Glucose uptake by skeletal muscle within the contexts of type 2 diabetes and exercise

[mhtyler]

The above is the title of a study I'm reviewing. It's taking me a while because I'm not a scientist, I'm just a diabetic with sarcopenia who wants to understand what muscles COULD be doing for me if I actually had any. I'll post a review when I've gone through it thoroughly. I've said this several times here, but I think that skeletal muscle is too often overlooked in the diabetes equation. Here is a key sentence at the start of the document:
"Skeletal muscle is the primary tissue for maintaining glucose homeostasis through glucose uptake
via insulin-dependent and -independent mechanisms."
My emphasis added. More soon.

 

[everydayupsanddowns]

Interesting @mhtyler

Are you part of the peer review process? I volunteer as a lay reviewer for BMJ and occasionally get asked to comment on papers and studies that are being submitted for publication.

I let the Dr and research reviewers comment on the science - they are only really interested in my lived experience perspective as someone with diabetes 🙂

 

[everydayupsanddowns]

Of course if you are part of the review process, you’ll have to be careful about confidentiality until it’s published!

 

[mhtyler]

Of course if you are part of the review process, you’ll have to be careful about confidentiality until it’s published!

No, I am, to quote Dr Johnson, merely a harmless drudge trying to understand what's happening in my body.

 

[mhtyler]

Quote from the study:
While debated, there is evidence in humans that skeletal muscle acquires insulin resistance before adipocytes and hepatocytes.
And...
Loss of skeletal muscle glucose uptake is associated with abnormal carbohydrate metabolism
One thing that Dr Roy Taylor said in a lecture on YouTube is that the earliest detectable sign that someone may develop T2D is skeletal muscle insulin resistance. This study makes the point that this issue gets worse over time as fat is stored viscerally including intra-organ.

So, here is the T2D scenario (with respect to skeletal muscle); you start with skeletal muscle that is more insulin resistant, then you slowly lose muscle mass, and then you finally add to the insult by infusing skeletal muscle with fat making it even more insulin resistant. Dr. Taylor notes that someone with T2D may get NO HELP from skeletal muscle in clearing glucose after a meal. This even though in a normal person, skeletal muscle plays a principal role in post-prandial glucose regulation. This is an issue that nobody is talking about, not even Dr Fung, or Dr Taylor. Dr Taylor does make the point in this same lecture that significant weight loss that puts you into remission of your T2D has no impact on skeletal muscle insulin resistance. He hints that his organization at the University of Newcastle is studying the issue, but that is all we get.

In his counterbalance study, the responders (those whose pancreas function revived by the end of 8 weeks) had an average a1c of about 6.2 mmol/L. That's a fantastic result, and definitely non-diabetic, but why weren't they in the 5's club? Why weren't averages below 6? To put the question a different way; what is the difference between someone who is in remission from T2D, and someone who doesn't have it, and never did? Couldn't normal skeletal muscle glucose uptake which is the very first symptom in the development of the disease, also be the final piece of the puzzle?

Below is a link to the lecture by Dr Taylor. Its well worth your time if you aren't familiar with the twin cycle theory.

 

[PerSpinasAdAstra]

Many thanks for this - will definitely be reading this later.

Here's another one from 2017 along similar lines, looking at the effects of resistance training as a way to improve insulin sensitivity. It mentions something you referred to in another thread - Type II muscle tissue, specifically two sub-types - Type IIx, which is apparently common in people with T2 Diabetes, and Type IIa, which has higher levels of glucose uptake. Also mentioned is the possible effect of Metformin in inhibiting changes to muscle tissue in response to resistance training. Unfortunately it doesn't offer much in the way of strong conclusions - it raises as many questions as it answers, but it's interesting stuff.

Resistance training to improve type 2 diabetes: working toward a prescription for the future - Nutrition & Metabolism

The prevalence of type 2 diabetes (T2D) is rapidly increasing, and effective strategies to manage and prevent this disease are urgently needed. Resistance training (RT) promotes health benefits through increased skeletal muscle mass and qualitative adaptations, such as enhanced glucose transport...

nutritionandmetabolism.biomedcentral.com

 

[mhtyler]

Many thanks for this - will definitely be reading this later.

