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

[Chris24Main]

Sometimes it is better just not to say anything - or at least that's what I tell myself before the start of the consultation (spoiler alert; doesn't always work)...

On a totally different note, and a positive one to boot - yesterday I had a cold. Lasted about two hours, but I had all the symptoms, just passed through in super-quick time.

Now - that could be random, could be totally psycho-somatic; but I do remember thinking "oh, here we go, I haven't had a cold for a while, in this low-carb, Keto state, I should be in a generally low-inflammatory state, and this should pass quickly"

But - I'm left feeling like I shouldn't really believe it - is it possible for an immune system that used to take 24 hours to deal with a cold to turn around a similar infection in a couple of hours?

Anyone have any personal experience of this?

This is a genuine thing, there are a few lingering issues I've had for years that are all getting better - I would often have a runny nose in the morning, and would take a one-per-day anti-allergen pretty much every day, and be susceptible to hay fever, and I'm a low-level asthmatic.. all of that improved enormously. I'd lost the feeling around my right big toe (not from advancing effect of blood glucose directly, or at least I thought not, I had a motorbiking accident a long time ago and the effects are catching up) - but the sensation is creeping back into my toes, little by little it's coming back; so the backdrop is that I'm genuinely healthier than I used to be - but is this just confirmation bias ?

Would love to hear whether anyone else feels like a low-carb high fat regime (and in my case a big focus over a few years to improve sleep too) has given them additional benefits over and above the better control of blood glucose and insulin resistance..

 

[MrsA2]

Yes to most of that.
Colds pass through very quickly but I do supplement 1000mg vitamin c a day as well as low carbing
Often of an evening I can feel temperature rise and nose run but its gone by bed time.
When initially low carbing I got all sorts of funny sensations in lower legs, like cold water running up the calf. Put it down to nerves coming back.
Although never had a particularly high hba1c my records show I was prediabetic back in 2006, a full 14 years before diagnosis so anything could have been affecting to my body as I'm sure I'd tipped over the edge sometime in those 14 years.
On the positive side since low carb/weight loss/good bg I no longer get
IBS
Lactose intolerance
Diverticulitis
Dental health is much improved
Skin tags are fewer and smaller

 

[Chris24Main]

Fascinating - it's almost like there is some science behind all this low-carb malarkey....

Actually, the more I read and learn, the more I realise just how off-base all the demonising about fat is... stripping fat out of our diets eventually means stripping fat off our cell membranes - I mean that is a ridiculous over-simplification, but it's no wonder that nerves work better ...

and ... ahem... if you can bear with me for a second, it's a well-known issue that us men can be affected with a certain dysfunction alongside T2DM, well; I can attest that this works in reverse too with a better balanced diet..

But I know (because it's happened so often) that any time anyone, medical or otherwise asks "what have you done" and you answer, "mainly I've eaten more fat" - you get this blank expression like, 'yeah, I'm waiting for the punchline....'

Meanwhile, the line that fat is bad (because now I'm super-activated recognising it in the media) - just hits you over and over...

 

[Chris24Main]

There have been a couple of locations around the forum where there has been a discussion around .. essentially whether insulin resistance is necessary as a stage you pass through on the way to T2DM. I've been doing some reading up on it; with an open mind - cards on the table, I'm in the Ben Bikman camp on this one that says it's part of the story every time ... but our own @Melgar suggests that 15% of diagnosed T2DM patients worldwide are insulin sensitive, as she is.

I don't in any way doubt that, I just struggle to make sense of it, and so I've been gnawing on it.

This really gets to my obsession to better understand the role of Insulin and insulin resistance as a way of guiding me into remission - and so I put this here for those who understand that what I put in here is for free debate - I don't pretend to "know" anything for sure.

One significant issue with understanding insulin resistance is that every cell in the body has an insulin receptor, and resistance to that varies from cell type to cell type, and the rate or reason that it may occur also varies - you will find insulin resistance in fat storage cells well before heart cells, for example, and with very different outcomes - so when you hear the term "insulin resistance" - it's actually fairly difficult to pin down exactly what is meant.

then, there are various forms by which we can develop insulin resistance. The most obvious method is to simply get to puberty or get pregnant. Everyone has severe insulin resistance at least once in their lives, and it's a necessary part of life. You need lots of insulin to grow that's it's primary job as arbiter of storage/ use of energy. As an adult, there are three main mechanisms;
Hyperinsulinemia - too much insulin too often - this is the classic glucose spike scenario
Chronic Inflammation - this is more of a cellular thing, and I won't even try to get into an explanation
Stress Hormones - again, this works on a cellular level.

