Guide for Selecting Obesity Treatment
Any effective treatment plan must consider the patient’s willingness to undergo therapy, his/her ability to comply with specific treatment approaches, access to skilled caregivers, and financial considerations. Lifestyle modification, which involves a program of appropriate diet, physical activity, and behavior therapy, should be considered for all patients with a Body Mass Index (BMI) more than 25 kg/m2. Long-term pharmacotherapy should be considered in appropriate patients who were unable to achieve adequate weight loss after 6 months of lifestyle therapy and who have a BMI more than 30 kg/m2, or more than 27 kg/m2 with concomitant obesity-related disease. Bariatric surgery may be necessary in patients with severe obesity who failed to lose weight with non-surgical therapy. Eligible surgical candidates should have a BMI more than 40 kg/m2 or a BMI more than 35 kg/m2 and a concomitant serious obesity-related disease. [1]
Steady and Long Term Weight Loss
The combination of an LCD (1000-1500 kcal/d) and increased physical activity is recommended because it produces weight loss that also may result in decreases in abdominal fat and increases in cardio-respiratory fitness. (Evidence category A) [2]
Relationship between Weight Change and Coronary Heart Disease Risk Factor Sum: Framingham Offspring Study
Data from the Framingham Offspring Study demonstrate that small changes in body weight are associated with significant changes in the sum of coronary heart disease (CHD) risk factors. A gain in weight of 2.25 kg (5 lb) or more over 16 years significantly increased the sum of risk factors for CHD by 20 % in men and 37 % in women. Conversely, a reduction in weight by 2.25 kg (5 lb) or more significantly decreased the risk factor sum by 48 % in men and 40 % in women. [3]
Insulin Sensitivity Improves With Weight Loss in Patients with Type 2 Diabetes
In obese patients with type 2 diabetes, modest weight loss improves insulin sensitivity and glycemic control in a dose dependent fashion. This figure represents data from a trial conducted in 114 patients with type 2 diabetes who were being treated with oral hypoglycemic agents only and who completed a 1-year weight control program. [4]
Fasting plasma insulin concentration, which provides an index of insulin sensitivity, decreased in a stepwise fashion with decreases in body weight. Even, a weight loss as small as 2.5 % was associated with a significant decrease in plasma insulin concentration. Reductions in glycosylated hemoglobin, fasting blood glucose, and diabetic medication requirements were also directly associated with weight loss. The need for hypoglycemic medication was decreased in all subjects who lost 15 % or more of their body weight.
Relationship between Rate of Weight Loss and Gallstone Formation
Weight loss is associated with an increased risk of gallstones because weight loss increases bile cholesterol supersaturating, enhances cholesterol crystal nucleation, and decreases gallbladder contractility [5]. The incidence of new gallstones is approximately 25 % – 35 % in obese patients who experience rapid weight loss after treatment with a very-low-calorie, low-fat diet (less than 600 kcal/d; 1 – 3 g fat/d) [6, 7] or gastric surgery [8]. This figure summarizes the data from 9 studies that evaluated the incidence of gallstones in obese patients undergoing weight loss. The risk of gallstone formation increased markedly when the rate of weight loss exceeded 1.5 kg (~1.5 % of body weight) per week [9].
Factors Affect Steady and Long Term Weight Loss
There are some factors that affect steady and long term weight loss such as:
- Maintenance therapy
- Diet therapy
- Energy content
- Macronutrient composition
- Food variety
- Portion size
- Combination diet and physical activity
- Combination diet and drug therapy
Long-Term Weight Loss Is Improved With Long-Term Maintenance Therapy
Maintenance therapy is important for long-term weight management success after initial weight loss is achieved by diet and behavior therapy. In this study, Perri and colleagues [10] randomized obese subjects who lost weight after 5 months of diet and behavior modification therapy to “no maintenance” or a “maintenance program” that involved biweekly contact. At 1 year after initial weight loss was achieved, participants who received maintenance therapy maintained long-term weight loss, whereas those who did not receive maintenance therapy regained half of their lost weight.
