Sleep Extension and Cardiometabolic Health: What is it, Possible Mechanisms, and Real-World Applications

Abstract

Short sleep duration is associated with heightened cardiometabolic disease risk and has reached epidemic proportions among children, adolescents, and adults. Potential mechanisms underlying this association are complex and multifaceted, including disturbances in circadian timing, food intake and appetitive hormones, brain regions linked to control of hedonic eating, physical activity, altered microbiome, and impaired insulin sensitivity. Sleep extension, or increasing total sleep duration, is an emerging and ecologically relevant intervention with significant potential to advance our understanding of the mechanisms underlying the association between short sleep duration and risk of cardiometabolic disease. If effective, sleep extension interventions have potential to improve cardiometabolic health across the lifespan. Existing data show sleep extension is feasible and may have potential cardiometabolic health benefits, though there are limitations the field must overcome. Notably, most existing studies are short-term (2–8 weeks), employ different sleep extension strategies, analyze a wide array of cardiometabolic health outcomes in different populations, and frequently lack adequate statistical power, thus limiting robust scientific conclusions. Overcoming these limitations will require fully powered, randomized studies conducted in people with habitual short sleep duration and existing cardiometabolic risk factors. Additionally, randomized controlled trials comparing different sleep extension strategies are essential to determine the most effect interventions. Ongoing and future research should focus on elucidating the potential cardiometabolic health benefits of sleep extension. Such studies have high potential to generate critical knowledge with potential to improve health and quality of life for those struggling with short sleep duration.

Graphical Abstract

A significant proportion of adults and adolescents regularly sleep less than recommended by the Sleep Research Society and American Academy of Sleep Medicine, which is associated with adverse cardiometabolic risk. One hypothesized strategy to combat such risk is to increase or extend nightly sleep duration. This topical review highlights potential mechanisms linking short sleep duration with adverse cardiometabolic risk and summarizes current evidence on potential cardiometabolic health benefits of sleep extension. As many unanswered questions remain, we conclude by outlining future research directions and suggesting best practices to help advance our understanding of sleep extension as an intervention to improve cardiometabolic health. (Created with BioRender.com).

CONTEXT

The Sleep Research Society (SRS) and American Academy of Sleep Medicine (AASM) recommend adults aged 18–60 years regularly obtain 7–9 hours of sleep per night to promote optimal health (Watson et al., 2015a; Watson et al., 2015b). Parallel recommendations for children aged 6–12 years and teenagers aged 13–18 years are to regularly obtain 9–12 hours and 8–10 hours of sleep each night, respectively (Paruthi et al., 2016). Despite these recommendations, over 35% of adults in the United States (US) report habitually sleeping less than 7 hours per night, and ~30% report sleeping less than 6 hours per night (Centers for Disease Control & Prevention, 2011; Centers for Disease Control & Prevention, 2014; Ford et al., 2015). Among adolescents, less than 1 in 3 obtain the recommended sleep duration on school nights (Wheaton et al., 2018), and ~40% sleep less than 7 hours per night (Twenge et al., 2017). Consequently, a substantial proportion of US adults and adolescents chronically obtain less than the SRS and AASM recommended amount of sleep, operationalized as habitual short sleep duration (HSSD). Despite these data there is no official consensus on differentiating acute versus chronic short sleep duration.

Among children, adolescents, and adults, HSSD is associated with risk of cardiometabolic disease including obesity, type 2 diabetes (T2D), and cardiovascular disease (Depner et al., 2014; Miller et al., 2018; Duraccio et al., 2019; Krietsch et al., 2019; Simon et al., 2021). Notably, adults with HSSD have an ~30% higher risk of T2D versus people who regularly obtain at least 7 hours of sleep per night (Cappuccio et al., 2010; Holliday et al., 2013). This represents a similar relative-risk to that posed by a sedentary lifestyle or consuming one or more sugar sweetened beverages per day (Schulze et al., 2004; Shai et al., 2006; Anothaisintawee et al., 2016). Similar risk profiles are also observed in younger populations, with HSSD occurring earlier in development being linked to later insulin resistance (Cespedes et al., 2014; Hjorth et al., 2014). Mendelian randomization analyses add to this evidence and suggest causal relationships where disrupted sleep is an underlying factor driving the associations between disrupted sleep and risk of T2D and myocardial infarction (Ai et al., 2021; Liu et al., 2022; Xiuyun et al., 2022).

