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Muscle weakness as an additional criterion for grading sarcopenia-related prognosis in patients with cancer.
Cereda, E, Tancredi, R, Klersy, C, Lobascio, F, Crotti, S, Masi, S, Cappello, S, Stobäus, N, Tank, M, Cutti, S, et al
Cancer medicine. 2022;(2):308-316
Abstract
BACKGROUND Low muscle strength has been pointed out as a key characteristic of sarcopenia, but the prognostic significance of muscle function next to reduced skeletal muscle mass (SMM) in patients with cancer has been scantily investigated. METHODS Data on muscle strength by handgrip (HG) dynamometry and total-body SMM estimated by bioelectrical impedance analysis (BIA) of Italian and German patients with cancer observed prospectively until death or censoring were analysed (N = 1076). Patients were stratified in four risk categories based on low HG (<10th percentiles of age and gender-specific normative values) and low total-body SMM according to SMM index cutoffs (<10.75 and <6.75 kg/m2 in men and women, respectively). RESULTS During a median follow-up of 58 months [25th-75th percentile, 37-60], 566 patients had died. Patients presenting low HG in combination or not with low SMM were characterised by shorter median survival (12.7 vs. 27.2 months, respectively; p < 0.001) compared to those with low SMM/normal HG and normal SMM/normal HG (>60 months for both). After adjusting for sex, age, body mass index and percentage of weight loss, disease's stage, performance status and type of cancer, compared to reference category (normal HG and SMM; N = 210) the hazard ratios were: low SMM/normal HG (N = 342), 0.83 [95% confidence interval, CI, 0.67-1.02] (p = 0.073); normal SMM/low HG (N = 158), 1.19 [95% CI, 1.07-1.32] (p = 0.002); low SMM/low HG (N = 366), 1.39 [95% CI, 1.27-1.53] (p < 0.001). CONCLUSIONS Muscle weakness was found to be a more powerful predictor of survival than BIA-estimated SMM and should be considered as an additional key feature of sarcopenia in patients with cancer.
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Dietary palmitate and oleate differently modulate insulin sensitivity in human skeletal muscle.
Sarabhai, T, Koliaki, C, Mastrototaro, L, Kahl, S, Pesta, D, Apostolopoulou, M, Wolkersdorfer, M, Bönner, AC, Bobrov, P, Markgraf, DF, et al
Diabetologia. 2022;(2):301-314
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Abstract
AIMS/HYPOTHESIS Energy-dense nutrition generally induces insulin resistance, but dietary composition may differently affect glucose metabolism. This study investigated initial effects of monounsaturated vs saturated lipid meals on basal and insulin-stimulated myocellular glucose metabolism and insulin signalling. METHODS In a randomised crossover study, 16 lean metabolically healthy volunteers received single meals containing safflower oil (SAF), palm oil (PAL) or vehicle (VCL). Whole-body glucose metabolism was assessed from glucose disposal (Rd) before and during hyperinsulinaemic-euglycaemic clamps with D-[6,6-2H2]glucose. In serial skeletal muscle biopsies, subcellular lipid metabolites and insulin signalling were measured before and after meals. RESULTS SAF and PAL raised plasma oleate, but only PAL significantly increased plasma palmitate concentrations. SAF and PAL increased myocellular diacylglycerol and activated protein kinase C (PKC) isoform θ (p < 0.05) but only PAL activated PKCɛ. Moreover, PAL led to increased myocellular ceramides along with stimulated PKCζ translocation (p < 0.05 vs SAF). During clamp, SAF and PAL both decreased insulin-stimulated Rd (p < 0.05 vs VCL), but non-oxidative glucose disposal was lower after PAL compared with SAF (p < 0.05). Muscle serine1101-phosphorylation of IRS-1 was increased upon SAF and PAL consumption (p < 0.05), whereas PAL decreased serine473-phosphorylation of Akt more than SAF (p < 0.05). CONCLUSIONS/INTERPRETATION Lipid-induced myocellular insulin resistance is likely more pronounced with palmitate than with oleate and is associated with PKC isoforms activation and inhibitory insulin signalling. TRIAL REGISTRATION ClinicalTrials.gov .NCT01736202. FUNDING German Federal Ministry of Health, Ministry of Culture and Science of the State North Rhine-Westphalia, German Federal Ministry of Education and Research, European Regional Development Fund, German Research Foundation, German Center for Diabetes Research.
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Low-dose fentanyl does not alter muscle sympathetic nerve activity, blood pressure, or tolerance during progressive central hypovolemia.
