to be burned during fasting.

In the high-carb and snacking (ie, normal) world - insulin is pretty much always high, so energy comes in, energy comes in, energy comes in.

Now, adipose tissue are highly sophisticated (they really are the underdogs of the anatomy - sorely misunderstood as just sitting under the skin, providing padding) - with deep signalling to the liver and brain, and even creating their own hormones (most obviously leptin and adiponectin, but many others). They are specialised to swell to hundreds of times their starting point - much more than any other cell type.

But - there are limits - in the case of "always storing" - there are effects of energy toxicity - so too much fuel for the mitochondria to use - but that's not even the point - there is a limit at which triglycerides start to "leak" back in to the stuff outside the cells. Despite insulin packing them in, some fat packages start to leak out of the cells, back into the blood - where they just flow around in a totally uncontrolled way - and this is what leads to fatty liver (more directly, because the liver is the first place to store, and in some cases - looking at you, fructose - the only place to store) but also all organs, and the heart, and the brain.

Understanding that insulin is also directly at the heart of the fat equation; and this is also mainly the liver, and therefore also highly dependent on the amount of carbs in the form of sugar and starches - (remember - none of the above happens if you are only eating fat) - this I think is the most important key to prising open the mysteries of how the body works, and starts to make sense of a bunch of things that otherwise seem impenetrable.

 

[Chris24Main]

By the way - there is a fascinating article in Politico about how "the Mediterranean Diet is a lie":

It's something I've mentioned before, that in it's time (early 50's southern Italy) it was really much more about sugar still being rationed post-war. This, being Politico, is much more of a wide-ranging article, that gets into current politics as well as the history of nutrition, but there are phrases from contemporaries in Nicotera, where Ancel Keys did his studies...

Keys essentially interviewed people and then wrote a book, and that formed the basis for the seven countries study, his career and fame; but according to someone around at the time, it was all made up, and for the American audience, not at all based on what people were really doing, they were really impoverished peasants and, for instance:

Keys “went to the people’s houses and people were ashamed. They’d say ‘Come back tomorrow because today we won’t eat anything.’

Which sounds a lot like daily intermittent fasting to me. Which is what I did - now, I have an appointment with my DN next month (first since remission, in fact first yearly check) - I think I'm going to say that in the early period I followed the Mediterranean diet, but with historical accuracy... see how that goes...

 

[Chris24Main]

So, this is a bit of a record for saying something and then needing to correct it. Just been schooled on Fructose metabolism by Nick Norwitz, and it resolves one of the "disagreements" I had with Roy Taylor - I'm sure he's very relieved <joke, in case that's necessary>

I'd said that the liver can only turn fructose into fat, which it stores itself, leading to inflammation of it's own fat storage which become insulin resistant ... yadda yadda..

Roy said that fructose is turned into glucose.

Both cannot be true; or can they....?

turns out yes.... kind of.
Real food containing fructose, ie, fruit, is digested in the intestine... where an amount of it is turned into glucose, before being transported to the liver.

In other words - depending on your adaptation to fruit (ie, how much fruit you normally eat, and the type of fruit etc) the majority of fructose can be turned into glucose before the liver even sees it, leaving it with nothing additional to do.

Dosage maketh the poison though, and anything above that (personal, individual) threshold capacity in the gut, and you will be delivering fructose to the liver. Critically, this also doesn't work with high fructose corn syrup, or smoothies, which will just overload any digestion, and flush into the liver.

 

[Chris24Main]

A little aside for a personal update. I was going to post this in one of the dietary forums, but I think I'm safer posting here - this is some reasonably high-level stuff, and I don't want to confuse anyone.

So - backing up a year - my plan was to rapidly pump the fat out of my liver by daily fasting and going what I thought then was low carb. After a month, I backed off the fasting to about fortnightly, and settled in to learning about insulin resistance.
I've more and more focused on eating to hold insulin low, in order to become fat adapted; my thinking being that insulin resistance is really chronically high insulin, so anything to hold insulin low will reverse that over time.
Low insulin should mean ketones, so I got a ketone monitor and started using that, eventually settling on measuring first thing in the morning, every day.
I was initially quite shocked and disappointed at the levels - but picked up that it may take a year to eighteen months to become fat adapted, so I settled in to measuring daily, but plotting averages, because the daily levels seemed all over the place.

