The Development of a Novel mHealth Tool for Obstructive Sleep Apnea: Tracking Continuous Positive Airway Pressure Adherence as a Percentage of Time in Bed.

BACKGROUND: Continuous positive airway pressure (CPAP) is the mainstay obstructive sleep apnea (OSA) treatment; however, poor adherence to CPAP is common. Current guidelines specify 4 hours of CPAP use per night as a target to define adequate treatment adherence. However, effective OSA treatment requires CPAP use during the entire time spent in bed to optimally treat respiratory events and prevent adverse health effects associated with the time spent sleeping without wearing a CPAP device. Nightly sleep patterns vary considerably, making it necessary to measure CPAP adherence relative to the time spent in bed. Weight loss is an important goal for patients with OSA. Tools are required to address these clinical challenges in patients with OSA. OBJECTIVE: This study aimed to develop a mobile health tool that combined weight loss features with novel CPAP adherence tracking (ie, percentage of CPAP wear time relative to objectively assessed time spent in bed) for patients with OSA. METHODS: We used an iterative, user-centered process to design a new CPAP adherence tracking module that integrated with an existing weight loss app. A total of 37 patients with OSA aged 20 to 65 years were recruited. In phase 1, patients with OSA who were receiving CPAP treatment (n=7) tested the weight loss app to track nutrition, activity, and weight for 10 days. Participants completed a usability and acceptability survey. In phase 2, patients with OSA who were receiving CPAP treatment (n=21) completed a web-based survey about their interpretations and preferences for wireframes of the CPAP tracking module. In phase 3, patients with recently diagnosed OSA who were CPAP naive (n=9) were prescribed a CPAP device (ResMed AirSense10 AutoSet) and tested the integrated app for 3 to 4 weeks. Participants completed a usability survey and provided feedback. RESULTS: During phase 1, participants found the app to be mostly easy to use, except for some difficulty searching for specific foods. All participants found the connected devices (Fitbit activity tracker and Fitbit Aria scale) easy to use and helpful. During phase 2, participants correctly interpreted CPAP adherence success, expressed as percentage of wear time relative to time spent in bed, and preferred seeing a clearly stated percentage goal ("Goal: 100%"). In phase 3, participants found the integrated app easy to use and requested push notification reminders to wear CPAP before bedtime and to sync Fitbit in the morning. CONCLUSIONS: We developed a mobile health tool that integrated a new CPAP adherence tracking module into an existing weight loss app. Novel features included addressing OSA-obesity comorbidity, CPAP adherence tracking via percentage of CPAP wear time relative to objectively assessed time spent in bed, and push notifications to foster adherence. Future research on the effectiveness of this tool in improving OSA treatment adherence is warranted.

Sleep quality and glycaemic variability in a real-life setting in adults with type 1 diabetes.

AIMS/HYPOTHESIS: Suboptimal subjective sleep quality is very common in adults with type 1 diabetes. Reducing glycaemic variability is a key objective in this population. To date, no prior studies have examined the associations between objectively measured sleep quality and overnight glycaemic variability in adults with type 1 diabetes. We aimed to test the hypothesis that poor sleep quality would be associated with greater overnight glycaemic variability. METHODS: Data were collected in the home setting from 20 adults (ten male and ten female participants) with type 1 diabetes who were current insulin pump users. Simultaneous assessments of objective sleep quality (Zmachine Insight+) and continuous glucose monitoring (CGM) were performed over multiple nights (up to 15 nights) in each participant. Due to the real-life nature of this study, the participants kept their usual CGM alerts for out-of-range glucose values. Sleep quality was categorised as 'good' or 'poor' using a composite of objective sleep features (i.e. sleep efficiency, wake after sleep onset and number of awakenings) based on the National Sleep Foundation's consensus criteria. Glycaemic variability was quantified using SD and CV of overnight glucose values based on overnight CGM profiles. RESULTS: A total of 170 nights were analysed. Overall, 86 (51%) nights were categorised as good sleep quality, and 84 (49%) nights were categorised as poor sleep quality. Using linear mixed-effects models, poor sleep quality was significantly associated with greater glycaemic variability as quantified by SD (coefficient: 0.39 [95% CI 0.10, 0.67], p = 0.009) and CV (coefficient: 4.35 [95% CI 0.8, 7.9], p = 0.02) of overnight glucose values, after accounting for age, sex, BMI and overnight insulin dose. There was large inter- and intra-individual variability in sleep and glycaemic characteristics. Both pooled and individual-level data revealed that the nights with poor sleep quality had larger SDs and CVs, and, conversely, the nights with good sleep quality had smaller SDs and CVs. No associations were found between sleep quality and time spent in the target glucose range, or above or below the target glucose range, where CGM alarms are most likely to occur. CONCLUSIONS/INTERPRETATION: Objectively measured sleep quality is associated with overnight glycaemic variability in adults with type 1 diabetes. These findings highlight an important role of sleep quality in overnight glycaemic control in type 1 diabetes. They also provide a strong incentive to both patients and healthcare providers for considering sleep quality in personalised type 1 diabetes glycaemic management plans. Future studies should investigate the mechanisms linking sleep quality to glycaemic variability.