Here's another one from 2017 along similar lines, looking at the effects of resistance training as a way to improve insulin sensitivity. It mentions something you referred to in another thread - Type II muscle tissue, specifically two sub-types - Type IIx, which is apparently common in people with T2 Diabetes, and Type IIa, which has higher levels of glucose uptake. Also mentioned is the possible effect of Metformin in inhibiting changes to muscle tissue in response to resistance training. Unfortunately it doesn't offer much in the way of strong conclusions - it raises as many questions as it answers, but it's interesting stuff.

Resistance training to improve type 2 diabetes: working toward a prescription for the future - Nutrition & Metabolism

The prevalence of type 2 diabetes (T2D) is rapidly increasing, and effective strategies to manage and prevent this disease are urgently needed. Resistance training (RT) promotes health benefits through increased skeletal muscle mass and qualitative adaptations, such as enhanced glucose transport...

nutritionandmetabolism.biomedcentral.com

You're more likely to find more type 1 in T2D, that's because type 1 slow twitch is extremely efficient. That is exactly what you don't want if you have T2D. The other thing is that type IIx is the best kind, but its very hard to get. You need to train and train with heavy weights up to muscle failure. Type IIa also requires some training near muscle failure, but is easier to make. Both type II fast twitch muscle types are sugar guzzlers. BTW, here is a link to Dr Ted Naiman's video on comparing T2D people with bodybuilders. This 13 min video was an epiphany for me:

 

[PerSpinasAdAstra]

You're more likely to find more type 1 in T2D, that's because type 1 slow twitch is extremely efficient. That is exactly what you don't want if you have T2D. The other thing is that type IIx is the best kind, but its very hard to get. You need to train and train with heavy weights up to muscle failure. Type IIa also requires some training near muscle failure, but is easier to make. Both type II fast twitch muscle types are sugar guzzlers. BTW, here is a link to Dr Ted Naiman's video on comparing T2D people with bodybuilders. This 13 min video was an epiphany for me:

From the paper I linked:
"Type IIx fibers are described as having a glycolytic phenotype, relying on glucose more than fat as a fuel, and facilitating short-duration anaerobic activities. It has been shown that Type IIx fibers are present in a higher proportion in individuals with T2D [4]. Hyperinsulinemia—a hallmark feature of insulin resistance and T2D—can shift muscle fiber type toward a glycolytic phenotype by increasing Type IIx myosin heavy chain gene expression [5]."

Reference #4 is behind a paywall so I can't read it, though the basic premise makes sense to me. Besides the hyperinsulinemia thing - having been obese and mostly sedentary for the past few years I've lost a lot of my upper body muscle, but my legs are still fairly well muscled. I was capable of walking a few km without any significant problem and would do so maybe once a week on average. At the time I was carrying around 34Kg of fat over and above my ideal weight, so walking those few km was the equivalent of someone at their ideal weight packing 34 litres of water in a big backpack and lugging it around. Also, every time I had to get up out of a chair is akin to a 34Kg squat. Climbing stairs is hard work. I think it might be possible that just being mobile and doing a little bit of exercise as an obese person may have a similar effect to lifting weights regularly, at least on the leg muscles. Maybe.

 

[mhtyler]

From the paper I linked:
"Type IIx fibers are described as having a glycolytic phenotype, relying on glucose more than fat as a fuel, and facilitating short-duration anaerobic activities. It has been shown that Type IIx fibers are present in a higher proportion in individuals with T2D [4]. Hyperinsulinemia—a hallmark feature of insulin resistance and T2D—can shift muscle fiber type toward a glycolytic phenotype by increasing Type IIx myosin heavy chain gene expression [5]."

