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

[Chris24Main]

@Melgar

I wasn't happy with my own explanation - which did come from the perspective of "there is no mechanism for measuring blood glucose" - but it is clear that this is generally the way it is described in much of the literature..

Glucose Sensing in Pancreatic β-Cells: A Model for the Study of Other Glucose-Regulated Cells in Gut, Pancreas, and Hypothalamus

Nutrient homeostasis is known to be regulated by pancreatic islet tissue. The function of islet β-cells is controlled by a glucose sensor that operates at

diabetesjournals.org

For example - this describes the glucose-sensing nature of the β-cell.
However, when you dig into it a little deeper... you get; "Briefly, pancreatic β-cells express GLUT2 glucose transporters, which permit rapid glucose uptake regardless of the extracellular sugar concentration"

ie, they react to glucose in the blood - but do not react differently to the amount of glucose in the blood, and the article then goes on to explain the signalling pathways via Glucagon, and various other things....
So, again, it's more complicated...

but, I think it's a routing thing - there is a physical pathway direct from the gut to the liver which triggers the pancreas. My understanding - and you've got me obsessed about this now - is that glucose created in the liver doesn't trigger an elevation in insulin because the glucose-rich blood is not coming from the gut, it's going from the liver.

Or - I may be wrong - but I can't see any evolutionary reason why we should have the ability to create new glucose (say during an extended fast), because the body or brain needs the energy, simply for a hormone to kick in which drags it out rather than release it to the cells for energy they needed. But clearly I have more work to do on this <grin>

 

[Melgar]

Not standard. It’s not unheard of to be added depending on why they test in the first place.

CRP test is routine here and forms part of your basic blood work panel. I’m surprised the UK doesn't test CRP levels given the importance of inflammatory markers.

 

[Melgar]

@Chris24Main its been a huge learning curve for me as well, so I know where you are coming from. The body‘s metabolic system is such a complicated affair with all the signalling that takes place between the cells in order to keep the body in homeostasis. If you try and hold it all in your head at once it’s too much, well for me anyways, so I try to drill down to the basics. I know when I do this I run the risk of over simplifying an extremely complex process. On top of this, trying to understand these medical research papers, many of them attempting to prove an hypothesis, can be contradictory and confusing, simply because they are exactly that, research papers. As with most things in life nothing is ever simple. So my simplification of complex matters can come back to bite me.

Thanks for the link. My oversimplification for me is a means by which I understand these complexities. The super sensitive beta cells, for want of a better word, monitor how much glucose is in the blood. The body has to measure the amount of glucose in the blood in someway else how does the pancreas and liver know how much glucose to secrete and whether it needs to adjust blood glucose for the body’s energy needs, and to keep the body in homeostasis. To me that makes sense. I also know that signalling takes place between the pancreas, the hepatic system , the gut and the brain. How this signalling takes place is another matter, but I do know it takes place. My come away from all this is that the body is a truly remarkable machine.

 

[Chris24Main]

So - another weekend, another set of videos, book chapters and time sat staring out into the middle distance...

@Melgar - the body is a truly remarkable machine indeed.. I've been chewing on this question of, essentially how the body controls glucose level, because on the one hand, in a totally normal healthy person, there is a very consistent ~4gm of glucose in the blood, never more, never less, yet there is also this quote from a metabolism professor that states that the body has no means to measure blood glucose - how can these both be correct?

And where I sit at the moment (note the total lack of absolute confidence on this one...) is that .. we forget about Glucagon.

The model we hold in our heads is that this all revolves around glucose, when glucose goes up, the Pancreas is triggered to produce more Insulin, and there is the control.. but most things in the body don't work like that - (like how machines work, with a sensor and a control loop) there are antagonistic triggers - one thing pushing one way, and another in the opposite..