Beyond potential direct links with adverse cardiometabolic risk, HSSD may also impede existing interventions designed to improve cardiometabolic health. For example, experimental sleep restriction during a diet-induced weight-loss study promoted retention of fat mass and loss of fat-free mass (Nedeltcheva et al., 2010). Although sleep restriction in this paradigm lasted just 14 days, these data illustrate that sleep duration can modulate body composition during weight-loss, potentially promoting retention of fat mass, which has long-term adverse cardiometabolic health consequences. Similar data exist in longitudinal studies of dietary weight-loss interventions where adolescents and adults with short sleep duration and/or poor sleep health experience impaired weight-loss compared to people with adequate sleep and/or better sleep health (Valrie et al., 2015; Papandreou et al., 2020; Kline et al., 2021; Bogh et al., 2023). It is perhaps due to these compelling research findings that the American Heart Association added “healthy sleep” as the eighth component of “Life’s Essential 8” for lifelong good health (Lloyd-Jones et al., 2022).

This existing evidence supports the hypothesis that HSSD is an independent, and potentially modifiable, risk factor for cardiometabolic disease (Zhu et al., 2019). However, these data do not inform the efficacy of sleep-based interventions in mitigating such risk among people with HSSD, representing a knowledge gap. To address this gap, fully powered randomized controlled trials (RCTs) with clinical outcomes are needed to robustly define the efficacy of sleep-based interventions to mitigate adverse cardiometabolic risk linked to HSSD. This is especially important given that traditional risk factors focused on diet and physical activity do not fully explain the increases in cardiometabolic disease in recent decades, and novel interventions focused on alternate risk factors, like HSSD, are urgently needed (Keith et al., 2006; Collaboration, 2017). Accordingly, a growing body of recent research has focused on examining the feasibility and efficacy of behavioral interventions to extend nightly sleep duration in people with HSSD, often termed “sleep extension”. This review seeks to highlight the links and possible mechanisms underlying adverse cardiometabolic risk in people with HSSD, overview key findings from published sleep extension studies, as well as outline key research needs and best practices to advance our understanding of sleep extension as an intervention to improve cardiometabolic health among children, adolescents, and adults. Because this is not a systematic review, we focus our discussion on key findings from studies published between 2013 and 2023, identified through a PubMed (hrrps://pubmed.ncbi.nlm.nih.gov/) search for terms “sleep extension” AND “cardiometabolic”, “glucose”, “insulin”, “blood pressure”, “appetite”, “weight”, and “physical activity”. Moreover, we refer readers to the following systemic reviews that include study quality evaluations (Baron et al., 2021; Niu et al., 2021).

PHYSIOLOGICAL MECHANISMS: FROM THE CIRCADIAN CLOCK TO BEHAVIORS AND MOLECULES (FIGURE 1)

Figure 1:

Physiological mechanisms potentially disrupted by habitual short sleep duration.

Several mechanisms ranging from behavioral to molecular likely contribute to the association between HSSD and adverse cardiometabolic risk (Figure 1). Our current understanding of such mechanisms is largely based on experimental sleep restriction in the laboratory. Thus, uncovering the primary mechanism(s) underlying these links in free-living people with HSSD is a critical next step. In this section we concisely highlight some potential mechanisms, with comprehensive details available in the following reviews (Depner et al., 2014; Duraccio et al., 2019; Matricciani et al., 2019; Simon et al., 2021; Chaput et al., 2023).

Behavioral Mechanisms.

Experimental sleep restriction in adolescents and adults has been found to increase energy intake, often shifting the timing of energy intake later in the day (Nedeltcheva et al., 2009; Beebe et al., 2013; Markwald et al., 2013; Duraccio et al., 2019; Zhu et al., 2019; Duraccio et al., 2023). Such increased energy intake patterns typically exceed any increases in energy expenditure, leading to positive energy balance and potential weight-gain (Markwald et al., 2013; Depner et al., 2014). Limited data on physical activity, measured by accelerometry, provide some indication that short sleep duration may be associated with greater sedentary activity the following day, with no significant changes in moderate-to-vigorous activity (Van Dyk et al., 2018; Krietsch et al., 2019; Mead et al., 2019; Thosar et al., 2021; Krietsch et al., 2022). If sustained, such increases in energy intake, sedentary behavior, and positive energy balance could lead to weight-gain and associated cardiometabolic risk in people with HSSD.

Appetitive Hormones.

Changes in the appetitive hormones leptin and ghrelin have been proposed to mediate altered energy intake during sleep restriction (Spiegel et al., 2004). However, data on altered leptin and ghrelin during experimental sleep restriction are mixed and likely depend on whether controlled or ad libitum feeding protocols are used, as well as the developmental period of the participants being assessed (Markwald et al., 2013; Krietsch et al., 2019; Zhu et al., 2019; Depner et al., 2021).

Gut Microbiome.

