Giving weight to incretin-based pharmacotherapy for obesity-related sleep apnea: a revolution or a pipe dream?Grunstein, Ronald R; Wadden, Thomas A; Chapman, Julia L; Malhotra, Atul; Phillips, Craig L
doi: 10.1093/sleep/zsad224pmid: 37668448
Obesity is a chronic disease affecting over 670 million adults globally, with multiple complications including obstructive sleep apnea (OSA). Substantial weight loss in patients with obesity-related OSA can reduce or even eliminate OSA as well as reduce sleepiness and improve cardio-metabolic health. Evidence suggests that these improvements exceed those that occur with device-based OSA therapies like continuous positive airway pressure which continue to be the first-line of therapy. Resistance to weight management as a first-line strategy to combat OSA could arise from the complexities in delivering and maintaining adequate weight management, particularly in sleep clinic settings. Recently, incretin-based pharmacotherapies including glucagon-like peptide 1 (GLP-1) receptor agonists alone or combined with glucose-dependent insulinotropic polypeptide (GIP) receptor agonists have been developed to target glycemic control in type 2 diabetes. These medications also slow gastric emptying and reduce energy intake. In randomized, placebo-controlled trials of these medications in diabetic and non-diabetic populations with obesity, participants on active medication lost up to 20% of their body weight, with corresponding improvements in blood pressure, lipid levels, physical functioning, and fat mass loss. Their adverse effects are predominantly gastrointestinal-related, mild, and transient. There are trials currently underway within individuals with obesity-related OSA, with a focus on reduction in weight, OSA severity, and cardio-metabolic outcomes. These medications have the potential to substantially disrupt the management of OSA. Pending coming data, we will need to consider pharmacological weight loss as a first-line therapy and how that influences training and management guidelines.
Cardiovascular Burden of Narcolepsy Disease (CV-BOND): a real-world evidence studyBen-Joseph, Rami H; Saad, Ragy; Black, Jed; Dabrowski, Elizabeth C; Taylor, Ben; Gallucci, Sophia; Somers, Virend K
doi: 10.1093/sleep/zsad161pmid: 37305967
Study ObjectivesNarcolepsy is associated with cardiovascular risk factors; however, the risk of new-onset cardiovascular events in this population is unknown. This real-world study evaluated the excess risk of new-onset cardiovascular events in U.S. adults with narcolepsy.MethodsA retrospective cohort study using IBM MarketScan administrative claims data (2014–2019) was conducted. A narcolepsy cohort, comprising adults (≥18 years) with at least two outpatient claims containing a narcolepsy diagnosis, of which at least one was non-diagnostic, was matched to a non-narcolepsy control cohort (1:3) based on cohort entry date, age, sex, geographic region, and insurance type. The relative risk of new-onset cardiovascular events was estimated using a multivariable Cox proportional hazards model to compute adjusted hazard ratios (HRs) and 95% confidence intervals (CIs).ResultsThe narcolepsy and matched non-narcolepsy control cohorts included 12 816 and 38 441 individuals, respectively. At baseline, cohort demographics were generally similar; however, patients with narcolepsy had more comorbidities. In adjusted analyses, the risk of new-onset cardiovascular events was higher in the narcolepsy cohort compared with the control cohort: any stroke (HR [95% CI], 1.71 [1.24, 2.34]); heart failure (1.35 [1.03, 1.76]); ischemic stroke (1.67 [1.19, 2.34]); major adverse cardiac event (1.45 [1.20, 1.74]); grouped instances of stroke, atrial fibrillation, or edema (1.48 [1.25, 1.74]); and cardiovascular disease (1.30 [1.08, 1.56]).ConclusionIndividuals with narcolepsy are at increased risk of new-onset cardiovascular events compared with individuals without narcolepsy. Physicians should consider cardiovascular risk in patients with narcolepsy when weighing treatment options.
