Impact of obstructive sleep apnea treatment in patients with metabolic syndrome: a randomized trial

INTRODUÇÃO: A apneia obstrutiva do sono (AOS) está associada à síndrome metabólica (SM). No entanto, não está claro se o tratamento da AOS com o aparelho de pressão positiva contínua nas vias áreas superiores (CPAP) pode reverter a SM independente de outros tratamentos. Portanto, o objetivo do presente estudo foi avaliar o impacto do tratamento da AOS com o CPAP por 6 meses na reversão da SM. MÉTODOS: Neste estudo randomizado controlado por placebo, recrutamos pacientes com diagnóstico recente de SM e AOS moderada a grave (índice de apneia e hipopneia [IAH] 15 eventos/h) para serem submetidos a 6 meses de tratamento com CPAP ou dilatador nasal (grupo placebo). Todos os pacientes eram não fumantes, não usavam medicamentos e não praticavam exercício físico. Antes e após cada intervenção, foram realizadas medidas antropométricas, medida padronizada da pressão arterial, análise de biomarcadores metabólicos, inflamatórios e de estresse, composição corporal (bioimpedância), gordura abdominal (tomografia computadorizada), função endotelial, bem como avaliação do nível de atividade física (Questionário Internacional de Atividade Física) e ingestão alimentar (Questionário de Frequência Alimentar). O desfecho primário foi a taxa de reversão da SM. O impacto do tratamento com CPAP em cada critério da SM, bem como nos biomarcadores estudados, composição corporal, gordura abdominal, função endotelial, atividade física e ingestão alimentar constituíram os desfechos secundários. RESULTADOS: Entre março de 2015 e abril de 2019, 103 pacientes foram recrutados e randomizados (n=50 para grupo placebo e n=53 para grupo CPAP). Seguindo o princípio de intenção de tratar modificado, 100 pacientes (79% homens; idade: 48±9 anos; índice de massa corporal [IMC]: 33±4 kg/m²; IAH: 58±29 eventos/h; Escala de Sonolência de Epworth: 13±5) completaram o estudo (n=50 em cada grupo). A adesão média ao CPAP foi de 5,5±1,5 h/noite. Como esperado, o CPAP promoveu melhoras significativas na gravidade da AOS, nos parâmetros hipoxêmicos e na sonolência diurna, sendo este último também atenuado no grupo placebo. Após 6 meses de tratamento, a maioria dos pacientes randomizados para o grupo CPAP mantiveram o diagnóstico de SM, porém a taxa de reversibilidade da SM foi maior do que a observada no grupo placebo (18% vs. 4%; OR: 5,27; IC 95% 1,27-35,86; P=0,04). A diferença média dos critérios da SM foi de -0,42±0,95 no grupo CPAP e 0,02±0,80 no grupo placebo (P=0,01). Acerca das análises secundárias, não foram observadas alterações significativas entre os grupos quanto aos critérios individuais da SM, peso, IMC, biomarcadores metabólicos e inflamatórios, composição corporal e doença hepática gordurosa não alcoólica. Todavia, o CPAP promoveu uma redução modesta da gordura abdominal visceral e uma melhora na função endotelial (todas as análises foram ajustadas para os valores basais). CONCLUSÕES: Em pacientes com SM e AOS, 6 meses de tratamento com CPAP foi capaz de promover um aumento de 5 vezes na chance de reversão da SM. Contudo, a falta de efeitos clinicamente significativos sobre o peso corporal e biomarcadores de adiposidade sustenta o modesto papel da AOS na modulação da SM. Esses resultados ressaltam a necessidade de terapia combinada com CPAP, com o objetivo de maximizar a recuperação da SM paralelamente à melhoria na gravidade da AOS e na sonolência diurnaBACKGROUND: Obstructive sleep apnea (OSA) is associated with metabolic syndrome (MS), but it is unclear whether OSA treatment with continuous positive airway pressure (CPAP) can revert MS independent of other treatments. Thus, the aim of this study was to evaluate the impact of 6 months of OSA treatment with CPAP on MS reversibility. METHODS: This randomized placebo-controlled trial enrolled patients with a recent diagnosis of MS, and moderate/severe OSA (apnea-hypopnea index [AHI] 15 events/h) to undergo 6 months of therapeutic CPAP or nasal dilator strips (placebo group). All patients were non-smokers, used no medications, and no physical exercise. Before and after each intervention, we measured anthropometric variables, blood pressure, metabolic, inflammatory, and stress biomarkers, body composition (bioimpedance), abdominal fat (computed tomography), endothelial function, as well as physical activity level (International Physical Activity Questionnaire), and food intake (Food Frequency Questionnaire). The primary endpoint was the rate of MS reversibility. Secondary endpoints included the impact of CPAP on each MS criterion, biomarkers, body composition, abdominal fat, endothelial function, physical activity, and food intake. RESULTS: Between March 2015 and April 2019, 103 patients were recruited and randomly assigned (n=50 to placebo and n=53 to CPAP). Following a modified intention-to-treat-principle analysis, 100 patients (79% men; age: 48±9 years; body mass index [BMI]: 33±4 kg/m2; AHI: 58±29 events/h; Epworth Sleepiness Scale: 13±5) completed the study (n=50 per group). The mean CPAP adherence was 5.5±1.5 h/night. As expected, CPAP promoted significant improvements in OSA severity, hypoxemic parameters, and daytime somnolence, while only the latter was improved in the placebo group. After 6-months treatment, most patients with OSA randomized to CPAP kept the MS diagnosis but the rate of MS reversibility was higher than observed in the placebo group (18% vs. 4%; OR: 5.27; 95% CI 1.27 to 35.86; P=0.04). The mean difference of MS criteria was -0.42±0.95 in the CPAP group and 0.02±0.80 in the placebo (P=0.01). In the secondary analysis, no significant changes between groups were observed on individual criteria of MS, weight, BMI, metabolic and inflammatory biomarkers, body composition, and non-alcoholic fatty liver disease. However, CPAP promoted a very modest reduction in visceral fat and an improvement in endothelial function (all analyses were adjusted for baseline values). CONCLUSIONS: In patients with MS and OSA, 6 months of CPAP treatment was able to promote a 5-fold increase chance to reverse MS. However, the lack of clinically significant effects on weight and adiposity biomarkers supports the modest role of OSA in modulating MS. These results underscore the need for combined therapy with CPAP, aiming to maximize MS recovery in parallel with improvements in OSA severity and daytime sleepines

