ABSTRACT
STUDY OBJECTIVES: To examine whether the initial benefit of weight loss on obstructive sleep apnea (OSA) severity at 1 year is maintained at 4 years. DESIGN: Randomized controlled trial with follow-up at 1, 2, and 4 years. SETTING: 4 Look AHEAD clinical centers. PARTICIPANTS: Two hundred sixty-four obese adults with type 2 diabetes and OSA. INTERVENTIONS: Intensive lifestyle intervention with a behavioral weight loss program or diabetes support and education. MEASUREMENTS: Change in apnea-hypopnea index on polysomnogram. RESULTS: The intensive lifestyle intervention group's mean weight loss was 10.7 ± 0.7 (standard error), 7.4 ± 0.7, and 5.2 ± 0.7 kg at 1, 2, and 4 years respectively, compared to a less than 1-kg weight loss for the control group at each time (P < 0.001). Apnea-hypopnea index difference between groups was 9.7 ± 2.0, 8.0 ± 2.0, and 7.7 ± 2.3 events/h at 1, 2 and 4 years respectively (P < 0.001). Change in apnea-hypopnea index over time was related to the amount of weight loss (P < 0.0001) and intervention, independent of weight loss (P = 0.001). Remission of OSA at 4 years was 5 times more common with intensive lifestyle intervention (20.7%) than diabetes support and education (3.6%). CONCLUSIONS: Among obese adults with type 2 diabetes and OSA, intensive lifestyle intervention produced greater reductions in weight and apnea-hypopnea index over a 4 year period than did diabetes support and education. Beneficial effects of intensive lifestyle intervention on apneahypopnea index at 1 year persisted at 4 years, despite an almost 50% weight regain. Effect of intensive lifestyle intervention on apnea-hypopnea index was largely, but not entirely, due to weight loss.
Subject(s)
Diabetes Mellitus, Type 2/therapy , Life Style , Obesity/therapy , Sleep Apnea, Obstructive/therapy , Weight Loss , Adult , Aged , Body Mass Index , Diabetes Mellitus, Type 2/complications , Feeding Behavior , Female , Follow-Up Studies , Humans , Male , Middle Aged , Obesity/complications , Patient Education as Topic , Polysomnography , Severity of Illness Index , Sleep Apnea, Obstructive/complications , Time Factors , Treatment OutcomeABSTRACT
STUDY OBJECTIVES: Type 2 diabetes mellitus (T2DM) and obstructive sleep apnea (OSA) are common, increasingly recognized as comorbid conditions, and individually implicated in the development of cardiovascular disease (CVD). We sought to determine the association between OSA and CVD in an overweight and obese population with T2DM. DESIGN: Cross-sectional. SETTING: Ancillary study to the Look AHEAD trial. PARTICIPANTS: Three hundred five participants of the Sleep AHEAD study who underwent unattended full polysomnography at home with measurement of the apnea-hypopnea index (AHI). MEASUREMENTS AND RESULTS: Self-reported prevalent CVD was obtained at the initial assessment of the parent study and included a history of the following conditions: stroke, carotid endarterectomy, myocardial infarction, coronary artery bypass grafting, and percutaneous coronary intervention. Logistic regression was used to assess the association of OSA, measured continuously and categorically, with prevalent CVD. OSA was present (AHI ≥ 5) in 86% of the population, whereas the prevalence of all forms of CVD was just 14%. The AHI was associated with stroke with an adjusted odds ratio (95% confidence interval) of 2.57 (1.03, 6.42). Neither the continuously measured AHI nor the categories of OSA severity were significantly associated with the other forms of CVD assessed. CONCLUSIONS: We found suggestive evidence of a greater prevalence of stroke at greater values of the AHI. OSA was not associated with prevalent coronary heart disease in the Sleep AHEAD trial. Future studies should confirm the link between OSA and stroke and examine mechanisms that link OSA to stroke in adults with T2DM.
