Ertugliflozin and incident obstructive sleep apnea: an analysis from the VERTIS CV trial.

PURPOSE: The sodium-glucose transporter 2 inhibitor (SGLT2i) empagliflozin may reduce the incidence of obstructive sleep apnea (OSA) in patients with type 2 diabetes (T2D) and cardiovascular (CV) disease. This analysis of VERTIS CV, the CV outcome trial for the SGLT2i ertugliflozin conducted in a similar group of patients, explored the effects of ertugliflozin on reported incident OSA. METHODS: In VERTIS CV, patients ≥ 40 years with T2D and atherosclerotic CV disease (ASCVD) were randomized to ertugliflozin 5 or 15 mg or placebo. The primary endpoint was the composite of major adverse CV events. This exploratory analysis evaluated the impact of ertugliflozin (5 and 15 mg pooled) on incident OSA. Patients with prevalent OSA were excluded. Incident OSA events were based on investigator-reported events using the MedDRA SMQ term "sleep apnea syndrome." A multivariable Cox proportional hazards regression model was constructed to assess the association between ertugliflozin and incident OSA. RESULTS: Of 8246 patients enrolled, 7697 (93.3%) were without baseline OSA (placebo, n = 2561; ertugliflozin, n = 5136; mean age 64.4 years; BMI 31.7 kg/m2; HbA1c, 8.2%; 69.2% male; 88.3% White). The OSA incidence rate was 1.44 per 1000 person-years versus 2.61 per 1000 person-years among patients treated with ertugliflozin versus placebo, respectively, corresponding to a 48% relative risk reduction (HR 0.52; 95% CI 0.28-0.96; P = 0.04). CONCLUSIONS: In VERTIS CV, ertugliflozin reduced by nearly half the incidence of OSA in patients with T2D and ASCVD. These data contribute to the literature that SGLT2is may have a significant beneficial impact on OSA. CLINICALTRIALS: gov identifier: NCT01986881.

Symptom Cluster Profiles Among Adults with Insomnia and Heart Failure.

OBJECTIVE/BACKGROUND: Both heart failure (HF) and insomnia are associated with high symptom burden that may be manifested in clustered symptoms. To date, studies of insomnia have focused only on its association with single symptoms. The purposes of this study were to: (1) describe daytime symptom cluster profiles in adults with insomnia and chronic HF; and (2) determine the associations between demographic and clinical characteristics, insomnia and sleep characteristics and membership in symptom cluster profiles. PARTICIPANTS: One hundred and ninety-five participants [M age 63.0 (SD12.8); 84 (43.1%) male; 148 (75.9%) New York Heart Association Class I/II] from the HeartSleep study (NCT0266038), a randomized controlled trial of the sustained effects of cognitive behavioral therapy for insomnia (CBT-I). METHODS: We analyzed baseline data, including daytime symptoms (fatigue, pain, anxiety, depression, dyspnea, sleepiness) and insomnia (Insomnia Severity Index), and sleep characteristics (Pittsburgh Sleep Quality Index, wrist actigraphy). We conducted latent class analysis to identify symptom cluster profiles, bivariate associations, and multinomial regression. RESULTS: We identified three daytime symptom cluster profiles, physical (N = 73 participants; 37.4%), emotional (N = 12; 5.6%), and all-high symptoms (N = 111; 56.4%). Body mass index, beta blockers, and insomnia severity were independently associated with membership in the all-high symptom profile, compared with the other symptom profile groups. CONCLUSIONS: Higher symptom burden is associated with more severe insomnia in people with stable HF. There is a need to understand whether treatment of insomnia improves symptom burden as reflected in transition from symptom cluster profiles reflecting higher to lower symptom burden.

Using Sleep Interventions to Engage and Treat Heavy-Drinking College Students: A Randomized Pilot Study.