Huang, M, Watso, JC, Belval, LN, Cimino, FA, Fischer, M, Jarrard, CP, Hendrix, JM, Laborde, CH, Crandall, CG
American journal of physiology. Regulatory, integrative and comparative physiology. 2022;(1):R55-R63
Abstract
Hemorrhage is a leading cause of battlefield and civilian trauma deaths. Several pain medications, including fentanyl, are recommended for use in the prehospital (i.e., field setting) for a hemorrhaging solider. However, it is unknown whether fentanyl impairs arterial blood pressure (BP) regulation, which would compromise hemorrhagic tolerance. Thus, the purpose of this study was to test the hypothesis that an analgesic dose of fentanyl impairs hemorrhagic tolerance in conscious humans. Twenty-eight volunteers (13 females) participated in this double-blinded, randomized, placebo-controlled trial. We conducted a presyncopal limited progressive lower body negative pressure test (LBNP; a validated model to simulate hemorrhage) following intravenous administration of fentanyl (75 µg) or placebo (saline). We quantified tolerance as a cumulative stress index (mmHg·min), which was compared between trials using a paired, two-tailed t test. We also compared muscle sympathetic nerve activity (MSNA; microneurography) and beat-to-beat BP (photoplethysmography) during the LBNP test using a mixed effects model [time (LBNP stage) × trial]. LBNP tolerance was not different between trials (fentanyl: 647 ± 386 vs. placebo: 676 ± 295 mmHg·min, P = 0.61, Cohen's d = 0.08). Increases in MSNA burst frequency (time: P < 0.01, trial: P = 0.29, interaction: P = 0.94) and reductions in mean BP (time: P < 0.01, trial: P = 0.50, interaction: P = 0.16) during LBNP were not different between trials. These data, the first to be obtained in conscious humans, demonstrate that administration of an analgesic dose of fentanyl does not alter MSNA or BP during profound central hypovolemia, nor does it impair tolerance to this simulated hemorrhagic insult.
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A new paradigm in sarcopenia: Cognitive impairment caused by imbalanced myokine secretion and vascular dysfunction.
Jo, D, Yoon, G, Kim, OY, Song, J
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2022;:112636
Abstract
Sarcopenia characterized by reduced skeletal muscle mass and decreased muscle strength is increasing in prevalence globally. The pathophysiology of sarcopenia is related to various factors including hormonal imbalance, increased intracellular oxidative stress, reduction of food intake, advanced age, low body mass index, and low physical activity. Recently, sarcopenia has been reported to be associated with cognitive decline, and the common risk factors between sarcopenia and memory loss were observed in cohort studies. Many researchers suggested that the prevalence of sarcopenia is associated with vascular disorder, such as atherosclerosis and alteration of intracellular mechanisms caused by changes in myokine secretion. We herein review the emerging evidence on the strong link between cognitive impairment and sarcopenia, focusing on myokine secretion and vascular dysfunction, and provide an understanding of the relevant mechanisms and crucial determinants in cognitive decline caused by sarcopenia.
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Fruit supplementation reduces indices of exercise-induced muscle damage: a systematic review and meta-analysis.
Doma, K, Gahreman, D, Connor, J
European journal of sport science. 2021;(4):562-579
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This systematic review and meta-analysis examined the effects of fruit supplements on indices of muscle damage and physical performance measures following muscle-damaging exercise protocols. The PEDro scale and Cochrane's risk of bias tool was used to critically appraise each study, whilst forest plots were generated to report on standardised mean differences (SMD) and p-values. The studies employed a crossover-randomised design, or a randomised controlled placebo design, with measures compared between the supplement (SUPP) and placebo (PLA) conditions at 24 and 48 h following the muscle-damaging exercise protocols. Compared to the PLA condition, the SUPP condition exhibited significantly lower levels of indirect muscle damage markers (p = 0.02; I2 = 44%), inflammatory markers (p = 0.03; I2 = 45%) and oxidative stress (p < 0.001; I2 = 58%), whilst antioxidant capacity was significantly increased (p = 0.04; I2 = 82%) at 24 h post-exercise. The maximal isometric voluntary contraction was significantly greater for the SUPP condition than the PLA at 24 h (p < 0.001; I2 = 81%) and 48 h (p < 0.001; 84%) post-exercise. Only a few studies reported on functional outcome measures (i.e. countermovement jump, cycling, sprint and running maximal oxygen uptake), and the findings appeared conflicting according to qualitative analyses. Fruit supplementation minimised the level of several biomarkers of muscle damage, inflammation and oxidative stress, whilst improved muscular contractility during periods of EIMD. These findings demonstrate that fruit supplements could be used as recovery strategies from strenuous exercise sessions.