Subject(s)
Coronary Disease/epidemiology , Diabetes Mellitus, Type 2/epidemiology , Overweight/epidemiology , Self Report , Sleep Apnea, Obstructive/epidemiology , Stroke/epidemiology , Comorbidity , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Obesity/epidemiology , Odds Ratio , Polysomnography/methods , Prevalence , Risk FactorsABSTRACT
STUDY OBJECTIVES: We evaluated associations among subjective and objective measures of sleep and the metabolic syndrome in a multi-ethnic sample of midlife women. DESIGN: Cross-sectional study. SETTING: Participants' homes. PARTICIPANTS: Caucasian (n = 158), African American (n = 125), and Chinese women (n = 57); mean age = 51 years. Age range = 46-57 years. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Metabolic syndrome was measured in the clinic and sleep quality was assessed by self-report. Indices of sleep duration, continuity/fragmentation, depth, and sleep disordered breathing were assessed by in-home polysomnography (PSG). Covariates included sociodemographics, menopausal status, use of medications that affect sleep, and self-reported health complaints and health behaviors known to influence metabolic syndrome risk. Logistic regression was used to test the hypothesis that the metabolic syndrome would be associated with increased subjective sleep complaints and PSG-assessed sleep disturbances. In univariate analyses, the metabolic syndrome was associated with decreased sleep duration and efficiency and increased NREM beta power and apnea-hypopnea index (AHI). After covariate adjustment, sleep efficiency (odds ratio [OR] = 2.06, 95% confidence interval [CI]: 1.08-3.93), NREM beta power (OR = 2.09, 95% CI: 1.09-3.98), and AHI (OR = 1.86, 95% CI: 1.40-2.48) remained significantly associated with the metabolic syndrome (odds ratio values are expressed in standard deviation units). These relationships did not differ by race. CONCLUSIONS: Objective indices of sleep continuity, depth, and sleep disordered breathing are significant correlates of the metabolic syndrome in midlife women, independent of race, menopausal status and other factors that might otherwise account for these relationships.
Subject(s)
Metabolic Syndrome/complications , Sleep Wake Disorders/complications , Black or African American , Analysis of Variance , Asian , Chi-Square Distribution , Cross-Sectional Studies , Female , Humans , Logistic Models , Metabolic Syndrome/epidemiology , Metabolic Syndrome/physiopathology , Middle Aged , Polysomnography , Prevalence , Sleep/physiology , Sleep Apnea Syndromes/complications , Sleep Apnea Syndromes/epidemiology , Sleep Apnea Syndromes/physiopathology , Sleep Wake Disorders/epidemiology , Sleep Wake Disorders/physiopathology , United States/epidemiology , White PeopleABSTRACT
PURPOSE: Some studies have found an association between sleep disturbances and metabolic risk, but none has examined this association in individuals with type 2 diabetes. The objective of this study was to determine the relationship between sleep disturbances and metabolic risk factors in obese patients with type 2 diabetes. PATIENTS AND METHODS: This study was a cross-sectional examination of the relationship between sleep parameters (apnea/hypopnea index [AHI], time spent in various sleep stages) and metabolic risk markers (fasting glucose, hemoglobin A1c, lipids) using baseline data of the Sleep AHEAD cohort. Subjects (n = 305) were participants in Sleep AHEAD (Action for Health in Diabetes), a four-center ancillary study of the Look AHEAD study, a 16-center clinical trial of overweight and obese participants with type 2 diabetes, designed to assess the long-term effects of an intensive lifestyle intervention on cardiovascular events. All participants underwent one night of in-home polysomnography and provided a fasting blood sample. Regression analyses estimated the relationship between sleep variables and metabolic risk factors. Models were adjusted for study center, age, sex, race/ethnicity, waist circumference, smoking, alcohol intake, diabetes duration, and relevant medications. RESULTS: Of 60 associations tested, only one was significant: fasting glucose was associated with sleep efficiency (estimate -0.53 ± [standard error] 0.26, P = 0.041). No associations were found between any of the sleep variables and lipid profile or hemoglobin A1c. CONCLUSIONS: The present data show only weak associations between select sleep variables and metabolic risk factors and do not provide strong support for a role of sleep on metabolic abnormalities in obese patients with type 2 diabetes.