If I was right - over time, my morning blood glucose would steady out, and my average ketone level should keep rising, and then (I guessed) should reach some kind of plateau in about a year.

More recently, I've discovered how to "extend" fasting with bullet-proof coffee. For example, I started off the day solidly in ketosis, went paddle boarding for 40mins (about half of which was sprinting- so quite high intensity), then had a bullet proof coffee - it's currently mid-morning, and I feel totally satisfied, and may skip lunch, or may have some bacon and eggs. - either way it will be around 18 hours since "eating" - 20 plus if I do skip lunch - that ends up being a really effective way to compress my eating window without ever feeling hungry. I can have a totally nutritious lunch and dinner, including some clotted cream and 85% chocolate - totally love what I eat, and I know I will be solid ketosis and feeling great in the morning.

anyway - here is the current plot:

 

[Chris24Main]

So - ignore most of it - the key thing is that the red line (the average fasting blood glucose) has settled around 5 mmol/L - it will be higher through the day - so that isn't going to predict my HbA1c (which I will get at the end of Feb) but you can see that it's doing what I expected, and the wiggly measurement line is less wiggly.

The blue ketone line is going up. I'm finding that I'm now (only really in the last month or so) quite reliably in ketosis in the morning. Where the blue line started off wobbling quite a lot - mostly down, then spiking high (usually on account of fasting - and that one very high spike was me paddling for two hours solid after fasting for a day and continuing to fast... that was quite the shock, though I felt fine, and had to actually calm myself down - it can't be DKA, because my blood glucose level is around 4... it can't be DKA...

For reference - that level is what this type of ketone monitor sets as dangerous - so 40 or so on this graph equates to 3 on the classic (you need to go straight to hospital) charts. - I was definitely above that level.

Anyway - the very short version of this is that I'm interpreting all of this as good evidence that I am gradually becoming fat-adapted. I'm going into, and staying in ketosis much more easily, so I'm burning more fat, and breathing out calories all the time (for those calories-in calories-out advocates).

All of that is good, and largely as predicted.
Bizarrely, what I need to consider next - is that being in ketosis all the time is not good, in exactly the same way that being in glucose-burning all the time is not good.

Part of the benefit of low insulin is that it promotes autophagy - which sounds horrendously complex, but is simply to health what recovery is to exercise - it's all a balance. Autophagy allows broken down bits of cells to be recycled; but you cannot be in a state of breaking stuff down all the time - sometimes you need to build - and that is what insulin is all about.

So - the next stage of the journey for me might well involve some of the things I've been avoiding for a year - I want to be able to knock myself out of ketosis, say one day a week - kind of the opposite of fasting, I'll probably want to deliberately have some carbs...

The next phase is about becoming metabolically flexible...

(I just need to think about how to do it without feeling unwell - I know if I have a plate of fried rice, I'm just going to feel terrible.)

 

[jeano999]

So - ignore most of it - the key thing is that the red line (the average fasting blood glucose) has settled around 5 mmol/L - it will be higher through the day - so that isn't going to predict my HbA1c (which I will get at the end of Feb) but you can see that it's doing what I expected, and the wiggly measurement line is less wiggly.

The blue ketone line is going up. I'm finding that I'm now (only really in the last month or so) quite reliably in ketosis in the morning. Where the blue line started off wobbling quite a lot - mostly down, then spiking high (usually on account of fasting - and that one very high spike was me paddling for two hours solid after fasting for a day and continuing to fast... that was quite the shock, though I felt fine, and had to actually calm myself down - it can't be DKA, because my blood glucose level is around 4... it can't be DKA...

For reference - that level is what this type of ketone monitor sets as dangerous - so 40 or so on this graph equates to 3 on the classic (you need to go straight to hospital) charts. - I was definitely above that level.

Anyway - the very short version of this is that I'm interpreting all of this as good evidence that I am gradually becoming fat-adapted. I'm going into, and staying in ketosis much more easily, so I'm burning more fat, and breathing out calories all the time (for those calories-in calories-out advocates).