Eight Hours of Nightly Continuous Positive Airway Pressure Treatment of Obstructive Sleep Apnea Improves Glucose Metabolism in Patients with Prediabetes. A Randomized Controlled Trial.

RATIONALE: Although obstructive sleep apnea (OSA) is associated with impaired glucose tolerance and diabetes, it remains unclear whether OSA treatment with continuous positive airway pressure (CPAP) has metabolic benefits. OBJECTIVES: To determine the effect of 8-hour nightly CPAP treatment on glucose metabolism in individuals with prediabetes and OSA. METHODS: In a randomized controlled parallel group study, 39 participants were randomly assigned to receive either 8-hour nightly CPAP (n = 26) or oral placebo (n = 13). Sleep was polysomnographically recorded in the laboratory on each night. CPAP adherence was ensured by continuous supervision. Participants continued their daily routine activities outside the laboratory. Glucose metabolism was assessed at baseline and after 2 weeks of assigned treatment using both the oral and intravenous glucose tolerance tests. The primary outcome was the overall glucose response as quantified by the area under the curve for glucose during 2-hour oral glucose tolerance testing. Secondary outcomes included fasting and 2-hour glucose and insulin, the area under the curves for insulin and insulin secretion, norepinephrine, insulin sensitivity, acute insulin response to glucose, and 24-hour blood pressure. MEASUREMENTS AND MAIN RESULTS: The overall glucose response was reduced (treatment difference: -1,276.9 [mg/dl] · min [95% confidence interval, -2,392.4 to -161.5]; P = 0.03) and insulin sensitivity was improved (treatment difference: 0.77 [mU/L](-1) · min(-1) [95% confidence interval, 0.03-1.52]; P = 0.04) with CPAP as compared with placebo. Additionally, norepinephrine levels and 24-hour blood pressure were reduced with CPAP as compared with placebo. CONCLUSIONS: In patients with prediabetes, 8-hour nightly CPAP treatment for 2 weeks improves glucose metabolism compared with placebo. Thus, CPAP treatment may be beneficial for metabolic risk reduction. Clinical trial registered with www.clinicaltrials.gov (NCT 01156116).

Sleep restriction increases free fatty acids in healthy men.

AIMS/HYPOTHESIS: Sleep loss is associated with insulin resistance and an increased risk for type 2 diabetes, yet underlying mechanisms are not understood. Elevation of circulating non-esterified (i.e. free) fatty acid (NEFA) concentrations can lead to insulin resistance and plays a central role in the development of metabolic diseases. Circulating NEFA in healthy individuals shows a marked diurnal variation with maximum levels occurring at night, yet the impact of sleep loss on NEFA levels across the 24 h cycle remains unknown. We hypothesised that sleep restriction would alter hormones that are known to stimulate lipolysis and lead to an increase in NEFA levels. METHODS: We studied 19 healthy young men under controlled laboratory conditions with four consecutive nights of 8.5 h in bed (normal sleep) and 4.5 h in bed (sleep restriction) in randomised order. The 24 h blood profiles of NEFA, growth hormone (GH), noradrenaline (norepinephrine), cortisol, glucose and insulin were simultaneously assessed. Insulin sensitivity was estimated by a frequently sampled intravenous glucose tolerance test. RESULTS: Sleep restriction relative to normal sleep resulted in increased NEFA levels during the nocturnal and early-morning hours. The elevation in NEFA was related to prolonged nocturnal GH secretion and higher early-morning noradrenaline levels. Insulin sensitivity was decreased after sleep restriction and the reduction in insulin sensitivity was correlated with the increase in nocturnal NEFA levels. CONCLUSIONS/INTERPRETATION: Sleep restriction in healthy men results in increased nocturnal and early-morning NEFA levels, which may partly contribute to insulin resistance and the elevated diabetes risk associated with sleep loss.

