Metabolic profiling reveals anomalous energy metabolism and oxidative stress pathways

[ChrisArmstrong]

Yes, my daughter, my son and I all got what seemed to be an acute viral infection followed by ME symptoms, all at roughly the same time. Although our symptoms were very very similar, there wasn't much in our (non-comprehensive) blood tests that was consistent. My daughter has since regained nearly full health.

The high anion gaps are one of the few blood test result anomalies my son and I share. My albumin levels are consistently low, my son's are consistently high-normal, whereas his levels of ALT and ALP are consistently low.

My CRP levels are consistently moderately elevated, my son's are not. My son's white cell, lymphocyte and neutrophil counts are consistently low normal to low; mine are not. Our iron tests look very different from each other and over time, except that transferrin saturation is consistently high in both of us.

One of the few advantages of having multiple family members contract this illness at the same time is that a whole range of hypotheses that would have looked very plausible with a sample size of one just don't stand up with a sample size of three.

Chris, yes, please do let us know via this forum when you are recruiting for your next studies. Best wishes for attracting funding - hopefully the excitement over the Rituximab results translates into increased funding for all types of ME biomedical research.

I never replied to this, sorry. Yes, blood is a tricky thing to deal with because the state at which you are in when you give the blood can affect it dramatically and it can affect changes. It's better to get the metabolite levels from within a cell but that is not possible at this point. The blood metabolism in a shared symptom state should be similar though, for example if you all felt muscle pain and fatigue at the time of giving the sample then i'd expect the results to be somewhat similar.

 

[JaimeS]

We're about to release some information on the microbes and fecal metabolites from these patients as well, will let you know when it's available. Thanks again!

How exciting! Looking forward to it.

 

[adreno]

@ChrisArmstrong, it's rare to see researchers coming here to answer questions and discuss their work. Thank you.

With Davis et al going down the same avenue with their recent findings, it seems to confirm that you are on to something important here.

Can't wait to hear more!

 

[ChrisArmstrong]

@ChrisArmstrong, it's rare to see researchers coming here to answer questions and discuss their work. Thank you.

With Davis et al going down the same avenue with their recent findings, it seems to confirm that you are on to something important here.

Can't wait to hear more!

Well I only came across this forum because JaimeS had done such a great job writing about it. I actually read here from time to time because you all do such a wonderful job of keeping up-to-date with research. Plus research is fairly isolating and it's really motivating to get some answers when you read through these forums.

I find the symptom expression variation quite fascinating as well, there's actually a lot of really interesting information on here that could be quite important if channeled through a standardised format. I was thinking of creating something to do that when I have time this year if people were interested.

 

[JaimeS]

I would love to help you with that, @ChrisArmstrong !

 

[Bob]

I find the symptom expression variation quite fascinating as well, there's actually a lot of really interesting information on here that could be quite important if channeled through a standardised format. I was thinking of creating something to do that when I have time this year if people were interested.

Yes, I would definitely be interested to see that.

 

[A.B.]

I find the symptom expression variation quite fascinating as well, there's actually a lot of really interesting information on here that could be quite important if channeled through a standardised format. I was thinking of creating something to do that when I have time this year if people were interested.

One of my pet questions is why some patients have demonstratable episodes of hypoglycemia even without any obvious endocrine disease. There are even more patients who benefit from eating small frequent meals, which is exactly what helps with this problem.

As far as I know this isn't even reported in the ME/CFS literature. I don't think this is common in the healthy population, right?

It's not a big issue but one would think that a problem that is so easy to identify would be better understood and more widely known.

 

[JaimeS]

One of my pet questions is why some patients have demonstratable episodes of hypoglycemia even without any obvious endocrine disease.

The endocrine disease may only be discoverable with the ITT, which is a hazardous test that is rarely administered, and can only be administered in a hospital. The goal is to hover the patient around a diabetic coma and see if the body responds to the 'trauma' properly.

If we are overly responsive to insulin, that may be what's causing the problem rather than a lack of production or an overproduction. In acute phase, I had a frightening hypoglycemic episode, and my whole life I've had a very mild tendency to reactive hypoglycemia -- as in, noticeably more tired, cranky, and irritable without food than other people, to the point that my parents used to joke about it when I was a child.

Apparently, overresponsiveness to epinepherine can also cause reactive hypoglycemia? It's yet another one of those disorders we don't really have a clear conception of in medicine.

-J

 

[ChrisArmstrong]

I would love to help you with that,

Yes, I would definitely be interested to see that.

Ok great, I will start fine-tuning the format for how it could be most useful for data analysis and I'll get your advice on some things from there JaimeS.

One of my pet questions is why some patients have demonstratable episodes of hypoglycemia even without any obvious endocrine disease. There are even more patients who benefit from eating small frequent meals, which is exactly what helps with this problem.

As far as I know this isn't even reported in the ME/CFS literature. I don't think this is common in the healthy population, right?