Dietary Therapy-Energy Content [11]
- Low Calorie Diets (LCDs) are recommended for weight loss in overweight and obese persons. (Evidence category A)
- Very Low Calorie Diets (VLCDs) produce greater initial weight loss than LCDs. However long-term (more than 1 year) weight loss is not different with the LCDs. (Evidence category A)
Suggested Energy Intake Based On Initial Body Weight
In practice, it is difficult to determine the amount of calories that should be prescribed to achieve a specific energy deficit, because it is difficult to know a patient’s total energy requirements. This table provides suggestions for dietary energy intake based on initial body weight [12].
The estimated energy deficit increases with increasing body weight. The target energy deficit in very heavy patients is higher than those recommended by the NIH guidelines [13], but may be desirable for many patients in these weight categories. Some patients may not fully comply with their prescribed diet or the estimate of desired energy intake may be inaccurate. Therefore, dietary energy content should be regularly adjusted based on a trial-and-error approach, to achieve an appropriate rate of weight loss (approximately 1 % weight loss per week). Diets containing more than 1000 kcal/day may need daily multivitamin supplements, particularly folic acid for women of child-bearing age.
Recommended Nutrient Content of a Weight-Reducing Diet
Dietary guidelines proposed by the National Institutes of Health [14] recommend a 500 kcal/d deficit for overweight persons (BMI 25.0 - 29.9 kg/m2) who have obesity-related complications and for persons with class I obesity (BMI 30 - 34.9 kg/m2). This energy deficit will result in approximately a 1-lb (0.45 kg) weight loss per week and about a 10% weight reduction at 6 months. A 500-1000 kcal/d deficit is recommended for those with class II (BMI 35.0 - 39.9 kg/m2) or class III (BMI more than 40 kg/m2) obesity, which will produce about a 1- to 2-lb weight loss per week and a 10 % weight loss at 6 months. The recommended macronutrient composition for a low-calorie weight loss diet is shown in this figure and includes 55 % or more of daily calories from carbohydrates, 15 % from protein, and 30 % or less from fat. In addition, specific recommendations are made regarding the composition of fat ingestion: total energy intake should be comprised of 8 % - 10 % calories from saturated fat, 10 % or fewer calories from polyunsaturated fats, and 15 % or fewer calories from monounsaturated fats. Daily cholesterol intake should not exceed 300 mg/d, and daily fiber intake should be between 20-30 g/d.
Dietary Therapy-Macronutrient Composition
- Low fat diet
- Low carbohydrate diet
Low fat diet and low carbohydrate diet cause a similar weight loss. It showed that energy intake determined the weight loss and not nutrient composition. [15, 16]
Effect of Macronutrient Composition on Lipid Profile
High carbohydrate diet significantly lowered their plasma total cholesterol, LDL cholesterol and HDL cholesterol. While, low carbohydrate diet only lowered plasma trygliceride level. [17]
Dietary Therapy- Low Fat Diet
Decreasing dietary fat intake to 20 - 30 % of total calorie results in decreased total energy intake and was directly associated with decreasing body weight. [18]
Dietary Therapy-Meal Variety
Increase meal variety with different taste will increase:
- Energy intake
- Positive energy balance
- Weight balance [19]
Effect of Portion Size on Energy Intake
Food portion size affects energy intake. In this study, young adult men and women were served four different portions of macaroni and cheese for lunch on different days, and were allowed to consume as much food as they liked [20]. The data demonstrate a linear relationship between portion size served and intake: increasing the amount of macaroni and cheese served increased the amount that was consumed.
Combination Diet and Physical Activity
The combination of a reduced calorie diet and increased physical activity produced greater weight loss than diet alone or physical activity alone. It is recommended since it produced weight loss that may also result in decreases abdominal fat and increases in cardio-respiratory fitness. (Evidence category A) [21] Weight maintenance can be achieved with either programmed or lifestyle activity. Physical activity help preserve fat free mass during weight loss
Combination Diet and Drug Therapy
Weight loss drug may only be used as part of comprehensive therapy of weight loss program including diet and physical activity for patients with a BMI more than equal 30 with no concomitant obesity-related risk factors or diseases, or for patients with a BMI more than equal 27 with concomitant obesity-related risk factors or diseases. (Evidence category B) [22]
Drugs Approved By FDA for Treating Obesity
Medications approved by the United States Food and Drug Administration (FDA) for treatment of obesity are orlistat (Xenical), sibutramine (Meridia), diethylpropion (Tenulate), phentermine (Adipex, lonamin), phendimetrazine (Bontril, Prelu-2), benzphetamine (Didrex). Only sibutramine and orlistat have been approved for long-term use. All the approved medications act as anorexiants, with the exception of orlistat, which blocks the absorption of dietary fat. Anorexiants increase satiation (level of fullness, which regulates the amount of food consumed during a meal) or satiety (level of fullness after a meal, which determines frequency of eating), or both. Methamphetamine is also approved by the FDA for short-term use, but it is a DEA schedule II drug and should be avoided because of its abuse potential. Three anorexiant medications have been removed from the marketplace because of increased risks of either valvular heart disease (fenfluramine and dexfenfluramine) [23] or hemorrhagic stroke (phenylpropanolamine) [24] associated with their use.