New frontiers in obstructive sleep apnoea.

OSA (obstructive sleep apnoea), the most common respiratory disorder of sleep, is caused by the loss of upper airway dilating muscle activity during sleep superimposed on a narrow upper airway. This results in recurrent nocturnal asphyxia. Termination of these events usually requires arousal from sleep and results in sleep fragmentation and hypoxaemia, which leads to poor quality sleep, excessive daytime sleepiness, reduced quality of life and numerous other serious health consequences. Furthermore, patients with untreated sleep apnoea are at an increased risk of hypertension, stroke, heart failure and atrial fibrillation. Although there are many predisposing risk factors for OSA, including male gender, endocrine disorders, use of muscle relaxants, smoking, fluid retention and increased age, the strongest risk factor is obesity. The aim of the present review is to focus on three cutting-edge topics with respect to OSA. The section on animal models covers various strategies used to simulate the physiology or the effects of OSA in animals, and how these have helped to understand some of the underlying mechanisms of OSA. The section on diabetes discusses current evidence in both humans and animal models demonstrating that intermittent hypoxia and sleep fragmentation has a negative impact on glucose tolerance. Finally, the section on cardiovascular biomarkers reviews the evidence supporting the use of these biomarkers to both measure some of the negative consequences of OSA, as well as the potential benefits of OSA therapies.

The effects of extended bedtimes on sleep duration and food desire in overweight young adults: a home-based intervention.

INTRODUCTION: Sleep curtailment is an endemic behavior in modern society. Well-controlled laboratory studies have shown that sleep loss in young adults is associated with increased desire for high-calorie food and obesity risk. However, the relevance of these laboratory findings to real life is uncertain. We conducted a 3 week, within-participant, intervention study to assess the effects of extended bedtimes on sleep duration and food desire under real life conditions in individuals who are at risk for obesity. METHODS: Ten overweight young adults reporting average habitual sleep duration of less than 6.5 h were studied in the home environment. Habitual bedtimes for 1-week (baseline) were followed by bedtimes extended to 8.5 h for 2-weeks (intervention). Participants were unaware of the intervention until after the baseline period. Participants received individualized behavioral counseling on sleep hygiene on the first day of the intervention period. Sleep duration was recorded by wrist actigraphy throughout the study. Participants rated their sleepiness, vigor and desire for various foods using visual analog scales at the end of baseline and intervention periods. RESULTS: On average, participants obtained 1.6 h more sleep with extended bedtimes (5.6 vs. 7.1; P < 0.001) and reported being less sleepy (P = 0.004) and more vigorous (P = 0.034). Additional sleep was associated with a 14% decrease in overall appetite (P = 0.030) and a 62% decrease in desire for sweet and salty foods (P = 0.017). Desire for fruits, vegetables and protein-rich nutrients was not affected by added sleep. CONCLUSIONS: Sleep duration can be successfully increased in real life settings and obtaining adequate sleep is associated with less desire for high calorie foods in overweight young adults who habitually curtail their sleep.

Impaired insulin signaling in human adipocytes after experimental sleep restriction: a randomized, crossover study.