The key thing to realise, is that these mechanisms build on each other - you can get into a positive feedback loop where one cause requires the body to create more insulin, and that results in hyperinsulinemia, which makes the problem worse. Also, you can have many reasons for requiring insulin that have nothing to do with diet, but all affecting insulin resistance.

On the other side of the equation - where you need insulin, the only place you are going to have it made, is the Pancreas;

This (again shamelessly borrowed from Ben Bikman) shows the trend over time how insulin resistance translates into T2DM, as the level of insulin production finally fails to keep up with demand, and you tip into ever higher levels of blood glucose. The interesting point that is made, is that even in this "beta cell failure" scenario - you are still producing significantly higher levels of insulin than you were at the very start - in other words, it isn't really "failure" of the beta cells, just failure to match demand given insulin resistance (primarily in the liver cells).

But - whether you buy this or not, it's important to recognise that the whole story is a balance of supply and demand. I read a report from The Journal of Clinical Endocrinology & Metabolism going back to 2000, which makes the point that if insulin resistance is the primary problem, then the treatment should focus on that, whereas if the pancreas is the main issue, then the treatment should focus on that. This gets us into type 3c territory of course, which is a totally different kettle of fish, so I'm trying to be careful about not making any pronouncements...

then, in the same study, there is an interesting statement:
Impaired insulin secretion can be considered to be universally present in all patients with type 2 diabetes, even those who are hyper insulinemic. Similarly, insulin resistance can be considered to be universally present in all obese individuals with type 2 diabetes and probably many, if not most, nonobese patients.

This would tend to back the, for want of a better phrase, the Ben Bikman view of the world (where all T2DM have had some insulin resistance preceding it) - and that the real focus is on obesity or not. This is where I think the real issue is; and it's about insulin resistance versus weight gain.

Clearly, for many people (me included) - elevated insulin means the weight scales inevitably going up - in 7 months of injecting insulin, I put on 3 stone without any change to diet. But - as I think I've stressed; insulin is a complex beast - and we are all unique. For some people, as Dr Robert Cywes would put it, who are "obesogenic" - they have no problem producing as much insulin as needed, and have very little risk of developing diagnosable diabetes - glucose is efficiently removed from the blood ... but at the expense of getting very large.

Is it not then likely that there will be others at the other end of the scale, who stay quite slim, have perfectly functioning pancreases, but don't respond in some of the same ways to the effects of insulin at the cellular level - i.e., their blood glucose levels go up much faster, and therefore have different responses to all the other things - the stress hormones etc?

That's basically where I fall. There clearly isn't a simple answer, but I don't think that there are 15% of the T2DM community who have no insulin resistance, I just think it's a spectrum, where some people take longer than others to hit that crossover point on the diagram above before being diagnosed; so for the people who get there much quicker, the thought is "that was too fast for traditional views of insulin resistance, so this patient must not be insulin resistant".

In my case of course, I was convinced that I had short-circuited the whole thing by "foi-gras ing my liver" - and I'll steal a diagram from Dr Jason Fung on this one;

Where Fructose plays a part in catalysing the "progression" of insulin resistance - I thought I had fattened up my liver in two months, but I now think I have to recognise at least a decade of drinking wine, with a packet of Pringles most nights. I had stopped that well before diagnosis, but there is less doubt in my mind now that I was actually quite insulin resistant well before my diagnosis, even though I was locked at my target weight at the time.

Anyway - just my 2c

 

[MrsA2]

You go at least 3 or4 steps deeper into the science than I can understand, but if I'm (nearly) keeping up, what about the genetic theory (or at least the genetic tendency theory) and the personal fat threshold theory, like Roy Taylor champions. Where do , or don't, they fit in?

 

[Melgar]

My personal opinion is Type 2 is such a broad category, a catch all for all things that collectively make the condition called type 2 diabetes. In other words anything that is not autoimmune related. So we struggle to find a unifying reason for raised blood sugars. Hence we have people here on this site, including myself, who are completely perplexed as to why they have raised blood sugars based on the so called reasons for why people develop type 2. No Dr can give a coherent answer. They go around in circles with assumption laid upon assumption, oh it’s Insulin resistance, oh more exercise, oh cut your carbs, oh drop your weight, but nothing works. I have yet to have an answer that adequately accounts for why some people are unable to lower blood sugars. @Chris24Main you yourself dropped your carbs and boom your blood sugars dropped from what were blood sugars so high they figured you must be Type1.Great and a big well done on your hard work, it didn’t work for me and my blood sugars are nowhere near as high as yours were. I cannot get them down despite burning thousands of calories, I’m barely holding onto my weight.

