
Obesity: How to Diagnose and Treat an Epidemic
In the United States, obesity is both an epidemic and a substantial public health crisis, resulting in many metabolic and biomechanical adverse consequences, such as type 2 diabetes, high blood pressure, dyslipidemia, cardiovascular disease, arthritis, and sleep apnea. According to the American Society of Bariatric Physicians, "Obesity is defined as a chronic, relapsing, multi-factorial, neurobehavioral disease, wherein an increase in body fat promotes adipose tissue dysfunction and abnormal fat mass physical forces, resulting in adverse metabolic, biomechanical, and psychosocial adverse consequences."[1] More than one third of adults (36.5%) and 17% of children and adolescents in the United States are considered obese based on body mass index. The World Health Organization defines obesity as a body mass index (BMI) greater than 30 kg/m2.[2] In 2015, the Endocrine Society released guidelines on the treatment of obesity in various populations, including patients with type 2 diabetes, patients with hypertension, and women of childbearing age.[3]
Obesity: How to Diagnose and Treat an Epidemic
The etiology of obesity and its complications are due to many factors; thus, the adverse consequences of obesity are more complex than simply being an imbalance between energy intake and energy output.[4] Obesity is a multifactorial disease with genetic, environmental, and medical factors, interfacing with immune, endocrine, and neurobehavioral elements. Genetic factors may help explain 40-70% of the variance in obesity, within a limited range of a BMI between 18 and 30 kg/m2.[4] Studies on monozygotic twins indicate that genetic factors are significantly involved in obesity in terms of how energy is stored as either fat or lean tissue.[5,6] Extragenetic factors that influence nutritional and physical activity habits may play a large role in obesity, as evidenced by the increase in the prevalence of obesity and its complications with changes in environment (eg, work schedules, oversized food portions, lack of access to healthy foods, food advertising, lack of neighborhood sidewalks).[1,5]
Obesity: How to Diagnose and Treat an Epidemic
In the United States, about 79 million adults older than 20 years (37 million men and 42 million women) and over 12 million children and adolescents are obese.[7] In 2011-2012, the prevalence of obesity among adult men and women was almost 35%.[2] The prevalence in children and adolescents has increased to 17.2%. Obesity also has a strong prevalence among non-Hispanic black women, with 26.8% of deaths in such patients associated with a BMI of 25 kg/m2 or higher.[1]
Obesity: How to Diagnose and Treat an Epidemic
Body fat percentage measures may be helpful for patients with extremes in muscle mass, such as increases in muscle mass for muscular individuals, or decreases in muscle mass (sarcopenia) in geriatric patients who may have a BMI in the normal range but may be likely to develop diabetes.[8]
Obesity: How to Diagnose and Treat an Epidemic
BMI is used more commonly than body fat percentage to define obesity. An individual's BMI is calculated as weight/height2. According to the WHO, overweight is defined as a BMI of 25-29.9 kg/m2, and obesity is defined as a BMI greater than 30 kg/m2. In children, overweight is commonly defined as a BMI above the 85th percentile, and obesity as a BMI above the 95th percentile.[9,10] When mapped, epidemiologic studies suggest a J-shaped curve relating weight distribution to mortality/morbidity, since along with high BMI, very low BMI is also associated with increased mortality risk.[11]
Obesity: How to Diagnose and Treat an Epidemic
Waist circumference and body fat percentage are also used in conjunction with BMI to screen for possible health risks. Waist circumference provides information regarding adipose tissue function. Waist circumference is a measure of abdominal obesity; abdominal adiposity is a risk factor for cardiovascular disease, high blood glucose, high blood pressure, and dyslipidemia. Abdominal obesity is defined in men as a waist circumference greater than 40 inches, and in women as a waist circumference greater than 35 inches.
