Glycolytic impairment - what are the practical implications?

So there is some evidence for impairment of glycolysis in pwME, leading to use of other fuel sources. I'm curious as to what the practical implications of this impairment on glucose itself (if anybody knows).

If glycolysis is impaired, does it meant that glucose is used up at the same rate as normal and the output of that process is less, or does it mean that the throughput of that process is lessened?

Additionally, if other fuel is used to make up for the lack of supply from glycolysis, would this then mean that less glucose is used than normal?

And if less glucose is being used for fuel then would that then lead to higher concentrations of glucose than normal somewhere in the system? If so, what would the implications of that be?

I have no answers myself, but it seems to be an interesting area to look at in my opinion.

@Simon M , any thoughts?

 

Thanks Trish. I think that my underlying question, which is based on several what-ifs, is "if glycolysis is impaired such that we have an excess of 'free' glucose AND if the normal mechanisms for dealing with that excess glucose is impaired in some way, what would be the result?". I'm more thinking aloud than anything else, in the hope that someone will have some insight.

 

A pwME will put on more fat if eating 5kg of cake a week than someone who doesn't have ME, even with exactly the same activity levels?

 

But would we? My n=1 is that I was underweight for many years without limiting my calories in anyway, and in situations where I've met other pwME, I haven't seen many examples of those who I would describe as excessively fat. Now that is still a small sample set, and there will no doubt be a wide variation, but I'm not convinced there is any evidence of above avergae excessive weight in patients, especially considering our reduced activity levels.

 

As far as I know the body only has two methods of handling excess and unused glucose.

It can either be excreted, or ut can be absorbed/converted into fat.

A possible hypothesis as to why some people get fat and some don't, or even get thinner, in the situation where glucose isn't being used correctly is that some oeoples kidneys have different thresholds for treating it as a txon and excreting it.

Is this threshold was, say, at the higher end of normal blood glucose levels then they would never have symptoms, other than the obvious, and never be tested or diagnosed for diabetes.

Just a hypothesis.

 

Adding muscle to your body burns fat because, well, muscle needs energy to survive.

My muscle mass has decreased quite a bit in the last 5 years, but I'm still not gaining pounds, it's just that my body weighs less because I have less muscle. Muscle is heavier than fat.

 

As a complete non expert who has read a lot I think all this is complicated by the individual's biochemistry. A very large study of the lean offspring of type 2 diabetics found that they had different way of processing fats and glucose. This matches the fact that diabetes is a particular problem in so called marginal areas where food was not always available. It is called a "thrifty genome". The implication is that being obese may be as much a product of this genome in a world of plenty as that diabetes is caused by being obese.

My husband's wider family are thin to very thin yet eat just as much as anyone else. If my husband misses a meal he stops being hungry. We think his liver is very good at releasing sugar whereas this does not happen with my relations.

Similarly, some people eat too much with depression whereas others stop eating.

Add to this that the control of blood sugar levels is controlled by the same mechanism of as temperature and things that don't work in ME and the fact we work on adrenalin a lot of the time which causes sugar cravings, it will take a supercomputer to work out what we should eat.

For myself, I need carbohydrates to function. I eat a fairly healthy diet and only have sugary things when I am hypoglycaemic but I have put on weight over the years.

In the early undiagnosed days, I was quite ill but forced to carry on. I was also very poor and missed a lot of meals but the weight kept piling up. Over the years I have noticed that if I do too much I put on weight so who knows what is going on.

 

My sister has Hashimoto and craves carbs and sweets. We can eat the same amounts of carbs/sweets and she will gain weight, but I won't. She is also quite active.

 

https://www.healthrising.org/blog/2...gregor-metabolism-chronic-fatigue-glycolysis/

Hypermetabolism
A section on 3 different glucose responses (n=777) seen in pwME. Implication that Creatinine being used as fuel substitute hence low urea and creatinine values seen in blood panels. Similar effects seen in sepsis and burns patients.
Creatine anecdotally cited by some pwME as a PEM buster.
High incidence of diabetes and insulin sensitivity/resistance I've read somewhere?
I struggle to tolerate much glucose and experience what I assume is hyperglycemic rebound at night. Keto resolved this but I'm concerned about keto long term so I'm back to normalish diet. Lowish carbs, I.F, plenty of protein and veg and considering BCAA.

 

would insulin resistance not also affect leptin and grehlin signalling and thus the hunger response- body has lost calibration of satiety?

 

Seems so.

(Not a medical opinion merely a personal one)

 

After 6 months of Keto I experienced some benefit but not enough. I know children with epilepsy can tolerate this for quite some time and the benefits are profound. A lot of suggestion in scientific community that there are long term risks but quite honestly it's so poorly researched I can't be sure.
I slept better, improved a little but the inconvenience (energywise) of catering for family and myself was draining in itself. After stopping I didn't deteriorate other than the sleep. I think the benefit of keto for me was down to cutting out glucose and gluten. If that's it I can do that in less drastic ways.
In the past I have IF and this for me provides the single biggest boost. I find eating, generally makes me feel worse. Even on keto some food triggered symptoms. By narrowing my eating window I personally cope better.

 

I think there are people in both camps as well, I had problems keeping weight and building muscle all my life and still in my 30's the BMI is on the low side without much activity. I think it does possibly tie with certain hypotheses of ME/CFS, one being that ME/CFS is kind of a hypometabolic or starvation type of response on the cellular level. In colloquial language people often tie a fast metabolism to losing weight and a low metabolism with the opposite, but I think it's not as simple in reality. It may be that we have metabolic issues making it difficult to process the energy in our food, but still some of us don't store it as extra fat, so the end result would be problems building up muscle and weight.