ABSTRACT
BACKGROUND AND OBJECTIVES: Sleep-disordered breathing (SDB) and excessive daytime sleepiness (EDS) are highly prevalent among hemodialysis (HD) patients. It is unclear to what extent SDB is associated with advanced chronic kidney disease (CKD; stages 4 to 5). This paper describes and compares the prevalence, severity, and patterns of SDB and EDS among patients with advanced CKD, HD-dependent patients, and community individuals without known renal disease. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Eighty-nine CKD and 75 HD patients were compared with 224 participants from the Sleep-Strategies Concentrating on Risk Evaluation Sleep-SCORE study of sleep and cardiovascular risk. Participants had in-home unattended polysomnography for quantifying SDB. EDS was defined by a score ≥10 on the Epworth Sleepiness Scale. RESULTS: The sample had a median age 58.1 years, was predominantly male (57.4%) and white (62.5%), and had a median body mass index of 28.1 kg/m(2). Controls and Sleep-SCORE Study CKD patients had significantly higher median total sleep time and sleep efficiency compared with HD patients. The adjusted odds of severe SDB were higher for CKD and HD groups compared with the controls. Nocturnal hypoxemia was significantly elevated in the HD group compared with the CKD group. There were similar proportions of participants with EDS between the controls (33%), the CKD patients (29.3%), and the HD patients (40.6%). CONCLUSIONS: Severe SDB (predominantly obstructive) and EDS are common among advanced CKD and HD patients. EDS correlated modestly with severe SDB and its obstructive and mixed patterns in the HD group.
Subject(s)
Kidney Failure, Chronic/epidemiology , Kidney Failure, Chronic/therapy , Renal Dialysis/statistics & numerical data , Sleep Apnea Syndromes/epidemiology , Sleep Stages , Adult , Aged , Female , Humans , Hypoxia/epidemiology , Kidney Failure, Chronic/etiology , Male , Middle Aged , Multivariate Analysis , Polysomnography , Prevalence , Severity of Illness Index , Sleep Apnea Syndromes/diagnosisABSTRACT
RATIONALE: Although obstructive sleep apnea is associated with physiological perturbations that increase risk of hypertension and are proatherogenic, it is uncertain whether sleep apnea is associated with increased stroke risk in the general population. OBJECTIVES: To quantify the incidence of ischemic stroke with sleep apnea in a community-based sample of men and women across a wide range of sleep apnea. METHODS: Baseline polysomnography was performed between 1995 and 1998 in a longitudinal cohort study. The primary exposure was the obstructive apnea-hypopnea index (OAHI) and outcome was incident ischemic stroke. MEASUREMENTS AND MAIN RESULTS: A total of 5,422 participants without a history of stroke at the baseline examination and untreated for sleep apnea were followed for a median of 8.7 years. One hundred ninety-three ischemic strokes were observed. In covariate-adjusted Cox proportional hazard models, a significant positive association between ischemic stroke and OAHI was observed in men (P value for linear trend: P = 0.016). Men in the highest OAHI quartile (>19) had an adjusted hazard ratio of 2.86 (95% confidence interval, 1.1-7.4). In the mild to moderate range (OAHI, 5-25), each one-unit increase in OAHI in men was estimated to increase stroke risk by 6% (95% confidence interval, 2-10%). In women, stroke was not significantly associated with OAHI quartiles, but increased risk was observed at an OAHI greater than 25. CONCLUSIONS: The strong adjusted association between ischemic stroke and OAHI in community-dwelling men with mild to moderate sleep apnea suggests that this is an appropriate target for future stroke prevention trials.