A condição de altitude simulada piora o estado de humor e aumenta a pressão arterial sistólica de jovens saudáveis

A literatura aponta que o estresse do ambiente aliado ao estresse do exercício físico produz alterações psicológicas e fisiológicas. Portanto, o objetivo do presente estudo foi investigar a associação entre o efeito agudo do exercício físico moderado realizado em condição de atitude simulada sobre o estado de humor, saturação da oxihemoglobina e pressão arterial de jovens saudáveis. Dez voluntários realizaram 45 min. de exercício físico e passaram por duas condições: Condição Normóxia (CN) e Condição Hipóxia (CH). Em ambas as condições eles responderam a dois instrumentos que avaliam as respostas de humor, a Escala de Humor de Brunel (BRUMS) e a Escala Subjetiva de Experiência em Exercício (SEES), bem como a avaliação da saturação de oxihemoglobina e da pressão arterial. Esses procedimentos foram realizados antes, imediatamente após, 30 min. e 60 min. após o término do protocolo. Após a prática do exercício físico na Condição Hipóxia, os voluntários apresentaram maiores escores de Fadiga, Confusão Mental, DTH, Raiva, Distresse Psicológico e menores valores de Vigor e Bem-Estar Positivo acompanhados de uma diminuição da saturação da oxihemoglobina. O exercício físico moderado realizado em altitude simulada de 4500m promove mudanças no estado de humor e aumento da pressão arterial sistólica de jovens saudáveis

Resistance training minimizes catabolic effect induced by sleep deprivation in rats

Sleep deprivation (SD) can induce muscle atrophy. We aimed to investigate the changes underpinning SD-induced muscle atrophy and the impact of this condition on rats that were previously submitted to resistance training (RT). Adult male Wistar EPM-1 rats were randomly allocated into one of five groups: control (CTRL), SHAM, SD (for 96 h) and groups that were submitted to resistance training (RT), and the combination of RT+SD. The major outcomes of this study were observed in muscle fiber cross-sectional area (CSA), anabolic and catabolic hormone profiles, and the abundance of select proteins involved in the muscle protein synthetic and protein degradation pathways. SD resulted in muscle atrophy; when combined with RT, the reduction in muscle fiber CSA was attenuated. The level of IGF-1 and testosterone was reduced in SD animals, and the RT+SD had higher levels of these variables than SD group. Corticosterone was increased in the SD group compared with the CTRL, and this increase was minimized in the RT+SD group. The increases in corticosterone concentrations between groups paralleled the abundance of the autophagic proteins LC3, p62/SQSTM1, and ubiquitinated proteins, suggesting that corticosterone may trigger these changes. SD induced weight loss, but the previously trained group had minimized this loss. We report that SD induced muscle atrophy, probably due to the increased corticosterone and catabolic signal. High intensity RT performed before SD was beneficial in containing muscle loss rate induced by SD. It also minimized the catabolic signal and increased the synthetic activity, thereby minimizing the body's weight loss.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