And of course, this is the relationship between Insulin and Glucagon. They are produced in the Pancreas, very near each other, and the trigger is whether or not there is more or less blood glucose than the "reference" 4gm - Ie, there is no measurement, just - is it higher - Insulin! is it lower - Glucagon! and in a metabolically healthy person, who is sensitive to the effects of these hormones, the body gets back to a balance relatively quickly.

The issue is when we follow a standard diet, and eat something sugary or starchy on a regular basis, because then the blood sugar is more or less always above that reference level, so always calling for insulin.

Maybe I missed the more important point which is that there is nothing that feeds back to the brain to shop eating sugar or starch, whereas this is what happens when we eat fats.

The (interesting but probably pointless) side thought, is that ... (while there is some disagreement about whether the Brain prefers Glucose for fuel) it seems that the only cells in the body that cannot use Ketones, because they have no Mitochondria, are red blood cells - that makes sense, because if they did, they would consume the oxygen that is their purpose to deliver. So - we have this exquisite mechanism for controlling food intake and appetite, and fullness, based around fats, and a simple "on/off" switch to maintain a small amount of glucose in the media of the only cells that absolutely need it, but no more, because of how dangerous it is...

Does that sound like we're well evolved to eat mainly Carbs? or something else...?

 

[Melgar]

Perfectly stated @Chris24Main . I’m guessing the concept of measurement is so much more advanced in our bodies than the crude scale measurements we have developed over millennium by us humans. Yes the livers contribution adds a complexity to my overly simplified understanding. For me I have to keep it simple else I’ll lose my way.
I didn’t know red blood cells didn’t have mitochondria ! I must have zoned out on that lesson.
I love your running blog. It always makes me think and reassess, even if at times I think hmmm well that can’t be right, then I find you are right haha.

 

[Chris24Main]

On a bit of a tangent here - I just had a bit of a breakdown moment...

I was watching an interview, only a couple of weeks old, of a guy who had reversed his Crohn's disease with a carnivore diet. Now, I don't want to make simple comparisons that confuse people, but there are a lot of commonalities - he was talking about sitting in front of a dietician who was telling him - you understand that your body needs carbs, please tell me that you will eat carbs; and he's replying with, "yes, but you understand that we don't need to eat them, you understand Gluconeogenesis, right?" - and feeling like the discussion is going around in circles - just like conversations I've had with Diabetes specialist consultants.

Thankfully, I've never had to decide to keep going in the face of stern advice that "if you don't listen to me and take these drugs, you will be dead in six weeks, are you willing to take that risk?" - but it just made me take stock of the weight I've been carrying, trying to push on with my own personal regime of intermittent fasting and low carb high fat, without meds; somewhat in the face of medical advice, and pressure from people close to me to "stop evangelising" about fat, and "all this talk about carbs is winding me up" -

I just had to take a minute to have a talk about this with my wife, I was in tears - I really don't want this to become a point of friction between us (I don't in the end think it will be, we're both each other's biggest supporters in the end) - but it just struck me listening to this guy who had gone on the same journey (he was talking in the light of his MRI which showed that there was no active Crohn's and was wondering how to put it to his doctor that this was all on account of not eating Carbs) - Sometimes you are not aware of the weight you carry until you see someone else carrying something similar..

I just wanted to express how grateful I am to have this ... outlet... it helps me to carry that weight...

 

[Bcgirl]

I feel your distress chris24main. I honestly think my husband gets fed up with me and my stance against carbs yet at the same time I know he understands why I avoid them. Everyone one I know thinks I’m killing myself even though I am controlling my A1C without medication. You have to eat veggies….i hear it all the time. I find now I just don’t talk about my food, it confuses and upsets people. It even confuses and upsets me!

 

[MrsA2]

Yeah, I'm sat here enjoying being invited on holiday with a friend for over 50 years, who is obese, who has had bariatric surgery, who has regained a lot of her weight loss, who eats constantly "but it's only small portions", who exclaims loudly she's glad diabetes must be hereditary as no one in her family has it, who watches what I eat and still doesn't seem to realise that maybe, just maybe there might be something in low carbing that might help her too.