HSSD has been associated with an increased risk of gut microbiome alterations in older adolescents and adults (Grosicki et al., 2020). Sleep restriction often accompanies circadian misalignment, which may alter gut microbial diversity, resulting in modified metabolites that could potentially promote chronic inflammation and positive energy balance (Withrow et al., 2021); these alterations may represent potential mechanisms that link HSSD with metabolic dysregulation.

Neurological Mechanisms.

Another hypothesis is that sleep restriction induces differential neural activation in brain areas that may influence desire and control for hedonic eating (Benedict et al., 2012; St-Onge et al., 2012; St-Onge et al., 2014; Jensen et al., 2019; DiFrancesco et al., 2023). Such changes in the nucleus accumbens, thalamus, insula, and prefrontal cortex may drive increased energy intake. Indeed, experimental sleep restriction results in elevated preferences for and willingness to spend more money on highly palatable foods (Duraccio et al., 2021; Duraccio et al., 2019; Duraccio et al., 2019). Other mechanisms such as emotion regulation and executive function have also been hypothesized to drive this link between short sleep and increased energy intake (Duraccio et al., 2019). Additional research is needed to fully elucidate the potential neurological and cognitive mechanisms driving increased energy intake during sleep restriction, particularly in the context of free-living people with HSSD outside the laboratory.

Insulin Sensitivity and T2D Risk.

Experimental sleep restriction has been shown to impair whole-body insulin sensitivity, an established risk factor for T2D (Lillioja et al., 1993; Spiegel et al., 1999; Broussard et al., 2015; Eckel et al., 2015; Broussard et al., 2016; Zhu et al., 2019). The precise mechanisms driving such impaired insulin sensitivity are not fully understood. However, proposed mechanisms include elevated cortisol and dysregulated fatty acid and lipid metabolism, all of which can causally increase T2D risk (Spiegel et al., 1999; Summers & Nelson, 2005; Depner et al., 2014; Depner et al., 2020; Tippetts et al., 2021). Another possible mechanism contributing to impaired insulin sensitivity during sleep restriction is circadian misalignment. Extended wakefulness during sleep restriction in the laboratory increases nighttime electrical light exposure, subsequently shifting the timing of the central circadian clock and inducing circadian misalignment (Eckel et al., 2015). Data show the magnitude of this circadian misalignment is associated with the extent of impaired insulin sensitivity in adults during sleep restriction and in adolescents with short sleep duration (Eckel et al., 2015; Simon et al., 2019). Intriguingly, some data suggest impaired glucose homeostasis is avoided when the extended wakefulness during sleep restriction occurs in dim-light conditions (<1 lux), which effectively minimizes this circadian misalignment (Yuan et al., 2021).

It is important to reiterate that these potential mechanisms were primarily identified in the context of acute experimental sleep restriction (2–14 days) among adults with habitual sleep durations of 7–9 hours per night. To advance the field, it is critical to identify which of these mechanisms are most relevant to free-living people with HSSD and which mechanisms are potentially modifiable through sleep-based interventions like sleep extension.

WHAT IS SLEEP EXTENSION

The term “sleep extension” was historically used to describe protocols designed to maximize time in bed, effectively extending total sleep duration. Broadly, the goal of earlier sleep extension research was to quantify changes in sleep structure and cognition resulting from sleep extension, in part, to help understand the homeostatic regulation of sleep (Roehrs et al., 1989; Wehr, 1991; Wehr et al., 1993; Barbato et al., 1994; Barbato & Wehr, 1998; Dement, 2005). For example, findings from one study in 8 healthy men showed four weeks of extending time in bed from 8 hours per day to 14 hours per day led to lower fatigue, increased vigor, and higher rapid eye movement (REM) density during REM sleep episodes that terminated in wakefulness (Barbato et al., 1994). Additionally, early research from Carskadon and Dement showed that 4 nights of 10 hours time in bed led to improved scores on the multiple sleep latency test, reflecting decreased homeostatic sleep pressure from sleep extension (Dement, 2005). Although promising, such findings may not directly apply to people with free-living HSSD, as previous sleep extension studies were often conducted in laboratory settings in healthy adults who otherwise maintained adequate sleep duration.

