Diabetes: Have We Got It All Wrong? (T2D)

[kokhongw]

I think losing weight is also a T1 symptom.

It is. So my endocrinologist did a fasting insulin test...and found I was still producing plenty of insulin...

 

[millenium]

It is. So my endocrinologist did a fasting insulin test...and found I was still producing plenty of insulin...

T1 should have little insulin theoretically.

 

[alienskin]

It is. So my endocrinologist did a fasting insulin test...and found I was still producing plenty of insulin...

That may be so, but that doesn't mean that you haven't lost significant beta-cell function.

1) a normal person can produce significant amounts of insulin effortlessly. You may be producing normal amounts but your beta-cells may be working as hard as they can to do so. i.e. this effort is not sustainable because this effort will cause further beta-cell dysfunction.

2) problems with insulin production tend at the earlier stage to manifest in the first-phase response. In normal, people there is a huge dump of insulin within minutes of eating but this can be severely attenuated in diabetics. (The fasting insulin test your doctor gave you doesn't show this first phase response).

You can see in this diagram showing Insulin Secretion Rate (ISR) upon eating at T=0. (b) green are normal people (weight and age-matched), (c) red are people with Type 2 Diabetes for less than 6 years.

(d) incidentally shows the improvement after 1 week of going on a VLC diet.

If you're curious about the bounce at 60mins. This is what happens after an arginine bolus was administered. Note how both the non and the T2D insulin rates shoot up but less in the latter. This shows that T2D patients can produce insulin but there are major problems with first-phase response indicating the dysfunction (noting this figure shows recently diagnosed patients). Also, this response may come at a cost to further beta-cell damage like a battered car that you over-rev. And to stretch this analogy: the fact that your battered car can drive on the motorway doesn't mean it's in good condition.

Although your body is producing insulin there is something wrong with the beta-cell function. i.e. Insulin Resistance is not only issue. If it were, T2D patients who were able to attain good insulin sensitivity would get consistently normal scores on the Glucose Drinking Test but they don't. The question of whether we can recover beta-cell function is one of the biggest challenges of present research. We simply do not know.

So the goal is to improve your insulin sensitivity, while at the same time maintaining as much beta-cell function as possible. It *may* be the case that beta-cell function will continue to get worse, but if you can slow this progression significantly, it may be a non-issue over your lifetime. How do we achieve this? Well, that's the million (billion!) dollar question isn't it

 

[kokhongw]

Although your body is producing insulin there is something wrong with the beta-cell function. i.e. Insulin Resistance is not only issue. If it were, people who were able to attain good insulin sensitivity would get normal scores on the Glucose Drinking Test but they don't.

So the goal is to improve your insulin sensitivity, while at the same time maintaining as much beta-cell function as possible. It *may* be the case that beta-cell function will continue to get worse, but if you can slow this progression significantly, it may be a non-issue over your lifetime.

Yes Libre Flash CGM charts showed the lack of 1st phase insulin response, but the robust delayed 2nd phase insulin will overcompensate on high carbs meal and result in reactive hypoglycemic symptoms... 5.7 mmol to 11.5 mmol with 90 minutes after meals and back down below 5.5 mmol after another 90 mins...

 

[alienskin]

Here is a more recent article on the same subject....
https://www.sciencedirect.com/science/article/pii/S2352345X18301620
No mention of full suitcases or forcing passengers onto a train

Acutely highlights the difference between actual researchers doing in-depth research in the field and those not. That paper references 98 other papers many of which are studying what's going on at the DNA and RNA level.

The splitting of pathways is well-known and researched discovered by Michael Brown and Joseph Bernstein who incidentally won the Nobel Prize for medicine a couple of decades before for their work on LDL receptors. There's no paradox in the logic sense as such. The paradox simply is referring to the fact that one would expect the resistance to affect both pathways equally, but it doesn't. i.e. the precise interactions of two pathways are not fully understood. Negative feedback loops are a possibility.

