The effects of resistance exercise on obstructive sleep apnea severity and body water content in older adults: A randomized controlled trial.

OBJECTIVES/BACKGROUND: The prevalence of obstructive sleep apnea (OSA) in people over 70 years can reach up to 95%. Aerobic or combined exercise programs have been shown to impact positively on OSA severity. Resistance training changes leg fluid retention. We hypothesized that through this mechanism it may have an impact on the OSA severity in older adults. PATIENTS/METHODS: We evaluated changes in the respiratory event index (REI) of older adults with moderate-severe obstructive sleep apnea in a randomized, masked, controlled, parallel group trial. Participants between the age of 65 and 80 years with REI between 20 and 50 events/hour were assigned randomly to 12 weeks of resistance training or healthy life-style recommendations. Change in REI was the primary outcome. Muscle thickness, maximum strength, and physical function were secondary outcomes and body mass index (BMI) and body water content were assessed as mediators. RESULTS: Twenty-three subjects were included, 57% men, aged 71 ± 5 years, randomized to training (n = 12) and control intervention (n = 11). The baseline REI in the training and control groups were 30 ± 7/h and 29 ± 9/h; at follow-up, the delta REI were -3.6/hour (95% confidence interval -0.7 to -5.4) and 6.7/hour (5.2-8.6), respectively, with significant time × group interaction that remained significant after adjusting the generalized estimating equations model for delta BMI and delta body water content. CONCLUSIONS: Twelve weeks of resistance training in older adults significantly changed the respiratory event index and was well tolerated. Changes in body water content were slight but cannot be dismissed as contributing to REI reduction.

Exploring the STOP-BANG questionnaire for obstructive sleep apnea screening in seniors.

STUDY OBJECTIVES: The accuracy of obstructive sleep apnea (OSA) screening instruments in seniors may change as the predictive role of sex, age, and body mass index (BMI) changes with aging. We investigated the diagnostic performance of the STOP-BANG questionnaire in older individuals with aging-adapted scores and thresholds. METHODS: Independent community-dwelling adults aged 65 years or older were screened for OSA. The STOP-BANG questionnaire was tested with different configurations and compared to the apnea-hypopnea index (AHI) obtained from home sleep apnea testing (HSAT). Epworth Sleepiness Scale (ESS) and Athens Insomnia Scale (AIS) were tested as possible supplementary screening criteria. RESULTS: We recruited 458 individuals with a mean age of 71 ± 5 years, 41% men, BMI of 28.5 ± 4.6 kg/m². Mild, moderate, and severe OSA were present in, respectively, 34%, 30%, and 19% of the sample. The STOP questions had an area under the curve (AUC) of the receiver operating characteristic curve significantly lower than the STOP-BANG and the STOP+BMI > 28 kg/m² (STOP-B28). Both STOP-BANG and STOP-B28 had high sensitivity and low specificity in all OSA levels with similar AUC to predict AHI ≥ 5 events/h, 0.64. ESS and AIS were nonsignificant as adjunctive instruments. CONCLUSIONS: Novel modifications of a standard instrument created the STOP-B28, a simpler-to-obtain and similarly performing variation of the STOP-BANG using fewer inputs, and useful to exclude OSA. Screening seniors via questionnaires to detect OSA is problematic. Considering the 83% OSA prevalence in this age group, it may be a sensible option to indicate objective tests, oximetry, HSAT, or even polysomnography, as a first step in OSA investigation.

Disrupted day-night pattern of cardiovascular death in obstructive sleep apnea.

BACKGROUND: Obstructive sleep apnea (OSA) patients who suffer sudden cardiac death die predominantly during the night. We aimed to investigate whether all cardiovascular-related deaths display the same night-time peak as sudden cardiac death. METHODS: Data from a large cohort of adults who underwent full-night polysomnography between 1985 and 2015 in a university-affiliated sleep clinic were analyzed. Time and cause of death of these patients and of persons from the general population were identified in death certificates from the State Health Secretariat. The day-night pattern of cardiovascular death was compared among groups of non-OSA, OSA (apnea-hypopnea index, AHI ≥5), CPAP users, and persons from the general population. RESULTS: Among 619 certificates, 160 cardiovascular-related deaths were identified. The time of death of the 142 persons with OSA was uniformly distributed over 24 h, with neither an identifiable peak nor a circadian pattern (Rayleigh test; P = 0.8); the same flat distribution was seen in those with purported CPAP use (n = 49). Non-OSA individuals presented a morning peak and a night nadir of deaths, clearer when analyzed in eight-hour intervals. The same pattern was observed in 92 836 certificates from the State general population, with cardiovascular deaths showing the expected morning peak, night nadir, and a significant circadian pattern (Rayleigh test; P < 0.001). CONCLUSIONS: In OSA patients, the distribution of cardiovascular-related deaths throughout the 24-h period is virtually flat, in contrast with the described nighttime peak of sudden cardiac death. OSA-related phenomena during nighttime might be blunting the mechanisms, arrhythmic or not, behind the morning peak of cardiovascular-related deaths.