More recently, “sleep extension” is used to describe behavioral interventions tailored to free-living people with HSSD. These therapies are designed to increase total sleep duration by increasing the time a person spends in their own bed. Most sleep extension studies focus on nighttime sleep but in some cases, especially among athletes, naps are used to increase total sleep duration (Silva et al., 2021). Behavioral sleep extension interventions can involve individual counselling, sleep hygiene psychoeducation, directly prescribed sleep and waketimes, and they may also be incorporated into laboratory manipulation paradigms (Baron et al., 2021; Niu et al., 2021). Meta-analyses show sleep extension can increase sleep duration in adolescents, young adults, and adults, and can potentially enhance sleep quality in children and adolescents (Baron et al., 2021; Niu et al., 2021). Notably, these meta-analyses highlight consistent heterogeneity in research methods used for sleep extension and the magnitude of increases in sleep duration. Among two-arm studies in adults, interventions directly prescribing target bed and waketimes tend to produce larger increases in sleep duration of 1.63 hours (95% CI: 0.67–2.59) compared to 0.40 hours (95% CI: −0.16–0.96) in indirect interventions that involve coaching and educational materials (Baron et al., 2021). Among two-arm studies in children and adolescents, data show wrist-actigraphy measured sleep duration is 31 minutes longer in the sleep extension versus control groups with effect sizes from moderate to huge (Niu et al., 2021). A prominent concern is that increasing time in bed could reduce sleep efficiency; however, current data suggest decreased sleep efficiency with sleep extension is not common, where potential reductions in sleep efficiency may be outweighed by improvements in daytime sleepiness and other health benefits, especially in children and adolescents (Henst et al., 2019; Stock et al., 2020; Baron et al., 2021; Niu et al., 2021). To advance the field and elucidate the potential cardiometabolic health benefits of sleep extension, it is especially important to study sleep extension in people with HSSD who also exhibit other cardiometabolic risk factors such as obesity, hypertension, pre-diabetes, elevated inflammation, or older age (Henst et al., 2019). Although sleep extension in people with HSSD and no pre-existing cardiometabolic risk factors might theoretically help prevent disease, detecting physiologically meaningful improvements in cardiometabolic risk factors in otherwise healthy people without elevated risk is a challenge. Consequently, such a research paradigm may provide limited potential to advance this field specifically.

SLEEP EXTENSION IN THE LAB

Several studies have focused on potential health benefits of sleep extension following sleep restriction in the laboratory, allowing for controlled assessments of sleep extension among healthy adults with habitual sleep durations of 7–9 hours per night. In a landmark study, healthy young men completed 6 nights of sleep restriction (4 hours time in bed) followed by 7 nights of recovery sleep (sleep extension; 12 hours time in bed). Results showed insulin resistance measured by Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) was worse following sleep restriction but improved during the subsequent recovery/sleep extension segment (Spiegel et al., 2005), indicating sleep extension improved glucose metabolism. A similar study employed 5 nights of experimental sleep restriction with 5h time in bed, followed by 5 nights of sleep extension with 9h time in bed. However, in this case, sleep extension did not fully restore insulin sensitivity to baseline, as assessed by intravenous glucose tolerance tests (IVGTT) (Eckel et al., 2015). More recently, the impact of sleep restriction (4.5 to 5 hours time in bed) followed by weekend recovery sleep (2 nights) was investigated (Broussard et al., 2016; Depner et al., 2019b; Ness et al., 2019). Among these studies, the weekend recovery sleep ranged from 10 hours time in bed to ad libitum where participants were free to sleep as much as they wanted. Findings are mixed with data from two studies (Depner et al., 2019b; Ness et al., 2019) showing weekend recovery sleep did not fully mitigate impaired insulin sensitivity induced by experimental sleep restriction, whereas data from one study (Broussard et al., 2016) showed weekend recovery sleep fully restored insulin sensitivity to baseline levels. In another study, healthy young adults completed 9 days of sleep restriction (4 hours time in bed) followed by 2 days of sleep extension (9 hours time in bed). Results showed 24-hour and average bedtime blood pressures increased after sleep restriction and remained elevated following two days of sleep extension (Covassin et al., 2021). These changes in blood pressure were most evident in women, highlighting the importance of examining potential sex-differences in response to sleep extension. In aggregate, these studies provide proof-of-principle evidence that sleep extension following experimental sleep restriction can improve insulin sensitivity in otherwise healthy adults that habitually sleep 7–9 hours per night. They also suggest more than 2–5 nights of sleep extension is necessary to achieve the full potential of cardiometabolic health benefits. However, it remains unclear if these findings derived from experimental sleep restriction in the laboratory will translate to sleep extension in free-living people with HSSD.

CURRENT EVIDENCE: REAL WORLD SLEEP EXTENSION AND CARDIOMETABOLIC HEALTH IN YOUTH (FIGURE 2)

Figure 2:

Current evidence for potential health benefits of sleep extension in people with habitual short sleep.

