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.
Although obesity is an individual clinical condition, it is increasingly viewed as a serious and growing 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.
Definition
Obesity can be defined in absolute or relative terms. In practical settings, obesity is typically evaluated in absolute terms by measuring BMI (body mass index), but also in terms of its distribution through waist circumference or waist-hip circumference ratio measurements. In addition, the presence of obesity needs to be regarded in the context of other risk factors and comorbidities (other medical conditions that could influence risk of complications).
BMI
BMI, or body mass index, is a simple and widely used method for estimating body fat. BMI was developed by the Belgian statistician and anthropometrist Adolphe Quetelet. It is calculated by dividing the subject's weight by the square of his/her height, typically expressed either in metric or US "Customary" units:
Metric: BMI = kg / m2
Where kg is the subject's weight in kilograms and m is the subject's height in metres.
US/Customary: BMI = lb * 703 / in2
Where lb is the subject's weight in pounds and in is the subject's height in inches.
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.
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.
In a cohort of almost 15,000 subjects from the National Health and Nutrition Examination Survey (NHANES) III study, waist circumference explained obesity-related health risk significantly better than BMI when metabolic syndrome was taken as an outcome measure.
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. Their routine use is discouraged.
Other measurements of body fat include computed tomography (CT/CAT scan), magnetic resonance imaging (MRI/NMR), and dual energy X-ray absorptiometry (DXA).
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.
Effects on health
A large number of medical conditions have been associated with obesity. Health consequences are categorised as being the result of either increased fat mass (osteoarthritis, obstructive sleep apnea, social stigma) or increased number of fat cells (diabetes, cancer, cardiovascular disease, non-alcoholic fatty liver disease).[12] Mortality is increased in obesity, with a BMI of over 32 being associated with a doubled risk of death. There are alterations in the body's response to insulin (insulin resistance), a proinflammatory state and an increased tendency to thrombosis (prothrombotic state).
Disease associations may be dependent or independent of the distribution of adipose tissue. Central obesity (male-type or waist-predominant obesity, characterised by a high waist-hip ratio), is an important risk factor for the metabolic syndrome, the clustering of a number of diseases and risk factors that heavily predispose for cardiovascular disease. These are diabetes mellitus type 2, high blood pressure, high blood cholesterol, and triglyceride levels (combined hyperlipidemia).
Apart from the metabolic syndrome, obesity is also correlated with a variety of other complications. For some of these complaints, it has not been clearly established to what extent they are caused directly by obesity itself, or have some other cause (such as limited exercise) that causes obesity as well.
* 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: erectile dysfunction, urinary incontinence, chronic renal failure, 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, idiopathic intracranial hypertension
* Respiratory: dyspnea, obstructive sleep apnea, hypoventilation syndrome, Pickwickian syndrome, asthma
* Psychological: Depression, low self esteem, body dysmorphic disorder, social stigmatization
While being severely obese has many health ramifications, those who are somewhat overweight face little increased mortality or morbidity. Osteoporosis is known to occur less in slightly overweight people.
Causes and mechanisms
Lifestyle
Most researchers have concluded that the combination of an excessive nutrient intake and a sedentary lifestyle are the main cause for the rapid acceleration of obesity in Western society in the last quarter of the 20th century.
Despite the widespread availability of nutritional information in schools, doctors' offices, on the internet and on groceries, it is evident that overeating remains a substantial problem. For instance, reliance on energy-dense fast-food meals tripled between 1977 and 1995, and calorie intake quadrupled over the same period.
However, dietary intake in itself is insufficient to explain the phenomenal rise in levels of obesity in much of the industrialized world during recent years. An increasingly sedentary lifestyle also has a significant role to play. More and more research into child obesity, for example, links such things as the school run, with the current high levels of this disease.
Less well established life style issues which may influence obesity include a stressful mentality and insufficient sleep.
Genetics
As with many medical conditions, the calorific 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 conditions that feature obesity have been identified (such as Prader-Willi syndrome, Bardet-Biedl syndrome, MOMO syndrome, leptin receptor mutations and melanocortin 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.
A 2007 study identified fairly common mutations in the FTO gene; heterozygotes had a 30% increased risk of obesity, while homozygotes faced a 70% increased risk.