All of that is good, and largely as predicted.
Bizarrely, what I need to consider next - is that being in ketosis all the time is not good, in exactly the same way that being in glucose-burning all the time is not good.

Part of the benefit of low insulin is that it promotes autophagy - which sounds horrendously complex, but is simply to health what recovery is to exercise - it's all a balance. Autophagy allows broken down bits of cells to be recycled; but you cannot be in a state of breaking stuff down all the time - sometimes you need to build - and that is what insulin is all about.

So - the next stage of the journey for me might well involve some of the things I've been avoiding for a year - I want to be able to knock myself out of ketosis, say one day a week - kind of the opposite of fasting, I'll probably want to deliberately have some carbs...

The next phase is about becoming metabolically flexible...

(I just need to think about how to do it without feeling unwell - I know if I have a plate of fried rice, I'm just going to feel terrible.)

I look forward to your posts - always informative. I too have been low carbing and fasting and hoping for ketosis to kick in and autophagy. Many books/articles I have read estimate over 20 hours of fasting for autophagy to kick in so I take it that breaking the fast with food will cause it to cease. I regularly do OMAD so fasting for 24 hrs I assume that I am going in and out of autophagy. Ketones I only measure occasionally with pee-sticks which I am aware are not very reliable - so I just assume that the above regime will work. So am I right in thinking that a) when my blood sugar rises (with or without food) I am out of ketosis and b) when I eat after fasting I am out of autophagy. Your thoughts on this would be appreciated.

 

[Chris24Main]

Hi @jeano999 - and thanks.
Timely reminder that I should mention that I don't really know anything, and that nothing I mention should at any point by anyone be regarded as anything other than totally suspect, and needing checking by someone who could tell his elbow from his pancreas a year ago - this is all purely a journal of my own journey of discovery; the only thing I promise is that when I spot my own ignorance before anyone else does, I'll be happy to share that too.

But to try to answer your question - it's all about timing...

In the first event - we have reactions to the acute environment - what we've just eaten, how warm it is, how safe we feel, what time of day ect.
In response to that - there are a whole bunch of reactions - some chemical, some enzyme, some hormonal, some direct protein signalling or even electrical signalling - all aiming to bring that first event back to "normal" - this is homeostasis in all it's complexity.

What "normal" is - depends on longer term things, like genetic expression, your chronic environment (what type of things you habitually eat, whether you have been ill, how much your job or your teenage daughter stresses you out... etc) - but can change over time.

Because we are people - it's easy to think of this like having gauges inside us - we talk about "the master regulator for temperature" - or the pancreas measuring blood glucose levels - but it's all ultimately competing pressure to do things based on what's around - more glucose in the blood coming into the pancreas (from the stomach and gut) creates more pressure for the β cells to produce insulin and create more pressure on the α cells to stop producing glucagon.

These flow into the liver, where the pressure to break down glycogen changes into pressure to create and store glycogen from glucose as the concentration of glucagon/insulin changes. After some time, the glucose level drops and the blood flowing back into the pancreas has a low enough glucose concentration that the pressure on the β and α cells switches over, and glucagon predominates - though you may spot that this is why we can feel low on energy after a spike - the fall, or crash is simply a question of the blood needing to flow about a bit before the pancreas picks up the signal.

Over time, insulin resistance (or sensitivity) changes the balance. For the same event, the same blood entering the pancreas and hitting the same β cells may cause the exact same amount of insulin to be generated, but now that insulin has less effect per cell in the liver (because the liver has become more insulin resistant, meaning less working insulin receptors - meaning the cell cannot "see" as many insulin molecules - so needs a higher concentration of insulin to have the same effect as before) so now the pancreas experiences high glucose concentration for longer, and thus produces more insulin.

This can take decades of gradual change to become significant - but it makes sense - high insulin drives insulin resistance, drives higher insulin - progressively over time. If it was just a matter of calories, I think Gary Taubes has it that we would need to (in order to create the same kind of weight-gain pattern over time, for example, and I understand that not all people put on weight, this is just an example, and I'm sure I'll remember it badly) eat precisely half a teaspoon of food more than we need every meal; how can you know, and how can you do it consistently for 20 years?

