Obesity

[justify]Obesity
Obesity is a condition in which the natural energy reserve, stored in the fatty tissue of humans and other mammals, is increased to a point where it is associated with certain health conditions or increased mortality.
Obesity is both an individual clinical condition and is increasingly viewed as a serious public health problem. Excessive body weight has been shown to predispose to various diseases, particularly cardiovascular diseases, diabetes mellitus type 2, sleep apnea, and osteoarthritis.
Effects on health
• Cardiovascular: congestive heart failure, enlarged heart and its associated arrhythmias and dizziness, cor pulmonale, varicose veins, and pulmonary embolism
• Endocrine: polycystic ovarian syndrome (PCOS), menstrual disorders, and infertility
• Gastrointestinal: gastroesophageal reflux disease (GERD), fatty liver disease, cholelithiasis (gallstones), hernia, and colorectal cancer
• Renal and genitourinary: urinary incontinence, glomerulopathy, hypogonadism (male), breast cancer (female), uterine cancer (female), stillbirth
• Integument (skin and appendages): stretch marks, acanthosis nigricans, lymphedema, cellulitis, carbuncles, intertrigo
• Musculoskeletal: hyperuricemia (which predisposes to gout), immobility, osteoarthritis, low back pain
• Neurologic: stroke, meralgia paresthetica, headache, carpal tunnel syndrome, dementia
• Respiratory: dyspnea, obstructive sleep apnea, hypoventilation syndrome, Pickwickian syndrome, asthma
• Psychological: Depression, low self esteem, body dysmorphic disorder, social stigmatization
Metrics
In the clinical setting, obesity is typically evaluated by measuring BMI (body mass index), waist circumference, and evaluating the presence of risk factors and comorbidities. In epidemiological studies, BMI alone is used to define obesity.
BMI
BMI, or Body Mass Index, was developed by the Belgian statistician and anthropometrist Adolphe Quetelet.[5] It is calculated by dividing the subject's weight in kilograms by the square of his/her height in metres (BMI = kg / m2) or (BMI = weight(lbs.) * 703 / height(inches)2).
The current definitions commonly in use establish the following values, agreed in 1997 and published in 2000:
• A BMI less than 18.5 is underweight
• A BMI of 18.5 - 24.9 is normal weight
• A BMI of 25.0 - 29.9 is overweight
• A BMI of 30.0 - 39.9 is obese
• A BMI of 40.0 or higher is severely (or morbidly) obese
• A BMI of 35.0 or higher in the presence of at least one other significant comorbidity is also classified by some bodies as morbid obesity.
BMI is a simple and widely used method for estimating body fat. In epidemiology BMI alone is used as an indicator of prevalence and incidence.
BMI as an indicator of a clinical condition is used in conjunction with other clinical assessments, such as waist circumference. In a clinical setting, physicians take into account race, ethnicity, lean mass (muscularity), age, sex, and other factors which can affect the interpretation of BMI. BMI overestimates body fat in persons who are very muscular, and it can underestimate body fat in persons who have lost body mass (e.g. many elderly). Mild obesity as defined by BMI alone is not a cardiac risk factor, and hence BMI cannot be used as a sole clinical and epidemiological predictor of cardiovascular health.
Waist circumference
BMI does not take into account differing ratios of adipose to lean tissue; nor does it distinguish between differing forms of adiposity, some of which may correlate more closely with cardiovascular risk. Increasing understanding of the biology of different forms of adipose tissue has shown that visceral fat or central obesity (male-type or apple-type obesity) has a much stronger correlation, particularly with cardiovascular disease, than the BMI alone.
The absolute waist circumference (>102 cm in men and >88 cm in women) or waist-hip ratio (>0.9 for men and >0.85 for women) are both used as measures of central obesity.