On a population level, the thrifty gene hypothesis postulates that certain ethnic groups 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 may have been 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 stable food supplies.
Medical illness
Certain physical and mental illnesses and particular pharmaceutical substances may predispose to obesity. Apart from the fact that correcting these situations may improve the obesity, the presence of increased body weight may complicate the management of others.
Medical illnesses that increase obesity risk include several rare congenital syndromes (listed above), hypothyroidism, Cushing's syndrome, growth hormone deficiency.[24] Smoking cessation is a known cause for moderate weight gain, as nicotine suppresses appetite. Certain medications (e.g. steroids, atypical antipsychotics, some fertility medication) may cause weight gain.
Mental illnesses may also increase obesity risk, specifically some eating disorders such as bulimia nervosa, binge eating disorder, and compulsive overeating (also known as food addiction).
Neurobiological mechanisms
Scientists investigating the mechanisms and treatment of obesity may use animal models such as mice to conduct experiments.
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, and 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. This resistance is thought to explain in part why administration of leptin has not been shown to be effective in suppressing appetite in most obese subjects.
While leptin and ghrelin are produced peripherally, they control appetite through their actions on the central nervous system. In particular, they and other appetite-related hormones act on the hypothalamus, a region of the brain central to the regulation of food intake and energy expenditure. There are several circuits within the hypothalamus that contribute to its role in integrating appetite, the melanocortin pathway being the most well understood. The circuit begins with an area of the hypothalamus, the arcuate nucleus, that has outputs to the lateral hypothalamus (LH) and ventromedial hypothalamus (VMH), the brain's feeding and satiety centers, respectively.
The arcuate nucleus contains two distinct groups of neurons. The first group coexpresses neuropeptide Y (NPY) and agouti-related peptide (AgRP) and has stimulatory inputs to the LH and inhibitory inputs to the VMH. The second group coexpresses pro-opiomelanocortin (POMC) and cocaine- and amphetamine-regulated transcript (CART) and has stimulatory inputs to the VMH and inhibitory inputs to the LH. Consequently, NPY/AgRP neurons stimulate feeding and inhibit satiety, while POMC/CART neurons stimulate satiety and inhibit feeding. Both groups of arcuate nucleus neurons are regulated in part by leptin. Leptin inhibits the NPY/AgRP group while stimulating the POMC/CART group. Thus a deficiency in leptin signaling, either via leptin deficiency or leptin resistance, leads to overfeeding and may account for some genetic and acquired forms of obesity.
Microbiological aspects
The role of bacteria colonizing the digestive tract in the development of obesity has recently become the subject of investigation. Bacteria participate in digestion (especially of fatty acids and polysaccharides), and alterations in the proportion of particular strains of bacteria may explain why certain people are more prone to weight gain than others. Human digestive tract are generally either members of the phyla of bacteroidetes or of firmicutes. In obese people, there is a relative abundance of firmicutes (which cause relatively high energy absorption), which is restored by weight loss. From these results it cannot yet be concluded whether this imbalance is the cause of obesity or an effect.
Social determinants
Some obesity co-factors are resistant to the theory that the "epidemic" is a new phenomenon. In particular, a class co-factor consistently appears across many studies. Comparing net worth with BMI scores, a 2004 study found obese American subjects approximately half as wealthy as thin ones. When income differentials were factored out, the inequity persisted—thin subjects were inheriting more wealth than fat ones. A higher rate of a lower level of education and tendencies to rely on cheaper fast foods is seen as a reason why these results are so dissimilar. Another study finds women who married into higher status are predictably thinner than women who married into lower status.
A 2007 study of more than 32,500 people indicated that people risked being obese if their friends, siblings or spouse were. The cohort was followed for 32 years. Friends (especially same-sex peers and even those many miles away) were the most important factor; this would indicate that social factors are a major determinant of body mass - either through behavioral issues or acceptance of increased body mass.
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 (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 large 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, supporting the finding that the body has various mechanisms that maintain weight at a certain set point.
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.
A clinical practice guideline by the US Preventive Services Task Force (USPSTF) concluded that the evidence is insufficient to recommend for or against routine behavioral counseling to promote a healthy diet in unselected patients in primary care settings, but that intensive behavioral dietary counseling is recommended in those with hyperlipidemia and other known risk factors for cardiovascular and diet-related chronic disease. Intensive counseling can be delivered by primary care clinicians or by referral to other specialists, such as nutritionists or dietitians.