Online sleep diaries: considerations for system development and recommendations for data managementShaffer, Kelly M; Daniel, Katharine E; Frederick, Christina; Buysse, Daniel J; Morin, Charles M; Ritterband, Lee M
doi: 10.1093/sleep/zsad199pmid: 37480840
Study ObjectivesTo present development considerations for online sleep diary systems that result in robust, interpretable, and reliable data; furthermore, to describe data management procedures to address common data entry errors that occur despite those considerations.MethodsThe online sleep diary capture component of the Sleep Healthy Using the Internet (SHUTi) intervention has been designed to promote data integrity. Features include diary entry restrictions to limit retrospective bias, reminder prompts and data visualizations to support user engagement, and data validation checks to reduce data entry errors. Despite these features, data entry errors still occur. Data management procedures relying largely on programming syntax to minimize researcher effort and maximize reliability and replicability. Presumed data entry errors are identified where users are believed to have incorrectly selected a date or AM versus PM on the 12-hour clock. Following these corrections, diaries are identified that have unresolvable errors, like negative total sleep time.ResultsUsing the example of one of our fully-powered, U.S. national SHUTi randomized controlled trials, we demonstrate the application of these procedures: of 45,598 total submitted diaries, 487 diaries (0.01%) required modification due to date and/or AM/PM errors and 27 diaries (<0.001%) were eliminated due to unresolvable errors.ConclusionTo secure the most complete and valid data from online sleep diary systems, it is critical to consider the design of the data collection system and to develop replicable processes to manage data.Clinical Trial RegistrationSleep Healthy Using The Internet for Older Adult Sufferers of Insomnia and Sleeplessness (SHUTiOASIS); https://clinicaltrials.gov/ct2/show/NCT03213132; ClinicalTrials.gov ID: NCT03213132
Disturbance of sleep maintenance, but not sleep duration, activates nuclear factor-κB and signal transducer and activator of transcription family proteins in older adults: sex differencesPiber, Dominique; Olmstead, Richard; Cho, Joshua H; Irwin, Michael R
doi: 10.1093/sleep/zsad130pmid: 37140651
Study ObjectivesDisturbances of sleep maintenance and sleep duration are common in older adults and associated with an increased risk for age-related mortality and morbidity. Converging evidence implicates inflammation as an underlying mechanism, especially in females. However, it is unknown what specific aspects of sleep disturbance impact inflammatory mechanisms in older adults.MethodsUsing data from community-dwelling older adults who participated in the Sleep Health and Aging Research (SHARE) field study (n = 262, mean age 71.9 ± 8.0 years), we conducted a secondary analysis to examine whether disturbance of sleep maintenance (i.e. greater amount of wake time after sleep onset [WASO]) and sleep duration (i.e. shorter total sleep time [TST]) assessed by sleep diary and actigraphy are associated with greater activation of nuclear factor (NF)-κB and signal transducer and activator of transcription (STAT) family proteins STAT1, STAT3, and STAT5 in peripheral blood monocytic cells. In addition, moderation effects of sex were explored.ResultsData were available for sleep diary (n = 82), actigraphy (n = 74), and inflammatory signaling and transcriptional measures (n = 132). As assessed by sleep diary, greater amount of WASO (β = 0.39, p < 0.01), but not TST, was associated with higher levels of NF-κB. Whereas diary-assessed sleep measures were not associated with STAT family proteins, a moderation analysis revealed that greater diary-assessed WASO was associated with higher levels of STAT1 (p < 0.05), STAT3 (p < 0.05), and STAT5 (p < 0.01) in females, but not in males. Actigraphy-assessed sleep measures were not associated either with NF-κB or STAT activation.ConclusionsIn older adults, self-reported disturbance of sleep maintenance assessed by sleep diary was uniquely associated with higher levels of NF-κB, along with higher levels of STAT family proteins in females, but not in males. Our data suggest that improvingself-reported sleep maintenance might mitigate age-related increases in inflammatory signaling and transcriptional pathways, possibly more strongly in females, with the potential to reduce mortality risk in older adults.