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

[Chris24Main]

Much more engagement from the chapesses at the moment.

On that point - something I did want to mention - you can imagine that my YouTube feed is heavily geared towards all sorts of related topics - one of the consistent themes I find is that a conversation between women is different to a conversation involving a man.
This is a totally reductive and sexist thing to say, but I find that women seem to be in general more interested in the topic, where men appear to listen and then repeat the one thing they want to assert.

 

[Chris24Main]

To your point - @Outlier - maybe I should demur, but if I can offer this...
It's somewhat a contentious topic, but from an evolutionary perspective, babies are exclusively gestated in women, that seems to me to be a good line to draw.
Therefore, space is somewhat reserved for the purpose, where men do not have that use for their belly.
As a species, we are designed to be able to survive long periods of time without food, so we all have available storage, it's just distributed differently between men and women (on average; this is in no way about any specific man or woman, as individuals we are all unique, but in large numbers we are statistics)

Metabolically speaking, this is better for women, the fat cells are more able to reproduce - lots of small fat cells are much better than a smaller number of inflated fat cells.

In fact, it's one of the key reasons that women statistically live longer than men; so there's that. (to clarify, men have more storage around their belly, which is all of a type that can only expand - this is bad - that's why visceral fat is such a thing)

But to simply answer your question, it kind of has to be related to insulin. Your reproductive system is only allowed to proceed if there is sufficient energy in the form of fat, and then pregnancy requires insulin resistance to allow the growth required ... literally to allow a baby to grow.
What happens after birth has also to be regulated by insulin. If it's high, you (anyone, not just someone who has just given birth) are locked in energy-storage, so your adipose tissue (wherever it's located and whatever state the cells are in) - will not release fat. If insulin is low, you will be able to mobilise the stored energy, and burn it as fuel.

Clearly, there are other hormonal changes going on during and after birth that as a man, I can have no concept of, and have no business commenting on, but that's the way I see it. Animals; post-birth will have low insulin. Ketosis is the natural state for most animals most of the time, so all of the energy no longer required to build a baby is regulated down. With humans, we can disrupt this and keep that energy locked in.

 

[Outlier]

Great thoughts!

Beware received wisdom (I know you do!) The allusion to where women mostly keep their fat compared to where men do is also Illusion that defies observation. An artist's eye will confirm that there is a number (grammar pedant here) of different body shapes in humans and from there we see different typical fat storage areas. The astute observer therefore notices that these may or may not be typical of XY or XX but are not exclusive to either. Yet what the eyes can see is not upheld by common reference to women store fat here for breeding survival, whereas men store fat there. *Sings* It ain't necessarily so.

 

[Chris24Main]

Indeed - I've deliberately only used phrases that are physiologically bound to science - I'm not going near comments like body shape.

In fact - you may notice that I've only said that men have more available visceral fat. - but that's a bad thing metabolically speaking.

For what it's worth - the study of adipose tissue, whether subcutaneous or visceral is really a line of research lending new insights all the time, fat storage cells are truly marvellous, and the idea that they are just kind of "there" to do nothing is totally off the mark.

Also - I should really emphasise - when I'm talking about visceral fat - this is the kind of fat that you may not even see... I'm in no way..

...in no way...

talking about what changes the shape of a body. That's a totally other discussion.

This is mainly about the (fact) that women have more fat cells that can multiply (safely and in a way that doesn't compromise metabolism) than men, who have more fat cells that can only expand - (which has a big impact on metabolism).

 

[Outlier]

It's probably a good thing survivally speaking for feast/famine situations from long ago. But - what I am trying to say is that the false information that is widely promulgated (not here, not by us) that there is fat round the middle for the male gender which is "worse" than fat on the thighs and bum for the females sidesteps actuality where such distribution appears just as often in the opposite gender.

 

[Chris24Main]

I hear you, and I'm trying desperately not to be pulled in to that line of thought <grin>

Because two things can be true at the same time - you are talking about one thing, and I am saying only that there is a physiological difference between the sexes.