BACKGROUND: Insufficient sleep increases the risk for insulin resistance, type 2 diabetes, and obesity, suggesting that sleep restriction may impair peripheral metabolic pathways. Yet, a direct link between sleep restriction and alterations in molecular metabolic pathways in any peripheral human tissue has not been shown. OBJECTIVE: To determine whether sleep restriction results in reduced insulin sensitivity in subcutaneous fat, a peripheral tissue that plays a pivotal role in energy metabolism and balance. DESIGN: Randomized, 2-period, 2-condition, crossover clinical study. SETTING: University of Chicago Clinical Resource Center. PARTICIPANTS: Seven healthy adults (1 woman, 6 men) with a mean age of 23.7 years (SD, 3.8) and mean body mass index of 22.8 kg/m(2) (SD, 1.6). INTERVENTION: Four days of 4.5 hours in bed or 8.5 hours in bed under controlled conditions of caloric intake and physical activity. MEASUREMENTS: Adipocytes collected from subcutaneous fat biopsy samples after normal and restricted sleep conditions were exposed to incremental insulin concentrations. The ability of insulin to increase levels of phosphorylated Akt (pAkt), a crucial step in the insulin-signaling pathway, was assessed. Total Akt (tAkt) served as a loading control. The insulin concentration for the half-maximal stimulation of the pAkt-tAkt ratio was used as a measure of cellular insulin sensitivity. Total body insulin sensitivity was assessed using a frequently sampled intravenous glucose tolerance test. RESULTS: The insulin concentration for the half-maximal pAkt-tAkt response was nearly 3-fold higher (mean, 0.71 nM [SD, 0.27] vs. 0.24 nM [SD, 0.24]; P = 0.01; mean difference, 0.47 nM [SD, 0.33]; P = 0.01), and the total area under the receiver-operating characteristic curve of the pAkt-tAkt response was 30% lower (P = 0.01) during sleep restriction than during normal sleep. A reduction in total body insulin sensitivity (P = 0.02) paralleled this impaired cellular insulin sensitivity. LIMITATION: This was a single-center study with a small sample size. CONCLUSION: Sleep restriction results in an insulin-resistant state in human adipocytes. Sleep may be an important regulator of energy metabolism in peripheral tissues. PRIMARY FUNDING SOURCE: National Institutes of Health.

Objective and Subjective Sleep Patterns in Adults With Maturity-Onset Diabetes of the Young (MODY).

OBJECTIVE: To examine sleep patterns in adults with maturity-onset diabetes of the young (MODY). RESEARCH DESIGN AND METHODS: Adults with glucokinase (GCK)-MODY and transcription factor (TF)-related MODY (HNF1A, HNF1B, HNF4A) were recruited (n = 24; age 46.0 years, 79% women, BMI 24.7 kg/m2) from The University of Chicago's Monogenic Diabetes Registry. Sleep patterns were assessed by 2-week wrist actigraphy (total 315 nights), one night of a home sleep apnea test, and validated surveys. RESULTS: Overall, compared with established criteria, 29% of participants had sleep latency ≥15 min, 38% had sleep efficiency ≤85%, 46% had wake after sleep onset >40 min, all indicating poor objective sleep quality. Among all participants, 54% had a sleep duration below the recommended minimum of 7 h, 88% reported poor sleep quality, 58% had obstructive sleep apnea, and 71% reported insomnia. Compared with GCK-MODY, participants with TF-related MODY had poorer objective sleep quality and increased night-to-night variability in sleep patterns. CONCLUSIONS: Sleep disturbances appear to be common in adults with MODY despite absent traditional risk factors for sleep disorders. Future research investigating the sleep-diabetes relationship is warranted in this population.

Diet Composition and Objectively Assessed Sleep Quality: A Narrative Review.

Insufficient sleep is highly prevalent in society and has tremendous negative health consequences. Despite the available treatments, there is continued demand for novel and natural strategies to promote better sleep. Dietary modifications could be a viable new target to improve sleep. A literature review using PubMed was conducted on studies that examined the relationship between diet composition (ie, macronutrients or special diets) and objectively assessed sleep quality. Twenty human studies (6 observational and 14 interventional) published between 1975 and March 2021 met the eligibility criteria and were included. The amount of dietary carbohydrates and fats was associated with both better and worse sleep quality indices. However, the type of carbohydrate and fat was an important factor in these associations, with diets higher in complex carbohydrates (eg, fiber) and healthier fats (eg, unsaturated) being associated with better sleep quality. Diets higher in protein were associated with better sleep quality. In general, diets rich in fiber, fruits, vegetables, and anti-inflammatory nutrients and lower in saturated fat (eg, Mediterranean diet) were associated with better sleep quality. The connection between diet and sleep quality warrants further investigation. Rigorous interventional studies of longer duration assessing the effects of whole foods, rather than isolated nutrients, and under free-living conditions, rather than in a research laboratory setting, as well as mechanistic studies are needed to better understand how dietary patterns relate to sleep quality. Future research could provide insights into whether dietary modifications could be an effective, personalized strategy for improving sleep quality in millions of Americans.

