Obesity

Heritability of BMI is about 66%. Genetic factors may affect the many signaling molecules and receptors used by parts of the hypothalamus and gastrointestinal tract to regulate food intake (see sidebar Pathways Regulating Food Intake Pathways Regulating Food Intake ). Genetic factors can be inherited or result from conditions in utero (called genetic imprinting). Rarely, obesity results from abnormal levels of peptides that regulate food intake (eg, leptin) or abnormalities in their receptors (eg, melanocortin-4 receptor).

Genetic factors also regulate energy expenditure, including basal metabolic rate, diet-induced thermogenesis, and nonvoluntary activity–associated thermogenesis. Genetic factors may have a greater effect on the distribution of body fat, particularly abdominal fat (which increases the risk of metabolic syndrome Metabolic Syndrome Metabolic syndrome is characterized by a large waist circumference (due to excess abdominal fat), hypertension, abnormal fasting plasma glucose or insulin resistance, and dyslipidemia. Causes... read more ), than on the amount of body fat.

Weight is gained when caloric intake exceeds energy needs. Important determinants of energy intake include

High-calorie foods (eg, processed foods), diets high in refined carbohydrates, and consumption of soft drinks, fruit juices, and alcohol promote weight gain. Diets high in fresh fruit and vegetables, fiber, complex carbohydrates, and lean proteins, with water as the main fluid consumed, minimize weight gain.

A sedentary lifestyle promotes weight gain.

Prenatal maternal obesity, prenatal maternal smoking, and intrauterine growth restriction can disturb weight regulation and contribute to weight gain during childhood and later. Obesity that persists beyond early childhood makes weight loss in later life more difficult.

The composition of the gut microbiome also appears to be an important factor; early use of antibiotics and other factors that alter the composition of the gut microbiome may promote weight gain and obesity later in life (1 Etiology references Obesity is excess body weight, defined as a body mass index (BMI) of ≥ 30 kg/m². Complications include cardiovascular disorders (particularly in people with excess abdominal fat)... read more ).

Early exposure to obesogens, a type of endocrine-disrupting chemical (eg, cigarette smoke, bisphenol A, air pollution, flame retardants, phthalates, polychlorinated biphenyls) can alter metabolic set points through epigenetics or nuclear activation, increasing the propensity of developing obesity (2 Regulatory factors ).

Adverse childhood events or abuse in early childhood increase risk of several disorders, including obesity. The Centers for Disease Control and Prevention's adverse childhood events study demonstrated that childhood history of verbal, physical, or sexual abuse predicted an 8% increase risk of BMI ≥ 30 and 17.3% of BMI ≥ to 40. Certain types of abuse carried the strongest risk. For example, frequent verbal abuse had the largest increase in risk (88%) for BMI > 40. Being often hit and injured increased the risk of BMI > 30 by 71% (3 Etiology references Obesity is excess body weight, defined as a body mass index (BMI) of ≥ 30 kg/m². Complications include cardiovascular disorders (particularly in people with excess abdominal fat)... read more ). Cited mechanisms for the association between abuse and obesity include neurobiologic and epigenetic phenomena (4 Etiology references Obesity is excess body weight, defined as a body mass index (BMI) of ≥ 30 kg/m². Complications include cardiovascular disorders (particularly in people with excess abdominal fat)... read more ).

About 15% of women permanently gain ≥ 20 lb with each pregnancy.

Insufficient sleep (usually considered < 6 to 8 hours/night) can result in weight gain by changing the levels of satiety hormones that promote hunger.

Drugs, including corticosteroids, lithium, traditional antidepressants (tricyclics, tetracyclics, monoamine oxidase inhibitors [MAOIs]), benzodiazepines, antiseizure drugs, thiazolidinediones (eg, rosiglitazone, pioglitazone), beta-blockers, and antipsychotic drugs, can cause weight gain.

