Obesity is becoming a global epidemic in both children and adults. It is associated with numerous comorbidities such as cardiovascular diseases (CVD), type 2 diabetes, hypertension, certain cancers, and sleep apnea/sleep-disordered breathing. In fact, obesity is an independent risk factor for CVD, and CVD risks have also been documented in obese children. Obesity is associated with an increased risk of morbidity and mortality as well as reduced life expectancy. Health service use and medical costs associated with obesity and related diseases have risen dramatically and are expected to continue to rise. Besides an altered metabolic profile, a variety of adaptations/alterations in cardiac structure and function occur in the individual as adipose tissue accumulates in excess amounts, even in the absence of comorbidities. Hence, obesity may affect the heart through its influence on known risk factors such as dyslipidemia, hypertension, glucose intolerance, inflammatory markers, obstructive sleep apnea/hypoventilation, and the prothrombotic state, in addition to as-yet-unrecognized mechanisms. On the whole, overweight and obesity predispose to or are associated with numerous cardiac complications such as coronary heart disease, heart failure, and sudden death because of their impact on the cardiovascular system. The pathophysiology of these entities that are linked to obesity will be discussed. However, the cardiovascular clinical evaluation of obese patients may be limited because of the morphology of the individual. In this statement, we review the available evidence of the impact of obesity on CVD with emphasis on the evaluation of cardiac structure and function in obese patients and the effect of weight loss on the cardiovascular system.

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Obesity and Cardiovascular Disease: Pathophysiology, Evaluation, and Effect of Weight Loss

This article reviews information on discriminatory attitudes and behaviors against obese individuals, integrates this to show whether systematic discrimination occurs and why, and discusses needed work in the field. Clear and consistent stigmatization, and in some cases discrimination, can be documented in three important areas of living: employment, education, and health care. Among the findings are that 28% of teachers in one study said that becoming obese is the worst thing that can happen to a person; 24% of nurses said that they are "repulsed" by obese persons; and, controlling for income and grades, parents provide less college support for their overweight than for their thin children. There are also suggestions but not yet documentation of discrimination occurring in adoption proceedings, jury selection, housing, and other areas. Given the vast numbers of people potentially affected, it is important to consider the research-related, educational, and social policy implications of these findings.

https://onlinelibrary.wiley.com/doi/pdf/10.1038/oby.2001.108

Bias, Discrimination, and Obesity

The prevalence of sleep-disordered breathing has not been well studied in women, especially in terms of the effects of age, body mass index (BMI), and menopause. We evaluated this question using a two-phase random sample from the general population. In Phase I, 12,219 women and 4,364 men ranging in age from 20 to 100 yr were interviewed; and in Phase II, 1,000 women and 741 men of the Phase I subjects were selected for one night of sleep laboratory evaluation. The results of our study indicated that, for clinically defined sleep apnea (apnea/hypopnea index > or = 10 and daytime symptoms), men had a prevalence of 3.9% and women 1.2%, resulting in an overall ratio of sleep apnea for men to women of 3.3:1 (p = 0.0006). The prevalence of sleep apnea was quite low in premenopausal women (0.6%) as well as postmenopausal women with hormone replacement therapy (HRT) (0.5%). Further, in these women the presence of sleep apnea appeared to be associated exclusively with obesity (BMI > or = 32.3 kg/m2). Postmenopausal women without HRT had a prevalence of sleep apnea that was significantly higher than the prevalence in premenopausal women with HRT (2.7 versus 0.6%, p = 0.02) and was more similar to the prevalence in men (3.9%), although it remained significantly less when controlling for age and BMI (p = 0.001). These data combined indicate that menopause is a significant risk factor for sleep apnea in women and that hormone replacement appears to be associated with reduced risk.

Prevalence of sleep-disordered breathing in women: effects of gender.

