Impact of protocol‐based physiotherapy on insulin sensitivity and peripheral glucose metabolism in critically ill patients

Carbon, Niklas M.; Engelhardt, Lilian Jo; Wollersheim, Tobias; Grunow, Julius J.; Spies, Claudia; Märdian, Sven; Mai, Knut; Spranger, Joachim; Weber‐Carstens, Steffen

doi:10.1002/jcsm.12920

Cited by 6 publications

(3 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Not only in chronic disease, but also in acute conditions of critical illness, insulin resistance has been linked to impaired mitochondrial biogenesis [ 180 ]. The phenomenon of insulin resistance was highlighted as a metabolic hallmark feature in critical illness myopathy and ICUAW [ 90 , 181 , 182 ]. Furthermore, overall gastrointestinal function may be impaired especially in critically ill patients with neuromuscular alterations [ 183 ].…”

Section: Structural and Functional Impairments Of Mitochondria In Icu...mentioning

confidence: 99%

“…Therefore, impairments of AKT-mediated FOXO suppression in critical illness may directly hamper mitochondrial function and promote muscle wasting. Furthermore, insulin-independent translocation of GLUT4 via activated AMPK was shown to be diminished in CIM patients [ 78 , 182 ]. The AMPK is another enzyme interlinking glucose metabolism, mitochondrial function and skeletal muscle integrity.…”

Section: Structural and Functional Impairments Of Mitochondria In Icu...mentioning

confidence: 99%

See 1 more Smart Citation

Mitochondrial Dysfunction in Intensive Care Unit-Acquired Weakness and Critical Illness Myopathy: A Narrative Review

Klawitter

Ehler

Bajorat

et al. 2023

IJMS

View full text Add to dashboard Cite

Mitochondria are key structures providing most of the energy needed to maintain homeostasis. They are the main source of adenosine triphosphate (ATP), participate in glucose, lipid and amino acid metabolism, store calcium and are integral components in various intracellular signaling cascades. However, due to their crucial role in cellular integrity, mitochondrial damage and dysregulation in the context of critical illness can severely impair organ function, leading to energetic crisis and organ failure. Skeletal muscle tissue is rich in mitochondria and, therefore, particularly vulnerable to mitochondrial dysfunction. Intensive care unit-acquired weakness (ICUAW) and critical illness myopathy (CIM) are phenomena of generalized weakness and atrophying skeletal muscle wasting, including preferential myosin breakdown in critical illness, which has also been linked to mitochondrial failure. Hence, imbalanced mitochondrial dynamics, dysregulation of the respiratory chain complexes, alterations in gene expression, disturbed signal transduction as well as impaired nutrient utilization have been proposed as underlying mechanisms. This narrative review aims to highlight the current known molecular mechanisms immanent in mitochondrial dysfunction of patients suffering from ICUAW and CIM, as well as to discuss possible implications for muscle phenotype, function and therapeutic approaches.

show abstract

Section: Structural and Functional Impairments Of Mitochondria In Icu...mentioning

confidence: 99%

Section: Structural and Functional Impairments Of Mitochondria In Icu...mentioning

confidence: 99%

Mitochondrial Dysfunction in Intensive Care Unit-Acquired Weakness and Critical Illness Myopathy: A Narrative Review

Klawitter

Ehler

Bajorat

et al. 2023

IJMS

View full text Add to dashboard Cite

show abstract

“…Early protocol-based mobilization has been shown to improve functionality and counteract muscle atrophy as well as insulin resistance [ 6 , 8 , 9 ]. Nevertheless, evidence has not always been uniform and some studies failed to demonstrated the association [ 10 ]. Although controversial, intensive insulin therapy has been shown to have a protective effect regarding the development of neuromuscular dysfunction [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