Effect of Sleep Extension on Objectively Assessed Energy Intake Among Adults With Overweight in Real-life Settings: A Randomized Clinical Trial.

IMPORTANCE: Short sleep duration has been recognized as a risk factor for obesity. Whether extending sleep duration may mitigate this risk remains unknown. OBJECTIVE: To determine the effects of a sleep extension intervention on objectively assessed energy intake, energy expenditure, and body weight in real-life settings among adults with overweight who habitually curtailed their sleep duration. DESIGN, SETTING, AND PARTICIPANTS: This single-center, randomized clinical trial was conducted from November 1, 2014, to October 30, 2020. Participants were adults aged 21 to 40 years with a body mass index (calculated as weight in kilograms divided by height in meters squared) between 25.0 and 29.9 and had habitual sleep duration of less than 6.5 hours per night. Data were analyzed according to the intention-to-treat principle. INTERVENTIONS: After a 2-week habitual sleep period at baseline, participants were randomized to either an individualized sleep hygiene counseling session that was intended to extend their bedtime to 8.5 hours (sleep extension group) or to continue their habitual sleep (control group). All participants were instructed to continue daily routine activities at home without any prescribed diet or physical activity. MAIN OUTCOMES AND MEASURES: The primary outcome was change in energy intake from baseline, which was objectively assessed as the sum of total energy expenditure and change in body energy stores. Total energy expenditure was measured by the doubly labeled water method. Change in body energy stores was computed using regression of daily home weights and body composition changes from dual-energy x-ray absorptiometry. Sleep duration was monitored by actigraphy. Changes from baseline were compared between the 2 groups using intention-to-treat analysis. RESULTS: Data from 80 randomized participants (mean [SD] age, 29.8 [5.1] years; 41 men [51.3%]) were analyzed. Sleep duration was increased by approximately 1.2 hours per night (95% CI, 1.0 to 1.4 hours; P < .001) in the sleep extension group vs the control group. The sleep extension group had a significant decrease in energy intake compared with the control group (-270 kcal/d; 95% CI, -393 to -147 kcal/d; P < .001). The change in sleep duration was inversely correlated with the change in energy intake (r = -0.41; 95% CI, -0.59 to -0.20; P < .001). No significant treatment effect in total energy expenditure was found, resulting in weight reduction in the sleep extension group vs the control group. CONCLUSIONS AND RELEVANCE: This trial found that sleep extension reduced energy intake and resulted in a negative energy balance in real-life settings among adults with overweight who habitually curtailed their sleep duration. Improving and maintaining healthy sleep duration over longer periods could be part of obesity prevention and weight loss programs. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02253368.

Impact of untreated obstructive sleep apnea on glucose control in type 2 diabetes.

RATIONALE: Obstructive sleep apnea (OSA), a treatable sleep disorder that is associated with alterations in glucose metabolism in individuals without diabetes, is a highly prevalent comorbidity of type 2 diabetes. However, it is not known whether the severity of OSA is a predictor of glycemic control in patients with diabetes. OBJECTIVES: To determine the impact of OSA on hemoglobin A1c (HbA1c), the major clinical indicator of glycemic control, in patients with type 2 diabetes. METHODS: We performed polysomnography studies and measured HbA1c in 60 consecutive patients with diabetes recruited from outpatient clinics between February 2007 and August 2009. MEASUREMENTS AND MAIN RESULTS: A total of 77% of patients with diabetes had OSA (apnea-hypopnea index [AHI] > or =5). Increasing OSA severity was associated with poorer glucose control, after controlling for age, sex, race, body mass index, number of diabetes medications, level of exercise, years of diabetes and total sleep time. Compared with patients without OSA, the adjusted mean HbA1c was increased by 1.49% (P = 0.0028) in patients with mild OSA, 1.93% (P = 0.0033) in patients with moderate OSA, and 3.69% (P < 0.0001) in patients with severe OSA (P < 0.0001 for linear trend). Measures of OSA severity, including total AHI (P = 0.004), rapid eye movement AHI (P = 0.005), and the oxygen desaturation index during total and rapid eye movement sleep (P = 0.005 and P = 0.008, respectively) were positively correlated with increasing HbA1c levels. CONCLUSIONS: In patients with type 2 diabetes, increasing severity of OSA is associated with poorer glucose control, independent of adiposity and other confounders, with effect sizes comparable to those of widely used hypoglycemic drugs.