Obesity: How to Diagnose and Treat an Epidemic
Obesity has a multitude of adverse metabolic health consequences. Obesity increases the prevalence of type 2 diabetes mellitus, hypertension, dyslipidemia, and metabolic syndrome.[12] The metabolic syndrome is a constellation of cardiometabolic risk factors (eg, abdominal obesity, high glucose levels, high blood pressure, elevated triglycerides, and reduced levels of high-density lipoprotein cholesterol) that reflect underlying adiposopathic complications of obesity. Obesity and the metabolic syndrome are risk factors for atherosclerotic cardiovascular disease, metabolic diseases, fatty liver, and several cancers. More than 80% of people with type 2 diabetes are overweight or obese, and the risk of hypertension increases in patients with upper body and abdominal obesity (apple shaped body configuration).[13]
Obesity: How to Diagnose and Treat an Epidemic
During positive caloric balance, adipocytes are increased in size and possibly in number. If limitations exist on the ability to proliferate new fat cells, then the excessive energy may be stored by further hypertrophy of existing fat cells (promoting their dysfunction) or may be stored in ectopic fat depots such as pericardiac fat, perivascular fat, and visceral fat. Thus, an increase in visceral adiposity may be considered a reflection of global fat dysfunction. Adiposopathy, or "sick fat," is defined as anatomic and functional abnormalities of the adipocyte and adipose tissue caused by adiposity, resulting in imbalances in the endocrine and immune systems. These endocrine and immune imbalances directly and indirectly lead to hyperglycemia, high blood pressure, dyslipidemia, and cardiovascular disease.[14-16]
Obesity: How to Diagnose and Treat an Epidemic
Many hormones impact appetite and food intake. An illustrative example is leptin, which is a peptide hormone secreted from fat cells and involved in the regulation of fat metabolism.[17] When a person gains weight, leptin secretion is increased. Leptin signals satiety to the hypothalamus, which promotes a reduction in dietary intake and fat storage while modulating energy expenditure and carbohydrate metabolism. Mutations resulting in defects of the leptin receptor in the hypothalamus may result in early onset obesity and hyperphagia despite normal or elevated leptin levels. Administration of leptin to leptin-deficient patients with obesity can be remarkably effective in reducing obesity. However, most individuals who are overweight or obese and have elevated leptin levels are sometimes described as leptin resistant. Administration of leptin to such individuals has not yet proven to substantially improve obesity or its complications. Attenuation of leptin secretion during the night or a change in other circadian satiety hormones lead to a situation called "night eating syndrome" in some individuals.[18]
Obesity: How to Diagnose and Treat an Epidemic
Complicating obesity clinical management is the obesity paradox. One of the most challenging aspects of obesity is the presence of more than one obesity paradox. For example, not all patients who are overweight have excessive fat-related metabolic disease (EFRMD), and not all patients with EFRMD are significantly overweight.[19-21] Other layers of the obesity paradox include anatomic, demographic, therapeutic, and cardiovascular event paradoxes, such as reports of more favorable cardiovascular event outcomes in overweight and obese patients.
