Human adaptation to immobilization: Novel insights of impacts on glucose disposal and fuel utilization, 2022, Schur et al

Abstract

Background
Bed rest (BR) reduces whole-body insulin-stimulated glucose disposal (GD) and alters muscle fuel metabolism, but little is known about metabolic adaptation from acute to chronic BR nor the mechanisms involved, particularly when volunteers are maintained in energy balance.

Methods
Healthy males (n = 10, 24.0 ± 1.3 years), maintained in energy balance, underwent 3-day BR (acute BR). A second cohort matched for sex and body mass index (n = 20, 34.2 ± 1.8 years) underwent 56-day BR (chronic BR). A hyperinsulinaemic euglycaemic clamp (60 mU/m2/min) was performed to determine rates of whole-body insulin-stimulated GD before and after BR (normalized to lean body mass). Indirect calorimetry was performed before and during steady state of each clamp to calculate rates of whole-body fuel oxidation. Muscle biopsies were taken to determine muscle glycogen, metabolite and intramyocellular lipid (IMCL) contents, and the expression of 191 mRNA targets before and after BR. Two-way repeated measures analysis of variance was used to detect differences in endpoint measures.

Results
Acute BR reduced insulin-mediated GD (Pre 11.5 ± 0.7 vs. Post 9.3 ± 0.6 mg/kg/min, P < 0.001), which was unchanged in magnitude following chronic BR (Pre 10.2 ± 0.4 vs. Post 7.9 ± 0.3 mg/kg/min, P < 0.05). This reduction in GD was paralleled by the elimination of the 35% increase in insulin-stimulated muscle glycogen storage following both acute and chronic BR. Acute BR had no impact on insulin-stimulated carbohydrate (CHO; Pre 3.69 ± 0.39 vs. Post 4.34 ± 0.22 mg/kg/min) and lipid (Pre 1.13 ± 0.14 vs. Post 0.59 ± 0.11 mg/kg/min) oxidation, but chronic BR reduced CHO oxidation (Pre 3.34 ± 0.18 vs. Post 2.72 ± 0.13 mg/kg/min, P < 0.05) and blunted the magnitude of insulin-mediated inhibition of lipid oxidation (Pre 0.60 ± 0.07 vs. Post 0.85 ± 0.06 mg/kg/min, P < 0.05). Neither acute nor chronic BR increased muscle IMCL content. Plentiful mRNA abundance changes were detected following acute BR, which waned following chronic BR and reflected changes in fuel oxidation and muscle glycogen storage at this time point.

Conclusions
Acute BR suppressed insulin-stimulated GD and storage, but the extent of this suppression increased no further in chronic BR. However, insulin-mediated inhibition of fat oxidation after chronic BR was less than acute BR and was accompanied by blunted CHO oxidation. The juxtaposition of these responses shows that the regulation of GD and storage can be dissociated from substrate oxidation. Additionally, the shift in substrate oxidation after chronic BR was not explained by IMCL accumulation but reflected by muscle mRNA and pyruvate dehydrogenase kinase 4 protein abundance changes, pointing to lack of muscle contraction per se as the primary signal for muscle adaptation.

Open access, https://onlinelibrary.wiley.com/doi/10.1002/jcsm.13075

 

Are they ignoring the reason a person is made bedbound in the first place . I am fed up with assumptions being made to suit the bias of researchers .

 

I don't know that these researchers are ignoring the multiplicity of possible reasons for being bed bound - this study seems to be basic research looking at what happens to a healthy body, and within its own terms the study seems to have been successful. It answers a legitimate question, and as basic physiology will presumably prompt others to seek to replicate.

What the relevance might be to long term enforced bedboundness will need to be explored in other studies with various lines of investigation e.g geriatrics, post op recovery, chronic illness etc.

 

I like basic biology and believe that it will help the way forward for ME understanding, but this is a bit different. Healthy people staying in bed is not a natural state of affairs. It is like looking at the biology of standing on one leg for hours, all it gives you is that one situation. It may be useful in the case of kidnapped and tortured people but tells us little about the biology of patients who need to stay in bed.

It may well be that the changes seen are evolutionary adaptations which fulfil some need and so increase the survival of the organism. The assumption that bedrest is always detrimental has been used against people with ME to justify graded exercise.

 

Even if it is just bad for us there is little we can do about it, most of us and probably running at 90% of what we can do in a day anyway, it's not like there is spare capacity to do more and we are being lazy. It's a consequence we can't avoid, it's not the cause of the condition.

 

There is a narrative that has been used against us since the biopsycho people have been involved. As with all these ideologies they took the advice to rest when you felt you had to, now called pacing, and distorted it to declare that people like the ME Association and the medical experts who believed ME was biological told patients they needed complete bedrest which then made patients decondition and afraid of exercise - kinsiophobia. The cure was to avoid ME groups and experts, stop thinking you were ill and do graded exercise. The fact that no one advised complete bed rest and thta a lot of people with ME were not deconditioned slowed them down not at all.

This had nothing to do with the severely affected who are bedridden. They were barely acknowledged and, if considered at all, were seen as an extreme case of being afraid. Even today, when the severely affected have a voice we know that many of the bedbound can still get to the bathroom, that is they are not totally immobile.

Sadly it is bad for us but we have no choice any more than with other diseases. It is apparent that one of the reasons ME is considered as being trivial and the sufferers just moaners (or terrorists or whatever insult flung at us) is because they present us as making the choice to be immobile.

 

There are some interesting perspectives here. The study was never aimed an investigation of ME. However, chronic bed-rest studies could bring new insights to ME research given the symptom driven inactivity and/or bed-rest experienced by ME patients are likely to mask or confound the true traits of this debilitating condition. Indeed, the chronic bed-rest model in healthy volunteers could prove to be an excellent control intervention to elucidate the pathophysiology of ME. Hopefully future research will take this perspective forward.

 

Only the very severe are consistently bed ridden and the majority of people with ME are not that deconditioned. I was very fit for the first twenty odd years I was ill. As long as I was able to rest ans break tasks into small pieces I managed all my own housework, shopping and child care.

When CFS was invented the focus went onto fatigue rather than an abnormal response to exercise so while there may be some relevant information to be gleaned from such experiments it would be closer to our situation to examine athletes after vigorous exercise.

Sadly it is right to say that those who are severe may need this research to find how to counteract the secondary consequences of enforced bed rest.

 

I have long been concerned about enforced bed rest in severe ME. Its necessary I think, but its also detrimental. I am less concerned about muscle deconditioning than another thing. Muscles can be rehabilitated once a patient's health problems are cured or effectively treated, which we cannot do yet of course. I am more concerned about bone deconditioning, and the bone disorders that go with it. Many years of bed rest is a huge risk factor.

Metabolic changes, unless they are locked in by something such as a metabolic trap, should also be reversible. It just might take time after recovery.

Recovery comes first. Its rare in long term ME (over 5 years) to see any recovery, not unknown, just rare. So severe patients do need science to figure out what is going on and to reduce the impact of bed rest. A cure would be better of course.