So - progressive changes in our sensitivity to the gamut of hormones over time change our "master" normal levels, but also change the acute reactions to various foods.

We - of course - concentrate on glucose - I mean, I just did... but really insulin is about energy management, and for humans that's more a question of fat - fat storage and release, and fat burning or turning into ketones. If you zoom out a bit - one of those master regulator "normals" is the level at which we can switch from glucose (storage or burning) to fat (storage, or release and burning).

In other words - anyone can generate some ketones, by eating a stick of butter, then nothing else for a week. Definitely not advisable, and significantly dangerous, but anyone could. [can't stress enough that I'm not suggesting anyone actually do this...]

However, if you eat in a way that keeps insulin very low (ie, such that a CGM shows more or less a flat line) over a long time.. the threshold at which the body flips into fat burning and/ or autophagy (they are different, but I'm trying to keep this simple, honest) drops, and you start to create ketones closer to what your body now considers "normal".

Long term and short term...

 

[jeano999]

Hi @jeano999 - and thanks.
Timely reminder that I should mention that I don't really know anything, and that nothing I mention should at any point by anyone be regarded as anything other than totally suspect, and needing checking by someone who could tell his elbow from his pancreas a year ago - this is all purely a journal of my own journey of discovery; the only thing I promise is that when I spot my own ignorance before anyone else does, I'll be happy to share that too.

But to try to answer your question - it's all about timing...

In the first event - we have reactions to the acute environment - what we've just eaten, how warm it is, how safe we feel, what time of day ect.
In response to that - there are a whole bunch of reactions - some chemical, some enzyme, some hormonal, some direct protein signalling or even electrical signalling - all aiming to bring that first event back to "normal" - this is homeostasis in all it's complexity.

What "normal" is - depends on longer term things, like genetic expression, your chronic environment (what type of things you habitually eat, whether you have been ill, how much your job or your teenage daughter stresses you out... etc) - but can change over time.

Because we are people - it's easy to think of this like having gauges inside us - we talk about "the master regulator for temperature" - or the pancreas measuring blood glucose levels - but it's all ultimately competing pressure to do things based on what's around - more glucose in the blood coming into the pancreas (from the stomach and gut) creates more pressure for the β cells to produce insulin and create more pressure on the α cells to stop producing glucagon.

These flow into the liver, where the pressure to break down glycogen changes into pressure to create and store glycogen from glucose as the concentration of glucagon/insulin changes. After some time, the glucose level drops and the blood flowing back into the pancreas has a low enough glucose concentration that the pressure on the β and α cells switches over, and glucagon predominates - though you may spot that this is why we can feel low on energy after a spike - the fall, or crash is simply a question of the blood needing to flow about a bit before the pancreas picks up the signal.

Over time, insulin resistance (or sensitivity) changes the balance. For the same event, the same blood entering the pancreas and hitting the same β cells may cause the exact same amount of insulin to be generated, but now that insulin has less effect per cell in the liver (because the liver has become more insulin resistant, meaning less working insulin receptors - meaning the cell cannot "see" as many insulin molecules - so needs a higher concentration of insulin to have the same effect as before) so now the pancreas experiences high glucose concentration for longer, and thus produces more insulin.

This can take decades of gradual change to become significant - but it makes sense - high insulin drives insulin resistance, drives higher insulin - progressively over time. If it was just a matter of calories, I think Gary Taubes has it that we would need to (in order to create the same kind of weight-gain pattern over time, for example, and I understand that not all people put on weight, this is just an example, and I'm sure I'll remember it badly) eat precisely half a teaspoon of food more than we need every meal; how can you know, and how can you do it consistently for 20 years?

So - progressive changes in our sensitivity to the gamut of hormones over time change our "master" normal levels, but also change the acute reactions to various foods.

We - of course - concentrate on glucose - I mean, I just did... but really insulin is about energy management, and for humans that's more a question of fat - fat storage and release, and fat burning or turning into ketones. If you zoom out a bit - one of those master regulator "normals" is the level at which we can switch from glucose (storage or burning) to fat (storage, or release and burning).