The effect of caffeine supplementation on exercise performance evaluated by a novel animal model

Introduction: Caffeinated drinks are used for improve performance. Animal models represent investigational strategy that circumvents most of the drawbacks of research in humans, including motivational factors and the placebo effect. No animal model that could test whether different forms of administering caffeine affect exercise propensity was found in the literature. Methods: An animal model of grouped voluntary exercise was tested. Two-month-old male C57/bl mice were housed in a cage fitted with one running wheel and a monitoring system. Six animals per cage were introduced individually. To assess the sensitivity of the model, the effect of different caffeinated drinks was observed in mice exercising ad libitum. During 2 days, the mice received: 1) pure anhydrous caffeine 0.125 mg/mL (PC), 2) cola drink (CC), and 3) caffeine-taurine-glucuronolactone drink (CTG), intercalating wash-out periods of 2 days, receiving pure water. Results: The distance run during the periods of water ingestion was significantly lower than during the periods of stimulant drinks ingestion: PC (5.6 ± 1.3 km; p = 0.02), of CC ingestion (7.6 ± 0.6 km; p = 0.001), and of CTG ingestion (8.3 ± 1.6 km; p = 0.009). The performances when ingesting the three caffeinated drinks do not follow a dose-response curve. Conclusions: The model described here was able to measure the effect of caffeine intake on voluntary exercise of mice. The sensitivity of the model to the effect of caffeine needs to be further validated. The action of each component of the drinks on exercise performance needs to be clarified in future research. The present model is adequate for such investigation (AU)

Melatonin prevents hyperglycemia in a model of sleep apnea.

OBJECTIVE: Obstructive sleep apnea is a common disorder associated with aging and obesity. Apneas cause repeated arousals, intermittent hypoxia, and oxidative stress. Changes in glucolipidic profile occur in apnea patients, independently of obesity. Animal models of sleep apnea induce hyperglycemia. This study aims to evaluate the effect of the antioxidants melatonin and N-acetylcysteine on glucose, triglyceride, and cholesterol levels in animals exposed to intermittent hypoxia. MATERIALS AND METHODS: Two groups of Balb/c mice were exposed to intermittent hypoxia (n = 36) or sham intermittent hypoxia (n = 36) for 35 days. The intermittent hypoxia group underwent a total of 480 cycles of 30 seconds reducing the inspired oxygen fraction from 21% to 7 ± 1% followed by 30 seconds of normoxia, during 8 hours daily. Melatonin or N-acetylcysteine were injected intraperitonially daily from day 21 on. RESULTS: At day 35, glucose levels were significantly higher in the intermittent hypoxia group than in the control group. The intermittent hypoxia groups receiving N-acetylcysteine and vehicle showed higher glucose levels than the group receiving melatonin. The lipid profile was not affected by intermittent hypoxia or antioxidant administration. CONCLUSIONS: The present results suggest that melatonin prevents the well-recognized increase in glucose levels that usually follows exposure to intermittent hypoxia. Further exploration of the role of melatonin in sleep apnea is warranted.

Uncoupling protein-2 mRNA expression in mice subjected to intermittent hypoxia.

OBJECTIVE: To investigate the effect of intermittent hypoxia-a model of obstructive sleep apnea (OSA)-on pancreatic expression of uncoupling protein-2 (UCP2), as well as on glycemic and lipid profiles, in C57BL mice. METHODS: For 8 h/day over a 35-day period, male C57BL mice were exposed to intermittent hypoxia (hypoxia group) or to a sham procedure (normoxia group). The intermittent hypoxia condition involved exposing mice to an atmosphere of 92% N and 8% CO2 for 30 s, progressively reducing the fraction of inspired oxygen to 8 ± 1%, after which they were exposed to room air for 30 s and the cycle was repeated (480 cycles over the 8-h experimental period). Pancreases were dissected to isolate the islets. Real-time PCR was performed with TaqMan assays. RESULTS: Expression of UCP2 mRNA in pancreatic islets was 20% higher in the normoxia group than in the hypoxia group (p = 0.11). Fasting serum insulin was higher in the hypoxia group than in the normoxia group (p = 0.01). The homeostasis model assessment of insulin resistance indicated that, in comparison with the control mice, the mice exposed to intermittent hypoxia showed 15% lower insulin resistance (p = 0.09) and 21% higher pancreatic ß-cell function (p = 0.01). Immunohistochemical staining of the islets showed no significant differences between the two groups in terms of the area or intensity of α- and ß-cell staining for insulin and glucagon. CONCLUSIONS: To our knowledge, this is the first report of the effect of intermittent hypoxia on UCP2 expression. Our findings suggest that UCP2 regulates insulin production in OSA. Further study of the role that UCP2 plays in the glycemic control of OSA patients is warranted.