Uncommonly, weight gain is caused by one of the following disorders:

At least 2 pathologic eating patterns may be associated with obesity:

Similar but less extreme patterns probably contribute to excess weight gain in more people. For example, eating after the evening meal contributes to excess weight gain in many people who do not have night-eating syndrome.

Body composition—the percentage of body fat and muscle—is also considered when obesity is diagnosed. Although probably unnecessary in routine clinical practice, body composition analysis can be helpful if clinicians question whether elevated BMI is due to muscle or excessive fat.

The percentage of body fat can be estimated by measuring skinfold thickness (usually over the triceps) or determining mid upper arm muscle area Physical examination .

Bioelectrical impedance analysis (BIA) can estimate percentage of body fat simply and noninvasively. BIA estimates percentage of total body water directly; percentage of body fat is derived indirectly. BIA is most reliable in healthy people and in people with only a few chronic disorders that do not change the percentage of total body water (eg, moderate obesity, diabetes mellitus). Whether measuring BIA poses risks in people with implanted defibrillators is unclear.

Underwater (hydrostatic) weighing is the most accurate method for measuring percentage of body fat. Costly and time-consuming, it is used more often in research than in clinical care. To be weighed accurately while submerged, people must fully exhale beforehand.

Imaging procedures, including CT, MRI, and dual-energy x-ray absorptiometry (DXA), can also estimate the percentage and distribution of body fat but are usually used only for research.

Obese patients should be screened for common comorbid disorders, such as obstructive sleep apnea Obstructive Sleep Apnea (OSA) Obstructive sleep apnea (OSA) consists of multiple episodes of partial or complete closure of the upper airway that occur during sleep and lead to breathing cessation (defined as a period of... read more , diabetes Screening for diabetes mellitus Diabetes mellitus is impaired insulin secretion and variable degrees of peripheral insulin resistance leading to hyperglycemia. Early symptoms are related to hyperglycemia and include polydipsia... read more , dyslipidemia Dyslipidemia Dyslipidemia is elevation of plasma cholesterol, triglycerides (TGs), or both, or a low high-density lipoprotein cholesterol level that contributes to the development of atherosclerosis... read more , hypertension Hypertension Hypertension is sustained elevation of resting systolic blood pressure (≥ 130 mm Hg), diastolic blood pressure (≥ 80 mm Hg), or both. Hypertension with no known cause (primary; formerly, essential... read more , fatty liver Nonalcoholic Fatty Liver Disease (NAFLD) Fatty liver is excessive accumulation of lipid in hepatocytes. Nonalcoholic fatty liver disease (NAFLD) includes simple fatty infiltration (a benign condition called fatty liver), whereas nonalcoholic... read more , and depression Diagnosis Depressive disorders are characterized by sadness severe enough or persistent enough to interfere with function and often by decreased interest or pleasure in activities. Exact cause is unknown... read more . Screening tools can help; for example, for obstructive sleep apnea, clinicians can use an instrument such as the STOP-BANG questionnaire (see table STOP-BANG Risk Score for Obstructive Sleep Apnea STOP-BANG Risk Score for Obstructive Sleep Apnea ) and often the apnea-hypopnea index Obstructive Sleep Apnea (OSA) Obstructive sleep apnea (OSA) consists of multiple episodes of partial or complete closure of the upper airway that occur during sleep and lead to breathing cessation (defined as a period of... read more (total number of apnea or hypopnea episodes occurring per hour of sleep). Obstructive sleep apnea is often underdiagnosed, and obesity increases the risk.

Balanced eating is important for weight loss and maintenance.

Strategies include

Low-calorie, high-fiber diets that modestly restrict calories (by 600 kcal/day) and that incorporate lean protein appear to have the best long-term outcome. Foods with a low glycemic index (see table Glycemic Index of Some Foods Glycemic Index of Some Foods ) and marine fish oils or monounsaturated fats derived from plants (eg, olive oil) reduce the risk of cardiovascular disorders and diabetes Diabetes Mellitus (DM) Diabetes mellitus is impaired insulin secretion and variable degrees of peripheral insulin resistance leading to hyperglycemia. Early symptoms are related to hyperglycemia and include polydipsia... read more .