Luckily we have much else to talk about and just avoid the topic. Thank heavens for my support tribe on here.

 

[Chris24Main]

@MrsA2 - That did give me a chuckle...

On my side, my Father had nearly constant Gout, my mother died of malignant Cushing's, my father in law just died of cancer of the colon, and my mother in law has Lupus. As I keep reading and learning, ALL of these are linked intimately with Insulin Resistance... Yet - almost nobody has even heard of Insulin Resistance, or the simplest (was going to say easiest, but in truth you can't say it's easy) way to reduce it..

For me, forget the T2DM, I have feeling returning along my right foot that had been going for years (always put it down to consequence of a motorbike accident when I was 18) - my tinnitus is slowly getting better, I have less night leg cramps, my skin is in much better shape than it was last summer, every metabolic indicator I can think of is on the right path, and really all I've done is stop taking meds, and swapped carbs for fat..

I suppose I just need to keep trying to be a force for good without being too much of a pain in @ss ...

 

[AndBreathe]

CRP test is routine here and forms part of your basic blood work panel. I’m surprised the UK doesn't test CRP levels given the importance of inflammatory markers.

Whenever I have a general blood panel, high sensitive hs-CRP is included. Thankfully, thus far mine is low.

 

[AndBreathe]

On a bit of a tangent here - I just had a bit of a breakdown moment...

I was watching an interview, only a couple of weeks old, of a guy who had reversed his Crohn's disease with a carnivore diet. Now, I don't want to make simple comparisons that confuse people, but there are a lot of commonalities - he was talking about sitting in front of a dietician who was telling him - you understand that your body needs carbs, please tell me that you will eat carbs; and he's replying with, "yes, but you understand that we don't need to eat them, you understand Gluconeogenesis, right?" - and feeling like the discussion is going around in circles - just like conversations I've had with Diabetes specialist consultants.

Thankfully, I've never had to decide to keep going in the face of stern advice that "if you don't listen to me and take these drugs, you will be dead in six weeks, are you willing to take that risk?" - but it just made me take stock of the weight I've been carrying, trying to push on with my own personal regime of intermittent fasting and low carb high fat, without meds; somewhat in the face of medical advice, and pressure from people close to me to "stop evangelising" about fat, and "all this talk about carbs is winding me up" -

I just had to take a minute to have a talk about this with my wife, I was in tears - I really don't want this to become a point of friction between us (I don't in the end think it will be, we're both each other's biggest supporters in the end) - but it just struck me listening to this guy who had gone on the same journey (he was talking in the light of his MRI which showed that there was no active Crohn's and was wondering how to put it to his doctor that this was all on account of not eating Carbs) - Sometimes you are not aware of the weight you carry until you see someone else carrying something similar..

I just wanted to express how grateful I am to have this ... outlet... it helps me to carry that weight...

To be honest, Chris, I don't talk about my diet a lot, and only talk about Low Carb with people on here, or other diabetes-related environments. Frankly, I find it unhelpful; sometimes in a big way.

When folks ask why I don't eat x, y or z, I just explain I'd had a few blood tests and that over time those foods weren't doing me any favours. If they haven't glazed over (because most really don't give a hoot what I do or don't eat....), I just reinforced I felt and looked better without those things in my life and my blood and general health had improved, so I'd be sticking with it.

On that basis, there's little to argue with.

I'm very open with my OH about my health and he agrees I am well. He isn't low carb, but then if I were 77, meds-free, still exercising at least 5 days a week (more normally 6), with a 32/34 waist and an A1c in the 20s, I'd crack on eating at will too.

That said, he has an excellent "off" switch, and rarely over eats. He's had a hiatus hernia for decades and manages it by remaining trim.

I know it can be challenging dealing with closed minded HCPs, but if faced with that situation, I would likely invited them to review my last 10 years of blood test and make suggestions.