Body fat measurement
An alternative way to determine obesity is to assess percent body fat. Doctors and scientists generally agree that men with more than 25% body fat and women with more than 30% body fat are obese. However, it is difficult to measure body fat precisely. The most accepted method has been to weigh a person underwater, but underwater weighing is a procedure limited to laboratories with special equipment. Two simpler methods for measuring body fat are the skinfold test, in which a pinch of skin is precisely measured to determine the thickness of the subcutaneous fat layer; or bioelectrical impedance analysis, usually only carried out at specialist clinics.
Other measurements of body fat include computed tomography (CT/CAT scan), magnetic resonance imaging (MRI/NMR), and dual energy X-ray absorptiometry (DXA).
Gestalt
In practice, for most examples of overweight that may designate risk, both doctor and patient can see "by eye" whether excess fat is a concern. In these cases, BMI thresholds provide simple targets all patients can understand.
Risk factors and comorbidities
The presence of risk factors and diseases associated with obesity are also used to establish a clinical diagnosis. Coronary heart disease, type 2 diabetes, and sleep apnea are possible life-threatening risk factors that would indicate clinical treatment of obesity. Smoking, hypertension, age and family history are other risk factors that may indicate treatment. Diabetes and heart disease are risk factors used in epidemiological studies of obesity.
Causes
Overeating
In its simplest conception, obesity is only made possible when the lifetime energy intake exceeds lifetime energy expenditure by more than it does for individuals of "normal weight".
When food energy intake exceeds energy expenditure, fat cells (and to a lesser extent muscle and liver cells) throughout the body take in the energy and store it as fat.
In all individuals, the excess energy utilized to generate fat reserves is minute relative to the total number of calories consumed. This means that very fine perturbations in the energy balance can lead to large fluctuations in weight over time. To illustrate, an obese 40 year old who carries 100 lb of adipose tissue has only consumed about 25 more calories per day than he has burned on average - or the equivalent of an apple every three days. In comparison a very lean 40-year-old who carries only 15 lb of body fat will have exceeded his daily energy expenditure by about four calories a day - the equivalent of an apple every 18 days.
Additional factors
Factors that have been suggested to contribute to the development of obesity include:
• Genetic factors and some genetic disorders (e.g., Prader-Willi syndrome)
• Underlying illness (e.g., hypothyroidism)
• Eating disorders (e.g., binge eating disorder)
• Certain medications (e.g., atypical antipsychotics)
• Sedentary lifestyle
• A high glycemic diet (i.e., a diet that consists of meals that give high postprandial blood sugar)
• Weight cycling, caused by repeated attempts to lose weight by dieting
• Stressful mentality
• Insufficient sleep
• Smoking cessation
As with many medical conditions, the caloric imbalance that results in obesity often develops from a combination of genetic and environmental factors. Polymorphisms in various genes controlling appetite, metabolism, and adipokine release predispose to obesity, but the condition requires availability of sufficient calories, and possibly other factors, to develop fully. Various genetic abnormalities that predispose to obesity have been identified (such as Prader-Willi syndrome and leptin receptor mutations), but known single-locus mutations have been found in only about 5% of obese individuals. While it is thought that a large proportion of the causative genes are still to be identified, much obesity is likely the result of interactions between multiple genes, and non-genetic factors are likely also important.
Some eating disorders are associated with obesity, especially binge eating disorder (BED). As the name indicates, patients with this disorder are prone to overeat, often in binges. A proposed mechanism is that the eating serves to reduce anxiety, and some parallels with substance abuse can be drawn. An important additional factor is that BED patients often lack the ability to recognize hunger and satiety, something that is normally learned in childhood. Learning theory suggests that early childhood conceptions may lead to an association between food and a calm mental state.
Tendencies of ethnic groups
Certain populations and individuals may be more prone to obesity than others, and the ability to take advantage of rare periods of abundance and use such abundance by storing energy efficiently was undoubtedly an evolutionary advantage in times when food was scarce. Individuals with greater adipose reserves were more likely to survive famine. This tendency to store fat is likely maladaptive in a society with adequate and stable food supplies.