Subject(s)
Sleep Apnea, Obstructive/epidemiology , Stroke/epidemiology , Aged , Female , Humans , Longitudinal Studies , Male , Middle Aged , Polysomnography , Proportional Hazards Models , Prospective Studies , Severity of Illness Index , Sex FactorsABSTRACT
BACKGROUND: The 1997 American Thoracic Society (ATS) statement "A Framework for Health Care Policy in the United States" outlined core principles for the Society's activities in the public health arena. In the succeeding 10 years, profound changes have taken place in the United States health care environment. In addition, the 2005 publication of the Society's Vision highlighted some differences between the original Statement and our current priorities. Therefore, the Health Policy Committee embarked on a re-analysis and re-statement of the Society's attitudes and strategies with respect to health and public policy. This Statement reflects the findings of the Committee. PURPOSE: To outline the key aspects of an internal ATS strategy for the promotion of respiratory and sleep/wake health and the care of the critically ill in the United States. METHODS: Committee discussion and consensus-building occurred both before and after individual members performed literature searches and drafted sections of the document. Comments were solicited on the draft document from ATS committee and assembly chairs and the Executive Committee, resulting in substantive revisions of the final document. RESULTS: Specific strategies are suggested for the ATS in the arenas of research, training and education, patient care, and advocacy so as to enhance the delivery of health care in the fields of respiratory medicine, sleep medicine, and critical care. CONCLUSIONS: The American Thoracic Society's Mission, Core Principles, and Vision provide clear guidance for the formulation of specific strategies that will serve to promote improved respiratory health and care of the critically ill in the United States.
Subject(s)
Critical Illness/therapy , Respiration , Sleep/physiology , Societies, Medical , Wakefulness/physiology , Health Policy , Health Promotion , Humans , Organizational Policy , Practice Guidelines as Topic , United StatesABSTRACT
BACKGROUND: The belief that weight loss improves obstructive sleep apnea (OSA) has limited empirical support. The purpose of this 4-center study was to assess the effects of weight loss on OSA over a 1-year period. METHODS: The study included 264 participants with type 2 diabetes and a mean (SD) age of 61.2 (6.5) years, weight of 102.4 (18.3) kg, body mass index (BMI) (calculated as weight in kilograms divided by height in meters squared) of 36.7 (5.7), and an apnea-hypopnea index (AHI) of 23.2 (16.5) events per hour. The participants were randomly assigned to either a behavioral weight loss program developed specifically for obese patients with type 2 diabetes (intensive lifestyle intervention [ILI]) or 3 group sessions related to effective diabetes management (diabetes support and education [DSE]). RESULTS: The ILI participants lost more weight at 1 year than did DSE participants (10.8 kg vs 0.6 kg; P < .001). Relative to the DSE group, the ILI intervention was associated with an adjusted (SE) decrease in AHI of 9.7 (2.0) events per hour (P < .001). At 1 year, more than 3 times as many participants in the ILI group than in the DSE group had total remission of their OSA, and the prevalence of severe OSA among ILI participants was half that of the DSE group. Initial AHI and weight loss were the strongest predictors of changes in AHI at 1 year (P < .01). Participants with a weight loss of 10 kg or more had the greatest reductions in AHI. CONCLUSIONS: Physicians and their patients can expect that weight loss will result in significant and clinically relevant improvements in OSA among obese patients with type 2 diabetes. Trial Registration clinicaltrials.gov Identifier: NCT00194259.
Subject(s)
Behavior Therapy , Diabetes Mellitus, Type 2/complications , Obesity/complications , Sleep Apnea, Obstructive/complications , Sleep Apnea, Obstructive/therapy , Weight Loss , Aged , Body Mass Index , Female , Humans , Hypoxia , Male , Middle Aged , Severity of Illness Index , Sleep Apnea, Obstructive/diagnosis , Treatment OutcomeABSTRACT
OBJECTIVE: To assess the risk factors for the presence and severity of obstructive sleep apnea (OSA) among obese patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: Unattended polysomnography was performed in 306 participants. RESULTS: Over 86% of participants had OSA with an apnea-hypopnea index (AHI) >or=5 events/h. The mean AHI was 20.5 +/- 16.8 events/h. A total of 30.5% of the participants had moderate OSA (15
Subject(s)