Orlistat Prevents Fat Digestion and Absorption by Binding to Gastrointestinal Lipases
Orlistat is a chemically synthesized hydrogenated derivative of lipstatin (a natural product of Streptomyces toxyricini). Orlistat binds to gastric, pancreatic, and carboxylester lipases in the gut lumen and blocks the digestion of dietary fat by preventing lipase from interacting with its lipid target [25]. Inhibition of fat digestion decreases mixed micelle formation and absorption of long-chain fatty acids, cholesterol, and certain fat-soluble vitamins. Orlistat does not affect the action of systemic lipases or lipases located in other organ systems because it is minimally (less than 1 %) absorbed from the gastrointestinal tract.
Effect of Long-Term Orlistat Therapy on Body Weight
This figure shows the results of a 4 year randomized controlled trial, conducted in over 3000 obese subjects, which compared orlistat therapy plus lifestyle intervention with placebo therapy plus lifestyle intervention [26]. The lowest body weight was achieved during the first year, and was greater in the orlistat-treated group (11 % weight loss) than in the placebo-treatment group (6 % weight loss). Subjects regained weight during the remainder of the trial, so orlistat-treated subjects had lost 6.9 % and placebo-treated subjects had lost 4.1 % of their initial body weight at the end of 4 years. Orlistat therapy also resulted in a 37 % reduction in the cumulative incidence of new-onset type 2 diabetes, primarily by preventing the development of diabetes in patients who had impaired glucose tolerance.
Sibutramine Blocks Neuronal Monoamine (Serotonin, Norepinephrine, Dopamine) Reuptake
Sibutramine is a derivative of the amphetamine precursor beta-phenylethylamine that has been chemically modified to eliminate its abuse potential. Sibutramine enhances satiation (level of fullness during a meal), by blocking the reuptake of monoamine neurotransmitters (serotonin, norepinephrine, and to a lesser extent, dopamine) in the hypothalamus. Monoamines, synthesized by presynaptic neurons, are stored in granules that release their contents into the cleft between pre- and postsynaptic nerves. Most of the monoamines released into the interneuronal cleft are taken back up by the presynaptic nerve, where they are either degraded or repackaged into new granules. A small portion of released monoamines bind to postsynaptic receptors, which transmits a signal from one nerve to the other. Blocking monoamine reuptake increases the signal transmitted to the postsynaptic nerve.
Initial Responders to Sibutramine Can Maintain Long-Term Weight Loss
The ability of sibutramine to maintain long-term weight loss in obese subjects who respond to short-term sibutramine therapy was evaluated in a randomized, controlled trial (STORM; Sibutramine Trial of Obesity Reduction and Maintenance) [27]. During the first 6 months (weight loss phase), all subjects received sibutramine (10 mg/d) and an individualized 600 kcal/d deficit diet program. Patients achieving at least a 5 % weight loss, without regain during months 4–6, were then randomly assigned to treatment with either sibutramine (increased to 15 or 20 mg/d) or placebo for an additional 18 months.
Sibutramine-treated subjects maintained their weight for the next year with a slight regain during the last 6 months (months 18–24) of the study. In contrast, subjects randomized to placebo experienced an immediate and steady increase in body weight. Of the 204 sibutramine-treated patients who completed the trial, 89 (43 %) maintained 80 % or more of their original 6-month weight loss compared with 9 (16 %) of the 57 patients in the placebo group; P<0.001.>
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Adapted from Fiastuti Witjaksono Presentation.
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