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The many actions of insulin in skeletal muscle, the paramount tissue determining glycemia.
Sylow, L, Tokarz, VL, Richter, EA, Klip, A
Cell metabolism. 2021;(4):758-780
Abstract
As the principal tissue for insulin-stimulated glucose disposal, skeletal muscle is a primary driver of whole-body glycemic control. Skeletal muscle also uniquely responds to muscle contraction or exercise with increased sensitivity to subsequent insulin stimulation. Insulin's dominating control of glucose metabolism is orchestrated by complex and highly regulated signaling cascades that elicit diverse and unique effects on skeletal muscle. We discuss the discoveries that have led to our current understanding of how insulin promotes glucose uptake in muscle. We also touch upon insulin access to muscle, and insulin signaling toward glycogen, lipid, and protein metabolism. We draw from human and rodent studies in vivo, isolated muscle preparations, and muscle cell cultures to home in on the molecular, biophysical, and structural elements mediating these responses. Finally, we offer some perspective on molecular defects that potentially underlie the failure of muscle to take up glucose efficiently during obesity and type 2 diabetes.
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Relationship between Energy Intake and Changes in Thigh Echo Intensity during the Acute Phase of Stroke in Older Patients with Hemiplegia.
Kokura, Y, Kato, M, Kimoto, K, Okada, Y, Habu, D
Medical principles and practice : international journal of the Kuwait University, Health Science Centre. 2021;(5):493-500
Abstract
OBJECTIVE The aim of this study was to investigate the relationship between energy intake and changes in thigh echo intensity (TEI) during the acute phase of stroke in older patients with hemiplegia. SUBJECTS AND METHODS Older hemiplegic inpatients with stroke were enrolled in this post hoc analysis of a prospective observational study. Patients were divided into 2 groups according to energy intake during the 7 days after admission as follows: energy sufficient (ES) and energy insufficient (EIS) groups. The outcome was the rate of changes in TEI of the paralyzed and nonparalyzed sides between admission and after 4 weeks. A decrease in skeletal muscle quality is defined as an increase in intramuscular adipose tissues, which shows as an increase in echo intensity. RESULTS The study included 44 males and 39 females (median age 81 years). The rate of change of TEI in each group was as follows: +4.5% in the ES/paralyzed group, +6.7% in the EIS/paralyzed group, -0.9% in the ES/nonparalyzed group, and +4.4% in the EIS/nonparalyzed group. The univariate analyses showed no significant difference in the rate of change in TEI between ES and EIS groups in both paralyzed side (p = 0.190) and nonparalyzed side (p = 0.183). Multivariate analysis showed that higher energy intake was associated with a smaller increase in the rate of change in TEI on the nonparalyzed side (B = -4.115, 95% confidence interval, -7.127 to -1.103). CONCLUSIONS Higher energy intake during 7 days after admission was associated with a smaller increase in the rate of change in TEI on the nonparalyzed side upon admission and after 4 weeks.
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Lack of Evidence for Non-Local Muscle Fatigue and Performance Enhancement in Young Adults.
Power, GMJ, Colwell, E, Saeterbakken, AH, Drinkwater, EJ, Behm, DG
Journal of sports science & medicine. 2021;(2):339-348
Abstract
Post-activation performance enhancement (PAPE) is an improvement to voluntary muscle performance following a conditioning activity. There is evidence of fatigue resistance deficits in non-exercised muscles following unilateral fatiguing exercise of a contralateral muscle. The purpose of this study was to determine if a unilateral conditioning exercise protocol could induce PAPE in a contralateral, non-exercised muscle in young healthy adults. Thirty-two recreationally trained (n = 16) and athletically trained (n = 16) participants (16 males; age: 22.9 ± 2.03 years; height: 1.81 ± 0.06 m; weight: 82.8 ± 9.43 kg, and 16 females; age: 23.1 ± 2.80 years; height: 1.67 ± 0.07 m; weight: 66.4 ± 11.09 kg) were randomly allocated into two groups (dominant or non-dominant limb intervention). The experimental intervention, involved a conditioning exercise (4-repetitions of 5-seconds knee extension maximal voluntary isometric contractions: MVIC) with either the dominant (DOM) (n = 16) or non-dominant (ND) (n = 16) knee extensors with testing of the same (exercised) or contralateral (non-exercised) leg as well as a control (no conditioning exercise: n = 32) condition. Testing was performed before, 1-minute and 10-minutes after a high intensity, low volume, conditioning protocol (2 sets of 2x5-s MVIC). Pre- and post-testing included MVIC force and F100 (force developed in the first 100 ms: a proxy measure of rate of force development) and unilateral drop jump (DJ) height and contact time. There were no significant MVIC peak force or EMG nor DJ height or contact time interactions (intervention x limb dominance x time). The pre-test (0.50 ± 0.13) dominant leg MVIC F100 forces exceeded (p = 0.02) both post-test and post-10 min by a small magnitude 8.7% (d = 0.31). There was also a significant (p = 0.02) time x intervention leg x testing leg intervention, although it was observed that the control condition was as likely to demonstrate small to large magnitude changes as were the dominant and non-dominant legs. Following the conditioning activity, there was no significant evidence for non-local improvements (PAPE), or performance decreases.