BACKGROUND: Continued high alcohol consumption levels by college students highlight the need for more effective alcohol interventions and novel treatment engagement strategies. The purpose of this study was to investigate a behavioral sleep intervention as a means to engage heavy-drinking college students in treatment and reduce alcohol use and alcohol-related consequences. METHODS: Heavy-drinking college students (N = 42) were assigned to 1 of 2 web-based interventions comprised of 4 modules delivered over 4 weeks. The experimental intervention focused primarily on sleep and included evidence-based sleep content (i.e., stimulus control instructions, sleep scheduling [consistent bed/rise times; ideal sleep duration for adolescents/young adults], sleep hygiene advice, relaxation training, cognitive strategies to target sleep-disruptive beliefs), and alcohol content (i.e., normative and blood alcohol level feedback, moderate drinking guidelines, controlled drinking strategies, effects of alcohol on sleep and the body, advice to moderate drinking for improved sleep) in young adults. The control condition Healthy Behaviors provided basic advice about nutrition, exercise, sleep (i.e., good sleep hygiene only), and drinking (i.e., effects of alcohol on the body, moderate drinking guidelines, advice to moderate drinking for sleep). Participants in both conditions monitored their sleep using daily web-based diaries and a wrist-worn sleep tracker. RESULTS: Recruitment ads targeting college students with sleep concerns effectively identified heavy-drinking students. The program generated a high number of inquiries and treatment completion rates were high. Both interventions significantly reduced typical week drinking and alcohol-related consequences and improved sleep quality and sleep-related impairment ratings. The control condition yielded greater reductions in total drinks in a heaviest drinking week. The effects on drinking were larger than those observed in typical brief alcohol intervention studies for college students. Greater sleep improvement tended to predict better subsequent drinking outcomes. CONCLUSIONS: The results suggest that sleep treatment may be a promising strategy for targeting and treating heavy-drinking college students.

Reducing cardiovascular risk through treatment of obstructive sleep apnea: 2 methodological approaches.

Obstructive sleep apnea (OSA) significantly impacts cardiovascular health, demonstrated by observational investigations showing an independently increased risk of ischemic heart disease, diabetes, hypertension, congestive heart failure, acute coronary syndrome, stroke, cardiovascular mortality, and all-cause mortality. Positive airway pressure (PAP), a medical therapy for sleep apnea, reverses airway obstruction and may help reduce cardiovascular risk. Prior to planning large phase III randomized controlled trials to test the impact of PAP on cardiovascular outcomes, several gaps in knowledge need to be addressed. This article describes 2 independent studies that worked collaboratively to fill these gaps. The populations, design features, and relative benefits/challenges of the 2 studies (SleepTight and BestAIR) are described. Both studies were encouraged to have multidisciplinary teams with expertise in behavioral interventions to improve PAP compliance. Both studies provide key information that will be useful to the research community in future large-scale, event-driven, randomized trials to evaluate the efficacy and/or effectiveness of strategies to identify and treat significant OSA for decreasing risk of major adverse cardiovascular events in high-risk patients.

Observational Study of Obstructive Sleep Apnea in Wake-Up Stroke: The SLEEP TIGHT Study.