Diabetes Mellitus, Type 2/complications , Obesity/complications , Sleep Apnea, Obstructive/epidemiology , Aged , Body Height , Body Weight , Diabetes Mellitus, Type 2/epidemiology , Female , Glycated Hemoglobin/analysis , Humans , Likelihood Functions , Male , Middle Aged , Obesity/epidemiology , Oxygen Consumption , Polysomnography , Respiration Disorders/classification , Respiration Disorders/epidemiology , Respiration Disorders/physiopathology , Risk Factors , Severity of Illness Index , Sleep Apnea, Obstructive/complications , Sleep Apnea, Obstructive/physiopathology , Sleep, REM/physiology , Waist CircumferenceABSTRACT
BACKGROUND: Studies examining sleep in the hemodialysis (HD) population have largely lacked an adequate comparison group. It therefore is uncertain whether poor sleep quality in the HD population reflects age, chronic health conditions, or effects of conventional HD therapy. STUDY DESIGN: Cross-sectional matched-group study. SETTING & PARTICIPANTS: Forty-six in-center HD patients were compared with 137 community participants participating in the Sleep Heart Health Study matched for age, sex, body mass index, and race. PREDICTOR: HD patients compared with community-dwelling non-HD participants. OUTCOMES & MEASUREMENTS: Home unattended polysomnography was performed and scored by using similar protocols. Sleep habits and sleepiness were assessed by using the Sleep Habits Questionnaire and Epworth Sleepiness Scale. RESULTS: Average age of study samples was 63 years, 72% were white, and average body mass index was 28 +/- 5 kg/m(2). HD patients were significantly more likely than community participants to have short sleep (odds ratio, 3.27; 95% confidence interval, 1.16 to 9.25) and decreased sleep efficiency (odds ratio, 5.5; 95% confidence interval, 1.5 to 19.6). HD patients reported more difficulty getting back to sleep (odds ratio, 2.25; 95% confidence interval, 1.11 to 4.60) and waking up too early (odds ratio, 2.39; 95% confidence interval, 1.01 to 5.66). There was no association between polysomnography sleep time and self-reported sleep time (r = 0.09; P = 0.6) or between the Epworth Sleepiness Scale and severity of sleep apnea (r = 0.10; P = 0.5) in the HD population. LIMITATIONS: The study was limited to participants older than 45 years. CONCLUSIONS: Kidney failure treated with thrice-weekly HD is significantly associated with poor subjective and objective sleep quality.
Subject(s)
Heart Rate/physiology , Kidney Failure, Chronic/therapy , Renal Dialysis/methods , Sleep Apnea Syndromes/epidemiology , Sleep/physiology , Aged , Aged, 80 and over , Body Mass Index , Cross-Sectional Studies , Disease Progression , Female , Follow-Up Studies , Humans , Incidence , Kidney Failure, Chronic/physiopathology , Male , Middle Aged , Odds Ratio , Pennsylvania/epidemiology , Polysomnography , Prognosis , Renal Dialysis/adverse effects , Retrospective Studies , Risk Factors , Severity of Illness Index , Sleep Apnea Syndromes/etiology , Sleep Apnea Syndromes/physiopathology , Surveys and QuestionnairesABSTRACT
STUDY OBJECTIVES: Commonly used definitions of sleep-disordered breathing (SDB) are based on identifying discrete events of breathing abnormalities during sleep that are accompanied by an oxyhemoglobin desaturation (delta SaO2) of at least 4%. However, it is not known whether disordered breathing events with oxyhemoglobin desaturation less than 4% are associated with clinical sequelae such as abnormalities in fasting glycemia. DESIGN: Cross-sectional study. SUBJECTS AND SETTING: Participants from the Sleep Heart Health Study (SHHS) with a fasting glucose measurement made within a year of the baseline polysomnogram. MEASUREMENTS AND RESULTS: SDB severity was defined using the apnea-hypopnea index (AHI) and the hypopnea index (HI) by counting events with different levels of oxyhemoglobin desaturation (0.0%-1.9%, 2.0%-2.9%, 3.0%-3.9%, > or = 4.0%). Fasting glucose levels were used to classify individuals into normal (<100 mg/dL), impaired (100-125 mg/dL), and diabetic (> or = 126 mg/dL) groups. Ordinal logistic regression was used to determine the adjusted relative odds of an abnormal glucose value across quartiles of the hypopnea index, independent of factors such as age, body mass index, waist circumference, and usual sleep duration. The prevalence of impaired and diabetic fasting glucose in the analytical sample was 32.9% and 5.8%, respectively. The covariate-adjusted relative odds of impaired or diabetic fasting glucose in the highest versus the lowest AHI quartile was 1.35 (95% CI: 1.04-1.76) for events with a delta SaO2 > or = 4.0%, 1.72 (95% CI: 1.20-2.48) for events with a delta SaO2 between 3.0%-3.9%, 1.41 (95% CI: 1.07-1.86) for events with a delta SaO2 between 2.0%-2.9%, and 1.07 (95% CI: 0.84-1.37) for events with a delta SaO2 between 0.0%-1.9%. The corresponding odds ratios for the HI were 1.47 (95% CI: 1.13-1.92), 2.25 (95% CI: 1.59-3.19), 1.44 (95% CI: 1.09-1.90), and 1.15 (95% CI: 0.90-1.47), respectively. CONCLUSIONS: The results of this study indicate that SDB events accompanied by oxyhemoglobin desaturation of between 2% to 4% are associated with fasting hyperglycemia. These findings suggest that milder degrees of SDB may predispose to adverse metabolic outcomes.
