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الأحد، 19 سبتمبر، 2010

Obesity

September 18, 2010
What is obesity?
The definition of obesity varies depending on what one reads, but in general, it is a chronic condition defined by an excess amount body fat. A certain amount of body fat is necessary for storing energy, heat insulation, shock absorption, and other functions. The normal amount of body fat (expressed as percentage of body fat) is between 25%-30% in women and 18%-23% in men. Women with over 30% body fat and men with over 25% body fat are considered obese.
The calculation of body mass index (BMI) has also been used in the definition of obesity. The body mass index (BMI) equals a person's weight in kilograms (kg) divided by their height in meters (m) squared. Since BMI describes body weight relative to height, it is strongly correlated with total body fat content in adults. "Obesity" is defined as a BMI of 30 and above.

How common is obesity?
Obesity has reached epidemic proportions in the United States. One in three Americans is obese. The prevalence of obesity in children has increased markedly, with approximately 20%-25 % of children either overweight or obese. Obesity is also increasing rapidly throughout the world, and the incidence of obesity nearly doubled form 1991 to 1998.

What are the health risks associated with obesity?
Obesity is not just a cosmetic consideration; it is a dire health dilemma directly harmful to one's health. In the United States, roughly 300,000 deaths per year are directly related to obesity, and more than 80% of these deaths are in patients with a BMI (body mass index, which will be discussed later in this article) over 30. For patients with a BMI over 40, life expectancy is reduces significantly (as much as 20 years for men and 5 years for women ). Obesity also increases the risk of developing a number of chronic diseases including:
  • Insulin Resistance. Insulin is necessary for the transport of blood glucose (sugar) into the cells of muscle and fat (which is then used for energy). By transporting glucose into cells, insulin keeps the blood glucose levels in the normal range. Insulin resistance (IR) is the condition whereby the effectiveness of insulin in transporting glucose (sugar) into cells is diminished. Fat cells are more insulin resistant than muscle cells; therefore, one important cause of insulin resistance is obesity. The pancreas initially responds to insulin resistance by producing more insulin. As long as the pancreas can produce enough insulin to overcome this resistance, blood glucose levels remain normal. This insulin resistance state (characterized by normal blood glucose levels and high insulin levels) can last for years. Once the pancreas can no longer keep up with producing high levels of insulin, blood glucose levels begin to rise, resulting in type 2 diabetes, thus insulin resistance is a pre-diabetes condition. In fact scientists now believe that the atherosclerosis (hardening of the arteries) associated with diabetes likely develops during this insulin resistance period.
  • Type 2 (adult-onset) diabetes. The risk of type 2 diabetes increases with the degree and duration of obesity. Type 2 diabetes is associated with central obesity; a person with central obesity has excess fat around his/her waist, so that the body is shaped like an apple.
  • High blood pressure (hypertension). Hypertension is common among obese adults. A Norwegian study showed that weight gain tended to increase blood pressure in women more significantly than in men. The risk of developing high blood pressure is also higher in obese people who are apple shaped (central obesity) than in people who are pear shaped (fat distribution mainly in hips and thighs).
  • Stroke (cerebrovascular accident or CVA)
  • Heart attack. A prospective study found that the risk of developing coronary artery disease increased three to four times in women who had a BMI greater than 29. A Finnish study showed that for every one kilogram (2.2 pounds) increase in body weight, the risk of death from coronary artery disease increased by one percent. In patients who have already had a heart attack, obesity is associated with an increased likelihood of a second heart attack.
  • Osteoarthritis (degenerative arthritis) of the knees, hips, and the lower back

What Causes Obesity?