Reference #4 is behind a paywall so I can't read it, though the basic premise makes sense to me. Besides the hyperinsulinemia thing - having been obese and mostly sedentary for the past few years I've lost a lot of my upper body muscle, but my legs are still fairly well muscled. I was capable of walking a few km without any significant problem and would do so maybe once a week on average. At the time I was carrying around 34Kg of fat over and above my ideal weight, so walking those few km was the equivalent of someone at their ideal weight packing 34 litres of water in a big backpack and lugging it around. Also, every time I had to get up out of a chair is akin to a 34Kg squat. Climbing stairs is hard work. I think it might be possible that just being mobile and doing a little bit of exercise as an obese person may have a similar effect to lifting weights regularly, at least on the leg muscles. Maybe.

I see what you've quoted, and I'm going to go through the study. I've never seen this before and it seems paradoxical to me. ...still, there it is. I'll get to the bottom of it. FYI, I'm 69. Everything is hard work ;-) BTW, if you've time, please take a look at the Naiman video for me. I'd like your opinion, because what he's saying...and he's a bodybuilder as well as a dr appears to me to contradict this study you're quoting. More soon when I'm digested....the study that is.

 

[mhtyler]

From the paper I linked:
"Type IIx fibers are described as having a glycolytic phenotype, relying on glucose more than fat as a fuel, and facilitating short-duration anaerobic activities. It has been shown that Type IIx fibers are present in a higher proportion in individuals with T2D [4]. Hyperinsulinemia—a hallmark feature of insulin resistance and T2D—can shift muscle fiber type toward a glycolytic phenotype by increasing Type IIx myosin heavy chain gene expression [5]."

Reference #4 is behind a paywall so I can't read it, though the basic premise makes sense to me. Besides the hyperinsulinemia thing - having been obese and mostly sedentary for the past few years I've lost a lot of my upper body muscle, but my legs are still fairly well muscled. I was capable of walking a few km without any significant problem and would do so maybe once a week on average. At the time I was carrying around 34Kg of fat over and above my ideal weight, so walking those few km was the equivalent of someone at their ideal weight packing 34 litres of water in a big backpack and lugging it around. Also, every time I had to get up out of a chair is akin to a 34Kg squat. Climbing stairs is hard work. I think it might be possible that just being mobile and doing a little bit of exercise as an obese person may have a similar effect to lifting weights regularly, at least on the leg muscles. Maybe.

Okay, here is Dr Naiman's video specific to muscle types. Frankly I need to review it myself to make sure I don't have things bass ackwards.

 

[PerSpinasAdAstra]

I watched the video. On one hand I didn't like it, mainly because the guy rubs me the wrong way. He makes generalised statements about Type 2 Diabetics that imply that we're all overweight or obese, whereas there are plenty of lean and/or fit people who develop T2D. He also states as fact that taking a bodybuilder's approach to diet and exercise will 'completely destroy' T2D, which is clearly false for the majority of people living with the disease. A relatively old article from 2009 (link below), which is currently the best I can find on how T2D progresses over time, states that pancreatic beta cell dysfunction can begin as early as 12 years prior to diagnosis. It refers to evidence from human autopsies which show a 63% relative decline in beta cell volume in the pancreases of T2 diabetics. No amount of protein eating and weight lifting is going to repair a damaged pancreas. To the best of my knowledge nobody has ever demonstrated a way to repair such damage.

On the other hand he might just be right about losing weight and gaining muscle as a practical way to maximize existing pancreatic function to whatever degree that may be possible for a given individual, to improve insulin sensitivity, and to create a 'glucose sink' in the form of muscle mass which is regularly depleted of glycogen stores though intense or prolonged exercise. I'm hoping that such an effort might help in delaying the onset of diabetic complications to a considerable degree. That general idea is something I'm taking seriously as I trawl the internet for clues on how it might work and how to get it done 😉

Defining and Characterizing the Progression of Type 2 Diabetes - PMC

www.ncbi.nlm.nih.gov

 

[mhtyler]