Counseling
A meta-analysis of randomized controlled trials concluded that "compared with usual care, dietary counseling interventions produce modest weight losses that diminish over time."
Diets
Various dietary approaches have been proposed, some of which have been compared by randomized controlled trials:
* A comparison of Dr Atkins' diet, Slim-Fast plan, Weight Watchers "pure points programme", and Rosemary Conley's found no significant differences.
* A comparison of Atkins diet, Zone diet, Weight Watchers, and Ornish diet noted:
"all 4 diets resulted in modest statistically significant weight loss at 1 year, with no statistically significant differences between diets"
"The higher discontinuation rates for the Atkins and Ornish diet groups suggest many individuals found these diets to be too extreme"
Low carbohydrate versus low fat
Main article: Medical research related to low-carbohydrate diets
Many studies have focused on diets that reduce calories via a low-carbohydrate (Atkins diet, Zone diet) diet versus a low-fat diet (LEARN diet, Ornish diet). The Nurses' Health Study, an observational cohort study, found that low carbohydrate diets based on vegetable sources of fat and protein are associated with less coronary heart disease.
A meta-analysis of randomized controlled trials by the international Cochrane Collaboration in 2002 concluded that fat-restricted diets are no better than calorie restricted diets in achieving long term weight loss in overweight or obese people.
A more recent meta-analysis that included randomized controlled trials published after the Cochrane review found that "low-carbohydrate, non-energy-restricted diets appear to be at least as effective as low-fat, energy-restricted diets in inducing weight loss for up to 1 year. However, potential favorable changes in triglyceride and high-density lipoprotein cholesterol values should be weighed against potential unfavorable changes in low-density lipoprotein cholesterol values when low-carbohydrate diets to induce weight loss are considered."
The Women's Health Initiative Randomized Controlled Dietary Modification Trial found that a diet of total fat to 20% of energy and increasing consumption of vegetables and fruit to at least 5 servings daily and grains to at least 6 servings daily resulted in:
* no reduction in cardiovascular disease
* an insignificant reduction in invasive breast cancer
* no reductions in colorectal cancer
Additional recent randomized controlled trials have found that:
* A comparison of Atkins, Zone diet, Ornish diet, and LEARN diet in premenopausal women found the greatest benefit from the Atkins diet.
* The choice of diet for a specific person may be influenced by measuring the invididual's insulin secretion:
In young adults "Reducing glycemic [carbohydrate] load may be especially important to achieve weight loss among individuals with high insulin secretion." This is consistent with prior studies of diabetic patients in which low carbohydrate diets were more beneficial.
Low glycemic index
"The glycaemic index factor is a ranking of foods based on their overall effect on blood sugar levels. Low glycaemic index foods, such as lentils, provide a slower more consistent source of glucose to the bloodstream, thereby stimulating less insulin release than high glycaemic index foods, such as white bread."
The glycemic load is "the mathematical product of the glycemic index and the carbohydrate amount".
In a randomized controlled trial that compared four diets that varied in carbohydrate amount and glycemic index found complicated results:
* Diet 1 and 2 were high carbohydrate (55% of total energy intake)
o Diet 1 was high-glycemic index
o Diet 2 was low-glycemic index
* Diet 3 and 4 were high protein (25% of total energy intake)
o Diet 3 was high-glycemic index
o Diet 4 was low-glycemic index
Diets 2 and 3 lost the most weight and fat mass; however, low density lipoprotein fell in Diet 2 and rose in Diet 3. Thus the authors concluded that the high-carbohydrate, low-glycemic index diet was the most favorable.
A meta-analysis by the Cochrane Collaboration concluded that low glycemic index or low glycemic load diets led to more weight loss and better lipid profiles. However, the Cochrane Collaboration grouped low glycemic index and low glycemic load diets together and did not try to separate the effects of the load versus the index.
Exercise
A meta-analysis of randomized controlled trials by the international Cochrane Collaboration found that "exercise combined with diet resulted in a greater weight reduction than diet alone".