Insulin signaling in skeletal muscle during inflammation and/or immobilisation

Grunow

Gan

Lewald

et al. 2023

ICMx

Self Cite

View full text Add to dashboard Cite

Background The decline in the downstream signal transduction pathway of anabolic hormone, insulin, could play a key role in the muscle atrophy and insulin resistance observed in patients with intensive care unit acquired weakness (ICUAW). This study investigated the impact of immobilisation via surgical knee and ankle fixation and inflammation via Corynebacterium parvum injection, alone and in combination, as risk factors for altering insulin transduction and, therefore, their role in ICUAW. Results Muscle weight was significantly decreased due to immobilisation [estimated effect size (95% CI) − 0.10 g (− 0.12 to − 0.08); p < 0.001] or inflammation [estimated effect size (95% CI) − 0.11 g (− 0.13 to − 0.09); p < 0.001] with an additive effect of both combined (p = 0.024). pAkt was only detectable after insulin stimulation [estimated effect size (95% CI) 85.1-fold (76.2 to 94.0); p < 0.001] irrespective of the group and phosphorylation was not impaired by the different perturbations. Nevertheless, the phosphorylation of GSK3 observed in the control group after insulin stimulation was decreased in the immobilisation [estimated effect size (95% CI) − 40.2 (− 45.6 to − 34.8)] and inflammation [estimated effect size (95% CI) − 55.0 (− 60.4 to − 49.5)] groups. The expression of phosphorylated GS (pGS) was decreased after insulin stimulation in the control group and significantly increased in the immobilisation [estimated effect size (95% CI) 70.6-fold (58.8 to 82.4)] and inflammation [estimated effect size (95% CI) 96.7 (85.0 to 108.5)] groups. Conclusions Both immobilisation and inflammation significantly induce insulin resistance, i.e., impair the insulin signaling pathway downstream of Akt causing insufficient GSK phosphorylation and, therefore, its activation which caused increased glycogen synthase phosphorylation, which could contribute to muscle atrophy of immobilisation and inflammation.

show abstract

Impact of protocol‐based physiotherapy on insulin sensitivity and peripheral glucose metabolism in critically ill patients

Carbon

Engelhardt

Wollersheim

et al. 2022

J cachexia sarcopenia muscle

Self Cite

View full text Add to dashboard Cite

Background The impact of physiotherapy on insulin sensitivity and peripheral glucose metabolism in critically ill patients is not well understood. Methods This pooled analysis investigates the impact of different physiotherapeutic strategies on insulin sensitivity in critically ill patients. We pooled data from two previous trials in adult patients with sequential organ failure assessment score (SOFA)≥ 9 within 72 h of intensive care unit (ICU) admission, who received hyperinsulinaemic euglycaemic (HE) clamps. Patients were divided into three groups: standard physiotherapy (sPT, n = 22), protocol‐based physiotherapy (pPT, n = 8), and pPT with added muscle activating measures (pPT+, n = 20). Insulin sensitivity index (ISI) was determined by HE clamp. Muscle metabolites lactate, pyruvate, and glycerol were measured in the M. vastus lateralis via microdialysis during the HE clamp. Histochemical visualization of glucose transporter‐4 (GLUT4) translocation was performed in surgically extracted muscle biopsies. All data are reported as median (25th/75th percentile) (trial registry: ISRCTN77569430 and ISRCTN19392591/ethics approval: Charité‐EA2/061/06 and Charité‐EA2/041/10). Results Fifty critically ill patients (admission SOFA 13) showed markedly decreased ISIs on Day 17 (interquartile range) 0.029 (0.022/0.048) (mg/min/kg)/(mU/L) compared with healthy controls 0.103 (0.087/0.111), P < 0.001. ISI correlated with muscle strength measured by medical research council (MRC) score at first awakening (r = 0.383, P = 0.026) and at ICU discharge (r = 0.503, P = 0.002). Different physiotherapeutic strategies showed no effect on the ISI [sPT 0.029 (0.019/0.053) (mg/min/kg)/(mU/L) vs. pPT 0.026 (0.023/0.041) (mg/min/kg)/(mU/L) vs. pPT+ 0.029 (0.023/0.042) (mg/min/kg)/(mU/L); P = 0.919]. Regardless of the physiotherapeutic strategy metabolic flexibility was reduced. Relative change of lactate/pyruvate ratio during HE clamp is as follows: sPT 0.09 (−0.13/0.27) vs. pPT 0.07 (−0.16/0.31) vs. pPT+ −0.06 (−0.19/0.16), P = 0.729, and relative change of glycerol concentration: sPT −0.39 (−0.8/−0.12) vs. pPT −0.21 (−0.33/0.07) vs. pPT+ −0.21 (−0.44/−0.03), P = 0.257. The majority of ICU patients showed abnormal localization of GLUT4 with membranous GLUT4 distribution in 37.5% (3 of 8) of ICU patients receiving sPT, in 42.9% (3 of 7) of ICU patients receiving pPT, and in 53.8% (7 of 13) of ICU patients receiving pPT+ (no statistical testing possible). Conclusions Our data suggest that a higher duration of muscle activating measures had no impact on insulin sensitivity or metabolic flexibility in critically ill patients with sepsis‐related multiple organ failure.

show abstract

Impact of protocol‐based physiotherapy on insulin sensitivity and peripheral glucose metabolism in critically ill patients

Cited by 6 publications

References 39 publications

Mitochondrial Dysfunction in Intensive Care Unit-Acquired Weakness and Critical Illness Myopathy: A Narrative Review

Mitochondrial Dysfunction in Intensive Care Unit-Acquired Weakness and Critical Illness Myopathy: A Narrative Review

Insulin signaling in skeletal muscle during inflammation and/or immobilisation

Impact of protocol‐based physiotherapy on insulin sensitivity and peripheral glucose metabolism in critically ill patients

Contact Info

Product

Resources

About