Obesity reference

Obesity is a disease in which excess body fat has accumulated to such an extent that health may be negatively affected.[1] It is commonly defined as a body mass index (weight divided by height squared) of 30 kg/m2 or higher.[1] This distinguishes it from being overweight as defined by a BMI of between 25-29.9.[1] Many studies show an association between excessive body weight and various diseases, particularly cardiovascular diseases, diabetes mellitus type 2, sleep apnea, certain types of cancer, and osteoarthritis.[2][3] As a result, obesity has been found to reduce life expectancy.[3] Although obesity is an individual clinical condition, most authorities view it as a serious and growing public health problem that needs to be addressed by encouraging healthy dietary choices and physical exercise on a population-wide scale.

Classification

Obesity in absolute terms is an increase of body fatty tissue mass. In a practical setting it is difficult to measure this directly, and obesity is typically measured by BMI (body mass index) and in terms of its distribution through waist circumference or waist-hip circumference ratio measurements.[5] In addition, the presence of obesity needs to be evaluated in the context of other risk factors and comorbidities (other medical conditions that could influence risk of complications).[2]

Obesity survival paradox

Although the negative health consequences of obesity in the general population are well support by the available evidence, health outcomes in certain subgroups seem to be improved at an increased BMI, thus leading to the obesity survival paradox.[20] The paradox was first described in 1999 in overweight and obese patients undergoing hemodialysis. Since then it has been found in a few other subgroups and explanations for its occurrence have been put forwards.[20]

In people with heart failure, those with a BMI between 30.0-34.9 had lower mortality then those with a normal weight. One explanation for this is that people often lose weight as they become progressively more ill.[21] This is also seen in those with other types of preexisting heart disease. People with class I obesity do not have greater rates of further cardiac problems over people who have heart disease and are of normal weight. In people with greater degrees of obesity, however, increased rates of heart disease are observed.[22][23] Even after coronary artery bypass graphs (CABG) no increase in mortality is seen in the overweight and obese. [24]

Causes

Most researchers agree that a combination of excessive calorie consumption and a sedentary lifestyle are the primary causes of obesity in the majority of the population.[25] Other less well established or minor influences include genetic causes, medical and psychiatric illnesses, and microbiological causes. A 2006 review identifies ten other possibly underinvestigated causes for recently increasing rates of obesity: (1) insufficient sleep, (2) endocrine disruptors - food substances that interfere with lipid metabolism, (3) decreased variability in ambient temperature, (4) decreased rates of smoking, which suppresses appetite, (5) increased use of medication that leads to weight gain, (6) increased distribution of ethnic and age groups that tend to be heavier, (7) pregnancy at a later age, (8) intrauterine and intergenerational effects, (9) positive natural selection of people with a higher BMI, (10) assortative mating, heavier people tending to form relationships with each other.[26]

Dietary

Despite the widespread availability of nutritional information in schools, doctors' offices, on the internet and on product packaging,[27] it is evident that overeating remains a substantial problem. In the period of 1971-2000, obesity rates in the United States increased from 14.5% to 30.9% of the population.[28] During the same time, an increase occurred in the average amount of calories consumed. For women, the average increase was 335 calories per day (1542 calories in 1971 and 1877 calories in 2004), while for men the average increase was 168 calories per day (2450 calories in 1971 and 2618 calories in 2004). Most of these extra calories came from an increase in carbohydrate consumption rather than an increase in fat consumption.[29] Dietary trends have also change with reliance on energy-dense fast-food meals tripling between 1977 and 1995, and calorie intake from fast food quadrupling over the same period.[30]

Sedentary lifestyle

An increasingly sedentary lifestyle plays a significant role in obesity. There has been a trend toward decreased physical activity due in part to increasingly mechanized forms of work, changing modes of transportation, and increasing urbanization. Studies in children and adults have found a association between the number of hours of television watched and the prevalence of obesity.[31] [32][33] Driving one's children to school also decreases the amount of exercise that these children get and has led to calls for reduced car use around schools.[34]

Genetics

Like many other medical conditions, obesity is the result of an interplay between genetic and environmental factors. Polymorphisms in various genes controlling appetite, metabolism, and adipokine release may predispose to obesity when sufficient calories are present. Obesity is a major feature in a number of rare genetic conditions: Prader-Willi syndrome, Bardet-Biedl syndrome, MOMO syndrome, leptin receptor mutations, melanocortin receptor mutations. In a people with early-onset severe obesity (defined by an onset before ten years of age and body mass index over three standard deviations above normal), 7% harbor a single locus mutation.[35] Apart from the above syndromes, an association has been found between an FTO gene polymorphism and weight. The 16% of adults in the study who were homozygous for this allele weighed about 3 kilograms more then those who had not inheireted this trait and subsequently had a 1.6 fold greater rate of obesity.[36] A study of 5092 identical twins found that childhood obesity has a strong (77%) inherited component, suggesting that many genetic influences underpinning the development of obesity are yet to be discovered.[37]

On a population level, the thrifty gene hypothesis postulates that certain ethnic groups may be more prone to obesity when exposed to an equivalent environment. Their ability to take advantage of rare periods of abundance by storing energy as fat would be advantagious during times of varing food availiablity. Individuals with greater adipose reserves would be more likely survive famine. This tendency to store fat however would be maladaptive in societies with stable food supplies.[38]

Medical illness

Certain physical and mental illnesses and the pharmaceutical substances used to treat them can increase one's risk of obesity. Medical illnesses that increase obesity risk include several rare genetic syndromes (listed above) as well as some congenital or acquired conditions: (1) hypothyroidism, (2) Cushing's syndrome, (3) growth hormone deficiency,[39] and (4) eating disorders such bulimia nervosa, binge eating disorder and compulsive overeating.