Although current evidence is limited, there are noteworthy findings showing potential cardiometabolic health benefits of sleep extension in children and adolescents with HSSD. In one study in adolescents with obesity, sleep extension enhanced the efficacy of caloric restriction for weight loss, with decreases in waist circumference and reductions in fasting insulin and interleukin-6 (Moreno-Frias et al., 2020). This study employed an interesting sleep extension strategy of instructing participants to gradually increase their time in bed at home by 5 minutes per night, Monday through Friday, until they achieved the target of one additional hour in bed, resulting in an increased sleep duration of 1.2 ± 0.9 (±SD) hours in the sleep extension group measured by sleep diary. Such gradual sleep extension, over several weeks, may be especially attainable for adolescents who face demanding schedules and a growing desire for autonomy in setting their routines (Crowley et al., 2018). Improvements in sleep routines can also extend to other aspects of daily life. For example, adolescents who successfully advanced their bedtime earlier in a six-week sleep intervention not only increased their sleep duration by 1.62 ± 1.64 (±SD) hours measured by sleep diary, but also increased consumption of low glycemic index foods (Asarnow et al., 2017). These findings imply that sleep extension, by advancing bedtime earlier, may help improve dietary choices among adolescents. In a separate 7-day sleep extension study in healthy young adults, increased sleep duration of 43.0 ± 6.2 (±SEM) minutes per night measured by wrist-actigraphy resulted in a clinically significant decrease in systolic blood pressure of 7.0 ± 3.0 mmHg (Stock et al., 2020). It is noteworthy that dietary and exercise interventions have been associated with similar decreases of ~10 mmHg in blood pressure in overweight men and women (Blumenthal et al., 2010), suggesting sleep extension may have a comparable impact on blood pressure as these widely accepted interventions. These findings underscore the promising outcomes of sleep extension, especially gradual sleep extension, for weight management and its potential for improving cardiometabolic health.

A novel and exciting sleep extension intervention for adolescents is based on the framework of the Transdiagnostic Sleep and Circadian Intervention for Youth (TranS-C) (Harvey, 2016). TranS-C offers a flexible and modular intervention with 8 core and 7 optional modules that address multiple sleep problems, including insomnia, hypersomnia, and sleep phase delays. Particularly relevant, the cross-cutting sleep module focuses on educating participants about circadian rhythms, and an optional sleep module aims to extend sleep by gradually advancing bedtime and circadian timing earlier. The emphasis on shifting circadian timing by altering zeitgebers may be especially helpful for adolescents given their biological predisposition to later/evening chronotype (Fischer et al., 2017; Kuula et al., 2018) and the challenges they experience with early school start times and early morning extra-curricular activities (e.g., sports and music). Preliminary findings from TranS-C have demonstrated efficacy in extending weeknight sleep, reducing evening circadian preference, shifting circadian phase earlier, minimizing social jet lag, and promoting better self-reported sleep, but evidence regarding the impact on physical health outcomes is mixed (Harvey et al., 2018; Dong et al., 2019; Dong et al., 2020; Becker et al., 2022; Gasperetti et al., 2022). Given these promising findings, research examining the cardiometabolic health impacts of TranS-C and other interventions that integrate sleep and circadian components is warranted.

CURRENT EVIDENCE: REAL WORLD SLEEP EXTENSION AND CARDIOMETABOLIC HEALTH IN ADULTS (FIGURE 2)

Studies in adults with HSSD have investigated the impact of behavioral sleep extension interventions on glucose metabolism, eating behaviors, body weight, and blood pressure. Initial findings mainly from pilot trials show promising outcomes, especially related to glucose metabolism and blood pressure. For glucose metabolism, per-protocol analyses from two sleep extension studies in healthy non-diabetic participants with HSSD revealed that larger increases in sleep duration were associated with greater improvements in insulin sensitivity, as measured by the fasting marker quantitative insulin-sensitivity check index (Leproult et al., 2015), HOMA-IR, early insulin response to glucose, and β-cell function (So-ngern et al., 2019). In a RCT in a higher risk population involving 18 men with HSSD and BMI≥25 kg/m² (Hartescu et al., 2022), the sleep extension group demonstrated a significant reduction in HOMA-IR and fasting insulin compared with the control group, suggesting improved insulin resistance. Notably, the sleep extension group achieved a relatively large increase in sleep duration in this study (79.00 min [95% CI: 68.9–88.05]), as measured by wrist-actigraphy, further supporting the hypothesis that larger increases in sleep duration may be required to elicit improvements in glucose metabolism. In contrast, another 4-week RCT with 42 non-obese adults with HSSD (Al Khatib et al., 2018) showed the sleep extension increased sleep duration by 21 min (95% CI: 6–36) measured by wrist-actigraphy, but there were no significant differences in fasting glucose, insulin, HOMA-IR, or c-peptide between the sleep extension and control groups. However, the sleep extension group showed a decrease in free-sugar intake suggesting potential benefits on diet quality. These findings emphasize that people with HSSD and heightened cardiometabolic risk profiles may have greater potential to experience cardiometabolic health benefits from sleep extension as compared to those with lower risk profiles.