Visceral fat for either sex is not good, for the same reason, and if you want to expand on that, then there is a line of thought that visceral fat is worse for women, because, having numerically fewer visceral fat storage cells, for any given amount of energy storage, the cells will have to have expanded more.

 

[Outlier]

I hear you too and thank you for the courtesy.

 

[Chris24Main]

So this one is really left-field.

A few weeks ago, I did a real deep dive on how Metformin works. I'm not going to go into the detail (short version, we just don't know all the ways).

I personally did not want to start taking the med, but this isn't about whether any one person should or should not take the med for T2DM - I would still say that of all the choices it has the smallest set of downsides.

But -

one of those downsides is that it messes with the electron transfer chain, particularly in muscle cells. (this may be behind some of the known "muscle pain" side effects listed, but again, I'm not saying that this by itself is notably bad).

Now, what the electron transfer chain is, and how metformin messes with it... well, that's a tough one to explain, but if we go back to the idea of how mitochondria developed a mechanism for dealing with the explosive power of oxygen by having a series of much smaller reactions, well, that's the electron transfer chain, and there are four separate stages ending up with ATP - which many will recognise as "cellular energy".

Anyway - the effect metformin seems to have is to "regulate" this set of reactions. My understanding of this is that it stops the reaction at "step 1" - which still produces available energy, but not as much as if it went through the full set.

Now - if your aim is to have as healthy mitochondria as possible, you might see that as a bad thing (though not bad if it's helping your blood glucose level - again, I'm not trying to bash metformin).

However - if you recall my earlier discussion about the way that cancerous cells have to switch to a much older form of energy production.. then this form of "regulation" is preferrable... so metformin can kind of give cells a way that they don't have to fall back on something that may lead to out of control (thus cancerous) growth. (note, why it may do that is more complicated again, but that's as simple as I can leave it and still make sense, kind of..)

Which is why the med is often claimed to give protection against various forms of cancer, and is even one of the interventions or supplements suggested by bio-hackers and longevity types. I believe that there may even be a study going on right now looking at whether metformin is viable as a longevity drug.

I'm making no assertions one way or the other - I personally think you are still better off with as healthy and efficient mitochondria as possible, but it's just another facet of metformin that makes this med so fascinating -

and - I suppose, if you are currently taking metformin, you can feel good that there is a potential upside too...

 

[Outlier]

Aaaand of course, while not in any way dissing these connections, longevity prediction is only ever surmise............

 

[Chris24Main]

It's part of a much bigger conversation, for sure. May even be considered to be in poor taste, if you are struggling with a constant high blood glucose level.

For the sake of total clarity - I do not mean to be flippant about any of this.

I guess the simplest way to think about this is, right - I've pulled my blood glucose down; now what? should I go back to normal, well; no, because I know that will just put me back in the T2DM diagnosis again, so what then...

and from there, it's really (for me) about which other strands of the "narrative" that got me here I can unpick. One of those is the thought that we get less well as we get old. There is a good argument for thinking that the other way around - we get old because we get less well. I'll see how that lands before I go any further....

 

[Chris24Main]

Elsewhere on the forum there is a mention of vitamin C, and I was reminded that before Christmas I was taking part in a pub quiz, and there was a question "what vitamin is found in potatoes and acts as anti-oxidant" - so of course everyone looked to me, and I said "well, the only vitamin you would describe as an anti-oxidant is vitamin C" -

Which was the right answer (phew!) but has stuck in my mind, and maybe the time is right for me to try to tackle the bigger question - What the hell do we actually mean by anti-oxidant?

Surely the whole thing about breathing is that we take in oxygen, so why is it that we need something that sounds like it acts against oxygen?

Oh - and by the way, why is it that the terms "anti-inflammatory" and "anti-oxidant" seem to be inter-changeable; what is the difference?

So - a perfectly good answer is; never mind; keep taking the vitamin C and vitamin D supplements - the answer is complicated, but you don't actually need to understand so long as you have enough of both.

... but ... that's not why we're here, right?

