Person:

Redline, Susan

Objectives: The aim of the current study was to compare the objective and subjective effects of continuous positive airway pressure to the use of nasal dilator strips in patients with acromegaly and moderate to severe obstructive sleep apnea. Methods: We studied 12 patients with acromegaly and moderate to severe obstructive sleep apnea (male/females = 8/4, age = 52(\pm)8 ys, body mass index = 33.5(\pm)4.6 Kg/m(^2), apnea–hypopnea index = 38(\pm)14 events/h) who had been included in a randomized, crossover study to receive three months of treatment with continuous positive airway pressure and nasal dilator strips. All patients were evaluated at study entry and at the end of each treatment by polysomnography, and Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index and treatment satisfaction questionnaires. Results: The apnea–hypopnea index values decreased significantly with continuous positive airway pressure treatment but did not change with the use of nasal dilator strips. All of the subjective symptoms improved with both treatments, but these improvements were significantly greater with continuous positive airway pressure than with the nasal dilator strips. Conclusion: The use of nasal dilator strips had a much smaller effect on the severity of obstructive sleep apnea in patients with acromegaly and moderate to severe obstructive sleep apnea in comparison to the use of continuous positive airway pressure. Moreover, the improvement in several subjective parameters without any significant objective improvement in obstructive sleep apnea resulting from the use of nasal dilator strips is compatible with a placebo effect.

Background: Whereas it is well established that plasma lipid levels have substantial heritability within populations, it remains unclear how many of the genetic determinants reported in previous studies (largely performed in European American cohorts) are relevant in different ethnicities. Methodology/Principal Findings: We tested a set of (\sim)50,000 polymorphisms from (\sim)2,000 candidate genes and genetic loci from genome-wide association studies (GWAS) for association with low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) in 25,000 European Americans and 9,000 African Americans in the National Heart, Lung, and Blood Institute (NHLBI) Candidate Gene Association Resource (CARe). We replicated associations for a number of genes in one or both ethnicities and identified a novel lipid-associated variant in a locus harboring ICAM1. We compared the architecture of genetic loci associated with lipids in both African Americans and European Americans and found that the same genes were relevant across ethnic groups but the specific associated variants at each gene often differed. Conclusions/Significance: We identify or provide further evidence for a number of genetic determinants of plasma lipid levels through population association studies. In many loci the determinants appear to differ substantially between African Americans and European Americans.

Circulating levels of adiponectin, a hormone produced predominantly by adipocytes, are highly heritable and are inversely associated with type 2 diabetes mellitus (T2D) and other metabolic traits. We conducted a meta-analysis of genome-wide association studies in 39,883 individuals of European ancestry to identify genes associated with metabolic disease. We identified 8 novel loci associated with adiponectin levels and confirmed 2 previously reported loci (P = (4.5×10^{−8}–1.2×10^{−43})). Using a novel method to combine data across ethnicities (N = 4,232 African Americans, N = 1,776 Asians, and N = 29,347 Europeans), we identified two additional novel loci. Expression analyses of 436 human adipocyte samples revealed that mRNA levels of 18 genes at candidate regions were associated with adiponectin concentrations after accounting for multiple testing (p<(3×10^{−4})). We next developed a multi-SNP genotypic risk score to test the association of adiponectin decreasing risk alleles on metabolic traits and diseases using consortia-level meta-analytic data. This risk score was associated with increased risk of T2D (p = (4.3×10^{−3}), n = 22,044), increased triglycerides (p = (2.6×10^{−14}), n = 93,440), increased waist-to-hip ratio (p = (1.8×10^{−5}), n = 77,167), increased glucose two hours post oral glucose tolerance testing (p = (4.4×10^{−3}), n = 15,234), increased fasting insulin (p = 0.015, n = 48,238), but with lower in HDL-cholesterol concentrations (p = (4.5×10^{−13}), n = 96,748) and decreased BMI (p = (1.4×10^{−4}), n = 121,335). These findings identify novel genetic determinants of adiponectin levels, which, taken together, influence risk of T2D and markers of insulin resistance.

Although obstructive sleep apnea (OSA) is known to have a strong familial basis, no genetic polymorphisms influencing apnea risk have been identified in cross-cohort analyses. We utilized the National Heart, Lung, and Blood Institute (NHLBI) Candidate Gene Association Resource (CARe) to identify sleep apnea susceptibility loci. Using a panel of 46,449 polymorphisms from roughly 2,100 candidate genes on a customized Illumina iSelect chip, we tested for association with the apnea hypopnea index (AHI) as well as moderate to severe OSA (AHI≥15) in 3,551 participants of the Cleveland Family Study and two cohorts participating in the Sleep Heart Health Study. Among 647 African-Americans, rs11126184 in the pleckstrin (PLEK) gene was associated with OSA while rs7030789 in the lysophosphatidic acid receptor 1 (LPAR1) gene was associated with AHI using a chip-wide significance threshold of p-value<2×(10^{−6}). Among 2,904 individuals of European ancestry, rs1409986 in the prostaglandin E2 receptor (PTGER3) gene was significantly associated with OSA. Consistency of effects between rs7030789 and rs1409986 in LPAR1 and PTGER3 and apnea phenotypes were observed in independent clinic-based cohorts. Novel genetic loci for apnea phenotypes were identified through the use of customized gene chips and meta-analyses of cohort data with replication in clinic-based samples. The identified SNPs all lie in genes associated with inflammation suggesting inflammation may play a role in OSA pathogenesis.