I watched the video. On one hand I didn't like it, mainly because the guy rubs me the wrong way. He makes generalised statements about Type 2 Diabetics that imply that we're all overweight or obese, whereas there are plenty of lean and/or fit people who develop T2D. He also states as fact that taking a bodybuilder's approach to diet and exercise will 'completely destroy' T2D, which is clearly false for the majority of people living with the disease. A relatively old article from 2009 (link below), which is currently the best I can find on how T2D progresses over time, states that pancreatic beta cell dysfunction can begin as early as 12 years prior to diagnosis. It refers to evidence from human autopsies which show a 63% relative decline in beta cell volume in the pancreases of T2 diabetics. No amount of protein eating and weight lifting is going to repair a damaged pancreas. To the best of my knowledge nobody has ever demonstrated a way to repair such damage.

On the other hand he might just be right about losing weight and gaining muscle as a practical way to maximize existing pancreatic function to whatever degree that may be possible for a given individual, to improve insulin sensitivity, and to create a 'glucose sink' in the form of muscle mass which is regularly depleted of glycogen stores though intense or prolonged exercise. I'm hoping that such an effort might help in delaying the onset of diabetic complications to a considerable degree. That general idea is something I'm taking seriously as I trawl the internet for clues on how it might work and how to get it done 😉

Defining and Characterizing the Progression of Type 2 Diabetes - PMC

www.ncbi.nlm.nih.gov

Dr Naiman is an acquired taste, but he well understands that thin people can get diabetes 2. However, lean and fit people don't get type T2D. However, thinner unfit people do. These are called TOFI's; Thin Outside, Fat Inside. They get type 2 because they have a very limited capacity to create subcutaneous fat, and instead put on visceral fat that can't be easily seen. Secondly, according to Dr Roy Taylor's 3 studies on the matter, something like 90% of T2D's can achieve remission if they catch the illness 4 to 6 years or less from diagnosis. Those people can usually recover full pancreas function, although it can take more than a year to do so. Significant pancreas function can return in 8 weeks. It is true of course that once your pancreas is truly burned out it won't recover, and therefore true remission for those people is impossible, but a small percentage who've had the disease for more than 25 years have recovered pancreatic function. You just can't tell until you've lost the weight and cleared the fat from the liver and pancreas. I've had diabetes for 7.5 years, and I'm in the 3rd week of his 12 week program and my sugar is absolutely normal, which is a strong early sign that my pancreas is still making insulin and will recover. I won't know for sure until the end of the program when I return to isocaloric eating and test my a1c.

You are also absolutely right and I was entirely wrong about muscle mass makeup of T2D people. I am right about sarcopenia though. it's a natural process with age, at least unless you fight it at the gym. Therefore as you say in your final point, building muscle and a glucose sink seems like the best answer and was the real point of Dr Naiman. One final thing that you've highlighted to me, and that the title study of this thread notes is that a primary issue in people with T2D isn't muscle makeup, but is instead the complex mechanism that allows muscle mass to uptake glucose which is damaged in T2D. Dr Taylor also makes it clear that although his program can achieve remission in many people, it doesn't address skeletal muscle insulin resistance. Exercise seems to circumvent the issue, so I suppose the final answer is outside my door in runners and sweat pants.

 

[PerSpinasAdAstra]

Dr Naiman is an acquired taste, but he well understands that thin people can get diabetes 2. However, lean and fit people don't get type T2D. However, thinner unfit people do. These are called TOFI's; Thin Outside, Fat Inside. They get type 2 because they have a very limited capacity to create subcutaneous fat, and instead put on visceral fat that can't be easily seen.

I'm pretty sure there are outliers who are categorized as Type 2 but do not fit the standard profile. I've encountered people on another forum who were diagnosed as Type 2 or as Prediabetic but who described themselves as slim and fit. My suspicion is that there are perhaps more sub-types of Type 2 that are yet to be fully defined. Perhaps they do indeed have fatty livers and pancreases, though if that's the case the issue of limited capacity to create subcutaneous fat is something I find hard to wrap my head around.