The balance between calorie intake and energy expenditure determines a person's weight. If a person eats more calories than he or she burns (metabolizes), the person gains weight (the body will store the excess energy as fat). If a person eats fewer calories than he or she metabolizes, he or she will lose weight. Therefore the most common causes of obesity are overeating and physical inactivity. At present, we know that there are many factors that contribute to obesity, some of which have a genetic component:
  • Genetics. A person is more likely to develop obesity if one or both parents are obese. Genetics also affect hormones involved in fat regulation. For example, one genetic cause of obesity is leptin deficiency. Leptin is a hormone produced in fat cells, and also in the placenta. Leptin controls weight by signaling the brain to eat less when body fat stores are too high. If, for some reason the body cannot produce enough leptin, or leptin cannot signal the brain to eat less, this control is lost, and obesity occurs. The role of leptin replacement as a treatment for obesity is currently being explored.
  • Overeating. Overeating leads to weight gain, especially if the diet is high in fat. Foods high in fat or sugar (for example, fast food, fried food, and sweets) have high energy density (foods that have a lot of calories in a small amount of food). Epidemiologic studies have shown that diets high in fat contribute to weight gain.
  • A diet high in simple carbohydrates. The role of carbohydrates in weight gain is not clear. Carbohydrates increase blood glucose levels, which in turn stimulate insulin release by the pancreas, and insulin promotes the growth of fat tissue and can cause weight gain. Some scientists believe that simple carbohydrates (sugars, fructose, desserts, soft drinks, beer, wine, etc.) contribute to weight gain because they are more rapidly absorbed into the blood-stream than complex carbohydrates (pasta, brown rice, grains, vegetables, raw fruits, etc.) and thus cause a more pronounced insulin release after meals than complex carbohydrates. This higher insulin release, some scientists believe, contributes to weight gain.
  • Frequency of eating. The relationship between frequency of eating (how often you eat) and weight is somewhat controversial. There are many reports of overweight people eating less often than people with normal weight. Scientists have observed that people who eat small meals four or five times daily, have lower cholesterol levels and lower and/or more stable blood sugar levels than people who eat less frequently (two or three large meals daily). One possible explanation is that small frequent meals produce stable insulin levels, whereas large meals cause large spikes of insulin after meals.
  • Slow metabolism. Women have less muscle than men. Muscle burns (metabolizes) more calories than other tissue (which includes fat). As a result, women have a slower metabolism than men, and hence, have a tendency to put on more weight than men, and weight loss is more difficult for women. As we age, we tend to lose muscle and our metabolism slows; therefore, we tend to gain weight as we get older particularly if we do not reduce our daily caloric intake.
  • Physical inactivity. Sedentary people burn fewer calories than people who are active. The National Health and Nutrition Examination Survey (NHANES) showed that physical inactivity was strongly correlated with weight gain in both sexes.
  • Medications. Medications associated with weight gain include certain antidepressants (medications used in treating depression), anti-convulsants [medications used in controlling seizures such as carbamazepine (Tegretol, Tegretol XR , Equetro, Carbatrol) and valproate], diabetes medications (medications used in lowering blood sugar such as insulin, sulfonylureas and thiazolidinediones), certain hormones such as oral contraceptives and most corticosteroids such as Prednisone. Weight gain may also be seen with some high blood pressure medications and antihistamines.
  • Psychological factors. For some people, emotions influence eating habits. Many people eat excessively in response to emotions such as boredom, sadness, stress or anger. While most overweight people have no more psychological disturbances than normal weight people, about 30 percent of the people who seek treatment for serious weight problems have difficulties with binge eating.
What can be done about obesity?
All too often, obesity prompts a strenuous diet in the hopes of reaching the "ideal body weight." Some amount of weight loss may be accomplished, but the lost weight usually quickly returns. More than 95% of the people who lose weight regain the weight within five years. It is clear that a more effective, long-lasting treatment for obesity must be found.
We need to learn more about the causes of obesity, and then we need to change the ways we treat it. When obesity is accepted as a chronic disease, it will be treated like other chronic diseases such as diabetes and high blood pressure. The treatment of obesity cannot be a short-term "fix," but has to be an ongoing life-long process.