BACKGROUND: Wake-up stroke (WUS) accounts for a quarter of all ischemic strokes. Its conspicuous occurrence during sleep suggests that WUS may be associated with obstructive sleep apnea (OSA). We investigated the potential association among WUS, OSA, and measures of sympathetic hyperactivity. METHODS: This is a cross-sectional analysis of data from the Sleep Apnea in Transient Ischemic Attack and Stroke (SLEEP TIGHT) study. Ischemic stroke patients were divided into WUS and non-WUS groups. Participants underwent polysomnography and ambulatory blood pressure monitoring. Collected data included demographic, medical, stroke characteristics (including severity by National Institutes of Health Stroke Scale), cholesterol, serum catecholamines, C-reactive protein, interleukin-6, B-type natriuretic peptide, blood pressure, and polysomnographic (apnea-hypopnea index (AHI); measures of hypoxia). Because both stroke and OSA affect men and women to varying degrees, the cohort was considered as a whole and by gender stratification. RESULTS: Among 164 participants, 30.3% had WUS. The mean age was 62.0 ± 11.3 and the mean body mass index was 30.2 ± 7.9 kg/m2. One-hundred-and-five participants (63.6%) were males and 92 participants (56.8%) were Caucasian. Neither AHI nor OSA (AHI ≥5) frequency differed between WUS and non-WUS groups. Men tended to be more likely than women to have WUS (74.0 vs. 59.6%; p = 0.08), but this was not statistically significant. In gender-stratified analyses, men with WUS compared to men with non-WUS had significantly higher rates of severe OSA (AHI >30: 45.0 vs. 17.6%; p = 0.03) and tended toward more 3% oxygen desaturation events (57.0 ± 63.9 vs. 31.8 ± 22.9; p = 0.06). These differences were not seen in women. WUS patients tended to be of the male gender (74.0 vs. 59.6%; p = 0.08). History of stroke, hypertension, diabetes, dyslipidemia, or atrial fibrillation, serum catecholamines, and inflammatory biomarkers was no different between the groups. Low-density lipoprotein (LDL) was significantly higher in WUS (114.5 ± 36.3 vs. 101.4 ± 37.6; p = 0.04). Baseline diastolic blood pressure (DBP) was significantly greater in the WUS group. There was no difference in systolic or ambulatory blood pressure (including nighttime blood pressure) between WUS and non-WUS groups. CONCLUSIONS: WUS may be associated with severe OSA with more oxygen desaturation in men but not in women. WUS may be associated with high DBP and increased LDL cholesterol.

Polysomnographic predictors of incident diabetes and pre-diabetes: an analysis of the DREAM study.

STUDY OBJECTIVES: We sought to evaluate sleep measures that better predict incident diabetes and prediabetes in a large cohort of veterans. METHODS: This secondary analysis included 650 patients without baseline diabetes from a multisite observational veterans' cohort. Participants underwent obstructive sleep apnea evaluation via laboratory-based polysomnography between 2000 and 2004 with follow-up through 2012. The primary outcomes were prediabetes and diabetes defined by fasting blood glucose, hemoglobin A1c, or use of glucose-lowering medication at study initiation. Exposure variables included respiratory event frequency, arousals, and oxygen desaturation. Cox models adjusted for body mass index, age, race, sex, change in body mass index, and continuous positive airway pressure device utilization. RESULTS: The adjusted analysis revealed that time spent with oxygen saturation less than 90 [hazards ratio (HR) 1.009], confidence interval (CI) 1.001-1.017, P = .02), respiratory arousals (HR 1.009, CI 1.003-1.015, P < 0.01) and total arousals (HR 1.006 CI 1.001-1.011 P = .02) were associated with an increased incidence of diabetes. Increases in mean nocturnal oxygen saturation were associated with decreased incidence of diabetes (HR 0.914 CI 0.857-0.975, P < .01) and prediabetes (HR 0.914 CI 0.857-0.975, P < .01). No significant relationships were demonstrated for apnea-hypopnea index (AHI), measures related to central apnea, Cheyne-Stokes respiration, periodic limb movements, or Epworth Sleepiness Scale score. CONCLUSIONS: There was no significant association of incident prediabetes or diabetes with AHI, the gold standard of sleep apnea severity. This study suggests that hypoxia may be a better predictor of glycemic outcomes than AHI in an obstructive sleep apnea population and may provide clues to the underlying mechanism(s) that link sleep-disordered breathing and its metabolic consequences. CITATION: Wojeck BS, Inzucchi SE, Qin L, Yaggi HK. Polysomnographic predictors of incident diabetes and pre-diabetes: an analysis of the DREAM study. J Clin Sleep Med. 2023;19(4):703-710.

Insomnia with objective short sleep duration in community-living older persons: A multifactorial geriatric health condition.

