Search

Sleep-disordered breathing (SDB) is often accompanied by noncommunicable diseases (NCDs), including gout. However, the association between serum uric acid (sUA) levels and NCDs is complicated in patients with SDB. We aimed to clarify this issue utilizing large-scale epidemiological data. This community-based study included 9850 inhabitants. SDB and its severity were assessed by a 3% oxygen desaturation index (3% ODI) corrected for sleep duration using wrist actigraphy. The associations between sUA and moderate to severe SDB (MS-SDB) and sUA and NCDs in patients with MS-SDB were analyzed. A total of 7895 subjects were eligible. In females, the prevalence of MS-SDB increased according to an elevation in sUA levels even after adjusting for confounders, and sUA ≥ 5 mg/dL was the threshold. These were not found in males. There was a positive interaction between sUA ≥ 5 mg/dL and female sex for MS-SDB. In females with MS-SDB, the prevalence of diabetes mellitus (DM) increased according to an elevation in sUA levels, and those with sUA ≥ 5 mg/dL showed a higher prevalence of DM than their counterparts. There is a clear correlation between sUA levels and the severity of SDB, and elevated sUA poses a risk for DM in females with MS-SDB.

Sleep disordered breathing (SDB), mainly obstructive sleep apnea (OSA), constitutes a major health problem due to the large number of patients. Intermittent hypoxia caused by SDB induces alterations in metabolic function. Nevertheless, metabolites characteristic for SDB are largely unknown. In this study, we performed gas chromatography-mass spectrometry-based targeted metabolome analysis using data from The Nagahama Study (n = 6373). SDB-related metabolites were defined based on their variable importance score in orthogonal partial least squares discriminant analysis and fold changes in normalized peak-intensity levels between moderate-severe SDB patients and participants without SDB. We identified 20 metabolites as SDB-related, and interestingly, these metabolites were frequently included in pathways related to fructose. Multivariate analysis revealed that moderate-severe SDB was a significant factor for increased plasma fructose levels (β = 0.210, P = 0.006, generalized linear model) even after the adjustment of confounding factors. We further investigated changes in plasma fructose levels after continuous positive airway pressure (CPAP) treatment using samples from patients with OSA (n = 60) diagnosed by polysomnography at Kyoto University Hospital, and found that patients with marked hypoxemia exhibited prominent hyperfructosemia and their plasma fructose levels lowered after CPAP treatment. These data suggest that hyperfructosemia is the abnormality characteristic to SDB, which can be reduced by CPAP treatment., (© 2023. Springer Nature Limited.)

Recently an association between blood glucose dysregulation and sleep disruption was suggested. The association between sleep disordered breathing, most of which is due to obstructive sleep apnea (OSA) in the general population, and diabetic severity, as well as the impact of antidiabetic treatment, remains unclear. This study aimed to investigate these associations as well as age and sex differences. This cross-sectional study evaluated 7,680 community participants as the main cohort (population-based cohort). OSA was assessed by the 3% oxygen desaturation index from pulse oximetry, which was corrected for sleep duration obtained by wrist actigraphy. For arguing the limitations for using pulse oximetry, 597 hospitalised patients, who were assessed by the apnea-hypopnea index from attended polysomnography, were also evaluated as the validation cohort (hospital-based cohort). Moderate-to-severe OSA was more prevalent as haemoglobin A1c (HbA1c) levels increased (<5.6%/5.6%-<6.5%/6.5%-<7.5%/≥7.5%, respectively) in both cohorts (p < 0.001), but only in those without antidiabetic treatment. The HbA1c level was an independent factor for moderate-to-severe OSA (population-based cohort, odds ratio [OR] 1.26, 95% confidence interval [CI] 1.10-1.45; hospital-based cohort, OR 1.69, 95% CI 1.22-2.33, per 1% increase). These associations were more prominent in the middle-aged (aged <60 years) than in the elderly (aged ≥60 years) and in women than in men in both cohorts. The prevalence of moderate-to-severe OSA in patients with antidiabetic treatment in the hospital-based cohort was ≥75% regardless of HbA1c levels. In conclusion, an association between the prevalence of OSA and HbA1c level even within or over the normal range was found only in patients without antidiabetic treatment and was more prominent in the middle-aged and in women., (© 2022 European Sleep Research Society.)