One correction to my previous post - the autopsies showing pancreas damage - the 63% figure was in comparison to non-diabetic obese people, not a 63% decline in beta cell mass.

 

[Bubbleblower]

This is an issue that nobody is talking about

Or nobody is interested in; https://forum.diabetes.org.uk/boards/threads/something-to-think-about.107042/
I have literally written a book about this subject, that’s how big my document on it has grown by now.
Not only about glucose uptake by skeletal muscle but also by the brain which doesn’t require insulin from the pancreas; glucose is so important to the brain it produces it’s own insulin.


Prof. Taylor got popstar status, but according to his data the Newcastle diet doesn’t really work; https://www.ncl.ac.uk/press/articles/latest/2023/04/type2diabetesintoremissionfor5years/
After 5 years only 8% was still in remission, 11 extra motivated participants from his study that also still received support. Yet another issue nobody is talking about, what happened to the other 92%?


But that’s not on this interesting topic, which is relevant to all of us; daily exercise preserves beta cells in all types of diabetes and obviously sarcopenia is a major cause of diabetes. Including mine. Twice.

 

[harbottle]

thinner unfit people do. These are called TOFI's; Thin Outside, Fat Inside. They get type 2 because they have a very limited capacity to create subcutaneous fat, and instead put on visceral fat that can't be easily seen. Secondly, according to Dr Roy Taylor's 3 studies on the matter, something like

This is absolute nonsense.
There is a phenotype of people who are T2D without having any form of insulin resistance or visceral fat.

 

[harbottle]

Or nobody is interested in; https://forum.diabetes.org.uk/boards/threads/something-to-think-about.107042/
I have literally written a book about this subject, that’s how big my document on it has grown by now.
Not only about glucose uptake by skeletal muscle but also by the brain which doesn’t require insulin from the pancreas; glucose is so important to the brain it produces it’s own insulin.


Prof. Taylor got popstar status, but according to his data the Newcastle diet doesn’t really work; https://www.ncl.ac.uk/press/articles/latest/2023/04/type2diabetesintoremissionfor5years/
After 5 years only 8% was still in remission, 11 extra motivated participants from his study that also still received support. Yet another issue nobody is talking about, what happened to the other 92%?


But that’s not on this interesting topic, which is relevant to all of us; daily exercise preserves beta cells in all types of diabetes and obviously sarcopenia is a major cause of diabetes. Including mine. Twice.

Depends on what you mean by 'it didn't work'. The research showed that losing weight restored beta cell functionality and first phase insulin response in 'responders' - and the aim of the research was to try to understand why surgery for weight loss can see a reverse of T2D.

The fact that around 90% of participants regained the weight and it came back is no surprise, as around 90% of people who lose weight tend to put it back on again and are back where they started in 5 years. The important finding, IMHO, is that the beta cells aren't dead, as was thought, but dormant, in some people, and the condition isn't necessarily progressive.

 

[mhtyler]

This is absolute nonsense.
There is a phenotype of people who are T2D without having any form of insulin resistance or visceral fat.

I've never heard of this. Please tell me more.

Or nobody is interested in; https://forum.diabetes.org.uk/boards/threads/something-to-think-about.107042/
I have literally written a book about this subject, that’s how big my document on it has grown by now.
Not only about glucose uptake by skeletal muscle but also by the brain which doesn’t require insulin from the pancreas; glucose is so important to the brain it produces it’s own insulin.


Prof. Taylor got popstar status, but according to his data the Newcastle diet doesn’t really work; https://www.ncl.ac.uk/press/articles/latest/2023/04/type2diabetesintoremissionfor5years/
After 5 years only 8% was still in remission, 11 extra motivated participants from his study that also still received support. Yet another issue nobody is talking about, what happened to the other 92%?


But that’s not on this interesting topic, which is relevant to all of us; daily exercise preserves beta cells in all types of diabetes and obviously sarcopenia is a major cause of diabetes. Including mine. Twice.