BACKGROUND: Insomnia or poor sleep quality with objective short sleep duration (hereafter referred to as ISSD) has been identified as a high-risk phenotype among middle-aged persons. We evaluated the prevalence and clinical correlates of ISSD among community-living older persons. METHODS: In 3053 men from the Osteoporotic Fractures in Men Sleep Study (MrOS; average age 76.4 ± 5.5 years) and 3044 women from the Study of Osteoporotic Fractures (SOF; average age 83.6 ± 3.8 years), we evaluated the prevalence of ISSD (trouble getting to sleep within 30 minutes, waking up in the middle of the night or early morning, and/or taking a medication to help with sleep ≥3 times per week and actigraphy-estimated sleep duration <6 h). Using separate logistic regression models in men and women, we evaluated the cross-sectional associations between predisposing, precipitating, and perpetuating factors for ISSD, as compared with normal sleep (no insomnia and actigraphy-estimated sleep duration of 6-9 h). RESULTS: Overall, 20.6% of older men and 12.8% of older women had insomnia with short sleep duration. Multiple predisposing, precipitating, and perpetuating factors were cross-sectionally associated with ISSD in both men and women. In multivariable models that adjusted for predisposing factors (demographics, multimorbidity, obesity), precipitating (depression, anxiety, central nervous system-active medication use, restless legs syndrome) and perpetuating (napping, falls) factors were significantly associated with ISSD in men and women (adjusted odds ratios ranging 1.63-4.57). CONCLUSIONS: In this cross-sectional study of community-living older men and women, ISSD was common and associated with multiple predisposing, precipitating, and perpetuating factors, akin to a multifactorial geriatric health condition. Future work should examine causal pathways and determine whether the identified correlates represent modifiable risk factors.

Self-reported and actigraphic short sleep duration in older adults.

STUDY OBJECTIVES: Persons > 65 years with short sleep duration (≤ 6 hours) are at risk for adverse outcomes, but the accuracy of self-reported sleep duration may be affected by reduced symptom awareness. We evaluated the performance characteristics of self-reported vs objectively measured sleep duration in this age group. METHODS: In 2,980 men from the Osteoporotic Fractures in Men Sleep Study and 2,855 women from the Study of Osteoporotic Fractures we examined the agreement and accuracy of self-reported vs actigraphy-measured short and normal (> 6 but < 9 hours) sleep duration. We evaluated associations of select factors (demographics; medical, physical, and neuropsychiatric conditions; medication and substance use; and sleep-related measures) with risk of false-negative (normal sleep duration by self-report but short sleep duration by actigraphy) and false-positive (short sleep duration by self-report and normal sleep duration by actigraphy) designations, respectively, using logistic regression. RESULTS: Average ages were 76.3 ± 5.5 and 83.5 ± 3.7 years in men and women, respectively. There was poor agreement between self-reported and actigraphic sleep duration (kappa ≤ 0.24). False negatives occurred in nearly half and false positives in over a quarter of older persons. In multivariable models in men and women, false negatives were independently associated with obesity, daytime sleepiness, and napping, while false positives were significantly lower with obesity. CONCLUSIONS: Under- and overreporting of short sleep is common among older persons. Reliance on self-report may lead to missed opportunities to prevent adverse outcomes or unnecessary interventions. Self-reported sleep duration should be objectively confirmed when evaluating the effect of sleep duration on health outcomes. CITATION: Miner B, Stone KL, Zeitzer JM, et al. Self-reported and actigraphic short sleep duration in older adults. J Clin Sleep Med. 2022;18(2):403-413.

Cognitive behavioral therapy for insomnia has sustained effects on insomnia, fatigue, and function among people with chronic heart failure and insomnia: the HeartSleep Study.