Regarding blood pressure, findings from two 6-week pilot sleep extension studies in people with HSSD and elevated blood pressure or stage I hypertension showed that sleep extension increased wrist-actigraphy measured sleep durations by 35 ± 9 (mean ± SD) minutes and 34.2 minutes (15.6 quartile 1; 64.2 quartile 3), respectively, and lowered blood pressure (Haack et al., 2013; Baron et al., 2019). These studies demonstrate feasibility and potential health benefits of sleep extension, but fully powered trials with longer follow-up durations are needed to test the effects over longer timeframes. There are also promising findings from studies examining changes in energy intake and body weight. The largest published RCT in this area in 80 overweight participants with HSSD showed two weeks of sleep extension versus control increased wrist-actigraphy measured sleep duration by 1.2 hours (95% CI: 1.0–1.4), decreased energy intake by 270.4kcal/d (95% CI: 147.4–393.4), and decreased body weight by 0.87kg (95% CI: 0.35–1.39) (Tasali et al., 2022). Additionally, total energy expenditure, as quantified by the doubly-labeled water technique, did not significantly change, leading to a negative energy balance in the sleep extension group. If these effects of sleep extension are sustained over longer timeframes, sleep extension could help promote weight-loss in people with overweight or obesity.

As research focused on sleep extension in adults with HSSD is expanding, various methods have been implemented to deliver sleep extension interventions. These include direct sleep scheduling (Baron et al., 2019), cognitive behavioral techniques, and personalized coaching (Hartescu et al., 2022; Tasali et al., 2022). One notable sleep extension intervention combines the use of a consumer sleep tracker, brief telephone coaching, and weekly educational content, and has demonstrated feasibility and acceptability across different populations in pilot studies (Baron et al., 2018; Reutrakul et al., 2022; Martyn-Nemeth et al., 2023). Despite these early promising findings, most studies suffer from limitations such as small sample sizes, limited assessments of multiple dimensions of sleep, and relatively short intervention and follow-up durations, typically ranging from 2–8 weeks. Furthermore, a scarcity of fully powered RCTs deploying robust gold-standard cardiometabolic assessments like the hyperinsulinemic-euglycemic clamp technique for insulin sensitivity have been published. Overcoming these limitations is crucial to enhance the rigor of data focused on potential cardiometabolic health benefits of sleep extension.

KNOWLEDGE GAPS AND CRITICAL QUESTIONS (FIGURE 3)

Figure 3.

Current evidence and future research needs. CBTi, cognitive behavioral therapy for insomnia; T2D, type 2 diabetes; CVD, cardiovascular disease.

What are the most effective components of sleep extension interventions?

It is important to recognize that a single optimal sleep extension intervention strategy will not exist, especially when considering diverse populations among children and adults with HSSD and cardiometabolic risk. Moreover, strategies for acute or short-term changes will likely differ from those designed to maintain long-term sleep changes. Existing evidence indicates direct interventions with assigned bed and waketimes tend to produce larger increases in sleep duration (1.63 hours [95% CI: 0.67–2.59]) compared to indirect interventions focused on sleep education (0.40 hours [95% CI: −0.16–0.96]), often delivered through mobile applications (Baron et al., 2021). Many direct sleep extension interventions utilize a one-on-one structured interview to develop a specific sleep extension schedule. This strategy demonstrates efficacy but is labor intensive and therefore susceptible to an efficacy-effectiveness gap as larger fully powered studies are conducted. Thus, research designed to optimize sleep extension interventions is needed.

For example, in a recent feasibility study, a 4-group factorial design was implemented to examine the relative impact of Fitbit, coaching, Fitbit+coaching, and self-management components of a sleep extension intervention (Baron et al., 2023). Among all groups, the fitbit+coaching group showed larger but non-significant increases in sleep duration of 0.41 hours (95% CI: −0.08–0.90) compared (p=0.11) with the self-management group, and the coaching group demonstrated significant improvements in sleep-related impairment. The majority of participants rated the interventions as “easy” or “very easy” and therefore the authors concluded that each intervention component was feasible, and that support and accountability are important components of sleep extension interventions. Other components that remain to be formally tested in RCTs include the frequency of feedback provided to participants (e.g., daily, weekly, monthly), the method of quantifying sleep (sleep diary, wrist-actigraphy, consumer wearable, polysomnography), addressing interactions between sleep duration, food intake, physical activity, and circadian timing, and exploring potential interactions with other aspects of sleep health like sleep regularity and timing. As the field advances, more RCTs directly comparing the efficacy of different sleep extension intervention components in specific target populations will be critical for determining the effective components while minimizing cost and burden. Furthermore, it is not currently known how different intervention components may influence cardiometabolic health outcomes, emphasizing the need to power such RCTs for analyzing clinical cardiometabolic health endpoints.