Drugs
A meta-analysis of randomized controlled trials by the international Cochrane Collaboration concluded that in diabetic patients found:
"Fluoxetine, orlistat, and sibutramine can achieve statistically significant weight loss over 12 to 57 weeks. The magnitude of weight loss is modest, however, and the long-term health benefits remain unclear. The safety of sibutramine is uncertain. There is a paucity of data on other drugs for weight loss or control in persons with type 2 diabetes."
Medication most commonly prescribed for diet/exercise-resistant obesity is orlistat (Xenical, which reduces intestinal fat absorption by inhibiting pancreatic lipase) and sibutramine (Reductil, Meridia, an anorectic). In the presence of diabetes mellitus, there is evidence that the anti-diabetic drug metformin (Glucophage) can assist in weight loss—rather than sulfonylurea derivatives and insulin, which often lead to further weight gain. The thiazolidinediones (rosiglitazone or pioglitazone) can cause slight weight gain, but decrease the "pathologic" form of abdominal fat, and are therefore often used in obese diabetics.
Bariatric surgery
Bariatric surgery (or "weight loss surgery") is the use of surgical interventions in the treatment of obesity. As every surgical intervention may lead to complications, it is regarded as a last resort when dietary modification and pharmacological treatment have proven to be unsuccessful. Weight loss surgery relies on various principles; the most common approaches are reducing the volume of the stomach, producing an earlier sense of satiation (e.g. by adjustable gastric banding and vertical banded gastroplasty) while others also reduce the length of bowel that food will be in contact with, directly reducing absorption (gastric bypass surgery). Band surgery is reversible, while bowel shortening operations are not. Some procedures can be performed laparoscopically. Complications from weight loss surgery are frequent.
Two large studies have demonstrated a mortality benefit from bariatric surgery. A marked decrease in the risk of diabetes mellitus, cardiovascular disease and cancer.Weight loss was most marked in the first few months after surgery, but the benefit was sustained in the longer term. In one study there was an unexplained increase in deaths from accidents and suicide that did not outweigh the benefit in terms of disease prevention. Gastric bypass surgery was about twice as effective as banding procedures.
Although obesity is an individual clinical condition, it is increasingly viewed as a serious and growing 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.
Definition
Obesity can be defined in absolute or relative terms. In practical settings, obesity is typically evaluated in absolute terms by measuring BMI (body mass index), but also in terms of its distribution through waist circumference or waist-hip circumference ratio measurements. In addition, the presence of obesity needs to be regarded in the context of other risk factors and comorbidities (other medical conditions that could influence risk of complications).
BMI
BMI, or body mass index, is a simple and widely used method for estimating body fat. BMI was developed by the Belgian statistician and anthropometrist Adolphe Quetelet. It is calculated by dividing the subject's weight by the square of his/her height, typically expressed either in metric or US "Customary" units:
Metric: BMI = kg / m2
Where kg is the subject's weight in kilograms and m is the subject's height in metres.
US/Customary: BMI = lb * 703 / in2
Where lb is the subject's weight in pounds and in is the subject's height in inches.
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.
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.
In a cohort of almost 15,000 subjects from the National Health and Nutrition Examination Survey (NHANES) III study, waist circumference explained obesity-related health risk significantly better than BMI when metabolic syndrome was taken as an outcome measure.
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. Their routine use is discouraged.
Other measurements of body fat include computed tomography (CT/CAT scan), magnetic resonance imaging (MRI/NMR), and dual energy X-ray absorptiometry (DXA).
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.
Effects on health
A large number of medical conditions have been associated with obesity. Health consequences are categorised as being the result of either increased fat mass (osteoarthritis, obstructive sleep apnea, social stigma) or increased number of fat cells (diabetes, cancer, cardiovascular disease, non-alcoholic fatty liver disease).[12] Mortality is increased in obesity, with a BMI of over 32 being associated with a doubled risk of death. There are alterations in the body's response to insulin (insulin resistance), a proinflammatory state and an increased tendency to thrombosis (prothrombotic state).
Disease associations may be dependent or independent of the distribution of adipose tissue. Central obesity (male-type or waist-predominant obesity, characterised by a high waist-hip ratio), is an important risk factor for the metabolic syndrome, the clustering of a number of diseases and risk factors that heavily predispose for cardiovascular disease. These are diabetes mellitus type 2, high blood pressure, high blood cholesterol, and triglyceride levels (combined hyperlipidemia).