Exercise performed at hypoxia influences mood state and anxiety symptoms

During hypoxia conditions, psychological states can be worsened. However, little information is available regarding the effect of physical exercise performed in hypoxia conditions on mood state and anxiety symptoms. The aim of the present study was to elucidate the acute effect of moderate physical exercise performed at hypoxia on mood states and anxiety symptoms in healthy young subjects. Ten volunteers were subjected to the following conditions: a normoxic condition (NC) and a hypoxic condition (HC). They performed 45 min of physical exercise. Their anxiety symptoms and mood states were evaluated at the initial time point as well as immediately following and 30 and 60 min after the exercise session. Our results showed a significant increase in post-exercise anxiety symptoms and a significant decrease in mood scores immediately after and 30 min after exercise performed in the HC. Moderate physical activity performed at hypoxia condition increased post-exercise anxiety and worsened mood state

Negative Energy Balance Induced by Paradoxical Sleep Deprivation Causes Multicompartmental Changes in Adipose Tissue and Skeletal Muscle

Objective. Describe multicompartmental changes in the fat and various muscle fiber types, as well as the hormonal profile and metabolic rate induced by SD in rats. Methods. Twenty adult male Wistar rats were equally distributed into two groups: experimental group (EG) and control group (CG). The EG was submitted to SD for 96 h. Blood levels of corticosterone (CORT), total testosterone (TESTO), insulin like growth factor-1 (IGF-1), and thyroid hormones (T3 and T4) were used to assess the catabolic environment. Muscle trophism was measured using a cross-sectional area of various muscles (glycolytic, mixed, and oxidative), and lipolysis was inferred by the weight of fat depots from various locations, such as subcutaneous, retroperitoneal, and epididymal. The metabolic rate was measured using oxygen consumption (V˙O2) measurement. Results. SD increased CORT levels and decreased TESTO, IGF-1, and T4. All fat depots were reduced in weight after SD. Glycolytic and mixed muscles showed atrophy, whereas atrophy was not observed in oxidative muscle. Conclusion. Our data suggest that glycolytic muscle fibers are more sensitive to atrophy than oxidative fibers during SD and that fat depots are reduced regardless of their location

Paradoxical Sleep Deprivation Causes Cardiac Dysfunction and the Impairment Is Attenuated by Resistance Training

<div><p>Background</p><p>Paradoxical sleep deprivation activates the sympathetic nervous system and the hypothalamus-pituitary-adrenal axis, subsequently interfering with the cardiovascular system. The beneficial effects of resistance training are related to hemodynamic, metabolic and hormonal homeostasis. We hypothesized that resistance training can prevent the cardiac remodeling and dysfunction caused by paradoxical sleep deprivation.</p><p>Methods</p><p>Male Wistar rats were distributed into four groups: control (C), resistance training (RT), paradoxical sleep deprivation for 96 hours (PSD96) and both resistance training and sleep deprivation (RT/PSD96). Doppler echocardiograms, hemodynamics measurements, cardiac histomorphometry, hormonal profile and molecular analysis were evaluated.</p><p>Results</p><p>Compared to the C group, PSD96 group had a higher left ventricular systolic pressure, heart rate and left atrium index. In contrast, the left ventricle systolic area and the left ventricle cavity diameter were reduced in the PSD96 group. Hypertrophy and fibrosis were also observed. Along with these alterations, reduced levels of serum testosterone and insulin-like growth factor-1 (IGF-1), as well as increased corticosterone and angiotensin II, were observed in the PSD96 group. Prophylactic resistance training attenuated most of these changes, except angiotensin II, fibrosis, heart rate and concentric remodeling of left ventricle, confirmed by the increased of NFATc3 and GATA-4, proteins involved in the pathologic cardiac hypertrophy pathway.</p><p>Conclusions</p><p>Resistance training effectively attenuates cardiac dysfunction and hormonal imbalance induced by paradoxical sleep deprivation.</p></div

Ventricular remodeling, fibrosis and expression of proteins involved in the pathologic cardiac hypertrophy pathway.

<p>Representative images (40x magnification) of HE-stained cross sections (A) of the LV of rats without manipulation (C; n = 6) or submitted to RT (RT; n = 6) or PSD (PSD96; n = 6) or RT followed by PSD (RT/PSD96; n = 6). (B) The images (40x magnification) are the LV tissue sections stained with picrosirius red. Red color stretches are collagen depositions. (C) Images (1.25x magnification) of HE-stained the LV cavity diameter of the heart. (D) Myocyte CSA calculated from the HE-stained sections as shown in A. (E) Histogram showing collagen volume fraction in the LV tissues. (F) Results of the analysis of the LV cavity diameter as shown in C. (G) Quantification of NFATc3 expression. (H) Representative blots of NFATc3, GATA-4 and GAPDH. (I) Quantification of GATA-4 expression. For analysis, we utilized one way ANOVA followed by Duncan’s post hoc. The data are shown as the mean ± standard deviation, significance accepted: p ≤ 0.05. *—Different from the C group; ^†—Different from the RT group; ^‡—Different from the PSD96 group.</p

Biochemical variables.

<p>Biochemical variables.</p