How does sleep extension impact behavioral and molecular mechanisms linking HSSD with adverse cardiometabolic health?

Although energy intake and physical activity have been assessed in some sleep extension studies, knowledge in this area is limited. Beyond total energy intake and physical activity, data on other potential mechanisms, including timing of energy intake, circadian timing, appetitive hormones, brain activity, gut microbiome, toxic lipids and fatty acids, and changes in cortisol, are largely lacking. Gaining an improved understanding of how sleep extension may impact these various mechanisms is crucial to inform the design of effective sleep extension interventions and advance our understanding of causal mechanisms linking HSSD and adverse cardiometabolic risk. Moreover, uncovering the precise mechanisms influenced by sleep extension could help identify people who are most likely to benefit from sleep extension, thus contributing to precision medicine (providing the optimal treatment to the right person at the optimal time). For example, if sleep extension were discovered to lower concentrations of specific toxic lipids in the blood, people with HSSD and elevated concentrations of these toxic lipids might have particularly high potential for sleep extension to improve their health.

Which populations experience cardiometabolic health benefits from sleep extension?

Existing data demonstrate that sleep extension interventions can increase sleep duration in children, adolescents, and adults with HSSD, including those with overweight or obesity and women with a history of gestational diabetes. For future larger RCTs, careful consideration of the population being studied is essential. For example, different people undoubtedly have different factors causing their HSSD and some people will have additional sleep disturbances including insomnia or sleep related breathing disorders. These different populations may experience different changes in health outcomes in response to sleep extension and these different populations may require different strategies to achieve sleep extension. Similarly, different levels of sleep quality prior to sleep extension may influence the potential health benefits of sleep extension. Related, genetically determined differences in sleep need could be a factor that influence cardiometabolic health responses to sleep extension between individuals. Identifying and understanding potential individual variability is an important area of future investigation. For cardiometabolic health outcomes, it is important to study higher risk populations that are more likely to benefit from sleep extension like older adults, people with obesity, pre-diabetes, or hypertension. It is also crucial to consider potential sex differences and to recruit participants from diverse racial and ethnic backgrounds, especially those with elevated risk of HSSD and cardiometabolic disease (Caraballo et al., 2022). Regarding age, although studies on young adults can sometimes be generalized to older adolescents, more research is needed in younger cohorts, particularly those in the initial stages of pubertal development, as early puberty onset is associated with worsened cardiovascular and metabolic outcomes later in life (Fonseca et al., 2019).

What is the dose needed and how can participants maintain sleep duration changes?

The existing data are derived from sleep extension interventions with varying changes in sleep duration of minutes to hours and varying intervention timelines (from weeks to months). Importantly, it remains unclear how the magnitude of short sleep duration prior to sleep extension may influence the required dose and duration of sleep extension needed to produce health benefits. Longer-term interventions with interim analyses could help define the optimal dose and duration of sleep extension for various cardiometabolic health outcomes. Given that cardiometabolic disease develops over years and even decades, longer duration RCTs will be needed to define the effectiveness of sleep extension to reduce incidence of cardiometabolic disease. Finally, given the early stage of this field, there is very little knowledge on what strategies will be successful to promote long-term maintenance of sleep extension, especially in the context of mitigating adverse cardiometabolic risk over the long-term. Strategies from cognitive behavioral therapy for insomnia (CBT-I) or other behavioral interventions should be considered as this line of research progresses.