In other words - anyone can generate some ketones, by eating a stick of butter, then nothing else for a week. Definitely not advisable, and significantly dangerous, but anyone could. [can't stress enough that I'm not suggesting anyone actually do this...]

However, if you eat in a way that keeps insulin very low (ie, such that a CGM shows more or less a flat line) over a long time.. the threshold at which the body flips into fat burning and/ or autophagy (they are different, but I'm trying to keep this simple, honest) drops, and you start to create ketones closer to what your body now considers "normal".

Long term and short term...

Thanks for the response. Been trying to make sense of all this since 2016 from my own low carb/keto journey but in spite of all the research studies, books and articles I have read I wasn't sure that there was a definitive answer. My latest Hba1c test in early January came in at 5.2% - yay! At the same time my retinopathy test was positive - not yay! BMI 21 now. So a bit despondent and trying to find some positives. Awaiting a follow up with GP - not till March. However, in spite of the good result for Hb1ac I know from my analysis of data collected daily since last July (self funded testing strips) that my morning fbs (typical 14-16 hr fast) is greater than 5.6 for 67% of the time although rarely greater than 7.0. I'll keep doing what I am doing and see what happens next.

 

[Chris24Main]

So - I'm going to post this and then run (figuratively) - it's been something I've been building toward, and being doing some research on, and much like a couple of pages ago - I've stumbled on something in Pubmed that just totally lands the very question I was striving toward... what if all of diabetes is actually a spectrum, not a bunch of interconnected conditions?

Now - I need to really, really stress something here. I will add more, and I will add the pubmed link, but I have to process it myself a bit, because it is extremely challenging to hold that thought in your head without having some kind of reaction - so what I first want to say is - if you are having a strong reaction to me offering that as a possibility - please stop reading. I am not saying that this is the case, but there are questions that can only have good possible answers in the pathology of the pancreas (like - what is it really that causes the immune system to just target the pancreas β cells in Type 1 - isn't major immune system issues closely associated with insulin resistance? - hmmnn).

So - just to be pondered for a bit - what if there is a spectrum with extreme autoimmune on one side and extreme insulin resistance on the other.

Understand that there is a bunch of thought behind this, and none of it involves any kind of suggestion relating to treatment - I am not positioning to suggest anybody does anything - it really all revolves around the question of damage and recovery of the part of the pancreas responsible for producing insulin. What - instead of the current situation, where you have T1 and T2 - but actually you might have late onset type 1, or you might have progressive deterioration of the pancreas, or failure of blood glucose post pancreatitis (inflammation of the pancreas) but they are all separate things - only they confusingly overlap in strange ways that causes endless argument... what if its all a mixture of inflammation (in extreme cases leading to a total breakdown of the immune system) and insulin resistance (which in some cases is the only thing going on).

Have a chew on that...

 

[Chris24Main]

Thanks for the response. Been trying to make sense of all this since 2016 from my own low carb/keto journey but in spite of all the research studies, books and articles I have read I wasn't sure that there was a definitive answer. My latest Hba1c test in early January came in at 5.2% - yay! At the same time my retinopathy test was positive - not yay! BMI 21 now. So a bit despondent and trying to find some positives. Awaiting a follow up with GP - not till March. However, in spite of the good result for Hb1ac I know from my analysis of data collected daily since last July (self funded testing strips) that my morning fbs (typical 14-16 hr fast) is greater than 5.6 for 67% of the time although rarely greater than 7.0. I'll keep doing what I am doing and see what happens next.

Hey - sounds like you are doing everything physically possible - and 5.2% is amazing!! - mine is currently 5.4% but given that one of the biggest variables (and actually one of the threads I was pulling on that I'm hinting at above) is the length of time between diagnosis and remission - in other words, if there is cause and effect going on with damage to the pancreas and insulin resistance, then the length of time that the pancreas is "under attack" should be critical - meaning that if you have been working on this since 2016, then that's a significantly bigger hill to climb than mine that started in 2023 - so very well done.