Subject(s)
Blood Glucose/metabolism , Diabetes Mellitus, Type 2/blood , Fasting/blood , Oxyhemoglobins/metabolism , Sleep Apnea, Obstructive/blood , Aged , Body Mass Index , Cohort Studies , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Odds Ratio , Oxygen/blood , Polysomnography , Reference ValuesABSTRACT
RATIONALE: Epidemiologic studies on the consequences of sleep-disordered breathing invariably use the apnea-hypopnea index as the primary measure of disease severity. Although hypopneas constitute a majority of disordered breathing events, significant controversy remains about the best criteria used to define these events. OBJECTIVES: The current investigation sought to assess the most appropriate definition for hypopneas that would be best correlated with cardiovascular disease. METHODS: A community sample of middle-aged and older adults was recruited as part of the Sleep Heart Health Study. Full-montage polysomnography was conducted and hypopneas were defined using different thresholds of oxyhemoglobin desaturation with and without arousals. Prevalent cardiovascular disease was assessed based on self-report. Logistic regression analysis was used to characterize the independent association between the hypopnea index and prevalent cardiovascular disease. MEASUREMENTS AND MAIN RESULTS: Using a sample of 6,106 adults with complete data on cardiovascular disease status and polysomnography, the current study found that hypopneas associated with an oxyhemoglobin desaturation of 4% or more were associated with prevalent cardiovascular disease independent of confounding covariates. The adjusted prevalent odds ratios for quartiles of the hypopnea index using a 4% desaturation criterion were as follows: 1.00 (<1.10 events/h), 1.10 (1.01-3.20 events/h), 1.33 (3.21-7.69 events/h), and 1.41 (>7.69 events/h). Hypopnea measures based on less than 4% oxyhemoglobin desaturation or presence of arousals showed no association with cardiovascular disease. CONCLUSIONS: Hypopneas comprise a significant component of sleep-disordered breathing in the general community. By varying the criteria for defining hypopneas, this study demonstrates that hypopneas with a desaturation of at least 4% are independently associated with cardiovascular disease. In contrast, no association was observed between cardiovascular disease and hypopneas associated with milder desaturations or arousals.
Subject(s)
Apnea/classification , Cardiovascular Diseases/physiopathology , Oxyhemoglobins/physiology , Polysomnography/methods , Sleep Apnea Syndromes/physiopathology , Aged , Cardiovascular Diseases/complications , Cohort Studies , Female , Humans , Male , Middle Aged , Odds Ratio , Oxyhemoglobins/analysis , Sleep Apnea Syndromes/complications , Terminology as TopicABSTRACT
The sleep medicine community has increasingly recognized the necessity that clinical care be based on high-quality levels of evidence. Although research supports a favorable influence of positive airway pressure (PAP) therapy on risk for significant adverse outcomes in patients with severe obstructive sleep apnea-hypopnea (OSAH), well-designed trials are still required to elucidate the effect of PAP on health, quality of life, and economic risks in patients with milder OSAH. Similarly, although there is strong evidence supporting various PAP titration strategies and PAP modalities in patients with severe OSAH without significant medical and psychiatric comorbidities, there is insufficient high-level evidence assessing and comparing the clinical efficacy and health care cost implications of various titration paradigms and various PAP modalities in individuals with milder OSAH and those with comorbid conditions. For ethical and other reasons, it may not be possible to apply a randomized controlled design to address all questions. However, whichever design is employed, it must be rigorously developed with attention to all potential confounders with adequate power to provide compelling, high-quality evidence.