Use of meal replacements can help with weight loss and maintenance; these products can be used regularly or intermittently.

Diets that are overly restrictive are unlikely to be maintained or to result in long-term weight loss. Diets that limit caloric intake to < 50% of basal energy expenditure Energy expenditure Many undernourished patients need nutritional support, which aims to increase lean body mass. Oral feeding can be difficult for some patients with anorexia or with eating or absorption problems... read more (BEE), described as very low calorie diets, can have as few as 800 kcal/day. A very low calorie diet may be indicated for obese patients; however, such diets must be supervised by a physician, and after weight is lost, intake must be increased gradually to prevent patients from regaining weight.

Exercise increases energy expenditure, basal metabolic rate, and diet-induced thermogenesis. Exercise also seems to regulate appetite to more closely match caloric needs. Other benefits associated with physical activity include

Exercise, including strengthening (resistance) exercises, increases muscle mass. Because muscle tissue burns more calories at rest than does fat tissue, increasing muscle mass produces lasting increases in basal metabolic rate. Exercise that is interesting and enjoyable is more likely to be sustained. A combination of aerobic and resistance exercise is better than either alone. Guidelines suggest physical activity of 150 minutes/week for health benefits and 300 to 360 minutes/week for weight loss and maintenance. Developing a more physically active lifestyle can help with weight loss and maintenance.

Clinicians can recommend various behavioral interventions to help patients lose weight. They include

Support may come from a group, a buddy, or family members. Participation in a support group can improve adherence to lifestyle changes and thus increase weight loss. The more frequently people attend group meetings, the greater the support, motivation, and supervision they receive and the greater their accountability, resulting in greater weight loss.

Self-monitoring may include keeping a food log (including the number of calories in foods), weighing regularly, and observing and recording behavioral patterns. Other useful information to record includes time and location of food consumption, the presence or absence of other people, and mood. Clinicians can provide feedback about how patients may improve their eating habits.

Stress management involves teaching patients to identify stressful situations and to develop strategies to manage stress that do not involve eating (eg, going for a walk, meditating, deep breathing).

Contingency management involves providing tangible rewards for positive behaviors (eg, for increasing time spent walking or reducing consumption of certain foods). Rewards may be given by other people (eg, from members of a support group or a health care practitioner) or by the person (eg, purchase of new clothing or tickets to a concert). Verbal rewards (praise) may also be useful.

Problem solving involves identifying and planning ahead for situations that increase the risk of unhealthy eating (eg, travelling, going out to dinner) or that reduce the opportunity for physical activity (eg, driving across country).

Stimulus control involves identifying obstacles to healthy eating and an active lifestyle and developing strategies to overcome them. For example, people may avoid going by a fast food restaurant or not keep sweets in the house. For a more active lifestyle, they may take up an active hobby (eg, gardening), enroll in scheduled group activities (eg, exercise classes, sports teams), walk more, make a habit of taking the stairs instead of elevators, and park at the far end of parking lots (resulting in a longer walk).

Internet resources, applications for mobile devices, and other technological devices may also help with adherence to lifestyle changes and weight loss. Applications can help patients set a weight-loss goal, monitor their progress, track food consumption, and record physical activity.

Drugs (eg, orlistat, phentermine, phentermine/topiramate, liraglutide, semaglutide, lorcaserin [not available in US]) may be used if BMI is ≥ 30 or if BMI is ≥ 27 in patients who have complications (eg, hypertension Hypertension Hypertension is sustained elevation of resting systolic blood pressure (≥ 130 mm Hg), diastolic blood pressure (≥ 80 mm Hg), or both. Hypertension with no known cause (primary; formerly, essential... read more , insulin resistance Type 2 diabetes Diabetes mellitus is impaired insulin secretion and variable degrees of peripheral insulin resistance leading to hyperglycemia. Early symptoms are related to hyperglycemia and include polydipsia... read more ). Usually, drug treatment results in modest (5 to 10%) weight loss.