Apart from the metabolic syndrome, obesity is also correlated with a variety of other complications. For some of these complaints, it has not been clearly established to what extent they are caused directly by obesity itself, or have some other cause (such as limited exercise) that causes obesity as well.
* 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: erectile dysfunction, urinary incontinence, chronic renal failure, 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, idiopathic intracranial hypertension
* Respiratory: dyspnea, obstructive sleep apnea, hypoventilation syndrome, Pickwickian syndrome, asthma
* Psychological: Depression, low self esteem, body dysmorphic disorder, social stigmatization
While being severely obese has many health ramifications, those who are somewhat overweight face little increased mortality or morbidity. Osteoporosis is known to occur less in slightly overweight people.
Causes and mechanisms
Lifestyle
Most researchers have concluded that the combination of an excessive nutrient intake and a sedentary lifestyle are the main cause for the rapid acceleration of obesity in Western society in the last quarter of the 20th century.
Despite the widespread availability of nutritional information in schools, doctors' offices, on the internet and on groceries, it is evident that overeating remains a substantial problem. For instance, reliance on energy-dense fast-food meals tripled between 1977 and 1995, and calorie intake quadrupled over the same period.
However, dietary intake in itself is insufficient to explain the phenomenal rise in levels of obesity in much of the industrialized world during recent years. An increasingly sedentary lifestyle also has a significant role to play. More and more research into child obesity, for example, links such things as the school run, with the current high levels of this disease.
Less well established life style issues which may influence obesity include a stressful mentality and insufficient sleep.
Genetics
As with many medical conditions, the calorific 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 conditions that feature obesity have been identified (such as Prader-Willi syndrome, Bardet-Biedl syndrome, MOMO syndrome, leptin receptor mutations and melanocortin 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.
A 2007 study identified fairly common mutations in the FTO gene; heterozygotes had a 30% increased risk of obesity, while homozygotes faced a 70% increased risk.
On a population level, the thrifty gene hypothesis postulates that certain ethnic groups 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 may have been 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 stable food supplies.
Medical illness
Certain physical and mental illnesses and particular pharmaceutical substances may predispose to obesity. Apart from the fact that correcting these situations may improve the obesity, the presence of increased body weight may complicate the management of others.
Medical illnesses that increase obesity risk include several rare congenital syndromes (listed above), hypothyroidism, Cushing's syndrome, growth hormone deficiency.[24] Smoking cessation is a known cause for moderate weight gain, as nicotine suppresses appetite. Certain medications (e.g. steroids, atypical antipsychotics, some fertility medication) may cause weight gain.
Mental illnesses may also increase obesity risk, specifically some eating disorders such as bulimia nervosa, binge eating disorder, and compulsive overeating (also known as food addiction).
Neurobiological mechanisms
Scientists investigating the mechanisms and treatment of obesity may use animal models such as mice to conduct experiments.
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, and 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. This resistance is thought to explain in part why administration of leptin has not been shown to be effective in suppressing appetite in most obese subjects.
While leptin and ghrelin are produced peripherally, they control appetite through their actions on the central nervous system. In particular, they and other appetite-related hormones act on the hypothalamus, a region of the brain central to the regulation of food intake and energy expenditure. There are several circuits within the hypothalamus that contribute to its role in integrating appetite, the melanocortin pathway being the most well understood. The circuit begins with an area of the hypothalamus, the arcuate nucleus, that has outputs to the lateral hypothalamus (LH) and ventromedial hypothalamus (VMH), the brain's feeding and satiety centers, respectively.
The arcuate nucleus contains two distinct groups of neurons. The first group coexpresses neuropeptide Y (NPY) and agouti-related peptide (AgRP) and has stimulatory inputs to the LH and inhibitory inputs to the VMH. The second group coexpresses pro-opiomelanocortin (POMC) and cocaine- and amphetamine-regulated transcript (CART) and has stimulatory inputs to the VMH and inhibitory inputs to the LH. Consequently, NPY/AgRP neurons stimulate feeding and inhibit satiety, while POMC/CART neurons stimulate satiety and inhibit feeding. Both groups of arcuate nucleus neurons are regulated in part by leptin. Leptin inhibits the NPY/AgRP group while stimulating the POMC/CART group. Thus a deficiency in leptin signaling, either via leptin deficiency or leptin resistance, leads to overfeeding and may account for some genetic and acquired forms of obesity.