Essentially, it's known that the insulin does bind, but the glucose pathway is resistant but the lipid one is not. Why this is so is not fully understood: it what the above paper tries to answer concluding possibly because "there is an interplay between the 2 pathways and the misregulation [of this interplay causes the observed 'paradox']".

There is absolutely no evidence to suggest it's because the cells are full of glucose already and to suggest the insulin "doesn't get into the cell" (whatever that means: insulin doesn't get into the cell anyway, it binds to the receptor on the cell which the paper explains essentially ruling out the alternative theory). If he's serious about this theory he needs to publish a paper with the same rigor as above.

Now an important point: this doesn't mean that intermittent fasting doesn't work. (We had no idea what Vitamin C was yet we knew oranges cured scurvy). It may well do, but the theoretical basis for its suggested effectiveness has no evidence. Furthermore, if you're using such a theory as a fundamental basis to explain why a certain treatment should work then it's your work that has no foundation.

 

[ickihun]

That may be so, but that doesn't mean that you haven't lost significant beta-cell function.

1) a normal person can produce significant amounts of insulin effortlessly. You may be producing normal amounts but your beta-cells may be working as hard as they can to do so. i.e. this effort is not sustainable because this effort will cause further beta-cell dysfunction.

2) problems with insulin production tend at the earlier stage to manifest in the first-phase response. In normal, people there is a huge dump of insulin within minutes of eating but this can be severely attenuated in diabetics. (The fasting insulin test your doctor gave you doesn't show this first phase response).

You can see in this diagram showing Insulin Secretion Rate (ISR) upon eating at T=0. (b) green are normal people (weight and age-matched), (c) red are people with Type 2 Diabetes for less than 6 years.

(d) incidentally shows the improvement after 1 week of going on a VLC diet.

View attachment 36125

If you're curious about the bounce at 60mins. This is what happens after an arginine bolus was administered. Note how both the non and the T2D insulin rates shoot up but less in the latter. This shows that T2D patients can produce insulin but there are major problems with first-phase response indicating the dysfunction. Also, this is for recently diagnosed patients. Also, this response may come at a cost to further beta-cell damage like a battered car that you over-rev. And to stretch this analogy: the fact that your battered car can drive on the motorway doesn't mean it's in good condition.

Although your body is producing insulin there is something wrong with the beta-cell function. i.e. Insulin Resistance is not only issue. If it were, T2D patients who were able to attain good insulin sensitivity would get consistently normal scores on the Glucose Drinking Test but they don't. The question of whether we can recover beta-cell function is one of the biggest challenges of present research. We simply do not know.

So the goal is to improve your insulin sensitivity, while at the same time maintaining as much beta-cell function as possible. It *may* be the case that beta-cell function will continue to get worse, but if you can slow this progression significantly, it may be a non-issue over your lifetime. How do we achieve this? Well, that's the million (billion!) dollar question isn't it

Does the liver response not muck all normal responses to first response insulin not being effective enough?

 

[Member496333]

Who mentioned insulin not getting into cells? First time I've heard that one. The backbone of Fung's hypothesis of hyperinsulinemia is that it is not a broken lock & key mechanism. I'm not a scientist but I see nothing in that paper which disproves the glucose overflow model. It also ends by saying that more work is needed to fully understand what's going on, which of course should be very clear to anyone with a passing interest.

Meanwhile, though, Fung's apparently incorrect ideas are successfully helping thousands rid themselves of obesity and type 2 diabetes while the academically endorsed standard of care is making people sicker.

 

[kokhongw]

How do we achieve this? Well, that's the million (billion!) dollar question isn't it

From what we have gathered over the past few years...we know what don't work for most, the insistence that carbs is essential. It may be... but certainly not at the current recommended levels...

And that adequate carbs reduction goes a long way to stretch out the remaining lifespan of our battered car...perhaps long enough for researchers to figure out if the loss in 1st phase insulin response is simply a signaling issue or physical loss of related beta cells...as they discover more about how FGF1 fits into the puzzle...
https://diabetes.diabetesjournals.org/content/67/Supplement_1/372-OR
https://diabetes.diabetesjournals.org/content/early/2019/04/23/db18-1175

https://uwmdi.org/labs/scarlett-laboratory/

 

[JohnEGreen]

who incidentally won the Nobel Prize for medicine

Not saying they didn't deserve it or owt but just put it in my mind that in 1939 Adolf Hitler was nominated for the Nobel Peace prize he obviously didn't get it but neither did anyone that year.