Orlistat inhibits intestinal lipase, decreasing fat absorption and improving blood glucose and lipids. Because orlistat is not absorbed, systemic effects are rare. Flatus, oily stools, and diarrhea are common but tend to resolve during the 2nd year of treatment. A dose of 120 mg orally 3 times a day should be taken with meals that include fat. A vitamin supplement should be taken at least 2 hours before or after taking orlistat. Malabsorption and cholestasis are contraindications; irritable bowel syndrome and other gastrointestinal disorders may make orlistat difficult to tolerate. Orlistat is available over-the-counter.

Phentermine is a centrally acting appetite suppressant for short-term use ( ≤ 3 months). Usual starting dose is 15 mg once/day, and dose may be increased to 30 mg once/day, 37.5 mg once/day, 15 mg twice a day, or 8 mg 3 times a day before meals. Common side effects include elevated blood pressure and heart rate, insomnia, anxiety, and constipation. Phentermine should not be used in patients with preexisting cardiovascular disorders, poorly controlled hypertension, hyperthyroidism, or a history of drug abuse or addiction. Twice a day dosing may help control appetite better throughout the day.

The combination of phentermine and topiramate (used to treat seizures and migraines) is approved for long-term use. This combination drug results in weight loss for up to 2 years. The starting dose of the extended-release form (phentermine 3.75 mg/topiramate 23 mg) should be increased to 7.5 mg/46 mg after 2 weeks; then the dose can be gradually increased to a maximum of 15 mg/92 mg if needed to maintain weight loss. Because birth defects are a risk, the combination should be given to women of reproductive age only if they are using contraception and are tested monthly for pregnancy. Other potential adverse effects include sleep problems, cognitive impairment, and increased heart rate. Long-term cardiovascular effects are unknown, and postmarketing studies are ongoing.

Lorcaserin (not available in the US) suppresses appetite via selective agonism of serotonin 2C (5-HT2C) brain receptors. Unlike serotonergic drugs previously used for weight loss, lorcaserin selectively targets 5-HT2C receptors in the hypothalamus, which, when targeted, result in hypophagia; it does not to stimulate the 5-HT2B receptors on heart valves. In clinical studies, incidence of valvulopathy was not significantly increased in patients taking lorcaserin compared with those taking placebo. The usual and maximum dose of lorcaserin is 10 mg orally every 12 hours. The most common adverse effects in patients without diabetes are headache, nausea, dizziness, fatigue, dry mouth, and constipation; these effects are usually self-limited. Lorcaserin should not be used with serotonergic drugs, such as selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), or monoamine oxidase inhibitors (MAOIs), because serotonin syndrome Serotonin Syndrome Serotonin syndrome is a potentially life-threatening condition resulting from increased central nervous system serotonergic activity that is usually drug related. Symptoms may include mental... read more is a risk. Lorcaserin was withdrawn from the US market after an increased cancer risk was identified in a postmarketing trial.

Naltrexone/bupropion extended-release tablets can be used as a weight-loss adjunct. Naltrexone (used to aid in alcohol cessation) is an opioid antagonist and is thought to block negative feedback on satiety pathways in the brain. Bupropion (used to treat depression and aid in smoking cessation) can induce hypophagia by adrenergic and dopaminergic activity in the hypothalamus. The starting dose is a single tablet of naltrexone 8 mg/bupropion 90 mg; dose is titrated over 4 weeks to the maximum dose of 2 tablets twice a day. The most common adverse effects include nausea, vomiting, headache, and increases in systolic and diastolic blood pressure of 1 to 3 mm Hg. Contraindications to this drug include uncontrolled hypertension and a history of or risk factors for seizures because bupropion reduces the seizure threshold.