The process of getting and then maintaining significant weight loss is only the hardest thing in the entire world to do. The counterbalance study showed that it worked for 100% of those who recovered pancreas function. Maintaining that weight loss is the weakest link.

 

[mhtyler]

This is absolute nonsense.
There is a phenotype of people who are T2D without having any form of insulin resistance or visceral fat.

I've never heard of this. Please tell me more.

Or nobody is interested in; https://forum.diabetes.org.uk/boards/threads/something-to-think-about.107042/
I have literally written a book about this subject, that’s how big my document on it has grown by now.
Not only about glucose uptake by skeletal muscle but also by the brain which doesn’t require insulin from the pancreas; glucose is so important to the brain it produces it’s own insulin.


Prof. Taylor got popstar status, but according to his data the Newcastle diet doesn’t really work; https://www.ncl.ac.uk/press/articles/latest/2023/04/type2diabetesintoremissionfor5years/
After 5 years only 8% was still in remission, 11 extra motivated participants from his study that also still received support. Yet another issue nobody is talking about, what happened to the other 92%?


But that’s not on this interesting topic, which is relevant to all of us; daily exercise preserves beta cells in all types of diabetes and obviously sarcopenia is a major cause of diabetes. Including mine. Twice.

The process of getting and then maintaining significant weight loss is only the hardest thing in the entire world to do. The counterbalance study showed that it worked for 100% of those who recovered pancreas function. Maintaining that weight loss is the weakest link.

Or nobody is interested in; https://forum.diabetes.org.uk/boards/threads/something-to-think-about.107042/
I have literally written a book about this subject, that’s how big my document on it has grown by now.
Not only about glucose uptake by skeletal muscle but also by the brain which doesn’t require insulin from the pancreas; glucose is so important to the brain it produces it’s own insulin.


Prof. Taylor got popstar status, but according to his data the Newcastle diet doesn’t really work; https://www.ncl.ac.uk/press/articles/latest/2023/04/type2diabetesintoremissionfor5years/
After 5 years only 8% was still in remission, 11 extra motivated participants from his study that also still received support. Yet another issue nobody is talking about, what happened to the other 92%?


But that’s not on this interesting topic, which is relevant to all of us; daily exercise preserves beta cells in all types of diabetes and obviously sarcopenia is a major cause of diabetes. Including mine. Twice.

I think saying it didn't work is a radical interpretation of the text. My understanding is that those who recovered beta cell function AND maintained weight loss, maintained remission regardless of the difficulty.

 

[Bubbleblower]

The research showed that losing weight restored beta cell functionality

Yes, losing weight works -if you are overweight- but the Newcastle diet doesn't.

Now the skeletal muscle takes up 80% of postprandial glucose and the brain uses 20% of all glucose.
Yet our glucose is too high.
We need to use that 20% to figure out what the problem is.

 

[PerSpinasAdAstra]

After 5 years only 8% was still in remission, 11 extra motivated participants from his study that also still received support. Yet another issue nobody is talking about, what happened to the other 92%?

The Newcastle diet is good in that it's simple, can be delivered by a health service, and clearly works, at least for a time. The downside is that it does nothing to help build new eating habits. I can cook, enough, I am currently motivated enough to plan my diet and lose weight week after week, and I'm committed to trying to do all I can to prevent or at least delay the onset of diabetic complications including trying to read scientific papers and whatnot. That said, I know how easy it would be for me to slip, buy some wine, some chocolate, order a large pizza, and watch a couple of movies. A few nights like that and my plans might all fall apart. Just like the way I went back to smoking cigarettes, twice, after having been off them for years at a time - it's just so easy to forget how hard it was to give them up and fall back into old habits.

If the prospect of keeping to a healthy diet for the rest of my life is daunting for highly-motivated me. I can only imagine how hard it might be for a group of people picked at random, put on a crash diet for a short time, advised to change their entire way of eating, then left largely to their own devices. I think it unfair to judge the value of Taylor's research and achievements based on the success or otherwise of a bunch of random people in staying out of McDonalds.