Funny the things that just pop into your head some times for no accountable reason.

 

[alienskin]

Who mentioned insulin not getting into cells? First time I've heard that one.

That's what he said in the podcast. Feel free to correct me if I misheard.

The backbone of Fung's hypothesis of hyperinsulinemia is that it is not a broken lock & key mechanism. I'm not a scientist but I see nothing in that paper which disproves the glucose overflow model.

That's not how science works. A paper about the surface of the Pluto may not disprove that the center is made of cheese, but it doesn't mean we have to take the cheese hypothesis seriously. Dr. Fung needs to write a similar paper of his own which the same rigour showing what mechanism he believes supports his ideas.

It also ends by saying that more work is needed to fully understand what's going on, which of course should be very clear to anyone with a passing interest.

Yes, it does.

Meanwhile, though, Fung's apparently incorrect ideas are successfully helping thousands rid themselves of obesity and type 2 diabetes while the academically endorsed standard of care is making people sicker.

Except we don't know that this is the case. When he does a rigourous study then we can know what percentage are successful with his protocol. He should do it himself.

One thing I do agree is that there is certainly a poor lack of guidance to newly diagnosed patients and this severely impacts the ability for individuals to manage their condition. Especially, there seems to be a hangup about adherence. It seems that professionals are so focussed on the idea that patients won't adhere to some protocol that they aren't doing anything at all. And I think this is where the issue lies.

Frankly, I believe that Dr. Fung's theoretical framework is nonsense, but there may be real merit in the diet itself. Hence the need for a proper study. Is his method better than Professory Taylor's? Maybe yes, maybe no. How about for long-term vs short-term? Asian ethnicity vs. non-Asian? Overweight T2d vs non? These are important questions, but we need the data.

 

[Member496333]

That's not how science works.

It's precisely how science works. Start with a hypothesis and attempt to disprove it. The paper in question here does not appear to disprove anything. That's not to say it has no merit, but it also doesn't provide sufficient evidence to demerit Fung's hypothesis. As far as I can see one doesn't necessarily discount the other. That is your interpretation, which of course you are entitled to, but it doesn't make anything fact.

 

[alienskin]

It's precisely how science works. Start with a hypothesis and attempt to disprove it.

Er no. You start with a hypothesis and gather evidence that shows it is true.

Now a proper hypothesis has to be falsifiable but this is not the same thing. We do not accept the truth of a hypothesis because it has not been disproved.

So take this hypothesis: the center of Alpha Centauri is made of cheese. Now that is falsifiable - if you had enough time and effort to get there you could indeed travel to the center and probably show that it is not made of cheese.

But in the meantime, the fact that you have been unable to disprove it means nothing regards its truth. I have presented no evidence regarding its truth, and thus you can dismiss it until I do. I cannot claim its truth because you have been unable to disprove it.

It is not up to other scientists to disprove Dr. Fung's hypothesis. It's up to him to demonstrate why it's true. And until he does so, it can be dismissed. And given the fact that there is strong evidence regarding the split pathway which is incompatible with his claims anyway, it's likely to be untrue anyway.

 

[millenium]

Acutely highlights the difference between actual researchers doing in-depth research in the field and those not. That paper references 98 other papers many of which are studying what's going on at the DNA and RNA level.

The splitting of pathways is well-known and researched discovered by Michael Brown and Joseph Bernstein who incidentally won the Nobel Prize for medicine a couple of decades before for their work on LDL receptors. There's no paradox in the logic sense as such. The paradox simply is referring to the fact that one would expect the resistance to affect both pathways equally, but it doesn't. i.e. the precise interactions of two pathways are not fully understood. Negative feedback loops are a possibility.

