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Over the past 20 years obesity has become a worldwide concern of frightening proportion. The World Health Organization estimates that there are over 400 million obese and over 1.6 billion overweight adults, a figure which is projected to almost double by 2015. This is not a disease restricted to adults - at least 20 million children under the age of 5 years were overweight in 2005 (WHO 2006). Overweight and obesity lead to serious health consequences including coronary artery disease, stroke, type-2 diabetes, heart failure, dyslipidemia, hypertension, reproductive and gastrointestinal cancers, gallstones, fatty liver disease, osteoarthritis and sleep apnea (Padwal et al 2003). Modest weight loss in the obese of between 5% and 10% of bodyweight is associated with improvements in cardiovascular risk profiles and reduced incidence of type 2 diabetes (Goldstein 1992; Avenell et al 2004; Padwal and Majumdar 2007). Orlistat, a gastric and pancreatic lipase inhibitor that reduces dietary fat absorption by approximately 30%, has been approved for use for around ten years (Zhi et al 1994; Hauptman 2000). There is now a growing body of evidence to suggest that Orlistat assists weight loss and that it may also have additional benefits. The aim of this review is to provide a brief update on the current literature studying the efficacy, safety and significance of the use of Orlistat in clinical practice.
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PMID:Obesity management: update on orlistat. 1820 Aug 2

Although obstructive sleep apnea and cardiovascular disease have common risk factors, epidemiologic studies show that sleep apnea increases risks for cardiovascular disease independently of individuals' demographic characteristics (i.e., age, sex, and race) or risk markers (i.e., smoking, alcohol, obesity, diabetes, dyslipidemia, atrial fibrillation, and hypertension). Individuals with severe sleep apnea are at increased risk for coronary artery disease, congestive heart failure, and stroke. The underlying mechanisms explaining associations between obstructive sleep apnea and cardiovascular disease are not entirely delineated. Several intermediary mechanisms might be involved including sustained sympathetic activation, intrathoracic pressure changes, and oxidative stress. Other abnormalities such as disorders in coagulation factors, endothelial damage, platelet activation, and increased inflammatory mediators might also play a role in the pathogenesis of cardiovascular disease. Linkage between obstructive sleep apnea and cardiovascular disease is corroborated by evidence that treatment of sleep apnea with continuous positive airway pressure reduces systolic blood pressure, improves left ventricular systolic function, and diminishes platelet activation. Several systematic studies are necessary to explicate complex associations between sleep apnea and cardiovascular disease, which may be compounded by the involvement of diseases comprising the metabolic syndrome (i.e., central obesity, hypertension, diabetes, and dyslipidemia). Large-scale, population-based studies testing causal models linking among sleep apnea, cardiovascular morbidity, and metabolic syndrome are needed.
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PMID:Obstructive sleep apnea and cardiovascular disease: role of the metabolic syndrome and its components. 1859 41

This article provides an overview on the management of risk factors to prevent primary strokes, the gaps in successful management, and future directions for the research and management of stroke risk factors. The major focus is given to the management of modifiable risk factors for stroke, including hypertension, diabetes, dyslipidemia, atrial fibrillation and other cardiac conditions, carotid artery stenosis, smoking, poor diet, physical inactivity, and obesity. A brief discussion on the management of potentially modifiable risk factors, such as alcohol and drug abuse, sleep apnea, and hyperhomocysteinemia, is included, as is the use of antiplatelet therapy in primary stroke prevention. Finally, prognostic scores to assess an individual risk for a first stroke are reviewed.
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PMID:Risk factor management to prevent first stroke. 1902 1

We investigate whether preadmission hyperglycemia is a risk factor for developing in-hospital symptomatic pulmonary embolism after major orthopedic surgery. Medical records of patients undergoing total hip or total knee arthroplasty from January 2001 to April 2006 were reviewed. The incidence of PE was 1.47% (107/7282 patients). Multivariate analysis showed that preadmission blood glucose (BG) of at least 200 mg/dL independently increased the risk of pulmonary embolism by 3.19 times (P = .015), when compared with patients with BG of less than 110 mg/dL. Other significant risks factors were age (>or=70 years old), body mass index of more than 30 kg/m(2), and congestive heart failure. Total knee had 2.19 times (P = .002) more risk than total hip arthroplasty and bilateral procedure increased the risk by 2.13 times (P = .015). Sex, American Society of Anesthesiologists status, duration of surgery, malignancy, pulmonary disease, hypertension, diabetes mellitus, dyslipidemia, sleep apnea, and stroke were not found to be significant risk factors for pulmonary embolism.
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PMID:Preadmission hyperglycemia is an independent risk factor for in-hospital symptomatic pulmonary embolism after major orthopedic surgery. 1905 17