Certain medications may cause weight gain and or negative changes in body composition, such as steroids, atypical antipsychotics, some fertility medication, insulin and sulfonylureas.

Microbiological

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 bacteria 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 be concluded whether this imbalance is the cause or effect of obesity.[40]

Social determinants

A correlation between social class and BMI appears across many studies. Comparing net worth with BMI scores, a 2004 study[41] 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 lower level of education and tendencies to rely on cheaper fast foods are seen as reasons why these results occur. Another study found women who married into higher status are predictably thinner than women who married into lower status.

A study of 12,067 people followed for 32 years found a correlation in BMI change between friends, siblings, and spouses. This was irrespective of geographical distance. The authors concluded that acceptance of body mass by people in your life plays an important role in changes in body size.[42]

Cessation of smoking verse continued smoking can leads to weight gain. A study found that those who quit smoking gained 4-5 kilograms over ten years. One sixth of the rise in obesity in North Americans can be attributed to falling rates of smoking . [43]

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[44] 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, most obese individuals are thought to be leptin resistant and have been found to have high levels of leptin.[45]. 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.[44]

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.[44] 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.[46]

The arcuate nucleus contains two distinct groups of neurons.[44] 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.[44]

Treatment

Main article: Weight loss

The main treatment for obesity consists of eating less and exercising more. Diet programs may produce weight lose over the short term,[47] but keeping this weight off can be a problem. It often requires making exercise and a lower calorie diet a permanent part of a person's lifestyle.[48][49]In the general population only 20% are successful at long-term weight loss maintenance.[50] In a more structured setting, however, 67% of people who lost greater then 10% of their body mass maintained or continued to lose weight one year later.[51] Even after five years a meta analysis found an average maintained weight lose of more then 3 kg or 3% of total body mass. [52] There are significant benefits to weight loss. In a prospective study, intentional weight loss of any amount was associated with a 20% reduction in all-cause mortality.[53]

Diet

Main article: Dieting

Diets to promote weight lose are general divided into four categories low-calorie, low-fat, low-carbohydrate, and very low calorie. Low calorie diets usually produce an energy deficit of 500 - 1000 calories per day. They include the DASH diet and Weight Watchers among others. The National Institutes of Health reviewed 34 randomized controlled trials to determine the effectiveness of low-calorie diets. They found that these diet lowered total body mass by 8% over 3-12 months.[54] Low fat diets involve the reduction of the percentage of fat in ones diet. Calorie consumption is reduced but not purposely so. Diets of this type include NCEP Step I and II. A meta-analysis of 16 trials of 2–12 months duration found that low-fat diets resulted in weight loss of 3.2 kg over eating as normal.[55] Low carbohydrate diets are ralatively high in fat and protein. They are very popular in the press however are not recommened by the American Heart Association. Diets of this type include Atkins and Protein Power. A review of 94 trials found that weight lose was assciated with decreased calorie consumption rather then any special properties of reduced carbohydrate consumption. No adverse affect from low carbohydrate diets were detected.[56]

A further meta-analysis of 6 randomized controlled trials found no difference in diet types, with a 2–4 kilogram weight lose in all studies.[57]

Exercise

Main article: Exercise

With use, muscles consume energy derived from both fat and glycogen. Due to the large size of leg muscles walking, running, and cycling are the most effective means of exercise to reduce body fat.[citation needed] A meta-analysis of 43 randomized controlled trials by the international Cochrane Collaboration found that exercising alone led to limited weight loss, but in combination with diet it resulted in a 1 kilogram weight loss over dieting alone.[58] Even though exercise as carried out in the general population has only modest effects a dose response curve is found and very intense exercise can lead to substantial weight lose. During 20 weeks of basic military training with no dietary restriction obese military recruit lost 12.5 kg.[59]

Drugs

Main article: Anti-obesity drug

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). Weight loss with these drugs is modest, and over the longer term average weight loss on orlistat is 2.9 kg, sibutramine 4.2 kg and rimonabant 4.7 kg. Orlistat and rimonabant lead to a reduced incidence of diabetes, and all drugs have some effect on lipoproteins (different forms of cholesterol). There is little data, however, on longer-term complications of obesity such as heart attacks. All drugs have side-effects and potential contraindications.[60] It is common for weight loss drugs to be tried for a period of time (e.g. 3 months), and to discontinue them or change to another agent if no benefit is achieved, such as weight loss less than 5% the total body weight.[4]

A meta-analysis of randomized controlled trials by the international Cochrane Collaboration concluded that in diabetic patients fluoxetine, orlistat and sibutramine could achieve significant but modest weight loss over 12-57 weeks, with long-term health benefits being unclear.[61]

Obesity may also influence the choice of drug treatment for diabetes. Metformin may lead to mild weight reduction (as opposed to sulfonylureas and insulin), and has been demonstrated to reduce the risk of cardiovascular disease in type 2 diabetics who are obese.[62] The thiazolidinediones may cause slight weight gain, but decrease the "pathologic" form of abdominal fat and may therefore be used in diabetics with central obesity.[63]

Bariatric surgery

Main article: 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.[64]

Two large studies have demonstrated a mortality benefit from bariatric surgery. A marked decrease in the risk of diabetes mellitus, cardiovascular disease and cancer has been found.[65][66] 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.[66]