 

[Chris24Main]

Back to the Pancreas.

First, a little background. for most of human history, or at least the part of human history where the word "anatomy" has any meaning, the pancreas is a smallish, fleshy (indeed the word pancreas literally means "all flesh") organ that sits along the stomach and pumps enzymes, or digestive juices into the top of the digestive system, after the stomach has started the process of digesting food.

In 1889, a couple of German researchers (in a fascinating, but totally out of scope story) - happened to remove the pancreas from a bunch of test dogs. These dogs all immediately developed the well-known symptoms of diabetes and shortly died - Clearly the pancreas was doing more than generating digestive juices. It was some decades after that that insulin was discovered, but the connection between pancreatic damage and diabetes took hold.

We now know that the endocrine function of the pancreas (producing half a dozen hormones as opposed to enzymes) is taken up by a tiny portion of the organ - somewhere between 1% and 5% of the total volume. The word insulin derives from "island" and this is because the endocrine portion of the pancreas is made up of tiny "islets" that are dotted all around the long "tail". - basically, the pancreas is shaped so that all the juices empty out in to the top of the intestine, where all the hormones are mixed in with the blood flow and sent to the liver.

So far, so good. Now; quick recap of my presentation history. I was diagnosed with diabetes, type unknown, and treated as type 1 for about a year, before a C-Peptide test showed insulin production, and I switched to a diagnosis of type 2. From my time on the forum, I still think that is quite unusual, but my suspicion is that it may be more common, and the unusual part is that I had a bolshy consultant who insisted on the C-Peptide test.

Let me explain. I've argued (in this thread) that I "was" LADA for a while - literally, I presented as a late onset type 1; but some argued back (quite rightly) that I was never physiologically LADA - the C-Peptide proved it. BUT - if I'd never had that test, I would still be injecting insulin right now, and would be solidly of the opinion that I was type 1 for life.

In my state of blissful ignorance of endocrinology, I was either suffering from an auto-immune attack on my pancreas (I've had several auto-immune conditions over my life, so this wasn't hard to accept) - or that I wasn't producing enough insulin, and at the same time my body wasn't using it effectively. In both situations, I could expect it to get worse, with the pancreas producing less insulin.

As I begun to treat with insulin, my dose doubled over that year, so clearly something was changing - this could either be that my pancreas was slowly shutting down, or that my body was using the insulin less effectively. Almost no aspect of this could be explained, it just was.

However, I was used to the "sometimes your body attacks itself, we don't know why" explanation, and didn't question it.

When I was re-diagnosed, and decided that I was not satisfied with what I was being told, because it seemed to me that everything had shifted 180 degrees, yet I was essentially being told to carry on doing the same thing... That was when I started to learn for myself.

It also why I'm kind of haunted by the idea that my pancreas had been assumed to be dying off - yet clearly it has recovered to fully working order, and I look at people who could be in the same position, and I worry that they may be being told the same thing - and that injecting insulin will make it appear that the pancreas is slowly dying - This doesn't give me any right to diagnose from afar, or give advice that could be dangerous, but it has motivated me to learn about the ways that the pancreas is damaged in the first place, and ways that it can recover.

 

[Chris24Main]

There were two pertinent sections in Roy Taylors book.

1. Patients with type 2 - where the pancreas is known to be pumping out more insulin than normal; they actually had shrunken pancreases (post mortem). That didn't seem to make sense, if the pancreas is doing more - why would it get smaller.
2. The problem was toxic fat deposits in the pancreas, and when you remove them (with sudden weight loss) the islet cells "come back to life" - in other words with T2, the insulin producing cells do not die, it's that their metabolism is dialled right down - to over-simplify, it's like there is too much fuel, so they go dormant.

He then went on to show that patients who used his method went on to recover the size of the pancreas.
It's difficult to argue with actual observation - he had measured both of these things - so any thoughts I had (I was firmly in the camp of "it's all insulin resistance") had to be compatible with these observations - you cannot just ignore things that don't fit your assumptions.