Rationale: Although sleep-disordered breathing (SDB) may increase urinary albumin excretion (UAE) by raising nocturnal blood pressure (BP) in addition to diurnal BP, the correlation has not been investigated in a general population. Objectives: To evaluate the relationships among UAE, SDB, and BP during sleep in a large population cohort. Methods: Among 9,850 community residents, UAE was assessed by the urinary albumin-to-creatinine ratio (UACR) in spot urine. Sleep duration and SDB were evaluated by a wearable actigraph and pulse oximeter, respectively. We calculated the actigraphy-modified 3% oxygen desaturation index (Acti-3%ODI) by correcting the time measured by pulse oximetry according to sleep duration obtained by actigraphy. Furthermore, participants were instructed to measure morning and sleep BP at home by a timer-equipped oscillometric device. Results: Measurements of sleep parameters, UAE, and office BP were obtained in 6,568 participants. The multivariate analysis that included confounders showed a significant association of Acti-3%ODI with UACR (β = 0.06, P  < 0.001). Furthermore, a positive interaction between office systolic BP (SBP) and Acti-3%ODI for UACR was found (β = 0.06, P  < 0.001). Among the 6,568 persons enrolled in the analysis, 5,313 completed measurements of BP at home. In this cohort, the association of Acti-3%ODI with UACR remained significant (β = 0.06, P  < 0.001) even after morning and sleep SBP were included in the analysis. Furthermore, a mediation analysis revealed that 28.3% (95% confidence interval, 14.9-41.7%; P  < 0.001) of the association of Acti-3%ODI with UACR was explained by the mediation of morning and sleep SBP metrics. Conclusions: SDB and office SBP were independently and synergistically associated with UAE, which is considered a risk factor for chronic kidney disease and cardiovascular events. SDB may raise UAE not only by increasing BP but also by involving other pathologic pathways.

Study Objectives: Since subjective sleep duration (SSD) is considered to be longer than objective sleep duration (OSD), results of SSD minus OSD (SSD-OSD) might always be thought to be positive. Some recent reports showed different results, but exact results have not been obtained. The difference between SSD and OSD may change according to OSD. We investigated this difference and its association with sleep-disordered breathing (SDB) or nonrestorative sleep., Methods: This cross-sectional study evaluated 6,908 community residents in Nagahama, Japan. SSD was determined by self-administered questionnaire. OSD was measured by wrist actigraphy and sleep diary. SDB was assessed according to the 3% oxygen desaturation index adjusted for OSD., Results: Worthy of notice was that SSD was shorter than OSD for those with SSD longer than 6.98 hours in all participants, 7.36 hours in males, and 6.80 hours in females. However, SSD was longer than OSD (mean ± SD: 6.49 ± 1.07 vs 6.01 ± 0.96; P < .001) overall, as SSD is considered to be longer than OSD. In patients with SDB, the difference between SSD-OSD was greater when OSD was s horter. The difference also depended on SDB severity. The degree of positivity between OSD and SSD was a significant factor in nonrestorative sleep (odds ratio: 2.691; P < .001)., Conclusions: When OSD was slightly less than 7 (6.98) hours, participants reported or perceived SSD > OSD. When OSD was > 6.98 hours, participants reported or perceived SSD < OSD. Patients with SDB reported longer SSD than OSD according to severity of SDB. Evaluating SSD, OSD, and their differences may be useful for managing sleep disturbances, including nonrestorative sleep., Citation: Takahashi N, Matsumoto T, Nakatsuka Y, et al. Differences between subjective and objective sleep duration according to actual sleep duration and sleep-disordered breathing: the Nagahama Study. J Clin Sleep Med . 2022;18(3):851-859., (© 2022 American Academy of Sleep Medicine.)