Microbiological aspects
The role of bacteria colonizing the digestive tract in the development of obesity has recently become the subject of investigation. Bacteria participate in digestion (especially of fatty acids and polysaccharides), and alterations in the proportion of particular strains of bacteria may explain why certain people are more prone to weight gain than others. Human digestive tract are generally either members of the phyla of bacteroidetes or of firmicutes. In obese people, there is a relative abundance of firmicutes (which cause relatively high energy absorption), which is restored by weight loss. From these results it cannot yet be concluded whether this imbalance is the cause of obesity or an effect.
Social determinants
Some obesity co-factors are resistant to the theory that the "epidemic" is a new phenomenon. In particular, a class co-factor consistently appears across many studies. Comparing net worth with BMI scores, a 2004 study found obese American subjects approximately half as wealthy as thin ones. When income differentials were factored out, the inequity persisted—thin subjects were inheriting more wealth than fat ones. A higher rate of a lower level of education and tendencies to rely on cheaper fast foods is seen as a reason why these results are so dissimilar. Another study finds women who married into higher status are predictably thinner than women who married into lower status.
A 2007 study of more than 32,500 people indicated that people risked being obese if their friends, siblings or spouse were. The cohort was followed for 32 years. Friends (especially same-sex peers and even those many miles away) were the most important factor; this would indicate that social factors are a major determinant of body mass - either through behavioral issues or acceptance of increased body mass.
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 (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 large 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, supporting the finding that the body has various mechanisms that maintain weight at a certain set point.
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.
A clinical practice guideline by the US Preventive Services Task Force (USPSTF) concluded that the evidence is insufficient to recommend for or against routine behavioral counseling to promote a healthy diet in unselected patients in primary care settings, but that intensive behavioral dietary counseling is recommended in those with hyperlipidemia and other known risk factors for cardiovascular and diet-related chronic disease. Intensive counseling can be delivered by primary care clinicians or by referral to other specialists, such as nutritionists or dietitians.
Counseling
A meta-analysis of randomized controlled trials concluded that "compared with usual care, dietary counseling interventions produce modest weight losses that diminish over time."
Diets
Various dietary approaches have been proposed, some of which have been compared by randomized controlled trials:
* A comparison of Dr Atkins' diet, Slim-Fast plan, Weight Watchers "pure points programme", and Rosemary Conley's found no significant differences.
* A comparison of Atkins diet, Zone diet, Weight Watchers, and Ornish diet noted:
"all 4 diets resulted in modest statistically significant weight loss at 1 year, with no statistically significant differences between diets"
"The higher discontinuation rates for the Atkins and Ornish diet groups suggest many individuals found these diets to be too extreme"
Low carbohydrate versus low fat
Main article: Medical research related to low-carbohydrate diets
Many studies have focused on diets that reduce calories via a low-carbohydrate (Atkins diet, Zone diet) diet versus a low-fat diet (LEARN diet, Ornish diet). The Nurses' Health Study, an observational cohort study, found that low carbohydrate diets based on vegetable sources of fat and protein are associated with less coronary heart disease.
A meta-analysis of randomized controlled trials by the international Cochrane Collaboration in 2002 concluded that fat-restricted diets are no better than calorie restricted diets in achieving long term weight loss in overweight or obese people.
A more recent meta-analysis that included randomized controlled trials published after the Cochrane review found that "low-carbohydrate, non-energy-restricted diets appear to be at least as effective as low-fat, energy-restricted diets in inducing weight loss for up to 1 year. However, potential favorable changes in triglyceride and high-density lipoprotein cholesterol values should be weighed against potential unfavorable changes in low-density lipoprotein cholesterol values when low-carbohydrate diets to induce weight loss are considered."