RESEARCH AGENDA AND SUGGESTIONS

We provide the following practical suggestions to help enhance rigor and advance our understanding of the potential cardiometabolic health benefits of sleep extension. (1) Future research should prioritize RCTs because they evenly distribute measured and unmeasured confounding between study groups, allowing for stronger scientific interpretations. (2) Trials should carefully formulate eligibility criteria to screen participants for sleep disorders using established clinical diagnostic criteria to ensure the observed effects are specific to sleep extension while balancing generalizability. (3) Trials should be pre-registered, and the comprehensive descriptions of the sleep extension interventions should be published, preferably in a methods paper published prior to the primary outcome analyses. Transparency in intervention design is crucial to reduce publication bias, improve replicability, and advance our understanding the mechanisms of action. (4) Research should ensure that sample sizes provide adequate statistical power to detect clinically meaningful differences in primary outcomes. (5) We encourage future trials to examine higher-risk populations including people with overweight or obesity, pre-diabetes, hypertension, those with a prior history of trauma, and older adults. These populations have greater probability of experiencing cardiometabolic health benefits from sleep extension and interventions may need to be tailored to these various populations. These include incorporating parent education and intervention in infancy and toddlerhood, consideration of structural contributors to sleep in high school and college students, and consideration of comorbid sleep, psychiatric and medical disorders among older adults (6) It is critical to focus on clinically relevant cardiometabolic health outcomes. In long-term trials, focusing on hard clinical endpoints like the incidence of T2D or major adverse cardiac events will provide more meaningful insights with potential to change clinical practice. (7). Intervention durations and follow-up periods for sleep extension studies should align with anticipated timeframes relevant to disease processes to capture meaningful changes. (8) It is critical to measure and report objective sleep duration before participants enroll in sleep extension studies. Use best practices for quantifying free-living sleep duration with wearable devices, optimally throughout the entire study duration (Depner et al., 2019a). (9) Implement additional measures of sleep to capture the multiple dimensions of sleep health including regularity, satisfaction, alertness, timing, efficiency, and duration (Buysse, 2014). Moreover, in-depth assessments of sleep using polysomnography, slow wave activity, and the multiple sleep latency test could help better define the impact of sleep extension on sleep physiology. (10) Conduct follow-up analyses to help analyze the maintenance of sleep duration changes and determine if benefits observed during the intervention persist over longer timeframes. (11) Consider capturing the timing of light exposure, physical activity, and food intake throughout the intervention. These factors may interact with sleep extension, and it is important to understand how these health behaviors may influence each other. (12). Finally, as sleep duration closely interacts with circadian timing, future research should consider quantifying the timing of the central circadian clock using dim-light melatonin onset (DLMO) protocols directly or using a biomarker approach (Broussard et al., 2017; Cheng et al., 2021; Klerman et al., 2022).

Before progressing to larger multi-site RCTs focusing on implementation methods and strategies, the field should first establish clear evidence of the cardiometabolic health benefits derived from sleep extension. This staged approach will help build a more robust foundation of knowledge, enabling more effective and impactful research in the future.

CONCLUSIONS

HSSD is a significant risk factor for adverse cardiometabolic health outcomes, highlighting the critical need for interventions that mitigate such risk. Sleep extension, as a clinical intervention holds potential to mitigate this risk and improve cardiometabolic health in people with HSSD. Increasing sleep duration through sleep extension behavioral interventions demonstrates feasibility in children, adolescents, and adults with HSSD. However, evidence regarding the potential cardiometabolic health benefits of sleep extension is in the early stages of investigation (Figure 2). Several factors appear to contribute to this variability, including differences in cardiometabolic health outcomes measured, differences in the magnitude of sleep extension, differences in the population studied, differences in the baseline sleep duration prior to sleep extension, and differences in the method of quantifying sleep duration. To advance the field, we recommend conducting fully powered RCTs focused on populations at higher risk for cardiometabolic disease. Such RCTs should use clinical endpoints to assess efficacy of sleep extension interventions and to identify strategies for implementing large-scale interventions. Furthermore, expanding research into children and adolescents is essential to gain insights into how sleep extension impacts individuals across various developmental stages and potentially inform cardiometabolic disease prevention. Despite current research limitations, sleep extension interventions have significant potential to help mitigate adverse cardiometabolic risk linked to HSSD. Regardless of the outcomes of fully powered RCTs, comprehensively understanding the impact of sleep extension is a vital step for the field. As the field continues to evolve, we anticipate that ongoing research will bring us closer to fully realizing the potential benefits of sleep extension on cardiometabolic health, ultimately improving the overall quality of life for people affected by HSSD.

Biographies

Kara M. Duraccio PhD completed her training at Brigham Young University and Cincinnati Children’s Hospital Medical Center. Her research is focused on uncovering risk factors for insufficient sleep in youth, understanding the mental, behavioral, and physical health consequences of obtaining insufficient sleep, and developing methods of studying diet, physical activity, and sleep in parallel to create effect pediatric obesity interventions.

Christopher M. Depner PhD completed his training at Oregon State University and University of Colorado Boulder. He directs the Sleep and Circadian Physiology Research Laboratory with a diverse group of talented students, staff, and collaborators. He leverages cross-disciplinary and translational approaches to investigate mechanisms underlying adverse cardiometabolic risk linked to short sleep duration and circadian misalignment with the goal of developing sleep and circadian-based interventions that improve health and wellbeing.