Sleep apnea and associated daytime sleepiness and fatigue are common manifestations of mainly obese middle-aged men. The onset of sleep apnea peaks in middle age, and its morbid and mortal sequelae include complications from accidents and cardiovascular events. The pathophysiology of sleep apnea remains obscure. The purpose of this study was to test three separate, albeit closely related, hypotheses. 1) Does sleep apnea contribute to the previously reported changes of plasma cytokine (tumor necrosis factor-alpha and interleukin-6) and leptin levels independently of obesity? 2) Among obese patients, is it generalized or visceral obesity that predisposes to sleep apnea? 3) Is apnea a factor independent from obesity in the development of insulin resistance? Obese middle-aged men with sleep apnea were first compared with nonapneic age- and body mass index (BMI)-matched obese and age-matched lean men. All subjects were monitored in the sleep laboratory for 4 consecutive nights. We obtained simultaneous indexes of sleep, sleep stages, and sleep apnea, including apnea/hypopnea index and percent minimum oxygen saturation. The sleep apneic men had higher plasma concentrations of the adipose tissue-derived hormone, leptin, and of the inflammatory, fatigue-causing, and insulin resistance-producing cytokines tumor necrosis factor-alpha and interleukin-6 than nonapneic obese men, who had intermediate values, or lean men, who had the lowest values. Because these findings suggested that sleep apneics might have a higher degree of insulin resistance than the BMI-matched controls, we studied groups of sleep-apneic obese and age- and BMI-matched nonapneic controls in whom we obtained computed tomographic scan measures of total, sc, and visceral abdominal fat, and additional biochemical indexes of insulin resistance, including fasting plasma glucose and insulin. The sleep apnea patients had a significantly greater amount of visceral fat compared to obese controls (<0.05) and indexes of sleep disordered breathing were positively correlated with visceral fat, but not with BMI or total or sc fat. Furthermore, the biochemical data confirmed a higher degree of insulin resistance in the group of apneics than in BMI-matched nonapneic controls. We conclude that there is a strong independent association among sleep apnea, visceral obesity, insulin resistance and hypercytokinemia, which may contribute to the pathological manifestations and somatic sequelae of this condition.

http://www.beauty-review.nl/wp-content/uploads/2014/10/Sleep-apnea-and-daytime-sleepiness-and-fatigue-relation-to-visceral-obesity-insulin-resistance-and-hypercytokinemia.pdf

Sleep Apnea and Daytime Sleepiness and Fatigue: Relation to Visceral Obesity, Insulin Resistance, and Hypercytokinemia

Context Pandemic influenza A(H1N1) emerged rapidly in California in April 2009. Preliminary comparisons with seasonal influenza suggest that pandemic 2009 influenza A(H1N1) disproportionately affects younger ages and causes generally mild disease. Objective To describe the clinical and epidemiologic features of pandemic 2009 influenza A(H1N1) cases that led to hospitalization or death. Design, setting, and participants Statewide enhanced public health surveillance of California residents who were hospitalized or died with laboratory evidence of pandemic 2009 influenza A(H1N1) infection reported to the California Department of Public Health between April 23 and August 11, 2009. Main outcome measure Characteristics of hospitalized and fatal cases. Results During the study period there were 1088 cases of hospitalization or death due to pandemic 2009 influenza A(H1N1) infection reported in California. The median age was 27 years (range, Conclusions In the first 16 weeks of the current pandemic, the median age of hospitalized infected cases was younger than is common with seasonal influenza. Infants had the highest hospitalization rates and persons aged 50 years or older had the highest mortality rates once hospitalized. Most cases had established risk factors for complications of seasonal influenza.

https://jamanetwork.com/journals/jama/articlepdf/184820/joc90126_1896_1902.pdf

Factors associated with death or hospitalization due to pandemic 2009 influenza A(H1N1) infection in California.

Objectives: To describe the frequency and severity of sleep apnea in obese patients without a primary sleep complaint and to assess the sleep patterns of obese patients without apnea and compare them with the sleep patterns of nonobese controls. Design and Setting: Prospective case series with historical controls in an obesity and sleep disorders clinic. Subjects: Two hundred obese women and 50 obese men (mean body mass index, 45.3) consecutively referred for treatment of their obesity and 128 controls matched for age and sex. Main Outcome Measures: Eight-hour sleep laboratory recording, including electroencephalogram, electro-oculogram, electromyogram, and respirations. Subjectively reported sleep-related symptoms and signs were also recorded. Results: Twenty men (40%) and six women (3%) demonstrated sleep apnea warranting therapeutic intervention. Another four men (8%) and 11 women (5.5%) showed sleep apneic activity that warranted recommendation for evaluation in the sleep laboratory. In contrast, none of the 128 controls demonstrated sleep apneic activity severe enough for therapeutic intervention. The best clinical predictors of sleep apnea in the obese population were severity of snoring, subjectively reported nocturnal breath cessation, and sleep attacks. Obese patients, both men and women, without any sleep-disordered breathing demonstrated a significant degree of sleep disturbance compared with nonobese controls. Wake time after sleep onset, number of awakenings, and percentage of stage 1 sleep were significantly higher in obese patients than in controls, while rapid eye movement sleep was significantly lower. Conclusion: Severely or morbidly obese men are at extremely high risk for sleep apnea and should be routinely evaluated in the sleep laboratory for this condition, while for severely or morbidly obese women the physician should include a thorough sleep history in the clinical assessment. (Arch Intern Med. 1994;154:1705-1711)

Sleep apnea and sleep disruption in obese patients.