There are Diabetics that simply do not fit the holy trinity of metabolic conditions that are associated with the type 2 condition ( I know that DM regardless of type can be classed as a metabolic condition) . People like me that can lose weight, go on low carb, ( around 35 grams of carbs and be in ketosis) are thin, fit and do not have the metabolic pressures, and are simply not able to normalize blood sugars. we tend to look for a single reason for what is a multifaceted condition shoved into a very board category that is not fit for purpose. And of course I know you know that. I have to confess I have not read Ben Bikman. I haven’t read him because I read the same stuff, lose weight, go on a very low carb diet, get fat adapted and hey presto you are in remission. Well no, that’s not the case for everyone, most but not everyone. So why not? Because something else is causing raised blood sugars. I’m making the distinction between merely raised to those that are high in the 20 mmol/ls plus category.

I base my lack of insulin resistance on my c-peptide numbers. My c-peptides are lowish, normal but lowish so I’m not over producing insulin. In other words I am not insulinemic. My only thought on this is I do not produce enough insulin and that has nothing to do with insulin resistance. I’m not alone , as people have attested to on here. And clearly research has indicated that there is a category of diabetics that are not insulin resistant. Now I’m not suggesting that the vast majority of Type 2 diabetics do not have the classic reasons for their raised/high blood sugars , just to reinforce that. And yes I fully accept that high amounts insulin will increase a persons weight and further add to IR.

I would, however argue that You cannot have Type 2 diabetes without having a degree of impaired insulin secretion. In other words insulin resistance alone does not cause Type 2 diabetes. And a quick note to say Let us not forget that normal healthy individuals have a very fluid degree of insulin resistance which rises and falls through out the day. In healthy people carbs increase IR, as does early morning secretion of cortisol, but the body quickly normalizes these brief periods of IR. So, yes IR is a frequent player in D2, but not everyone who is obese has Type 2. So how can we account for 70% of obese individuals not having Type 2 diabetes. They are as sure as hell insulin resistant. As you point out, and as Dr Robert Cywes states there are insulin resistant individuals who are obese but are able to produce copious amounts of insulin. They are hyper insulinemic with normal blood sugars. So why? Other reasons are at play but we are so stuck on single factor reasons.
I am always searching for reasons, if you start digging into the vaults of research papers past on IR and insufficient insulin then you start finding outliers that ask the questions around thin fit diabetics that are unable to produce enough insulin, are not insulinemic and are diabetic.
@Chris24Main I’m simply trying to get answers and nobody seems to have them, this far. Like you it is a journey of discovery that is fascinating but frustrating at the same time.

 

[Bcgirl]

Love these conversations! I am very much like melgar, albeit I do have some degree of damage to my pancreas from pancreatitis. I have low mid range c-peptide and low fasting insulin, I am not insulin resistant. I too cannot for the life of me lower my blood sugar via the traditional methods. Exercise does nothing (I walk 10 km every single day, if not more) and when I wore a Cgm I saw relatively little change in glucose. I eat less than 10 carbs per day, drink lots of water…and the glucose just hangs at around 6 (5.5-7.0 range)all day, all night. My charts say I’m type 2 and I asked my doc about this as I am clearly 3c….she said it doesn’t matter, we just treat symptoms…grrr…she’s great but….

i am trying very hard to gain some weight, it’s a struggle! Heavy weights at the gym, as much food as I can tolerate…
low carb keeps me in the prediabetic category so that’s a good thing. My ice cream experiment a few weeks ago was frightening….i spiked to 300 (16.8 I think) before my insulin kicked in, but it did kick in and dropped to below normal in less than two hours. Watching that rise was so interesting to me (not so my husband who was very concerned).

think i will ask my doctor for another c peptide and fasting insulin when I see her next month. If my pancreas is slowly dying I want to know. It’s gets scanned again on Friday to check for changes.

Melgar, have you had your fasting insulin checked?

 

[Melgar]

@Bcgirl no I haven’t, but I think I might push for it plus another C-Peptide test. I might get the C-Peptide test done in the UK when I’m over there later this month. I’ll just pay for it. It seems easier to get things done there especially if you are willing to pay for it.
If I have a very small amount of carbs my blood sugars shoot up. Any amount. 10 grams of carbs will see my blood sugars over 12 mmol/ls. Funny I had some ice cream a few weeks back when we had all that extreme heat, I didn’t even check it as I knew it would be way up there.