Liraglutide is a glucagon-like peptide 1 (GLP-1) receptor agonist used initially in the treatment of type 2 diabetes. Liraglutide augments glucose-mediated insulin release from the pancreas to induce glycemic control; liraglutide also stimulates satiety and reduces food intake. Studies have shown that liraglutide 3 mg daily results in a 12.2% weight loss after 56 weeks. The initial dose is 0.6 mg injected subcutaneously once/day; the dose is increased 0.6 mg/week to the maximum dose of 3 mg once/day. Liraglutide must be given by injection. Adverse effects include nausea and vomiting; liraglutide has warnings that include acute pancreatitis and risk of thyroid C-cell tumors.

Semaglutide is a GLP-1 receptor agonist approved for the treatment of type 2 diabetes. Semaglutide augments glucose-mediated insulin release and reduces appetite and energy intake via effects on appetite centers in the hypothalamus. Semaglutide 2.4 mg subcutaneously has resulted in a mean body weight loss of 14.9% at 68 weeks as compared to 2.4% in patients treated with placebo (1 Treatment reference Obesity is excess body weight, defined as a body mass index (BMI) of ≥ 30 kg/m². Complications include cardiovascular disorders (particularly in people with excess abdominal fat)... read more ). Patients on semaglutide also had greater improvements in cardiovascular risk factors as well as patient-reported physical functioning. Like liraglutide, the most common adverse effects of semaglutide include nausea and diarrhea, which are usually transient and mild to moderate in severity. Warnings for semaglutide include thyroid tumors and pancreatitis. The starting dose is 0.25 mg once a week for 4 weeks, increasing every 4 weeks to the maintenance dose of 2.4 mg once a week by week 17.

Weight-loss drugs should be stopped if patients do not have documented weight loss after 12 weeks of treatment.

Most over-the-counter weight-loss drugs are not recommended because they have not been shown to be effective. Examples of such drugs are brindleberry, L-carnitine, chitosan, pectin, grapeseed extract, horse chestnut, chromium picolinate, fucus vesiculosus, and ginkgo biloba. Some (eg, caffeine, ephedrine, guarana, phenylpropanolamine) have adverse effects that outweigh their advantages. Also, some of these drugs are adulterated or contain harmful substances banned by the US Food and Drug Administration (eg, ephedra, bitter orange, sibutramine).

Bariatric surgery Bariatric Surgery Bariatric surgery is the surgical alteration of the stomach, intestine, or both to cause weight loss. In the US, about 250,000 bariatric operations are done in each year. Development of safer... read more is the most effective treatment for severely obese patients.

For obese children, complications are more likely to develop because they are obese longer. More than 25% of children and adolescents are overweight or obese. (See also Obesity in Adolescents Obesity in Adolescents Obesity is now twice as common among adolescents than it was 30 years ago and is one of the most common reasons for visits to adolescent clinics. Although fewer than one third of adults with... read more .)

Risk factors for obesity in infants are low birth weight and maternal obesity Maternal Weight Risk factors for complications during pregnancy include Preexisting maternal disorders Physical and social characteristics (eg, age) Problems in previous pregnancies (eg, a previous history... read more , diabetes Diabetes Risk factors for complications during pregnancy include Preexisting maternal disorders Physical and social characteristics (eg, age) Problems in previous pregnancies (eg, a previous history... read more , and smoking Tobacco Tobacco use is a major individual and public health problem. Dependence develops rapidly. Major consequences include premature death and morbidity caused by cardiovascular disease, lung and... read more .

After puberty, food intake increases; in boys, the extra calories are used to increase protein deposition, but in girls, fat storage is increased.