Of course, I'd have to expect the "special" lipids conversation, but I'd deal with that.

 

[Melgar]

Whenever I have a general blood panel, high sensitive hs-CRP is included. Thankfully, thus far mine is low.

If you don’t mind me asking @AndBreathe what are your CRP figures? Mine were 1.9 mg/L but my last CRP lab results were 1.1 mg/L. I do have extensive osteoarthritis, they keep checking I do not have RA , as my mom had RA. My CRP levels would be way higher if that was the case.

@Chris24Main sorry I don’t want to hijack your post.

 

[AndBreathe]

If you don’t mind me asking @AndBreathe what are your CRP figures? Mine were 1.9 mg/L but my last CRP lab results were 1.1 mg/L. I do have extensive osteoarthritis, they keep checking I do not have RA , as my mom had RA. My CRP levels would be way higher if that was the case.

@Chris24Main sorry I don’t want to hijack your post.

Usually around 0.3, with the "normal range" <10.

My father had RA, so I am tested periodically. As you likely know, aside from the RF in bloods there are difference in terms of how the conditions exhibit, but I'm sure you already know that.

 

[Melgar]

Usually around 0.3, with the "normal range" <10.

My father had RA, so I am tested periodically. As you likely know, aside from the RF in bloods there are difference in terms of how the conditions exhibit, but I'm sure you already know that.

You have optimum CRP stats @AndBreathe . I can only wish mine were that low.

 

[Chris24Main]

Much of what I'm currently spouting is coming from Ben Bickman's book "Why we get sick" - he's a professor of cell biology, and once you get past the language barrier (he speaks doctor) it's fascinating. Spoiler alert - it's all about insulin resistance. As T2DM - we kind of think we have a monopoly on this, but you can see T2DM as just one point at which insulin resistance jumps beyond a trajectory into a big problem. We should, as a society, be acting to educate people before they are diagnosed with the conditions that indicate that your body has already had too much insulin resistance.


I'm on much thinner ground with arthritis.. but let me jump in as usual...

Osteoarthritis was long considered to be a condition of wear and tear, and thus is often associated with carrying too much weight (sound familiar?) or just an inevitable consequence of getting old - but could better be considered a metabolic disease, with (huge simplification here) the repair mechanisms around the joint and joint lining becoming less effective due to Insulin Resistance. (ie a side effect of Insulin Resistance, regardless of the initial cause)

Rheumatoid arthritis is totally different, and the presence of one has no bearing on the other. However - as it's a chronic inflammatory response condition - that repeated inflammation can lead to developing insulin resistance..

There are three main routes to insulin resistance (ie, absent anything else) - Too much insulin, Too much repeated inflammation, and Too much stress

Reading this book has been like the end of the Crazy 88's scene in Kill Bill (for the movie nerds out there) - Uma Thurman has despatched all but one of the goons, a kid who stands there trembling, and she grabs him an ... basically spanks him with her Samurai sword - punctuating thusly; "This.. [slap] is what you get [slap] for messing about [slap] with Yakusa [slap] - go home to your mommy!"

each chapter is like that - Insulin Resistance causes this [slap] and this condition [slap] and this disease [slap] - Go home to your mommy!

Anyway - I may have digressed a little there... it's been one of those days...

 

[Chris24Main]

On a more serious note, and it would be interesting and constructive to gauge how people feel about this here...

The more I learn, the more I feel that, yes - the present danger for T2DM is of course high blood glucose levels - all the literature is not wrong in that, but .... but... once you have gotten yourself off the precipice of very high levels of Glucose - whether with drugs, diet or fasting - that isn't enough, you have to engage with Insulin Resistance because that will still affect all the other ways that can lead to similarly bad outcomes.