 

[Chris24Main]

OK - fascinating..
First - @MrsA2 - genetics are both everything and nothing. One great example I came across, was "imagine a group of builders on a platform, they have a raised table in the centre with a set of blueprints and in turn, they walk over to the blueprints, and walk away, picking up a brick or a tool, and going off to do something" Now - imagine you are an alien in a cloaked ship, hovering above and observing. What is going on, and what are the most important things, the workers, bricks, tools or blueprints?

At the very least, you can see that nothing happens with the blueprints themselves - they are only plans, and so it is with DNA. There is a whole branch of medical science called epi-genetics that describes what the workers do.. and to stretch the metaphor, when the workers get sick, or mis-read the plans, or .. whatever.. We kind of know this; twins can be very similar, but they do not have the same response to everything, and how we interact with those plans can be affected by things we've done and choices we've made.

So - the personal fat threshold is a whole big topic to itself, with quite a lot that would generate discussion. I think that it's affected by what you do during puberty (your mind and body are kind of "reset" during puberty .. it's not the same as saying you get new DNA, but to abuse my analogy above, you may have different HR relationships with your workers depending on how you treated them during puberty, so they may be more likely to strike in troubled times...).

That said, I think that you, one, is likely to have a level of fat that your body considers "good" - you cannot become pregnant unless the body recognises you are at least at this level, for example, so it's far more likely that this is different from one person to the next. (oh, and have a womb..)

The theory then is that if you get carbs out of the way, your body should tend toward that level - though clearly that is not the case for some..

 

[Chris24Main]

@Bcgirl and @Melgar - I'm sure you understand this, but for the sake of anyone reading, I'm absolutely not offering anything approaching advice or diagnosis... for the sake of total clarity, nobody should take anything I say with anything other than mild curiosity ...

But - you both identify as insulin sensitive, you, @Melgar are in ketosis, you struggle to put on weight, and have extreme reactions to any amount of external glucose.

so - just riffing now... ketosis is immediately stopped in the presence of insulin - this I take as an absolute, it forms the basis of my own personal regime, it's why I measure ketones.

Glucose production in the liver, Neoglucogenesis, is triggered by Glucagon, which is suppressed in the presence of insulin.

There is clearly a relationship between energy storage and insulin, and you are both whip thin.

You can probably see where my thought are going.. Dr Rob Cywes (again) talks about insulin depletion as being a possible risk of a carnivore or Ketogenic diet. He recommends some small amount of dairy (in his case some cream in his coffee) in order to deliberately create a demand for insulin.

Ie, it's all very well for the likes of me, trying to reduce insulin resistance, but it can go the other way, and we should not demonise insulin.. it's incredibly importance ... to have the right balance.. but the right balance does not mean zero insulin, and could actually get you into ... wait for it... Glucagon resistance...

But the reason for pushing Ben Bikman is actually the opposite to your reaction - he isn't about exercise and low carb - he's very much a metabolism nerd; and it's the interplay of hormones in the different types of cells, and the way that you have to think about the three levels - whole body/ organ/ cell - at the same time, because a cellular driver can sometimes be observed as something totally different at the organ or human level..

For example - in a petri dish, you can surround liver cells with saturated fat, and they will become insulin resistant - literally it damages the insulin receptors, and insulin stops working. But - in a whole body, when we eat saturated fat - nothing like that happens; you just cannot get saturated fat "bits" anywhere near a liver cell..

anyway - probably a poor example, and it doesn't directly answer anything, quite honestly I was hoping you would read the book and illuminate something for me...

But, I think that's where I fall; your blood glucose is too high - should indicate insulin resistance, but everything else indicates the opposite. C-Peptides are good, therefore you are capable of producing insulin, so look at other hormones that suppress insulin.

That's painfully thin as a theory, and I aim to dig further; growth hormone plays a part too. Have you had your Uric acid levels tested? There is a strand of thought that too much protien can upset the balance and cause increased blood glucose with no corresponding insulin response..

But again, please accept for what this is.. I'm really an engineer poking at a problem; not a doctor and definitely not offering criticism, judgement or advice about anything...

 

[Chris24Main]

@Bcgirl - The very strong steer I'm seeing from those in the field is that there is an ...unreliable... expectation that Pancreas will continue to deteriorate. I hesitate to even say this because - I personally know nothing - but my understanding is that the treatment can be heavy handed, and contributes to insulin resistance which looks like a deterioration of the Pancreas, so the response is to up the dosages .. and you are in a positive feedback cycle. There isn't a great deal of research that explains a mechanism for a slowly deteriorating pancreas. As an organ, it should be able to heal as much or as little as other similar organs, it's just that there isn't the funding to look into this.
All of which to say, good luck with your scan tomorrow; I hope it results in good news..