Obesity treatment must acknowledge that even modest weight loss can be beneficial. For example, a modest weight loss of 5% to 10% of the initial weight, and long-term maintenance of that weight loss can bring significant health gains, including:
  • Lowered blood pressure
  • Reduced blood levels of cholesterol
  • Reduced risk of type 2 (adult-onset) diabetes. In the Nurses Health Study, women who lost 5 kilograms (11 pounds) of weight reduced their risk of diabetes by 50% or more.
  • Decreased chance of stroke
  • Decreased complications of heart disease
  • Decreased overall mortality
It is not necessary to achieve an "ideal weight" to derive health benefits from obesity treatment. Instead, the goal of treatment should be to reach and hold to a "healthier weight." The emphasis of treatment should be to commit to the process of life-long healthy living including eating more wisely and increasing physical activity.
In sum, the goal in dealing with obesity is to achieve and maintain a "healthier weight."
What is the role of medication in the treatment of obesity?
Medication treatment of obesity should be used only in patients who have health risks related to obesity. Medications should be used in patients with a BMI greater than 30 or in those with a BMI of greater than 27 who have other medical conditions (such as high blood pressure, diabetes, high blood cholesterol) that put them at risk for developing heart disease. Medications should not be used for cosmetic reasons.
Like diet and exercise, the goal of medication treatment has to be realistic. With successful medication treatment, one can expect an initial weight loss of at least 5 pounds during the first month of treatment, and a total weight loss of 10%-15% of the initial body weight. It is also important to remember that these medications only work when they are taken. When they are discontinued, weight gain can occur.
The first class (category) of medication used for weight control cause symptoms that mimic the sympathetic nervous system. They cause the body to feel "under stress" or " nervous." As a result, the major side effect of this class of medication is high blood pressure. This class of medication includes sibutramine (Meridia) and phentermine (Fastin, Adipex P). These medications also decrease appetite and create a sensation of fullness. Hunger and fullness (satiety) are regulated by brain chemicals called neurotransmitters. Examples of neurotransmitters include serotonin, norepinephrine, and dopamine. Anti-obesity medications that suppress appetite do so by increasing the level of these neurotransmitters at the junction (called synapse) between nerve endings in the brain.
Phentermine
Phentermine (Fastin, Adipex P) - (the other half of fen/phen) suppresses appetite by causing a release of norepinephrine by the cells. Phentermine alone is still available for treatment of obesity, but only on a short-term basis (a few weeks). The common side effects of phentermine include headache, insomnia, irritability and nervousness. Fenfluramine (the fen of fen/phen) and dexfenfluramine (Redux) suppress appetite mainly by increasing release of serotonin by the cells. Both fenfluramine and dexfenfluramine were withdrawn from the market in September 1997 because of association of these two medications with pulmonary hypertension (a rare but serious disease of the arteries in the lungs), and association of fen/phen with damage to the heart valves. Since the withdrawal of fenfluramine, some have suggested combining phentermine with fluoxetine (Prozac) - a combination that has been referred to as phen/pro. However, no clinical trials have been conducted to confirm the safety and effectiveness of this combination. Therefore, this combination is not an accepted treatment for obesity.
Sibutramine (Meridia)
Sibutramine (Meridia) suppresses appetite by increasing the amount of neurotransmitters serotonin and norepinephrine in the brain synapses. Unlike fenfluramine and dexfenfluramine, sibutramine does not increase release of these neurotransmitters from the cells. Instead, sibutramine inhibits the re-uptake of these neurotransmitters by the nerve cells. Therefore, the action of sibutramine is similar to that of anti-depressants that inhibit re-uptake of serotonin such as fluoxetine (Prozac), a medication that has been used for years without known association with pulmonary hypertension or heart valve damage.
