Background
This is an overview of the mechanisms of obesity and its relation to cardiovascular risks, describing the available treatment options to manage this condition.
Main body
The pathogenesis of obesity includes the balance between calories consumed and energy expenditure followed by the maintenance of body weight. Diet, physical activity, environmental, behavioral and physiological factors are part of the complex process of weight loss, since there are several hormones and peptides involved in regulation of appetite, eating behavior and energy expenditure. The cardiovascular complications associated to obesity are also driven by processes involving hormones and peptides and which include inflammation, insulin resistance, endothelial dysfunction, coronary calcification, activation of coagulation, renin angiotensin or the sympathetic nervous systems. Pharmacological treatments are often needed to insure weight loss and weight maintenance as adjuncts to diet and physical activity in people with obesity and overweight patients.
Conclusion
To accomplish satisfactory goals, patients and physicians seek for weight loss, weight maintenance and improvement of the risk factors associated to this condition, especially cardiovascular risk.
Obstructive sleep apnea-hypopnea syndrome involves recurring episodes of total obstruction (apnea) or partial obstruction (hypopnea) of airways during sleep. Obstructive sleep apnea-hypopnea syndrome affects mainly obese individuals and it is defined by an apnea-hypopnea index of five or more episodes per hour associated with daytime somnolence. In addition to anatomical factors and neuromuscular and genetic factors, sleep disorders are also involved in the pathogenesis of sleep apnea. Obesity affects upper airway anatomy because of fat deposition and metabolic activity of adipose tissue. Obstructive sleep apnea-hypopnea syndrome and metabolic syndrome have several characteristics such as visceral obesity, hypertension and insulin resistance. Inflammatory cytokines might be related to the pathogenesis of sleep apnea and metabolic syndrome. Sleep apnea treatment includes obesity treatment, use of equipment such as continuous positive airway pressure, drug therapy and surgical procedures in selected patients. Currently, there is no specific drug therapy available with proven efficacy for the treatment of obstructive sleep apnea-hypopnea syndrome. Body-weight reduction results in improvement of sleep apnea, and obesity treatment must be emphasized, including lifestyle changes, anti-obesity drugs and bariatric surgery.
Obese women may have increased cerebral metabolism when compared with women of normal weight, and this appears to reverse after weight loss induced by bariatric surgery, accompanied by improved executive function.
Objective: To evaluate the efficacy of diethylpropion on a long-term basis, with emphasis in cardiovascular and psychiatric safety aspects. Design: Randomized, double-blind, placebo-controlled trial Measurements: Following a 2-week screening period, 69 obese healthy adults received a hypocaloric diet and were randomized to diethylpropion 50 mg BID (n ¼ 37) or placebo (n ¼ 32) for 6 months. After this period, all participants received diethylpropion in an open-label extension for an additional 6 months. The primary outcome was percentage change in body weight. Electrocardiogram (ECG), echocardiography and clinical chemistry were performed at baseline and every 6 months. Psychiatric evaluation and application of Hamilton rating scales for depression and anxiety were also performed by experienced psychiatrists at baseline and every 3 months. Results: After 6 months, the diethylpropion group lost an average of 9.8% (s.d. 6.9%) of initial body weight vs 3.2% (3.7%) in the placebo group (Po0.0001). From baseline to month 12, the mean weight loss produced by diethylpropion was 10.6% (8.3%). Participants in the placebo group who were switched to diethylpropion after 6 months lost an average of 7.0% (7.7%) of initial body weight. The difference between groups at month 12 was not significant (P ¼ 0.07). No differences in blood pressure, pulse rate, ECG and psychiatric evaluation were observed. Dry mouth and insomnia were the most frequent adverse events. Conclusion: Diethylpropion plus diet produced sustained and clinically significant weight loss over 1 year. It seems to be safe in relation to cardiovascular and psychiatric aspects in a well-selected population.
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