If you're still reading, let's continue - remember the thing about all life on Earth being an eternal struggle between the energy-giving and destructive nature of Oxygen? - well, that's really what this is all about. Complex life requires the energy that only oxygen can provide. However, we also have to cope with the consequences. There's no smoke without fire, and there is no fire without oxygen. At the most simplistic level, that's it - smoke. Depending on how efficient your fires are (read, mitochondrial oxidative phosphorylase) you will be producing more or less ... smoke (read, reactive oxygen species, ROS, or free radicals). The more smoke we produce, the more we need to get it out of our bodies, and this ...pressure to get rid of the smoke... is called oxidative stress.

Literally how much stress (at the cellular and organ and whole body level) you are under trying to cope with the removal of the gunk inevitably produced in order to keep you alive.

Vitamin C's job (and of course we know that vitamin C is really another acid - ascorbic acid) - is to bind to these gunky particles so that they can be flushed out of the body. Remove products of oxidation, thus anti-oxidant. If this doesn't happen, then these particles will bind to and degrade other acid chains - and what are those - cell membranes (if anyone can remember that discussion about fishing nets). This is literally what scurvy is - your cell membranes are breaking down, and stuff starts to leak through barriers that are no longer secure - like blood through gums.

This is clearly a bad thing to happen, so under oxidative stress, the cells have various ways of shouting for help, (read, mainly releasing cytokines) and this is called inflammation - and hopefully by now, you can see that this is all part of a healthy system, provided it isn't overloaded.

In fact - this gets to why some additional inflammation (for example some omega-6) is important - to amplify the signal so that the immune response can kick in and deal with the oxidative stress.

ok - for bonus points - why is it that we have evolved with this critical balance between oxygen and the need for removal of products of oxidation, and the only solution seems to be from oranges (and of course limes)?

Why would that be? - surely that in itself is the reason why we need to eat fruits and carbs in general, didn't I even start off talking about potatoes?

.. and I'll leave that as a bit of a cliff-hanger. There is an answer, and a massively interesting one at that...

 

[MrsA2]

and I'll leave that as a bit of a cliff-hanger. There is an answer, and a massively interesting one at that...

You tease!
I've been taking 1000mg vitamin c daily since covid and t2 (both coincided for me) and vit d every winter.
Am I harming myself/my mitochondria?

 

[Chris24Main]

You tease!
I've been taking 1000mg vitamin c daily since covid and t2 (both coincided for me) and vit d every winter.
Am I harming myself/my mitochondria?

Thoroughly appreciate the input...

I watched the latest episode from Dr Boz last night, and in her practice, she uses a set of animated slides, using a campfire as an analogy for the way that mitochondria work - so I think I'm on the same kind of lines...

To recap - if you think about a campground as an equivalent of a cell, there will be many campfires - these are mitochondria, and if they are plentiful, and you are "burning" cleanly - everything is fine.

Lots of smoky gunk, just means everything is unpleasant and difficult to be around - this is oxidative stress. Inflammatory and anti-inflammatory kind of just works - anything ramping up the production of gunk is inflammatory - anything reducing or damping down the fire is anti-inflammatory. So - there is the camp supervision - do we need to go put out any of these fires? - that's the anti-inflammatory brigade - or immune system.

The confusing thing is how the word "anti-oxidant" really works - because (and I'm in danger of putting words in your mouth @MrsA2 ) this makes it sound like an "anti-oxidant" is somehow working against the "fire" that we know uses "oxygen".

So - to be more precise, when we are talking about the cleanest burning - that is called oxidative phosphorylation - and it's the critical thing that mitochondria evolved to do. If you think of the energy from Oxygen being a baton - just too hot... and the mitochondria being a relay team... it's clumsy but it works - the relay team pass the baton through a chain of four distinct processes, so that when they have done, the baton is cool enough for the cell to use as energy.

Things produced when this process is not going well, are called Reactive Oxygen Species - so think about dropped batons - too hot!!

Your vitamin C acts as an anti-oxidant, so binds to these ROS, and keeps the campground cleaner.
Your vitamin D recruits more camp guards - so they can react more quickly and damp down any badly burning fires.