Obesity: How to Diagnose and Treat an Epidemic
Because visceral adiposity may reflect global fat dysfunction and is an anatomic manifestation of adiposopathy, an increase in abdominal waist circumference is associated with increased cardiovascular and metabolic disease.[22] Body fat distribution can also be affected by age, sex, ethnicity, hormonal factors, diet, sedentary lifestyle, pharmacologic agents, and other environmental and lifestyle factors such as smoking and stress.[22] Visceral obesity–related cardiometabolic risks are influenced by physiologic characteristics of abdominal adipose tissues, such as adipocyte size and number, lipolytic responsiveness, lipid storage capacity, and inflammatory cytokine production.[23]
Visceral fat is an active endocrine gland that produces hormones and pro-inflammatory cytokines that have direct impact on insulin sensitivity and increased risk for type 2 diabetes and cardiovascular disease.[24,25]
Obesity: How to Diagnose and Treat an Epidemic
A number of physiologic and environmental reasons help explain eating habits and include specific physiologic factors; eating on the basis of timing or emotions; environmental factors; and information gaps. Lack of proper nutritional education and proper nutritional information can contribute to unintended increased caloric consumption. Another important influence is the reward system, wherein eating occurs for reasons other than hunger. Some patients with overweight or obesity may have eating disorders such as binge eating disorder, bulimia nervosa, and night eating syndrome. Binge eating disorder affects 2-3% of US adults and is classified as frequent episodes of consuming large amounts of foods at least once a week for a period of 3 months and may occur in up to 50% of patients with severe obesity. Bulimia is categorized as a cycle of recurrent binge eating and compensatory purging. Laxative and diuretic abuse are also aspects of bulimia. Bulimia occurs in about 1% of adults, mostly women. The Russell sign (ie, calluses and abrasions on the dorsum of the hands from self-purging) points to bulimia, as does laboratory tests for hypokalemia due to hypomagnesemia. Night eating syndrome is when at least 25% of daily food consumption occurs after the evening meal. Eating is often required to return to sleep after recurrent awakenings.
Obesity: How to Diagnose and Treat an Epidemic
Adiposity-relevant blood testing includes a fasting lipid panel, liver function studies, thyroid function tests, and fasting glucose and hemoglobin A1c (HbA1c). These initial laboratory studies are suggested to routinely screen for type 2 diabetes mellitus, dyslipidemia and fatty liver disease. Lipid panel testing is recommended for children and adolescents with a BMI at or above the 85th percentile for age and sex beginning at 10 years of age. Fasting glucose is recommended for all children and adolescents with a BMI at or above the 95th percentile beginning at 10 years of age. Clinicians should also assess for a family history of overweight and related complications.[26]
Obesity: How to Diagnose and Treat an Epidemic
Patients with overweight or obesity may benefit from individualized testing. Individualized testing should be based on medical history, symptoms, signs, and overall health risk, such as evidence of central nervous system or endocrine causes of obesity, or other risk factors for cardiopulmonary diseases.
Obesity: How to Diagnose and Treat an Epidemic
While almost all patients with obesity should be screened for diabetes, some clinicians find clinical use in assessing for insulin resistance, which may include measures of increased serum levels of fasting insulin and C-peptide. Prediabetes may be suggested by impaired fasting glucose (fasting plasma glucose levels of 100-125 mg/dL [5.6-6.9 mmol/L]) or impaired glucose tolerance (2-hour oral glucose tolerance test values of 140-199 mg/dL [7.8-11.0 mmol/L]) or A1C between 5.7-6.4%. Patients with these findings are at relatively high risk for the future development of diabetes. Type 2 diabetes is diagnosed when 2 successive fasting glucose levels are 126 mg/dL or greater or HbA1c is 6.5% or higher.[27]
Obesity: How to Diagnose and Treat an Epidemic
Treatment options for patients who are overweight or obese often include coordination of a patient's nutrition and physical activity, along with behavior therapy, as well as potential pharmacotherapy and/or bariatric surgery. Therapies that decrease body fat will often improve adipocyte and adipose tissue function (thus improving metabolic disease) and improve fat mass disease.[11] Multidisciplinary programs that include a physician, a psychologist or psychiatrist, physical and exercise therapists, dietitians, and other subspecialists may often result in long-term modest weight loss, typically between 5% and 10%,[28] although this may be highly variable depending on the patient, provider, and program. Long-term weight loss was also achieved with multidisciplinary intervention in patients with diabetes in real-world clinical practice.[29]
Obesity: How to Diagnose and Treat an Epidemic
Caloric restriction, self-monitoring, patient preference, and program adherence may be more important than any specific "diet." A low-calorie diet is categorized as an intake of 800-1800 kcal/day. A very low calorie diet is categorized as an intake of less than 800 kcal/day.[11] According to the National Weight Control Registry (NWCR), patterns that are associated with successful weight loss maintenance include maintaining a low-calorie, low-fat diet or low carbohydrates; self-monitoring one's weight; 60 minutes of physical activity daily; minimal sedentary activities (eg, minimal TV watching); and eating breakfast every day.[30]
Obesity: How to Diagnose and Treat an Epidemic
While an increase in physical activity may contribute to weight loss, negative caloric balance is generally the most effective intervention. However, perhaps the main advantage of a routine increase in physical activity is maintaining long-term weight loss.[31] Prolonged sitting is associated with harmful health risks regardless of an individual's level of physical activity.[32] Technologies available that can help track and assess nutritional and physical activity include wearable bracelets that track an individual's number of steps per day to help decrease the amount of sedentary time.