The most positive way to spin this - is that having been diagnosed T2DM, and having to face those outcomes.. the things you can do to pull things off that precipice are the very same things you can do to reverse insulin resistance, we get that and we can support each other to do those things.. but if you have no idea about any of this (as I did only this January) - how are you supposed to know or make any change ? - all the fluff in the media switching from one super food to another or "thing to avoid" of the week?- I'm shocked (knowing what to look for) just how much disinformation there is...

 

[AndBreathe]

On a more serious note, and it would be interesting and constructive to gauge how people feel about this here...

The more I learn, the more I feel that, yes - the present danger for T2DM is of course high blood glucose levels - all the literature is not wrong in that, but .... but... once you have gotten yourself off the precipice of very high levels of Glucose - whether with drugs, diet or fasting - that isn't enough, you have to engage with Insulin Resistance because that will still affect all the other ways that can lead to similarly bad outcomes.

The most positive way to spin this - is that having been diagnosed T2DM, and having to face those outcomes.. the things you can do to pull things off that precipice are the very same things you can do to reverse insulin resistance, we get that and we can support each other to do those things.. but if you have no idea about any of this (as I did only this January) - how are you supposed to know or make any change ? - all the fluff in the media switching from one super food to another or "thing to avoid" of the week?- I'm shocked (knowing what to look for) just how much disinformation there is...

For a significant majority of those impacted by insulin resistance, losing weight would be a great start. Whilst, pre-diagnosis, we hadn't heard (much?) about insulin resistance, we have all heard being a healthy weight (by the blunt instrument of the BMI scale.

Frankly, telling folks X is likely to happen rarely results in real, sustained change.

 

[Melgar]

Fascinating perspective @Chris24Main . I can only speak from my own personal experience. I am sensitive to insulin . As far as I’m aware I don’t have insulin resistance. Why do I think that? I’m on a med called Bupropion . It comes with warnings that it can cause hypoglycaemia. Studies show that Bupropion inversely significantly stimulates insulin secretion. It inhibits KATP channel activity in pancreatic B-cell membranes and induce insulin secretion in relatively high concentration.
see ‘Bupropion can close KATP channel and induce insulin secretion ‘ by Yifei Yang et al.
I was given this drug for another condition, but found I had to be very careful because I was and am prone to hypos.
Sure enough taking this drug significantly brought my blood sugars down. I was bumping along at 4 mmol/ls as a baseline / natural basal secretion. After months of taking this drug I have noticed that my blood sugar baseline has risen to nearly 6. Had Buproprion stopped reducing my blood sugars. So a few days ago I didn’t take my Bupropion pill to see if it had any effect on my blood sugars. To my surprise my blood sugar reading went up, not just a bit, where one might think it’s just natural blood fluctuations but up. I took the pill the following day and it went back down again. Yesterday I didn’t take my Bupropion and lo and behold my blood sugars are up again. To me this means I am sensitive to insulin . Please feel free to challenge that statement.

Osteoarthritis - I have it all over my body. My knees, my toes, my ankles, hips, lower and spine , elbows, wrists and fingers. It started in my knees while running in my early 40‘s. Classic over use joint issues. It has slowly progressed and now it’s everywhere. I got tested for RA. They say no it’s Osteoarthritis ( my mom had RA and was in a wheelchair, her father had it and was bed ridden) . They say my CRP levels would be much higher, if was RA. They are currently 1.1 mg/dl.
So drawing those two points together, I am insulin sensitive, and I have Osteoarthritis. Where does insulin resistance play a part in this?

Maybe I have built a house of cards, I don’t know, but I keep very fit, walking 25,000 - 30,000 steps a day plus repetitive weight training. No fat, very lean, not sure.

 

[Melgar]

And I forgot to mention my C-peptides are in the lower half of normal at 539 if I recall

 

[Outlier]

With the all-seeing eyes of hindsight, I realised I had been suffering from insulin resistance decades before I became T2. If only I'd known - if only more of us knew about it, both medical professionals and everyday people. So much grief could have been avoided by those of us who would have been willing to make what would then have been small changes. Better late than never, though.