STUDY OBJECTIVES: Insomnia is common among adults with chronic heart failure (HF) and associated with daytime symptoms and decrements in function. The purpose of this randomized controlled trial (RCT) was to evaluate the sustained effects over one year of CBT-I (Healthy Sleep: HS) compared with HF self-management education (Healthy Hearts; attention control: HH) on insomnia severity, sleep characteristics, symptoms, and function among people with stable HF. The primary outcomes were insomnia severity, actigraph-recorded sleep efficiency, and fatigue. METHODS: We randomized adults with stable HF with preserved or reduced ejection fraction who had at least mild insomnia (Insomnia severity index >7) in groups to HS or HH (4 sessions/8 weeks). We obtained wrist actigraphy and measured insomnia severity, self-reported sleep characteristics, symptoms (fatigue, excessive daytime sleepiness, anxiety, depression), and six-minute walk distance at baseline, within one month of treatment, and at 6 and 12 months. We used general linear mixed models (GLMM) and generalized estimating equations (GEE) to evaluate the effects. RESULTS: The sample included 175 participants (M age = 63 ± 12.9 years; 43% women; 18% Black; 68% New York Heart Association Class II or II; 33%; LVEF < 45%) randomized to HS (n = 91) or HH (n = 84). HS had sustained effects on insomnia severity, sleep quality, self-reported sleep latency and efficiency, fatigue, excessive daytime sleepiness, and six-minute walk distance at 12 months. CONCLUSIONS: CBT-I produced sustained improvements in insomnia, fatigue, daytime sleepiness, and objectively measured physical function among adults with chronic HF, compared with a robust HF self-management program that included sleep hygiene education. CLINICAL TRIAL INFORMATION: Insomnia Self-Management in Heart Failure; https://clinicaltrials.gov/ct2/show/NCT02660385; NCT02660385.

PreScription DigitaL ThErapEutic for Patients with Insomnia (SLEEP-I): a protocol for a pragmatic randomised controlled trial.

INTRODUCTION: Cognitive behavioural therapy for insomnia (CBT-I) is effective at treating chronic insomnia, yet in-person CBT-I can often be challenging to access. Prior studies have used technology to bridge barriers but have been unable to extensively assess the impact of the digital therapeutic on real-world patient experience and multidimensional outcomes. Among patients with insomnia, our aim is to determine the impact of a prescription digital therapeutic (PDT) (PEAR-003b, FDA-authorised as Somryst; herein called PDT) that provides mobile-delivered CBT-I on patient-reported outcomes (PROs) and healthcare utilisation. METHODS AND ANALYSIS: We are conducting a pragmatically designed, prospective, multicentre randomised controlled trial that leverages Hugo, a unique patient-centred health data-aggregating platform for data collection and patient follow-up from Hugo Health. A total of 100 participants with insomnia from two health centres will be enrolled onto the Hugo Health platform, provided with a linked Fitbit (Inspire 2) to track activity and then randomised 1:1 to receive (or not) the PDT for mobile-delivered CBT-I (Somryst). The primary outcome is a change in the insomnia severity index score from baseline to 9-week postrandomisation. Secondary outcomes include healthcare utilisation, health utility scores and clinical outcomes; change in sleep outcomes as measured with sleep diaries and a change in individual PROs including depressive symptoms, daytime sleepiness, health status, stress and anxiety. For those allocated to the PDT, we will also assess engagement with the PDT. ETHICS AND DISSEMINATION: The Institutional Review Boards at Yale University and the Mayo Clinic have approved the trial protocol. This trial will provide important data to patients, clinicians and policymakers about the impact of the PDT device delivering CBT-I on PROs, clinical outcomes and healthcare utilisation. Findings will be disseminated to participants, presented at professional meetings and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04909229.

Obstructive sleep apnea as a risk factor for coronary events or cardiovascular death.

