US Pharm. 2007;32(4):HS40-HS47.

Obesity has become an epidemic on a global scale and poses one of the biggest concerns to human health and well-being. The World Health Organization has declared that obesity is a disease of pandemic significance, which threatens the developing world.1 Also alarming is that an estimated 80% of people with type 2 diabetes are obese at the time of diagnosis or have a history of obesity. The link between the two conditions is so strong that Shape Up America! trademarked the term diabesity, and it has since been used commonly among health care professionals.

In the United States, obesity has become a chronic disease that affects nearly one third of the adult population (approximately 60 million people). Since 1960, the number of overweight and obese Americans has continued to increase, a trend that is not abating. Today, about 127 million American adults (64.5%) are categorized as being overweight or obese. Each year in the U.S., at least 300,000 deaths occur due to obesity-related causes, and health care costs of American adults with obesity amount to approximately $100 billion.1

Because of its impact on health, obesity deserves to receive more attention from the government, health care profession, and health care insurance industry. Research is severely limited by a shortage of funds as well as by inadequate insurance coverage and access to treatment. Mistreatment of people with obesity is widespread and often considered socially acceptable.2 This article discusses the causes of obesity, the link between obesity and diabetes, and methods of prevention and treatment.

Obesity is defined as being 20% heavier than one's ideal body weight. There are two classic patterns of obesity--the android or "apple" shape, known as central or visceral obesity, which represents increased intra-abdominal fat and is associated with type 2 diabetes due to insulin resistance, and the gynoid or "pear" shape, which represents increased fat in the hips and thighs and is typically seen in women.3

Insulin resistance is associated with both visceral and subcutaneous adiposity fat. Visceral fat results in hepatic insulin resistance via a "portal" effect of free fatty acids released by increased omental fat. The increased flux of fatty acids to the liver leads to increased hepatic glucose production and decreased hepatic insulin clearance, which in turn leads to insulin resistance and hyperinsulinemia.4

Although obesity originates in the hypothalamus, its causes to date have not been totally understood. However, many factors contribute to this serious condition, some of which appear to be simple and others to be very complicated. The most important causes are genetic factors, metabolic factors, sedentary lifestyle, psychological factors, sociocultural factors, neuroendocrines (high levels of cortisol, low levels of thyroids, polycystic ovary syndrome, and growth hormone deficiency), and high caloric nutrition (junk food, supersizing of meal portions, and emotional eating).5

Assessment of weight involves evaluating body mass index (BMI), abdominal fat, and the patient's risk factors.

Body Mass Index
BMI should be calculated for all adults. Normal body weight is defined as a BMI of 18.5 to 24.9 kg/m2. Overweight is defined as a BMI of 25 to 29.9 kg/m2. Obesity is defined as a BMI of 30 kg/m2 or greater. There are three classes of obesity: Class I (BMI = 30-34.9 kg/m2 ), Class II (BMI = 35-39.9 kg/m2), Class III (BMI ?40 kg/m2). Individuals with a normal BMI should be reassessed every two years. In addition, a muscular person may have a high BMI without the additional health risks.

Abdominal Fat
Excess abdominal fat, not proportional to total body fat, is an independent predictor for risk of diabetes and morbidity. Among those with a BMI of 25 to 34.9 kg/m2, a waist circumference of more than 40 inches in men and more than 35 inches in women is associated with increased risk of diabetes.

Risk Factors
Coronary heart disease, hypertension, stroke, type 2 diabetes, gallbladder disease, osteoarthritis, sleep apnea, and other respiratory problems are associated with a very high risk of disease complications and mortality in obese individuals. Obesity is also associated with complications of pregnancy, menstrual irregularities, stress incontinence, and psychological disorders (e.g., depression).