For obese children, psychologic complications (eg, poor self-esteem, social difficulties, depression) and musculoskeletal complications can develop early. Some musculoskeletal complications, such as slipped capital femoral epiphyses Slipped Capital Femoral Epiphysis (SCFE) Slipped capital femoral epiphysis is movement of the femoral neck upward and forward on the femoral epiphysis. Diagnosis is with x-rays of both hips; sometimes other imaging is needed. Treatment... read more , occur only in children. Other early complications may include obstructive sleep apnea Obstructive Sleep Apnea (OSA) in Children Obstructive sleep apnea (OSA) is episodes of partial or complete closure of the upper airway that occur during sleep and lead to breathing cessation. Symptoms include snoring and sometimes restless... read more , insulin resistance Type 2 diabetes Diabetes mellitus is impaired insulin secretion and variable degrees of peripheral insulin resistance leading to hyperglycemia. Early symptoms are related to hyperglycemia and include polydipsia... read more , hyperlipidemia, and nonalcoholic steatohepatitis Nonalcoholic Fatty Liver Disease (NAFLD) Fatty liver is excessive accumulation of lipid in hepatocytes. Nonalcoholic fatty liver disease (NAFLD) includes simple fatty infiltration (a benign condition called fatty liver), whereas nonalcoholic... read more . Risk of cardiovascular, respiratory, metabolic, hepatic, and other obesity-related complications increases when these children become adults.

Risk of obesity persisting into adulthood depends partly on when obesity first develops:

In children, preventing further weight gain, rather than losing weight, is a reasonable goal. Diet should be modified, and physical activity increased. Increasing general activities and play is more likely to be effective than a structured exercise program. Participating in physical activities during childhood may promote a lifelong physically active lifestyle. Limiting sedentary activities (eg, watching TV, using the computer or handheld devices) can also help. Drugs and surgery are avoided but, if complications of obesity are life threatening, may be warranted.

Measures that control weight and prevent obesity in children may have the largest public health benefits. Such measures should be implemented in the family, schools, and primary care programs.

In the US, the percentage of obese older people has been increasing.

With age, body fat increases and is redistributed to the abdomen, and muscle mass is lost, largely because of physical inactivity, but decreased androgens and growth hormone (which are anabolic) and inflammatory cytokines produced in obesity may also play a role.

Risk of complications depends on

Increased waist circumference, suggesting abdominal fat distribution, predicts morbidity (eg, hypertension Hypertension Hypertension is sustained elevation of resting systolic blood pressure (≥ 130 mm Hg), diastolic blood pressure (≥ 80 mm Hg), or both. Hypertension with no known cause (primary; formerly, essential... read more , diabetes mellitus Diabetes Mellitus (DM) Diabetes mellitus is impaired insulin secretion and variable degrees of peripheral insulin resistance leading to hyperglycemia. Early symptoms are related to hyperglycemia and include polydipsia... read more , coronary artery disease Overview of Coronary Artery Disease Coronary artery disease (CAD) involves impairment of blood flow through the coronary arteries, most commonly by atheromas. Clinical presentations include silent ischemia, angina pectoris, acute... read more ) and mortality risk better in older adults than does BMI. With aging, fat tends to accumulate more in the waist.

For older adults, physicians may recommend that caloric intake be reduced and physical activity be increased. However, if older patients wish to substantially reduce their caloric intake, their diet should be supervised by a physician. Physical activity also improves muscle strength, endurance, and overall well-being and reduces the risk of developing chronic disorders such as diabetes. Activity should include strengthening and endurance exercises.

Regardless of whether caloric restriction is considered necessary, nutrition should be optimized.

Weight-loss drugs are often not studied specifically in older adults, and possible benefits may not outweigh the adverse effects. However, orlistat may be useful for obese older patients, particularly those with diabetes mellitus Diabetes Mellitus (DM) Diabetes mellitus is impaired insulin secretion and variable degrees of peripheral insulin resistance leading to hyperglycemia. Early symptoms are related to hyperglycemia and include polydipsia... read more or hypertension Hypertension Hypertension is sustained elevation of resting systolic blood pressure (≥ 130 mm Hg), diastolic blood pressure (≥ 80 mm Hg), or both. Hypertension with no known cause (primary; formerly, essential... read more . Surgery can be considered in healthy older patients with good functional status.