Careful selection of bariatric patients is critical for successful outcomes. In 1991, the NIH first established patient selection guidelines; however, some surgeons operate on individuals outside of these criteria, i.e., extreme age groups. We developed appropriateness criteria for the spectrum of patient characteristics including age, BMI, and severity of eight obesity-related comorbidities. Candidate criteria were developed using combinations of patient characteristics including BMI: > or =40 kg/m(2), 35-39, 32-34, 30-31, <30; age: 12-18, 19-55, 56-64, 65+ years old; and comorbidities: prediabetes, diabetes, hypertension, dyslipidemia, sleep apnea, venous stasis disease, chronic joint pain, and gastroesophageal reflux (plus severity level). Criteria were formally validated on their appropriateness of whether the benefits of surgery clearly outweighed the risks, by an expert panel using the RAND/UCLA modified Delphi method. Nearly all comorbidity severity criteria for patients with BMI > or =40 kg/m(2) or BMI = 35-39 kg/m(2) in intermediate age groups were found to be appropriate for surgery. In contrast, patients in the extreme age categories were considered appropriate surgical candidates under fewer conditions, primarily the more severe comorbidities, such as diabetes and hypertension. For patients with a BMI of 32-34, only the most severe category of diabetes (Hgb A1c >9, on maximal medical therapy), is an appropriate criterion for those aged 19-64, whereas many mild to moderate severity comorbidity categories are "inappropriate." There is overwhelming agreement among the panelists that the current evidence does not support performing bariatric surgery in lower BMI individuals (BMI <32). This is the first development of appropriateness criteria for bariatric surgery that includes severity categories of comorbidities. Only for the most severe degrees of comorbidities were adolescent and elderly patients deemed appropriate for surgery. Patient selection for bariatric procedures should include consideration of both patient age and comorbidity severity.
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PMID:Appropriateness criteria for bariatric surgery: beyond the NIH guidelines. 1934 19

Favorable health outcomes at 2 years postbariatric surgery have been reported. With exception of the Swedish Obesity Subjects (SOS) study, these studies have been surgical case series, comparison of surgery types, or surgery patients compared to subjects enrolled in planned nonsurgical intervention. This study measured gastric bypass effectiveness when compared to two separate severely obese groups not participating in designed weight-loss intervention. Three groups of severely obese subjects (N = 1,156, BMI >or= 35 kg/m(2)) were studied: gastric bypass subjects (n = 420), subjects seeking gastric bypass but did not have surgery (n = 415), and population-based subjects not seeking surgery (n = 321). Participants were studied at baseline and 2 years. Quantitative outcome measures as well as prevalence, incidence, and resolution rates of categorical health outcome variables were determined. All quantitative variables (BMI, blood pressure, lipids, diabetes-related variables, resting metabolic rate (RMR), sleep apnea, and health-related quality of life) improved significantly in the gastric bypass group compared with each comparative group (all P < 0.0001, except for diastolic blood pressure and the short form (SF-36) health survey mental component score at P < 0.01). Diabetes, dyslipidemia, and hypertension resolved much more frequently in the gastric bypass group than in the comparative groups (all P < 0.001). In the surgical group, beneficial changes of almost all quantitative variables correlated significantly with the decrease in BMI. We conclude that Roux-en-Y gastric bypass surgery when compared to severely obese groups not enrolled in planned weight-loss intervention was highly effective for weight loss, improved health-related quality of life, and resolution of major obesity-associated complications measured at 2 years.
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PMID:Health outcomes of gastric bypass patients compared to nonsurgical, nonintervened severely obese. 1949 44