Cardiovascular risk factors include hypertension, cigarette smoking, obesity (BMI ?30), inactive lifestyle, dyslipidemia, diabetes, microalbuminuria or an estimated glomerular filtration rate of less than 60 mL/minute, age (men, >55; women, >65), and family history of premature cardiovascular disease.5

The most common presenting symptoms of obesity are shortness of breath on minor exertion, tiredness, depression, difficulty sleeping, low back pain, hip pain, and knee pain. Other less well-known problems that can be related to being overweight are stress, a reduction in libido, and menstrual disturbances, including menorrhagia, oligomenorrhea, and infertility. Sweating is increased through the elevated metabolic rate of being obese, and this contributes to certain skin problems.3

Quality of life for obese individuals is affected not only by the above-mentioned problems but also by the way others treat them, low self-esteem, and difficulties with activities of daily living. Obese individuals may face discrimination, reduced prospects, and social isolation, which in turn may lead to depression.3

The increasing prevalence of type 2 diabetes or diabesity among children is of particular concern. Prevention, through healthy eating and lifestyle, must take the highest priority. Therefore, the most fundamental, and perhaps important, task in addressing the epidemic of obesity is prevention. To date, the strategies that have been developed to prevent obesity have been disappointing, and the problem of obesity is worsening. It is believed that obesity has both genetic and environmental origins and that these factors are linked.

In our modern Western society, attractive, energy-dense foods and an environment that encourages a sedentary lifestyle contribute to the obesity problem. Solutions should range from protecting children against the bombardment of advertising from processed food manufacturers to promoting physical activity guidelines in schools as an essential component of daily activities.

The Centers for Obesity Research and Education (C.O.R.E.) has been established to provide such advocacy and to lead the way in promoting and supporting the changes necessary to make a difference. Even modest weight loss, achieved through lifestyle changes, reduces the risk of impaired fasting glucose, which leads to the development of type 2 diabetes.

A major role of C.O.R.E. is to provide the health care profession with education regarding the identification of those at risk in the community, as well as with management strategies for the prevention and treatment of obesity-related diseases.6

The goals of treatment are to prevent further weight gain, to reduce body weight (initially, by 10% from baseline over a period of six months), and to maintain a lower body weight in the long term.

Nonpharmacologic Treatment
Nonpharmacologic therapy should include an individually planned diet that involves a reduction in fat as well as total calories. Physical activity of moderate intensity should be gradually increased to a goal of 30 minutes per day. Behavior therapy should include tools to help overcome individual barriers to weight loss.

Diet: Patients should achieve energy balance and a healthy weight. They should limit energy intake from total fats and shift away from consumption of saturated fats toward that of unsaturated fats and the elimination of trans-fatty acids. Consumption of fruits and vegetables, legumes, whole grains, and nuts should be increased. In addition, intake of free sugars and salt (sodium) from all sources should be limited. Patients should ensure that salt is iodized.3

Physical Activity: A large body of evidence shows that regular physical activity is associated with a reduction in all-cause mortality, fatal and nonfatal total cardiovascular disease, and coronary heart disease. It is also associated with a reduction in the incidence of obesity and type 2 diabetes and an improvement in the metabolic control of individuals with established type 2 diabetes. Also, physical activity is associated with a reduction in the incidence of colon cancer and osteoporosis. Further benefits of regular physical activity include improved physical function and independent living in the elderly.3

Individuals with high levels of physical activity are less likely than those with lower levels to develop depressive illness. In those with mild-to-moderate depression and anxiety, prescribed physical activity is associated with improved symptoms. Other benefits of physical activity include reduction in blood pressure, improvement in plasma lipid profile, and alterations in coagulation and hemostatic factors. Thirty minutes of regular physical activity of moderate intensity on most days is highly recommended.

Rehabilitation: Rehabilitation literally means "the restoration of lost capabilities." It helps individuals believe that they have the capacity to improve their health, walk farther, feel better, maintain a healthy weight, and add years to life. Rehabilitation specialists use an integrative, holistic approach to wellness. They coordinate teams of physical therapists, occupational therapists, social workers, psychologists, and nutritionists to help patients meet their goals. For this reason, it is believed that rehabilitation specialists are the best equipped to provide the kind of complex, long-term solution that is required to reverse the diabesity epidemic.7

Getting people to adopt a healthy lifestyle in a short period of time has not worked in the past and will not work in the future. The medical history of the patient should be carefully taken into consideration when helping him or her to change health-associated behaviors. Therefore, obesity should be treated as a disease of the body as well as of the mind.7

Pharmacologic Treatment
Pharmacotherapy is normally started in patients who do not lose weight or maintain weight loss after diet, exercise, and behavioral therapy for six months. Drug therapy can be started along with dietary therapy and physical activity.

There are several broad categories of medications--lipase inhibitors such as orlistat, anorexiants such as sibutramine, and short-term adjunct therapy such as phentermine.