The identification and exploration of genetic loci that influence smoking behaviors have been conducted primarily in populations of the European ancestry. Here we report results of the first genome-wide association study meta-analysis of smoking behavior in African Americans in the Study of Tobacco in Minority Populations Genetics Consortium (n=32 389). We identified one non-coding single-nucleotide polymorphism (SNP; rs2036527[A]) on chromosome 15q25.1 associated with smoking quantity (cigarettes per day), which exceeded genome-wide significance ((\beta)=0.040, s.e.=0.007, P=1.84 × 10(^{−8})). This variant is present in the 5′-distal enhancer region of the CHRNA5 gene and defines the primary index signal reported in studies of the European ancestry. No other SNP reached genome-wide significance for smoking initiation (SI, ever vs never smoking), age of SI, or smoking cessation (SC, former vs current smoking). Informative associations that approached genome-wide significance included three modestly correlated variants, at 15q25.1 within PSMA4, CHRNA5 and CHRNA3 for smoking quantity, which are associated with a second signal previously reported in studies in European ancestry populations, and a signal represented by three SNPs in the SPOCK2 gene on chr10q22.1. The association at 15q25.1 confirms this region as an important susceptibility locus for smoking quantity in men and women of African ancestry. Larger studies will be needed to validate the suggestive loci that did not reach genome-wide significance and further elucidate the contribution of genetic variation to disparities in cigarette consumption, SC and smoking-attributable disease between African Americans and European Americans.

Context Short sleep duration is associated with adverse health outcomes, but the mechanisms involved are unknown. It has been postulated that short sleep duration may elevate cortisol levels, but studies have had conflicting results. It is unclear whether these differing findings may be due to methodological issues, such as assessment of sleep duration. Specifically, objective versus subjective methods of measuring habitual sleep duration may account for the conflicting results found in epidemiological studies. Objective: Our goal was to determine whether habitual sleep duration, measured objectively (by actigraphy) and subjectively (by self-report), was associated with 24-hour urine free cortisol (UFC), a measure of integrated cortisol secretion. Our secondary goal was to determine whether slow wave sleep (SWS, determined by polysomnography) was associated with 24-hour UFC. Design/Setting Cross sectional study of community dwelling older men. Patients/Participants 325 men (mean age = 76.6 years, SD = 5.5) from the Portland site of the MrOS Sleep Study, who underwent 24-hour urine collection, polysomnography, actigraphy and sleep questionnaire. Primary Outcome 24-hour UFC. Results: In this study of community dwelling older men, self-reported sleep duration was inversely related to 24-hour UFC levels. Participants reporting <5 hours of habitual sleep had an adjusted mean 24-hour UFC of 29.8 ug, compared to 28.0 ug in participants reporting >5 to <8 hours of sleep 25.5 ug in those reporting >8 hours of habitual sleep. However, sleep duration determined by actigraphy was not associated with 24-hour UFC in either univariable or multivariable regression models. SWS was not associated with 24-hour UFC. Conclusion: Objectively measured (i.e., actigraphic) sleep duration is not associated with 24-hour UFC in these community dwelling older men. This finding, together with prior studies, suggests that elevated levels of integrated cortisol secretion is not the mechanisms by which short sleep duration leads to adverse health outcomes.

Objectives: To use wrist-actrigrphy to collect objective measures of sleep and to characterise actigraphy-measured sleep patterns among children with disabilities. We also assessed the extent to which, if at all, caregivers’ education is associated with children's sleep disturbances. Design: Cross-sectional study. Setting: A rehabilitation centre in the Patagonia region, Chile. Methods: This study was conducted among 125 children aged 6–12 years with disabilities (boys: 55.2%) and their primary caregivers in Chile. Children wore ActiSleep monitors for 7 days. A general linear model was fitted to generate least-square means and SEs of sleep efficiency (proportion of the sleep period spent asleep) across caregivers’ education levels adjusting for children's age, sex, disability type, caregiver–child relationship and caregivers’ age. Multivariable logistic regression analyses were conducted to estimate ORs and 95% CIs of longer sleep latency (≥30 min) and longer wake after sleep onset (WASO) (≥90 min) (a measure of sleep fragmentation) in relation to caregivers’ educational attainment. Results: Median sleep latency was 27.3 min, WASO 88.1 min and sleep duration 8.0 h. Mean sleep efficiency was 80.0%. Caregivers’ education was positively and significantly associated with children's sleep efficiency (p trend<0.001). Adjusted mean sleep efficiency was 75.7% (SE=1.4) among children of caregivers <high school education, and 81.9% (SE=1.0) among children of caregivers >high school education. Compared to children whose caregivers had >high school, children of caregivers with <high school had higher odds of longer sleep latency (OR=3.27; 95% CI 1.12 to 9.61) and longer WASO (OR=5.95; 95% CI 1.91 to 18.53). Associations were consistent across disability types. Conclusions: Children with disabilities experience difficulties initiating sleep (prolonged sleep latency) and maintaining sleep (long WASO, low sleep efficiency). Among children with disabilities, lower level of caregivers’ education is associated with more sleep disturbances.