This is what led me down the path of "hang on, insulin resistance in the fat storage cells actually leads to fat leaking out into the blood, and you end up with fat in the liver and pancreas" - both things can be true at the same time; it's a kind of chicken and egg argument. Also, fat metabolism (from fructose especially) leads to the liver storing fat in a way that directly causes insulin resistance and inflammation - so that's the "egg and chicken" view - in other words - it doesn't matter, the important bit is that the ability of the pancreas to produce insulin is affected...

So - in T2 - there is an interplay between insulin resistance and impaired pancreas function, though all reversible in the right conditions, and the amount of influence - is it the IR or is it the pancreas? - will be a personal question of acute environment, but also genetic expression, and all the rest - but it shouldn't matter - it doesn't change what may or may not work as a treatment.

 

[Chris24Main]

But, what about type 1 (thought I) - what exactly is it that causes the immune system to go wild and attack this one percent of one organ - it's like a mob forming in a major city, and going on a looting rampage - but only stealing from one corner shop exclusively - it just doesn't stack up.

And what about the "honeymoon period" - isn't that just another way of describing building insulin resistance, just resistance to the injected insulin.? - and again - I'm only really comparing this to my own experience - had I continued to inject insulin, I would - without doubt - have talked about my honeymoon period in late summer 2023 before my pancreas shut down completely - that's how it was going.

Because - the islet cells in a person with LADA and a person with T2 have to be fundamentally the same cells - subject to the same thing - so if you accept the "fat deposit leads to reduced metabolism in the presence of insulin" argument - it has to be the same universally. Why would it be different? - and there is plenty of evidence of insulin resistance in T1 patients - it's just much less common than the general population, mainly because there are loads of non-food reasons for the pancreas to generate insulin (which doesn't happen in T1).

And - that still doesn't answer the fundamental question - why does the body go after these cells in particular - even leaving the more or less identical alpha cells alone (or any of the cells that produce the half dozen hormones in the pancreas) - to go back to that looting analogy, the mob must have some personal grievance against that one corner-shop. Could it be something directly to do with insulin?

Because other massive immune system failure conditions are (can be; this is not 100% non-controversial) associated with insulin (resistance) - including Lupus and Multiple Sclerosis; or at the very low level of chronic inflammation, where you consider insulin to be the grand driver of inflammation. I'm definitely speculating at this point - I'm not saying that I have any real insight into the root cause of the immune attack that is at the heart of T1 - all I'm saying is that I'm suspicious of the hand waving that goes on ("we don't know why it happens."). Clearly, there has always been T1DM - well before "modern lifestyles" - but the rate of increase of T1 is also alarming, and also picks up in a way that simply cannot be explained by normal human evolution.

If all auto-immune failures are associated with chronic inflammation (and that's not a stretch, it's really just changing the words - inflammation is the immune system) and there is something specific between insulin (which is at the heart of inflammation) and the cells that create insulin ? Could it be a coping mechanism to attack the cells that are helping the inflammation run amuk?

That, at least, passes the sniff test, for me.. so I started to look into what was known about the actual root cause of the auto-immune attack on the islets of Lagerhans... and that led me to this;

Autoimmune Inflammation and Insulin Resistance: Hallmarks So Far and Yet So Close to Explain Diabetes Endotypes - PMC

Diabetes mellitus can be categorized into two major variants, type 1 and type 2. A number of traits such as clinical phenotype, age at disease onset, genetic background, and underlying pathogenesis distinguish the two forms. Recent evidence ...

pmc.ncbi.nlm.nih.gov

It's extremely heavy on jargon, but basically argues that we may benefit from thinking about all diabetes as existing on a spectrum, with the auto-immune attack (killing β cells) on one end - and IR/ impaired β cell metabolism (reversible) on the other.

 

[Chris24Main]

Now - I acknowledge that this may be challenging for some, and I don't think I would even make any part of this argument outside of this thread -

I'm not even sure I totally agree that thinking this way is helpful, and I'm definitely not advocating for it - I think It's an interesting perspective, and it may help some, but from a treatment point of view, you have to focus on the thing most affected, so nothing much would change.

Personally - I'd like to see more research on the humble pancreas, and a shift towards protecting and recovering function wherever possible to do safely. I totally accept that there is no point looking after the pancreas while someone is in DKA or in a hypo coma. Time does seem to be critical - the longer the pancreas is "switched off" - the more difficult to switch back on.