Uncoupling protein-2 mRNA expression in mice subjected to intermittent hypoxia / Expressão do mRNA da uncoupling protein-2 em camundongos submetidos à hipóxia intermitente

Objective: To investigate the effect of intermittent hypoxia-a model of obstructive sleep apnea (OSA)-on pancreatic expression of uncoupling protein-2 (UCP2), as well as on glycemic and lipid profiles, in C57BL mice. Methods: For 8 h/day over a 35-day period, male C57BL mice were exposed to intermittent hypoxia (hypoxia group) or to a sham procedure (normoxia group). The intermittent hypoxia condition involved exposing mice to an atmosphere of 92% N and 8% CO2 for 30 s, progressively reducing the fraction of inspired oxygen to 8 ± 1%, after which they were exposed to room air for 30 s and the cycle was repeated (480 cycles over the 8-h experimental period). Pancreases were dissected to isolate the islets. Real-time PCR was performed with TaqMan assays. Results: Expression of UCP2 mRNA in pancreatic islets was 20% higher in the normoxia group than in the hypoxia group (p = 0.11). Fasting serum insulin was higher in the hypoxia group than in the normoxia group (p = 0.01). The homeostasis model assessment of insulin resistance indicated that, in comparison with the control mice, the mice exposed to intermittent hypoxia showed 15% lower insulin resistance (p = 0.09) and 21% higher pancreatic β-cell function (p = 0.01). Immunohistochemical staining of the islets showed no significant differences between the two groups in terms of the area or intensity of α- and β-cell staining for insulin and glucagon. Conclusions: To our knowledge, this is the first report of the effect of intermittent hypoxia on UCP2 expression. Our findings suggest that UCP2 regulates insulin production in OSA. Further study of the role that UCP2 plays in the glycemic control of OSA patients is warranted. .

Objetivo: Investigar o efeito da hipóxia intermitente com um modelo de apneia obstrutiva do sono (AOS) sobre a expressão de uncoupling protein-2 (UCP2), assim como sobre perfis glicêmicos e lipídicos, em camundongos C57BL. Métodos: Camundongos C57BL machos foram expostos a hipóxia intermitente ou hipóxia simulada (grupo controle) 8 h/dia durante 35 dias. A condição de hipóxia intermitente envolveu a exposição dos camundongos a uma atmosfera de 92% de N e 8% de CO2 por 30 s, com redução progressiva de fração de O2 inspirado até 8 ± 1%, seguida por exposição a ar ambiente por 30 s e repetições do ciclo (480 ciclos no período experimental de 8 h). Os pâncreas foram dissecados para isolar as ilhotas. Foi realizada PCR em tempo real utilizando o método TaqMan. Resultados: A expressão do mRNA da UCP2 nas ilhotas pancreáticas foi 20% maior no grupo controle que no grupo hipóxia (p = 0,11). A insulina sérica de jejum foi maior no grupo hipóxia do que no grupo controle (p = 0,01). O modelo de avaliação da homeostase de resistência à insulina indicou que, em comparação com os camundongos controle, aqueles expostos à hipóxia intermitente apresentaram 15% menor resistência à insulina (p = 0,09) e 21% maior função das células beta (p = 0,01). A coloração das ilhotas pancreáticas por imuno-histoquímica não mostrou diferenças significativas entre os grupos em termos da área ou da intensidade das células alfa e beta, marcadas por insulina e glucagon. Conclusões: Segundo nosso conhecimento, esta é a primeira descrição do efeito da hipóxia intermitente sobre a expressão da UCP2. Nossos achados sugerem que UCP2 regula a produção de insulina na AOS. Futuras investigações sobre o papel da UCP2 no controle glicêmico em pacientes com AOS são justificadas. .

Melatonin prevents hyperglycemia in a model of sleep apnea

Objective Obstructive sleep apnea is a common disorder associated with aging and obesity. Apneas cause repeated arousals, intermittent hypoxia, and oxidative stress. Changes in glucolipidic profile occur in apnea patients, independently of obesity. Animal models of sleep apnea induce hyperglycemia. This study aims to evaluate the effect of the antioxidants melatonin and N-acetylcysteine on glucose, triglyceride, and cholesterol levels in animals exposed to intermittent hypoxia. Materials and methods Two groups of Balb/c mice were exposed to intermittent hypoxia (n = 36) or sham intermittent hypoxia (n = 36) for 35 days. The intermittent hypoxia group underwent a total of 480 cycles of 30 seconds reducing the inspired oxygen fraction from 21% to 7 ± 1% followed by 30 seconds of normoxia, during 8 hours daily. Melatonin or N-acetylcysteine were injected intraperitonially daily from day 21 on. Results At day 35, glucose levels were significantly higher in the intermittent hypoxia group than in the control group. The intermittent hypoxia groups receiving N-acetylcysteine and vehicle showed higher glucose levels than the group receiving melatonin. The lipid profile was not affected by intermittent hypoxia or antioxidant administration. Conclusions The present results suggest that melatonin prevents the well-recognized increase in glucose levels that usually follows exposure to intermittent hypoxia. Further exploration of the role of melatonin in sleep apnea is warranted. Arch Endocrinol Metab. 2015;59(1):66-70 .