It's not a big issue but one would think that a problem that is so easy to identify would be better understood and more widely known.

When you say demonstratable hypoglycemia, is that by blood test? If by blood test is it common to see a bunch of other things low too?

I ask because many things can result in the reduction of glucose in the blood and things other than hypoglycemia can appear to have the same symptoms.

 

[adreno]

Ok great, I will start fine-tuning the format for how it could be most useful for data analysis and I'll get your advice on some things from there JaimeS.

I believe many of us have urine organic acids tests. Would those results be useful? Mine showed high pyruvate and lactate, for example.

 

[ChrisArmstrong]

I believe many of us have urine organic acids tests. Would those results be useful? Mine showed high pyruvate and lactate, for example.

Certainly, I think the more information the better.

 

[JaimeS]

When you say demonstratable hypoglycemia, is that by blood test?

I actually did have the ITT. My blood sugar would not come up again. I was there for ages.

Demonstrably unaffected by it, too. Blood sugar in the 20s and perfectly coherent. I freaked the techs out a little, I think: one of my few truly funny memories from acute phase, even if it is a bit of dark humor.

Techs: CAN YOU SPEAK. DO YOU KNOW WHAT YEAR IT IS.

...I was at Mayo, so by then I was trained: they make you give your name and birthday at every single station to make sure that the right person is coupled to the right test! Sometimes you get asked three or four times over the course of the same test or short appointment. I rattled off my full name, birthday, the year and who was president.

Me: Is this when people stop making sense?

Tech 1: This is usually when people pass out. DRINK MORE JUICE. CAN WE GET A SECOND GLUCOSE DRIP.

Long story short, I consumed over 100-g of sugar but it did zip.

...I consumed 100-g of sugar... and...

huh. Suddenly seeing this in a new light. They have you on a glucose drip, too. It still didn't help. They had to inject dextrose directly into my muscle to get my blood sugar to climb and stay there.

Maybe PWME don't rely much on sugars for energy at all anymore, and that was why such a low blood sugar didn't have the effect on me that it might on somebody else. My body may have already made a number of accommodations to favor fat and protein breakdown for energy, and the drop-off in glucose, while off-putting, was not nearly the disaster for me it might have been for someone else.

Just thinking aloud.

@ChrisArmstrong feel free to PM me re: gathering blood test results and such from people.

-J

 

[ChrisArmstrong]

I actually did have the ITT. My blood sugar would not come up again. I was there for ages.

Demonstrably unaffected by it, too. Blood sugar in the 20s and perfectly coherent. I freaked the techs out a little, I think: one of my few truly funny memories from acute phase, even if it is a bit of dark humor.

Techs: CAN YOU SPEAK. DO YOU KNOW WHAT YEAR IT IS.

...I was at Mayo, so by then I was trained: they make you give your name and birthday at every single station to make sure that the right person is coupled to the right test! Sometimes you get asked three or four times over the course of the same test or short appointment. I rattled off my full name, birthday, the year and who was president.

Me: Is this when people stop making sense?

Tech 1: This is usually when people pass out. DRINK MORE JUICE. CAN WE GET A SECOND GLUCOSE DRIP.

Long story short, I consumed over 100-g of sugar but it did zip.

...I consumed 100-g of sugar... and...

huh. Suddenly seeing this in a new light. They have you on a glucose drip, too. It still didn't help. They had to inject dextrose directly into my muscle to get my blood sugar to climb and stay there.

Maybe PWME don't rely much on sugars for energy at all anymore, and that was why such a low blood sugar didn't have the effect on me that it might on somebody else. My body may have already made a number of accommodations to favor fat and protein breakdown for energy, and the drop-off in glucose, while off-putting, was not nearly the disaster for me it might have been for someone else.

Just thinking aloud.

@ChrisArmstrong feel free to PM me re: gathering blood test results and such from people.

-J

Hmm, they put glucose into the same circulation they were testing for glucose and couldn't see a rise? 100g sugar in a 5L circulation is like 200 mg/dl, you had 20 initially - should've gone to 220mg/dl but they saw nothing. I wonder if they were collecting your blood properly..

Anyway, I guess it's possible that you adapted without glucose, do you have flexible joints or stretchy skin?

 

[alex3619]

Maybe PWME don't rely much on sugars for energy at all anymore, and that was why such a low blood sugar didn't have the effect on me that it might on somebody else. My body may have already made a number of accommodations to favor fat and protein breakdown for energy, and the drop-off in glucose, while off-putting, was not nearly the disaster for me it might have been for someone else.

Yeah. Back when I was monitoring my blood glucose it used to get really low before I felt hypoglycemic. Low enough that nobody believed me when I spoke about it.

 

[adreno]

Anyway, I guess it's possible that you adapted without glucose, do you have flexible joints or stretchy skin?

I have that. What's the connection to glucose metabolism?