The Women's Health Initiative Randomized Controlled Dietary Modification Trial found that a diet of total fat to 20% of energy and increasing consumption of vegetables and fruit to at least 5 servings daily and grains to at least 6 servings daily resulted in:
* no reduction in cardiovascular disease
* an insignificant reduction in invasive breast cancer
* no reductions in colorectal cancer
Additional recent randomized controlled trials have found that:
* A comparison of Atkins, Zone diet, Ornish diet, and LEARN diet in premenopausal women found the greatest benefit from the Atkins diet.
* The choice of diet for a specific person may be influenced by measuring the invididual's insulin secretion:
In young adults "Reducing glycemic [carbohydrate] load may be especially important to achieve weight loss among individuals with high insulin secretion." This is consistent with prior studies of diabetic patients in which low carbohydrate diets were more beneficial.
Low glycemic index
"The glycaemic index factor is a ranking of foods based on their overall effect on blood sugar levels. Low glycaemic index foods, such as lentils, provide a slower more consistent source of glucose to the bloodstream, thereby stimulating less insulin release than high glycaemic index foods, such as white bread."
The glycemic load is "the mathematical product of the glycemic index and the carbohydrate amount".
In a randomized controlled trial that compared four diets that varied in carbohydrate amount and glycemic index found complicated results:
* Diet 1 and 2 were high carbohydrate (55% of total energy intake)
o Diet 1 was high-glycemic index
o Diet 2 was low-glycemic index
* Diet 3 and 4 were high protein (25% of total energy intake)
o Diet 3 was high-glycemic index
o Diet 4 was low-glycemic index
Diets 2 and 3 lost the most weight and fat mass; however, low density lipoprotein fell in Diet 2 and rose in Diet 3. Thus the authors concluded that the high-carbohydrate, low-glycemic index diet was the most favorable.
A meta-analysis by the Cochrane Collaboration concluded that low glycemic index or low glycemic load diets led to more weight loss and better lipid profiles. However, the Cochrane Collaboration grouped low glycemic index and low glycemic load diets together and did not try to separate the effects of the load versus the index.
Exercise
A meta-analysis of randomized controlled trials by the international Cochrane Collaboration found that "exercise combined with diet resulted in a greater weight reduction than diet alone".
Drugs
A meta-analysis of randomized controlled trials by the international Cochrane Collaboration concluded that in diabetic patients found:
"Fluoxetine, orlistat, and sibutramine can achieve statistically significant weight loss over 12 to 57 weeks. The magnitude of weight loss is modest, however, and the long-term health benefits remain unclear. The safety of sibutramine is uncertain. There is a paucity of data on other drugs for weight loss or control in persons with type 2 diabetes."
Medication most commonly prescribed for diet/exercise-resistant obesity is orlistat (Xenical, which reduces intestinal fat absorption by inhibiting pancreatic lipase) and sibutramine (Reductil, Meridia, an anorectic). In the presence of diabetes mellitus, there is evidence that the anti-diabetic drug metformin (Glucophage) can assist in weight loss—rather than sulfonylurea derivatives and insulin, which often lead to further weight gain. The thiazolidinediones (rosiglitazone or pioglitazone) can cause slight weight gain, but decrease the "pathologic" form of abdominal fat, and are therefore often used in obese diabetics.
Bariatric surgery
Bariatric surgery (or "weight loss surgery") is the use of surgical interventions in the treatment of obesity. As every surgical intervention may lead to complications, it is regarded as a last resort when dietary modification and pharmacological treatment have proven to be unsuccessful. Weight loss surgery relies on various principles; the most common approaches are reducing the volume of the stomach, producing an earlier sense of satiation (e.g. by adjustable gastric banding and vertical banded gastroplasty) while others also reduce the length of bowel that food will be in contact with, directly reducing absorption (gastric bypass surgery). Band surgery is reversible, while bowel shortening operations are not. Some procedures can be performed laparoscopically. Complications from weight loss surgery are frequent.
Two large studies have demonstrated a mortality benefit from bariatric surgery. A marked decrease in the risk of diabetes mellitus, cardiovascular disease and cancer.Weight loss was most marked in the first few months after surgery, but the benefit was sustained in the longer term. In one study there was an unexplained increase in deaths from accidents and suicide that did not outweigh the benefit in terms of disease prevention. Gastric bypass surgery was about twice as effective as banding procedures.
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