PURPOSE: This study aims to determine whether obstructive sleep apnea independently increases the risk of coronary events, including death from cardiovascular causes. METHODS: We conducted an observational cohort study among consecutive patients >or=50 years of age who were referred during 1997-2001 to the Yale Center for Sleep Medicine for suspected sleep-disordered breathing and were followed longitudinally for subsequent coronary events or cardiovascular death. Each study participant underwent an overnight polysomnography; obstructive sleep apnea was defined as an apnea-hypopnea index >or=5/h. The composite outcome during a mean duration of follow-up of 2.9 years was myocardial infarction, coronary artery revascularization procedures (angioplasty, stent placement, or coronary artery bypass graft surgery), or death from cardiovascular causes. RESULTS: Among 1,436 enrolled patients, 1,024 (71%) had an apnea-hypopnea index >or=5/h. In an unadjusted analysis, obstructive sleep apnea was associated with an increased risk of coronary events or cardiovascular death (hazard ration (HR) 2.57, 95% confidence interval (CI) 1.39-4.72, P = 0.003). After adjustment for traditional cardiovascular risk factors (including body mass index and hypertension), obstructive sleep apnea retained a statistically significant association with this composite outcome (HR 2.06, 95% CI 1.10-3.86, P = 0.024). CONCLUSION: Obstructive sleep apnea increases the risk of coronary events or death from cardiovascular causes.

Sleep and Glycemia in Youth With Type 1 Diabetes.

INTRODUCTION: Short sleep duration and quality are problems for many youth, and are associated with difficulties in executive function. Our purpose was to describe subjective and objective sleep characteristics and their associations with executive function, stress and coping, adjustment, and self-management in youth with type 1 diabetes (T1D). METHOD: Youth with T1D (N = 40; mean age, 13.4 ± 1.9 years; 60% female; 77.1% non-Hispanic white; diabetes duration, 7.1 ± 4.6 years; and hemoglobin A1c, 8.2 ± 1.2%) wore an actigraph and a continuous glucose monitor for 3-7 days and completed questionnaires. Descriptive and bivariate analyses were conducted. RESULTS: Sleep variability was associated with stress and depressive symptoms, as well as more glucose variability. Consistent rest-activity rhythm timing was associated with fewer trait anxiety symptoms. Robust rhythms were associated with better diabetes self-management. DISCUSSION: Providers should routinely assess sleep habits in youth, especially those with T1D. Improving consistency in sleep timing and sleep duration may be a potential therapeutic target to improve diabetes clinical outcomes.

The Epidemiology of Patient-Reported Hypersomnia in Persons With Advanced Age.

OBJECTIVE: To examine the epidemiology and key demographic and clinical correlates of patient-reported hypersomnia in persons with advanced age. DESIGN: Cross-sectional design. SETTING: Community. PARTICIPANTS: A total of 357 community-dwelling persons from the Yale Precipitating Events Project with a mean age of 84.2 years (range = 78-102 years). MEASUREMENTS: We studied patient-reported hypersomnia, defined categorically by an Epworth Sleepiness Scale (ESS) score of 10 or greater; as well as the severity of hypersomnia symptoms, defined continuously by an ESS score range of 0 to 24 (higher scores denote greater sleepiness). In multivariable regression models, we examined cross-sectional associations between key correlates and ESS score, expressed as categorical and continuous variables. Key correlates included: demographics, education, smoking status, body mass index, self-reported medical conditions, Center for Epidemiologic Studies Depression score, Mini-Mental State Examination score, Physical Activity Scale for the Elderly, restless legs syndrome (RLS), self-reported sleep-disordered breathing (SDB), medications, and Insomnia Severity Index. RESULTS: Mean ESS score for all participants was 6.4. Patient-reported hypersomnia (ESS score ≥10) was established in 82 participants (23.0%)-their mean ESS score was 13.0. In multivariable models, male sex, nonwhite race, arthritis, depressive symptoms, low physical activity, RLS, SDB, central nervous system depressant medications, and insomnia severity were cross-sectionally associated with patient-reported hypersomnia (higher adjusted odds ratios, ranging from 1.93-2.86) and/or with the severity of hypersomnia symptoms (higher ESS scores, ranging from 0.11-2.86 points). CONCLUSION: Patient-reported hypersomnia was prevalent in a sample of community-dwelling persons with advanced age. In addition, based on cross-sectional associations with the ESS score, key demographic and clinical characteristics were identified that may inform screening strategies for hypersomnia in advanced age. J Am Geriatr Soc 67:2545-2552, 2019.