So no - both are good - though you have an upper limit of Vitamin C - too much and you just chuck it out, whereas Vitamin D (or precisely vitamin D3 with K2 for better absorption) has no upper limit, and is better described as the anti-inflammatory hormone - it's really an unsung hero of metabolism and most likely none of us are taking enough (particularly during the winter when we don't get enough sunlight).

One of it's problems is that there is nothing new about vitamin D3 - so nobody can patent it or justify large development budgets, testing regimes, or marketing campaigns. That makes it incredibly effective and cheap. But less well known, because - no profit from shouting about it.

 

[Chris24Main]

Then - to carry on the line of thought about why we need vitamin C.

This is almost more of a philosophical question - it's an essential vitamin (meaning we cannot generate vitamin C in the body - we need to eat it - "essential" means that it has to be taken in) - so how, given how fundamental the process of cleaning up the campground clearly is - how have we evolved not being able to produce this vital element, which is essential?

None of the great apes can produce vitamin C. In some texts, this is described as an "evolutionary accident" - in others, looking at Gorillas and Orangutangs, this is taken as evidence that we must therefore really be evolved to eat the fruit and veg that contains vitamin C - after all, it's the realisation of this very thing that results in the British being called "limeys" because the Royal Navy had realised that a small amount of lime juice could stave off scurvy.

so, it all seems to make sense - and the next step is really not received wisdom, nor generally accepted, but there is good science behind it. I'm totally behind this, but I cannot claim that this is even a majority held view.


In all of our serum lipid panel results - there is one (actually many) thing missing - Lp(a) - pronounced "L", "P", "little a"

It's almost identical to LDL - I tend not to put in diagrams, but here's one:

 

[Chris24Main]

Now - there are two things to note -
firstly - that additional protein tail, totally changes the function of Lp(a) - it binds to gunk. From the NIH:
"The physiological functions of Lp(a) include wound healing, promoting tissue repair and vascular remodeling."

The second thing, is that - at the time that the work on the heart-health hypothesis was going on in the sixties - there was no way of telling these apart - so if you take the understanding that - we may have evolved this particular particle to do the same job as vitamin C - it binds to and breaks down gunk - then it shouldn't be much of a surprise to find it in blood clots - particularly blood clots sitting in arterial plaques.

However - seeing such things in plaques sixty years ago, having no idea what they were - is still one of the key drivers of the opinion that LDL is "bad" - isn't that interesting?

if you google Lp(a) - you will see lots of "it is associated with artherosclerosis" and "a risk factor for CVD" - yet it's function couldn't be clearer - imagine if we thought that Vitamin C was "bad" - and told people to eat less food with vitamin C in it - and then lots and lots and lots of people became more and more unwell...

oh.

 

[Melgar]

@Chris24Main I had some positive results from some tests I had. Firstly, my lipids are down. I’m taking a Rosuvastatin 10mg , so a small dose. No side effects so far, but here are my results:
June 2024 they were out of range. Eating very little fat so these cholesterol results were down to my liver. Fasted state 6 hours

Cholesterol - 6.5 mmol/L
Cholesterol in LDL - 4.54
Cholesterol in HDL - 1.71
Cholesterol Non HDL - 4.79

Cholesterol / Cholesterol in HDL - 3.80
Triglyceride - 0.54

Results of my last panel January 2025 Fasted state 14 hours

Cholesterol - 4.39 mmol/L
Cholesterol in LDL - 2.23
Cholesterol in HDL - 1.87
Cholesterol Non HDL - 2.52

Cholesterol / Cholesterol in HDL - 2.35
Triglyceride - 0.63

I must say I am very pleased with those results, having resisted Statins for all the reasons we discuss here on your rolling blog.
Having read McKendricks thesis , ‘The Clot Thickens’, and being somewhat influenced by his argument against statin use, I was still very unhappy with the level of my LDL fats. Maybe I have been unduly influenced by decades of LDL = bad fats. I had fears that if I started Statins my lipids would somehow fall too low and I would be at risk of , well as a woman, suddenly dropping dead.