Study Objectives: Whether the association between sleep-disordered breathing (SDB) and cardiovascular disease is independent of comorbid risk factors for cardiovascular disease is controversial. The objective of this study was to elucidate whether the association between SDB severity and the surrogate markers of cardiovascular disease events differs in relation to the number of comorbidities., Methods: This cross-sectional study included 7,731 participants. Severity of SDB was determined by the oxygen desaturation index adjusted by actigraph-measured objective sleep time. Participants were stratified according to SDB severity and the number of comorbidities (hypertension, diabetes, dyslipidemia, and obesity), and the associations between the maximum value of intima-media thickness of the common carotid artery (CCA-IMT-max), brachial-ankle pulse wave velocity, and cardio-ankle vascular index were evaluated., Results: Among participants with no risk factors, CCA-IMT-max increased according to SDB severity (n = 1022, P < .0001). Even after matching the background, the median CCA-IMT-max value was 14% higher in moderate-severe SDB patients than those without SDB (n = 45 in each group, P = .020). The difference was not significant for brachial-ankle pulse wave velocity and cardio-ankle vascular index. On the other hand, a significant difference in CCA-IMT-max was not found in those with multiple comorbidities. Consistently, multiple regression analysis revealed an independent association between CCA-IMT-max and moderate-severe SDB for all study participants (β: 0.0222, 95% confidence interval: 0.0039-0.0405, P = .017), but the association was not significant for stratified participants with multiple comorbidities., Conclusions: SDB severity is associated with the CCA-IMT-max level, but the independent association becomes weaker for those with multiple comorbidities., Citation: Nakatsuka Y, Murase K, Matsumoto T, et al. Markers of cardiovascular disease risk in sleep-disordered breathing with or without comorbidities: the Nagahama Study. J Clin Sleep Med . 2021;17(12):2467-2475., (© 2021 American Academy of Sleep Medicine.)

Study Objectives: It is well known that a family history of diabetes (FHD) is a definitive risk factor for type 2 diabetes. It has not been known whether sleep-disordered breathing (SDB) increases the prevalence of diabetes in those with an FHD., Methods: We assessed SDB severity in 7,477 study participants by oximetry corrected by objective sleep duration determined by wrist actigraphy. Glycated hemoglobin ≥6.5% and/or current medication for diabetes indicated the presence of diabetes. In addition to the overall prevalence, the prevalence of recent-onset diabetes during the nearly 5 years before the SDB measurements were made was investigated., Results: Of the 7,477 participants (mean age: 57.9; range: 34.2-80.7; SD: 12.1 years; 67.7% females), 1,569 had an FHD. The prevalence of diabetes in FHD participants with moderate-to-severe SDB (MS-SDB) was higher than in those without SDB (MS-SDB vs without SDB: all, 29.3% vs 3.3% [P < .001]; females, 32.6% vs 1.9% [P < .001]; males, 26.2% vs 11.7% [P = .037]). However, multivariate analysis showed that MS-SDB was significantly associated with a higher prevalence of diabetes only in FHD-positive females (odds ratio [95% confidence interval]: females, 7.43 [3.16-17.45]; males, 0.92 [0.37-2.31]). Among the FHD-positive participants, the prevalence of recent-onset diabetes was higher in those with MS-SDB than those without SDB, but only in females (MS-SDB vs without SDB: 21.4% vs 1.1%; P < 0.001)., Conclusions: MS-SDB was associated with diabetes risk in females with an FHD, and future studies are needed on whether treatment of SDB in females with an FHD would prevent the onset of diabetes., (© 2021 American Academy of Sleep Medicine.)