Background Daytime sleepiness and fatigue is a frequent complaint of obese patients even among those who do not demonstrate sleep apnea. Objective To assess in the sleep laboratory whether obese patients without sleep apnea are sleepier during the day compared with healthy controls with normal weight. Methods Our sample consisted of 73 obese patients without sleep apnea, upper airway resistance syndrome, or hypoventilation syndrome who were consecutively referred for treatment of their obesity and 45 controls matched for age. All patients and healthy controls were monitored in the sleep laboratory for 8 hours at night and at 2 daytime naps, each for 1 hour the following day. Results Obese patients compared with controls were sleepier during the day and their nighttime sleep was disturbed. During both naps, sleep latency, wake time after onset of sleep, and total wake time were significantly lower, whereas the percentage of sleep time was significantly higher in obese patients compared with controls. In contrast, during the nighttime testing, obese patients compared with controls demonstrated significantly higher wake time after onset of sleep, total wake time, and lower percentage of sleep time. An analysis of the relation between nighttime and daytime sleep suggested that daytime sleepiness in obese patients is a result of a circadian abnormality rather than just being secondary to nighttime sleep disturbance. Conclusions Daytime sleepiness is a morbid characteristic of obese patients with a potentially significant impact on their lives and public safety. Daytime sleepiness in individuals with obesity appears to be related to a metabolic and/or circadian abnormality of the disorder.

https://jamanetwork.com/journals/jamainternalmedicine/articlepdf/207201/ioi70636.pdf

Obesity without sleep apnea is associated with daytime sleepiness.

Ten patients, each of whom had been using hypnotic drugs for periods ranging from months to years, were monitored in the sleep laboratory while continuing to receive medication. Comparison with insomniac controls who were not receiving medication demonstrated a significant decrease of rapid eye movement (REM) sleep in the chronic drug users. A striking finding was the fact that all of these patients had as great or greater difficulty in falling asleep or staying asleep, or both, than the insomniac controls who were not using medication. Abrupt withdrawal of ineffective drugs is not recommended due to psychological and physiological changes that contribute to drug-withdrawal insomnia and hypnotic-drug dependence. The ineffectiveness of hypnotic drugs demonstrated in this study and in our earlier sleep laboratory drug evaluation studies indicates the need for changes in the guidelines used for evaluating and advertising hypnotic drugs.

https://jamanetwork.com/HttpHandlers/ArticlePdfHandler.ashx?journal=JAMA&articleId=352768&pdfFileName=jama_227_5_004.pdf

Chronic Hypnotic-Drug Use: Ineffectiveness, Drug-Withdrawal Insomnia, and Dependence

Comparison of the costs associated with medical and surgical treatment of obesity.

WE PREVIOUSLY reported that altered sleep patterns occur during the administration and following withdrawal of glutethimide (Doriden), methyprylon (Noludar), and pentobarbital (Nembutal). 1 The clinical problems associated with these alterations, such as unpleasant dreams, nightmares, drug dependency, and insomnia, were also discussed. These studies suggested that further investigation of the effects of other drugs would be necessary in order to find hypnotics which did not result in sleep alterations and adverse clinical disturbance. Preliminary findings suggested that the nonbarbiturate hypnotics chloral hydrate (Noctec), 2 flurazepam (Dalmane) , 3,4 and methaqualone (Quaalude) 5 might fulfill these requirements. We decided, therefore, to systematically study each of these hypnotic drugs. Methods Subjects were male, 20 to 30 years of age without any medical illnesses, allergies, drug use, or sleep disturbance. During the experiment they were instructed to continue to abstain from using any drugs, including alcohol, to maintain their usual level of physical

Tjiauw Ling Tan

Papers

Sleep apnea and sleep disruption in obese patients.

Obesity without sleep apnea is associated with daytime sleepiness.

Chronic Hypnotic-Drug Use: Ineffectiveness, Drug-Withdrawal Insomnia, and Dependence

Comparison of the costs associated with medical and surgical treatment of obesity.

II. All-night EEG Studies of Chloral Hydrate, Flurazepam, and Methaqualone