In December 1997, the United States Food and Drug Administration (FDA) approved sibutramine (Meridia) to treat obesity (both in attaining and in maintaining weight loss). According to FDA guidelines, Meridia should be considered only for patients with a BMI of 30 or higher, or for those with a BMI of 27 or higher who also have other conditions (such as high blood pressure, diabetes mellitus, sleep apnea) that can improve with weight loss. Meridia should be accompanied by regular exercise and a reduced-calorie diet.
Meridia is available in 5, 10, and 15mg capsules. The recommended starting dose is one 10 mg capsule per day. The dose of Meridia can be increased if weight loss is inadequate. Meridia should always be prescribed by doctors familiar with the patients' medical condition, and familiar with the use and side effects of the medicine.
In clinical trials involving 6,000 individuals, Meridia produced statistically significantly more weight loss when compared to placebo (sugar pill). Generally, weight loss achieved with Meridia is modest. On average, patients treated with Meridia lost 5% to 10% of initial weight at various dosage levels. In two 12-month studies, maximal weight loss was achieved by six months, and statistically significant weight loss was maintained over 12 months.
Thus far, there are no reported increases in pulmonary hypertension or heart valve damage associated with the use of Meridia. Like any medication, however, close monitoring will be necessary to determine the drug's long-term safety and effectiveness. Certain side effects may not become apparent until months to years after release.
The known side effects of Meridia are mild and transient. They include dry mouth, headache, constipation, and insomnia. Meridia also causes a small increase in average blood pressure and heart rate. But in some individuals, the increase in blood pressure can be more pronounced. Therefore, patients on Meridia should have regular monitoring of their blood pressure. Meridia should not be used in patients with uncontrolled high blood pressure, history of stroke, coronary heart disease, and congestive heart failure.
Orlistat (Xenical, alli)
The next class (category) of drugs changes the metabolism of fat. Orlistat (Xenical, alli) is the only drug of this category that is U.S. FDA approved. This is a class of anti-obesity drugs called lipase inhibitors, or fat blockers. Fat from food can only be absorbed into the body after being broken up (a process called digestion) by digestive enzymes called lipases in the intestines. By inhibiting the action of lipase enzymes, orlistat prevents the intestinal absorption of fat by 30%. Drugs in this class do not affect brain chemistry. Theoretically, orlistat also should have minimal or no systemic side effects (side effects in other parts of the body) because the major locale of action is inside the gut lumen and very little of the drug is absorbed.
The U.S. Food and Drug Administration approved orlistat capsules, branded as alli, as an over-the-counter (OTC) treatment for overweight adults in February 2007. The drug had previously been approved in 1999 as a prescription weight loss aid, whose brand name is Xenical). The OTC preparation has a lower dosage than prescription Xenical.
Orlistat is recommended only for people 18 years of age and over in combination with a diet and exercise regimen. People who have difficulties with the absorption of food or who are not overweight should not take orlistat. Overweight is defined by the U.S. National Institutes of Health as having a body mass index (BMI) of 27 or greater.
Orlistat can be taken up to three times a day, with each fat-containing meal. The drug may be taken during the meal or up to one hour after the meal. If the meal is missed or is very low in fat content, the medications should not be taken.
The most common side effects of orlistat are changes in bowel habits. These include gas, the urgent need to have a bowel movement, oily bowel movements, oily discharge or spotting with bowel movements, an increased frequency of bowel movements, and the inability to control bowel movements. Women may also notice irregularities in the menstrual cycle while taking orlistat. Side effects are most common in the first few weeks after beginning to take orlistat. In some people the side effects persist for as long as they are taking the drug.
People with diabetes, thyroid conditions, who have received an organ transplant, or who are taking prescription medications that affect blood clotting should check with their physician before using OTC orlistat (alli), since drug interactions with certain medications are possible.
A long-term decrease in fat absorption can cause deficiency of fat-soluble vitamins (such as vitamins A, D, E, K). Therefore, patients on orlistat should receive adequate vitamin supplementation.

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