It is well known that the prevalence of sleep disordered breathing (SDB) is increased in patients with obesity or metabolic comorbidities. However, the way in which the prevalence of SDB increases in relation to comorbidities according to the severity of obesity remains unclear.This cross-sectional study evaluated 7713 community participants using nocturnal oximetry ≥2 nights. SDB was assessed by the 3% oxygen desaturation index corrected for sleep duration obtained by wrist actigraphy (acti-ODI3%). SDB severity was defined by acti-ODI3%. Obesity was defined as body mass index ≥25 kg·m -2 The prevalence of SDB was 41.0% (95% CI 39.9-42.1%), 46.9% (45.8-48.0%), 10.1% (9.5-10.8%) and 2.0% (1.7-2.3%) in normal, mild, moderate and severe SDB, respectively, with notable sex differences evident (males>post-menopausal females>premenopausal females). Comorbidities such as hypertension, diabetes and metabolic syndrome were independently associated with the prevalence of moderate-to-severe SDB, and coincidence of any one of these with obesity was associated with a higher probability of moderate-to-severe SDB (hypertension OR 8.2, 95% CI 6.6-10.2; diabetes OR 7.8, 95% CI 5.6-10.9; metabolic syndrome OR 6.7, 95% CI 5.2-8.6). Dyslipidaemia in addition to obesity was not additively associated with the prevalence of moderate-to-severe SDB. The number of antihypertensive drugs was associated with SDB (p for trend <0.001). Proportion of a high cumulative percentage of sleep time with oxygen saturation measured by pulse oximetry <90% increased, even among moderate-to-severe SDB with increases in obesity.Metabolic comorbidities contribute to SDB regardless of the degree of obesity. We should recognise the extremely high prevalence of moderate-to-severe SDB in patients with obesity and metabolic comorbidities., Competing Interests: Conflict of interest: T. Matsumoto has nothing to disclose. K. Murase reports grants from Philips-Respironics, Teijin Pharma, Fukuda Denshi, Fukuda Lifetec Keiji, ResMed and Japan Society for the Promotion of Science, outside the submitted work. Conflict of interest: Y. Tabara reports grants from Japan Agency for Medical Research and Development (AMED) and The Ministry of Education, Culture, Sports, Science and Technology in Japan, during the conduct of the study. Conflict of interest: T. Minami reports personal fees from Teijin Zaitakuiryou, outside the submitted work. Conflict of interest: O. Kanai has nothing to disclose. Conflict of interest: H. Takeyama reports grants from Philips-Respironics, ResMed, Fukuda Denshi, Fukuda Lifetec Keiji and Teijin Pharma, outside the submitted work. Conflict of interest: N. Takahashi reports grants from Philips-Respironics, ResMed, Fukuda Denshi and Fukuda Lifetec Keiji, outside the submitted work. Conflict of interest: S. Hamada reports grants from Teijin Pharma, outside the submitted work. Conflict of interest: K. Tanizawa has nothing to disclose. Conflict of interest: T. Wakamura has nothing to disclose. Conflict of interest: N. Komenami has nothing to disclose. Conflict of interest: K. Setoh has nothing to disclose. Conflict of interest: T. Kawaguchi has nothing to disclose. Conflict of interest: T. Tsutsumi has nothing to disclose. Conflict of interest: S. Morita has nothing to disclose. Conflict of interest: Y. Takahashi has nothing to disclose. Conflict of interest: T. Nakayama has nothing to disclose. Conflict of interest: T. Hirai has nothing to disclose. Conflict of interest: F. Matsuda reports grants from Kyoto University, the Ministry of Education, Culture, Sports, Science and Technology in Japan, Japan Agency for Medical Research and Development (AMED) and The Takeda Medical Research Foundation, during the conduct of the study. Conflict of interest: K. Chin reports grants from the Japanese Ministry of Education, Culture, Sports, Science and Technology, grants from the Intractable Respiratory Diseases and Pulmonary Hypertension Research Group, the Ministry of Health, Labour and Welfare, Japan, grants from the Research Foundation for Healthy Aging, grants from Health, Labour and Welfare Sciences Research Grants, Research on Region Medical, grants from the Center of Innovation Program, and the Global University Project from Japan Science and Technology Agency, Japan Agency for Medical Research and Development, during the conduct of the study; grants and personal fees from Philips-Respironics, Teijin Pharma, Fukuda Denshi, Fukuda Lifetec Keiji, GlaxoSmithKline and Resmed, grants from KYORIN Pharmaceutical Co., Ltd and Nippon Boehringer Ingelheim Co., Ltd, personal fees from MSD, Astellas Pharma and Eisai Co., Ltd, outside the submitted work., (Copyright ©ERS 2020.)