 

[JaimeS]

Hmm, they put glucose into the same circulation they were testing for glucose and couldn't see a rise? 100g sugar in a 5L circulation is like 200 mg/dl, you had 20 initially - should've gone to 220mg/dl but they saw nothing. I wonder if they were collecting your blood properly..

Anyway, I guess it's possible that you adapted without glucose, do you have flexible joints or stretchy skin?

I drank 100-g of sugar. They put two glucose drips directly in my vein. The glucose rose briefly, but dropped too fast.

They keep a line in your arm to constantly monitor your blood sugar; the blood is tested frequently. To the patient, it's obvious when the blood sugar starts to swoop down again: you can feel it.

And yes, one of the first things I was diagnosed with was "benign joint hypermobility disorder". I don't have the hyper-stretchy skin but I'm very flexible.

-J

 

[ChrisArmstrong]

I have that. What's the connection to glucose metabolism?

I drank 100-g of sugar. They put two glucose drips directly in my vein. The glucose rose briefly, but dropped too fast.

They keep a line in your arm to constantly monitor your blood sugar; the blood is tested frequently. To the patient, it's obvious when the blood sugar starts to swoop down again: you can feel it.

And yes, one of the first things I was diagnosed with was "benign joint hypermobility disorder". I don't have the hyper-stretchy skin but I'm very flexible.

-J

Have you both always had hypermobility or did it get worse at the start of ME?

The joint hypermobility and stretchy skin are related to collagen. Collagen is the most abundant protein in the body and is entirely made up of non-essential amino acids. The non-essential amino acids are the ones being depleted and we suspect its because they are more inclined to be used for ATP production. The largest stores of collagen are in the joints and skin. So our theory of amino acid catabolism being increased to produce ATP due to an inhibition of glycolysis is linked to this symptom.

So yes your ability to tolerate lower glucose could be related although I would certainly need to test that.

 

[A.B.]

When you say demonstratable hypoglycemia, is that by blood test? If by blood test is it common to see a bunch of other things low too?

Measured with a glucose meter, so nothing else was measured at the time. I had a standard 2h glucose tolerance test (with insulin measurements) which was normal. I think it was normal because it was done in the morning, and I never have any blood sugar issues in the morning (typically in the afternoon, or at night). Fasting glucose is always normal. It also typically takes longer than two hours after a meal for anything to happen.

I did a glucose tolerance test at home and wrote down the results which are still somewhere in my medical documents. From memory, it took 3 or 4 hours before blood sugar dropped, but then it dropped to 43 mg/dL, with strong symptoms and signs.

I have also experienced an episode of hypoglycemia while away from home and without anything to eat. What happens is that after several minutes the blood sugar raises again on its own. So the the body is quite capable of recovering without help. It is quite draining though.

I tend to get hungry quickly after meals and eat frequently. I think that this helps and improves every day fatigue a little.

There is a familial tendency to this problem. My mother has had occasional episodes, as did my grandfather. No diabetes though.

Over the years the susceptibility to this problem has decreased. In the last year I hink I ony had two episodes of hypoglycemia. In part this is due to eating frequenty, in part because some things seem to get better on their own while others get worse.

 

[ChrisArmstrong]

Measured with a glucose meter, so nothing else was measured at the time. I had a standard 2h glucose tolerance test (with insulin measurements) which was normal. I think it was normal because it was done in the morning, and I never have any blood sugar issues in the morning (typically in the afternoon, or at night). Fasting glucose is always normal. It also typically takes longer than two hours after a meal for anything to happen.

I did a glucose tolerance test at home and wrote down the results which are still somewhere in my medical documents. From memory, it took 3 or 4 hours before blood sugar dropped, but then it dropped to 43 mg/dL, with strong symptoms and signs.

I have also experienced an episode of hypoglycemia while away from home and without anything to eat. What happens is that after several minutes the blood sugar raises again on its own. So the the body is quite capable of recovering without help. It is quite draining though.

I tend to get hungry quickly after meals and eat frequently. I think that this helps and improves every day fatigue a little.

There is a familial tendency to this problem. My mother has had occasional episodes, as did my grandfather. No diabetes though.

Over the years the susceptibility to this problem has decreased. In the last year I hink I ony had two episodes of hypoglycemia. In part this is due to eating frequenty, in part because some things seem to get better on their own while others get worse.

Very interesting, the length of time after a meal for digestion and absorbing of sugars is especially interesting to me.

 

[Sidereal]

My FBG has always been normal or in the upper end of normal range. Several years ago I had a 5-hour OGTT in hospital which was normal but subjectively I felt awful and hypoglycaemic. My issues subsequently got even worse after a trial of prednisone. When I went off of it, for the following couple of months I experienced fairly severe episodes where suddenly I'd start losing the ability to move my limbs and would almost lose consciousness. These symptoms would clear up after ingestion of food but carbs on their own wouldn't do it, it had to be protein + carbs. This would happen out of nowhere with no warning signs, btw. I learned to eat frequent meals as a result but of course that resulted in significant weight gain.