Background: Children with disabilities are more likely to have sleep disturbances than children without disabilities. Identifying attitudes, beliefs, knowledge, and perceptions of caregivers and health professionals is essential in developing effective intervention programs to improve disabled children’s sleep health. However, no such qualitative data about adults who have key roles in the life and daytime activities of children with disabilities are available. This qualitative study aimed to understand attitudes, beliefs, knowledge, and perceptions about disabled children’s sleep hygiene among caregivers and rehabilitation providers of children with disabilities. Methods: Twenty seven adults, including nine primary caregivers and eighteen rehabilitation providers, participated in five focus group discussions between September and December 2012 at the Rehabilitation Center in Punta Arenas, Chile. A trained facilitator guided focus group discussions using a semi-structured script. Audiotapes and transcripts of focus group discussions were reviewed and analyzed for recurrent themes. Results: Participants identified seven themes related to children’s sleep hygiene: lifestyle behaviors, family factors, children’s disabilities and/or comorbidities, environmental factors, adults’ responsibilities for children’s sleep, perception of good sleep, and parental distress about children’s sleep problems. While both caregivers and rehabilitation providers recognized the importance of sleep for children’s health and functioning, they differed in their understanding of how sleep hygiene practices influence sleep. Rehabilitation providers recognized the negative influence of electronics on sleep and the positive influence of sleep routines. In contrast, caregivers reported use of television/movie watching and stimulants as coping strategies for managing children’s sleep problems. Conclusions: Caregivers may benefit from better understanding the influence of electronics and stimulant use on child sleep health. Rehabilitation providers are well positioned to provide educational messages to both children and caregivers in order to change their attitudes, perceptions, and practices surrounding sleep. These qualitative data are valuable in developing intervention programs aimed at improving sleep health among children with disabilities.

OBJECTIVE Recently, sleep-disordered breathing (SDB) has been reported to be associated with the development of gestational diabetes mellitus (GDM). Accordingly, as this is emergent area of research that has significant clinical relevance, the objective of this meta-analysis is to examine the relationship between SDB with GDM. RESEARCH DESIGN AND METHODS We searched several electronic databases for all of the studies published before January 2013 and reviewed references of published articles. Meta-analytic procedures were used to estimate the unadjusted and BMI-adjusted odds ratios (ORs) using a random effects model. Significant values, weighted effect sizes, and 95% CIs were calculated, and tests of homogeneity of variance were performed. RESULTS Results from nine independent studies with a total of 9,795 pregnant women showed that SDB was significantly associated with an increased risk of GDM. Women with SDB had a more than threefold increased risk of GDM, with a pooled BMI-adjusted OR 3.06 (95% CI 1.89–4.96). CONCLUSIONS These findings demonstrate a significant association between SDB and GDM that is evident even after considered confounding by obesity. This meta-analysis indicates a need to evaluate the role of early recognition and treatment of SDB early during pregnancy.

OBJECTIVE To examine racial differences in sleep duration and its relationship with diabetes. RESEARCH DESIGN AND METHODS We used data from a nationally representative sample of U.S. adults (n = 130,943) participating in the National Health Interview Survey from 2004 to 2011. Usual sleep duration was self-reported and categorized as <7 h (short), 7 h (optimal), and >7 h (long). Diabetes status was based on self-reported diagnosis from a health professional. RESULTS Participants’ mean age was 50.6 years, 49% were men, and 13% were black. Compared with whites, blacks were more likely to report short sleep (37 vs. 28%) and less likely to get 7 h of sleep (24 vs. 33%). Diabetes (9,643 cases [9%] in whites and 3,612 cases [15%] in blacks) had a U-shaped distribution with sleep in whites (10, 7, and 9%, for short, optimal, and long sleep, respectively) and blacks (16, 13, and 15%). Suboptimal sleep duration was more strongly associated with diabetes in whites than in blacks among short (prevalence ratio 1.49 [95% CI 1.40–1.58] vs. 1.21 [1.09–1.34]) and long (1.32 [1.25–1.40] vs. 1.11 [1.00–1.23]) sleepers on the relative scale. Adjustment for socioeconomic status (SES) attenuated the short sleep–diabetes association in blacks (1.15 [1.02–1.29]), and the racial/ethnic difference in the short sleep–diabetes association became nonsignificant after SES adjustments. CONCLUSIONS Suboptimal sleep duration was positively associated with diabetes in blacks and whites, although diabetes prevalence was higher at any level of sleep in blacks. Socioeconomic factors appear to partly explain the association for short sleep in blacks as well as disparity between racial groups.