Respiratory impairment and mortality in older persons: a novel spirometric approach.

BACKGROUND: The Lambda-Mu-Sigma (LMS) method calculates the lower limit of normal for spirometric measures of pulmonary function as the fifth percentile of the distribution of z scores, suitably accounting for age-related changes in pulmonary function. Extending prior work, and to assess whether the LMS method is clinically valid when evaluating respiratory impairment in the elderly, our current objective was to evaluate the association of LMS-defined respiratory impairment (airflow limitation and restrictive pattern) with all-cause mortality and respiratory symptoms (chronic bronchitis, dyspnea, or wheezing) in older persons. METHODS: Spirometric data and outcome data on white participants aged 65 to 80 years were obtained from the Third National Health and Nutrition Examination Survey (NHANES-III, n = 1497) and the Cardiovascular Health Study (CHS, n = 3583). Multivariable analyses determined the corresponding associations, adjusting for important covariates. RESULTS: In the NHANES-III and CHS populations, respectively, LMS-defined airflow limitation had adjusted hazard ratios (95% confidence interval) of 1.64 (1.28-2.11) and 1.69 (1.48-1.92) for mortality; adjusted odds ratios for respiratory symptoms were 2.71 (1.92-3.83) and 2.63 (2.11-3.27). The LMS-defined restrictive pattern was also significantly associated with mortality (adjusted hazard ratios of 1.98 [1.54-2.53] and 1.68 [1.44-1.95]), as well as with respiratory symptoms (adjusted odds ratios of 1.55 [1.03-2.34] and 1.37 [1.07-1.75]) in NHANES-III and CHS, respectively. CONCLUSIONS: The LMS-defined airflow limitation and restrictive pattern confers a significantly increased risk of death and likelihood of having respiratory symptoms. These results support the use of LMS-derived spirometric z scores as a basis for evaluating respiratory impairment in older persons.

Obstructive sleep apnea as a risk factor for type 2 diabetes.

PURPOSE: Cross-sectional studies have documented the co-occurrence of obstructive sleep apnea (hereafter, sleep apnea) with glucose intolerance, insulin resistance, and type 2 diabetes mellitus (hereafter, diabetes). It has not been determined, however, whether sleep apnea is independently associated with the subsequent development of diabetes, accounting for established risk factors. METHODS: This observational cohort study examined 1233 consecutive patients in the Veteran Affairs Connecticut Healthcare System referred for evaluation of sleep-disordered breathing; 544 study participants were free of preexisting diabetes and completed a full, attended, diagnostic polysomnogram. The study population was divided into quartiles based on severity of sleep apnea as measured by the apnea-hypopnea index. The main outcome was incident diabetes defined as fasting glucose level >126 mg/dL and a corresponding physician diagnosis. Compliance with positive airway pressure therapy, and its impact on the main outcome, also was examined. RESULTS: In unadjusted analysis, increasing severity of sleep apnea was associated with an increased risk of diabetes (P for linear trend <.001). After adjusting for age, sex, race, baseline fasting blood glucose, body mass index, and weight change, an independent association was found between sleep apnea and incident diabetes (hazard ratio per quartile 1.43; confidence interval 1.10-1.86). Among patients with more severe sleep apnea (upper 2 quartiles of severity), 60% had evidence of regular positive airway pressure use, and this treatment was associated with an attenuation of the risk of diabetes (log-rank test P=.04). CONCLUSION: Sleep apnea increases the risk of developing diabetes, independent of other risk factors. Among patients with more severe sleep apnea, regular positive airway pressure use may attenuate this risk.