 

[Melgar]

Thanks for your response @Chris24Main . As always thoughtful and thought provoking . I lied I have read one of Bikman’s books, it quite escaped me, I must be in cognitive decline. Yes, I read ‘Why We Get Sick’. I thought it a good book, but over indulgent on his thesis that all roads lead to Insulin Resistance. He over ‘egged‘ his omelette in my very humble opinion. He did, however, make some very interesting points and for sure IR is the devil in the detail, but I wasn’t swayed by his argument that it plays a major part in all chronic diseases. He does conveniently list them all for us. That aside I did take up his challenge on exercise, working your muscles to failure. I was comfortable with his theory that squeezing your muscles, to the extent they have nothing left to give, decreases insulin resistance. I bought into that concept. 3 weeks of forcing my major muscles, legs, abdomen and arms to muscle failure has result in zero movement in blood sugar. I hope to see a benefit at some point. I am going to pay to have my c-peptides tested again when I’m in the UK. Just to see what they are doing, has c-peptide secretion remained stable or has it decreased.

I have read, in other studies, that insulin resistance precedes raised blood sugars in those destined to reach diabetic levels. I don’t doubt that, and I would agree that a very high proportion of individuals destined for diabetes will be insulin resistant for many years prior, but not everyone.

I’m not a big meat eater. I would say 50% of my meals are vegetarian, salmon and chicken are my main sources of meat protein when I do eat meat. My uric acid levels are normal as were my chemistry and hematology levels. My own unsubstantiated theory is that I have a depleted beta cell mass that doesn’t replenish as it should, so catastrophic damage. I’ve suffered some insult on my pancreas and it’s never recovered. My blood sugars were perfect just 7 years back, like in the low 5’s regardless of what I’d eaten. Something happened. Now I did get sepsis pneumonia in 2018/19. It was at the end of 2019 I was told my blood sugars were at prediabetic levels. That’s my only clue, but that maybe a red herring. I have read very little around insults to the beta cell mass.

I‘m interested in your point about energy levels and insulin. And glycogen resistance ? I’ll look into that. I have Gone though episodes of exercise induced hypoglycaemia so storage issues, maybe? My thoughts at the time, and I believe still relevant, that one can use up all your glucose storage, but no one tells your pancreas.

 

[Chris24Main]

er... Glucagon...

Yeah, ok, so you and Dr Bikman don't meet eye to eye, huh. He is an acquired taste, for sure... it just makes sense to me at the cellular level, but as an engineer. The thing I have to keep reminding myself is that I'm just as likely to "fall" for a simple theory that sounds right as anyone else... Saturated fat leading to heart disease sounds like it makes sense, and even knowing the way we gravitate to simple, right-sounding concepts doesn't make one any less likely to do it nonetheless.
(I'm acknowledging my own biases here, if my rambling is loosing you...)

And I'm impressed with your take up of the exercise element - seemed too much like hard work to me...

But - the idea is that taking muscle to failure will increase the insulin sensitivity of those muscle strands. If you are already insulin sensitive generally for whatever reason, that shouldn't result directly in a change to blood glucose, because ... well, nothing will have changed.

You can definitely use up all available glucose - at least that is another plank in my own regime (I could of course be totally wrong) - about once a fortnight I fast for a full day, so with both nights that is around 36 hours. The entire idea behind that is that after about 24 hours, all the available glucose storage (actually this time it is Glycogen, you cannot store Glucose anywhere, it's toxic unless being used) is used up, from the liver, and the muscles - about 3 Mars Bars worth, and you have a small period of autophagy, but not so long that you need to be too careful about planning to end your fast.

Even at the end of that kind of fast, I can go Paddleboarding and my blood glucose will be 6 or 7, which can only mean that my liver is producing it from new ... This effect is slowly getting smaller as I get more fat adapted, and I expect that process to go on for a couple of years, which is fine.

However, if you are seeing hypo events, then yes, you will have burned up all available Glucose, you are not producing enough new to compensate, and you are not burning fat either (though I'm still too new at this Ketosis game to say anything useful about the speed of delivery of ketones for energy provision).

At that point, I'm thinking "you may want to add fat" - as it's a phrase that comes up a lot in Ketosis discussions. Clearly I couldn't actually say that; would be far too close to being prescriptive ... but the thing I'm constantly learning is that fat is actually a good guy in all of this, we just tend to mis-cast him.

As always, I enjoy the discussion, and offer this in the spirit of exploration...