Maybe that's all that happened to me - maybe because of the way I short-circuited the normal pathology be eating too much honey, I "got" to a diagnostic threshold very fast, leaving it possible for me to recover my pancreas - maybe that's the only thing I can learn from my whole attempt to figure this out.

But I doubt that I'm unique - that doesn't stack up either.

I feel pretty strongly that there is too much of an assumption that the pancreas is inevitably on a downward trajectory - when there could be more of an assumption that if we let it - it can heal. - the way to do that is all about lowering insulin, because it causes stress in the cells from producing all that insulin, and the effect of too much insulin is to degrade the function of the cells - it's a double whammy that you can filp by not expecting them to produce any insulin.

[just to be 100% clear - none of this should be taken as me saying that T1 can be reversed in this manner once it's established]

[but - I am saying that while I will not and cannot advise anyone on anything; it may be an improvement to clinical guidance about the honeymoon period to explain this, so that people can make better informed decisions]

 

[Melgar]

I enjoyed reading that paper @Chris24Main . Thanks for the share. For me personally I would welcome a complete rethink in how we classify diabetes. Trying to ram diabetics into the two classifications T1 or T2 doesn’t work in my opinion. They suggest classifying diabetes into endotypes, as per the small venn diagram made sense. The T2 classification is way too broad as to be not fit for purpose, but obviously that is not why you shared the paper!

The idea that T1 and T2 fall into a spectrum is an interesting one. I was interested in the concept that T1 and T2 share similarities and works on a continuum rather than seeing the two types of diabetes as two separate diseases. If you are T2 then it’s because you are insulin resistant , if you are T1 then it’s autoimmune. The way it is often written T1’s are not insulin resistance and it doesn’t play a role. When in fact T1’s develop IR too. And in fact T2’s can show autoimmune reactions because of T cell activation , inflammation and visceral adipose tissue. Highlighting the presence of autoimmune inflammation in the visceral adipose tissue and role of said autoantibodies. So there are similarities between the two.

Having the variants for T1 , and there are a number but the usual ones are the DQ and DR alleles and haplotypes for T1 was mentioned and to my mind, if you do not have the genetic variants how do you develop T1, they did cover that though.

Those are my thoughts, but I certainly didn’t do the paper justice and will reread it again later.

 

[Chris24Main]

Yes - absolutely @Melgar - I suspected you more than most would see it that way.

And, just mulling over for a day, I thought it was worth stressing (especially when I started off saying "I've been building up to this") - This is just where my thoughts have led me, it isn't that this is the culmination of some grand plan...

It's more that thinking this way simply makes arguing over "is it the pancreas or is it insulin resistance" defunct - it's both, and auto-immune (or, combination of inflammation and genetic tendency) at the same time, but to varying degree per person. When you look at what's happening as a metabolic process in the cells - it's more difficult to ignore how one thing can be both cause and effect, or that one thing might affect another.

And similarly - you don't need to get stuck on the "is it fat or sugar" - it's both... though for a lot of people, the fat is the sugar, we're just not taught to think of it that way...

and of course - insulin is somewhat key to all of it.

I was talking this through with a colleague who was a life-saver when I was first diagnosed - he has been T1 for 28 years. My thought was that nobody had ever been able to explain why his body attacked his pancreas way back when; and he agreed, but in his case, it was that he was very sick with a virus, and at the end of that episode, he no longer had a functioning pancreas.

Really confusing - and he will have been told "well, we really don't know what causes this to happen" -

But - when you see it all through the lens of insulin being the master regulator of energy, and a massive immune response to a viral infection (think how many people have reported diagnosis post Covid..) - where insulin is right at the heart of that, needing vastly more to manage the inflammation response, but also that inflammation response directly affecting the pancreas cells - so if you have a pre-disposition for it.. those cells will suffer.

I need to do more research myself on T Cells - everything on the genetic and autoimmune side has been secondary to insulin resistance for me up till now, but if I believe what I'm writing, I need to dig deeper.