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Rationale and Design for a Higher (Dairy) Protein Weight Loss Intervention That Promotes Muscle Quality and Bone Health in Older Adults with Obesity: A Randomized, Controlled Pilot Study.
Miller, MG, Porter Starr, KN, Rincker, J, Orenduff, MC, McDonald, SR, Pieper, CF, Fruik, AR, Lyles, KW, Bales, CW
Journal of nutrition in gerontology and geriatrics. 2021;(2-3):150-170
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In contrast to recommendations for young and middle-aged adults, intentional weight loss among older adults remains controversial and is inconsistently advised. Recent research suggests that a higher protein diet can mitigate loss of lean mass during periods of intentional weight loss among older adults with obesity; however, the effects of intentional weight loss on skeletal muscle and bone are not fully understood. The Dairy in the Diet Yields New Approaches for Muscle Optimization (DDYNAMO) trial is a 6-month, randomized, controlled pilot study assessing the effects of combining regular, generous intakes of high quality protein (30 g/meal; primarily from dairy) with caloric restriction (-500kcal/d) and low-intensity resistance exercise (30 min/3 times per week) on muscle quality, muscle composition, bone mineral density in men and women aged ≥60 years with obesity and mild to moderate functional impairment (Short Physical Performance Battery [SPPB] score ≥4 to ≤10). Participants will be re-assessed at 18 months to evaluate weight maintenance, bone mineral density, physical function, and other secondary measures. ClinicalTrials.gov Identifier: NCT02437643.
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Acute Whole-Body Vibration Exercise Promotes Favorable Handgrip Neuromuscular Modifications in Rheumatoid Arthritis: A Cross-Over Randomized Clinical.
Coelho-Oliveira, AC, Lacerda, ACR, de Souza, ALC, Santos, LMM, da Fonseca, SF, Dos Santos, JM, Ribeiro, VGC, Leite, HR, Figueiredo, PHS, Fernandes, JSC, et al
BioMed research international. 2021;:9774980
Abstract
OBJECTIVE Rheumatoid arthritis (RA) causes progressive changes in the musculoskeletal system compromising neuromuscular control especially in the hands. Whole-body vibration (WBV) could be an alternative for the rehabilitation in this population. This study investigated the immediate effect of WBV while in the modified push-up position on neural ratio (NR) in a single session during handgrip strength (HS) in women with stable RA. METHODS Twenty-one women with RA (diagnosis of disease: ±8 years, erythrocyte sedimentation rate: ±24.8, age: 54± 11 years, BMI: 28 ± 4 kg·m-2) received three experimental interventions for five minutes in a randomized and balanced cross-over order: (1) control-seated with hands at rest, (2) sham-push-up position with hands on the vibration platform that remained disconnected, and (3) vibration-push-up position with hands on the vibration platform turned on (45 Hz, 2 mm, 159.73 m·s-2). At the baseline and immediately after the three experimental interventions, the HS, the electromyographic records (EMGrms), and range of motion (ROM) of the dominant hand were measured. The NR, i.e., the ratio between EMGrms of the flexor digitorum superficialis (FDS) muscle and HS, was also determined. The lower NR represented the greater neuromuscular efficiency (NE). RESULTS The NR was similar at baseline in the three experimental interventions. Despite the nonsignificance of within-interventions (p = 0.0611) and interaction effect (p = 0.1907), WBV exercise reduced the NR compared with the sham and control (p = 0.0003, F = 8.86, η 2 = 0.85, power = 1.00). CONCLUSION Acute WBV exercise under the hands promotes neuromuscular modifications during the handgrip of women with stable RA. Thus, acute WBV exercise may be used as a preparatory exercise for the rehabilitation of the hands in this population. This trial is registered with trial registration 2.544.850 (ReBEC-RBR-2n932c).