Exercise should include stretching, aerobic and strength training. Short bouts of exercise of 10 minutes each may be preferred when prescribing exercise to obese adults. Short bouts of exercise may enhance exercise adherence, enhance weight loss and produce similar changes in cardiorespiratory fitness when compared to long bouts of exercise.[33]
Obesity: How to Diagnose and Treat an Epidemic
Adult patients with overweight or obesity who have not had successful weight loss through appropriate nutritional and physical activity intervention may be considered for weight management pharmacotherapy. Weight management pharmacotherapy should be used in tandem with nutritional approaches, increased physical activity, and behavioral therapies. Prescription weight-loss drugs are approved for patients with a BMI of 30 kg/m2 or more and for patients with a BMI of 27 kg/m2 or more having adverse consequences of being overweight, such as hypertension, type 2 diabetes, or dyslipidemia.[31] Studies show that a 5-10% weight loss may improve metabolic and fat mass diseases,[11] improve endothelial function and reduce inflammation.[34,35]
Obesity: How to Diagnose and Treat an Epidemic
Orlistat, approved by the FDA in 1999, blocks the action of intestinal lipase, which reduces fat absorption by the gastrointestinal tract. Phentermine, approved for decades, has an indicated use for short-term treatment of obesity (8-12 weeks).[31] Lorcaserin, approved by the FDA in 2012, selectively activates 5-HT2C receptors on anorexigenic pro-opiomelanocortin neurons in the hypothalamus to promote satiety. The combination of phentermine HCl and extended-release topiramate, approved by the FDA in 2012, may also increase satiety. Two other approved anti-obesity agents include (1) extended-release naltrexone (opioid antagonist)/bupropion (antidepressant) and (2) liraglutide (glucagon-like peptide-1 agonist).
Obesity: How to Diagnose and Treat an Epidemic
Candidates for bariatric surgery include patients with obesity having a BMI >40 kg/m2, or a BMI ≥35 kg/m2 (sometimes ≥30 kg/m2) in the presence of significant obesity complications, such as type 2 diabetes, hypertension, and obstructive sleep apnea. Bariatric surgery, in carefully selected patients within a multidisciplinary support team, can substantially improve morbidities associated with severe obesity, such as obstructive sleep apnea, type 2 diabetes, hypertension, and heart failure.
Obesity: How to Diagnose and Treat an Epidemic
Bariatric procedures are increasingly being performed laparoscopically, and a number of procedures are available. Preoperative considerations include prior efforts of nonsurgical methods toward weight loss, evaluation and management by a clinician trained in obesity medicine, and a willingness of the patient to commit to and comply with postoperative medical surveillance. Preoperative evaluations also usually involve overall assessment by a clinician trained in obesity medicine (perhaps board certified) and a trained bariatric surgeon, as well as a comprehensive evaluation of the cardiac, pulmonary, gastrointestinal, and mental health status of the patient. Both preoperatively and postoperatively, patients undergoing bariatric surgery should also maintain interactions with specialized health care professionals such as dietitians, as well as exercise and behavioral specialists. Several nutrition deficiencies may occur after gastric bypass surgery and will require life-long replacements.
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