 

[Bcgirl]

Oh my, so much to think about. My pancreas has never been treated, I’m on no medication (except thyroid). Interesting hormone theory. When I was diagnosed (after a zillion years of prediabetic) I was taking tamoxifen for breast cancer (Honestly, against my better judgement) When my doctor called regarding my diabetes diagnosis immediately researched the little know side effects of tamoxifen and sure enough…diabetes! I immediately stopped….but nothing really changed.
i do remember Dr Cywes mentioning adding of some sort of carb to basically keep the pancreas guessing…and I have incorporated more carbs into my diet…today indulging in full fat yogurt and two strawberries. My three month carnivore experiment didn’t work at all…
my pancreatitis was 17 years ago this December. It was only last year when I got any kind of medical intervention after abnormalities were found on a scan of a different area. I then underwent an MRI and an ultrasonic endoscopy….all showing a dang mess but no tumours.., with a push towards a scan every year. Scares me to bits.
i will continue to research and play with my food! Sorry mom.

 

[Chris24Main]

Keep the pancreas guessing - love that...

It is stupendously complicated .. of course (now doffing my Ben Bikman cap again) there are some who would say that Breast Cancer is only another outcome of insulin resistance - and that anything that affects your Thyroid is going to play a part as well; it's all about the hormones. But not me, I'm not putting a foot in that direction...

I do genuinely believe, however, that having the attitude you demonstrate is one of the biggest things we can keep some control over. There is a danger in placing too much faith in positivity ... you can fall into the trap of "it didn't work because you weren't positive enough" - but there is a deeper wisdom buried in your last statement - i will continue to research and play with my food!

If this thread is "about" anything, it's about trying to filter down to the small number of things that do make sense, and that anyone could take on board. It strikes me that this is one of them..

 

[Melgar]

Oh my god yes, glucagon. I Can’t get my head to differentiate between glucagon and glycogen. Glucagon resistance, unhappy fatty liver; glycogen and repeated muscle contractions stimulate glycogenolysis . If I write that 200 times I might remember the difference!
Playing with food , I like that too. And keep the pancreas guessing, I like that. Isn’t intermittent fasting a bit like that, the body is always left wondering aka your pancreas. I’m certainly not in ketosis anymore, I increased my carbs, but also increased my work outs to compensate. It Will be interesting to see what my c-peptides will be with the increase in carbs. Can’t do the high fat diet as I have issues with animal fats. I stick with Olive oil and I keep that oil to a minimum too.
As for my resistance training and Insulin Resistance, for me any excuse to push my body. I am also aware that keeping insulin sensitivity at a good level is vital. Everyone has IR to some degree that ebbs and flows depending on external factors, but none diabetics’ bodies deal with IR and any rise in blood sugar very quickly, so their Blood sugar levels don’t reach levels that would tip them over the prediabetes mark. That’s the difference, we diabetics suffer with our pancreas’ inability to produce enough insulin regardless of IR. At some point, if way too much insulin is floating around our bodies, the pancreas just can’t keep up, despite a valiant effort by our beta cells then diabetes will eventually follow.

If I fast for that length of time @Chris24Main my blood sugars will go low, so I can’t do it. They drop like a stone. So is it possible my glucagon producing cells are not able to respond to falling blood sugars? I have no idea.

I note that my own natural basal secretion can vary as can my bolus reserve and production which makes me conclude there is something wrong with my pancreas plus I can’t metabolize fats well which comes down to the secretion of lipase also a product of the pancreas. The reason for my Low Triglycerides ? I take a lot of supplemental vitamins because of my coeliac, so A,D, E, and K vitamins are at good levels. I’m Just throwing thoughts out there with this response

 

[Chris24Main]

Always fascinating to discuss, @Melgar
Again, mainly for anyone else reading this (in the unlikely event that there is anyone else reading... ) - your situation and mine are very different, and I'm absolutely not, in any way, saying anything like "look at what I do, you should do the same".
[starting to feel I should put something to that effect in a sig line, do not under any circumstances pay any attention to what I'm saying..]

Yup - so the fact that you would struggle to fast for a length of time more than your (temporary in evolutionary terms) glucose storage, means what? You suspect your pancreas, you clearly have little fat, in adipose tissue or diet (understand, and it's none of my business in any case; for me; a big part of this is learning to adjust my thinking - a year ago I would have described myself in much the same way, 50% vegetarian, very little fat in diet).

