Metabolic Study of Sleep Apnea in Men and Women

Duke University, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

The purpose of this study is to look at the metabolic (use of energy) and hormonal features of sleep problems in men and women.

Obesity is a major risk factor for obstructive sleep apnea (OSA), a condition characterized by repetitive respiratory disturbances, intermittent hypoxia, sleep fragmentation by frequent microarousals and low amounts of deep slow wave sleep (SWS). Today, more than 10 million American women suffer from OSA. OSA has been identified as an independent risk factor for the metabolic syndrome. Because OSA is more prevalent in men than in women, a disproportionate number of studies of OSA and its consequences have been conducted in men. Thus, OSA has been characterized as a disorder associated with gender-based health care inequity. Recent evidence, including data from our group, suggests that reduced amounts and intensity of SWS (i.e. slow-wave activity [SWA]) may play a pivotal role in the development of metabolic and cardiovascular disturbances in obese men and women, particularly those with OSA. This project will focus on sex differences in SWA and their relationship with daytime sleepiness and metabolic vulnerability in obese men and women with and without OSA. We propose to simultaneously characterize: 1. sleep-wake regulation; 2. measures of diabetes risk; 3. measures of cardiovascular risk; and 4. profiles of sex steroids, cortisol and adipokines in a. obese men without OSA, b. obese men with OSA before and after treatment with continuous positive airway pressure (CPAP), c. obese pre-menopausal women without OSA, and d. obese pre-menopausal women with OSA before and after CPAP treatment. The completion of these interdisciplinary studies will provide a unique data set contrasting in obese women versus obese men the relationships between sleep and the metabolic syndrome, OSA and the metabolic syndrome and the impact of CPAP treatment on the metabolic syndrome. This work will provide important insights regarding the pathophysiology of OSA and its adverse consequences in obese men and women, and the basis for the development of effective sex-specific prevention and treatment strategies.

Obese men and pre-menopausal women with OSA will receive 6 weeks of CPAP treatment, and assessed with a 3-day experimental protocol.

Obese men and pre-menopausal women without OSA will be characterized with a single 3-day experimental protocol

apnea-hypopnea index: number of apneas and hypopneas per hour of recording; a measure of the severity of obstructive sleep apnea; varies from min=0 to max=120; AHI between 0 and <5: no significant sleep apnea; AHI between 5 and <15: mild sleep apnea; AHI between 15 and <30: moderate sleep apnea; AHI of 30 and above: severe sleep apnea.

Stage N3, sometimes referred to as "delta sleep" or "slow wave sleep", is characterized by slow waves in the electro-encephalogram (EEG) that reflect synchronization of firing of cortical neurons. N3 sleep is considered the most restorative stage of sleep for both the brain and the rest of the body.

Sleep efficiency: a measure of objective sleep quality; calculated from the polygraphic sleep recording as the ratio of time spent asleep during the scheduled sleep period to total scheduled sleep period. Expressed in %. Varies from 0% (the subject did not sleep at all) to 100% (the subject spent the entire scheduled sleep period asleep).

Sensitivity Index (SI): a measure of how much insulin the body needs to metabolize a given amount of glucose. SI is calculated using a mathematical model describing the profiles of blood glucose and serum insulin after intravenous glucose injection. SI varies from 0 to an undefined upper limit but generally under 20. Higher values of SI represent a better outcome.

Acute Insulin Response is calculated as the area under the insulin curve for the first 19 minutes after intravenous glucose injection. "Area under the insulin curve" is expressed in pmol x min/L.

Disposition Index (DI) is the product of sensitivity index (SI) by the amount of insulin secreted in response to blood glucose levels. It is a marker of the risk of type 2 diabetes. Low DI reflects a high risk of diabetes. DI can vary from 0 to an undefined upper limit. The physiological range for the Disposition Index is 500 to 5,000. Higher values represent a better outcome.

Inclusion Criteria: Obese (BMI of at least 30 kg/m2) Exclusion Criteria: Clinically significant depression Positive pregnancy test Diagnosis of diabetes mellitus Hypertension (systolic > 140 mmHg and/or diastolic > 90 mmHg) not well-controlled on stable medication with either ACE inhibitors or diuretics Habitual alcohol use Excessive caffeine intake of more than 300 mg/day Hemoglobin < 11g/dL and/or hematocrit < 33% Systemic illnesses, including heart, renal, liver, or malignant disease Taking steroid preparations (including oral contraceptives), medications known to alter insulin secretion and/or action, or medications known to influence sleep during the 2 months prior to starting the study Travel across time zones during the 4 weeks prior to starting the study Irregular sleeping habits (including shift work)

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