The other positive that has come out of my current medical issues and the battery of tests that have followed, is this - I do not have a fatty liver. No NAFLD. I had never heard of fatty liver prior to your discussion here. So it became a thing in my mind. I was relieved to see my results.
The stats for T2 diabetics and the general population, in North America with NAFLD is scary high. In general 20% of Canadians have fatty livers, regardless of blood sugar elevation.

https://www.liver.ca/patients-caregivers/liver-diseases/fatty-liver-disease/#:~:text=As%20the%20name%20implies%2C%20the,of%20their%20body%20(waist).

Lower alanine aminotransferase levels are associated with increased all-cause and cardiovascular mortality in nonalcoholic fatty liver patients - PMC

Serum alanine aminotransferase (ALT) levels are often considered a marker to evaluate liver disease and its severity. To investigate the association between ALT levels and all-cause and cause-specific mortality in patients with nonalcoholic fatty ...

pmc.ncbi.nlm.nih.gov

It made me wonder about the correlation between NAFLD and the accumulation of fat around other organs.

 

[Chris24Main]

Well, the association with the liver is simply because that's where the fats are being made (or transported from the gut). If you are in a poor metabolic state and fats are "leaking" from adipose tissue, they are still in the bloodstream before being picked up by something... but that would be anywhere.

So - great - glad that you have some news that you are happy with - and no question that Statins will reduce LDL - only that it's questionable whether that's actually a good thing, when all-cause mortality is associated over and over with high cholesterol and all the rest of that part of this thread.

Am I right in thinking that your triglycerides have gone up...?
Per metabolic syndrome, you'll be aware that I'm personally focused on the ratio of Trig/HDL - these both being part of the diagnosis for that, where LDL is not relevant.

Your previous was 0.54/1.71 = 0.31 where Jan is 0.63/1.87 = 0.33
Both are better than my last of 0.44 (anything below 2 would be considered good in this way of looking at the lipid panel).

I'm not going to run through the set of arguments again, you are totally entitled to your views, but I would say that all of these results are perfectly fine; and a total cholesterol level of 6.3 would be smack in the mean for Switzerland with one of the lowest CVD rates in Europe. I still would not be happy with the risks associated with taking statins, but you are clearly feeling better about it, so that's great.

I think I would still want someone to be able to explain what the difference is, chemically, between good cholesterol and bad cholesterol before agreeing to take such a thing. That and - explain to me the difference between LDL and Lp(a)..?

You are interested in enzymes - are you going to be taking Coenzyme Q10 supplements for the disruption in production that the statins will cause (not an opinion, just how they actually work in the chain of events that should normally lead to cholesterol being produced) ?

 

[Chris24Main]

@Melgar - just reading back through the above and worried that I'm sounding somehow negative - the main thrust should be - all the results you have shared; I would personally be completely happy about if they were mine - I just don't see anything in any of it (either set) that would concern me.

But - you were concerned about LDL - it's gone down - great, lets hope that puts you on a better path.

 

[Bcgirl]

Chris24main….i have a question for you. I’m pretty sure I know the answer but love your insights!
I do have high cholesterol and not worried about it BUT….my latest tests had my triglycerides up a bit and HDL down a bit and I’m not impressed. My ratio is now at .57
so, what happened during those six months? I am a tiny thing and do a lot of heavy weight lifting, takes forever for me to gain any muscle. This last month we were on holidays and although I walked an awful lot I did not lift anything heavy and as a consequence I lost over five pounds, all muscle I am sure (on a frame of 5’7” I now weigh just 111 lb). Then I was sick. As soon as we were home, and feeling better these new tests were done.
So, did my muscle loss have anything to do with the poorer results? I have heard that lifting heavy increases HDL. Does illness affect results?

thanks in advance

Melgar, glad you’re happy with your results. Question, did your doctor persuade you with the statins?

 

[Melgar]

@Bcgirl , yes, she simply says give them a go. No pressure at all. I was concerned at the level of my LDL’s . Despite the trending thoughts around LDL’s not being the bad guys, I still wasn’t happy. So I said I would try them. I am happy with where they are at now. My Triglycerides rose slightly, but they do fluctuate between 0.64 - 0.53. They have been in that cycle for a number of years.