Study Objectives: The individual prevalence of sleep-disordered breathing (SDB), short sleep duration, and obesity is high and increasing. The study aimed to investigate potential associations between SDB, objective sleep duration, obesity, diabetes and hypertension across genders, and the effect of pre- or post-menopausal status., Methods: A cross-sectional study evaluated 7051 community participants with wrist actigraphy for a week, and nocturnal oximetry ≥ 2 nights. SDB was assessed by 3 per cent oxygen desaturation index (ODI) corrected for sleep duration obtained from wrist actigraphy. Moderate-to-severe SDB was defined as ODI3% levels ≥ 15 per hour., Results: Both logODI3% and body mass index showed independent negative associations with sleep duration (β = -0.16, p < 0.001 and β = -0.07, p < 0.001, respectively). Moderate-to-severe SDB (men/premenopausal women/postmenopausal women; 23.7/1.5/9.5%, respectively) was associated with a higher risk of diabetes in premenopausal women (OR 28.1; 95%CI 6.35-124.6; p < 0.001) and postmenopausal women (OR 3.25; 95%CI 1.94-5.46; p < 0.001), but not in men (OR 1.47; 95%CI 0.90-2.40; p = 0.119). Moderate-to-severe SDB was associated with a higher risk of hypertension in men (OR 3.11; 95%CI 2.23-4.33; p < 0.001), premenopausal women (OR 3.88; 95%CI 1.42-10.6; p = 0.008), and postmenopausal women (OR 1.96; 95%CI 1.46-2.63; p < 0.001). Short sleep duration was not associated with diabetes or hypertension. The associations of obesity with diabetes or hypertension were indirectly mediated by SDB (24.0% and 21.5%, respectively), with possible sex differences emerging (men/women; 15.3/27.8% and 27.0/16.9%, respectively)., Conclusions: Notwithstanding the cross-sectional design, SDB and obesity, but not short sleep duration, were independently associated with diabetes and hypertension, with gender and menopausal status-related differences in risk emerging.

This paper provides a procedure for estimating the maximal stationary metabolic rate (SMRmax) in free-moving rats. The SMRmax was estimated by simultaneously comparing energy expenditure with motor activity measured at 10 min intervals for 24 h. The SMRmax was close to but naturally higher than the resting metabolic rates determined by other conventional methods. The coefficient of variation for 3 consecutive days was below 3%. The ratio of SMRmax to daily minimum energy expenditure was 1.25 in young rats and 1.19 in adult rats. SMRmax is a useful key parameter for analyzing daily energy expenditure and behavior.

We investigated the effect of chronic infusion of neuropeptide Y (NPY) aimed at the hypothalamic suprachiasmatic nucleus (SCN) or the lateral cerebral ventricle (LCV) on food intake. The experiments were performed in adult male Wistar rats infused for 7 days with saline or NPY (10 and 100 pmol microliters-1 h-1) into the SCN (n = 18) or LCV (n = 17). Infusion of the lower dose of NPY in the SCN significantly decreased food intake, whereas infusion of the higher dose did not. There was no change in food intake specific to saline or either dose of NPY with infusion in the LCV. It is concluded that chronic infusion of NPY into the SCN at a dose of 10 pmol h-1 inhibits food intake in rats.

In this paper, we presented a new procedure to determine daily minimum energy expenditure (MEE) in free-moving rats and mice kept in a chamber. Energy expenditure was measured for 23 h period and averaged every 10 min. Data were sorted in ascending order. MEE was estimated from the regression line with the smallest slope and the biggest intercept among the regression lines calculated between the sorted energy expenditure and the data ranking. Among three duplicate measurements in individual animals, MEE gave the smallest coefficient of variation (2.2%) as compared with actual measured-values: either the single lowest value (4.0%) or the average of the 6 lowest values (2.5%). Judging from diurnal patterns of energy expenditure and locomotor activity and from video tape observation of the rat's performance, it was confirmed that MEE represented an energy expenditure at rest. MEE decreased with fasting from days 1 to 5. MEE per body weight also declined with age, but stayed around 71-72 kcal/day/kg3/4 at 18 and 34 weeks of age in male Wistar rats. MEE in mice increased at lower ambient temperatures between 16 and 32 degrees C, but stayed fairly constant at the same temperature in repeated experiments. Thus, MEE estimated by the present regression procedure was highly reproducible and valid to determine the fundamental value of daily energy expenditure under free-moving conditions.