There are plenty of reasons to think that as humans, it should be perfectly natural to be able to survive and thrive while having nothing to eat for whole days at a time, a 36 hour fast (while difficult in a lot of cases, I don't mean to minimise) should be possible without getting into Hypo territory, unless something is wrong, but you start off in that position, I'm not judging, only repeating what you say...

so - yes, at the point that you are (one is) running low on stored glucose in the form of glycogen (one thing that helps me think about this is to think of glycogen as "animal starch" because it's just strings of glucose to make it less toxic), which are mainly stored in skeletal muscles and the liver, and we have established that you do not have large stores of fat in your skeletal muscles (again, an interesting way of thinking about this, is that this is what "marbling" is in steak.. a really healthy and expensive steak will have lots of threads of fat in among the meat - same for big muscles).

You should have an entirely normally functioning liver, but it stores about a third of your total glycogen - so when your liver is demanding (and your brain will also be asking for more energy, but only your pancreas can determine the amount of blood glucose, the brain will be just as happy with ketones) that you need more glucose, firstly that will be happening sooner - you simply have less reserves because there is less storage for it - and then what, you struggle to produce more, because ... well neoglucogenesis is driven by glucagon, growth hormone, epinephrine, and cortisol. All of which is suppressed in the presence of insulin, but the key driver is Glucagon, which is produced in the pancreas, but this time in the alpha cells (and I wonder if the alpha and beta nomenclature is really about the antagonistic relationship between insulin and glucagon).

Which means we spiral back to the pancreas, and the possibility that you are not getting enough glucagon (or, like IR, you are producing enough, but that it has become less effective over time, meaning a resistance).

So, if you think about all the discussions we've had about insulin and weight and exercise, and putting a strain on your pancreas to keep up with the need for insulin, your pattern is quite the opposite, you are asking a lot from your pancreas a lot of the time, in much the same way as someone with lifestyle-related insulin resistance, but in your case, lots of endurance exercise is asking your liver to produce glucose under the supervision of glucagon, maybe more often that it should. With low fat reserves (not eating much fat, you cannot have stores of fat in adipose tissue either) you need your liver to produce glucose, fast, from amino acids and other substrates and the evolutionary control mechanism of lipolysis - breaking down stored fat into free fatty acids (the main fuel for your heart) and glycerol for energy - is also going to be running short, and so you start to get into hypo territory. Ketosis isn't there as a backstop, again because you have very little fat.

Having a problem with lipase is also pointing a finger at the pancreas, as you say...

All of which comes back to another running discussion about whether the pancreas is something fundamentally and permanently damaged, or whether you need to find the right conditions to let it heal. (or, I suppose, whether it can heal)

I think you know that in my case, I'm starting to believe that 7 months of injecting insulin, while being a terrible treatment, may have been the thing that gave my pancreas a rest (literally not having to product as much insulin naturally) - and allowed my beta cells to recover. I wonder if there is a set of conditions that would do the same for your alpha cells...?

or at the least, a treatment plan that would allow you to see whether those conditions were making a difference or not? (you recognise I'm being totally vague here, if I'm suggesting anything, it's only talking points for a discussion with your endocrinologist)

 

[Chris24Main]

So here is a bit of a diversion - or at least it may seem to be that way, but I think it's very relevant for anyone who is looking at responding to T2DM (or any form of diabetes really) with lowering carbs in any way.

Cancer.

It comes up a lot. There are multiple links across from disease control looking at T2DM and insulin resistance syndrome through to the underlying science of cancer, both developing cancer and it spreading.

Personally, I've lost many close to me from cancer, so I've resisted saying anything (well, mostly anything) relating to it, as I didn't feel I'd grasped enough about the links between diabetes and cancer to say anything that might be seen as either minimising or trivialising.. but I think I'm now there or thereabouts.

The parallels with the understanding of "why saturated fats are dangerous" and "cancer is a genetic disease" are striking. Much of the concentration of knowledge and research pre-war was around Germany, Otto Warberg was the leading scientist on cancer and got a nobel prize, would have gotten a second if he hadn't been blocked, and post-war everything changed.

His central thesis was that cancer was a metabolic disorder - more specifically (and I'll try to simplify again, but retain as much meaning as possible) - cancer is a process where the affected cells go into a way of creating energy that relies on fermenting glucose rather than oxidising - we talk about burning fuel, it's a process of oxidisation. You can ferment sugar, but you cannot ferment fat. Cancer therefore requires sugar in the blood (or an amino acid called glutamine, but that goes beyond what we need for basic understanding)

This happens because of damage to the "engine" of the cells, the mitochondria, and part of the damage causes the cells to go into uncontrolled growth, because one of the jobs of the mitochondria is essentially to stop this thing from happening.