Neurobiological mechanisms
Scientists investigating the mechanisms and treatment of obesity may use animal models such as mice to conduct experiments.
Flier summarizes the many possible pathophysiological mechanisms involved in the development and maintenance of obesity. This field of research had been almost unapproached until leptin was discovered in 1994. Since this discovery, many other hormonal mechanisms have been elucidated that participate in the regulation of appetite and food intake, storage patterns of adipose tissue, development of insulin resistance. Since leptin's discovery, ghrelin, orexin, PYY 3-36, cholecystokinin, adiponectin, and many other mediators have been studied. The adipokines are mediators produced by adipose tissue; their action is thought to modify many obesity-related diseases.
Leptin and ghrelin are considered to be complementary in their influence on appetite, with ghrelin produced by the stomach modulating short-term appetitive control (i.e. to eat when the stomach is empty and to stop when the stomach is stretched). Leptin is produced by adipose tissue to signal fat storage reserves in the body, and mediates long-term appetitive controls (i.e. to eat more when fat storages are low and less when fat storages are high). Although administration of leptin may be effective in a small subset of obese individuals who are leptin-deficient, many more obese individuals are thought to be leptin-resistant, and this resistance has been implicated in obesity in some people, is thought to explain in part why administration of leptin has not been shown to be effective in suppressing appetite in most obese subjects.
Neuroscientific approaches hinge on the action of the aforementioned mediators on the hypothalamus, the part of the brain that is thought to process signals related to metabolic state and energy storage and to shift the energy balance in either a positive or negative direction, primarily by acting on appetite and energy expenditure. Lesion studies in the 1940s and 1950s identified two regions of the hypothalamus — the lateral hypothalamus (LH) and ventromedial hypothalamus (VMH) — as the brain's hunger and satiety centers, respectively. Specific lesions to a mouse's LH suppressed its appetite while damaging the VMH caused overeating.
Studies of the distribution of the leptin receptor in the mid-1990s cast doubt upon this dual center theory of hunger and satiety. Leptin's effect on the arcuate nucleus melanocortin system is now considered central to the regulation of feeding and metabolism.
Therapy
The mainstay of treatment for obesity is an energy-limited diet and increased exercise. In studies, diet and exercise programs have consistently produced an average weight loss of approximately 8% of total body mass on average (excluding study drop-outs). While not all dieters will be satisfied with this outcome, studies have shown that a loss of as little as 5% of body mass can create enormous health benefits.
A more intractable therapeutic problem appears to be weight loss maintenance. Of dieters who manage to lose 10% or more of their body mass in studies, 80-95% will regain that weight within two to five years. It appears that the homeostatic mechanisms regulating body weight are very robust (see leptin, for example), and vigorously defend against weight loss. Much important research is now being devoted to determining what factors can improve the currently dismal weight loss maintenance rates.
Recent scientific research has cast some doubt over whether or not dieting actually improves health, with some studies indicating that dieting may in fact be more detrimental than remaining overweight.
In a clinical practice guideline by the American College of Physicians, the following five recommendations are made:
1. People with a BMI of over 30 should be counseled on diet, exercise and other relevant behavioral interventions, and set a realistic goal for weight loss.
2. If these goals are not achieved, pharmacotherapy can be offered. The patient needs to be informed of the possibility of side-effects and the unavailability of long-term safety and efficacy data.
3. Drug therapy may consist of sibutramine, orlistat, phentermine, diethylpropion, fluoxetine, and bupropion. For more severe cases of obesity, stronger drugs such as amphetamine and methamphetamine may be used on a selective basis. Evidence is not sufficient to recommend sertraline, topiramate, or zonisamide.
4. In patients with BMI > 40 who fail to achieve their weight loss goals (with or without medication) and who develop obesity-related complications, referral for bariatric surgery may be indicated. The patient needs to be aware of the potential complications.
5. Those requiring bariatric surgery should be referred to high-volume referral centers, as the evidence suggests that surgeons who frequently perform these procedures have fewer complications.[/justify]