Subject(s)
Continuous Positive Airway Pressure , Sleep Apnea, Obstructive/therapy , Adult , Comorbidity , Evidence-Based Medicine , Humans , Longevity , Quality of Life , Research Design , Sleep Apnea, Obstructive/mortality , Sleep Apnea, Obstructive/physiopathologyABSTRACT
RATIONALE AND OBJECTIVES: Although many clinical physiology and epidemiology studies show an association between obstructive sleep apnea (OSA) and markers of insulin resistance, no causal pathway has been established. The purpose of the current study was to determine if the intermittent hypoxia (IH) stimulus that characterizes OSA causes insulin resistance in the absence of obesity. Furthermore, we assessed the impact of IH on specific metabolic function in liver and muscle. Finally, we examined the potential mechanistic role of the autonomic nervous system (ANS) in mediating insulin resistance in response to IH. METHODS AND RESULTS: Hyperinsulinemic euglycemic clamps were conducted and whole-body insulin sensitivity, hepatic glucose output, and muscle-specific glucose utilization assessed in conscious, chronically instrumented adult male C57BL/6J mice exposed to (1) IH (achieving a nadir of Fi(O(2)) = 5-6% at 60 cycles/h for 9 h), (2) intermittent air as a control, (3) IH with ANS blockade (hexamethonium), or (4) IA with ANS blockade. IH decreased whole-body insulin sensitivity compared with intermittent air (38.8 +/- 2.7 vs. 49.4 +/- 1.5 mg/kg/min, p < 0.005) and reduced glucose utilization in oxidative muscle fibers, but did not cause a change in hepatic glucose output. Furthermore, the reduction in whole-body insulin sensitivity during IH was not restored by ANS blockade. CONCLUSION: We conclude that IH can cause acute insulin resistance in otherwise lean, healthy animals, and that the response is associated with decreased glucose utilization of oxidative muscle fibers, but that it occurs independently of activation of the ANS.
Subject(s)
Hypoxia/complications , Insulin Resistance/physiology , Animals , Autonomic Nervous System/physiopathology , Body Mass Index , Corticosterone/blood , Glucose/metabolism , Glucose Clamp Technique , Hypoxia/metabolism , Insulin/blood , Liver/metabolism , Male , Mice , Mice, Inbred C57BL , Muscle Fibers, Skeletal/metabolismABSTRACT
The hemodynamic response to hypoxia may be influenced by exposure pattern and inducible biological signals, such as nitric oxide synthase (iNOS) expression. The systemic blood pressure (BP) and heart rate (HR) response to intermittent and continuous hypoxia (IH and CH) were examined as was the relationship between these responses and iNOS expression in 10 normal subjects. BP and HR were recorded during exposure to IH or CH (total hypoxic time=60 min/dayx3 days for each exposure profile), whereas arterial oxygen saturation (SpO2) was maintained at 80-90%. Total RNA was isolated from peripheral blood lymphocytes before exposure on Day 1 and 2 hours after the last exposure on Day 3, and it was assayed for iNOS messenger RNA (mRNA) expression using quantitative polymerase chain reaction (PCR). HR, systolic BP (SBP), and diastolic BP (DBP) increased during both experimental conditions (P<0.05), with no difference by exposure pattern or evidence of facilitation over 3 days. No significant change occurred in iNOS mRNA during IH or CH when pre- and post-exposure values were compared. However, iNOS expression at the end of Day 3 was negatively correlated with the average end-exposure DBP (r=-0.79) and mean BP (MBP; r=-0.76) on Days 1-3 of the IH (P<0.05), but not CH exposure. It is concluded that both IH and CH are associated with significant but comparable hemodynamic changes. The negative correlation between BP and iNOS mRNA with IH, but not CH, may suggest differential modulation of the hemodynamic response to the 2 exposure patterns.