Slow-wave sleep and the risk of type 2 diabetes in humans.

There is convincing evidence that, in humans, discrete sleep stages are important for daytime brain function, but whether any particular sleep stage has functional significance for the rest of the body is not known. Deep non-rapid eye movement (NREM) sleep, also known as slow-wave sleep (SWS), is thought to be the most "restorative" sleep stage, but beneficial effects of SWS for physical well being have not been demonstrated. The initiation of SWS coincides with hormonal changes that affect glucose regulation, suggesting that SWS may be important for normal glucose tolerance. If this were so, selective suppression of SWS should adversely affect glucose homeostasis and increase the risk of type 2 diabetes. Here we show that, in young healthy adults, all-night selective suppression of SWS, without any change in total sleep time, results in marked decreases in insulin sensitivity without adequate compensatory increase in insulin release, leading to reduced glucose tolerance and increased diabetes risk. SWS suppression reduced delta spectral power, the dominant EEG frequency range in SWS, and left other EEG frequency bands unchanged. Importantly, the magnitude of the decrease in insulin sensitivity was strongly correlated with the magnitude of the reduction in SWS. These findings demonstrate a clear role for SWS in the maintenance of normal glucose homeostasis. Furthermore, our data suggest that reduced sleep quality with low levels of SWS, as occurs in aging and in many obese individuals, may contribute to increase the risk of type 2 diabetes.

Role of obstructive sleep apnea in metabolic risk in PCOS.

Women with polycystic ovary syndrome (PCOS) have a substantially increased risk for diabetes and cardiovascular disease. Obstructive sleep apnea (OSA) is the most common sleep disorder in PCOS. Recent population-based studies indicate a high incidence of OSA among adult women with PCOS. Obesity and increasing age are the main factors for this association. There is strong evidence indicating that OSA is an important modulator of metabolic risk in the general population. There is also some evidence to suggest that OSA may contribute to insulin resistance and glucose intolerance among women PCOS, and thus increase their metabolic risk. The potential mechanisms for adverse metabolic consequences of OSA are likely to be multiple. Whether treatment of OSA in PCOS improves metabolic outcomes requires further rigorous research.

Optimal Continuous Positive Airway Pressure Treatment of Obstructive Sleep Apnea Reduces Daytime Resting Heart Rate in Prediabetes: A Randomized Controlled Study.

Background It has been widely recognized that obstructive sleep apnea (OSA) is linked to cardiovascular disease. Yet, randomized controlled studies failed to demonstrate a clear cardiovascular benefit from OSA treatment, mainly because of poor adherence to continuous positive airway pressure (CPAP). To date, no prior study has assessed the effect of CPAP treatment on daytime resting heart rate, a strong predictor of adverse cardiovascular outcomes and mortality. Methods and Results We conducted a randomized controlled study in 39 participants with OSA and prediabetes, who received either in-laboratory all-night (ie, optimal) CPAP or an oral placebo for 2 weeks. During daytime, participants continued daily activities outside the laboratory. Resting heart rate was continuously assessed over 19 consecutive days and nights using an ambulatory device consisting of a single-lead ECG and triaxis accelerometer. Compared with placebo, CPAP reduced daytime resting heart rate (treatment difference, -4.1 beats/min; 95% CI, -6.5 to -1.7 beats/min; P=0.002). The magnitude of reduction in daytime resting heart rate after treatment significantly correlated with the magnitude of decrease in plasma norepinephrine, a marker of sympathetic activity (r=0.44; P=0.02), and the magnitude of decrease in OSA severity (ie, apnea-hypopnea index [r=0.48; P=0.005], oxygen desaturation index [r=0.50; P=0.003], and microarousal index [r=0.57; P<0.001]). Conclusions This proof-of-concept randomized controlled study demonstrates, for the first time, that CPAP treatment, when optimally used at night, reduces resting heart rate during the day, and therefore has positive cardiovascular carry over effects. These findings suggest that better identification and treatment of OSA may have important clinical implications for cardiovascular disease prevention. Registration URL: https:/// www.clini​caltr​ials.gov; Unique identifier: NCT01156116.