Fermentation energy is how everything got its energy back in the day, of course, in the good old days before oxygen, two and a half million years ago ... so, this is an old pathway that the cells have ... it's sounds unlikely, but that part of the science is easy, and beyond question. If you hold your breath, quite soon you get a build-up of lactic acid - same pathway.

Some parts of his central theory have caused controversy ever since, and the general issue is about the presence of damaged DNA, and the fact that such cells still take in oxygen - it's pretty technical, but the short version is that the entire cancer research effort worldwide could be barking up the wrong tree -looking at the effect of all of this (the damage to the DNA) where it's ignoring the cause (damage to the mitochondria, or reduced oxidative phosphorylase to be more specific).

Why does any of this matter to us? well, there are some obvious issues, but fundamentally, if you buy into diabetes being about reducing carbs and insulin (clearly, I'm meaning T2DM, but anyone reading this thread will recognise that I firmly believe that everyone benefits from a general reduction in carbs and insulin) - well, one of the benefits you gain is a fundamental reduction in the risk of developing cancer, or the development of cancer if you do.

Way back in my personal journey, I was learning about the value of sleep, and that one of the lesser-known benefits of sleep is on exactly this - sleep deprived mice can be shown to be terribly susceptible to cancer and it grows at an alarming rate compared to mice allowed normal sleep. I was pretty horrified at the time, and it formed one of my bigger life-changes, to value sleep more. I now understand it more along the lines of good sleep being a cornerstone of hormone balance - it's all part of the same thing, if you have the right balance of sleep, exercise and eating (both in terms of eating vs not-eating, and eating food that triggers insulin or not) - you will keep your blood sugars low, and ketones high. With the right balance of eating vs not-eating, you give your cells time to look after themselves...

and with healthy cell mitochondria, and no available glucose, cancer simply cannot happen, as Otto Warberg showed nearly a hundred years ago. Ketones are kind of a second layer to this - cancer just cannot use ketones, so if you are aiming for that, you get the benefit; but I'm not pushing keto - just reducing blood glucose is a significant thing by itself.

The causes of Cancer are manyfold, but as diabetics we understand this, the causes of diabetes are manyfold and can be contradictory, and difficult to keep up with the advice you get from the mainstream media, but there is a fundamental underlying issue with metabolism, and if we understand that, then simple things that we do will make a huge difference.

 

[Outlier]

Fascinating discussion.

Re: cancer - stepping into what kills other mammals (including other creatures big and small that kill them) for the wild 'uns it's disease, starvation or predation. Our domestic mammals are well-fed and protected by us, live a lot longer than their wild relatives, and they mostly die from cancer when old, if they escape accident or organ failure. Everything has to die of something. We can delay illness, including cancer, but we can't do any more than that once we exceed our individual natural span. So it makes sense to do everything we can to stay well as long as we can, but something will get us in the end, it isn't anyone's fault, and maybe we should make our peace with that and enjoy what we have in the meantime.

 

[Chris24Main]

Fascinating discussion.

Re: cancer - stepping into what kills other mammals (including other creatures big and small that kill them) for the wild 'uns it's disease, starvation or predation. Our domestic mammals are well-fed and protected by us, live a lot longer than their wild relatives, and they mostly die from cancer when old, if they escape accident or organ failure. Everything has to die of something. We can delay illness, including cancer, but we can't do any more than that once we exceed our individual natural span. So it makes sense to do everything we can to stay well as long as we can, but something will get us in the end, it isn't anyone's fault, and maybe we should make our peace with that and enjoy what we have in the meantime.

Much of my poor interpretation comes from Prof Thomas Seyfried - I'm trying to digest his "Cancer as a Metabolic disease" - and I also caught an interview with him which sparked my interest - his example was the death of Queen Elizabeth:

"one day she was shaking hands with a foreign leader, the next she's dead - that's the way it should be, your body gets to the point where all your cells simply cannot generate enough energy to overcome the natural tendency to disorder, that's what aging is in the end, and we should all just be well until that point, then keel over".

I think that's a pretty amazing goal to aim for -

... and ... there are some cancers that are infectious and fall outside of this ...generalisation... but cancer in pets is at a rate far far greater than out in the wild.. We recently had to take our cats in for a checkup, and the discussion turned to food, the vet was suggesting such and such a brand, because there was a good mix of macronutrients, including carbs. "What does a cat want with carbs?", I said, before I had a chance to think. She looked at me as if I was mad, but really, what does a cat want with carbs? They'll get addicted to them the same way we do, but really, what does a cat want with carbs...?