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Obesity is a state of excess adipose tissue mass. About 70% of U.S. adults are categorized as overweight or obese, and the prevalence of obesity is increasing rapidly in most of the industrialized world. Children and adolescents also are becoming more obese, indicating that the current trends will accelerate over time. Obesity is associated with an increased risk of multiple health problems, including hypertension, type 2 diabetes, dyslipidemia, obstructive sleep apnea, nonalcoholic fatty liver disease, degenerative joint disease, and some malignancies.

Obesity should not be defined by body weight alone, as muscular individuals may be overweight by arbitrary standards without having increased adiposity. The most widely used method to classify weight status and risk of disease is the body mass index (BMI), which is equal to weight/height2 in kg/m2 . At a similar BMI, women have more body fat than men. Furthermore, regional fat distribution may influence the risks associated with obesity. Central (primarily visceral) obesity (high ratio of the circumference of the waist to the circumference of the hips [waist-to-hip ratio], >0.9 in women and 1.0 in men) is independently associated with a higher risk for metabolic syndrome, diabetes mellitus, hyperandrogenism in women, and cardiovascular disease.

Etiology !!navigator!!

Obesity can result from increased energy intake, decreased energy expenditure, or a combination of the two. Excess accumulation of body fat is the consequence of environmental and genetic factors; social factors and economic conditions also represent important influences. The recent increase in obesity can be attributed to a combination of excess caloric intake and decreasing physical activity. Poorly understood reasons for increased food assimilation due to dietary composition have also been postulated, as have sleep deprivation and an unfavorable gut flora. The susceptibility to obesity is polygenic in nature, and 30-50% of the variability in total fat stores is believed to be genetically determined. Among monogenic causes, mutations in the melanocortin receptor 4 are most common and account for 1% of obesity in the general population and 6% in severe, early-onset obesity. Syndromic obesity forms include Prader-Willi syndrome and Laurence-Moon-Biedl syndrome. Other monogenetic or syndromic causes are extremely rare. Secondary causes of obesity include hypothalamic injury, hypothyroidism, Cushing's syndrome, and hypogonadism. Drug-induced weight gain is also common in those who use antidiabetes agents (insulin, sulfonylureas, thiazolidinediones), glucocorticoids, psychotropic agents, mood stabilizers (lithium), antidepressants (tricyclics, monoamine oxidase inhibitors, paroxetine, mirtazapine), or antiepileptic drugs (valproate, gabapentin, carbamazepine). Insulin-secreting tumors can cause overeating and weight gain.

Clinical Features !!navigator!!

Obesity has major adverse effects on health. Increased mortality from obesity is primarily due to cardiovascular disease, hypertension, gall bladder disease, diabetes mellitus, and several types of cancer, such as cancer of the esophagus, colon, rectum, pancreas, liver, and prostate, and gallbladder, bile ducts, breasts, endometrium, cervix, and ovaries in women. Sleep apnea in severely obese individuals poses serious health risks. Obesity is also associated with an increased incidence of steatohepatitis, gastroesophageal reflux, osteoarthritis, gout, back pain, skin infections, and depression. Hypogonadism in men and infertility in both sexes are prevalent in obesity; in women this may be associated with hyperandrogenism (polycystic ovarian syndrome).

TREATMENT

Obesity

Obesity is a chronic medical condition that requires ongoing treatment and lifestyle modifications. Treatment is important because of the associated health risks, but is made difficult by a limited repertoire of effective therapeutic options. Weight regain after weight loss is common with all forms of therapy. The urgency and selection of treatment modalities should be based on BMI and a risk assessment.

Diet, exercise, and behavior therapy are recommended for all pts with a BMI 25 kg/m2 . Behavior modification including group counseling, diet diaries, and changes in eating patterns should be initiated. Food-related behaviors should be monitored carefully (avoid cafeteria-style settings, eat small and frequent meals, eat breakfast). A deficit of 7500 kcal will produce a weight loss of approximately 1 kg. Therefore, eating 100 kcal/d less for a year should cause a 5-kg weight loss, and a deficit of 1000 kcal/d should cause a loss of 1 kg per week. Physical activity should be increased to a minimum of 150 min of moderate intensity per week.

Pharmacotherapy may be added to a lifestyle program for pts with a BMI 30 kg/m2 or 27 kg/m2 with concomitant obesity-related diseases. Medications for obesity have traditionally fallen into two major categories: appetite suppressants (anorexiants) and gastrointestinal fat blockers. Four anti-obesity medications were approved by the U.S. Food and Drug Administration (FDA) since 2012: lorcaserin, phentermine/topiramate (PHEN/TPM) extended release, naltrexone sustained release (SR)/bupropion SR, and liraglutide. Gastrointestinal fat blockers (Orlistat) reduce the absorption of selective macronutrients, such as fat, from the gastrointestinal tract. Response to medications should be assessed after 3 months. Metformin, exenatide, and liraglutide tend to decrease body weight in pts with obesity and type 2 diabetes mellitus, but they are not indicated for pts without diabetes.

Bariatric surgery should be considered for pts with severe obesity (BMI 40 kg/m2 ) or moderate obesity (BMI 35 kg/m2 ) associated with a serious medical condition, with repeated failures of other therapeutic approaches, at eligible weight for >3 years, capable of tolerating surgery, and without addictions or major psychopathology. Weight-loss surgeries are either restrictive (limiting the amount of food the stomach can hold and slowing gastric emptying), such as laparoscopic adjustable silicone gastric banding, or restrictive-malabsorptive, such as Roux-en-Y gastric bypass (Fig. 175-1. Bariatric Surgical Procedures). These procedures generally produce a 30-35% weight loss that is maintained in about 40% of pts at 4 years. In many pts, there is significant improvement in co-morbid conditions including type 2 diabetes mellitus, hypertension, sleep apnea, hyperlipidemia, and cardiovascular events. The metabolic benefits appear to be the combined result of weight loss and physiologic responses of gut hormones and adipose tissue metabolism. Complications include stomal stenosis, marginal ulcers, and dumping syndrome. Procedures with a malabsorptive component require lifelong supplementation of micronutrients (iron, folate, calcium, vitamins B12 and D) and are associated with a risk of islet cell hyperplasia and hypoglycemia.

Outline

Section 13. Endocrinology and Metabolism