Essentially, it's known that the insulin does bind, but the glucose pathway is resistant but the lipid one is not. Why this is so is not fully understood: it what the above paper tries to answer concluding possibly because "there is an interplay between the 2 pathways and the misregulation [of this interplay causes the observed 'paradox']".

There is absolutely no evidence to suggest it's because the cells are full of glucose already and to suggest the insulin "doesn't get into the cell" (whatever that means: insulin doesn't get into the cell anyway, it binds to the receptor on the cell which the paper explains essentially ruling out the alternative theory). If he's serious about this theory he needs to publish a paper with the same rigor as above.

Now an important point: this doesn't mean that intermittent fasting doesn't work. (We had no idea what Vitamin C was yet we knew oranges cured scurvy). It may well do, but the theoretical basis for its suggested effectiveness has no evidence. Furthermore, if you're using such a theory as a fundamental basis to explain why a certain treatment should work then it's your work that has no foundation.

In the case of hyperlipidemia, the insulin resistance with regards to fat to acids? Are there other pathways for amino acids?

 

[Member496333]

Er no. You start with a hypothesis and gather evidence that shows it is true.

Er no. Attempting to prove a hypothesis to be true introduces potential bias at every level imaginable. Actual science is performed by attempting to disprove a hypothesis. The pursuit of proving hypotheses is precisely why nutritional “science” is the mess of biased research that it currently is.

But anyway, the topic is now veering off track. I don’t want the discussion to descend into back-and-forth bickering so I shall bow-out debating it with you. I’m sure we can disagree amicably and leave it there.

 

[alienskin]

Who mentioned insulin not getting into cells? First time I've heard that one.

I've listened quickly again, and I can't find the exact quote so apologies there, but it doesn't change much. This is what he said word for word:

"You have both resistance and supersensitivity. That's not really possible. And that's the central paradox if IR, and it doesn't really make any sense...it's like making a brick wall with no bricks. It's just impossible."

This is simply nonsense. The above paper shows exactly the split-pathway mechanism which makes it possible, and this has been around for years. He puts great store in the present model not being possible, but in fact it is very possible.

 

[alienskin]

Er no. Attempting to prove a hypothesis to be true introduces potential bias at every level imaginable. Actual science is performed by attempting to disprove a hypothesis. The pursuit of proving a hypotheses is precisely why nutritional “science” is the mess of biased research that it currently is.

I am a scientist and I can tell you, you're wrong here. I deliberately didn't use the word 'prove' here as science doesn't tend to prove things. You gather evidence that supports your claim.

Actual science is performed by attempting to disprove a hypothesis.

This clearly can't be the case. Because then it would make every half-assed hypothesis true by default which would be absurd.

But anyway, the topic is now veering off track. I don’t want the discussion to descend into back-and-forth bickering so I shall bow-out debating it with you. I’m sure we can disagree amicably and leave it there.

No worries. Have a good day!

 

[Member496333]

You gather evidence that supports your claim.

Oh dear. Ok.

 

[ickihun]

Not saying they didn't deserve it or owt but just put it in my mind that in 1939 Adolf Hitler was nominated for the Nobel Peace prize he obviously didn't get it but neither did anyone that year.

Funny the things that just pop into your head some times for no accountable reason.

Keep taking the tablets John.

 

[ickihun]

We will get there, I'm sure. Especially once half of the population will be gathering evidence (obesity) to support their claim (too much insulin creates fat cells).

Not good enough, is it?

To STOP obesity (in T2D) then IR has to hv more support to reverse it. Knowledge is a start then ACTION is needed. Supported til reversal, at least.

I'm 5st lighter and 250 uniits of insulin injected lighter too. I'm still obese maybe still morbibly obese.
My pancreas must be still throwing loads out. Or my liver is on double time.
I think my liver loves dumping even when I'm full of glucose already. A disfunctioning Pancreas and Liver, for sure.

 

[NicoleC1971]

Who is treating Diabetes T2 by injecting insulin?

Insulin is the last resort when all else has been tried. Since treating with increasing doses of insulin causes further resistance it is considered unhelpful in the context of a high carb diet.