Orlistat: Orlistat is the first of a new class of antiobesity agents with a unique mode of action that targets dietary fat. Orlistat is an inhibitor of gastrointestinal lipases, which are required for the systemic absorption of dietary triglycerides, and it prevents the absorption of 30% of dietary fat, thus producing some weight loss.

Orlistat is indicated for long-term treatment of individuals who are obese (BMI ?30) or who are significantly overweight (BMI ?27) and have other risk factors. It should be used in conjunction with a hypocaloric diet (i.e., up to 2,000 kcal) containing no more than 30% in fat calories. Daily intake of fat should be distributed over three main meals.

Orlistat is best administered in one 120-mg capsule during, or up to one hour after, each meal. Higher dosages have no added benefit, nor will they increase side effects. Because orlistat has been shown to reduce the absorption of some fat-soluble vitamins and beta-carotene, consideration should be given to taking a multivitamin supplement for long-term use. However, as mentioned, the serum levels of these vitamins do not seem to fall below recommended levels, and the need for vitamin supplements is still open to research and debate.8

Sibutramine: This drug blocks the neuronal uptake of norepinephrine and, to a lesser extent, serotonin and dopamine. It is used in the management of obesity, as well as for weight loss and maintenance of weight loss. Sibutramine should be used in conjunction with a reduced-calorie diet.

Sibutramine is classified as a class IV controlled substance. This drug is recommended only for obese patients with a BMI of 30 kg/m2 or greater or of 27 kg/m2 or greater in the presence of other risk factors, such as hypertension, diabetes, and/or dyslipidemia. Obesity due to untreated hypothyroidism should be ruled out.

Side effects include nausea, constipation, dizziness, drowsiness, menstrual cramps/pain, and rare thoughts of suicide. Physical and psychological dependence on this medication may occur. If any of these side effects occur, patients should speak with their doctor before stopping treatment.

Dosage in adults age 16 or older is 10 mg once daily. After four weeks, the dosage may be titrated up to 15 mg once daily as needed and tolerated (may be used for up to two years, per manufacturer labeling).9

Phentermine: Phentermine is a short-term adjunct to a regimen of weight reduction that includes exercise, behavioral modification, and caloric reduction for the management of exogenous obesity in the presence of other risk factors (diabetes, hypertension).

Phentermine is structurally similar to dextroamphetamine and comparable as an appetite suppressant. It is generally associated with a lower incidence and severity of central nervous system side effects. Phentermine, like other anorexiants, stimulates the hypothalamus, resulting in decreased appetite via norepinephrine and dopamine metabolism.

Symptoms of overdose include hyperactivity, agitation, hyperthermia, hypertension, and seizures. In obese adults, the dosage is 8 mg three times a day taken 30 minutes before meals or food or 15 to 37.5 mg/day taken before breakfast or 10 to 14 hours before bedtime.10

Bariatric Surgery
Patients with severe clinical obesity (i.e., BMI ?40 or BMI ?35 with coexisting conditions) can be considered for weight loss surgery when other methods have failed.

Bariatric surgery is a long-term treatment and successful technique for the treatment of obesity. Patients without comorbid conditions who have a BMI of 40 kg/m2 or greater are good candidates for bariatric surgery. Some patients with a BMI of 35 to 40 kg/m2 are also candidates for this technique. This method results in a major weight loss as well as in improvement in type 2 diabetes, hyperlipidemia, hypertension, and sleep apnea. Lifelong surveillance after surgery is necessary.11

How Pharmacists Can Help
Pharmacists have an exceptional opportunity to educate patients about dietary supplements, weight-loss medications, and what to expect from therapy. They can also help to improve adherence to medication regimens. Patients should be aware that obesity is associated with an increased risk of various chronic diseases, such as diabetes and cardiovascular problems. In addition, they should be informed that because weight loss is a long process, patience and adherence to daily regimens are essential for achieving beneficial results.

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3. Beaser RS. Joslin's Diabetes Deskbook. Boston, Mass: Joslin Diabetes Center; 2003.
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6. Tuomilehto J, Lindstrom J, Eriksson JG, et al. Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med. 2001;344:1343-1350.
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11. Miller S. Pharmacotherapy for weight loss. US Pharm. 2006;12:75-84.

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