Impact of obstructive sleep apnea on insulin resistance and glucose tolerance in women with polycystic ovary syndrome.

CONTEXT: Insulin resistance, impaired glucose tolerance, and type 2 diabetes are common in women with polycystic ovary syndrome (PCOS). Obstructive sleep apnea (OSA) has been linked to metabolic dysfunction. We studied women with and without PCOS to determine the extent to which OSA is responsible for insulin resistance and glucose intolerance in PCOS. METHODS: In a prospective design, 52 women with PCOS and 21 women without PCOS of similar age and body mass index had an overnight polysomnogram and a 75-g oral glucose tolerance test. RESULTS: Twenty-nine women (56%) with PCOS had OSA compared with four controls (19%) (adjusted odds ratio 7.1; 95% confidence interval, 1.7-45.7; P = 0.01). PCOS women with OSA were more insulin resistant than those without OSA [homeostasis model assessment (HOMA) index 5.7 +/- 0.4 vs. 3.5 +/- 0.4; P = 0.006] after controlling for age, body mass index, and ethnicity. Impaired glucose tolerance was found in 16 of 29 (55%) PCOS women with OSA and only six of 23 (26%) of those without OSA (unadjusted P = 0.049). Insulin resistance and glucose intolerance were highly correlated with the presence and severity of OSA. Among PCOS women with normal glucose tolerance, the presence of OSA was associated with a nearly 2-fold higher fasting insulin level and HOMA index. The severity of OSA was a highly significant predictor of the fasting concentrations of glucose and insulin as well as the 2-h glucose concentration and HOMA index. CONCLUSIONS: OSA is a highly prevalent and important determinant of insulin resistance, glucose intolerance, and type 2 diabetes in PCOS.

Obstructive sleep apnea and type 2 diabetes: interacting epidemics.

Type 2 diabetes is a major public health concern with high morbidity, mortality, and health-care costs. Recent reports have indicated that the majority of patients with type 2 diabetes also have obstructive sleep apnea (OSA). There is compelling evidence that OSA is a significant risk factor for cardiovascular disease and mortality. Rapidly accumulating data from both epidemiologic and clinical studies suggest that OSA is also independently associated with alterations in glucose metabolism and places patients at an increased risk of the development of type 2 diabetes. Experimental studies in humans and animals have demonstrated that intermittent hypoxia and reduced sleep duration due to sleep fragmentation, as occur in OSA, exert adverse effects on glucose metabolism. Based on the current evidence, clinicians need to address the risk of OSA in patients with type 2 diabetes and, conversely, evaluate the presence of type 2 diabetes in patients with OSA. Clearly, there is a need for further research, using well-designed studies and long-term follow-up, to fully demonstrate a causal role for OSA in the development and severity of type 2 diabetes. In particular, future studies must carefully consider the confounding effects of central obesity in examining the link between OSA and alterations in glucose metabolism. The interactions among the rising epidemics of obesity, OSA, and type 2 diabetes are likely to be complex and involve multiple pathways. A better understanding of the relationship between OSA and type 2 diabetes may have important public health implications.

Shared Genetic Control of Brain Activity During Sleep and Insulin Secretion: A Laboratory-Based Family Study.

Over the past 20 years, a large body of experimental and epidemiologic evidence has linked sleep duration and quality to glucose homeostasis, although the mechanistic pathways remain unclear. The aim of the current study was to determine whether genetic variation influencing both sleep and glucose regulation could underlie their functional relationship. We hypothesized that the genetic regulation of electroencephalographic (EEG) activity during non-rapid eye movement sleep, a highly heritable trait with fingerprint reproducibility, is correlated with the genetic control of metabolic traits including insulin sensitivity and ß-cell function. We tested our hypotheses through univariate and bivariate heritability analyses in a three-generation pedigree with in-depth phenotyping of both sleep EEG and metabolic traits in 48 family members. Our analyses accounted for age, sex, adiposity, and the use of psychoactive medications. In univariate analyses, we found significant heritability for measures of fasting insulin sensitivity and ß-cell function, for time spent in slow-wave sleep, and for EEG spectral power in the delta, theta, and sigma ranges. Bivariate heritability analyses provided the first evidence for a shared genetic control of brain activity during deep sleep and fasting insulin secretion rate.