Sleep apnea-hypopnea syndrome (SAHS) is characterized by recurrent episodes of hypoxia/reoxygenation, which seems to promote oxidative stress. SAHS patients experience increases in hypertension, obesity, and dyslipidemia, and the oxidative state has been related to the genesis of these disorders. The purpose of this study was to examine the changes in oxidative stress markers and metabolic parameters in S AHS patients after 1 month of treatment with continuous positive airway pressure (CPAP), in relation to their previous metabolic disorders. The study included 78 SAHS patients who required CPAP. The patients were classified according to their disorders, including hypertension, obesity, and dyslipidemia. Measurements were made before and after 1 month of treatment with CPAP. The diastolic blood pressure decreased after treatment in all the patients, significantly so in those who were nondyslipidemic, obese, or hypertensive (the systolic pressure also fell in these latter patients). Plasma oxidative stress biomarkers showed a significant antioxidant capacity and increased activity (P<0.05) after treatment, more so in the nondyslipidemic and hypertensive patients. Furthermore, serum lipid peroxidation levels decreased after CPAP (P<0.01). No change was observed in insulin resistance (IR) after CPAP treatment in any of the different disorders. In conclusion, oxidative stress markers improved significantly after CPAP treatment in SAHS patients, especially in the nondyslipidemic and hypertensive patients. Moreover, the blood pressure decreased after CPAP treatment, particularly in the obese, nondyslipidemic, and hypertensive patients. No significant change in IR was found in any of the SAHS patients after CPAP treatment.
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PMID:Oxidative stress and metabolic changes after continuous positive airway pressure treatment according to previous metabolic disorders in sleep apnea-hypopnea syndrome patients. 1966 87

A burgeoning pandemic of obesity is well characterized. 41% of U.S. adults are projected to be obese by 2015 and obesity, a potentially modifiable risk, is emerging as a leading predictor of lifetime health. The wide spectrum of morbidities related to excess body mass includes risks for diabetes, hypertension, coronary artery disease, dyslipidemia, malignancy, venous thrombosis, degenerative joint disease, pulmonary compromise, sleep apnea, cholelithiasis, depression and overall reduced quality of life. Beyond the myriad major and minor morbidities linked to obesity, increased all-cause mortality and cardiovascular mortality is recognized in the obese. Bariatric surgery literature suggests that, in the morbidly obese, increase in the lifespan is achievable with reversal of obesity, reinforcing the realization that sequelae therein are by no means inevitable. Aggressive efforts must be targeted towards population-based strategies to educate and sensitize all generations on contributors to and sequelae of excess body mass as obesity represents one of the few modifiable factors that impact on the quantity and quality of lifespan.
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PMID:Predictors of chronic disease at midlife and beyond--the health risks of obesity. 1979 85

Obstructive sleep apnea (OSA) adversely affects multiple organs and systems, with particular relevance to cardiovascular disease. Several conditions associated with OSA, such as high BP, insulin resistance, systemic inflammation, visceral fat deposition, and dyslipidemia, are also present in other conditions closely related to OSA, such as obesity and reduced sleep duration. Weight loss has been accompanied by improvement in characteristics related not only to obesity but to OSA as well, suggesting that weight loss might be a cornerstone of the treatment of both conditions. This review seeks to explore recent developments in understanding the interactions between body weight and OSA. Weight loss helps reduce OSA severity and attenuates the cardiometabolic abnormalities common to both diseases. Nevertheless, weight loss has been hard to achieve and maintain using conservative strategies. Since bariatric surgery has emerged as an alternative treatment of severe or complicated obesity, impressive results have often been seen with respect to sleep apnea severity and cardiometabolic disturbances. However, OSA is a complex condition, and treatment cannot be limited to any single symptom or feature of the disease. Rather, a multidisciplinary and integrated strategy is required to achieve effective and long-lasting therapeutic success.
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PMID:Interactions between obesity and obstructive sleep apnea: implications for treatment. 2020 54

Obesity and insulin resistance are highly prevalent in subjects diagnosed with sleep apnea. One factor common to obesity, sleep and insulin resistance is autonomic nervous system dysfunction, in particular, sympathetic overactivity. Although the causal links among these factors are not well understood, it is likely that the vicious cycle of interplay among these factors predisposes to the emergence of "metabolic syndrome", a convergence of obesity, hypertension, insulin resistance and dyslipidemia that is appearing in epidemic proportions in the United States and other countries. This chapter provides an overview of the ongoing experimental and modeling studies in my laboratory aimed at elucidating and quantifying the relationships among autonomic dysfunction, insulin resistance and severity of sleep apnea in overweight subjects. These studies employ a "minimal modeling" approach to extract information characterizing autonomic function from noninvasive cardiorespiratory measurements. We subsequently determine the relationship of these model parameters to the parameters estimated from the Bergman minimal insulin-glucose model using data obtained from the frequently sampled intravenous glucose tolerance test performed on the same individuals.
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PMID:Model-based studies of autonomic and metabolic dysfunction in sleep apnea. 2021 65


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