Subject(s)
Adaptation, Physiological/physiology , Blood Pressure/physiology , Heart Rate/physiology , Hypoxia/physiopathology , Nitric Oxide Synthase Type II/genetics , Adult , Gene Expression Regulation, Enzymologic/physiology , Humans , Lymphocytes/enzymology , Male , Oxygen/administration & dosage , RNA, Messenger/metabolismABSTRACT
Sleep-disordered breathing (SDB) has been noted commonly in hemodialysis (HD) patients, but it is not known whether this is related directly to the treatment of kidney failure with HD or to the higher prevalence of obesity and older age. Forty-six HD patients were compared with 137 participants from the Sleep Heart Health Study (SHHS) who were matched for age, gender, body mass index (BMI), and race. Home unattended polysomnography was performed and scored using similar protocols. The study sample was 62.7 +/- 10.1 yr, was predominantly male (72%) and white (63%), and had an average BMI of 28 +/- 5.3 kg/m(2). The HD sample had a higher systolic BP (137 versus 121 mmHg; P < 0.01) and a higher prevalence of diabetes (33 versus 9%; P < 0.01) and cardiovascular disease (33 versus 13%; P < 0.01) compared with the SHHS sample. The HD group had significantly less sleep time (320 versus 379 min; P < 0.0001) but similar sleep efficiency. HD patients had a higher frequency of arousals per hour (25.1 versus 17.1; P < 0.0001) and apnea-hypopneas per hour (27.2 versus 15.2; P < 0.0001) and greater percentage of the total sleep time below an oxygen saturation of 90% (7.2 versus 1.8; P < 0.0001). HD patients were more likely to have severe SDB (>30 respiratory events per hour) compared with the SHHS sample (odds ratio 4.07; 95% confidence interval 1.83 to 9.07). There was a strong association of HD with severe SDB and nocturnal hypoxemia independent of age, BMI, and the higher prevalence of chronic disease. The potential mechanisms for the higher likelihood of SDB in the HD population must be identified to provide specific prevention and therapy.
Subject(s)
Kidney Failure, Chronic/therapy , Renal Dialysis/adverse effects , Sleep Apnea Syndromes/epidemiology , Blood Pressure , Body Mass Index , Cardiovascular Diseases/epidemiology , Case-Control Studies , Cross-Sectional Studies , Diabetes Mellitus/epidemiology , Female , Humans , Male , Middle Aged , Prevalence , Severity of Illness Index , Sleep Apnea Syndromes/etiologyABSTRACT
A significant number of patients with obstructive sleep apnea neither tolerate positive airway pressure (PAP) therapy nor achieve successful outcomes from either upper airway surgeries or use of an oral appliance. The purpose of this paper, therefore, was to systematically evaluate available peer-reviewed data on the effectiveness of adjunctive medical therapies and summarize findings from these studies. A review from 1985 to 2005 of the English literature reveals several practical findings. Weight loss has additional health benefits and should be routinely recommended to most overweight patients. Presently, there are no widely effective pharmacotherapies for individuals with sleep apnea, with the important exceptions of individuals with hypothyroidism or with acromegaly. Treating the underlying medical condition can have pronounced effects on the apnea/hypopnea index. Stimulant therapy leads to a small but statistically significant improvement in objective sleepiness. Nonetheless, residual sleepiness remains a significant health concern. Supplemental oxygen and positional therapy may benefit subsets of patients, but whether these therapies reduce morbidities as PAP therapy does will require rigorous randomized trials. PAP therapy has set the bar high for successful treatment of sleep apnea and its associated morbidities. Nonetheless, we should strive towards the development of universally effective pharmacotherapies for sleep apnea. To accomplish this, we require a greater knowledge of the neurochemical mechanisms underlying sleep apnea, and we must use this infrastructure of knowledge to design well-controlled, adequately powered studies that examine, not only effects on the apnea/hypopnea index, but also the effects of pharmacotherapies on all health related outcomes shown beneficial with PAP therapy.